Donald A. Wilson, Ph.D.

Odor fear conditioning modifies piriform cortex local field potentials both during conditioning and during post-conditioning sleep
Barnes, Dylan C; Chapuis, Julie; Chaudhury, Dipesh; Wilson, Donald A
2011 ;6(3):e18130-e18130, PLoS ONE
BACKGROUND: Sleep plays an active role in memory consolidation. Sleep structure (REM/Slow wave activity [SWS]) can be modified after learning, and in some cortical circuits, sleep is associated with replay of the learned experience. While the majority of this work has focused on neocortical and hippocampal circuits, the olfactory system may offer unique advantages as a model system for exploring sleep and memory, given the short, non-thalamic pathway from nose to primary olfactory (piriform cortex), and rapid cortex-dependent odor learning. METHODOLOGY/PRINCIPAL FINDINGS: We examined piriform cortical odor responses using local field potentials (LFPs) from freely behaving Long-Evans hooded rats over the sleep-wake cycle, and the neuronal modifications that occurred within the piriform cortex both during and after odor-fear conditioning. We also recorded LFPs from naive animals to characterize sleep activity in the piriform cortex and to analyze transient odor-evoked cortical responses during different sleep stages. Naive rats in their home cages spent 40% of their time in SWS, during which the piriform cortex was significantly hypo-responsive to odor stimulation compared to awake and REM sleep states. Rats trained in the paired odor-shock conditioning paradigm developed enhanced conditioned odor evoked gamma frequency activity in the piriform cortex over the course of training compared to pseudo-conditioned rats. Furthermore, conditioned rats spent significantly more time in SWS immediately post-training both compared to pre-training days and compared to pseudo-conditioned rats. The increase in SWS immediately after training significantly correlated with the duration of odor-evoked freezing the following day. CONCLUSIONS/SIGNIFICANCE: The rat piriform cortex is hypo-responsive to odors during SWS which accounts for nearly 40% of each 24 hour period. The duration of slow-wave activity in the piriform cortex is enhanced immediately post-conditioning, and this increase is significantly correlated with subsequent memory performance. Together, these results suggest the piriform cortex may go offline during SWS to facilitate consolidation of learned odors with reduced external interference
— id: 133435, year: 2011, vol: 6, page: e18130, stat: Journal Article,

Interaction between delta opioid receptors and benzodiazepines in CO2-induced respiratory responses in mice
Borkowski, Anne H; Barnes, Dylan C; Blanchette, Derek R; Castellanos, F Xavier; Klein, Donald F; Wilson, Donald A
2011 Jun 17;1396:54-59, Brain research
The false-suffocation hypothesis of panic disorder (Klein, 1993) suggested delta-opioid receptors as a possible source of the respiratory dysfunction manifested in panic attacks occurring in panic disorder (Preter and Klein, 2008). This study sought to determine if a lack of delta-opioid receptors in a mouse model affects respiratory response to elevated CO(2), and whether the response is modulated by benzodiazepines, which are widely used to treat panic disorder. In a whole-body plethysmograph, respiratory responses to 5% CO(2) were compared between delta-opioid receptor knockout mice and wild-type mice after saline, diazepam (1mg/kg), and alprazolam (0.3mg/kg) injections. The results show that lack of delta-opioid receptors does not affect normal response to elevated CO(2), but does prevent benzodiazepines from modulating that response. Thus, in the presence of benzodiazepine agonists, respiratory responses to elevated CO(2) were enhanced in delta-opioid receptor knockout mice compared to wild-type mice. This suggests an interplay between benzodiazepine receptors and delta-opioid receptors in regulating the respiratory effects of elevated CO(2), which might be related to CO(2) induced panic
— id: 138822, year: 2011, vol: 1396, page: 54, stat: Journal Article,

Bidirectional plasticity of cortical pattern recognition and behavioral sensory acuity
Chapuis, Julie; Wilson, Donald A
2011 ;15(1):155-161, Nature neuroscience
Learning to adapt to a complex and fluctuating environment requires the ability to adjust neural representations of sensory stimuli. Through pattern completion processes, cortical networks can reconstruct familiar patterns from degraded input patterns, whereas pattern separation processes allow discrimination of even highly overlapping inputs. Here we show that the balance between pattern separation and completion is experience dependent. Rats given extensive training with overlapping complex odorant mixtures showed improved behavioral discrimination ability and enhanced piriform cortical ensemble pattern separation. In contrast, behavioral training to disregard normally detectable differences between overlapping mixtures resulted in impaired piriform cortical ensemble pattern separation (enhanced pattern completion) and impaired discrimination. This bidirectional effect was not found in the olfactory bulb; it may be due to plasticity within olfactory cortex itself. Thus pattern recognition, and the balance between pattern separation and completion, is highly malleable on the basis of task demands and occurs in concert with changes in perceptual performance
— id: 149929, year: 2011, vol: 15, page: 155, stat: Journal Article,

GENERALIZED VERSUS STIMULUS-SPECIFIC LEARNED FEAR DIFFERENTIALLY MODIFIES STIMULUS ENCODING IN PRIMARY SENSORY CORTEX OF AWAKE RATS
Chen CF; Barnes DC; Wilson DA
2011 Dec;106(6):3136-3144, Journal of neurophysiology
Experience shapes both central olfactory system function and odor perception. In piriform cortex, odor experience appears critical for synthetic processing of odor mixtures which contributes to perceptual learning and perceptual acuity, as well as contributing to memory for events and/or rewards associated with odors. Here, we examined the effect of odor fear conditioning on piriform cortical single-unit responses to the learned aversive odor, as well as its effects on similar (overlapping mixtures) in freely moving rats. We found that odor-evoked fear responses were training paradigm-dependent. Simple association of a CS+ odor with foot-shock (US) led to generalized fear (cue-evoked freezing) to similar odors. However, after differential conditioning, which included trials where a CS- odor (a mixture overlapping with the CS+) was not paired with shock, freezing responses were CS+ odor-specific and less generalized. Pseudo-conditioning led to no odor-evoked freezing. These differential levels of stimulus control over freezing were associated with different training-induced changes in single-unit odor responses in anterior piriform cortex (aPCX). Both simple and differential conditioning induced a significant decrease in aPCX single-unit spontaneous activity compared to pre-training levels while pseudo-conditioning did not. Simple conditioning enhanced mean receptive field size (breadth of tuning) of the aPCX units, while differential conditioning reduced mean receptive field size. These results suggest that generalized fear is associated with an impairment of olfactory cortical discrimination. Furthermore, changes in sensory processing are dependent on the nature of training, and can predict the stimulus controlled behavioral outcome of the training
— id: 140391, year: 2011, vol: 106, page: 3136, stat: Journal Article,

Daily rhythms in olfactory discrimination depend on clock genes but not the suprachiasmatic nucleus
Granados-Fuentes, Daniel; Ben-Josef, Gal; Perry, Gavin; Wilson, Donald A; Sullivan-Wilson, Alexander; Herzog, Erik D
2011 Dec;26(6):552-560, Journal of biological rhythms
The suprachiasmatic nucleus (SCN) regulates a wide range of daily behaviors and has been described as the master circadian pacemaker. The role of daily rhythmicity in other tissues, however, is unknown. We hypothesized that circadian changes in olfactory discrimination depend on a genetic circadian oscillator outside the SCN. We developed an automated assay to monitor olfactory discrimination in individual mice throughout the day. We found olfactory sensitivity increased approximately 6-fold from a minimum during the day to a peak in the early night. This circadian rhythm was maintained in SCN-lesioned mice and mice deficient for the Npas2 gene but was lost in mice lacking Bmal1 or both Per1 and Per2 genes. We conclude that daily rhythms in olfactory sensitivity depend on the expression of canonical clock genes. Olfaction is, thus, the first circadian behavior that is not based on locomotor activity and does not require the SCN
— id: 149928, year: 2011, vol: 26, page: 552, stat: Journal Article,

Pattern separation: a common function for new neurons in hippocampus and olfactory bulb
Sahay, Amar; Wilson, Donald A; Hen, Rene
2011 May 26;70(4):582-588, Neuron
While adult-born neurons in the olfactory bulb (OB) and the dentate gyrus (DG) subregion of the hippocampus have fundamentally different properties, they may have more in common than meets the eye. Here, we propose that new granule cells in the OB and DG may function as modulators of principal neurons to influence pattern separation and that adult neurogenesis constitutes an adaptive mechanism to optimally encode contextual or olfactory information. See the related Perspective from Aimone, Deng, and Gage, 'Resolving New Memories: A Critical Look at the Dentate Gyrus, Adult Neurogenesis, and Pattern Separation,' in this issue of Neuron
— id: 136464, year: 2011, vol: 70, page: 582, stat: Journal Article,

Sensory Network Dysfunction, Behavioral Impairments, and Their Reversibility in an Alzheimer's beta-Amyloidosis Mouse Model
Wesson DW; Borkowski AH; Landreth GE; Nixon RA; Levy E; Wilson DA
2011 Nov 2;31(44):15962-15971, Journal of neuroscience
The unique vulnerability of the olfactory system to Alzheimer's disease (AD) provides a quintessential translational tool for understanding mechanisms of synaptic dysfunction and pathological progression in the disease. Using the Tg2576 mouse model of beta-amyloidosis, we show that aberrant, hyperactive olfactory network activity begins early in life, before detectable behavioral impairments or comparable hippocampal dysfunction and at a time when amyloid-beta (Abeta) deposition is restricted to the olfactory bulb (OB). Hyperactive odor-evoked activity in the piriform cortex (PCX) and increased OB-PCX functional connectivity emerged at a time coinciding with olfactory behavior impairments. This hyperactive activity persisted until later in life when the network converted to a hyporesponsive state. This conversion was Abeta-dependent, because liver-X receptor agonist treatment to promote Abeta degradation rescued the hyporesponsive state and olfactory behavior. These data lend evidence to a novel working model of olfactory dysfunction in AD and, complimentary to other recent works, suggest that disease-relevant network dysfunction is highly dynamic and region specific, yet with lasting effects on cognition and behavior
— id: 145504, year: 2011, vol: 31, page: 15962, stat: Journal Article,

Mechanisms of neural and behavioral dysfunction in Alzheimer's disease
Wesson, Daniel W; Nixon, Ralph A; Levy, Efrat; Wilson, Donald A
2011 Jun;43(3):163-179, Molecular neurobiology
This review critically examines progress in understanding the link between Alzheimer's disease (AD) molecular pathogenesis and behavior, with an emphasis on the impact of amyloid-beta. We present the argument that the AD research field requires more multifaceted analyses into the impacts of Alzheimer's pathogenesis which combine simultaneous molecular-, circuit-, and behavior-level approaches. Supporting this argument is a review of particular research utilizing similar, 'systems-level' methods in mouse models of AD. Related to this, a critique of common physiological and behavioral models is made-highlighting the likely usefulness of more refined and specific tools in understanding the relationship between candidate molecular pathologies and behavioral dysfunction. Finally, we propose challenges for future research which, if met, may greatly extend our current understanding of how AD molecular pathology impacts neural network function and behavior and possibly may lead to refinements in disease therapeutics
— id: 131960, year: 2011, vol: 43, page: 163, stat: Journal Article,

Respiratory and sniffing behaviors throughout adulthood and aging in mice
Wesson, Daniel W; Varga-Wesson, Adrienn G; Borkowski, Anne H; Wilson, Donald A
2011 Sep 30;223(1):99-106, Behavioural brain research
Orienting responses are physiological and active behavioral reactions evoked by novel stimulus perception and are critical for survival. We explored whether odor orienting responses are impacted throughout both adulthood and normal and pathological aging in mice. Novel odor investigation (including duration and bout numbers) and its subsequent habituation as assayed in the odor habituation task were preserved in adult C57BL/6J mice up to 12mo of age with <6% variability between age groups in investigation time. Separately, using whole-body plethysmography we found that both spontaneous respiration and odor-evoked sniffing behaviors were strikingly preserved in wildtype (WT) mice up to 26mo of age. In contrast, mice accumulating amyloid-beta protein in the brain by means of overexpressing mutations in the human amyloid precursor protein gene (APP) showed preserved spontaneous respiration up to 12mo, but starting at 14mo showed significant differences from WT. Similar to WTs, odor-evoked sniffing was not impacted in APP mice up to 26mo. These results show that odor-orienting responses are minimally impacted throughout aging in mice, and suggest that the olfactomotor network is mostly spared of insults due to aging
— id: 134307, year: 2011, vol: 223, page: 99, stat: Journal Article,

Age and gene overexpression interact to abolish nesting behavior in Tg2576 amyloid precursor protein (APP) mice
Wesson, Daniel W; Wilson, Donald A
2011 Jan 1;216(1):408-413, Behavioural brain research
Elucidating the modulators of social behavioral is important in understanding the neural basis of behavior and in developing methods to enhance behavior in cases of disorder. The work here stems from the observation that the Alzheimer's disease mouse model Tg2576, overexpressing human mutations of the amyloid-beta precursor protein (APP), fails to construct nests when supplied paper towels in their home cages. Experiments using commercially available cotton nesting material found similar results. Additional experiments revealed that the genotype effect is progressively modulated by age in APP mice but not their WT counterparts. There was no effect of sex on nesting behavior in any group. Finally, this effect was independent of ambient temperature - even when subjected to a cold environment, APP mice fail to build nests whereas WT mice do. These results suggest that the APP gene plays a role in affiliative behaviors and are discussed in relation to disorders characteristic of mutations in the APP gene and in affective dysfunction, including Alzheimer's disease
— id: 114172, year: 2011, vol: 216, page: 408, stat: Journal Article,

Sniffing out the contributions of the olfactory tubercle to the sense of smell: Hedonics, sensory integration, and more?
Wesson, Daniel W; Wilson, Donald A
2011 Jan;35(3):655-668, Neuroscience & biobehavioral reviews
Since its designation in 1896 as a putative olfactory structure, the olfactory tubercle has received little attention in terms of elucidating its role in the processing and perception of odors. Instead, research on the olfactory tubercle has mostly focused on its relationship with the reward system. Here we provide a comprehensive review of research on the olfactory tubercle-with an emphasis on the likely role of this region in olfactory processing and its contributions to perception. Further, we propose several testable hypotheses regarding the likely involvement of the olfactory tubercle in both basic (odor detection, discrimination, parallel processing of olfactory information) and higher-order (social odor processing, hedonics, multi-modal integration) functions. Together, the information within this review highlights an understudied yet potentially critical component in central odor processing
— id: 115419, year: 2011, vol: 35, page: 655, stat: Journal Article,

State-dependent functional connectivity of rat olfactory system assessed by fMRI
Wilson, D A; Hoptman, M J; Gerum, S V; Guilfoyle, D N
2011 Jun 22;497(2):69-73, Neuroscience letters
Functional connectivity between the piriform cortex and limbic and neocortical areas was assessed using functional magnetic resonance imaging (fMRI) of urethane anesthetized rats that spontaneously cycled between slow-wave and fast-wave states. Slow-wave and fast-wave states were determined indirectly through monitoring of respiration rate, which was confirmed to co-vary with state as determined by electrophysiological recordings. Previous electrophysiological data have suggested that the piriform cortex shifts between responsiveness to afferent odor input during fast-wave states and enhanced functional connectivity with limbic areas during slow-wave state. The present results demonstrate that fMRI-based resting state functional connectivity between the piriform cortex and both limbic and neocortical areas is enhanced during slow-wave state compared to fast-wave state using respiration as an indirect measure of state in urethane anesthetized rats. This state-dependent shift in functional connectivity may be important for sleep-dependent odor memory consolidation
— id: 133463, year: 2011, vol: 497, page: 69, stat: Journal Article,

Local and regional network function in behaviorally relevant cortical circuits of adult mice following postnatal alcohol exposure
Wilson, Donald A; Peterson, Jesse; Basavaraj, Balapal S; Saito, Mariko
2011 Nov;35(11):1974-1984, Alcoholism: clinical & experimental research
BACKGROUND: Ethanol consumption during pregnancy can lead to fetal alcohol spectrum disorder (FASD), which consists of the complete spectrum of developmental deficits including neurological dysfunction. FASD is associated with a variety of neurobehavioral disturbances dependent on the age and duration of exposure. Ethanol exposure in neonatal rodents can also induce widespread apoptotic neurodegeneration and long-lasting behavioral abnormalities similar to FASD. The developmental stage of neonatal rodent brains that are at the peak of synaptogenesis is equivalent to the third trimester of human gestation. METHODS: Male and female C57BL/6By mice were injected with ethanol (20%, 2.5 g/kg, 2 s.c. injections) or an equal volume of saline (controls) on postnatal day 7 (P7). Animals were allowed to mature and at 3 months were tested on an olfactory habituation task known to be dependent on piriform cortex function, a hippocampal-dependent object place memory task, and used for electrophysiological testing of spontaneous and odor-evoked local field potential (LFP) activity in the olfactory bulb, piriform cortex, and dorsal hippocampus. RESULTS: P7 ethanol induced widespread cell death within 1 day of exposure, with highest levels in the neocortex, intermediate levels in the dorsal hippocampus, and relatively low levels in the primary olfactory system. No impairment of odor investigation or odor habituation was detected in P7 ethanol-exposed 3-month-old mice compared to saline controls. However, hippocampal-dependent object place memory was significantly impaired in the P7 ethanol-treated adult mice. Odor-evoked LFP activity was enhanced throughout the olfacto-hippocampal pathway, primarily within the theta frequency band, although the hippocampus also showed elevated evoked delta frequency activity. In addition, functional coherence between the piriform cortex and olfactory bulb and between the piriform cortex and dorsal hippocampus was enhanced in the beta frequency range in P7 ethanol-treated adult mice compared to controls. CONCLUSIONS: P7 ethanol induces an immediate wave of regionally selective cell death followed by long-lasting changes in local circuit and regional network function that are accompanied by changes in neurobehavioral performance. The results suggest that both the activity of local neural circuits within a brain region and the flow of information between brain regions can be modified by early alcohol exposure, which may contribute to long-lasting behavioral abnormalities known to rely on those circuits
— id: 146225, year: 2011, vol: 35, page: 1974, stat: Journal Article,

Cortical processing of odor objects
Wilson, Donald A; Sullivan, Regina M
2011 Nov 17;72(4):506-519, Neuron
Natural odors, generally composed of many monomolecular components, are analyzed by peripheral receptors into component features and translated into spatiotemporal patterns of neural activity in the olfactory bulb. Here, we will discuss the role of the olfactory cortex in the recognition, separation and completion of those odor-evoked patterns, and how these processes contribute to odor perception. Recent findings regarding the neural architecture, physiology, and plasticity of the olfactory cortex, principally the piriform cortex, will be described in the context of how this paleocortical structure creates odor objects
— id: 141711, year: 2011, vol: 72, page: 506, stat: Journal Article,

Therapeutic effects of remediating autophagy failure in a mouse model of Alzheimer disease by enhancing lysosomal proteolysis
Yang, Dun-Sheng; Stavrides, Philip; Mohan, Panaiyur S; Kaushik, Susmita; Kumar, Asok; Ohno, Masuo; Schmidt, Stephen D; Wesson, Daniel W; Bandyopadhyay, Urmi; Jiang, Ying; Pawlik, Monika; Peterhoff, Corrinne M; Yang, Austin J; Wilson, Donald A; St George-Hyslop, Peter; Westaway, David; Mathews, Paul M; Levy, Efrat; Cuervo, Ana M; Nixon, Ralph A
2011 Jul 1;7(7):788-789, Autophagy
The extensive autophagic-lysosomal pathology in Alzheimer disease (AD) brain has revealed a major defect: in the proteolytic clearance of autophagy substrates. Autophagy failure contributes on several levels to AD pathogenesis and has become an important therapeutic target for AD and other neurodegenerative diseases. We recently observed broad therapeutic effects of stimulating autophagic-lysosomal proteolysis in the TgCRND8 mouse model of AD that exhibits defective proteolytic clearance of autophagic substrates, robust intralysosomal amyloid-beta peptide (Abeta) accumulation, extracellular beta-amyloid deposition and cognitive deficits. By genetically deleting the lysosomal cysteine protease inhibitor, cystatin B (CstB), to selectively restore depressed cathepsin activities, we substantially cleared Abeta, ubiquitinated proteins and other autophagic substrates from autolysosomes/lysosomes and rescued autophagic-lysosomal pathology, as well as reduced total Abeta40/42 levels and extracellular amyloid deposition, highlighting the underappreciated importance of the lysosomal system for Abeta clearance. Most importantly, lysosomal remediation prevented the marked learning and memory deficits in TgCRND8 mice. Our findings underscore the pathogenic significance of autophagic-lysosomal dysfunction in AD and demonstrate the value of reversing this dysfunction as an innovative therapeautic strategy for AD
— id: 134440, year: 2011, vol: 7, page: 788, stat: Journal Article,

Reversal of autophagy dysfunction in the TgCRND8 mouse model of Alzheimer's disease ameliorates amyloid pathologies and memory deficits
Yang, Dun-Sheng; Stavrides, Philip; Mohan, Panaiyur S; Kaushik, Susmita; Kumar, Asok; Ohno, Masuo; Schmidt, Stephen D; Wesson, Daniel; Bandyopadhyay, Urmi; Jiang, Ying; Pawlik, Monika; Peterhoff, Corrinne M; Yang, Austin J; Wilson, Donald A; St George-Hyslop, Peter; Westaway, David; Mathews, Paul M; Levy, Efrat; Cuervo, Ana M; Nixon, Ralph A
2011 Jan;134(Pt 1):258-277, Brain
Autophagy, a major degradative pathway for proteins and organelles, is essential for survival of mature neurons. Extensive autophagic-lysosomal pathology in Alzheimer's disease brain contributes to Alzheimer's disease pathogenesis, although the underlying mechanisms are not well understood. Here, we identified and characterized marked intraneuronal amyloid-beta peptide/amyloid and lysosomal system pathology in the Alzheimer's disease mouse model TgCRND8 similar to that previously described in Alzheimer's disease brains. We further establish that the basis for these pathologies involves defective proteolytic clearance of neuronal autophagic substrates including amyloid-beta peptide. To establish the pathogenic significance of these abnormalities, we enhanced lysosomal cathepsin activities and rates of autophagic protein turnover in TgCRND8 mice by genetically deleting cystatin B, an endogenous inhibitor of lysosomal cysteine proteases. Cystatin B deletion rescued autophagic-lysosomal pathology, reduced abnormal accumulations of amyloid-beta peptide, ubiquitinated proteins and other autophagic substrates within autolysosomes/lysosomes and reduced intraneuronal amyloid-beta peptide. The amelioration of lysosomal function in TgCRND8 markedly decreased extracellular amyloid deposition and total brain amyloid-beta peptide 40 and 42 levels, and prevented the development of deficits of learning and memory in fear conditioning and olfactory habituation tests. Our findings support the pathogenic significance of autophagic-lysosomal dysfunction in Alzheimer's disease and indicate the potential value of restoring normal autophagy as an innovative therapeutic strategy for Alzheimer's disease
— id: 126481, year: 2011, vol: 134, page: 258, stat: Journal Article,

Odor fear conditioning and olfactory system slow-wave sleep
Barnes D.C.; Chapuis J.; Wilson D.A.
2010 ;35(7):A80-A80, Chemical Senses
Sleep plays an active role in memory consolidation. Sleep structure (REM/ Slow-wave sleep [SWS]) is modified after conditioning, and in some cortical circuits, SWS is associated with replay of the learned experience. Interestingly, the sleep modifications can be local, only affecting activity in the brain regions active during the training. Here, we wanted to ascertain possible changes in sleep structure within olfactory cortex following odor fear conditioning. We recorded local field potentials (LFP) from the anterior piriform cortex (aPCX) in behaving animals and analyzed odor-evoked changes during fear conditioning and subsequent sleep structure modifications. Long-Evans hooded rats were chronically implanted with telemetry electrodes in the aPCX. Rats were placed in a conditioning box for 30 min on three baseline days, conditioned with ten paired odor-shock stimuli on the fourth day, and tested with five odor pulses on the fifth day. On the conditioning and test days, behavioral (freezing or vocalization), autonomic (heart rate) and LFP responses to the conditioned odor were examined. After each daily session, we placed the animal in a dark, sound attenuating chamber and recorded LFPs and EMG for 4 hours. Preliminary data show that rats learned behavioral and autonomic fear responses to the odor and that aPCX odor-evoked beta (15-40 Hz) oscillatory activity may correlate with the magnitude of the fear response. Furthermore, aPCX SWS increased following odor-shock conditioning compared to baseline days. Unpaired control rats showed neither odor fear responses nor an increase in SWS. Finally, the activity of aPCX single-units during SWS was shaped by recent odor experience and there was enhanced functional connectivity between the aPCX and hippocampus during SWS compared to other period
— id: 120661, year: 2010, vol: 35, page: A80, stat: Journal Article,

Odor fear conditioning effects on piriform cortical odor processing in awake rats
Chen C.-F.F.; Wilson D.A.
2010 ;35(7):A33-A33, Chemical Senses
Odors that we encounter everyday are usually very complex. While the olfactory system is capable of discriminating complex yet similar odors (e.g. mocha and latte) with practice, the underlying mechanisms are not clear. As more data have been reported in anesthetized animals, data from awake animals are few. This experiment was therefore designed to investigate two related questions in awake rats: 1) odor coding of complex mixture in the anterior piriform cortex (a PCX) and 2) fear conditioning effects on odor coding in the a PCX. To record activity from awake animals, Long-Evans hooded rats were chronically implanted with movable bundles of microwires aimed at the a PCX. Up to 7 units were recorded simultaneously, and the electrode bundle was moved over time to sample additional cells. Odor-shock conditioning was performed to induce odor-related aversive experience on the rats, with a complex 10-odorant mixture as the conditioned stimulus (CS). The CS odor, along with overlapping odor mixtures and limonene were presented to the animals before the conditioning trials and for several days post-training. The results (n = 206 units) showed a slight decrease in percentage of units that showed excitation after conditioning, and a significant increase in suppression. A significant decrease in average spontaneous activity was observed after conditioning. Finally, an analysis of single-unit responsiveness revealed a late suppressive response after conditioning to all three mixtures overlapping with the CS but not limonene. Interestingly, while responsiveness to control odors decreased after conditioning, responses to the CS became temporally focused, with a more narrow range of onset and offset latencies. Together, odor fear conditioning should enhance signal:noise and CS coding acuity in a PCX
— id: 120660, year: 2010, vol: 35, page: A33, stat: Journal Article,

Dynamics of Active Sensing and perceptual selection
Schroeder, Charles E; Wilson, Donald A; Radman, Thomas; Scharfman, Helen; Lakatos, Peter
2010 Apr;20(2):172-176, Current opinion in neurobiology
Sensory processing is often regarded as a passive process in which biological receptors like photoreceptors and mechanoreceptors transduce physical energy into a neural code. Recent findings, however, suggest that: first, most sensory processing is active, and largely determined by motor/attentional sampling routines; second, owing to rhythmicity in the motor routine, as well as to its entrainment of ambient rhythms in sensory regions, sensory inflow tends to be rhythmic; third, attentional manipulation of rhythms in sensory pathways is instrumental to perceptual selection. These observations outline the essentials of an Active Sensing paradigm, and argue for increased emphasis on the study of sensory processes as specific to the dynamic motor/attentional context in which inputs are acquired
— id: 114778, year: 2010, vol: 20, page: 172, stat: Journal Article,

Smelling sounds: Olfactory-auditory sensory convergence in the olfactory tubercle
Wesson D.W.; Wilson D.A.
2010 ;35(7):A9-A10, Chemical Senses
The olfactory code is influenced by numerous factors, including behavioral state, odor-sampling patterns and cross-modal sensory convergence. Growing evidence supports the view that primary olfactory cortical regions are not unimodal, but instead represent information from several sensory modalities - providing a substrate for sensory convergence early in olfactory processing. Adding to previous reports of both gustatory and visual influences on the cortical processing of odors, here we report novel findings revealing that the olfactory code is subject to auditory cross-modal influences. In vivo extracellular recordings from the olfactory tubercle, a trilaminar structure within the basal forebrain, of anesthetized mice revealed that olfactory tubercle single-units selectively respond to odors - with 65% of units showing significant odor-evoked activity. Remarkably, 19% of olfactory tubercle single-units also showed robust responses to an auditory tone. Furthermore, 29% of single-units tested displayed supra-additive or suppressive responses to the simultaneous presentation of odor and tone, suggesting cross-modal modulation. In contrast, olfactory bulb units did not show significant responses to tone presentation, nor modulation of odor-evoked activity by tone - suggesting a lack of olfactory- auditory convergence upstream from the olfactory tubercle. Thus, the tubercle presents itself as a source for direct multimodal convergence within an early stage of odor processing, and may serve as a seat for psychophysical interactions between smells and sounds
— id: 120659, year: 2010, vol: 35, page: A9, stat: Journal Article,

Olfactory dysfunction correlates with amyloid-beta burden in an Alzheimer's disease mouse model
Wesson, Daniel W; Levy, Efrat; Nixon, Ralph A; Wilson, Donald A
2010 Jan 13;30(2):505-514, Journal of neuroscience
Alzheimer's disease often results in impaired olfactory perceptual acuity-a potential biomarker of the disorder. However, the usefulness of olfactory screens to serve as informative indicators of Alzheimer's is precluded by a lack of knowledge regarding why the disease impacts olfaction. We addressed this question by assaying olfactory perception and amyloid-beta (Abeta) deposition throughout the olfactory system in mice that overexpress a mutated form of the human amyloid-beta precursor protein. Such mice displayed progressive olfactory deficits that mimic those observed clinically-some evident at 3 months of age. Also, at 3 months of age, we observed nonfibrillar Abeta deposition within the olfactory bulb-earlier than deposition within any other brain region. There was also a correlation between olfactory deficits and the spatial-temporal pattern of Abeta deposition. Therefore, nonfibrillar, versus fibrillar, Abeta-related mechanisms likely contribute to early olfactory perceptual loss in Alzheimer's disease. Furthermore, these results present the odor cross-habituation test as a powerful behavioral assay, which reflects Abeta deposition and thus may serve to monitor the efficacy of therapies aimed at reducing Abeta
— id: 126491, year: 2010, vol: 30, page: 505, stat: Journal Article,

Smelling sounds: olfactory-auditory sensory convergence in the olfactory tubercle
Wesson, Daniel W; Wilson, Donald A
2010 Feb 24;30(8):3013-3021, Journal of neuroscience
Historical and psychophysical literature has demonstrated a perceptual interplay between olfactory and auditory stimuli-the neural mechanisms of which are not understood. Here, we report novel findings revealing that the early olfactory code is subjected to auditory cross-modal influences. In vivo extracellular recordings from the olfactory tubercle, a trilaminar structure within the basal forebrain, of anesthetized mice revealed that olfactory tubercle single units selectively respond to odors-with 65% of units showing significant odor-evoked activity. Remarkably, 19% of olfactory tubercle single units also showed robust responses to an auditory tone. Furthermore, 29% of single units tested displayed supraadditive or suppressive responses to the simultaneous presentation of odor and tone, suggesting cross-modal modulation. In contrast, olfactory bulb units did not show significant responses to tone presentation nor modulation of odor-evoked activity by tone-suggesting a lack of olfactory-auditory convergence upstream from the olfactory tubercle. Thus, the tubercle presents itself as a source for direct multimodal convergence within an early stage of odor processing and may serve as a seat for psychophysical interactions between smells and sounds
— id: 107391, year: 2010, vol: 30, page: 3013, stat: Journal Article,

Should olfactory dysfunction be used as a biomarker of Alzheimer's disease?
Wesson, Daniel W; Wilson, Donald A; Nixon, Ralph A
2010 May;10(5):633-635, Expert review of neurotherapeutics
— id: 126487, year: 2010, vol: 10, page: 633, stat: Journal Article,

Single-Unit Activity in Piriform Cortex during Slow-Wave State Is Shaped by Recent Odor Experience
Wilson, Donald A
2010 Feb 3;30(5):1760-1765, Journal of neuroscience
Memory and its underlying neural plasticity play important roles in sensory discrimination and cortical pattern recognition in olfaction. Given the reported function of slow-wave sleep states in neocortical and hippocampal memory consolidation, we hypothesized that activity during slow-wave states within the piriform cortex may be shaped by recent olfactory experience. Rats were anesthetized with urethane and allowed to spontaneously shift between slow-wave and fast-wave states as recorded in local field potentials within the anterior piriform cortex. Single-unit activity of piriform cortical layer II/III neurons was recorded simultaneously. The results suggest that piriform cortical activity during slow-wave states is shaped by recent (several minutes) odor experience. The temporal structure of single-unit activity during slow waves was modified if the animal had been stimulated with an odor within the receptive field of that cell. If no odor had been delivered, the activity of the cell during slow-wave activity was stable across the two periods. The results demonstrate that piriform cortical activity during slow-wave state is shaped by recent odor experience, which could contribute to odor memory consolidation
— id: 106516, year: 2010, vol: 30, page: 1760, stat: Journal Article,

Olfactory cortex
Wilson, Donald A; Barkai, Edi
Handbook of brain microcircuits New York, NY, US: Oxford University Press; US, 2010,
(from the chapter) The olfactory cortex is defined as those brain areas receiving direct input from mitral and tufted cells of the olfactory bulb (Neville and Haberly, 2004). The olfactory cortex thus includes anterior olfactory nucleus, olfactory tubercle, nucleus of the lateral olfactory tract, cortical nucleus of the amygdala, tenia tecta, piriform cortex, and entorhinal cortex. The largest component of the olfactory cortex is the piriform cortex, and descriptions in this chapter will be limited to the piriform cortex. Piriform cortex is also referred to as pyriform cortex (most common in primates) or prepyrifom cortex (less common usage). Piriform cortex is a phylogenetically old, three-layered paleocortex, as opposed to the six-layered neocortex. The primary afferent to the piriform cortex is mitral cells from the olfactory bulb, which receive direct excitatory input from olfactory sensory neurons within the olfactory epithelium. Thus, piriform cortex is only two synapses from the outside world. Although the piriform cortex anatomical structure is simple and well defined compared to neocortical structures, it subserves higher brain function like other associative cortices. While the piriform cortex is engaged in relatively basic functions like identifying familiar odors and discriminating between similar odors, it also has a central role in complex tasks such as integration of information about the identity and the reward value of odors. Such a variegated capability is enabled by its intrinsic hardwiring, which resembles that seen in higher neocortical areas, and by the efficient sets of connections with ascending and descending brain areas with which it generates synchronized activity.
— id: 5504, year: 2010, vol: , page: 263, stat: Chapter,

Sleep-like states modulate functional connectivity in the rat olfactory system
Wilson, Donald A; Yan, Xiaodan
2010 Dec;104(6):3231-3239, Journal of neurophysiology
The present study was an examination of state-dependent functional connectivity during spontaneous activity between the piriform cortex and its upstream and downstream connections. Rats were anesthetized with urethan and allowed to spontaneously cycle between fast- and slow-wave states similar to fast- and slow-wave sleep states. Local field potential recordings were made from the olfactory bulb, piriform cortex, dorsal hippocampus, amygdala, and primary visual cortex. The results demonstrate that during slow-wave sleep-like states, when the piriform cortex shows reduced sensitivity to odor input via the olfactory bulb, there is enhanced coherence with other forebrain structures. Granger causality analyses suggest that the link between piriform cortical and hippocampal activity during slow-wave state is in the direction of the hippocampus to the piriform cortex rather than the reverse. The results suggest that slow-wave sleep-like states may provide an opportunity for the transfer and/or consolidation of information related to odor memories, specifically at a time when the piriform cortex is less sensitive to sensory input
— id: 133845, year: 2010, vol: 104, page: 3231, stat: Journal Article,

Cortical Processing of Learned Aversive Odors in Awake Rats
Chen, CFF; Wilson, DA
2009 SEP ;34(7):A67-A67, Chemical Senses
— id: 101942, year: 2009, vol: 34, page: A67, stat: Journal Article,

Odor-specific habituation arises from interaction of afferent synaptic adaptation and intrinsic synaptic potentiation in olfactory cortex
Linster, Christiane; Menon, Alka V; Singh, Christopher Y; Wilson, Donald A
2009 Jul;16(7):452-459, Learning & memory
Segmentation of target odorants from background odorants is a fundamental computational requirement for the olfactory system and is thought to be behaviorally mediated by olfactory habituation memory. Data from our laboratory have shown that odor-specific adaptation in piriform neurons, mediated at least partially by synaptic adaptation between the olfactory bulb outputs and piriform cortex pyramidal cells, is highly odor specific, while that observed at the synaptic level is specific only to certain odor features. Behavioral data show that odor habituation memory at short time constants corresponding to synaptic adaptation is also highly odor specific and is blocked by the same pharmacological agents as synaptic adaptation. Using previously developed computational models of the olfactory system we show here how synaptic adaptation and potentiation interact to create the observed specificity of response adaptation. The model analyzes the mechanisms underlying the odor specificity of habituation, the dependence on functioning cholinergic modulation, and makes predictions about connectivity to and within the piriform neural network. Predictions made by the model for the role of cholinergic modulation are supported by behavioral results
— id: 140380, year: 2009, vol: 16, page: 452, stat: Journal Article,

Habituation revisited: An updated and revised description of the behavioral characteristics of habituation
Rankin, Catharine H; Abrams, Thomas; Barry, Robert J; Bhatnagar, Seema; Clayton, David F; Colombo, John; Coppola, Gianluca; Geyer, Mark A; Glanzman, David L; Marsland, Stephen; McSweeney, Frances K; Wilson, Donald A; Wu, Chun-Fang; Thompson, Richard F
2009 Sep;92(2):135-138, Neurobiology of learning & memory
The most commonly cited descriptions of the behavioral characteristics of habituation come from two papers published almost 40 years ago [Groves, P. M., & Thompson, R. F. (1970). Habituation: A dual-process theory. Psychological Review, 77, 419-450; Thompson, R. F., & Spencer, W. A. (1966). Habituation: A model phenomenon for the study of neuronal substrates of behavior. Psychological Review, 73, 16-43]. In August 2007, the authors of this review, who study habituation in a wide range of species and paradigms, met to discuss their work on habituation and to revisit and refine the characteristics of habituation. This review offers a re-evaluation of the characteristics of habituation in light of these discussions. We made substantial changes to only a few of the characteristics, usually to add new information and expand upon the description rather than to substantially alter the original point
— id: 90055, year: 2009, vol: 92, page: 135, stat: Journal Article,

Development and Testing of a Neural Recording System for Chemosensory Behavioral Neuroscience
Rennaker, R; Wilson, D
2009 SEP ;34(7):A70-A70, Chemical Senses
— id: 101943, year: 2009, vol: 34, page: A70, stat: Journal Article,

Auditory stimulation dishabituates olfactory responses via noradrenergic cortical modulation
Smith, Jonathan J; Shionoya, Kiseko; Sullivan, Regina M; Wilson, Donald A
2009 ;2009:754014-754014, Neural Plasticity
Dishabituation is a return of a habituated response if context or contingency changes. In the mammalian olfactory system, metabotropic glutamate receptor mediated synaptic depression of cortical afferents underlies short-term habituation to odors. It was hypothesized that a known antagonistic interaction between these receptors and norepinephrine ss-receptors provides a mechanism for dishabituation. The results demonstrate that a 108 dB siren induces a two-fold increase in norepinephrine content in the piriform cortex. The same auditory stimulus induces dishabituation of odor-evoked heart rate orienting bradycardia responses in awake rats. Finally, blockade of piriform cortical norepinephrine ss-receptors with bilateral intracortical infusions of propranolol (100 microM) disrupts auditory-induced dishabituation of odor-evoked bradycardia responses. These results provide a cortical mechanism for a return of habituated sensory responses following a cross-modal alerting stimulus
— id: 109082, year: 2009, vol: 2009, page: 754014, stat: Journal Article,

Olfactory Perceptual Correlates of b-Amyloid Plaque Burden in Alzheimer's Disease Mouse Models
Wesson, DW; Levy, E; Nixon, RA; Wilson, DA
2009 SEP ;34(7):A26-A27, Chemical Senses
— id: 101941, year: 2009, vol: 34, page: A26, stat: Journal Article,

The Nose is Just the Beginning: Patterns, Objects and Experience in Olfaction
Wilson, DA
2009 SEP ;34(7):A14-A14, Chemical Senses
— id: 101940, year: 2009, vol: 34, page: A14, stat: Journal Article,

Olfaction as a model system for the neurobiology of mammalian short-term habituation
Wilson, Donald A
2009 Sep;92(2):199-205, Neurobiology of learning & memory
Olfaction represents an ideal model system for the study of mammalian habituation given that it is an anatomically relatively simple system with strong reciprocal connections to the limbic system, driving both reflexive and non-reflexive (motivated) behaviors that are easily quantifiable. Data are reviewed here demonstrating short-term habituation of the odor-evoked heart-rate orienting reflex described according to the criteria for habituation outlined by Thompson and Spencer [Thompson, R. F., & Spencer, W. A. (1966). Habituation: A model phenomenon for the study of neuronal substrates of behavior. Psychological Reviews, 73(1), 16-43]. A necessary and sufficient mechanism of short-term habituation is then described, which involves a metabotropic glutamate receptor mediated depression of afferent input to the piriform (primary olfactory) cortex. Finally, evidence for, and a mechanisms of, dishabituation of the orienting reflex and cortical adaptation are described
— id: 94317, year: 2009, vol: 92, page: 199, stat: Journal Article,

Pattern separation and completion in olfaction
Wilson, Donald A
2009 Jul;1170:306-312, Annals of the New York Academy of Sciences
The nervous system must provide a mechanism for very precise discrimination of differing patterns of activity, yet at the same time, there must be a mechanism for generalization to prevent all experiences from being independent and novel. Pattern separation and completion by cortical circuits contribute to these processes, respectively. Based on theoretical and computational models of the piriform cortex and experimental designs developed for hippocampal spatial memory, we provide evidence for pattern separation and completion in the olfactory system and demonstrate the predictive power of these two processes for behavioral odor perception
— id: 101647, year: 2009, vol: 1170, page: 306, stat: Journal Article,

Chemoreception scientists gather under the Florida sun: The 31st Annual Association for Chemoreception Sciences meeting
Wilson, Donald A; Baker, Harriet; Brunjes, Peter; Gilbertson, Timothy A; Hermer, Linda; Hill, David L; Matsunami, Hiroaki; Meredith, Michael; Mistretta, Charlotte M; Smeets, Monique A M; Stowers, Lisa; Zhuang, Hanyi
2009 Aug;1170 Suppl 1:1-11, Annals of the New York Academy of Sciences
The 31st Annual Association for Chemoreception Sciences (AChemS) met in Sarasota, Florida April 22-26, 2009, attracting approximately 600 registrants and nearly 400 abstracts. In addition to poster and platform presentations, the program offered symposia, special lectures, and various National Institutes of Health (NIH)-sponsored workshops, including one on computational approaches to olfaction
— id: 102935, year: 2009, vol: 1170 Suppl 1, page: 1, stat: Journal Article,

Sniffing out a function for prion proteins
Wilson, Donald A; Nixon, Ralph A
2009 Jan;12(1):7-8, Nature neuroscience
— id: 94316, year: 2009, vol: 12, page: 7, stat: Journal Article,

Olfactory perceptual stability and discrimination
Barnes, Dylan C; Hofacer, Rylon D; Zaman, Ashiq R; Rennaker, Robert L; Wilson, Donald A
2008 Dec;11(12):1378-1380, Nature neuroscience
No two roses smell exactly alike, but our brain accurately bundles these variations into a single percept 'rose'. We found that ensembles of rat olfactory bulb neurons decorrelate complex mixtures that vary by as little as a single missing component, whereas olfactory (piriform) cortical neural ensembles perform pattern completion in response to an absent component, essentially filling in the missing information and allowing perceptual stability. This piriform cortical ensemble activity predicts olfactory perception
— id: 90054, year: 2008, vol: 11, page: 1378, stat: Journal Article,

Neurobehavioral consequences of cortical adaptation disruption during ontogeny
Bell, Heather; Chenoweth, Brian; Wilson, Donald A
2008 Nov 7;445(1):47-52, Neuroscience letters
Filtering of redundant or stable inputs is a critical function of all sensory pathways. Normal sensory gating can allow processing resources to be differentially devoted to changing or otherwise biologically significant stimuli. In olfaction, short-term odor habituation is mediated by a metabotropic glutamate receptor (mGluR)-mediated depression of afferent synapses in the piriform cortex. Given the role of early experience in shaping cortical function and anatomy, the present experiments examined the effects of chronic habituation disruption during development on behavior and local circuit anatomy. Rats were chronically intra-cerebrally infused with the mGluR group III antagonist (RS)-a-cyclopropyl-4-phosphonophenylglycine (CPPG) during early development. The results demonstrated that early onset mGluRIII blockade resulted in a long-lasting decrement in odor habituation compared to controls, evident for at least 2 weeks post-infusion offset. Odor investigation time in the youngest animals was correlated with cortical laminar thickness, though the long-lasting behavioral effect showed no such correlation. No changes in apical dendritic spine density in the piriform cortex were detected. Combined with previous work, these results suggest that sensory gating disruption during development can have both immediate and long-lasting effects on sensory-guided behavior
— id: 90057, year: 2008, vol: 445, page: 47, stat: Journal Article,

The 15th International Symposium on Olfaction and Taste
McClintock, Timothy S; Wilson, Donald A; Munger, Steven D; Geran, Laura; Herness, Scott
2008 Oct;33(8):735-738, Chemical Senses
— id: 90056, year: 2008, vol: 33, page: 735, stat: Journal Article,

Distinct neural mechanisms mediate olfactory memory formation at different timescales
McNamara, Ann Marie; Magidson, Phillip D; Linster, Christiane; Wilson, Donald A; Cleland, Thomas A
2008 Mar;15(3):117-125, Learning & memory
Habituation is one of the oldest forms of learning, broadly expressed across sensory systems and taxa. Here, we demonstrate that olfactory habituation induced at different timescales (comprising different odor exposure and intertrial interval durations) is mediated by different neural mechanisms. First, the persistence of habituation memory is greater when mice are habituated on longer timescales. Second, the specificity of the memory (degree of cross-habituation to similar stimuli) also depends on induction timescale. Third, we demonstrate a pharmacological double dissociation between the glutamatergic mechanisms underlying short- and long-timescale odor habituation. LY341495, a class II/III metabotropic glutamate receptor antagonist, blocked habituation only when the induction timescale was short. Conversely, MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, prevented habituation only when the timescale was long. Finally, whereas short-timescale odor habituation is mediated within the anterior piriform cortex, infusion of MK-801 into the olfactory bulbs prevented odor habituation only at longer timescales. Thus, we demonstrate two neural mechanisms underlying simple olfactory learning, distinguished by their persistence and specificity, mediated by different olfactory structures and pharmacological effectors, and differentially utilized based solely on the timescale of odor presentation
— id: 94319, year: 2008, vol: 15, page: 117, stat: Journal Article,

Developmental emergence of fear learning corresponds with changes in amygdala synaptic plasticity
Thompson, Jason V; Sullivan, Regina M; Wilson, Donald A
2008 Mar 20;1200C:58-65, Brain research
Mother-infant attachment is facilitated in altricial rodents through unique neural mechanisms that include impaired neonatal fear conditioning until the time that pups first begin to leave the nest (sensitive period). Here, we confirmed the developmental emergence of odor fear conditioning in neonatal rat pups, and examined synaptic plasticity of inputs to the basolateral amygdala in vitro. Coronal slices through the amygdala were obtained from sensitive (<10 days) and post-sensitive (>10, <19 days) period pups. Field potentials were recorded in the basolateral amygdala in response to stimulation of either the external capsule (neocortical inputs) or fibers from the cortical nucleus of the amygdala (olfactory inputs). The effects of tetanic stimulation were examined in each pathway. In both pathways, tetanic stimulation induce significant long-term synaptic plasticity in post-sensitive period pups, but no significant plasticity in sensitive period pups incapable of learning odor aversions. GABA(A) receptor blockade in post-sensitive period slices reverts synaptic plasticity to sensitive period characteristics. The results suggest that sensitive period deficits in fear conditioning may be related to impaired amygdala synaptic plasticity and the immature state of GABAergic inhibition and/or its modulation in the neonatal amygdala
— id: 78571, year: 2008, vol: 1200C, page: 58, stat: Journal Article,

Neurobiology of a simple memory
Wilson, Donald A; Linster, Christiane
2008 Jul;100(1):2-7, Journal of neurophysiology
Habituation is one of the simplest forms of memory, yet its neurobiological mechanisms remain largely unknown in mammalian systems. This review summarizes recent multidisciplinary analyses of the neurobiology of mammalian odor habituation including in vitro and in vivo synaptic physiology, sensory physiology, behavioral pharmacology, and computational modeling approaches. The findings show that a metabotropic glutamate receptor-mediated depression of afferent synapses to the olfactory cortex is necessary and perhaps sufficient to account for cortical sensory adaptation and short-term behavioral habituation. Furthermore, long-term habituation is an N-methyl-d-aspartate (NMDA) receptor-dependent process within the olfactory bulb. Thus there is both a pharmacological and anatomical distinction between short-term and long-term memory for habituation. The differential locus of change underlying short- and long-term memory leads to predictable differences in their behavioral characteristics, such as specificity
— id: 94318, year: 2008, vol: 100, page: 2, stat: Journal Article,

Synaptic adaptation and odor-background segmentation
Linster, Christiane; Henry, Lauren; Kadohisa, Mikiko; Wilson, Donald A
2007 Mar;87(3):352-360, Neurobiology of learning & memory
Habituation is a form of non-associative memory that plays an important role in filtering stable or redundant inputs. The present study examines the contribution of habituation and cortical adaptation to odor-background segmentation. Segmentation of target odorants from background odorants is a fundamental computational requirement for the olfactory system. Recent electrophysiological data have shown that odor specific adaptation in piriform cortex neurons, mediated at least partially by synaptic adaptation between the olfactory bulb outputs and piriform cortex pyramidal cells, may provide an ideal mechanism for odor-background segmentation. This rapid synaptic adaptation acts as a filter to enhance cortical responsiveness to changing stimuli, while reducing responsiveness to static, potentially background stimuli. Using previously developed computational models of the olfactory system, we here show how synaptic adaptation at the olfactory bulb input to the piriform cortex, as demonstrated electrophysiologically, creates odor specific adaptation. We show how this known feature of olfactory cortical processing can contribute to adaptation to a background odor and to odor-background segmentation. We then show in a behavioral experiment that the odor-background segmentation is perceptually important and functions at the same time-scale as the synaptic adaptation observed between the olfactory bulb and cortex
— id: 94323, year: 2007, vol: 87, page: 352, stat: Journal Article,

Olfactory system modulation of hippocampal cell death
Pope, Kenneth; Wilson, Donald A
2007 Jul 5;422(1):13-17, Neuroscience letters
The hippocampal dentate gyrus is a major recipient of olfactory input in rodents, via connections from the olfactory (piriform) cortex and the olfactory bulb to the entorhinal cortex. Given this connectivity and the known role of activity in dentate gyrus granule cell survival, the present experiment examined the immediate effects of loss of olfactory input to the hippocampus on apoptosis. Adults rats underwent unilateral or bilateral olfactory bulb ablations (OBX), and allowed to recover 24-72 h before the piriform cortex and hippocampal dentate gyrus were processed for terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling [TUNEL] of apoptotic cells. OBX transiently increased TUNEL-positive cells in the ipsilateral piriform cortex and dentate gyrus. Increased TUNEL-labeling was apparent within 24h in both structures, but was more extensive and prolonged in piriform cortex. The results suggest a trans-synaptic regulation of cell survival through at least two synapses
— id: 94321, year: 2007, vol: 422, page: 13, stat: Journal Article,

Spatial and temporal distribution of odorant-evoked activity in the piriform cortex
Rennaker, Robert L; Chen, Chien-Fu F; Ruyle, Andrea M; Sloan, Andrew M; Wilson, Donald A
2007 Feb 14;27(7):1534-1542, Journal of neuroscience
Despite a remarkably precise spatial representation of odorant stimuli in the early stages of olfactory processing, the projections to the olfactory (piriform) cortex are more diffuse and show characteristics of a combinatorial array, with extensive overlap of afferent inputs and widespread intracortical association connections. Furthermore, although there is increasing evidence for the importance of temporal structure in olfactory bulb odorant-evoked output, little is known about how this temporal patterning is translated within cortical neural ensembles. The present study used multichannel electrode arrays and paired single-unit recordings in rat anterior piriform cortex to test several predictions regarding ensemble coding in this system. The results indicate that odorants evoke activity in a spatially scattered ensemble of anterior piriform cortex neurons, and the ensemble activity includes a rich temporal structure. The most pronounced discrimination between different odorants by cortical ensembles occurs during the first inhalation of a 2 s stimulus. The distributed spatial and temporal structure of cortical activity is present at both global and local scales, with neighboring single units contributing to coding of different odorants and active at different phases of the respiratory cycle. Finally, cross-correlogram analyses suggest that cortical unit activity reflects not only afferent input from the olfactory bulb but also intrinsic activity within the intracortical association fiber system. These results provide direct evidence for predictions stemming from anatomical- and theoretical-based models of piriform cortex
— id: 94322, year: 2007, vol: 27, page: 1534, stat: Journal Article,

Odour perception: an object-recognition approach
Stevenson, Richard J; Wilson, Donald A
2007 ;36(12):1821-1833, Perception
Object recognition is a crucial component of both visual and auditory perception. It is also critical for olfaction. Most odours are composed of 10s or 100s of volatile components, yet they are perceived as unitary perceptual events against a continually shifting olfactory background (i.e. figure-ground segregation). We argue here that this occurs by rapid central adaptation to background odours combined with a pattern-matching system to recognise discrete sets of spatial and temporal olfactory features-an odour object. We present supporting neuropsychological, learning, and developmental evidence and then describe the neural circuitry which underpins this. The vagaries of an object-recognition approach are then discussed, with emphasis on the putative importance of memory, multimodal representations, and top-down processing
— id: 94320, year: 2007, vol: 36, page: 1821, stat: Journal Article,

Olfactory cortical adaptation facilitates detection of odors against background
Kadohisa, Mikiko; Wilson, Donald A
2006 Mar;95(3):1888-1896, Journal of neurophysiology
Detection and discrimination of odors generally, if not always, occurs against an odorous background. On any given inhalation, olfactory receptor neurons will be activated by features of both the target odorant and features of background stimuli. To identify a target odorant against a background therefore, the olfactory system must be capable of grouping a subset of features into an odor object distinct from the background. Our previous work has suggested that rapid homosynaptic depression of afferents to the anterior piriform cortex (aPCX) contributes to both cortical odor adaptation to prolonged stimulation and habituation of simple odor-evoked behaviors. We hypothesize here that this process may also contribute to figure-ground separation of a target odorant from background stimulation. Single-unit recordings were made from both mitral/tufted cells and aPCX neurons in urethan-anesthetized rats and mice. Single-unit responses to odorant stimuli and their binary mixtures were determined. One of the odorants was randomly selected as the background and presented for 50 s. Forty seconds after the onset of the background stimulus, the second target odorant was presented, producing a binary mixture. The results suggest that mitral/tufted cells continue to respond to the background odorant and, when the target odorant is presented, had response magnitudes similar to that evoked by the binary mixture. In contrast, aPCX neurons filter out the background stimulus while maintaining responses to the target stimulus. Thus the aPCX acts as a filter driven most strongly by changing stimuli, providing a potential mechanism for olfactory figure-ground separation and selective reading of olfactory bulb output
— id: 94327, year: 2006, vol: 95, page: 1888, stat: Journal Article,

Separate encoding of identity and similarity of complex familiar odors in piriform cortex
Kadohisa, Mikiko; Wilson, Donald A
2006 Oct 10;103(41):15206-15211, Proceedings of the National Academy of Sciences of the United States of America
Piriform cortical circuits are hypothesized to form perceptions from responses to specific odorant features, but the anterior piriform cortex (aPCX) and posterior piriform cortex (pPCX) differ markedly in their anatomical organization, differences that could lead to distinct roles in odor encoding. Here, we tested whether experience with a complex odorant mixture would modify encoding of the mixture and its components in aPCX and pPCX. Rats were exposed to an odorant mixture and its components in a go/no-go rewarded odor discrimination task. After reaching behavioral performance criterion, single-unit recordings were made from the aPCX and pPCX in these rats and in odor-naive, control, urethane-anesthetized rats. After odor experience, aPCX neurons were more narrowly tuned to the test odorants, and there was a decorrelation in aPCX population responses to the mixture and its components, suggesting a more distinct encoding of the familiar mixture from its components. In contrast, pPCX neurons were more broadly tuned to the familiar odorants, and pPCX population responses to the mixture and its components became more highly correlated, suggesting a pPCX encoding of similarity between familiar stimuli. The results suggest aPCX and pPCX play different roles in the processing of familiar odors and are consistent with an experience-dependent encoding (perceptual learning) of synthetic odorant identity in aPCX and an experience-dependent encoding of odor similarity or odor quality in pPCX
— id: 94324, year: 2006, vol: 103, page: 15206, stat: Journal Article,

Dual circuitry for odor-shock conditioning during infancy: corticosterone switches between fear and attraction via amygdala
Moriceau, Stephanie; Wilson, Donald A; Levine, Seymour; Sullivan, Regina M
2006 Jun 21;26(25):6737-6748, Journal of neuroscience
Rat pups must learn maternal odor to support attachment behaviors, including nursing and orientation toward the mother. Neonates have a sensitive period for rapid, robust odor learning characterized by increased ability to learn odor preferences and decreased ability to learn odor aversions. Specifically, odor-0.5 mA shock association paradoxically causes an odor preference and coincident failure of amygdala activation in pups until postnatal day 10 (P10). Because sensitive-period termination coincides with a declining 'stress hyporesponsive period' when corticosterone release is attenuated, we explored the role of corticosterone in sensitive-period termination. Odor was paired with 0.5 mA shock in either sensitive-period (P8) or postsensitive-period (P12) pups while manipulating corticosterone. We then assessed preference/aversion learning and the olfactory neural circuitry underlying its acquisition. Although sensitive-period control paired odor-shock pups learned an odor preference without amygdala participation, systemic (3 mg/kg, i.p.; 24 h and 30 min before training) or intra-amygdala corticosterone (50 or 100 ng; during training) permitted precocious odor-aversion learning and evoked amygdala neural activity similar to that expressed by older pups. In postsensitive-period (P12) pups, control paired odor-shock pups showed an odor aversion and amygdala activation, whereas corticosterone-depleted (adrenalectomized) paired odor-shock pups showed odor-preference learning and activation of an odor learning circuit characteristic of the sensitive period. Intra-amygdala corticosterone receptor antagonist (0.3 ng; during training) infused into postsensitive-period (P12) paired odor-shock pups also showed odor-preference learning. These results suggest corticosterone is important in sensitive-period termination and developmental emergence of olfactory fear conditioning, acting via the amygdala as a switch between fear and attraction. Because maternal stimulation of pups modulates the pups' endogenous corticosterone, this suggests maternal care quality may alter sensitive-period duration
— id: 78556, year: 2006, vol: 26, page: 6737, stat: Journal Article,

Relative medial and dorsal cortex volume in relation to sex differences in spatial ecology of a snake population
Roth, Eric D; Lutterschmidt, William I; Wilson, Donald A
2006 ;67(2):103-110, Brain behavior & evolution
In non-avian reptiles the medial and dorsal cortices are putative homologues of the hippocampal formation in mammals and birds. Studies on mammals and birds commonly report neuro-ecological correlations between hippocampal volume and aspects of spatial ecology. We examined the relationship between putative homologous cortical volumes and spatial use in a population of the squamate reptile, Agkistrodon piscivorus, that exhibits sex differences in spatial use. Do male A. piscivorus that inhabit larger home ranges than females also have larger putative hippocampal volumes? Male and female brains were sectioned and digitized to quantify regional cortical volumes. Although sex differences in dorsal cortex volume were not observed, males had a significantly larger medial cortex relative to telencephalon volume. Similar to studies on mammals and birds, relative hippocampal or medial cortex volume was positively correlated with patterns of spatial use. We demonstrate volumetric sex differences within a reptilian putative hippocampal homologue
— id: 94328, year: 2006, vol: 67, page: 103, stat: Journal Article,

The International Society for Developmental Psychobiology annual meeting symposium: Impact of early life experiences on brain and behavioral development
Sullivan, Regina; Wilson, Donald A; Feldon, Joram; Yee, Benjamin K; Meyer, Urs; Richter-Levin, Gal; Avi, Avital; Michael, Tsoory; Gruss, Michael; Bock, Jorg; Helmeke, Carina; Braun, Katharina
2006 Nov;48(7):583-602, Developmental psychobiology
Decades of research in the area of developmental psychobiology have shown that early life experience alters behavioral and brain development, which canalizes development to suit different environments. Recent methodological advances have begun to identify the mechanisms by which early life experiences cause these diverse adult outcomes. Here we present four different research programs that demonstrate the intricacies of early environmental influences on behavioral and brain development in both pathological and normal development. First, an animal model of schizophrenia is presented that suggests prenatal immune stimulation influences the postpubertal emergence of psychosis-related behavior in mice. Second, we describe a research program on infant rats that demonstrates how early odor learning has unique characteristics due to the unique functioning of the infant limbic system. Third, we present work on the rodent Octodon degus, which shows that early paternal and/or maternal deprivation alters development of limbic system synaptic density that corresponds to heightened emotionality. Fourth, a juvenile model of stress is presented that suggests this developmental period is important in determining adulthood emotional well being. The approach of each research program is strikingly different, yet all succeed in delineating a specific aspect of early development and its effects on infant and adult outcome that expands our understanding of the developmental impact of infant experiences on emotional and limbic system development. Together, these research programs suggest that the developing organism's developmental trajectory is influenced by environmental factors beginning in the fetus and extending through adolescence, although the specific timing and nature of the environmental influence has unique impact on adult mental health
— id: 78560, year: 2006, vol: 48, page: 583, stat: Journal Article,

Cortical contributions to olfaction: plasticity and perception
Wilson, Donald A; Kadohisa, Mikiko; Fletcher, Max L
2006 Aug;17(4):462-470, Seminars in cell & developmental biology
In most sensory systems, the sensory cortex is the place where sensation approaches perception. As described in this review, olfaction is no different. The olfactory system includes both primary and higher order cortical regions. These cortical structures perform computations that take highly analytical afferent input and synthesize it into configural odor objects. Cortical plasticity plays an important role in this synthesis and may underlie olfactory perceptual learning. Olfactory cortex is also involved in odor memory and association of odors with multimodal input and contexts. Finally, the olfactory cortex serves as an important sensory gate, modulating information throughput based on recent experience and behavioral state
— id: 94325, year: 2006, vol: 17, page: 462, stat: Journal Article,

Learning to smell: Olfactory perception from neurobiology to behavior
Wilson, Donald A; Stevenson, Richard J
Baltimore, MD : Johns Hopkins University Press, 2006,
The traditional approach for understanding olfactory perception involves identifying how particular features of a chemical stimulus are represented in the olfactory system. This perspective is at odds with a growing body of evidence, from both neurobiology and psychology, which places primary emphasis on synthetic processing and experiential factors--perceptual learning--rather than on the structural features of the stimulus as critical for odor discrimination. We propose that experience and cortical plasticity play a critical, defining role in odor perception. The focus of this book is the nature and consequences of odor object perception. Exciting new findings in the psychophysics, neurophysiology, and functional anatomy of the olfactory system are brought together to support our thesis.
— id: 1403, year: 2006, vol: , page: , stat: ,

Cortical metabotropic glutamate receptors contribute to habituation of a simple odor-evoked behavior
Best, Aaron R; Thompson, Jason V; Fletcher, Max L; Wilson, Donald A
2005 Mar 9;25(10):2513-2517, Journal of neuroscience
Defining the circuits that are involved in production and cessation of specific behaviors is an ultimate goal of neuroscience. Short-term behavioral habituation is the response decrement observed in many behaviors that occurs during repeated presentation of non-reinforced stimuli. Within a number of invertebrate models of short-term behavioral habituation, depression of a defined synapse has been implicated as the mechanism. However, the synaptic mechanisms of short-term behavioral habituation have not been identified within mammals. We have shown previously that a presynaptic metabotropic glutamate receptor (mGluR)-dependent depression of synapses formed by olfactory bulb afferents to the piriform (olfactory) cortex significantly contributes to adaptation of cortical odor responses. Here we show that blockade of mGluRs within the olfactory cortex of awake, behaving rats diminishes habituation of a simple odor-induced behavior, strongly implicating a central mechanism for sensory gating in olfaction
— id: 140381, year: 2005, vol: 25, page: 2513, stat: Journal Article,

High-frequency oscillations are not necessary for simple olfactory discriminations in young rats
Fletcher, Max L; Smith, Abigail M; Best, Aaron R; Wilson, Donald A
2005 Jan 26;25(4):792-798, Journal of neuroscience
Individual olfactory bulb mitral/tufted cells respond preferentially to groups of molecularly similar odorants. Bulbar interneurons such as periglomerular and granule cells are thought to influence mitral/tufted odorant receptive fields through mechanisms such as lateral inhibition. The mitralgranule cell circuit is also important in the generation of the odor-evoked fast oscillations seen in the olfactory bulb local field potentials and hypothesized to be an important indicator of odor quality coding. Infant rats, however, lack a majority of these inhibitory interneurons until the second week of life. It is unclear if these developmental differences affect olfactory bulb odor coding or behavioral odor discrimination. The following experiments are aimed at better understanding odor coding and behavioral odor discrimination in the developing olfactory system. Single-unit recordings from mitral/tufted cells and local field-potential recordings from both the olfactory bulb and anterior piriform cortex were performed in freely breathing urethane-anesthetized rats (postnatal day 7 to adult). Age-dependent behavioral odor discrimination to a homologous series of ethyl esters was also examined using a cross-habituation paradigm. Odorants were equated in all experiments for concentration (150 ppm) using a flow dilution olfactometer. In concordance with the reduced interneuron population, local field potentials in neonates lacked detectable odor-evoked gamma-frequency oscillations that were observed in mature animals. However, mitral/tufted cell odorant receptive fields and behavioral odor discrimination did not significantly change, despite known substantial changes in local circuitry and neuronal populations, over the age range examined. The results suggest that high-frequency local field-potential oscillations do not reflect processes critical for simple odor discrimination
— id: 140382, year: 2005, vol: 25, page: 792, stat: Journal Article,

Odor perception is dynamic: consequences for interpretation of odor maps
Wilson, Donald A
2005 Jan;30 Suppl 1:i105-i106, Chemical Senses
— id: 140388, year: 2005, vol: 30 Suppl 1, page: i105, stat: Journal Article,

The role of metabotropic glutamate receptors and cortical adaptation in habituation of odor-guided behavior
Yadon, Carly A; Wilson, Donald A
2005 Nov-Dec;12(6):601-605, Learning & memory
Decreases in behavioral investigation of novel stimuli over time may be mediated by a variety of factors including changes in attention, internal state, and motivation. Sensory cortical adaptation, a decrease in sensory cortical responsiveness over prolonged stimulation, may also play a role. In olfaction, metabotropic glutamate receptors on cortical afferent pre-synaptic terminals have been shown to underlie both cortical sensory adaptation and habituation of odor-evoked reflexes. The present experiment examined whether blockade of sensory cortical adaptation through bilateral infusion of the group III metabotropic glutamate receptor antagonist cyclopropyl-4-phosphonophenylglycine (CPPG) into the anterior piriform cortex could reduce habituation of a more complex odor-driven behavior such as investigation of a scented object or a conspecific. The results demonstrate that time spent investigating a scented jar, or a conspecific, decreases over the course of a continuous 10 minute trial. Acute infusion of CPPG bilaterally into the anterior piriform cortex significantly enhanced the time spent investigating the scented jar compared to investigation time in control rats, without affecting overall behavioral activity levels. Infusions into the brain outside of the piriform cortex were without effect. CPPG infusion into the piriform cortex also produced an enhancement of time spent investigating a conspecific, although this effect was not significant
— id: 94326, year: 2005, vol: 12, page: 601, stat: Journal Article,

Coordinate Synaptic Mechanisms Contributing to Olfactory Cortical Adaptation
Best, Aaron R; Wilson, Donald A
2004 ;24(3):652-660 Feb, Journal of neuroscience
Anterior piriform cortex (aPCX) neurons rapidly filter repetitive odor stimuli despite relatively maintained input from mitral cells. This cortical adaptation is correlated with short-term depression of afferent synapses, in vivo. The purpose of this study was to elucidate mechanisms underlying this nonassociative neural plasticity using in vivo and in vitro preparations and to determine its role in cortical odor adaptation. Lateral olfactory tract (LOT)-evoked responses were recorded in rat aPCX coronal slices. Extracellular and intraceUular potentials were recorded before and after simulated odor stimulation of the LOT. Results were compared with in vivo intracellular recordings from aPCX layer II/III neurons and field recordings in urethane-anesthetized rats stimulated with odorants. Similar to the odor specificity of cortical odor adaptation in vivo, there was no evidence of heterosynaptic depression between independent inputs in vitro. Importantly, in line with the in vitro findings, both adaptation of odor responses in the beta (15-35 Hz) spectral range and the associated synaptic depression can also be blocked by intracortical infusion of CPPG in vivo.
— id: 78621, year: 2004, vol: 24, page: 652, stat: Journal Article,

Neurobehavioral Development of Infant Learning and Memory: Implications for Infant Attachment
Roth, Tania L; Wilson, Donald A; Sullivan, Regina M
Advances in The study of behavior, Vol 34 San Diego, CA, US: Elsevier Academic Press, 2004,
(from the chapter) The environmental demands on an altricial newborn are simple: procure food, warmth, and protection from a caregiver, and rapidly form an attachment to the caregiver. While pheromones mediate this attachment in some species (reviewed in Bartoshuk and Beauchamp, 1994; Hudson and Distel, 1999; Schaal et al, 1995), other species use learning, with avian imprinting being one of the most widely known examples of the latter. Similar learning during infancy has also been documented in mammals such as the human (DeCasper and Fifer, 1980; Sullivan et al., 1991), sheep (Nowak and Lindsay, 1992; Nowak et al., 1997), and rat (reviewed in Hofer and Sullivan, 2001). While this infant learning shares many characteristics with adult learning, some of the neural structures supporting learning and memory consolidation in the adult are not yet fully developed in the infant, suggesting that the neural basis for learning and memory differs between infants and adults. In this article we present evidence that the infant's behavior and its brain are specifically designed to meet the demands of infancy and to ensure attachment to the caregiver.
— id: 4666, year: 2004, vol: , page: 103, stat: Chapter,

Plasticity in the olfactory system: lessons for the neurobiology of memory
Wilson, D A; Best, A R; Sullivan, R M
2004 Dec;10(6):513-524, Neuroscientist
We are rapidly advancing toward an understanding of the molecular events underlying odor transduction, mechanisms of spatiotemporal central odor processing, and neural correlates of olfactory perception and cognition. A thread running through each of these broad components that define olfaction appears to be their dynamic nature. How odors are processed, at both the behavioral and neural level, is heavily dependent on past experience, current environmental context, and internal state. The neural plasticity that allows this dynamic processing is expressed nearly ubiquitously in the olfactory pathway, from olfactory receptor neurons to the higher-order cortex, and includes mechanisms ranging from changes in membrane excitability to changes in synaptic efficacy to neurogenesis and apoptosis. This review will describe recent findings regarding plasticity in the mammalian olfactory system that are believed to have general relevance for understanding the neurobiology of memory
— id: 140354, year: 2004, vol: 10, page: 513, stat: Journal Article,

Fish smell. Focus on "Odorant specificity of single olfactory bulb neurons to amino acids in the channel catfish"
Wilson, Donald A
2004 Jul;92(1):38-39, Journal of neurophysiology
— id: 140392, year: 2004, vol: 92, page: 38, stat: Journal Article,

Acetylcholine and olfactory perceptual learning
Wilson, Donald A; Fletcher, Max L; Sullivan, Regina M
2004 Jan-Feb;11(1):28-34, Learning & memory
Olfactory perceptual learning is a relatively long-term, learned increase in perceptual acuity, and has been described in both humans and animals. Data from recent electrophysiological studies have indicated that olfactory perceptual learning may be correlated with changes in odorant receptive fields of neurons in the olfactory bulb and piriform cortex. These changes include enhanced representation of the molecular features of familiar odors by mitral cells in the olfactory bulb, and synthetic coding of multiple coincident odorant features into odor objects by cortical neurons. In this paper, data are reviewed that show the critical role of acetylcholine (Ach) in olfactory system function and plasticity, and cholinergic modulation of olfactory perceptual learning at both the behavioral and cortical level
— id: 78543, year: 2004, vol: 11, page: 28, stat: Journal Article,

A postnatal sensitive period for plasticity of cortical afferents but not cortical association fibers in rat piriform cortex
Best, A R; Wilson, D A
2003 Jan 24;961(1):81-87, Brain research
Male and female rats underwent unilateral naris occlusion or sham surgery on either post-natal day (PN) 1 or after PN30. Following at least 30 days of unilateral olfactory deprivation, rats were urethane anesthetized and recordings were made from anterior piriform cortex (aPCX). Shock stimulation of afferent fibers (lateral olfactory tract) and association/commissural fibers evoked field potentials in aPCX that were analyzed across groups and between ages. The results demonstrate that early-onset unilateral olfactory deprivation depresses field potentials evoked by stimulation of the deprived cortical afferent, while late-onset deprivation did not. In contrast, intracortical association fiber mediated field potentials in the deprived cortex were enhanced after both early-onset and late-onset deprivation. These results suggest differential developmental plasticity of afferent and association fiber pathways in paleocortex that mirrors that previously described in neocortical sensory systems
— id: 140402, year: 2003, vol: 961, page: 81, stat: Journal Article,

Olfactory bulb mitral-tufted cell plasticity: odorant-specific tuning reflects previous odorant exposure
Fletcher, Max L; Wilson, Donald A
2003 Jul 30;23(17):6946-6955, Journal of neuroscience
Olfactory system second-order neurons, mitral-tufted cells, have odorant receptive fields (ORFs) (molecular receptive ranges in odorant space for carbon chain length in organic odorant molecules). This study quantified several dimensions of these excitatory odorant receptive fields to novel odorants in rats and then examined the effects of passive odorant exposure on the shape of the ORF-tuning curve. ORFs for carbon chain length of novel ethyl esters (pure odorants that the animals had not been exposed to previously) were determined before and after a 50 sec prolonged exposure to one of the odorants. In response to novel odorants, quantitative analysis of mitral-tufted cell excitatory ORFs revealed that the median ORF width spanned 3-4 carbons, generally with a single-most excitatory odorant. Exposure to either the most excitatory odorant (ON-PEAK) or an odorant that was two carbons longer (OFF-PEAK) for 50 sec produced whole ORF suppression immediately after the end of the prolonged exposure, with the ON-PEAK exposure producing the greatest suppression. These results are consistent with a feature-detecting function for mitral-tufted cells. Redetermination of the ORF 15 and 60 min after the exposure revealed that OFF-PEAK exposure produced a reduction in responsiveness to the best odorant and an increase in responsiveness to the exposed odorant. In contrast, exposure to the ON-PEAK odorant or no odorant did not affect ORFs. Given that mitral-tufted cells receive exclusive excitatory input from olfactory receptor neurons expressing identical receptor proteins, it is hypothesized that experience-induced mitral-tufted cell ORF changes reflect modulation of lateral and centrifugal olfactory bulb circuits
— id: 140353, year: 2003, vol: 23, page: 6946, stat: Journal Article,

Trans-neuronal regulation of cortical apoptosis in the adult rat olfactory system
Leung, Carol Ho-Wing; Wilson, Donald A
2003 Sep 12;984(1-2):182-188, Brain research
Previous work has identified a population of neurons within the anterior piriform cortex that undergo rapid apoptosis following de-afferentation by olfactory bulbectomy in adult rats. The specific initiation signal for apoptosis in this paradigm is unknown, but may include an activity-dependent trans-neuronal cascade. The present report examined the effect of adult-onset unilateral naris occlusion, which reduces olfactory bulb afferent excitation of piriform cortex, on apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling [TUNEL]) in the rat anterior piriform cortex. Adult Long-Evans hooded rats received unilateral naris occlusion or a control manipulation and were sacrificed after 1, 5, 7, 10 or 20 days later. For comparison, a second group of rats received a unilateral bulbectomy and were sacrificed 24 h later. Counts of TUNEL-stained cell profiles were performed for layers I/II and layer III of the anterior piriform cortex ipsilateral and contralateral to the manipulation. The results confirmed that unilateral bulbectomy produced a dramatic increase in TUNEL labeling in layers I/II of the ipsilateral piriform cortex 24 h after bulbectomy. Unilateral naris closure also produced enhanced TUNEL labeling, although the magnitude of the effect was less than that produced by bulbectomy, and enhanced TUNEL labeling was apparent both ipsilateral and contralateral to the sealed naris compared to controls. Deprivation-induced TUNEL labeling was detectable by 24 h post-closure, peaked at 5 days and was no different from controls by 20 days post-closure. Neither bulbectomy nor naris closure affected TUNEL labeling in layer III. Together, these results suggest that there is a population of superficial cells in piriform cortex whose survival is tightly regulated by sensory input
— id: 140401, year: 2003, vol: 984, page: 182, stat: Journal Article,

Molecular biology of early olfactory memory
Sullivan, Regina M; Wilson, Donald A
2003 Jan-Feb;10(1):1-4, Learning & memory
— id: 78540, year: 2003, vol: 10, page: 1, stat: Journal Article,

Rapid, experience-induced enhancement in odorant discrimination by anterior piriform cortex neurons
Wilson, Donald A
2003 Jul;90(1):65-72, Journal of neurophysiology
Current views of odorant discrimination by the mammalian olfactory system suggest that the piriform cortex serves as a site of odor object synthesis. Given the enormous number of odorant feature combinations possible in nature, however, it seems unlikely that cortical synthetic receptive fields (RFs) are innate but rather require experience for their formation. The present experiment addressed two issues. First, we made a direct comparison of mitral/tufted cell and anterior piriform cortex (aPCX) neuron abilities to discriminate odorant mixtures from their components to further test whether aPCX neurons can treat collections of features different from the features themselves (synthetic coding). Second, we attempted to determine the minimum duration of experience necessary for formation of cortical synthetic RFs. Single-unit recordings were made from mitral/tufted cells and aPCX layer II/III neurons in urethan-anesthetized rats. Cross-habituation between novel binary mixtures and their novel components was used to determine odor discrimination abilities. The results suggest that after >/=50 s of experience with a binary mixture, aPCX neurons can discriminate the mixture from its components, whereas mitral/tufted cells cannot. However, when limited to 10 s of experience with the mixture, aPCX neurons appear similar to mitral/tufted cells and do not discriminate mixtures from components. These results suggest experience-dependent synthetic processing in aPCX and suggest an important role for perceptual learning in normal odor discrimination
— id: 140393, year: 2003, vol: 90, page: 65, stat: Journal Article,

Olfactory perceptual learning: the critical role of memory in odor discrimination
Wilson, Donald A; Stevenson, Richard J
2003 Sep;27(4):307-328, Neuroscience & biobehavioral reviews
The major problem in olfactory neuroscience is to determine how the brain discriminates one odorant from another. The traditional approach involves identifying how particular features of a chemical stimulus are represented in the olfactory system. However, this perspective is at odds with a growing body of evidence, from both neurobiology and psychology, which places primary emphasis on synthetic processing and experiential factors--perceptual learning--rather than on the structural features of the stimulus as critical for odor discrimination. In the present review of both psychological and sensory physiological data, we argue that the initial odorant feature extraction/analytical processing is not behaviorally/consciously accessible, but rather is a first necessary stage for subsequent cortical synthetic processing which in turn drives olfactory behavior. Cortical synthetic coding reflects an experience-dependent process that allows synthesis of novel co-occurring features, similar to processes used for visual object coding. Thus, we propose that experience and cortical plasticity are not only important for traditional associative olfactory memory (e.g. fear conditioning, maze learning, and delayed-match-to-sample paradigms), but also play a critical, defining role in odor discrimination
— id: 140338, year: 2003, vol: 27, page: 307, stat: Journal Article,

The fundamental role of memory in olfactory perception
Wilson, Donald A; Stevenson, Richard J
2003 May;26(5):243-247, Trends in neurosciences
Current emphasis on odorant physiochemical features as the basis for perception largely ignores the synthetic and experience-dependent nature of olfaction. Olfaction is synthetic, as mammals have only limited ability to identify elements within even simple odor mixtures. Furthermore, olfaction is experience-bound, as exposure alone can significantly affect the extent to which stimuli can be discriminated. We propose that early analytical processing of odors is inaccessible at the behavioral level and that all odors are initially encoded as 'objects' in the piriform cortex. Moreover, we suggest that odor perception is wholly dependent on the integrity of this memory system and that its loss severely impairs normal perception
— id: 140339, year: 2003, vol: 26, page: 243, stat: Journal Article,

Experience modifies olfactory acuity: acetylcholine-dependent learning decreases behavioral generalization between similar odorants
Fletcher, Max L; Wilson, Donald A
2002 Jan 15;22(2):RC201-RC201, Journal of neuroscience
Perceptual learning has been demonstrated in several thalamocortical sensory systems wherein experience enhances sensory acuity for trained stimuli. This perceptual learning is believed to be dependent on changes in sensory cortical receptive fields. Sensory experience and learning also modifies receptive fields and neural response patterns in the mammalian olfactory system; however, to date there has been little reported evidence of learned changes in behavioral olfactory acuity. The present report used a bradycardial orienting response and cross-habituation paradigm that allowed assessment of behavioral discrimination of nearly novel odorants, and then used the same paradigm to examine odorant discrimination after associative olfactory conditioning with similar or dissimilar odorants. The results demonstrate that associative conditioning can enhance olfactory acuity for odors that are the same as or similar to the learned odorant, but not for odors dissimilar to the learned odorant. Furthermore, scopolamine injected before associative conditioning can block the acquisition of this learned enhancement in olfactory acuity. These results could have important implications for mechanisms of olfactory perception and memory, as well as for correlating behavioral olfactory acuity with observed spatial representations of odorant features in the olfactory system
— id: 140383, year: 2002, vol: 22, page: RC201, stat: Journal Article,

Ontogeny of odor discrimination: a method to assess novel odor discrimination in neonatal rats
Fletcher, M; Wilson, D A
2001 Nov-Dec;74(4-5):589-593, Physiology & behavior
Recent research using molecular and functional imaging techniques has demonstrated a highly precise spatial representation of odor quality in the rodent olfactory bulb, which is enhanced by extensive lateral inhibitory circuitry. Much of this olfactory bulb circuitry develops postnatally in the rat, leading to the prediction that behavioral discrimination of odor quality may also emerge postnatally. However, currently no behavioral paradigm has been identified to test this prediction. The present report describes the expression and habituation of odor-evoked heart rate-orienting responses in neonatal rats. The results demonstrate that odor-evoked-orienting responses can be observed at least as early as postnatal day 4 (PN 4), and in those animals showing orienting responses, habituation is constant throughout the postnatal period. Furthermore, the results suggest that examination of cross-habituation using this paradigm can be used to explore odor discrimination ability in neonates. These results lay the foundation for future studies of precise mapping of the ontogeny of novel odor discrimination
— id: 140384, year: 2001, vol: 74, page: 589, stat: Journal Article,

Receptive fields in the rat piriform cortex
Wilson, D A
2001 Jun;26(5):577-584, Chemical Senses
Current models of odor discrimination in mammals involve molecular feature detection by a large family of diverse olfactory receptors, refinement of molecular feature extraction through precise projections of olfactory receptor neurons to the olfactory bulb to form an odor-specific spatial map of molecular features across glomerular layer, and synthesis of these features into odor objects within the piriform cortex. This review describes our recent work on odor and spatial receptive fields within the anterior piriform cortex and compares these fields with receptive fields of their primary afferent, olfactory bulb mitral/tufted cells. The results suggest that receptive fields in the piriform cortex are ensemble in nature, highly dynamic, and may contribute to odor discrimination and odor memory
— id: 140389, year: 2001, vol: 26, page: 577, stat: Journal Article,

Scopolamine enhances generalization between odor representations in rat olfactory cortex
Wilson, D A
2001 Sep-Oct;8(5):279-285, Learning & memory
Acetylcholine (ACh) has a critical, modulatory role in plasticity in many sensory systems. In the rat olfactory system, both behavioral and physiological data indicate that ACh may be required for normal odor memory and synaptic plasticity. Based on these data, neural network models have hypothesized that ACh muscarinic receptors reduce interference between learned cortical representations of odors within the piriform cortex. In this study, odor receptive fields of rat anterior piriform cortex (aPCX) single-units for alkane odors were mapped before and after either a systemic injection of the muscarinic receptor antagonist scopolamine (0.5 mg/kg) or aPCX surface application of 500 microM scopolamine (or saline/ACSF controls). Cross-habituation between alkanes differing by two to four carbons was then examined following a 50-sec habituating stimulus. The results demonstrate that neither aPCX spontaneous activity nor odor-evoked activity (receptive field) was affected by scopolamine, but that cross-habituation in aPCX neurons was enhanced significantly by either systemic or cortical scopolamine. These results indicate that scopolamine selectively enhances generalization between odor representations in aPCX in a simple memory task. Given that ACh primarily affects intracortical association fibers in the aPCX, the results support a role for the association system in odor memory and discrimination and indicate an important ACh modulatory control over this basic sensory process
— id: 140400, year: 2001, vol: 8, page: 279, stat: Journal Article,

Exposure to behaviourally relevant odour reveals differential characteristics in rat central olfactory pathways as studied through oscillatory activities
Chabaud, P; Ravel, N; Wilson, D A; Mouly, A M; Vigouroux, M; Farget, V; Gervais, R
2000 Oct;25(5):561-573, Chemical Senses
This study investigated how changes in nutritional motivation modulate odour-related oscillatory activities at several levels of the olfactory pathway in non-trained rats. Local field potential recordings were obtained in freely moving animals in the olfactory bulb (OB), anterior and posterior parts of the piriform cortex (APC and PPC respectively) and lateral entorhinal cortex (EC). Dynamic signal analysis detected changes in power during odour presentation for several frequency bands The results showed that in most cases odour presentation was associated with changes in a wide 15-90 Hz frequency band of activity in each olfactory structure. However, nutritional state modulated initial responses to food odour (FO) in the OB and EC selectively in the 15-30 Hz frequency band. Changes in nutritional state also modulated responses to repeated FO stimuli. Habituation was expressed differentially across structures with a clear dissociation between the two parts of the piriform cortex. Finally, systemic injections of scopolamine (0.125 mg/kg) selectively blocked expression of the nutritional modulation in the OB found in the beta band. These results suggest that internal state can differentially modulate odour processing among different olfactory areas and point to a cholinergic-sensitive beta band oscillation during presentation of a behaviourally meaningful odorant
— id: 140390, year: 2000, vol: 25, page: 561, stat: Journal Article,

Good memories of bad events in infancy
Sullivan, R M; Landers, M; Yeaman, B; Wilson, D A
2000 Sep 7;407(6800):38-39, Nature
— id: 140356, year: 2000, vol: 407, page: 38, stat: Journal Article,

Association of an odor with activation of olfactory bulb noradrenergic beta-receptors or locus coeruleus stimulation is sufficient to produce learned approach responses to that odor in neonatal rats
Sullivan, R M; Stackenwalt, G; Nasr, F; Lemon, C; Wilson, D A
2000 Oct;114(5):957-962, Behavioral neuroscience
These experiments examined the sufficiency of pairing an odor with either intrabulbar activation of noradrenergic beta-receptors or pharmacological stimulation of the locus coeruleus to support learned odor preferences in Postnatal Day 6-7 rat pups. The results showed that pups exposed to odor paired with beta-receptor activation limited to the olfactory bulb (isoproterenol, 50 microM) displayed a conditioned approach response on subsequent exposure to that odor. Furthermore, putative stimulation of the locus coeruleus (2 microM idazoxan or 2 mM acetylcholine) paired with odor produced a subsequent preference for that odor. The effects of locus coeruleus stimulation could be blocked by a pretraining injection of the beta-receptor antagonist propranolol (20 mg/kg). Together these results suggest that convergence of odor input with norepinephrine release from the locus coeruleus terminals within the olfactory bulb is sufficient to support olfactory learning
— id: 140355, year: 2000, vol: 114, page: 957, stat: Journal Article,

Comparison of odor receptive field plasticity in the rat olfactory bulb and anterior piriform cortex
Wilson, D A
2000 Dec;84(6):3036-3042, Journal of neurophysiology
Recent work in the anterior piriform cortex (aPCX) has demonstrated that cortical odor receptive fields are highly dynamic, showing rapid changes of both firing rate and temporal patterning within relatively few inhalations of an odor, despite relatively maintained, patterned input from olfactory bulb mitral/tufted cells. The present experiment examined the precision (odor-specificity) of this receptive field plasticity and compared it with the primary cortical afferent, olfactory bulb mitral/tufted cells. Adult Long-Evans hooded rats, urethan anesthetized and freely breathing, were used for single-unit recording from mitral/tufted and aPCX layer II/III neurons. Partial mapping of receptive fields to alkane odors (pentane, heptane, and nonane) was performed before and immediately after habituation (50-s exposure) to one of the alkanes. The results demonstrated that odor habituation of aPCX responses was odor specific, with minimal cross-habituation between alkanes differing by as few as two carbons. Mitral/tufted cells, however, showed strong cross-habituation within the odor set with the most profound cross effects to carbon chains shorter than the habituating stimulus. The results suggest that although mitral/tufted cells and aPCX neurons have roughly similar odor receptive fields, aPCX neurons have significantly better odor discrimination within their receptive field. The results have important implications for understanding the underlying bases of receptive fields in olfactory system neurons and the mechanisms of odor discrimination and memory
— id: 140394, year: 2000, vol: 84, page: 3036, stat: Journal Article,

Odor specificity of habituation in the rat anterior piriform cortex
Wilson, D A
2000 Jan;83(1):139-145, Journal of neurophysiology
Exposure to odorants results in a rapid (<10 s) reduction in odor-evoked activity in the rat piriform cortex despite relatively maintained afferent input from olfactory bulb mitral cells. To further understand this form of cortical plasticity, a detailed analysis of its odor specificity was performed. Habituation of odor responses in anterior piriform cortex single units was examined in anesthetized, freely breathing rats. The magnitude of single-unit responses of layer II/III neurons to 2-s odor pulses were examined before and after a 50-s habituating stimulus of either the same or different odor. The results demonstrated that odor habituation was odor specific, with no significant cross-habituation between either markedly different single odors or between odors within a series of straight chain alkanes. Furthermore, habituation to binary 1:1 mixtures produced minimal cross-habituation to the components of that mixture. These latter results may suggest synthetic odor processing in the olfactory system, with novel odor mixtures processed as unique stimuli. Potential mechanisms of odor habituation in the piriform cortex must be able to account for the high degree of specificity of this effect
— id: 140395, year: 2000, vol: 83, page: 139, stat: Journal Article,

Trans-neuronal modification of anterior piriform cortical circuitry in the rat
Wilson, D A; Best, A R; Brunjes, P C
2000 Jan 24;853(2):317-322, Brain research
Long-Evans rats received unilateral naris closure on postnatal day 1 (PN1) or sham surgery. On PN30, brains were processed for anterograde horseradish peroxidase (HRP) labeling of lateral olfactory tract (LOT) fibers in anterior piriform cortex (aPCX) Layer Ia, Timm staining of association/commissural fibers in aPCX Layer Ib, or Golgi staining for reconstruction of aPCX semilunar cell dendrites. The results demonstrate that the width of aPCX Layer Ia was reduced ipsilateral to the sealed naris compared to undeprived controls. No significant change in Layer Ib was detected. Furthermore, semilunar cell dendrites were reduced by unilateral deprivation compared to undeprived controls. The reduction in dendritic tree size was localized to distal dendritic segments, roughly corresponding to Layer Ia. These results suggest an activity-dependent change in both the distribution of cortical afferents and in the dendritic field of their target cells. While these results are similar to those reported for other sensory systems, the relatively simple architecture and laminated organization of bilateral inputs to the aPCX make the olfactory system an ideal model system to examine experience-dependent synaptic reorganization and its functional consequences
— id: 140403, year: 2000, vol: 853, page: 317, stat: Journal Article,

Respiratory airflow pattern at the rat's snout and an hypothesis regarding its role in olfaction
Wilson, D A; Sullivan, R M
1999 Mar;66(1):41-44, Physiology & behavior
Respiratory airflow outside the external nares of the rat was mapped by monitoring temperature fluctuations with a thermistor and simultaneous piezoelectric monitoring of respiration-associated chestwall movement. The results demonstrated that both exhalation and inhalation airflow were directed laterally. Relatively little air exchange occurred anterior to the nares. These results suggest that the two nares of the rat take independent, bilateral samples of the odor environment. Combined with recent descriptions of laterally specific, spatial receptive fields in piriform cortical neurons, an hypothesis is outlined describing a mechanism of odor orientation in the rat involving comparisons of timing or intensity of bilateral odor stimulation
— id: 140357, year: 1999, vol: 66, page: 41, stat: Journal Article,

Habituation of odor responses in the rat anterior piriform cortex
Wilson, D A
1998 Mar;79(3):1425-1440, Journal of neurophysiology
Simultaneous recordings of main olfactory bulb (MOB) and anterior piriform cortex (aPCX) neuron responses to repeated and prolonged odor pulses were examined in freely breathing, urethan-anesthetized rats. Comparisons of odor responses were made between multi-unit recordings of MOB activity and single-unit extracellular and intracellular recordings of Layer II/III aPCX neurons. Odor stimuli consisted of either 2-s pulses repeated at 30-s intervals or a single, prolonged 50-s stimulus. Respiration rate was monitored throughout. MOB and aPCX neuron responses to odor were quantified both through firing frequency and through the temporal patterning of firing over the respiratory cycle. The results demonstrate that aPCX neurons habituate significantly more (faster) than MOB neurons with both repeated and prolonged stimulation paradigms. This enhanced habituation is expressed as both a decrease in aPCX firing despite maintained odor-evoked MOB input and as a decrease in aPCX respiratory cycle entrainment despite maintained MOB cyclic input. Intracellular aPCX recordings suggest that several mechanisms may be involved in this experience-induced change in aPCX function, including 1) decreased excitatory driveof aPCX neurons, 2) decreased excitability of aPCX neurons,and/or 3) enhancement in odor-evoked inhibition of aPCX neurons. These studies provide the initial basis for understanding the mechanisms of nonassociative plasticity in olfactory cortex
— id: 140397, year: 1998, vol: 79, page: 1425, stat: Journal Article,

Synaptic correlates of odor habituation in the rat anterior piriform cortex
Wilson, D A
1998 Aug;80(2):998-1001, Journal of neurophysiology
Responses of anterior piriform cortex layer II/III neurons to both odors and electrical stimulation of the lateral olfactory tract (LOT) were measured with intracellular recordings in urethan-anesthetized, freely breathing rats. Odor-evoked, respiration-entrained postsynaptic potentials (PSPs) rapidly habituated during a 50-s odor stimulus, then spontaneously recovered within 2 min of odor termination. Associated with the decrease in odor-evoked PSP amplitude was a decrease in the monosynaptic excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation of the LOT. The decrement in LOT-evoked EPSPs recovered with a time course similar to the odor response recovery. These results demonstrate that odor habituation is associated with a decrease in afferent synaptic efficacy in the anterior piriform cortex
— id: 140396, year: 1998, vol: 80, page: 998, stat: Journal Article,

Binaral interactions in the rat piriform cortex
Wilson, D A
1997 Jul;78(1):160-169, Journal of neurophysiology
Single-unit recordings were made from layer II/III anterior piriform cortex (aPCX) neurons in adult Wistar rats to examine odor response patterns to unilaterally and bilaterally delivered stimuli. Isoamyl acetate odor stimulation was presented either unilaterally through tubes inserted into the external nares, or bilaterally during unilateral olfactory bulb lidocaine infusions. Olfactory bulb multiunit or slow-wave activity was recorded simultaneously bilaterally to monitor selectivity of unilateral odor stimulation. The results demonstrate that 1) commissural input to aPCX neurons is sufficient to drive odor responses, and 2) aPCX neurons can be classified on the basis of spatial receptive field type. These receptive fields include cells that respond 1) selectively to ipsilateral stimulation, 2) selectively to contralateral stimulation, 3) to either ipsilateral or contralateral stimulation, and 4) selectively to bilateral stimulation. The potential functions of binaral convergence in the piriform cortex are discussed, and may include enhancement of perceived odor intensity and bilateral access to olfactory memory
— id: 140398, year: 1997, vol: 78, page: 160, stat: Journal Article,

NMDA-receptor modulation of lateral inhibition and c-fos expression in olfactory bulb
Wilson, D A; Sullivan, R M; Gall, C M; Guthrie, K M
1996 May 6;719(1-2):62-71, Brain research
Olfactory bulb primary output neurons, mitral/tufted cells, are glutamatergic and excite inhibitory interneurons, granule cells, by activation of both alpha-amino-3-hydroxy-5-methyl-ioxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) glutamate receptors. The data presented here demonstrate that the NMDA antagonists MK-801 and CGP39551, but not ketamine, significantly enhanced expression of c-fos mRNA by mitral cells as measured by in situ hybridization. All three antagonists significantly reduced mitral/tufted cell excitation of granule cells as measured with extracellular field potentials following antidromic stimulation of the lateral olfactory tract (LOT). In turn, the NMDA antagonists significantly reduced granule cell mediated feedback inhibition of mitral/tufted cells, as measured with field potential recordings of paired-pulse LOT stimulation, suppression of mitral/tufted cell single-unit spontaneous activity following LOT stimulation, and intracellularly recorded IPSP amplitude in mitral/tufted cells following LOT stimulation. While there was not a perfect correlation between the effects of the NMDA antagonists on c-fos mRNA expression and on inhibition, the results suggest that disinhibition of mitral/tufted cells accounts for the observed enhancement in c-fos mRNA expression induced by NMDA receptor antagonists
— id: 140359, year: 1996, vol: 719, page: 62, stat: Journal Article,

Early locus coeruleus lesions increase the density of beta-adrenergic receptors in the main olfactory bulb of rats
Woo, C C; Wilson, D A; Sullivan, R M; Leon, M
1996 Nov;14(7-8):913-919, International journal of developmental neuroscience
Norepinephrine is supplied to both deep and superficial layers of the olfactory bulb through dense projections from the locus coeruleus. Beta-adrenergic receptors are located in nearly all bulb laminae, with high-density foci of beta-1 and beta-2-adrenoceptors present in the glomerular layer. Early olfactory experiences that increase norepinephrine levels in the bulb also decrease the density of beta-1- and beta-2-adrenoceptors, as well as the number of high-density glomerular foci of beta-2-receptors. Changes in bulb norepinephrine levels, therefore, may affect the density of beta-adrenoceptors in the bulb. In the current study, we test this hypothesis by performing unilateral lesions of the locus coeruleus with 6-hydroxydopamine on postnatal day 4, and examining the density of beta-1- and beta-2-adrenergic receptors in the main olfactory bulb of the rat using 125I-labeled iodopindolol receptor autoradiography on postnatal day 19. Locus coeruleus destruction resulted in a statistically significant increase in the density of adrenergic receptors in the ipsilateral bulb compared to the contralateral bulb. Both beta-1- and beta-2-adrenoceptor subtypes increased in density with this manipulation, although the number of glomerular layer high-density beta-2 foci was not significantly different between the two bulbs. These results are consistent with the hypothesis that changes in olfactory bulb norepinephrine can regulate the density of beta-adrenergic receptors in the bulb
— id: 140358, year: 1996, vol: 14, page: 913, stat: Journal Article,

Dissociation of behavioral and neural correlates of early associative learning
Sullivan, R M; Wilson, D A
1995 May;28(4):213-219, Developmental psychobiology
Wistar rat pups were trained in an olfactory associative conditioning task on postnatal Day 6, 12, or 20. The training consisted of 20 pairings of a novel odor (peppermint) with footshock (1.5 mA, 1 s) with an intertrial interval of 3 min. Additional pups were trained in either unpaired or naive control conditions. On the day following training, pups were either tested for their behavioral response to the conditioned odor in a two-odor choice test, or injected with 14C-2-deoxyglucose and exposed to the odor for examination of olfactory bulb neural responses to the odor. The results demonstrate that, although pups at all ages learned to avoid the odor, only pups trained during the first postnatal week had a modified olfactory-bulb glomerular-layer response to the odor. These results suggest that although olfactory memory is correlated with modification of olfactory bulb glomerular layer function in newborns, these changes are not required for normal memory in older pups
— id: 140361, year: 1995, vol: 28, page: 213, stat: Journal Article,

NMDA receptors mediate expression of one form of functional plasticity induced by olfactory deprivation
Wilson, D A
1995 Apr 24;677(2):238-242, Brain research
Unilateral olfactory deprivation for the first 3 postnatal weeks results in an enhancement of granule cell mediated, feedback inhibition of mitral cells in the rat olfactory bulb. Granule cells are excited by mitral cells by both non-NMDA and NMDA receptors. The present report describes the effect of the NMDA antagonist MK-801 (0.75 mg/kg) on the expression of deprivation enhanced inhibition. The results demonstrate that (1) enhancement of lateral olfactory tract paired-pulse inhibition of evoked potentials in deprived bulbs was stimulus intensity dependent, with the greatest difference expressed at highest stimulus intensities; (2) MK-801 reduced inhibition in both undeprived and deprived bulbs in a stimulus intensity dependent manner, with the greatest reduction occurring at highest stimulus intensities; (3) MK-801 eliminated the stimulus intensity effect on inhibition in both groups; and (4) following MK-801, deprived bulbs showed the same or less inhibition than undeprived bulbs
— id: 140405, year: 1995, vol: 677, page: 238, stat: Journal Article,

The D2 antagonist spiperone mimics the effects of olfactory deprivation on mitral/tufted cell odor response patterns
Wilson, D A; Sullivan, R M
1995 Aug;15(8):5574-5581, Journal of neuroscience
Wistar rats had a single nare occluded on postnatal day 30, depriving the ipsilateral olfactory bulb of odor stimulation. The deprivation lasted for either 1-2 months (short-term) or 12 months (long-term). As previously reported, deprivation greatly reduced tyrosine hydroxylase immunoreactivity (the rate limiting enzyme for dopamine synthesis) in the glomerular layer of the ipsilateral olfactory bulb. The nare was then reopened and odor response patterns of mitral/tufted cells were examined. The proportion of mitral/tufted cell single-units responding to a single odor was enhanced by deprivation. Furthermore, the proportion of mitral/tufted cells responding to more than one odor was increased by deprivation, suggesting a decrease in discrimination. Finally, in undeprived bulbs, the dopamine D2 receptor antagonist spiperone mimicked the effects of deprivation on mitral/tufted cell odor response patterns. The results are interpreted as an activity-dependent dopamine modulation of lateral and feedback inhibition in the olfactory bulb, and are compared with similar events in the dark-adapted retina
— id: 140360, year: 1995, vol: 15, page: 5574, stat: Journal Article,

Post-activation potentiation and depression in the neocortex of the rat: II. Chronic preparations
Racine, R J; Teskey, G C; Wilson, D; Seidlitz, E; Milgram, N W
1994 Feb 21;637(1-2):83-96, Brain research
Although long-term potentiation (LTP) has been demonstrated in a number of subcortical sites in chronic preparations, there have been no demonstrations of LTP in the neocortex of chronic preparations. Even neocortical slice and acute preparations often require a drug-induced suppression of inhibition before LTP effects can be reliably induced. We have attempted to induce LTP in neocortical sites in 7 different experiments using chronically prepared adult rats. We were unable to obtain any evidence, even a trend, for the induction of LTP. The following manipulations were tested: (1) standard stimulation train parameters that have been shown to be highly effective in subcortical and hippocampal sites; (2) a 10-fold increase in the intra-train pulse durations; (3) variations in train pulse frequency (1 Hz to 300 Hz) and train duration (100 ms to 15 min); (4) co-activation of multiple inputs by stimulation of combinations of cortical sites or cortical and thalamic sites; (5) reduction of inhibition by administration of picrotoxin; 5) Housing of animals in an enriched environment; (6) utilization of the neocortical stimulation trains as a cue in a learning task; (7) application of pilocarpine to co-activate cholinergic systems. Although none of these manipulations produced LTP, the application of pilocarpine did facilitate the induction of a long-lasting depression effect. These findings contrast with the results obtained from anesthetized rats and from studies using brain slices, where LTP can be reliably induced. These results are discussed in light of other recent findings with respect to LTP and LTD effects
— id: 140406, year: 1994, vol: 637, page: 83, stat: Journal Article,

Post-activation potentiation in the neocortex: I. Acute preparations
Racine, R J; Wilson, D; Teskey, G C; Milgram, N W
1994 Feb 21;637(1-2):73-82, Brain research
Long-term potentiation is widely studied as a memory model, and has been demonstrated in a number of subcortical sites in both acute and chronic preparations. In the neocortex, however, most of the demonstrations of LTP have been in neocortical slice or acute preparations, and even these have often required a drug-induced attenuation of inhibition before the LTP could be reliably expressed. In this paper we show that LTP can be reliably expressed in adult rats in a number of neocortical sites, both ipsilateral and contralateral to the site of callosal stimulation. We also show that, when recording field potentials, LTP is expressed roughly equally at all cortical depths. In a third experiment, we monitored input/output (I/O), paired-pulse inhibition and short-term potentiation effects over the course of LTP induction. The ipsilateral responses were, as expected, of shorter latency and larger amplitude than contralateral responses. They also showed small spike-like components that correlated with cell discharge. Nevertheless, the contralateral responses tended to show the largest LTP effects. The paired pulse effect was mainly depression, lasting for up to 3000 ms, at both ipsilateral and control sites. The short-term potentiation components were best fit by two summed exponentials with time constants of about 70 s and 12 min. The LTP effect lasted at least two h which was the longest period monitored in these experiments
— id: 140407, year: 1994, vol: 637, page: 73, stat: Journal Article,

Neural coding and synaptic transmission: Participation exercises for introductory psychology
Reardon, Richard; Durso, Francis T; Wilson, Donald A
1994 ;21(2):96-99 Apr, Teaching of psychology
Describes 2 simulations of neural transmission for use in an introductory psychology class. The simulations illustrate the complex coding properties of a single neuron, including how excitatory and inhibitory postsynaptic potentials accumulate to produce an action potential. A follow-up exercise, using the framework of the children's game 'Musical Chairs,' illustrates synaptic transmission, including the effects of psychoactive drugs at the synapse. The effectiveness of the exercise was assessed in 8 sections of introductory psychology courses. Responses to a multiple-choice quiz administered 1 wk after the exercise suggest that the exercise improved students' understanding of the complexity of coding.
— id: 78622, year: 1994, vol: 21, page: 96, stat: Journal Article,

The locus coeruleus, norepinephrine, and memory in newborns
Sullivan, R M; Wilson, D A
1994 ;35(5-6):467-472, Brain research bulletin
Use of learned odor cues by newborn rats is critical for pup survival. Rat pups acquire approach responses to maternal odors through an associative conditioning mechanism. This learned behavioral response is accompanied by a modification of olfactory bulb neural response patterns to the learned odor. Both the behavioral and neural response changes involved and require norepinephrine release in the olfactory bulb. The source of this norepinephrine is the locus coeruleus. It is proposed that the unique response properties of the locus coeruleus during the early postnatal period in the rat may facilitate acquisition of these critical early memories
— id: 140365, year: 1994, vol: 35, page: 467, stat: Journal Article,

Bilateral 6-OHDA lesions of the locus coeruleus impair associative olfactory learning in newborn rats
Sullivan, R M; Wilson, D A; Lemon, C; Gerhardt, G A
1994 Apr 18;643(1-2):306-309, Brain research
On postnatal day 4 (PN4) Wistar rat pups were anesthetized and received bilateral infusions of 6-OHDA into the locus coeruleus or received vehicle infusions. On PN6 pups were trained in a classical conditioning paradigm with intra-oral milk infusions as the UCS and citral odor as the CS. Pups were trained in either 'paired', 'odor-only', 'milk-only' or 'backward' (milk then odor) conditions. On PN7 acquisition of a learned odor preference to the CS was tested in a two-odor choice test. HPLC analysis showed that locus coeruleus lesions significantly reduced olfactory bulb NE content but had no effect on olfactory bulb DA or 5-HT levels compared to controls. Pups receiving locus coeruleus lesions did not differ in behavioral response patterns during training compared to their littermate, vehicle controls. However, locus coeruleus lesions impaired acquisition of conditioned odor preferences. These results suggest that NE output from the locus coeruleus is critical for early olfactory learning
— id: 140363, year: 1994, vol: 643, page: 306, stat: Journal Article,

Norepinephrine and posttraining memory consolidation in neonatal rats
Wilson, D A; Pham, T C; Sullivan, R M
1994 Dec;108(6):1053-1058, Behavioral neuroscience
Wistar rat pups, aged Postnatal Day 5, were trained in an olfactory associative learning task with citral odor as the conditioned stimulus (CS) and intraoral infusions of milk as the unconditioned stimulus (US). Following a 30-min training session, pups were injected with either the norepinephrine beta-receptor antagonist propranolol or the beta-receptor agonist isoproterenol. Pups were tested 24 hr later for an acquired relative odor preference for the CS. Propranolol injected immediately following training impaired memory for the CS in a dose-dependent manner. This posttraining effect lasted less than 4 hr. Isoproterenol injected immediately after training also impaired memory performance, even at very low doses. These results suggest that posttraining levels of norepinephrine play a critical role in memory consolidation in the newborn, with elevations or decrements in noradrenergic activity resulting in impaired memory
— id: 140362, year: 1994, vol: 108, page: 1053, stat: Journal Article,

Neurobiology of associative learning in the neonate: early olfactory learning
Wilson, D A; Sullivan, R M
1994 Jan;61(1):1-18, Behavioral & neural biology
Mammalian neonates have been simultaneously described as having particularly poor memory, as evidenced by infantile amnesia, and as being particularly excellent learners with unusually plastic nervous systems that are easily influenced by experience. An understanding of the neurobiological constraints and mechanisms of early learning may contribute to a unified explanation of these two disparate views. Toward that end, we review here our work on the neurobiology of learning and memory in neonates. Specifically, we have examined the neurobiology of early learning using an olfactory classical conditioning paradigm. Olfactory classical conditioning in neonates at the behavioral level conforms well with the requirements and outcomes of classical conditioning described in adults. Furthermore, specific neural correlates of this behavioral conditioning have been described including anatomical and physiological changes, neural pathways, and modulatory systems. In this Review, we outline the behavioral paradigm, the identified neural correlates, and apparent mechanisms of this learning. Finally, we compare the neurobiology of early learning with that reported for mature animals, with specific reference to the role of US-CS convergence, memory modulation, consolidation, and distributed memory
— id: 140364, year: 1994, vol: 61, page: 1, stat: Journal Article,

Neural correlates of memory for odor detection conditioning in adult rats
Hamrick, W D; Wilson, D A; Sullivan, R M
1993 Nov 26;163(1):36-40, Neuroscience letters
Adult male Wistar rats were trained in a simple odor detection task, with peppermint odor serving as either an S+, S- or as a randomly presented odor. Twenty-four hours after the last training session, rats were injected with [14C]2-deoxyglucose and exposed to the odor. Mean relative 2-deoxyglucose uptake to the odor was enhanced in the pars dorsalis of the anterior olfactory nucleus of S+ and S- trained rats compared to controls. In contrast, no differences in uptake were detected in either odor-specific focal regions of the olfactory bulb glomerular layer, the pyriform cortex, or the hippocampus
— id: 140366, year: 1993, vol: 163, page: 36, stat: Journal Article,

Role of the amygdala complex in early olfactory associative learning
Sullivan, R M; Wilson, D A
1993 Apr;107(2):254-263, Behavioral neuroscience
Although olfactory associative conditioning in newborn rats produces marked structural and functional changes in the olfactory bulb, recent evidence suggests that extrabulbar circuits must be involved in storing these early memories. The present experiments examined the role of the amygdala complex on early olfactory learning. Bilateral amygdala lesions or sham lesions were performed on Postnatal Day (PN) 5. On PN6, pups were trained in a standard classical conditioning paradigm associating odor with tactile stimulation. Behavioral testing on PN7 revealed that amygdala lesions blocked odor preferences but had no effect on conditioned behavioral activation. Similar sized neocortical lesions did not impair odor preferences. Importantly, amygdala lesion effects on learned odor preferences could be reversed by extensive overtraining. These results suggest that the amygdala complex plays a critical role in modulating associative learning as early as the first postnatal week in the rat
— id: 140367, year: 1993, vol: 107, page: 254, stat: Journal Article,

The role of olfactory bulb norepinephrine in early olfactory learning
Sullivan, R M; Zyzak, D R; Skierkowski, P; Wilson, D A
1992 Dec 18;70(2):279-282, Brain research. Developmental brain research
Wistar rat pups were implanted with bilateral olfactory bulb cannulas on postnatal day 5 (PN5). On PN6, pups were trained in an olfactory classical conditioning task with peppermint odor as the CS and tactile stimulation/stroking as the UCS. Pups were randomly assigned to either PAIRED, BACKWARD or ODOR-only conditions. Half the pups in each group received intrabulbar infusions of 100 microM propranolol and half received intrabulbar infusions of saline during the training session. Propranolol infusions blocked acquisition of the learned odor preference expressed by PAIRED saline-infused pups. Diffusion of the infusate was checked in additional pups by infusing [3H]NE and performing LSC analysis. Infusate concentration did not significantly differ between the anterior and posterior halves of the bulb, but were sharply lower in the olfactory peduncle and more posterior areas. The results suggest that olfactory bulb NE is critical for early olfactory learning
— id: 140368, year: 1992, vol: 70, page: 279, stat: Journal Article,

Blockade of mitral/tufted cell habituation to odors by association with reward: a preliminary note
Wilson, D A; Sullivan, R M
1992 Oct 23;594(1):143-145, Brain research
Association of odor and reward during the early postnatal period modifies rat pup behavioral responses and olfactory bulb neural responses to subsequent presentations of that odor. Recent evidence has shown that olfactory bulb output neurons, mitral/tufted cells, receive convergent odor and reward inputs. The present report demonstrates that contiguous odor-reward pairings prevent mitral/tufted cell habituation to the odor that normally occurs to repeated odor-only stimulation. It is hypothesized that the maintenance of olfactory bulb responses to conditioned odors during training may allow for activation of long-term memory mechanisms
— id: 140369, year: 1992, vol: 594, page: 143, stat: Journal Article,

The role of norepinephrine in the expression of learned olfactory neurobehavioral responses in infant rats
Sullivan RM; Wilson DA
1991 ;19(4):308-312, Psychobiology (Austin, Tex.)
In neonatal rats, norepinephrine (NE) is necessary and sufficient for the acquisition of an olfactory preference and its associated olfactory bulb neural modifications as assessed by [(14)C] 2-deoxyglucose (2-DG) and electrophysiology. In the present studies, we assessed the influence of NE on the expression of a conditioned odor preference and its associated olfactory bulb neural modifications in neonatal rats. On Postnatal Day 5 (PN 5), pups were trained to prefer an odor in a 1-h classical conditioning paradigm. Experimental paired odor-stroke pups received 20 forward pairings of a 10-sec peppermint odor and a 9-sec reinforcing tactile stimulation (stroking). Control pups received either random stroke-odor pairings or were naive (received neither the odor nor stroking). The next day (PN 6), the pups were injected with either an NE beta-receptor antagonist, (propranolol or timolol) or saline, 1 h prior to testing. The pups were tested for a behavioral olfactory preference and assessed for differential olfactory bulb activity with [(14)C] 2-DG autoradiography. The results indicate that NE is not necessary for the expression of the learned neurobehavioral response
— id: 140372, year: 1991, vol: 19, page: 308, stat: Journal Article,

Neural correlates of conditioned odor avoidance in infant rats
Sullivan, R M; Wilson, D A
1991 Apr;105(2):307-312, Behavioral neuroscience
Newborn rat pups can learn to either approach or avoid odor cues through associative conditioning. The present results demonstrate that preference conditioning and avoidance conditioning both modify olfactory bulb responses (focal 2-deoxyglucose uptake and mitral-tufted cell single unit responses) to the conditioned odor. Despite opposing behavioral responses to the conditioned odor, however, olfactory bulb neural responses did not detectably differ between learned odor cues signaling approach and those signaling avoidance. Control pups exhibited neither the behavioral nor neural changes. Furthermore, both the behavioral and neural changes to these odor cues could be extinguished. These results suggest that the olfactory bulb in neonates may code learned odor importance, but specific information attached to that importance may require processing in other brain regions
— id: 140371, year: 1991, vol: 105, page: 307, stat: Journal Article,

Olfactory associative conditioning in infant rats with brain stimulation as reward: II. Norepinephrine mediates a specific component of the bulb response to reward
Wilson, D A; Sullivan, R M
1991 Dec;105(6):843-849, Behavioral neuroscience
One of the circuits modified by early olfactory learning is in the olfactory bulb. Specifically, response patterns of mitral-tufted cells are modified by associative conditioning during the early postnatal period. In addition, previous work has demonstrated that mitral-tufted cell single units respond to both olfactory conditioned stimuli and rewarding stimulation of the medial forebrain bundle-lateral hypothalamus (MFB-LH). The present study suggests that norepinephrine beta-receptor activation is required for early olfactory learning using MFB-LH stimulation as reward. Propranolol injected before odor-MFB-LH pairings blocks the acquisition of conditioned behavioral responses and their neural correlates to the conditioned odor. Furthermore, propranolol blocks a specific class of the mitral-tufted cell responses to MFB-LH reward stimulation. The relationship of this response to reward and early learning is discussed
— id: 140370, year: 1991, vol: 105, page: 843, stat: Journal Article,

A search for the neural mechanisms of olfactory learning in young rats
Wilson, Donald A; Sullivan, Regina M; Leon, Michael A
Developmental psychobiology: New methods and changing concepts New York, NY, US: Oxford University Press, 1991,
(from the chapter) focuses on how we [the authors] selected a behavioral learning task for neonates and how we modified existing psychobiological techniques to examine neural plasticity in the developing nervous system /// outlines the changes that occur in the olfactory system [of rat pups] after early learning
— id: 4668, year: 1991, vol: , page: 287, stat: Chapter,

Modified behavioral and olfactory bulb responses to maternal odors in preweanling rats
Sullivan, R M; Wilson, D A; Wong, R; Correa, A; Leon, M
1990 May 1;53(2):243-247, Brain research. Developmental brain research
Rat pups acquire an attraction for maternal odors, which can vary with maternal diet. In the two experiments reported here, maternal diet was modified and both pup behavioral responses and pup olfactory bulb neural responses [( 14C]2-DG uptake) to maternal odors were examined. In experiment 1, pups were reared from birth to postnatal day 19 with either a dam fed normal rat chow or a dam fed a sucrose-based diet which suppressed her normal maternal odor. In experiment 2, pups were raised from birth to postnatal day 19 with either a dam fed the sucrose-based diet adulterated with peppermint, or the non-scented sucrose-based diet. Pups selectively expressed both a behavioral attraction and an enhanced olfactory bulb neural response to odors that they experienced in the nest
— id: 140373, year: 1990, vol: 53, page: 243, stat: Journal Article,

Olfactory associative conditioning in infant rats with brain stimulation as reward. I. Neurobehavioral consequences
Wilson, D A; Sullivan, R M
1990 May 1;53(2):215-221, Brain research. Developmental brain research
In Experiment 1, infant rats were implanted with a stimulating electrode in the medial forebrain bundle/lateral hypothalamus (MFB/LH) on postnatal day 12 (PN12). Four to 6 hours later, the pups underwent associative olfactory conditioning, with half of the pups trained with 30 temporal pairings of odor (5 s) and MFB/LH stimulation (200 Hz, 300 ms), and the other half trained with random presentations of odor and MFB/LH stimulation. On PN13, pups were tested for: (1) behavioral preference for the conditioned odor; (2) focal glomerular layer 2-DG uptake to the odor; or (3) mitral/tufted cell single-unit response pattern to the odor. Odor-MFB/LH pairings produced a relative behavioral preference, enhanced focal 2-DG uptake and a modified mitral/tufted cell response pattern to the conditioned odor. Random training resulted in none of these changes. In Experiment 2, PN12 pups were anesthetized with urethane and single-unit responses of mitral/tufted cells to MFB/LH stimulation were examined. MFB/LH stimulation produced a brief suppression of mitral/tufted cell activity followed either by a prolonged excitation (18/30 cells; 8-10 s duration) or a prolonged suppression (12/30 cells; 10-30 s). These results suggest that pairing olfactory nerve input with MFB/LH stimulation modifies subsequent behavioral and physiological responses to olfactory nerve input alone. Furthermore, the prolonged olfactory bulb response to MFB/LH stimulation may be critical in this modification
— id: 140374, year: 1990, vol: 53, page: 215, stat: Journal Article,

Associative Processes in Early Olfactory Preference Acquisition: Neural and Behavioral Consequences
Sullivan RM; Wilson DA; Leon M
1989 ;17(1):29-33, Psychobiology (Austin, Tex.)
Acquisition of behavioral conditioned responding and learned odor preferences during olfactory classical conditioning in rat pups requires forward or simultaneous pairings of the conditioned stimulus (CS) and the unconditioned stimulus (US). Other temporal relationships between the CS and US do not usually result in learning. The present study examined the influence of this CS-US relationship upon the neural olfactory bulb modifications that are acquired during early classical conditioning. Wistar rat pups were trained from Postnatal Days (PN) 1-18 with either forward (odor overlapping temporally with reinforcing stroking) or backward (stroking followed by odor) CS-US pairings. On PN 19, pups received either a behavioral odor preference test to the odor CS or an injection of (14)C 2-DG and exposure to the odor CS, or olfactory bulb single unit responses were recorded in response to exposure to the odor CS. Only pups that received forward presentations of the CS and US exhibited both a preference for the CS and modified olfactory bulb neural responses to the CS. These results, then, suggest that the modified olfactory bulb neural responses acquired during classical conditioning are guided by the same temporal constraints as those which govern the acquisition of behavioral conditioned responses
— id: 78565, year: 1989, vol: 17, page: 29, stat: Journal Article,

Norepinephrine and learning-induced plasticity in infant rat olfactory system
Sullivan, R M; Wilson, D A; Leon, M
1989 Nov;9(11):3998-4006, Journal of neuroscience
Postnatal olfactory learning produces both a conditioned behavioral response and a modified olfactory bulb neural response to the learned odor. The present report describes the role of norepinephrine (NE) on both of these learned responses in neonatal rat pups. Pups received olfactory classical conditioning training from postnatal days (PN) 1-18. Training consisted of 18 trials with an intertrial interval of 24 hr. For the experimental group, a trial consisted of a pairing of unconditioned stimulus (UCS, stroking/tactile stimulation) and the conditioned stimulus (CS, odor). Control groups received either only the CS (Odor only) or only the UCS (Stroke only). Within each training condition, pups were injected with either the NE beta-receptor agonist isoproterenol (1, 20, or 4 mg/kg), the NE beta-receptor antagonist propranolol (10, 20, 40 mg/kg), or saline 30 min prior to training. On day 20, pups received one of the following tests: (1) behavioral conditioned responding, (2) injection with 14C-2-deoxyglucose (2-DG) and exposed to the CS odor, or (3) tested for olfactory bulb mitral/tufted cell single-unit responses to the CS odor. The results indicated that training with either: (1) Odor-Stroke-Saline, (2) Odor-Stroke-Isoproterenol-Propranolol, or (3) Odor only-Isoproterenol (2 mg/kg) was sufficient to produce a learned behavioral odor preference, enhanced uptake of 14C-2-DG in the odor-specific foci within the bulb, and a modified output signal from the bulb as measured by single-cell recordings of mitral/tufted cells. Moreover, propranolol injected prior to Odor-Stroke training blocked the acquisition of both the learned behavior and olfactory bulb responses. Thus, NE is sufficient and may be necessary for the acquisition of both learned olfactory behavior and olfactory bulb responses
— id: 140375, year: 1989, vol: 9, page: 3998, stat: Journal Article,

Information processing in the olfactory system
Wilson, Donald A; Leon, Michael
Sensory processing in the mammalian brain: Neural substrates and experimental strategies New York, NY, US: Oxford University Press, 1989,
(from the chapter) overview of olfactory system neuroanatomy / neural coding of olfactory stimuli / future prospects /// much research has been done in recent years on the coding of olfactory information and in this chapter we discuss the progress that has been made
— id: 4671, year: 1989, vol: , page: 7, stat: Chapter,

Behavioral and neural correlates of postnatal olfactory conditioning: I. Effect of respiration on conditioned neural responses
Sullivan, R M; Wilson, D A; Kim, M H; Leon, M
1988 ;44(1):85-90, Physiology & behavior
Following olfactory classical conditioning, infant rats exhibit a preference for the conditioned odor and exhibit enhanced uptake of focal 14C 2-deoxyglucose (2-DG) within the olfactory bulb. The present experiments assessed the role of respiration on the expression of the enhanced 2-DG uptake response. Pups were conditioned from postnatal day (PN) 1-18 with an olfactory stimulus paired with a reinforcing tactile stimulus which mimics maternal contact (Odor-Stroke). Control pups received odor only or tactile stimulation only. On PN 19, pups received 1 of 3 tests: 1) a two-odor choice test, 2) an odor/2-DG test with normal respiration allowed, or 3) an odor/2-DG test with respiration experimentally controlled. The results indicated that: 1) Odor-Stroke pups learned the conditioned odor preference, 2) Odor-Stroke, normally respiring pups exhibited enhanced olfactory bulb 2-DG uptake when compared to control pups. No difference in respiration rate was detected between groups in normally respiring pups. 3) Odor Stroke pups whose breathing was experimentally controlled exhibited enhanced olfactory bulb 2-DG uptake when compared to control pups with an identical number of respirations. Together, these results demonstrate that modified respiration during testing is not required for the expression of a modified olfactory bulb response to learned attractive odors. Therefore, the data suggest that the olfactory system itself is modified by early learning
— id: 140377, year: 1988, vol: 44, page: 85, stat: Journal Article,

Physical stimulation reduces the brain temperature of infant rats
Sullivan, R M; Wilson, D A; Leon, M
1988 Apr;21(3):237-250, Developmental psychobiology
Previous work indicated that physical stimulation, such as that which mimics the stimulation pups receive from the dam, reduces pup body temperature. The present paper reports that the body and brain temperature of 5-day-old pups covaried under steady-state thermal conditions, cold exposure, and warmth exposure (Expt. 1) suggesting that body thermoregulatory mechanisms may also regulate brain temperature. Indeed, physically stimulating pups decreased brain temperature in the neocortex (Expt. 2) and the olfactory bulb (Expt. 3). The mechanism for this brain temperature decrease appears to be an increase in ventilatory heat exchange, the same mechanism responsible for the decrease in body temperature. Pups increased respiration during stimulation, thereby increasing air flow to the lungs where convective and evaporative heat exchange occurred. Indeed, stimulating pups in a high-humidity environment blocked the decrease in brain temperature (Expt. 4). The ability of physical stimulation to decrease brain temperature appears to be limited to neonatal pups, as 10-, 15-, and 20-day-old pups did not exhibit a brain temperature decrease in response to stimulation (Expt. 5)
— id: 140376, year: 1988, vol: 21, page: 237, stat: Journal Article,

Noradrenergic modulation of olfactory bulb excitability in the postnatal rat
Wilson, D A; Leon, M
1988 Jul 1;470(1):69-75, Brain research
Noradrenergic centrifugal inputs to the rat olfactory bulb mainly terminate on granule cells, which are inhibitory interneurons. In the mature bulb, norepinephrine suppresses granule cell activity, thus increasing the excitability of the primary output neurons of the bulb. However, since the majority of granule cells develop postnatally, the effectiveness of noradrenergic inputs to the bulb during development is unclear. The present report describes the postnatal development of noradrenergic modulation of olfactory bulb function by examining the effects of noradrenergic beta-receptor agonists and antagonists on paired-pulse inhibition at the granule cell/mitral cell reciprocal synapse. The results demonstrate that noradrenergic modulation of olfactory bulb excitability emerges during the first postnatal week in the rat. These results suggest that noradrenergic centrifugal control of olfactory bulb activity appears early during postnatal development, and thus is capable of playing an important role in pup responses to olfactory cues early in life
— id: 140408, year: 1988, vol: 470, page: 69, stat: Journal Article,

Spatial patterns of olfactory bulb single-unit responses to learned olfactory cues in young rats
Wilson, D A; Leon, M
1988 Jun;59(6):1770-1782, Journal of neurophysiology
1. Neonatal rat pups were classically conditioned to an odor stimulus from postnatal day 1 (PN1) to PN18. Tactile stimulation (stroking) was used as the unconditioned stimulus. On PN19, mitral/tufted cell single-unit responses to the conditioned odor were examined in both conditioned and control pups. Recordings were made from mitral/tufted cells in two regions of the olfactory bulb: 1) an area typically associated with focal [14C]2-deoxyglucose (2-DG) uptake in response to the conditioned odor and 2) an area distant from focal 2-DG uptake to the conditioned odor. Animals were anesthetized with urethane and were naturally respiring during the single-unit recording procedure. 2. Changes in mitral/tufted cell firing rate in response to odors in both bulbar regions and all training groups were classified as either excitatory, suppressive, or no response. This response classification was used to compare response patterns to the conditioned odor between bulbar regions and training groups. 3. Classical conditioning selectively modified the response patterns of mitral/tufted cells to the conditioned odor when those cells were associated with regions of focal 2-DG uptake for that odor. Mitral/tufted cells demonstrated significantly more suppressive and fewer excitatory responses to the conditioned odor than cells in control pups. Response patterns to a novel odor were not similarly modified. 4. Response patterns of mitral/tufted cells distant from the focal region of 2-DG uptake to the conditioned odor were not modified by conditioning compared with control pups. 5. The difference in response pattern between cells in the 2-DG focus and cells distant to the 2-DG focus was apparent within 500 ms of the stimulus onset. Given the respiratory rate of these pups (2 Hz), these data suggest that the modified response pattern occurred on the first inhalation of the learned odor. 6. These data demonstrate that both spatial and temporal patterns of olfactory bulb output neuron activity are used in the coding of olfactory information in the bulb. Furthermore, these spatial/temporal response patterns can be modified by early learning
— id: 140399, year: 1988, vol: 59, page: 1770, stat: Journal Article,

Neural and behavioral plasticity induced by early olfactory learning
Leon, Michael; Coopersmith, Robert; Lee, Suzanne; Sullivan, Regina M; Wilson, Donald A; Woo, Cynthia C
Perinatal development: A psychobiological perspective San Diego, CA, US: Academic Press, 1987,
(from the chapter) maternal olfactory attractant / experiential basis for attraction to maternal and other odors / enhanced olfactory bulb response / lack of differential respiration / the enhanced response is odor-specific / familiarity alone is insufficient to produce the enhanced response /// mechanisms for the development of the enhanced glomerular response / structural changes / do mitral cells mediate the enhanced glomerular response / glomerular-layer neurons / prospectus
— id: 4670, year: 1987, vol: , page: 145, stat: Chapter,

Abrupt decrease in synaptic inhibition in the postnatal rat olfactory bulb
Wilson, D A; Leon, M
1987 May;430(1):134-138, Brain research
Olfactory bulb responses to paired-pulse stimulation of the lateral olfactory tract were examined in urethane-anesthetized rats, aged 5 days to adult. Brief inter-pulse intervals resulted in a depression of test responses at all ages. The magnitude of this depression decreased dramatically between postnatal days 19 and 20 to approach adult levels. Longer inter-pulse intervals resulted in a facilitation of test response amplitude in adult animals. This facilitation was evident at adult levels by postnatal day 10. These results suggest that both inhibitory and facilitatory synaptic mechanisms appear early in the course of rat olfactory bulb development. Furthermore, presumed granule cell-mediated inhibition is present at unusually high levels in the developing bulb, decreasing sharply between days 19 and 20
— id: 140410, year: 1987, vol: 430, page: 134, stat: Journal Article,

Evidence of lateral synaptic interactions in olfactory bulb output cell responses to odors
Wilson, D A; Leon, M
1987 Aug 4;417(1):175-180, Brain research
Lateral inhibitory circuits are found throughout the nervous system. While the neuroanatomical basis for lateral inhibitory interactions exists in the olfactory bulb of Norway rats, there has been no direct demonstration of lateral inhibition in the responses of olfactory bulb output neurons to odor stimulation. In this report we recorded the extracellular activity of a large number of sequentially recorded mitral/tufted cells in response to odor stimuli at two different concentrations, as well as the inter-cell distance between these cells. The probability of recording two cells with excitatory responses to the same odor was then determined for inter-cell distances up to 500 microns. For cells stimulated with high concentration odors, the probability of two cells 100-200 microns apart both being excited by the same odor was significantly lower than that predicted if all cells responded independently. Cells separated by greater or shorter inter-cell distances did not differ from the predicted value. Responses to the low odor concentration were not dependent on inter-cell distance. These results demonstrate that lateral synaptic interactions within the olfactory bulb influence output cell responses to odor stimulation
— id: 140409, year: 1987, vol: 417, page: 175, stat: Journal Article,

Single-unit analysis of postnatal olfactory learning: modified olfactory bulb output response patterns to learned attractive odors
Wilson, D A; Sullivan, R M; Leon, M
1987 Oct;7(10):3154-3162, Journal of neuroscience
Neonatal rats learn to approach odors associated with stimulation normally provided by their mother. The present report describes changes in olfactory bulb single-unit activity following olfactory learning in young rats. Rat pups were exposed from postnatal day 1 to 18 to either (1) peppermint-scented air while receiving tactile stimulation (Pepp-Stroked), (2) peppermint-scented air with no tactile stimulation (Pepp-Only), (3) clean air and tactile stimulation (Stroked-Only), or (4) clean air and no tactile stimulation (Naive). On day 19, single-unit activity was recorded from mitral/tufted cells in urethane-anesthetized, freely breathing pups in response to either peppermint or a novel orange odor. Mitral/tufted cell response patterns to peppermint were significantly altered in Pepp-Stroked animals compared to control pups. Peppermint exposure alone, not associated with tactile stimulation (Pepp-Only), did not affect subsequent single-cell response patterns to that odor. In addition, the modification of response patterns was specific to peppermint and was not associated with a change in respiration rate. Furthermore, Pepp-Stroked pups had a relative behavioral preference for peppermint on day 19 compared to control pups. These results demonstrate that postnatal olfactory learning selectively modifies the subsequent response patterns of olfactory bulb output cells to the attractive odor. Furthermore, these results indicate that the initial coding of an odor's attractive value occurs within the olfactory bulb
— id: 140378, year: 1987, vol: 7, page: 3154, stat: Journal Article,

Early appearance of inhibition in the neonatal rat olfactory bulb
Wilson, D A; Leon, M
1986 May;391(2):289-292, Brain research
The functional development of inhibition in the rat olfactory bulb was examined in the present study. Inhibition of presumed mitral cell spontaneous activity following stimulation of the lateral olfactory tract was present by postnatal day 5, the youngest age tested. The duration of this inhibition was greatest in young animals, decreasing after postnatal day 15. Possible mechanisms of this enhanced inhibition in neonates were discussed
— id: 140411, year: 1986, vol: 391, page: 289, stat: Journal Article,

Odor familiarity alters mitral cell response in the olfactory bulb of neonatal rats
Wilson, D A; Sullivan, R M; Leon, M
1985 Oct;354(2):314-317, Brain research
Previous studies have shown that rat pups have an enhanced metabolic activity to familiar odors in specific glomeruli of the olfactory bulb. The present study examined extracellularly recorded mitral cell responses to odors in this glomerular region, in odor-familiar and odor-unfamiliar pups. Mitral cells in odor-familiar pups had significantly fewer excitatory and more inhibitory responses to the familiar odor than controls. There were no differences between groups in responses to a novel odor. These results demonstrate that neonatal exposure to odors selectively alters subsequent mitral cell responsiveness to that odor
— id: 140379, year: 1985, vol: 354, page: 314, stat: Journal Article,

A comparison of the postnatal development of post-activation potentiation in the neocortex and dentate gyrus of the rat
Wilson, D A
1984 Sep;318(1):61-68, Brain research
The postnatal development of short-term potentiation (STP) and long-term potentiation (LTP) was examined in the neocortex and dentate gyrus of rats aged 7 days to adult. STP and LTP of the transcallosal response in the neocortex could not be demonstrated until the third postnatal week. STP and LTP of the perforant path-dentate response could not be demonstrated until the second postnatal week. In both cases, STP appeared several days before LTP. Structural and neurochemical correlates of STP/LTP development, and their implications for possible STP/LTP mechanisms, are discussed
— id: 140412, year: 1984, vol: 318, page: 61, stat: Journal Article,

The postnatal development of post-activation potentiation in the rat neocortex
Wilson, D A; Racine, R J
1983 Apr;283(2-3):271-276, Brain research
The postnatal development of short-term potentiation (STP) and long-term potentiation (LTP) of the transcallosal response (TCR) was examined in anesthetized rats, aged 7 days (PN7) to adult (greater than or equal to PN180). Stimulation of callosal fibers produced a biphasic, positive-negative TCR recorded at the surface of the anterior neocortex in all age groups. The TCR showed a decrease in threshold, latency and halfwidth, and an increase in peak amplitude with age. High frequency callosal stimulation produced marked STP and LTP of the mature TCR. STP in young animals, however, could not be reliably detected until after PN16. LTP was not detected until PN18. STP and LTP approached adult levels rapidly after their initial appearance. The correlations between STP/LTP onset and development and known structural developments such as initial synaptogenesis, spine formation and myelinogenesis were not particularly strong. The implications of these results for specific hypotheses of STP/LTP mechanisms were discussed
— id: 140413, year: 1983, vol: 283, page: 271, stat: Journal Article,