Margaret E. Rice

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Margaret Rice

Professor, Department of Neurosurgery
Professor, Department of Neuroscience and Physiology


Contact Info

Address
455 First Avenue
New York, NY 10016

212/263-5438
Margaret.Rice@nyumc.org

Research Summary

Research in Dr. Rice's laboratory is focused on regulation of dopamine, a key transmitter in motor and reward pathways in the brain. The Rice group uses carbon-fiber microelectrodes with fast-scan cyclic voltammetry to provide real-time monitoring of axonal dopamine release in dorsal and ventral striatum and somatodendritic release in the substantia nigra and ventral tegmental area, primarily in brain slices. Complementary techniques include whole-cell recording of basal ganglia neurons, fluorescence imaging of calcium and reactive oxygen species (ROS), and immunocytochemistry. Current research is centered on a novel finding from the Rice group that hydrogen peroxide (H2O2), produced by mitochondrial respiration, is an endogenous regulator of synaptic and somatodendritic dopamine release, as well as dopamine neuron activity in the substantia nigra. Both dopamine release and dopamine neuron activity are suppressed by H2O2 via the activation of ATP-sensitive potassium (KATP) channels. Importantly, modulation by H2O2 is greater in the nigrostriatal dopamine pathway, which degenerates in Parkinson's disease (PD), than in the mesolimbic dopamine reward pathway that is relatively spared in PD. Given that mitochondrial dysfunction and oxidative damage have been linked causally to PD, these findings suggest that modulation by H2O2 is a double-edged sword. This diffusible messenger can rapidly link metabolism to neuron excitability; however, if generation or metabolism of H2O2 were disrupted, this could lead to oxidative damage. On-going studies are examining how H2O2 activates KATP channels, the time course of dopamine release regulation by H2O2, and how other neurons in the basal ganglia are affected by endogenous H2O2. In addition to these core project, the Rice group also studies regulation of axonal dopamine release by glutamate, GABA, calcium, cannabinoids and caffeine, the mechanism and regulation of somatodendritic dopamine release, and dopamine dysfunction in transgenic mouse models of dystonia and PD.

Research Keywords

neurochemistry and neurophysiology of the nigrostriatal dopamine pathway, channels and transporters, molecular, cellular, & translational neuroscience

Lithium increases synaptic GluA2 in hippocampal neurons by elevating the delta-catenin protein
Farooq, Mobeen; Kim, Seonil; Patel, Sunny; Khatri, Latika; Hikima, Takuya; Rice, Margaret E; Ziff, Edward B. Lithium increases synaptic GluA2 in hippocampal neurons by elevating the delta-catenin protein. Neuropharmacology. 2017 Feb;113(Pt A):426-433 (2288922)

Regulation of Extracellular Dopamine: Release and Uptake
Sulzer, D; Cragg, SJ; Rice, ME. Regulation of Extracellular Dopamine: Release and Uptake. Handbook of behavioral neuroscience. 2017 ;24:373-402 (2402902)

Detection of evoked acetylcholine release in mouse brain slices
Asri, R; O'Neill, B; Patel, J C; Siletti, K A; Rice, M E. Detection of evoked acetylcholine release in mouse brain slices. Analyst. 2016 Nov 14;141(23):6416-6421 (2278262)

Striatal dopamine neurotransmission: regulation of release and uptake
Sulzer, David; Cragg, Stephanie J; Rice, Margaret E. Striatal dopamine neurotransmission: regulation of release and uptake. Basal ganglia. 2016 Aug;6(3):123-148 (2101182)

Insulin enhances striatal dopamine release by activating cholinergic interneurons and thereby signals reward
Stouffer, Melissa A; Woods, Catherine A; Patel, Jyoti C; Lee, Christian R; Witkovsky, Paul; Bao, Li; Machold, Robert P; Jones, Kymry T; de Vaca, Soledad Cabeza; Reith, Maarten E A; Carr, Kenneth D; Rice, Margaret E. Insulin enhances striatal dopamine release by activating cholinergic interneurons and thereby signals reward. Nature communications. 2015 Oct 27;6:8543-8543 (1816772)