Throughout our lives, our brains are tasked with representing the intangible significance of our experiences in a way that allows us to navigate our complex world successfully. However, the way that different brain areas communicate to accomplish this is still unclear. The significance of any particular occurrence is given by neuromodulators that interact with different areas of the brain to create an appropriate response to the current situation. Neuromodulators are transmitters such as oxytocin, dopamine, or noradrenaline that change neurons in a way that translates to specific behavioral responses like “love,” “feel good,” or “stress out.”

It is widely accepted that brain areas like the cortex respond to these neuromodulators by changing responses according to the particular experience. However, it is unclear how neuromodulatory centers themselves might change and adapt in response to relevant environmental stimuli. Think about how the smell of cookies reminds you of your grandmother. Or how that ’90s pop song makes you feel like a teenager again. These sensory stimuli bring about memories of past events with vivid sensations associated with them.

How does that work?

Having in mind the well-known fact that stressful moments tend to be remembered longer and more vividly, sometimes for months or even years after one single occurrence, authors Martins and Froemke set out to study how stressful events might change the locus coeruleus (LC), the source of noradrenaline for the central nervous system. Furthermore, the authors look at how those changes are coordinated with the cortical changes brought about by neuromodulator release.

Toward this goal, a stressful event was simulated by activating the LC in a manner similar to how highly stressful situations would. At the same time, a sensory stimulus of choice, a sound, is presented. The response to that paired sound, before and after the manipulation, in both the LC and auditory cortex after one single episode of LC activation is recorded and is the readout for change.

The authors found that after activation, LC neurons that were initially unresponsive to sounds become responsive specifically to the paired sound. Furthermore, this new response is long-lasting, observed up to 10 or more hours after one single pairing episode. At the cortical level, changes occur also in the direction of the paired sound: neurons start responding better to that sound than before the manipulation, and this is maintained for 11 or more hours after one single pairing episode. Pharmacological experiments indicate the duration of this effect in both areas is directly dependent on noradrenaline release from sound-sensitized LC neurons, in response to passive presentation of the paired sound. Behaviorally, animals tested in auditory tasks undergoing this same single LC activation paired with a sound showed lasting effects for days and even weeks in the direction of the paired sound specifically, as opposed to other sounds presented.

Beyond presenting a novel perspective on how neuromodulatory centers interact with other brain areas, the results discussed here have important implications in anxiety spectrum disorders, such as post-traumatic stress disorder, that might help complement current pharmacological and behavioral therapies in the clinic.

—Ana Raquel O. Martins, PhD

Read the paper “Coordinated forms of noradrenergic plasticity in the locus coeruleus and primary auditory cortex” in Nature Neuroscience, published August 24, 2015.