Acetylcholine as a neuromodulator: ACh signaling in the basolateral amygdala at baseline and in reward learning

Abstract: The basolateral amygdala (BLA) is critical for associating initially neutral cues with appetitive and aversive stimuli and receives dense neuromodulatory acetylcholine (ACh) projections. We measured BLA ACh signaling and principal neuron activity in mice during cue-reward learning using a fluorescent ACh sensor and calcium indicators. We found that ACh levels and activity of nucleus basalis of Meynert (NBM) cholinergic terminals in the BLA (NBM-BLA) increased sharply in response to reward-related events and shifted as mice learned the tone-reward contingency. BLA principal neuron activity followed reward retrieval and moved to the reward-predictive tone after task acquisition. Optical stimulation of cholinergic NBM-BLA terminal fibers during cue-reward learning led to more rapid learning of the cue-reward contingency. These results indicate that BLA ACh signaling carries important information about salient events in cue-reward learning and provides a framework for understanding how ACh signaling contributes to shaping BLA responses to emotional stimuli.

Bio: Marina R. Picciotto is the Charles BG Murphy Professor in Psychiatry and Deputy Chair for Basic Science, Professor of Neuroscience, of Pharmacology and in the Child Study Center at Yale University. Dr. Picciotto’s laboratory studies the function of acetylcholine and its receptors in the brain, including research related to addiction, depression, learning and appetite. Her work spans molecular genetic, biochemical, cell biological, anatomical, electrophysiological, behavioral and human studies, highlighting her philosophy that strong basic neuroscience can be clinically relevant.

In her early work, Dr. Picciotto was one of the first to use genetic engineering to generate mice in which a behavioral phenotype relevant to psychiatric illness was evaluated, and her work on mice with manipulations of nicotinic acetylcholine receptors helped define the specific subtypes required for the initiation of nicotine addiction. These studies have helped established the connections between biochemistry of nicotinic receptors, and their roles in brain circuits and systems leading to clinically-relevant behaviors. Her ongoing work combines fundamental neuroscience with translational studies, and has identified abnormalities in the cholinergic system that occur in both rodent models of depression and humans with mood disorders. The studies performed in her laboratory have helped inform development of treatments for smoking cessation, as well as for psychiatric disorders that are often co-morbid with smoking. 

Dr. Picciotto has served as a member of NIDA’s Scientific Council (2011-2014), as Treasurer of the Society for Neuroscience (2013) and as President of the Society for Research on Nicotine & Tobacco (2018-2019). Dr. Picciotto has been awarded the Presidential Early Career Award for Scientists and Engineers, The Human Frontiers Science Program Organization 10th Anniversary Award, the Waletzky Prize for Research on Substance Abuse and the Carnegie Prize in Mind and Brain Sciences. She was elected to the National Academy of Medicine in 2012 and as a Fellow of the American Association for the Advancement of Science in 2014, where she served as Chair of the Section on Neuroscience from 2019-2020. Dr. Picciotto has served on a number of editorial boards and is currently Editor-in-Chief of the Journal of Neuroscience.

Artwork

Each year, the Andrew Carnegie winner receives an original piece of artwork commissioned from artist Greg Dunn.

Nicotinic Acetylcholine