James L. McGaugh Distinguished Seminar Series

Tuesday, May 13, 2025 at 11:00am

The seminar will be In-Person.

Marina R. Picciotto, Ph.D.

Charles B.G. Murphy Professor in Psychiatry and Deputy Chair for Basic Science Research,

Departments of Psychiatry, Neuroscience and Pharmacology, Yale University

“Cholinergic modulation of circuits involved in behavioral responses to stress.”

Abstract:  Acetylcholine (ACh) is a critical neurotransmitter important for communication in the autonomic nervous system (fight-or-flight response) and in the brain. We know that stress increases release of ACh and that pharmacological blockade of ACh breakdown induces symptoms of depression in human subjects and increases stress-related behaviors in rodents. In addition, radioligand imaging in human subjects has shown that ACh levels are elevated when unipolar and bipolar individuals are actively depressed. In our laboratory we have found that pharmacological or molecular genetic manipulations of ACh signaling through ACh esterase, nicotinic (nAChRs) or muscarinic (mAChRs) in basolateral amygdala (BLA), hippocampus and medial prefrontal cortex (mPFC) is sufficient to recapitulate effects of systemic modulation of the cholinergic system on stress-induced behaviors in mice. In ongoing studies, we have measured ACh dynamics during stress-induced behaviors using genetically-encoded fluorescent sensors and altered cholinergic input to these brain regions using chemogenetic and optogenetic strategies, coupled with pharmacological approaches. These studies demonstrate that ACh signaling modulates behavioral responses to acute and chronic stress in mice. These data demonstrate that ACh signaling in the BLA, hippocampus and mPFC is critical for coordinating behavioral responses to stressful stimuli and support the hypothesis that dysregulated ACh signaling contributes to stress-related disorders in depressed patients.