# Cholinergic Contribution to Circuits Guiding Behavioral Responses to Stressors

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $418,750

## Abstract

Project Summary
The relationship between chronic stress and human anxiety disorders and depression is clear from
epidemiological and clinical studies. Stress induces the release of neuromodulators that coordinate
adaptive behavioral responses, but sustained activation of stress pathways results in dysregulation of
circuits that can bias behavior toward maladaptive behavioral ensembles. Further, it is not clear why
some individuals are susceptible to long term behavioral changes induced by stress and others are not.
Acetylcholine (ACh) is released in response to stressful stimuli in multiple brain areas that govern
behavioral responses to stressors. ACh signaling is important for adaptive behaviors, but also facilitates
stress-related learning and hypervigilance and promotes stress-related avoidance. We have identified
receptor subtypes that mediate effects of ACh in the amygdala, hippocampus and prefrontal cortex in
response to stressors, and have begun to identify mechanisms that may modulate transitions to
maladaptive behavioral ensembles. In the studies proposed here we will study the role of ACh in 1)
acute, and 2) experience-dependent behavioral responses to stressors, and 3) test a novel hypothesis
that prolonged ACh signaling may alter the balance in attention/encoding of aversive vs. appetitive
stimuli. A negative cognitive bias is commonly observed in patients with anxiety disorders, depression or
post-traumatic stress disorder; therefore, discovering a role for ACh in modulation of stress and reward
encoding could result in novel directions for therapeutic development based on cholinergic mechanisms.

## Key facts

- **NIH application ID:** 10867403
- **Project number:** 5R01MH077681-17
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** YANN Sebastien MINEUR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $418,750
- **Award type:** 5
- **Project period:** 2006-08-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10867403

## Citation

> US National Institutes of Health, RePORTER application 10867403, Cholinergic Contribution to Circuits Guiding Behavioral Responses to Stressors (5R01MH077681-17). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10867403. Licensed CC0.

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