# Central Amygdala Glutamatergic Circuits in Fear Learning and Extinction

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $540,834

## Abstract

PROJECT SUMMARY Acquisition and extinction of learned fear responses are critical for survival and require
modification of conserved neural circuits that promote or suppress fear expression, respectively. Disruption of
these important physiological processes are thought to underlie the development of stressor and trauma-
related disorders including posttraumatic stress disorders. Understanding the neuronal circuits and synaptic
mechanisms regulating fear memory formation and extinction could have important implications for elucidating
pathophysiological mechanisms of stress-related disorders and provide insight into fundamental mechanisms
subserving learning and memory processes. The central nucleus of the amygdala (CeA) is a striatal-like
subcortical brain structure that sits functionally at the limbic-motor interface. Recent studies have identified
distinct cell-types within this region that are sufficient to generate diverse survival-oriented behavioral
responses including freezing, flight, hunting, and feeding. Relevant to the current proposal, very recent work
has identified the CeA as a novel locus of fear-learning and identified distinct cell-types responsible for
generating learned fear responses in the form of freezing and flight-like escape behavior. Despite these
advances, how top-down cortical signals are able to select distinct behavioral outputs via targeted activation of
different CeA cell-types is not well understood. Here we will utilize a combination of cutting-edge cell-type-
specific electrophysiological, optogenetic, chemogenetic and viral reporter approaches combined with a
Pavlovian fear-conditioning and extinction paradigm to gain insight into this critical open question. Aim 1 of this
proposal will test the hypothesis that acquisition and extinction of conditioned fear responses is associated with
dynamic shifts in the relative glutamatergic drive from the basolateral amygdala (BLA) to CeA corticotrophin
releasing factor expressing (CRF+) and somatostatin-expressing (SOM+) neurons. We hypothesize that fear
acquisition shifts BLA excitatory drive to favor SOM+ neurons, which have been shown to drive conditioned
freezing behavior, while extinction learning reverses the relative input bias from the BLA to favor CRF+
neurons, which we show facilitate extinction of conditioned freezing behavior. Aim 2 will test the requirement
for neuronal activity in the induction of this form of experience-dependent plasticity and its necessity for the
expression of conditioned fear and extinction using circuit-specific chemogenetic and behavioral approaches.
Aim 3 will test the hypothesis that retrograde endocannabinoid signaling is an important mediator of
experience-dependent changes in synaptic strength between the BLA and CeA CRF+ and SOM+ neurons, and
that modulation of eCB signaling within the BLA-CeA-SOM+ circuit promotes fear extinction. Completion of
these studies will provide novel insight into the circuit and cell-type-specific m...

## Key facts

- **NIH application ID:** 10013294
- **Project number:** 5R01MH119817-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Sachin Patel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $540,834
- **Award type:** 5
- **Project period:** 2019-09-09 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10013294

## Citation

> US National Institutes of Health, RePORTER application 10013294, Central Amygdala Glutamatergic Circuits in Fear Learning and Extinction (5R01MH119817-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10013294. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*