# Role of amygdala inhibitory circuit neuromodulation in stress disorders

> **NIH VA I01** · SOUTHEAST LOUISIANA VETERANS HEALTH CARE · 2021 · —

## Abstract

Project Title: Role of amygdala inhibitory circuit neuromodulation in stress disorders
Project Summary
Traumatic stress exposure can lead to long-term stress disorders and represents a considerable risk factor for
suicide. Stress disorders such as posttraumatic stress disorder (PTSD) and alcohol use disorder have significant
links with suicidality and are characterized by plasticity of neural circuits and neurochemical signaling in the
amygdala, particularly in the basolateral complex of the amygdala (BLA). The BLA integrates neural inputs from
multiple sources and assigns emotional valence to information by establishing distinct streams of information
outflow. BLA circuits process inputs to form emotional memories based on the excitation/inhibition balance set
by the relative excitatory and inhibitory synaptic inputs to the principal output neurons of the BLA. While
potentiation at excitatory synapses is the foundation of memory formation, inhibitory circuits regulate the
excitation/inhibition balance to control synaptic potentiation, and neuromodulatory signals tune the synaptic
interactions. Noradrenergic modulation is thought to signal arousal and contribute significantly to the emotional
salience of information processed in the amygdala. Our preliminary preclinical findings in mice suggest that
norepinephrine (NE) exerts robust regulatory control over GABAergic parvalbumin (PV) and cholecystokinin
(CCK) inhibitory inputs to the BLA principal neurons, and that this control is compromised following traumatic
stress exposure. We propose to characterize the noradrenergic modulation of PV and CCK synaptic inputs to
the BLA principal neurons, and to define the role of noradrenergic modulation of synaptic inhibition in BLA-
mediated fear memory formation. We will target the noradrenergic afferent regulation of PV and CCK
interneuronal circuits using chemogenetic and optogenetic strategies. We will interrogate local PV and CCK
interneuron inhibitory synaptic signaling in the BLA for noradrenergic neuromodulation using patch clamp
recordings in slices of amygdala. We will use behavioral paradigms to determine the role of the noradrenergic
modulation of BLA inhibitory circuits in fear consolidation and extinction. Finally, we will test for traumatic stress-
induced plasticity of the noradrenergic modulation of inhibitory circuits and the PV and CCK circuit regulation of
fear learning. These studies together will reveal the mechanisms of the noradrenergic modulation of BLA circuits
and provide important insights into the role(s) of distinct perisomatic inhibitory circuits in the control of BLA-
dependent fear memory formation, as well as into how these circuits are disrupted by traumatic stress exposure.

## Key facts

- **NIH application ID:** 10124069
- **Project number:** 1I01BX005118-01A1
- **Recipient organization:** SOUTHEAST LOUISIANA VETERANS HEALTH CARE
- **Principal Investigator:** JEFFREY G TASKER
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10124069

## Citation

> US National Institutes of Health, RePORTER application 10124069, Role of amygdala inhibitory circuit neuromodulation in stress disorders (1I01BX005118-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10124069. Licensed CC0.

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