# Amygdala Circuit Mechanisms for Stress-escalated Aggression

> **NIH NIH K99** · MCLEAN HOSPITAL · 2024 · $127,710

## Abstract

Interpersonal violence is a leading cause of posttraumatic stress disorder (PTSD), a debilitating syndrome
characterized by sleep disturbances, flashbacks, and dysregulated emotional reactivity. For some trauma-
exposed individuals, deficits in emotion regulation can escalate to aggression, thereby perpetuating a cycle of
interpersonal violence and trauma. Understanding how stressors affect the neural circuitry of aggression is
fundamental to developing effective therapies for this form of violence. Central amygdala (CeA) neurons that
express the well-characterized stress signaling neuropeptide, corticotropin releasing hormone (Crh), are critical
mediators of fear-induced reactions, and through my postdoctoral single-cell calcium imaging training in the
Ressler Lab, I have identified a distinct Crh+ CeA cell activity signature during the emergence of offensive
aggression. In Aim 1 (K99), I will use closed-loop optogenetics to extend these preliminary findings to understand
the causal role of Crh+ CeA cells in initiating aggression. Using my novel and recently validated model for social
trauma-induced aggression – where experimental mice are attacked inside of their home environment by a
dominant intruder – it is possible to explore the impact of violence on fear circuitry. Such trauma-exposed mice
adopt heightened defensive tactics including atypical, generalized aggression toward non-threatening social
partners. In Aim 2 (R00), this model for social trauma will be used to determine if stress recruits pro-aggressive
Crh+ CeA cell activity, and to experimentally block this recruitment and the development of trauma-induced
aggression. Aim 3 (R00) will begin to explore top-down cortical regulation of this translational stress-induced
aggressive phenotype. The insular cortex (IC) innervates Crh+ CeA cells and this projection is functionally linked
to hostility in clinical experiments. Aim 3 will establish if social trauma increases aggression by amplifying IC
inputs to Crh+ CeA neurons. This K99/R00 will support an important stage of my postdoctoral training in single-
cell imaging and closed-loop all-optical approaches which will be necessary to continue exploring cortical
underpinnings of dysregulated emotional reactivity. Mastering these versatile methodological approaches will
guide my future independent research program in identifying translational connections between stress-sensitive
neural systems and the complex orchestration of violent behaviors.

## Key facts

- **NIH application ID:** 10917386
- **Project number:** 5K99MH133869-02
- **Recipient organization:** MCLEAN HOSPITAL
- **Principal Investigator:** Emily L Newman
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $127,710
- **Award type:** 5
- **Project period:** 2023-09-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10917386

## Citation

> US National Institutes of Health, RePORTER application 10917386, Amygdala Circuit Mechanisms for Stress-escalated Aggression (5K99MH133869-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10917386. Licensed CC0.

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