# Deconstruction of a Neural Circuit for Aggression

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $746,458

## Abstract

SUMMARY STATEMENT
Aggression is an innate social behavior seen across vertebrate species. Although an essential
means to compete for resources and defend oneself, aggression is also a costly behavior with
potentially deadly consequences. Hence, it is important for animals to direct aggression toward
the correct targets to maximize benefits and minimize risk associated with fighting. In humans,
misdirected aggression is particularly destructive as it often targets the most important people in
one’s life—spouse, children, caregivers, or even oneself. Such misdirected aggression can strain
relationship and cause tremendous physical and mental stress. For example, individuals with
certain psychiatric disorders, such as bipolar disorder and post-traumatic stress disorder, are
more likely to express misdirected aggression, jeopardizing their own and others' lives. The goal
of the current project is to elucidate the neural mechanisms that allow an animal to
generate properly directed aggression. Doing so involves multiple behavioral processes. In
mice, for example, individuals in a social group first learn the social status of each member
through repeated agonistic interactions. Then, in subsequent encounters, they recognize the
social status of an opponent and use this information to determine whether to initiate attack. Here,
we will investigate the neural mechanisms supporting each of these behavioral processes that
ultimately allow mice to selectively initiate aggression. Given the well-known role of dopamine in
reinforcement learning, Aim 1 will address whether dopamine from the ventral tegmental area
(VTA) plays an important role in fighting-outcome-based social learning and aggression
expression. We will use a systematic approach to identify the key site(s) of dopamine action in
modulating aggression. Aim 2 will examine the neural representation of social status information,
with particular focus on the posterior part of the medial preoptic nucleus (pMPOA), a key upstream
region of multiple nodes in the aggression circuit. In Aim 3, we will examine the functional role of
pMPOA projections in directing aggression via pathway-specific optogenetic manipulation. In
summary, this study will reveal how social status information is represented in the brain and used
to direct aggression toward the right social targets. It further promises to provide new
understanding of dopamine's role in aggression and associated social learning. If successful, our
proposed investigations will provide new insight into the fine neural control of aggression, and
may yield new therapeutic targets for suppressing the exaggerated and mistargeted aggression
accompanying some psychiatric conditions.

## Key facts

- **NIH application ID:** 10764193
- **Project number:** 5R01MH101377-12
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Dayu Lin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $746,458
- **Award type:** 5
- **Project period:** 2013-07-15 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10764193

## Citation

> US National Institutes of Health, RePORTER application 10764193, Deconstruction of a Neural Circuit for Aggression (5R01MH101377-12). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10764193. Licensed CC0.

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