# Deconstruction of a neural circuit for aggression - Renewal - 1

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $684,106

## Abstract

SUMMARY STATEMENT
 Aggression is an innate social behavior across vertebrate species. However, excessive
aggression—ranging from school bullying to terrorist attacks—imposes a devastating risk to our
society. Individuals with certain psychiatric disorders, such as bipolar disorder and post-
traumatic stress disorder, are more likely to act violently, jeopardizing their own lives and those
around them. While classic models of aggression have long-suggested that improper
aggression results from dysfunction of “top-down” executive control of aggression-relevant
circuitry, there is little direct physiological or neural circuit evidence to support this. Here, we will
take an alternative “bottom-up” approach to investigate the inhibitory control impinged onto a
neural locus with a clear role in aggression. We hypothesize that these inhibitory controls are
essential to ensure aggression is expressed at the right time and towards the right target. We
have identified the ventrolateral part of the ventromedial hypothalamus (VMHvl) as an essential
locus for both “reactive” and “proactive” aggression. Whereas optogenetic activation of the
VMHvl can promote both attack and aggression-seeking behavior, VMHvl inhibition has the
opposite effect. In this study, we will address how local and long-range inhibitory inputs
modulate responses of VMHvl cells, and consequently aggressive behaviors. Although neurons
in the VMHvl are primarily excitatory, the VMHvl is directly and strongly inhibited by VMHvl
“shell” neurons that are situated lateral and ventral to the VMHvl core. Thus, we hypothesize
that the VMHvl shell is well positioned to shape aggression-relevant activity in excitatory VMHvl
neurons. In the first part of the study, we will employ in vivo recording, functional manipulation,
channelrhodopsin-assisted circuit mapping, and viral tracing to define the relationship between
this inhibitory shell and excitatory “core” of the VMHvl. In the second part of the study, we will
zoom out and examine the function of long-range inhibitory inputs to the VMHvl. Specifically, we
will test the hypothesis that the inhibitory inputs from the medial preoptic area, a hypothalamic
region critical for reproduction and parental care, is essential for suppressing VMHvl responses
towards improper aggression targets and preventing misdirected attack. In summary, this study
will provide a much needed framework to understand how inhibitory mechanisms control
aggressive behavior, and pave the way for new types of circuit-level therapeutics for aggression
control.

## Key facts

- **NIH application ID:** 9848446
- **Project number:** 5R01MH101377-08
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Dayu Lin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $684,106
- **Award type:** 5
- **Project period:** 2013-07-15 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9848446

## Citation

> US National Institutes of Health, RePORTER application 9848446, Deconstruction of a neural circuit for aggression - Renewal - 1 (5R01MH101377-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9848446. Licensed CC0.

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