# Sexually Dimorphic Vasopressin Circuits in the Control of Social Interest

> **NIH NIH R01** · GEORGIA STATE UNIVERSITY · 2024 · $727,479

## Abstract

Project Summary
Disorders of social behavior are increasingly prevalent and pose a substantial burden to society. These
disorders often show sex differences in prevalence, expression, and severity. One explanation for these
differences reflects dysfunction in the sexually differentiated social brain. A particularly relevant neuropeptide
system in this respect is the arginine vasopressin (AVP) innervation of the brain, which shows marked sex
differences across many species, including humans, and has been implicated in aggressive as well as
affiliative behavior. Indeed, the main receptor for AVP in the brain, V1aR, has been linked to social behavior,
including that of humans. Despite the significance of this system, few studies have directly assessed how,
when, and where AVP and V1aR systems interact to influence social interest in adults. Here we focus on the
interaction between the sexually dimorphic AVP cells of the bed nucleus of the stria terminalis (BNST) and its
major target, the lateral septum (LS), an area with the highest expression of V1aR in vertebrate brains. In the
first aim, we will test the necessity of LS V1aR cells for social interest by optogenetic inhibition of these cells or
by genetically knocking out V1aR in LS. In addition, we will combine optogenetic stimulation of BNST AVP
cells and V1aR knockdown in LS in vivo and ex vivo to test whether AVP from the BNST specifically acts on
LS V1aR cells to alter behavior and cellular physiology. The second aim will test whether V1aRs in the LS are
sufficient for driving social interest by optogenetic excitation of these cells. The third aim will test whether V1aR
cells in the LS encode social interest in a sexually dimorphic manner, and whether this encoding is altered by
BNST AVP cell activity (via chemogenetic inhibition). This project will significantly enhance our mechanistic
understanding of how the brain controls social behavior differently in males and females and may give insight
as to why many behavioral disorders show striking sex differences in morbidity. Although recently major
advances have been made in understanding the neural basis of social behavior, how such behavior is
controlled differently in males and females is, by and large, unknown. This grant will address these issues.

## Key facts

- **NIH application ID:** 10980228
- **Project number:** 1R01MH135553-01A1
- **Recipient organization:** GEORGIA STATE UNIVERSITY
- **Principal Investigator:** Geert J. De Vries
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $727,479
- **Award type:** 1
- **Project period:** 2024-09-03 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980228

## Citation

> US National Institutes of Health, RePORTER application 10980228, Sexually Dimorphic Vasopressin Circuits in the Control of Social Interest (1R01MH135553-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10980228. Licensed CC0.

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