# Development and function of a neural circuit underlying sex-specificity of social behaviors

> **NIH NIH R00** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $246,508

## Abstract

PROJECT SUMMARY/ABSTRACT
Why do males and females behave differently in response to the same sensory cues? Behavioral sex-
specificity is most evident in the displays of social behaviors by males and females in response to identical
social cues. According to classical models of brain sex differentiation, molecular and architectural differences
in brain circuitry are responsible for mediating sex differences in behavior. Alternatively, male and female
brains may share a central circuit that is modulated differently. Strong support for this second model emerged
from studies of Trpc2 knockout mice in which vomeronasal sensing is impaired, and from recent observations
in various animal species including humans. In turn, these data raise the question - how does the brain
generate behavior sex specificity? Moreover, little is known about how changes in circulating hormones and
neural activity during puberty activate dormant neural circuits for sex specific behaviors – a process likely to be
associated with coordinated changes in synaptic strength and gene expression. I am developing a powerful
new tool for studying in situ gene expression dynamics in genetically defined neural circuits. I will use this
approach and test the hypothesis that gene expression programs during puberty act on similar circuits in males
and females to determine the sex specificity of social behaviors. In preliminary experiments, I have genetically
identified a subset of neurons in the mouse hypothalamus that gate behavioral sex-specificity. In the research
proposed here, I will investigate the development and function of this neural circuit associated with behavioral
sex-specificity by fulfilling the following aims: In Aim 1, I will establish the role of genetically identified neurons
in the hypothalamus in gating behavioral sex-specificity using cre-dependent viral tools for cell ablation. Next, I
will use a novel tool for cell type specific gene expression analysis to examine the molecular changes in these
neurons over puberty. In Aim 2, I will use cre-dependent viral tools to trace the monosynaptic inputs and
outputs of these neurons. Finally, in Aim 3, I will use whole cell patch clamp electrophysiology combined with
optogenetics and gene expression analysis to examine input specific synaptic and molecular changes in these
neurons that accompany the transition through puberty.
The training phase of the award, conducted in the laboratories of Dr. Catherine Dulac and Dr. Venkatesh
Murthy at Harvard University, outlines a comprehensive plan for the acquisition of technical and professional
skills that will enable my transition to an independent research position. The successful completion of this
project will provide a platform for future experiments aimed at understanding the development and architecture
of neural circuits underlying social behaviors.

## Key facts

- **NIH application ID:** 10784603
- **Project number:** 5R00HD092542-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Dhananjay Bambah-Mukku
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $246,508
- **Award type:** 5
- **Project period:** 2022-02-10 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10784603

## Citation

> US National Institutes of Health, RePORTER application 10784603, Development and function of a neural circuit underlying sex-specificity of social behaviors (5R00HD092542-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10784603. Licensed CC0.

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