# Cell-type and whole-brain dynamics underlying operant social stress resiliency

> **NIH NIH F31** · UNIVERSITY OF WASHINGTON · 2024 · $48,974

## Abstract

Project Summary
 Prolonged elevated levels of stress are comorbid with many neuropsychiatric illnesses such as major
depressive disorder (MDD), and can have devastating effects on individuals, their caretakers, and healthcare
professionals. MDD is typically demarcated as exhibiting emotions of sadness, significant loss of motivation,
and can be defined by social deficits. A growing literature indicates that major depressive disorder is influenced
by dysregulation in limbic brain regions including stress and reward circuitry. Despite a significant clinical
awareness, direct preclinical characterization of affective disorder circuitry and associated neuronal
mechanisms inclusive of sex as a biological variable are currently absent, and notably do not include social
decision making and motivation as behavioral metrics. Therefore, the aim of my proposal is to obtain the
necessary computational, behavioral and anatomical training to identify, interrogate, and manipulate neural
populations that modulate these complex social behaviors.
 This project will focus on identifying nucleus accumbens (NAc) circuit and cell type specific mechanisms
that regulate resiliency to operant social stress (OSS), and then further interrogate the afferent projections
driving these populations. OSS incorporates social decision making and social reward as metrics for social
stress resiliency. The choice of this brain region is based on converging preliminary data, implicating that the
NAc dopamine receptor (Drd) 1 and Drd2 medium spiny neurons (MSNs) confer opposing roles in regulating
resiliency to social stress. NAc circuit and cell-type specific activation will be identified using a combination of
whole brain clearing, Fos (a marker of neuronal activity) immunohistochemistry, and retrograde viral tracing.
Because of the limited temporal resolution of Fos during these behaviors, awake-behaving fiber photometry
recordings will be used to observe how NAc MSNs encode varying levels of susceptibility and resiliency to
OSS in real-time. Next, the causal significance of the NAc and its afferent projections will be examined using
region, circuit, and cell type specific optogenetic manipulations. Understanding the neural mechanisms driving
operant social stress in a sex-dependent manner will allow for the development of more specific and effective
treatments for affective mood disorders such as major depressive disorder (MDD).

## Key facts

- **NIH application ID:** 10848242
- **Project number:** 5F31MH133295-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Jovana Navarrete
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 5
- **Project period:** 2023-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10848242

## Citation

> US National Institutes of Health, RePORTER application 10848242, Cell-type and whole-brain dynamics underlying operant social stress resiliency (5F31MH133295-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10848242. Licensed CC0.

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