# Cell types controlling social behavior in extended amygdala and nucleus accumbens

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $442,750

## Abstract

Project summary
Social anxiety disorder is the most common anxiety disorder in the United States, and ~40% of affected
individuals do not respond to existing treatments. A limited knowledge of the neural circuits modulating anxiety
impedes innovation for new therapeutic strategies. Recent sequencing data highlight the diversity of neuronal
cell types in the brain, but a key challenge is determining how different cell types function in behaviorally
relevant contexts. The answer to this question is important because many genetically defined cell types are
evolutionarily conserved across humans, primates, and rodents. One way to link cell types to behavior is with
activity-dependent tagging. The first methods (TRAP, tetTag) used the expression of immediate early genes to
label neurons that are active in specific behavioral contexts. These systems were revolutionary, but the
temporal resolution of these methods is limited (hours) while behavior can occur over minutes. The Fast Light
and Calcium-Regulated Expression (FLiCRE) system combines light- and calcium-dependent tagging methods
to label cells that are activated during a discrete timepoint (~10 min), when a behavior of interest is expressed.
We will use the FLiCRE system to tag cells in brain regions that modulate social approach (nucleus
accumbens, NAc) and avoidance behaviors (bed nucleus of the stria terminalis, BNST). We will genetically
define these cells using single cell RNAseq and then functionally define them using optogenetic manipulations.
We will use FLiCRE to tag cells in the BNST of mice exhibiting social avoidance and use single nucleus RNA
sequencing (snRNAseq) to genetically define these cells to test the hypothesis that a subset of Oxtr cell types
are active in stressful social contexts. Pharmacological activation of oxytocin receptors in the BNST is
necessary and sufficient for drive social avoidance. We will then use optogenetics to functionally define these
cells. We predict that inhibition of BNST cells tagged during social avoidance will increase social approach.
Next, we will use FLiCRE to tag cells in the NAc of mice exhibiting social approach. We will use snRNAseq to
test the hypothesis that Oxtr interneurons are active during social approach, because oxytocin receptors in the
NAc promote social approach. We will then use optogenetics to inhibit these cells and predict that inhibition will
decrease social approach. Our research team is ideally suited to execute these studies. Dr. Trainor's lab
delineated oxytocin receptor-dependent pathways of social approach and avoidance. Dr. Kim developed the
FLiCRE construct and used it to identify a novel cell type in NAc that drives aversion. Dr. Tollkuhn is a
molecular biologist and expert on using single nucleus RNAsequencing in brain. Dr. Wiltgen has successfully
performed optogenetic manipulations of neurons labeled via activity-dependent tagging. Our analyses will
identify cell types that modulate social approach and avoidanc...

## Key facts

- **NIH application ID:** 10975323
- **Project number:** 1R21MH135349-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** BRIAN C TRAINOR
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $442,750
- **Award type:** 1
- **Project period:** 2024-07-03 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10975323

## Citation

> US National Institutes of Health, RePORTER application 10975323, Cell types controlling social behavior in extended amygdala and nucleus accumbens (1R21MH135349-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10975323. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*