# Frontal cortical neural dynamics and chronic social stress

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $418,750

## Abstract

PROJECT SUMMARY
The frontal-basal ganglia network supports our ability to update action plans based on reward feedback. A
prevailing theory posits that stress perturbs frontal cortical function, thereby impairing motivated behavior.
Although this theory is supported by morphological and molecular evidence, data detailing the maladaptive
changes in neural activity in vivo are lacking. One challenge is heterogeneity, because frontal cortical neurons
exhibit diverse task-related activity patterns. To overcome this challenge, we developed experimental
approaches to record from an ensemble of neurons as mice perform an instrumental sucrose preference task.
Our preliminary results showed that layer 2/3 medial frontal cortical neurons display distinct activity patterns
associated with the timing and initiation of voluntary actions. These results led us to propose two hypotheses
for how chronic stress may impair the cortical circuitry for voluntary actions. One, chronic stress diminishes the
activity of cells involved in action initiation. Two, frontal corticostriatal neurons send command-like signal in
service of action initiation. To test these hypotheses, we propose two specific aims. In Aim 1, we will
investigate the longitudinal effects of chronic stress on frontal cortical ensemble activity. We will use a
computational model to gain insights into how the neural activity modifications can alter instrumental behavior.
In Aim 2, we will record from corticostriatal neurons during the instrumental task. Using optogenetics and
targeted ablation, we will test their potential causal roles in mediating purposive actions. Accomplishing these
aims will provide circuit-level insights into the neural basis of voluntary behavior. Framework of chronic stress
that includes the complexity of neural dynamics will allow a better understanding of depressive-like behaviors.

## Key facts

- **NIH application ID:** 10070003
- **Project number:** 5R01MH112750-05
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** CHUN-HAY ALEX KWAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $418,750
- **Award type:** 5
- **Project period:** 2017-02-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10070003

## Citation

> US National Institutes of Health, RePORTER application 10070003, Frontal cortical neural dynamics and chronic social stress (5R01MH112750-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10070003. Licensed CC0.

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