Frontal cortical neural dynamics and chronic social stress

NIH RePORTER · NIH · R01 · $418,750 · view on reporter.nih.gov ↗

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
YALE UNIVERSITY
Principal Investigator
CHUN-HAY ALEX KWAN
Activity code
R01
Funding institute
NIH
Fiscal year
2021
Award amount
$418,750
Award type
5
Project period
2017-02-15 → 2022-06-30