# Prefrontal ensemble dynamics during response execution and inhibition

> **NIH NIH R21** · UNIVERSITY OF MASSACHUSETTS AMHERST · 2022 · $199,375

## Abstract

PROJECT SUMMARY/ABSTRACT
The balance between response execution and response inhibition (i.e., going vs. not-going or stopping) plays a
fundamental role in regulating normal behavior, and it is disrupted in many psychiatric diseases associated
with impulsivity, including ADHD, OCD, schizophrenia, and substance abuse. Action control is regulated by a
number of brain structures, and prefrontal cortex (PFC) plays a particularly prominent role in shaping go vs. no-
go or stop decisions. However, the mechanisms of how PFC neurons control this response execution vs.
inhibition balance are currently unknown. The projects in this proposal will address this issue by testing a
number of hypotheses related to the dynamic nature of PFC neuron ensembles in behavior control. The
overarching hypothesis to be tested is that separate ensembles of PFC neurons, distributed across multiple
PFC subregions are defined by the intersection between 1) diverging connectivity with downstream targets,
and 2) selective activation with precise temporal dynamics during either action initiation or action suppression.
We will study PFC ensemble contributions in rats performing a novel Go/NoGo task designed to specifically
extract information related to action decisions. In Aim 1 we will use new calcium integrator tools to identify
task-activated ensembles of neurons, map their efferent connectivity, and optogenetically manipulate them,
thereby demonstrating a causal role for neuron populations defined by temporal co-activation anatomical
features in regulating action control. In Aim 2, we will identify the specific temporal dynamics of action-specific
ensembles through large-scale cellular neurophysiological recording across the PFC and will identify how
anatomically-defined ensembles are differentially activated using optogenetics-paired ensemble
neurophysiology. The results from these studies will provide key evidence supporting or refuting the
hypothesis that PFC neuron ensembles, aligned into groups via temporally correlated activity and anatomical
connectivity, regulate decisions to initiate or withhold behaviors. The results from these studies will also
provide a launchpad for future work investigating additional anatomical, molecular, and genetic identities of
neural ensembles related to response selection, both within PFC and in other associated structures. In
addition to significantly advancing our understanding of executive control, these and future studies will identify
novel treatments for mental diseases involving impulsivity and other aspects of disrupted response selection
based on the intersection of circuitry, molecular identity, and physiology.

## Key facts

- **NIH application ID:** 10329989
- **Project number:** 5R21MH122798-02
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST
- **Principal Investigator:** DAVID E MOORMAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $199,375
- **Award type:** 5
- **Project period:** 2021-01-15 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10329989

## Citation

> US National Institutes of Health, RePORTER application 10329989, Prefrontal ensemble dynamics during response execution and inhibition (5R21MH122798-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10329989. Licensed CC0.

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