# Defining cell types that control action selection and execution

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $353,281

## Abstract

PROJECT SUMMARY/ABSTRACT
A fundamental task of the brain is to choose what to do next, and an impaired ability to select appropriate
behaviors and repress inappropriate actions is thought to underlie conditions including schizophrenia,
addiction, and Huntington's disease. How the brain weighs available actions to choose and execute the most
adaptive is not understood. In the canonical model, effector structures such as the superior colliculus (SC) are
constantly poised to generate behaviors, but are repressed by tonically active GABAergic neurons of the basal
ganglia (BG) output nuclei substantia nigra pars reticulata (SNr) and internal globus pallidus; before an action,
the specific subset of BG output neurons inhibiting that action pause firing to “release” its effector pathway.
However, several studies have revealed that SNr harbors multiple GABAergic inhibitory cell types of which
some are only phasically active, and both tonic and phasic inhibitory SNr neurons can converge on the same
target neurons in structures such as SC. These cell types are intermingled in SNr, which has hindered efforts
to apply the genetic tools of modern neuroscience to decipher how their convergent phasic and tonic inhibitory
signals influence downstream neural processing to control behavioral choice and execution. To surmount this
obstacle, my lab has developed approaches to selectively express genetic tools in either phasic or tonic SNr
neurons. Here I propose to apply our approach to reveal how phasic and tonic inhibitory BG subtypes
coordinate behavior. First, we will test the hypothesis that phasic SNr neurons encode both behavioral choice
and execution by recording their activity during behavior. Second, we will test the hypothesis that phasic
inhibitory neurons shape both choice and execution of the chosen behavior using targeted manipulations.
Third, to understand the transcriptional basis of physiologic differences between these phasic and tonic types,
we will define the genetic identities of both using a novel barcoding approach in single-cell sequencing.
Collectively, these studies will provide a comprehensive portrait of how phasic and tonic inhibitory BG cell
types coordinate behavioral choice and execution. The findings from these studies may help us to understand
the etiology of and lead to new treatments for conditions including addiction, schizophrenia, Parkinson's, and
Huntington's disease.

## Key facts

- **NIH application ID:** 10337273
- **Project number:** 5R01NS109060-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Evan Harriman Feinberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $353,281
- **Award type:** 5
- **Project period:** 2019-02-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10337273

## Citation

> US National Institutes of Health, RePORTER application 10337273, Defining cell types that control action selection and execution (5R01NS109060-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10337273. Licensed CC0.

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