# Novel Role of a Ventral Striatal Circuit in Motor Control

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $470,631

## Abstract

Project Summary
The striatum is an evolutionarily conserved structure involved in cognitive and limbic regulation of motor
control. Striatal circuits are implicated in the initiation and execution of ethologically relevant motor output,
ranging from exploratory actions to highly stereotyped motor patterns. Dysfunction of these circuits leads to
motor control abnormalities that frequently manifest as excessive repetitive behaviors. Self-directed grooming,
a highly stereotyped repetitive motor pattern, is observed in virtually all animals, serving vital functions in
hygiene maintenance, thermoregulation, de-arousal, stress reduction, and social communication. Abnormally
repetitive grooming is a central behavioral phenotype observed in numerous models for neurological and
neuropsychiatric diseases. A better understanding of the neural control of grooming may thus yield
fundamental insights into how the brain controls repetitive motor output in both normal and diseased
conditions. Our preliminary work suggests that an understudied population of interneurons within the olfactory
tubercle (OT; the most ventral part of the striatum), predominantly in the Islands of Calleja (IC), is involved in
mediating this behavior. The striatum has a fairly uniform cellular composition, with ~95% of the neurons being
spiny projection neurons (SPNs), classified as D1- or D2-type according to the dopamine receptors they
express. One exception to this uniformity is the existence of evolutionarily conserved IC, clusters of densely-
packed, GABAergic granule cells, which express the D3 dopamine receptor. By means of optogenetic
manipulations, we have shown that activation of OT D3 neurons initiates robust grooming behavior via arrest of
other alternative ongoing behaviors. In contrast, inactivation of these neurons halts ongoing grooming. These
findings lead to the central hypothesis that OT D3 neurons play critical roles in controlling grooming behavior.
Through an array of modern neuroscience approaches (optogenetics, ex vivo and in vivo electrophysiology,
fiber photometry, neural circuit tracing, and behavior), we will pursue three specific aims to determine (1) in
vivo activity patterns of OT D3 neurons and SPNs in grooming and other behaviors, (2) contributions of OT D3
neurons to grooming in relation to other brain regions, and (3) the effects of dopamine release into the OT on
grooming behavior. Overall, this project will provide insights into the neural circuitry of the IC/OT D3 neurons
and its role in neurobiological control of a highly important motor pattern.

## Key facts

- **NIH application ID:** 10929979
- **Project number:** 5R01NS117061-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Marc V Fuccillo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $470,631
- **Award type:** 5
- **Project period:** 2021-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10929979

## Citation

> US National Institutes of Health, RePORTER application 10929979, Novel Role of a Ventral Striatal Circuit in Motor Control (5R01NS117061-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10929979. Licensed CC0.

---

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