# Dissecting basal ganglia circuit mechanisms underlying instrumental learning

> **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $362,250

## Abstract

SUMMARY
The basal ganglia (BG) are critical for motor control and instrumental learning. In particular, classic lesion
studies have demonstrated that different regions of the striatum, the major BG input nucleus, are
associated with distinct aspects of action selection and learning: the dorsomedial striatum is responsible
for action-outcome learning and action selection based on outcome expectancy, whereas the dorsolateral
striatum is responsible for the development of habits and behavioral automaticity. There is also growing
consensus that maladaptive instrumental learning and performance contribute to numerous disorders
such as addiction and schizophrenia that also implicate the BG. Although recent studies have begun to
show a key role for corticostriatal plasticity in instrumental learning and habit formation, the detailed circuit
mechanisms remain unclear. The overall aim of this proposal is to determine the circuit mechanisms in
the BG underlying instrumental learning and performance. We will use a integrative approach, combining
intersectional strategies to target defined neuronal populations and pathways and precise behavioral
assays to quantify learning and behavior. To monitor and manipulate neural activity of defined cell
populations, we will use in vivo calcium imaging, optogenetics, and transgenic mouse lines that make it
possible to target the key neuronal populations and pathways in the BG. To assess the content of
learning and quantify behavior continuously, we will use established behavioral assays from instrumental
conditioning combined with 3D motion capture. Four aims are proposed. Aims 1 and 2 will determine the
contribution of the direct (striatonigral) pathway and indirect (striatopallidal) pathways in different striatal
regions to instrumental learning and performance. Aims 3-4 will determine the contributions of distinct
corticostriatal pathways (intratelencephalic and pyramidal tract) to instrumental learning and
performance. Results from proposed research can shed light on the neural mechanisms underlying goal-
directed actions and habit formation, and how dysfunctions in the BG circuit mechanisms can result in
key symptoms of multiple psychiatric and neurological disorders.

## Key facts

- **NIH application ID:** 10766773
- **Project number:** 5R01DA040701-08
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Henry Yin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $362,250
- **Award type:** 5
- **Project period:** 2016-09-30 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10766773

## Citation

> US National Institutes of Health, RePORTER application 10766773, Dissecting basal ganglia circuit mechanisms underlying instrumental learning (5R01DA040701-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10766773. Licensed CC0.

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