# Dissecting basal ganglia circuits underlying motivated behaviors

> **NIH NIH R01** · COLD SPRING HARBOR LABORATORY · 2024 · $700,906

## Abstract

Dissecting basal ganglia circuits underlying motivated behaviors
Project Summary
 The basal ganglia, in particular the dorsal striatum, play essential roles in motor control, motivational regulation
and reinforcement learning. On the other hand, striatal dysfunctions have been implicated in a number of
neurological and psychiatric disorders, including Parkinson's disease, Huntington’s disease, obsessive
compulsive disorder, autism, depression and drug addiction. A notable feature of the dorsal striatum is its
separation into two neurochemically distinct compartments, the striosome (or “patch”) compartment and the
surrounding matrix compartment. It is thought that neurons in the matrix and those in the striosome have distinct
functions, with the former critical for motor functions, whereas the latter important for evaluation functions during
learning and for regulation of motivation. In addition, the striosome compartment has been especially implicated
in the non-motor aspects of the neurological disorders, such as learning deficits, and mood and motivational
aberrations. However, despite intensive study, to date the functionality of neurons in the striosome remains
largely uncharacterized. Consequently, how striosome neurons contribute to reinforcement learning and
regulation of motivation is unclear. Whether and how dysfunctions in these neurons occur and contribute to the
diseases are also unknown.
 A major challenge to studying the striosome lies in the fact that it is labyrinthine in shape and has no clear
anatomical boundaries, making it difficult to precisely target for in vivo recording or manipulation. To address this
issue, we recently exploited mouse genetics for targeting neurons in the striosome. This strategy laid the
foundation for selectively monitoring and manipulating the activities of different populations of striosome neurons.
In the proposed study, we will capitalize on our approach and findings to investigate the behavioral roles of
distinct striosome populations in health and disease, and to uncover the underlying circuit and cellular
mechanisms. Our central hypothesis is that functionally distinct striosome populations differentially control
reward seeking and punishment avoidance through different circuit mechanisms. We further hypothesize that
these striosome neurons become dysfunctional after major stressful life events, thereby causing maladaptive
behaviors. We will test our hypotheses in the following Aims:
 Aim 1. To determine the behavioral roles of distinct classes of striosome neurons.
 Aim 2. To determine the circuit and cellular mechanisms underlying striosome functions.
 Aim 3. To elucidate the striosome dysfunctions underlying stress-induced maladaptive behaviors.

## Key facts

- **NIH application ID:** 10756506
- **Project number:** 5R01MH108924-08
- **Recipient organization:** COLD SPRING HARBOR LABORATORY
- **Principal Investigator:** Jessica Tollkuhn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $700,906
- **Award type:** 5
- **Project period:** 2015-09-28 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10756506

## Citation

> US National Institutes of Health, RePORTER application 10756506, Dissecting basal ganglia circuits underlying motivated behaviors (5R01MH108924-08). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10756506. Licensed CC0.

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