# Epigenetic Regulation Of Striatal Circuit Function For Action And Habit Learning

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $501,287

## Abstract

PROJECT SUMMARY
Growing evidence suggests addiction and other diseases of behavioral control result from the development of
maladaptive habits. Indeed, an overreliance on habit is associated with the compulsive phenotype found in
patients diagnosed with addiction and alcoholism, and comorbid conditions including obsessive-compulsive
disorder and schizophrenia. Addictive substances and stress are thought to hijack the brain systems that
normally support habit learning, causing habits to form faster and more strongly influence behavior than normal.
This results in behavior that is insensitive to its consequences, even when those consequences are negative.
Our ultimate goal is to expose the epigenetic-genomic-physiological-functional conduit that allows stress and
exposure to addictive substances to promote these maladaptive habits. To achieve this, our specific goal here
is to expose the multi-layered biological architecture required for mechanistic understanding of adaptive and
maladaptive habits. Thus, this work will provide insight into how pathological states arise and what can be done
to combat them.
 The striatum has long been known to function in habit learning. Where information is lacking is on how each
striatal projection pathway, the direct- and indirect-projections to basal ganglia output nuclei, contribute and how
their function might differ depending on the anatomically and functionally distinct medial and lateral striatal
subdivisions. We will use a multi-faceted and integrative approach to expose the physiological and molecular
changes that occur in each striatal subcircuit during goal-directed and habit learning. Our preliminary
investigations have indicated that one major epigenetic repressor, HDAC3, functions in the striatum as a negative
regulator of habit formation. Our hypothesis is that dorsal striatal HDAC3 functions as a molecular gate over
habit, being engaged at the promoters of key neuronal activity genes to slow the transition to habit and being
removed when conditions are ripe for habits to dominate. Thus, chronic stress and exposure to addictive
substances might open this gate, creating an epigenetic landscape that biases future behavioral strategy towards
habit, even with this is not adaptive, producing the compulsivity that marks many mental illnesses. Our proposed
research begins to test this by investigating the molecular and cellular mechanisms that allows HDAC3 to
regulate habit. This will enable future investigations into how disruptions in these mechanisms promote
maladaptive behavior.

## Key facts

- **NIH application ID:** 9891987
- **Project number:** 5R01DA046679-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Kate M Wassum
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $501,287
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9891987

## Citation

> US National Institutes of Health, RePORTER application 9891987, Epigenetic Regulation Of Striatal Circuit Function For Action And Habit Learning (5R01DA046679-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9891987. Licensed CC0.

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