# Plasticity and Function of Dopamine Circuits Regulating the Transition to Habit

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2024 · $502,708

## Abstract

PROJECT SUMMARY/ABSTRACT
Habits and motor skills are essential to survival, allowing for the fast, fluid, and automatic execution of actions
that have repeatedly proved beneficial. Despite their utility, habits and motor skills come at a cost: a loss of
behavioral flexibility. Automated actions that were previously beneficial can become maladaptive if action-
outcome contingencies shift. Because automated actions are hard to adjust once established, maladaptive
behaviors can persist, as is hypothesized to occur in obsessive-compulsive disorder (OCD) and addiction, for
example. A major long-term goal of my laboratory is to understand how and why actions become automated
through the closely related processes of habit formation and motor skill acquisition. What is the normal process
of automation and how may it go awry in psychiatric disorders? Previous studies have identified a key role for
the dorsolateral striatum (DLS), but it remains unclear how the DLS becomes engaged in behavior over time as
goal-directed actions are repeated and automated. Existing theories have been difficult to test empirically, stalling
the field. This project takes advantage of recent technological advancements in neural circuit tracing,
intersectional genetic targeting of cell types, and optogenetics and fiber photometry, innovatively combined, to
bring new data to bear on the problem and to inspire work on fresh hypotheses. Our main objective in this
proposal is to characterize the neural circuits controlling dopaminergic input to the DLS, which is critical for
regulating synaptic plasticity in this brain region. We will identify synaptic plasticity mechanisms in the
dopaminergic midbrain that underlie changes in DLS dopamine release related to habit formation and motor skill
acquisition, and empirically test a long-standing hypothesis in the field, the Ascending Spiral Hypothesis, which
posits that activity in goal-directed regions of the striatum disinhibits DLS dopamine release. We will reformulate
the Ascending Spiral Hypothesis as needed based on new data. Our innovative approach integrates circuit
tracing, electrophysiology, optogenetics, fiber photometry, and behavioral studies across three specific aims,
spanning levels of analysis from detailed subcellular synaptic input mapping to in vivo circuit function. With the
successful completion of this project, we will provide a robust characterization of the Ascending Spiral circuit and
its role in controlling DLS dopamine dynamics before, during, and after action automation. This research will
have a broad impact as it will answer fundamental questions about the neural mechanisms underlying action
automation. By understanding the brain circuit activity allowing transitions from goal-directed control to habits
and motor skills, we will unlock a new point of entry into studying how complex polygenic diseases such as OCD
and addiction emerge from the confluence of genetic and environmental factors on circuit function.

## Key facts

- **NIH application ID:** 10866481
- **Project number:** 5R01MH125885-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Talia Newcombe Lerner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $502,708
- **Award type:** 5
- **Project period:** 2023-06-16 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10866481

## Citation

> US National Institutes of Health, RePORTER application 10866481, Plasticity and Function of Dopamine Circuits Regulating the Transition to Habit (5R01MH125885-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10866481. Licensed CC0.

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