# Defining the role of compartment-specific dopamine dynamics in reinforcement learning

> **NIH NIH F32** · VANDERBILT UNIVERSITY · 2021 · $65,994

## Abstract

Project Summary and Abstract
Substance use disorder (SUD) is a debilitating disorder that has a societal cost of more than 700 million dollars
per year in the US alone. Despite the prevalence and significant global financial burden of SUD, the
pathophysiology of the disorder is poorly understood, and current treatments have limited efficacy. At the core
of SUD is a dysregulation in reward learning and appetitive motivation. These effects are mediated by drug-
induced alterations in dopamine transmission in the ventral tegmental area (VTA) to nucleus accumbens (NAc)
projection pathway, which has been causally linked to these behavioral phenotypes. Further, animal models of
SUD show dysregulation of VTA to NAc excitability and accumbal dopamine release at terminals, further
supporting the critical role that this system plays in the expression of dysregulated drug and non-drug associated
behaviors. Within this VTA to NAc pathway, dopamine is released from multiple cellular compartments –
including somatodendritic and terminals - that are regulated by different molecular, circuit-based, and receptor-
based mechanisms. However, while work has focused on ex vivo measurements of dopamine release at
terminals, relatively little is known about the roles of release in other compartments within this pathway, such as
somatodendritic release within the VTA and how this relates to the execution of motivated behaviors in a basal
state. The goal of this proposal is to understand the compartment-specific experience-dependent plasticity that
underlies appetitive motivation and reward learning in vivo and then define the molecular mechanisms for this
plasticity. To this end, we will use a combination of cutting-edge techniques, including in vivo fiber photometry
combined with fluorescent dopamine sensors during operant behavior to image dopamine transients within the
VTA and NAc longitudinally over time. We will then use ex vivo fast scan cyclic voltammetry combined with
optogenetic stimulation and pharmacology in somatodendritic and terminal compartments to define the receptor-
based mechanisms by which this dopaminergic plasticity occurs. By defining these molecular targets that
underlie reward and motivation, these experiments will help to identify targets that may be driving learning-
dependent plasticity mechanisms within the mesolimbic pathway. As such, the results of these experiments have
broad implications for identifying and understanding the potential mechanisms of dopamine dysregulation in SUD
and may provide therapeutic avenues in order to reverse deficits in these processes.

## Key facts

- **NIH application ID:** 10241269
- **Project number:** 5F32DA051136-02
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Suzanne Olivia Nolan
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $65,994
- **Award type:** 5
- **Project period:** 2020-08-10 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241269

## Citation

> US National Institutes of Health, RePORTER application 10241269, Defining the role of compartment-specific dopamine dynamics in reinforcement learning (5F32DA051136-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241269. Licensed CC0.

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