# Neural control of Reinforcement Learning in SUD

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2020 · $45,520

## Abstract

Project Summary/Abstract
Substance use disorder (SUD) has proven challenging to effectively treat due to the long-term changes in both
behavior and neuronal function that persist long after drug has left the system. Drug-induced changes in neuronal
plasticity are particularly important as they can disrupt both drug-associated behaviors as well as adaptive
behaviors in basal states, thus necessitating a more comprehensive understanding of how the neuronal
populations that underlie this plasticity control basal behaviors as they relate to reward processing and
motivation. At the core of value-based decision making and motivation is the nucleus accumbens, which is
primarily composed of D1 and D2 medium spiny projection neurons (MSNs) that are thought to have opposing
actions on behavior with D1 MSNs promoting reward and D2 MSNs promoting aversion. A large body of work
has outlined the transcriptional, physiological, and in vivo encoding alterations in these populations that occur
as a result of drug exposure and has linked these alterations to drug seeking and consumption. However, these
cellular populations are also integrally involved in learning, selecting, and executing goal-oriented behaviors, and
function as a key neural substrate of cue-reward associations for drug and non-drug stimuli. Currently, the
precise information that is encoded within these populations, and how they guide adaptive behaviors in different
contexts, remains to be definitively elucidated. By combining complex reinforcement tasks that can dissociate
behavioral action from stimulus and outcome value with optical approaches for recording and manipulating D1
and D2 MSNs in awake, behaving mice we will define the specific information that is encoded within these cellular
populations. In Aim 1, I will utilize fiber photometry calcium imaging to define the temporal signature of D1 and
D2 medium spiny neurons (MSNs) during complex behavioral tasks. We hypothesize - based on robust
preliminary data - that D1 and D2 MSNs are not simply “rewarding” and “aversive”, but instead encode specific
components of learned and executed behavior. In Aim 2, I will utilize optogenetics to manipulate activity in D1
and D2 MSNs respectively during discrete time points to demonstrate the functional importance of these
neuronal populations to reinforcement learning. While this proposal encompasses the use of a number of
innovative techniques, it is the technical and theoretical training, gained in combining these techniques with
complex behavioral tasks, that will provide the foundational expertise and conceptual thinking needed to address
larger questions regarding how plastic changes in the brain in response to drug exposure support development
of SUD. Together, this proposal will provide an exceptional training opportunity while simultaneously providing
foundational evidence for the specific changes that occur within genetically defined neuronal populations in
adaptive – and maladaptive – states...

## Key facts

- **NIH application ID:** 10066895
- **Project number:** 1F31DA051153-01A1
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Jennifer Zachry
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 1
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10066895

## Citation

> US National Institutes of Health, RePORTER application 10066895, Neural control of Reinforcement Learning in SUD (1F31DA051153-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10066895. Licensed CC0.

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