# Characterization of NAc D1 MSNs in Encoding Reward, Aversion, and Decision-Making During Conflict

> **NIH NIH FI2** · U.S. NATIONAL INSTITUTE OF MENTAL HEALTH · 2021 · —

## Abstract

PROJECT SUMMARY
Impaired reward and aversion processing underlie the symptomatology of a diverse set of psychiatric
disorders. However, the precise neural basis of reward and aversive stimuli remains to be elucidated. The
nucleus accumbens (NAc) is a key brain region implicated in hedonic processing, encoding reward and
aversion signals via medium spiny neurons (MSNs) that express dopamine D1 receptors (D1) or dopamine
D2 receptors (D2). The canonical view of NAc functioning is that D1- MSNs encode reward, and D2- MSNs
encode aversion. However, recent work has challenged this view, as D1 MSNs have been found to encode
aversive states or inhibit reward seeking. Our preliminary data using single unit recording with miniscope
imaging, revealed that only some NAc D1 MSNs activate in response to a footshock whereas others do
not. NAc D1-MSNs project to the LH, VTA, and VP, whereas D2-MSNs only project to the VP. Hence, one
possibility is that there are subsets of D1 MSNs that encode both reward and aversion based depending
on their output regions. To address this gap, we propose that NAc D1 MSNs encode reward or aversion
based on their efferent organization and participate in adaptive decision -making during conflict between
reward and aversion. This hypothesis will be tested in two specific aims: Aim 1 tests the hypothesis that
different ensembles of NAc D1 MSNs encode reward or aversion depending on efferent organization. In
Aim 2, we will test the hypothesis that D1 MSNs encode decision making during motivational conflict
between reward and aversion, advancing our understanding of D1 MSNs independent of the outcomes
obtained in Aim 1. To test the hypothesis, these experiments will combine novel methods, such as
transgenic/viral approaches, single-cell Ca2+ imaging, optogenetics, and machine learning. Thus, I will gain
training in in these techniques forming a strong foundation for my independent research program to answer
questions in line with my interests in motivation and decision making in a technically elegant and
translationally relevant manner. These results will contribute to our understanding of motivational and
emotional neural circuits implicated in the pathophysiology of psychiatric disorders, such as depression and
addiction.

## Key facts

- **NIH application ID:** 10276180
- **Project number:** 1FI2GM143131-01
- **Recipient organization:** U.S. NATIONAL INSTITUTE OF MENTAL HEALTH
- **Principal Investigator:** Rodolfo Flores Garcia
- **Activity code:** FI2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10276180

## Citation

> US National Institutes of Health, RePORTER application 10276180, Characterization of NAc D1 MSNs in Encoding Reward, Aversion, and Decision-Making During Conflict (1FI2GM143131-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10276180. Licensed CC0.

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