# The role of dopamine in OFC-DMS plasticity in punishment-resistant reward-seeking behavior

> **NIH NIH F31** · NORTHWESTERN UNIVERSITY · 2024 · $44,187

## Abstract

PROJECT SUMMARY/ABSTRACT
Decision-making is an important cognitive function that animals use to seek life-preserving rewards like
food while avoiding dangers like predation and injury. Understanding how animals balance between risk and
reward is important, with implications for psychiatric disorders like substance use disorder (SUD), in which
decision-making is impaired. The orbitofrontal cortex (OFC) and dorsal medial striatum (DMS) are brain regions
that are part of the decision-making circuitry. The OFC sends a strong projection to the DMS and it has been
found that OFC-DMS plasticity is important for punishment-resistant reward-seeking behavior. Dopamine (DA)
signaling in the DMS has also been found to play a crucial role in the development of punishment-resistant
reward-seeking behavior. However, whether DA controls changes at OFC-DMS synapses that are important for
punishment-resistant reward-seeking behavior is not known.
 The Lerner Lab found that mice prone to developing punishment-resistance have increased phasic DA
activity in the DMS on rewarded nosepokes and dips in DA activity on unrewarded nosepokes.
I hypothesize that
both events (increases and dips in DA) are important for the development of punishment-resistant reward-
seeking behavior because they separately control the plasticity of OFC synapses onto D1- and D2-receptor
expressing DMS neurons. In Aim 1, I will test OFC-DMS plasticity in punishment-resistant sucrose seeking mice,
to understand how plasticity changes with a natural reward. I will use an operant behavior that elicits punishment-
resistant behavior and then look at plasticity using whole cell electrophysiology. In Aim 2, I will investigate if DA
increases in the DMS lead to plasticity changes in the OFC-DMS circuity using optogenetics and whole cell
electrophysiology. In Aim 3, I will test if dips in DA lead to punishment-resistant behavior as well as plasticity
changes in the OFC-DMS circuit. My proposal, in accordance with NIDA’s mission statement, will aide in the
advancement of science on drug use and drug addiction by providing a better understanding of the decision-
making circuitry that is impaired in SUD. Under this training grant, I will receive training in oral and written
communication skills through presenting at conferences, and through supervised grant and manuscript writing.
I will also receive training in programming, data analysis, and mentoring. The training under this grant will provide
me with the tools necessary to become a high-achieving postdoctoral fellow and eventually a successful principal
investigator.

## Key facts

- **NIH application ID:** 10897451
- **Project number:** 1F31DA060615-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Nkatha Karimi Mwenda
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $44,187
- **Award type:** 1
- **Project period:** 2024-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10897451

## Citation

> US National Institutes of Health, RePORTER application 10897451, The role of dopamine in OFC-DMS plasticity in punishment-resistant reward-seeking behavior (1F31DA060615-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10897451. Licensed CC0.

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