# Molecular Genetics of Associative Reward Learning

> **NIH NIH R21** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $185,625

## Abstract

The ability to form and maintain associations between environmental cues, actions, and rewarding stimuli is an
elementary yet fundamental aspect of learned behavior that is necessary for survival. Multiple lines of research
have identified that such reward-related learning is mediated by dopamine neurons located in the midbrain.
Dopamine neurons encode stimulus-reward relationships in a way that is dynamically modified during learning,
and impaired dopamine neuron functioning inhibits reward learning. However, almost nothing is known about
how the molecular mechanisms in dopamine neurons that are relevant for learning. While pioneering studies
have identified that Egr1 (Early growth response 1; an activity-responsive transcription factor) is rapidly
upregulated in dopamine neurons after learning and correlates with learning strength, the functional
consequence of this upregulation for learning and mechanistic consequences of this upregulation has not been
examined. Specific Aim 1 of this proposal will use bidirectional CRISPR-based manipulation of Egr1 to
determine it’s role in reward learning. Specific Aim 2 will define downstream gene targets of Egr1 induction
using innovative single-cell sequencing as well as chromatin immunoprecipitation. This novel approach will
demonstrate the necessity of Egr1 for learning and will pave the way for future experiments to explore how
experience-dependent gene expression programs contribute to motivated behavior.

## Key facts

- **NIH application ID:** 9949663
- **Project number:** 5R21DA048348-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** JEREMY J DAY
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $185,625
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9949663

## Citation

> US National Institutes of Health, RePORTER application 9949663, Molecular Genetics of Associative Reward Learning (5R21DA048348-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9949663. Licensed CC0.

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