# A gut-brain interaction controlling reward learning

> **NIH NIH R01** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2022 · $352,436

## Abstract

Project Summary/Abstract
The functions and computations supported by changes in the activity of meso-striatal dopamine systems are
some of the most heavily researched, and hotly debated, topics in modern neuroscience. Predominant theories
propose that they support reinforcement learning by broadcasting prediction-error signals, encode stimulus
salience, or generally motivate reward seeking by representing internal states. Furthermore, it is widely accepted
that these systems have been shaped by natural selection to reinforce adaptive behaviors. Eating, or the pursuit
of nutrients, is fundamental for survival, and previous work has demonstrated that striatal DA circuits are critical
components of the neurobiological systems that support this behavior. Importantly, emerging research supports
a model whereby midbrain DA populations receive signals from the gut about food content that modify their
activity and contribute to food learning and motivation. However, the timescale over which these gut-derived
signals modulate DA release, and how they interact with DA signals previously identified as critical for food
reward learning and motivation, is largely unknown. Here, we propose to address these gaps in our knowledge
by using state of the art techniques to 1) Identify the ensembles of neurons in midbrain dopamine populations
that are recruited by post-ingestive signals to control food reward. 2) Characterize the ability of post-ingestive
signals to modify reward learning via effects on dopamine release in subregions of the striatum. 3)Test the causal
role of post-ingestive signals for dopamine control of food reward. To accomplish these aims, we have
assembled a team including behavioral and systems neuroscientists with expertise in modern technologies for
recording and manipulating genetically defined cell populations, translational neuroscientists with expertise in
the neurobiology of appetitive behaviors, statisticians specializing in big-data analysis, as well as leaders in the
field of computational neuroscience. Completion of these studies will provide an opportunity to integrate
peripheral modulation of midbrain dopamine systems into current models of dopamine control of reward learning
and motivation, and provide a foundation for future studies of peripheral-central dopamine contributions to
multiple adaptive functions and disease states.

## Key facts

- **NIH application ID:** 10496603
- **Project number:** 1R01DK133823-01
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** William Matthew Howe
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $352,436
- **Award type:** 1
- **Project period:** 2022-08-05 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10496603

## Citation

> US National Institutes of Health, RePORTER application 10496603, A gut-brain interaction controlling reward learning (1R01DK133823-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10496603. Licensed CC0.

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