# Investigating the persistent effects of obesity on effortful behavior and underlying neural circuits

> **NIH NIH F32** · WASHINGTON UNIVERSITY · 2022 · $46,822

## Abstract

Project Summary/Absract
Obesity is a leading cause of preventable death in this country. However, despite widespread knowledge of the
prevalence and health disparities linked to chronic obesity, effective treatments remain elusive – most people
who lose weight will re-gain it. Though prior research has often explored metabolic or energy adaptations to
explain weight re-gain, this does not address the proven contribution of hedonic feeding mechanisms to weight
re-gain after obesity. Human and rodent studies show that weight loss after obesity causes increased motivation
to consume palatable foods, and that activity in brain areas involved in food motivation – namely the medial
prefrontal cortex (mPFC) and the nucleus accumbens (NAc) – is altered with obesity. Yet both enhancements
and reductions in synaptic connectivity between mPFC and NAc during obesity have been reported, rendering
conclusions about how hedonic feeding circuits change with obesity difficult to draw, and therefore challenging
to target with potential therapies. The long-term objective of the experiments proposed here is to define the
neural mechanisms governing chronic, obesity-linked changes in food motivation in the mPFC-NAc circuit. I
propose to do this by investigating how activity in NAc neural ensembles tuned to food seeking is affected by
obesity and subsequent weight loss. I hypothesize that obesity increases mPFC-NAc connectivity onto discrete
NAc neural ensembles modulated during food seeking, and that this persists after weight loss. Here I propose
to test this hypothesis in three aims: Aim 1) I will identify how weight gain and weight loss alter NAc ensemble
activity during food seeking, Aim 2) I will identify how activity of a genetically identified subset of NAc neurons
associated with reward changes during food seeking as a result of weight gain and subsequent weight loss, and
Aim 3) I will investigate how weight loss after obesity disrupts synaptic plasticity mechanisms. These aims will
be investigated using novel behavioral techniques, in vivo recording of single neuron activity, and optogenetic
stimulation to induce and study corticostriatal synaptic connectivity mechanisms. The data from these
experiments will elucidate a persistent neural mechanism through which obesity increases food motivation and
ultimately allow for the generation of targeted therapies to combat obesity.

## Key facts

- **NIH application ID:** 10468004
- **Project number:** 5F32DK126355-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Bridget Matikainen-Ankney
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,822
- **Award type:** 5
- **Project period:** 2021-06-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10468004

## Citation

> US National Institutes of Health, RePORTER application 10468004, Investigating the persistent effects of obesity on effortful behavior and underlying neural circuits (5F32DK126355-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10468004. Licensed CC0.

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