# Dissecting circuits underlying loss of control relevant to binge eating

> **NIH NIH K08** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $162,502

## Abstract

ABSTRACT
Obesity is a critical public health problem associated with substantial morbidity and mortality. Binge eating
(BE), a compulsive episodic overeating behavior, is associated with increased rates of obesity and weight gain.
Despite the negative impact of BE on physiological health and obesity risk, the underlying neural mechanisms
contributing to BE are largely unknown. Loss of control (LOC) over eating - i.e., being unable to control the
quantity of food consumed - is a core feature of BE and a significant predictor of obesity. However, there have
been no mechanistic investigations of in vivo neural activity patterns underlying LOC during BE, limiting
development of new treatments. LOC is associated with difficulties disengaging from eating (i.e., feeding
offset), and pre-clinical models are an optimal system to precisely measure this behavioral event. In this set of
integrated training and scientific Aims, the candidate will identify neural correlates of feeding offset using an
animal model for BE to understand the underlying neural substrates of LOC. Data in mice show that activity in
dorsolateral striatum (DLS), a key region associated with behavior cessation, is blunted at feeding offset after
chronic BE. Preliminary data also suggest that activity in secondary motor cortex (M2) to DLS projecting cells
is reduced prior to feeding offset. This project will examine the role of DLS and M2 to DLS projecting cells in
feeding offset using a robust behavioral paradigm for binge eating in mice. The overarching hypotheses are: 1)
D1 and D2 spiny projection neurons in DLS will differentially contribute to feeding offset in BE vs. non-BE mice;
2) reversing blunted DLS activity in BE mice via closed-loop stimulation will improve pathologic behavior; 3)
specific ensembles of M2 to DLS projecting cells tuned to feeding offset will be less active in BE mice; and 4)
increasing activity of M2 to DLS specific neurons will improve maladaptive feeding behavior. Cellular resolution
in vivo calcium imaging will be used to identify neural activity patterns in specific DLS cell populations during
feeding offset (Aim 1). Closed-loop optogenetics will be used determine whether manipulation of neural activity
in DLS cell populations facilitates changes in feeding offset (Aim 2). Finally, in vivo calcium imaging and
optogenetics will be used to identify, track, and manipulate M2 to DLS projecting cells at feeding offset in BE
and non-BE mice to investigate a potential cortical treatment target for non-invasive treatment of BE (Aim 3).
The integrated training plan will ensure the candidate achieves her career goal of developing an independent
program in translational BE and obesity research. The candidate will expand her training in 4 core areas: 1)
learn cellular resolution in vivo calcium imaging; 2) develop statistical analysis skills applicable to complex
neural data aligned to behavioral events; 3) apply circuit manipulation techniques to inform future treat...

## Key facts

- **NIH application ID:** 10875436
- **Project number:** 5K08DK136916-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Britny Hildebrandt
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $162,502
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10875436

## Citation

> US National Institutes of Health, RePORTER application 10875436, Dissecting circuits underlying loss of control relevant to binge eating (5K08DK136916-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10875436. Licensed CC0.

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