# 5-HT NEURONS INTEGRATE NEURAL INPUTS TO REGULATE FOOD INTAKE

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $431,018

## Abstract

Obesity is a major risk factor for type II diabetes and metabolic syndromes. Increased understanding of
food intake and body weight regulation may lead to effective strategies to combat obesity and diabetes.
Serotonin (5-HT) neurons in the dorsal Raphe nucleus (DRN) play an essential role in regulating feeding
behavior. Enhanced brain 5-HT actions robustly inhibit food intake and body weight but little is known about
how firing activity of 5-HTDRN neurons is regulated. Based on pilot observations, the Xu and Tong labs put
forward a general hypothesis that 5-HTDRN neurons integrate dopamine (DA) and GABA inputs to
promote food intake. The first objective is to determine whether DA released by neurons in the ventral
tegmental area inhibits 5-HTDRN neurons to promote food intake. In vivo optogenetic studies will be carried
out to determine whether photostimulation of the DAÆDRN circuit increases food intake while photoinhibition
of the same circuit inhibits eating; a DA receptor (DRD2) will be deleted in 5-HT neurons to test whether this
deletion decreases food intake and body weight and block effects of DAÆDRN activation in mice. The
second objective is to determine whether GABA released by neurons in the lateral hypothalamus inhibits
5-HTDRN neurons to promote food intake. Similar optogenetic studies will be carried out to determine whether
photostimulation of the GABAÆDRN circuit increases food intake while photoinhibition of the same circuit
inhibits eating; a GABA receptor (Ȗ2) will be deleted in 5-HT neurons to test whether this deletion decreases
food intake and body weight and block effects of GABAÆDRN activation in mice. The third objective is to
determine whether DA and GABA signals converge on the same or distinct subsets of 5-HTDRN neurons and
whether stimulation of both DA and GABA-originated circuits produce redundant or synergistic effects on
food intake. Thus, accomplishment of these experiments may advance our understanding about the
physiological roles of brain 5-HT system in the regulation of feeding and energy balance, we may also
identify novel targets (e.g. DRD2 and Ȗ) for therapeutic development of human diseases, e.g. obesity.

## Key facts

- **NIH application ID:** 10259803
- **Project number:** 5R01DK120858-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Qingchun Tong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $431,018
- **Award type:** 5
- **Project period:** 2020-09-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10259803

## Citation

> US National Institutes of Health, RePORTER application 10259803, 5-HT NEURONS INTEGRATE NEURAL INPUTS TO REGULATE FOOD INTAKE (5R01DK120858-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10259803. Licensed CC0.

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