# A CHOLINERGIC NEUROCIRCUIT REGULATES FEEDING BEHAVIOR

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $621,812

## Abstract

PROJECT SUMMARY
Obesity is a major risk factor for many chronic medical conditions, including diabetes, cardiovascular disease,
depression, and cancer. Elucidating the neural networks that regulate feeding behavior and body weight control
is critically needed towards the development of effective strategies to combat obesity and its co-morbidities. We
recently found that the ventral subiculum (vSub), a component of the hippocampal formation, provides
monosynaptic inputs to the ventromedial hypothalamus (VMH). We further revealed that these VMH-projecting
vSub neurons are responsive to food, and chemogenetic activation of VMH-projecting vSub neurons suppresses
food intake in mice. However, we noted that the vSub→VMH circuitry has robust collateral projections to two
other brain regions, the lateral septum (LS) and the accumbens nucleus shell (AcbSh), which could also
contribute to the anorexigenic effects. Thus, our first objective is to systematically dissect which of these vSub
collaterals mediate anorexigenic action. Importantly, we will explore the physiological relevance of this circuit in
chronic feeding and weight regulation by using a mouse model with these vSub neurons genetically ablated. We
also found that cholinergic neurons in the diagonal band of Broca (DBBChAT neurons) provide extensive synaptic
inputs onto vSub neurons. The second objective of this research is to examine the effects of the DBBChAT→vSub
circuit on feeding, and to explore the physiological relevance of this upstream circuit in the chronic regulation of
proper feeding behavior and body weight control. Further, we found that vSub neurons abundantly express the
α7 subunit of nAChRs, and these cells can be activated by α7-nAChR agonists. Thus, the third objective of the
proposed research is to generate mice lacking α7-nChAR from vSub neurons, and use this model to elucidate
the physiological relevance of α7-nAChR within vSub circuitry towards feeding behavior and obesity
development. Together, these studies will rigorously examine the functions of both the downstream outputs and
upstream inputs of vSub neurons in feeding circuitry, and further identify the role of nAChR signaling in vSub
neurons that suppresses feeding. Accomplishment of these studies will fill a critical gap in knowledge by
identifying a novel neural circuit in the context of body weight regulation. Further, our results may provide needed
framework to develop novel therapeutic strategies towards obesity treatment.

## Key facts

- **NIH application ID:** 10816901
- **Project number:** 1R01DK138518-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Benjamin R Arenkiel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $621,812
- **Award type:** 1
- **Project period:** 2024-06-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10816901

## Citation

> US National Institutes of Health, RePORTER application 10816901, A CHOLINERGIC NEUROCIRCUIT REGULATES FEEDING BEHAVIOR (1R01DK138518-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10816901. Licensed CC0.

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