# GABAergic Interneurons Regulate Brainstem Neural Circuitry

> **NIH NIH R01** · GEORGETOWN UNIVERSITY · 2021 · $349,875

## Abstract

The goal of this proposal is to determine the role of two specific GABAergic interneurons, somatostatin
(Sst) and neuropeptide Y (Npy) expressing neurons, in the regulation of Brainstem neural circuitry
controlling gastric function. Our studies, focusing on the major brain nuclei of this circuit that form the dorsal
vagal complex (DVC) in the hindbrain, namely the medial nucleus tractus solitarius (mNTS) and dorsal motor
nucleus of the vagus (DMV), indicate that local GABA signaling in these nuclei is critical for modulation of vagal
output to the stomach. However, the identity of the GABA neurons to which this inhibitory signaling can be
attributed is lacking. Recent advances in transgenic mouse models, virus injection and optogenetic techniques
have made it possible to isolate and selectively stimulate specific cell types. Using these technologies, we
have begun to acquire nascent data on the identity and role of the neurons involved in GABA signaling in the
DVC. Furthermore, these techniques have been instrumental in obtaining information on the likely mechanisms
by which a regulator of energy homeostasis, namely an endogenous agonist of the melanocortin receptor
system (McR), produces its differential effects on gastric function (e.g., tone and motility) in the NTS (inhibitory)
and in the DMV (excitatory). The focus of the present proposal is on the genetically and virally defined Sst and
Npy neurons in the DVC. We will investigate the functional role of these neurons in DVC circuitry by
determining their electrophysiological and morphological characteristics in relation to other neurons that
comprise the neural circuitry controlling gastric function via trans-synaptic labeling. Our previously published
data and preliminary findings show that optogenetic stimulation of Sst/Npy neurons in the NTS or DMV strongly
influence the activity of neurons along the Brain-Gut axis. Based on these results, we will pursue our overall
hypothesis that Sst and Npy neurons in the DVC serve as key complementary components that regulate
the vago-vagal gastric circuitry. Finally, we will assess the role of Sst and Npy neurons in an in vivo model
of gastric function. In this model, we will test the hypothesis that stimulation of Sst and Npy GABA neurons in
the mNTS and DMV will selectively affect gastric tone and motility. The knowledge gained from our proposed
studies will contribute greatly to understanding vago-vagal circuitry controlling gastric function, with the
potential of providing an important template for studying homeostasis in other autonomic reflex systems.

## Key facts

- **NIH application ID:** 10163174
- **Project number:** 5R01DK117508-04
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** Stefano Vicini
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $349,875
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10163174

## Citation

> US National Institutes of Health, RePORTER application 10163174, GABAergic Interneurons Regulate Brainstem Neural Circuitry (5R01DK117508-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10163174. Licensed CC0.

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