# Astrocyte-Dependent Modulation of Synaptic Strength in Response to Acute High Fat Diet

> **NIH NIH F31** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2020 · $32,159

## Abstract

ABSTRACT
 Obesity and its comorbid disorders are estimated to affect more than one-third of adults in the U.S.
alone, and is rapidly growing as a worldwide health concern. The dramatic rise in obesity has underscored the
importance of understanding the neural mechanisms involved in energy homeostasis and visceral functions
such as feeding and digestion. While diet-induced obesity (DIO) and long-term exposure to high-fat diet (HFD)
have been shown to modulate neurotransmission in many areas of the brainstem, including vago-vagal
neurocircuits, we have demonstrated previously that even acute exposure to HFD modulates vagal
neurocircuits. Specifically, short term exposure to HFD (3-5 days) modulates glutamatergic transmission in the
dorsal motor nucleus of the vagus (DMV), increasing synaptic NMDA currents, DMV neuronal excitability and,
in turn, increases gastric tone and motility. Recent studies from our lab have also suggested that activation of
astrocytes or extrasynaptic NMDA receptors may be involved in this modulation. The mechanism that results in
this increased NMDA current following acute HFD exposure has, however, not been elucidated.
Previous studies have suggested that increased synaptic NMDA receptor activation may occur subsequent to
activation of extrasynaptic NMDA receptors, which causes sufficient local depolarization to remove the Mg2+
block on synaptic NMDA receptors. Furthermore, previous studies suggest that astrocytic release of glutamate
may responsible for this extrasynaptic NMDA receptor activation. The aim of this study is to test the hypothesis
that, acute HFD exposure induces the release of astrocytic glutamate that activates extrasynaptic and synaptic
NMDA-R activation in the DVC. Aim 1 will investigate the hypothesis that, following acute HFD exposure,
astrocytic gliotransmitter release increases NMDA receptor activation following acute HFD exposure. Aim 2 will
investigate the hypothesis that, acute HFD-induced increase in synaptic NMDA currents is dependent upon
astrocytic glutamate release.
 The potential to examine plasticity in brainstem neurocircuitry resulting from alterations in nutrition
brings with it the opportunity to uncover the mechanistic basis for brain-gut homeostasis and regulation of
feeding behavior which, in turn, may provide insights into the dysregulation of these pathways which leads to
impaired energy balance and obesity.

## Key facts

- **NIH application ID:** 9884518
- **Project number:** 5F31DK118833-02
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Courtney E Clyburn
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $32,159
- **Award type:** 5
- **Project period:** 2019-03-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9884518

## Citation

> US National Institutes of Health, RePORTER application 9884518, Astrocyte-Dependent Modulation of Synaptic Strength in Response to Acute High Fat Diet (5F31DK118833-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9884518. Licensed CC0.

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