Work

GABAAR-δ-subunit mediates increased GABAergic inhibition in cardiac DMV neurons after high-fat diet

Year: 2025

Type: article

Abstract: Activity of cardiac-projecting neurons in the dorsal motor nucleus of the vagus (CVN DMV ) is vital in cardiac reflexes contributing to maintaining cardiovascular health. However, how this population adapts to metabolic challenges, such as high-fat diet (HFD), is unclear. This study aimed to identify neuroplasticity changes induced by HFD in CVN DMV . Using whole-cell patch-clamp electrophysiology, we found that 15-day HFD feeding increased tonic, but not phasic, gamma-aminobutyric acid type A (GABA A ) inhibitory neurotransmission, exclusive to CVN DMV . Single-cell quantitative reverse-transcription PCR (scRT-qPCR) analysis revealed a higher number of CVN DMV expressing GABA A receptor δ-subunit (GABA A (δ)R) in HFD compared to normal fat diet (NFD). Deletion of GABA A (δ)R in ChAT-positive motor neurons abolished HFD-induced increased tonic GABA A neurotransmission in CVN DMV . Altogether, this evidence suggests that CVN DMV exhibits early onset HFD-induced increased GABAergic neurotransmission, likely mediated by GABA A (δ)R. This increased inhibitory tone could explain previously reported reduced cardiac vagal motor output, thus contributing to poor cardiometabolic health after HFD.

Source: iScience

DOI: 10.1016/j.isci.2025.112268

Authors: Yoko Brigitte Wang, Kaylie E. Dow, Carie R. Boychuk

Institution: University of Missouri

Language: English

Topic: Neuroscience and Neuropharmacology Research

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,240