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GABAAR-δ-subunit mediates increased GABAergic inhibition in cardiac DMV neurons after high-fat diet
Yoko Brigitte Wang1,2, Kaylie E Dow1,2, Carie R Boychuk1,2
1Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA.
Abstract:
Activity of cardiac-projecting neurons in the dorsal motor nucleus of the vagus (CVNDMV) 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 CVNDMV. Using whole-cell patch-clamp electrophysiology, we found that 15-day HFD feeding increased tonic, but not phasic, gamma-aminobutyric acid type A (GABAA) inhibitory neurotransmission, exclusive to CVNDMV. Single-cell quantitative reverse-transcription PCR (scRT-qPCR) analysis revealed a higher number of CVNDMV expressing GABAA receptor δ-subunit (GABAA(δ)R) in HFD compared to normal fat diet (NFD). Deletion of GABAA(δ)R in ChAT-positive motor neurons abolished HFD-induced increased tonic GABAA neurotransmission in CVNDMV. Altogether, this evidence suggests that CVNDMV exhibits early onset HFD-induced increased GABAergic neurotransmission, likely mediated by GABAA(δ)R. This increased inhibitory tone could explain previously reported reduced cardiac vagal motor output, thus contributing to poor cardiometabolic health after HFD.
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