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

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.