Wang Yoko Brigitte, Dow Kaylie E, Boychuk Carie R
Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA.
Department of Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.
iScience. 2025 Mar 22;28(4):112268. doi: 10.1016/j.isci.2025.112268. eCollection 2025 Apr 18.
Activity of cardiac-projecting neurons in the dorsal motor nucleus of the vagus (CVN) 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. Using whole-cell patch-clamp electrophysiology, we found that 15-day HFD feeding increased tonic, but not phasic, gamma-aminobutyric acid type A (GABA) inhibitory neurotransmission, exclusive to CVN. Single-cell quantitative reverse-transcription PCR (scRT-qPCR) analysis revealed a higher number of CVN expressing GABA receptor δ-subunit (GABA(δ)R) in HFD compared to normal fat diet (NFD). Deletion of GABA(δ)R in ChAT-positive motor neurons abolished HFD-induced increased tonic GABA neurotransmission in CVN. Altogether, this evidence suggests that CVN exhibits early onset HFD-induced increased GABAergic neurotransmission, likely mediated by GABA(δ)R. This increased inhibitory tone could explain previously reported reduced cardiac vagal motor output, thus contributing to poor cardiometabolic health after HFD.
迷走神经背运动核（CVN）中投射至心脏的神经元活动在心脏反射中至关重要，有助于维持心血管健康。然而，这群神经元如何适应诸如高脂饮食（HFD）等代谢挑战尚不清楚。本研究旨在确定高脂饮食在CVN中诱导的神经可塑性变化。使用全细胞膜片钳电生理学方法，我们发现喂食15天的高脂饮食增加了CVN特有的持续性而非阶段性的γ-氨基丁酸A型（GABA）抑制性神经传递。单细胞定量逆转录PCR（scRT-qPCR）分析显示，与正常脂肪饮食（NFD）相比，高脂饮食组中表达GABA受体δ亚基（GABA(δ)R）的CVN数量更多。在胆碱乙酰转移酶阳性运动神经元中删除GABA(δ)R可消除高脂饮食诱导的CVN中持续性GABA神经传递增加。总之，这些证据表明，CVN表现出早期高脂饮食诱导的GABA能神经传递增加，可能由GABA(δ)R介导。这种增加的抑制性张力可以解释先前报道的心脏迷走运动输出减少，从而导致高脂饮食后心脏代谢健康状况不佳。
