Abstract：
The obesity epidemic is principally driven by the consumption of more calories than the body requires. It is therefore essential that the mechanisms underpinning feeding behavior are defined. Neurons within the brainstem dorsal vagal complex (DVC) receive direct information from the digestive system and project to second-order regions in the brain to regulate food intake. Although γ-aminobutyric acid is expressed in the DVC (GABADVC), its function in this region has not been defined. In order to discover the unique gene expression signature of GABADVC cells, we used single-nucleus RNA sequencing (Nuc-seq), and this revealed 19 separate clusters. We next probed the function of GABADVC cells and discovered that the selective activation of GABADVC neurons significantly controls food intake and body weight. Optogenetic interrogation of GABADVC circuitry identified GABADVC → hypothalamic arcuate nucleus (ARC) projections as appetite suppressive without creating aversion. Electrophysiological analysis revealed that GABADVC → ARC stimulation inhibits hunger-promoting neuropeptide Y (NPY) neurons via GABA release. Adopting an intersectional genetics strategy, we clarify that the GABADVC → ARC circuit curbs food intake. These data identify GABADVC as a new modulator of feeding behavior and body weight and a controller of orexigenic NPY neuron activity, thereby providing insight into the neural underpinnings of obesity.
摘要：
肥胖流行主要是由消耗超过身体所需的卡路里驱动的。因此，至关重要的是确定支撑摄食行为的机制。脑干背侧迷走神经复合体（DVC）内的神经元从消化系统接收直接信息，并投射到大脑中的二级区域以调节食物摄入。尽管γ-氨基丁酸在DVC（GABADVC）中表达，它在这个地区的功能尚未定义。为了发现GABADVC细胞独特的基因表达特征，我们使用单核RNA测序（Nuc-seq），这揭示了19个独立的集群。接下来，我们研究了GABADVC细胞的功能，发现GABADVC神经元的选择性激活显着控制食物摄入和体重。GABADVC电路的光遗传学询问将GABADVC→下丘脑弓状核（ARC）投射视为食欲抑制而不会产生厌恶。电生理分析表明，GABADVC→ARC刺激通过GABA释放抑制饥饿促进神经肽Y（NPY）神经元。采用交叉遗传学策略，我们澄清了GABADVC→ARC电路抑制了食物摄入。这些数据表明GABADVC是摄食行为和体重的新调节剂，也是食欲性NPY神经元活动的控制器，从而深入了解肥胖的神经基础。
