Abstract：
The hormone leptin reduces food intake through actions in the peripheral and central nervous systems, including in the hindbrain nucleus of the solitary tract (NTS). The NTS receives viscerosensory information via vagal afferents, including information from the gastrointestinal tract, which is then relayed to other central nervous system (CNS) sites critical for control of food intake. Leptin receptors (lepRs) are expressed by a subpopulation of NTS neurons, and knockdown of these receptors increases both food intake and body weight. Recently, we demonstrated that leptin increases vagal activation of lepR-expressing neurons via increased NMDA receptor (NMDAR) currents, thereby potentiating vagally evoked firing. Furthermore, chemogenetic activation of these neurons was recently shown to inhibit food intake. However, the vagal inputs these neurons receive had not been characterized. Here we performed whole cell recordings in brain slices taken from lepRCre × floxedTdTomato mice and found that lepR neurons of the NTS are directly activated by monosynaptic inputs from C-type afferents sensitive to the transient receptor potential vanilloid type 1 (TRPV1) agonist capsaicin. CCK administered onto NTS slices stimulated spontaneous glutamate release onto lepR neurons and induced action potential firing, an effect mediated by CCKR1. Interestingly, NMDAR activation contributed to the current carried by spontaneous excitatory postsynaptic currents (EPSCs) and enhanced CCK-induced firing. Peripheral CCK also increased c-fos expression in these neurons, suggesting they are activated by CCK-sensitive vagal afferents in vivo. Our results indicate that the majority of NTS lepR neurons receive direct inputs from CCK-sensitive C vagal-type afferents, with both peripheral and central CCK capable of activating these neurons and NMDARs able to potentiate these effects.
摘要：
激素瘦素通过外周和中枢神经系统的作用减少食物摄入，包括孤立道（NTS）的后脑核。NTS通过迷走神经传入接收内脏感觉信息，包括来自胃肠道的信息，然后将其传递到对控制食物摄入至关重要的其他CNS位点。瘦素受体（lepRs）由NTS神经元亚群表达，这些受体的敲除会增加食物摄入量和体重。最近,我们证明了瘦素通过增加NMDAR电流增加了表达lepR的神经元的迷走神经激活，从而增强迷走神经诱发的放电。此外，最近显示这些神经元的化学遗传激活抑制食物摄取。然而,这些神经元接受的迷走神经输入尚未被表征。在这里，我们在取自lepRCreXfloxedTdTomato小鼠的脑切片中进行了全细胞记录，发现NTS的lepR神经元被对TRPV1激动剂辣椒素敏感的C型传入的单突触输入直接激活。在NTS切片上施用CCK刺激了lepR神经元上的自发谷氨酸释放并诱导了动作电位放电；CCKR1介导的作用。有趣的是,NMDAR激活有助于自发性EPSC携带的电流并增强CCK诱导的放电。外周CCK也增加了这些神经元的c-fos表达，表明它们在体内被CCK敏感的迷走神经传入神经激活。我们的结果表明，大多数NTSlepR神经元接受来自CCK敏感的C迷走神经型传入的直接输入，外周和中枢CCK都能够激活这些神经元，NMDAR能够增强这些作用。
