Florey Institute of Neuroscience and Mental Health, and.
Department of Physiology, University of Melbourne, Parkville, Victoria 3010, Australia.
J Neurosci. 2019 Oct 9;39(41):8038-8050. doi: 10.1523/JNEUROSCI.3036-18.2019. Epub 2019 Aug 30.
Integration and modulation of primary afferent sensory information begins at the first terminating sites within the CNS, where central inhibitory circuits play an integral role. Viscerosensory information is conveyed to the nucleus of the solitary tract (NTS) where it initiates neuroendocrine, behavioral, and autonomic reflex responses that ensure optimal internal organ function. This excitatory input is modulated by diverse, local inhibitory interneurons, whose functions are not clearly understood. Here we show that, in male rats, 65% of somatostatin-expressing (SST) NTS neurons also express GAD67, supporting their likely role as inhibitory interneurons. Using whole-cell recordings of NTS neurons, from horizontal brainstem slices of male and female SST-yellow fluorescent protein (YFP) and SST-channelrhodopsin 2 (ChR2)-YFP mice, we quantified the impact of SST-NTS neurons on viscerosensory processing. Light-evoked excitatory photocurrents were reliably obtained from SST-ChR2-YFP neurons ( = 16) and the stimulation-response characteristics determined. Most SST neurons (57%) received direct input from solitary tract (ST) afferents, indicating that they form part of a feedforward circuit. All recorded SST-negative NTS neurons ( = 72) received SST-ChR2 input. ChR2-evoked PSCs were largely inhibitory and, in contrast to previous reports, were mediated by both GABA and glycine. When timed to coincide, the ChR2-activated SST input suppressed ST-evoked action potentials at second-order NTS neurons, demonstrating strong modulation of primary viscerosensory input. These data indicate that the SST inhibitory network innervates broadly within the NTS, with the potential to gate viscerosensory input to powerfully alter autonomic reflex function and other behaviors. Sensory afferent input is modulated according to state. For example the baroreflex is altered during a stress response or exercise, but the basic mechanisms underpinning this sensory modulation are not fully understood in any sensory system. Here we demonstrate that the neuronal processing of viscerosensory information begins with synaptic gating at the first central synapse with second-order neurons in the NTS. These data reveal that the somatostatin subclass of inhibitory interneurons are driven by visceral sensory input to play a major role in gating viscerosensory signals, placing them within a feedforward circuit within the NTS.
初级传入感觉信息的整合和调制始于中枢神经系统内的第一个终止部位，其中中枢抑制回路起着重要作用。内脏感觉信息传递到孤束核（NTS），在那里它启动神经内分泌、行为和自主反射反应，以确保最佳的内脏器官功能。这种兴奋性输入受到各种局部抑制性中间神经元的调制，其功能尚不清楚。在这里，我们表明，在雄性大鼠中，65%表达生长抑素（SST）的 NTS 神经元也表达 GAD67，这支持了它们作为抑制性中间神经元的可能作用。使用雄性和雌性 SST-黄色荧光蛋白（YFP）和 SST-通道视紫红质 2（ChR2）-YFP 小鼠水平脑桥切片的全细胞膜片钳记录，我们量化了 SST-NTS 神经元对内脏感觉处理的影响。从 SST-ChR2-YFP 神经元（n = 16）可靠地获得光诱导的兴奋性光电流，并确定了刺激反应特征。大多数 SST 神经元（57%）接收来自孤束（ST）传入的直接输入，表明它们构成了前馈回路的一部分。所有记录的 SST-阴性 NTS 神经元（n = 72）均接收 SST-ChR2 输入。ChR2 诱导的 PSCs 主要是抑制性的，与之前的报道相反，它们是由 GABA 和甘氨酸介导的。当同时发生时，ChR2 激活的 SST 输入抑制了二级 NTS 神经元的 ST 诱发动作电位，证明了对初级内脏感觉输入的强烈调制。这些数据表明，SST 抑制性网络广泛地支配着 NTS，有可能对内脏感觉输入进行门控，从而有力地改变自主反射功能和其他行为。感觉传入输入根据状态进行调制。例如，在应激反应或运动期间，血压反射会发生变化，但在任何感觉系统中，这种感觉调制的基本机制都不完全清楚。在这里，我们证明了内脏感觉信息的神经元处理始于 NTS 中与二级神经元的第一个中央突触处的突触门控。这些数据表明，生长抑素亚类抑制性中间神经元受内脏感觉输入的驱动，在门控内脏感觉信号中发挥主要作用，将其置于 NTS 中的前馈回路内。
