In the brain, compact clusters of neuron cell bodies, termed nuclei, are essential for maintaining parameters of host physiology within a narrow range optimal for health. Neurons residing in the brainstem dorsal motor nucleus (DMN) project in the vagus nerve to communicate with the lungs, liver, gastrointestinal tract, and other organs. Vagus nerve-mediated reflexes also control immune system responses to infection and injury by inhibiting the production of tumor necrosis factor (TNF) and other cytokines in the spleen, although the function of DMN neurons in regulating TNF release is not known. Here, optogenetics and functional mapping reveal cholinergic neurons in the DMN, which project to the celiac-superior mesenteric ganglia, significantly increase splenic nerve activity and inhibit TNF production. Efferent vagus nerve fibers terminating in the celiac-superior mesenteric ganglia form varicose-like structures surrounding individual nerve cell bodies innervating the spleen. Selective optogenetic activation of DMN cholinergic neurons or electrical activation of the cervical vagus nerve evokes action potentials in the splenic nerve. Pharmacological blockade and surgical transection of the vagus nerve inhibit vagus nerve-evoked splenic nerve responses. These results indicate that cholinergic neurons residing in the brainstem DMN control TNF production, revealing a role for brainstem coordination of immunity.

在大脑中，紧凑的神经元细胞体簇（称为细胞核）对于将宿主生理学参数维持在最适合健康的狭窄范围内至关重要。脑干背运动核 (DMN) 中的神经元投射到迷走神经中，与肺、肝、胃肠道和其他器官进行通讯。迷走神经介导的反射还通过抑制脾脏中肿瘤坏死因子（TNF）和其他细胞因子的产生来控制免疫系统对感染和损伤的反应，尽管 DMN 神经元在调节 TNF 释放中的功能尚不清楚。在这里，光遗传学和功能图谱揭示了 DMN 中的胆碱能神经元，投射到腹腔肠系膜上神经节，显着增加脾神经活动并抑制 TNF 产生。终止于腹腔肠系膜上神经节的传出迷走神经纤维形成围绕支配脾脏的单个神经细胞体的曲张样结构。 DMN 胆碱能神经元的选择性光遗传学激活或颈迷走神经的电激活可唤起脾神经的动作电位。迷走神经的药理学阻断和手术横断抑制迷走神经诱发的脾神经反应。这些结果表明，脑干 DMN 中的胆碱能神经元控制 TNF 的产生，揭示了脑干协调免疫的作用。