The substantia nigra modulates proximal colon tone and motility in a vagally-dependent manner in the rat.
The substantia nigra modulates proximal colon tone and motility in a vagally-dependent manner in the rat.
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黑质以迷走神经依赖性方式调节大鼠近端结肠张力和运动。
DOI：
10.1113/jp284238
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Travagli,RAlberto
中科院分区：
文献类型：
--
作者：
Xing,Tiaosi;Nanni,Giorgia;Burkholder,CameronR;Browning,KirsteenN;Travagli,RAlberto
迷走神经背侧运动核（DMV）神经元与黑质背侧部（SNpc）之间有一条单突触通路。这种单突触通路调节迷走神经对胃运动的控制。然而，目前尚不清楚这种黑迷走神经通路是否也调节近端结肠的张力和运动。在大鼠中，近端结肠中逆行示踪剂和SNpc中顺行示踪剂的显微注射表明，DMV中的双侧标记的结肠投射神经元接受来自SNpc神经元的输入。微量注射离子型谷氨酸受体激动剂，NMDA，在SNPC增加近端结肠的运动和张力，通过应变仪与结肠环形平滑肌对齐测量;运动的增加被抑制由急性迷走神经切断术。在用pAAV-hSyn-hM 3D（Gq）-mCherry转染SNpc后，通过脑干应用氯氮平-N-氧化物对黑迷走神经末梢的化学发生激活增加了DMV神经元的放电率和近端结肠运动;这两种反应都被多巴胺能D1样拮抗剂SCH 23390脑干预处理所消除。用pAAV-hSyn-hM 4D（Gi）-mCherry SNpc转染后，黑迷走神经末梢的化学发生抑制降低了DMV神经元的放电率并抑制了近端结肠运动。这些数据表明，黑质-迷走神经通路通过离散的多巴胺能突触以依赖于迷走神经传出神经活动的方式对近端结肠运动的活动进行张力性调节。在帕金森病患者和动物模型中观察到，这种黑质-迷走神经通路的损伤可能导致结肠运输严重减少和便秘突出。关键点黑质背侧部（SNpc）神经元通过一种假定的直接通路与迷走神经背侧运动核（DMV）神经元相连。DMV外侧的脑干神经元支配近端结肠。结肠投射DMV神经元接受SNpc神经元的输入。黑迷走神经通路通过DMV中的D1样受体调节近端结肠的张力和运动。本研究为解释SNpc改变如何导致帕金森病患者便秘的高发生率提供了机制基础。
AbstractA monosynaptic pathway connects the substantia nigra pars compacta (SNpc) to neurons of the dorsal motor nucleus of the vagus (DMV). This monosynaptic pathway modulates the vagal control of gastric motility. It is not known, however, whether this nigro‐vagal pathway also modulates the tone and motility of the proximal colon. In rats, microinjection of retrograde tracers in the proximal colon and of anterograde tracers in SNpc showed that bilaterally labelled colonic‐projecting neurons in the DMV received inputs from SNpc neurons. Microinjections of the ionotropic glutamate receptor agonist, NMDA, in the SNpc increased proximal colonic motility and tone, as measured via a strain gauge aligned with the colonic circular smooth muscle; the motility increase was inhibited by acute subdiaphragmatic vagotomy. Upon transfection of SNpc with pAAV‐hSyn‐hM3D(Gq)‐mCherry, chemogenetic activation of nigro‐vagal nerve terminals by brainstem application of clozapine‐N‐oxide increased the firing rate of DMV neurons and proximal colon motility; both responses were abolished by brainstem pretreatment with the dopaminergic D1‐like antagonist SCH23390. Chemogenetic inhibition of nigro‐vagal nerve terminals following SNpc transfection with pAAV‐hSyn‐hM4D(Gi)‐mCherry decreased the firing rate of DMV neurons and inhibited proximal colon motility. These data suggest that a nigro‐vagal pathway modulates activity of the proximal colon motility tonically via a discrete dopaminergic synapse in a manner dependent on vagal efferent nerve activity. Impairment of this nigro‐vagal pathway may contribute to the severely reduced colonic transit and prominent constipation observed in both patients and animal models of parkinsonism.Key pointsSubstantia nigra pars compacta (SNpc) neurons are connected to the dorsal motor nucleus of the vagus (DMV) neurons via a presumed direct pathway.Brainstem neurons in the lateral DMV innervate the proximal colon. Colonic‐projecting DMV neurons receive inputs from neurons of the SNpc.The nigro‐vagal pathway modulates tone and motility of the proximal colon via D1‐like receptors in the DMV.The present study provides the mechanistic basis for explaining how SNpc alterations may lead to a high rate of constipation in patients with Parkinson's Disease.