Whole-Brain Monosynaptic Inputs to Hypoglossal Motor Neurons in Mice
Whole-Brain Monosynaptic Inputs to Hypoglossal Motor Neurons in Mice
复制标题
小鼠舌下运动神经元的全脑单突触输入
DOI：
10.1007/s12264-020-00468-9
复制
发表时间：
2020-02-24
影响因子：
5.6
通讯作者：
Huang, Zhi-Li
中科院分区：
文献类型：
--
作者：
Guo, Han;Yuan, Xiang-Shan;Huang, Zhi-Li
舌下运动神经元（HMNs）支配舌肌，在吞咽、咀嚼、哺乳、发声和呼吸等多种生理功能中发挥关键作用。HMNs的功能障碍与一些疾病有关，如阻塞性睡眠呼吸暂停（OSA）和婴儿猝死综合征。阻塞性睡眠呼吸暂停是一种严重的呼吸障碍，与不同睡眠-觉醒状态下HMNs的活动有关。明确控制HMNs状态依赖性活动的神经机制，有助于为OSA的有效治疗提供理论依据。然而，控制hmn活性的突触前伙伴仍有待阐明。在本研究中，我们使用了一种基于改良狂犬病毒的细胞类型特异性逆行追踪系统以及Cre/loxP基因表达策略来绘制小鼠全脑单突触输入到hmm的图谱。我们从杏仁核、下丘脑、中脑、脑桥、髓质和小脑等6个脑区确定了53个靶向HMNs的核。我们发现中央杏仁核的gaba能神经元和下丘脑副核的calretinin神经元向HMNs发送单突触投射。此外，HMNs接收到与呼吸相关的几个区域的直接输入，如前botzinger复合体、臂旁核、孤立束核和下丘脑。一些参与睡眠-觉醒调节的区域（面旁区、臂旁核、延髓腹侧、嗅觉下被盖核、中缝背核、导水管周围灰质和下丘脑）也向hmm提供主要输入。这些结果有助于进一步阐明由HMNs功能障碍引起的神经回路紊乱。
Hypoglossal motor neurons (HMNs) innervate tongue muscles and play key roles in a variety of physiological functions, including swallowing, mastication, suckling, vocalization, and respiration. Dysfunction of HMNs is associated with several diseases, such as obstructive sleep apnea (OSA) and sudden infant death syndrome. OSA is a serious breathing disorder associated with the activity of HMNs during different sleep–wake states. Identifying the neural mechanisms by which the state-dependent activities of HMNs are controlled may be helpful in providing a theoretical basis for effective therapy for OSA. However, the presynaptic partners governing the activity of HMNs remain to be elucidated. In the present study, we used a cell-type-specific retrograde tracing system based on a modified rabies virus along with a Cre/loxP gene-expression strategy to map the whole-brain monosynaptic inputs to HMNs in mice. We identified 53 nuclei targeting HMNs from six brain regions: the amygdala, hypothalamus, midbrain, pons, medulla, and cerebellum. We discovered that GABAergic neurons in the central amygdaloid nucleus, as well as calretinin neurons in the parasubthalamic nucleus, sent monosynaptic projections to HMNs. In addition, HMNs received direct inputs from several regions associated with respiration, such as the pre-Botzinger complex, parabrachial nucleus, nucleus of the solitary tract, and hypothalamus. Some regions engaged in sleep–wake regulation (the parafacial zone, parabrachial nucleus, ventral medulla, sublaterodorsal tegmental nucleus, dorsal raphe nucleus, periaqueductal gray, and hypothalamus) also provided primary inputs to HMNs. These results contribute to further elucidating the neural circuits underlying disorders caused by the dysfunction of HMNs.