Volume 36, Issue. 6, June, 2020

Whole-Brain Monosynaptic Inputs to Hypoglossal Motor Neurons in Mice

Han Guo 1,3 • Xiang-Shan Yuan 1,2 • Ji-Chuan Zhou 1 • Hui Chen 1 • Shan-Qun Li 3   • Wei-Min Qu 1 • Zhi-Li Huang 1

Department of Pharmacology, School of Basic Medical Sciences; State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China

2 Department of Anatomy, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China

3 Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China


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 statedependent 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 preBotzinger 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.


Hypoglossal motor neuron; Monosynaptic input; Rabies virus; Respiration; Sleep and wake


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