Whole-Brain Monosynaptic Inputs to Hypoglossal Motor Neurons in Mice

Abstract

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 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. Keywords Hypoglossal motor neuron Á Monosynaptic input Á Rabies virus Á Respiration Á Sleep and wake Han Guo and Xiang-Shan Yuan contributed equally to this work.

A basal ganglia-like cortical–amygdalar–hypothalamic network mediates feeding behavior

“…In our study, we left the PB CGRP to the CEAc pathway untouched, as the PSTN is connected to the CEAm and caudal SI. Therefore, we impacted the network downstream from the CEAc, indicating either that damaging the network at any level diminishes the anorexic response associated with sickness or that an intact PSTN/CbN is necessary to relay the CEA information processing and anxietyrelated signals to downstream centers (59,60) or back to the telencephalon through the thalamus (61,62).…”

Neurotropic Viruses as a Tool for Neural Circuit-Tracing

“…Two kinds of PRV carrying different fluorescent proteins were injected into different parts of the experimental animals, followed by detection of expressions and distributions of fluorescent proteins in certain brain regions after days of virus infection. Neurons labeled by two kinds of fluorescent proteins indicated that the brain area where labeled neurons distributed was involved in the regulation of two different injection sites [82,83]. For example, in our study, PRV531 (GFP) and PRV724 (mRFP) were injected into the heart and small intestine of C57 BL/6J mice, respectively.…”

The pre-Bötzinger complex is necessary for the expression of post-inspiration

“…The suppression hypoglossal nerve activity causes diminished genioglossus protrusion and retraction during inspiration (Fuller et al ., 1999; Gestreau et al ., 2005, Lee et al ., 2012). Together, these findings suggest that the pre-BötC contains a critical pool of pre-motor neurons that project to hypoglossal and vagal motor neurons (Guo et al ., 2020; Menuet et al ., 2020), which have an essential function in the dynamic regulation of upper airway patency. Thus, the present study further extends the role of the pre-BötC from its established role as the inspiratory rhythm generator (Feldman & Del Negro 2006; Feldman et al ., 2008; Del Negro et al ., 2018) to the dynamic regulation of upper airway patency and is also consistent with its recently identified role in the mediation of cough (Shen et al, 2022) that specifically requires post-inspiratory laryngeal constriction to generate high velocity expiratory airflow (see Dutschmann et al, 2014).…”