Retrograde labeling reveals extensive distribution of genioglossal motoneurons possessing 5-HT2A receptors throughout the hypoglossal nucleus of adult dogs

Inspiratory hypoglossal motoneurons (IHMNs) innervate the muscles of the tongue and play an important role in maintaining upper airway patency. However, this may be reduced during sleep and by sedatives, potent analgesics, and volatile anesthetics. The genioglossal (GG) muscle is the main protruder and depressor muscle of the tongue and contributes to upper airway patency during inspiration. In vitro data suggest that serotonin (5-hydroxytryptamine, 5-HT), via the 5-HT2A receptor (5-HT2AR) subtype, plays a key role in controlling the excitability of IHMNs. The distribution of GG motoneurons (GGMNs) within the hypoglossal (XII) nucleus has not been studied in the adult dog. Further, it is uncertain whether the 5-HT2AR is located on GGMNs in the adult dog. We therefore used the cholera toxin B (CTB) subunit as a retrograde tracer to map the location of GGMNs in combination with immunofluorescent labeling to determine the presence and colocalization of 5-HT2AR within the XII nucleus in adult mongrel dogs. Injection of CTB into the GG muscle resulted in retrogradely labeled cells in a compact column throughout the XII nucleus, extending from 0.75 mm caudal to 3.45 mm rostral to the obex. Fluorescence immunohistochemistry revealed extensive 5-HT2AR labeling on CTB-labeled GGMNs. Identification of the 5-HT2AR on GGMNs in the XII nucleus of the adult dog supports in vitro data and suggests a physiological role for this receptor subtype in controlling the excitability of GGMNs, which contribute to the maintenance of upper airway patency.