Figure 16.

Pathways transmitting activation from the hypothalamic wake-active orexin neurons to orofacial motoneurons. Anatomical studies indicate that ACh, 5-HT, and NE brainstem neurons as well as motoneurons, are among the major targets of axons descending from hypothalamic orexin-containing neurons. However, physiological and pharmacological studies reveal that nonorexin cells located in the posterior hypothalamic orexinergic region also can significantly influence the respiratory output, including upper airway motoneurons. In particular, neither the combined antagonism of 5-HT and NE-mediated excitation at the XII nucleus level (147), nor microinjections of a dual orexin receptor antagonist into the XII nucleus (518), could significantly attenuate activation of XII motoneurons from the hypothalamic region containing orexin neurons. On the other hand, microinjections of a dual orexin receptor antagonist into the hypothalamic orexin cell field significantly attenuated activation of XII motoneurons from this hypothalamic region (518). These results support the presence of an excitatory pathway that descends from the posterior hypothalamus parallel to the orexinergic pathway and targets different components of the respiratory system, including upper airway motoneurons. Additional connections may exist, such as nonorexinergic excitatory hypothalamo-brainstem pathways to ACh, 5-HT and NE neurons, and there may be additional orexinergic connections to central respiratory neurons, although specific details are not yet available. Cholinergic effects within the respiratory network may be excitatory or inhibitory (marked with yellow circles).