Figure 11.

Hypothesis for the generation of active expiration and arousal by RTN and C1 neurons. A, RTN neurons (Phox2b+Nmb) promote active expiration via two mechanisms: a direct excitatory input to glutamatergic premotor neurons (cVRG) that drive abdominal muscle contractions via direct excitatory projections to spinal motor neurons and a shortening of the inhibition of the cVRG premotor neurons during the Post-I phase of the respiratory cycle. The latter mechanism probably relies on RTN projections to multiple segments of the respiratory pattern generator: Bötzinger (BötC), Pre-Bötzinger (Pre-BötC), and Kölliker-Fuse nucleus (Barnett et al., 2018). Inspiration is driven by RTN neurons via activation of the Pre-BötC (rate control), and inspiratory premotor neurons located in the rostral ventral respiratory group (rVRG; amplitude control). The modest arousal potential of the RTN may rely on direct inputs to the PBel or by pathways associated with breathing activation, that is, via excitation of central respiratory centers or changes in sensory feedback stimulated by increased lung ventilation. B, C1 neurons may promote arousal through dense projections to the Th neurons of the LC, CGRP neurons in the PBel, and hypothalamic regions (data not shown). C1 neurons do not project to cVRG expiratory premotor neurons and therefore do not effectively stimulate active expiration. However, C1 neurons are capable of stimulating breathing and sighs possibly through their connections with BötC/Pre-BötC.