Fig. 16.3.

Five mechanisms may cooperate to produce the high sensitivity of RTN Phox2b-VGLUT2 neurons to hypercapnia. Mechanism 1: RTN neurons respond to acidification through an unidentified cell autonomous response that persists in presence of blockers of glutamate and purinergic transmission in slices (Mulkey et al. 2004). Mechanism 2: ventral surface glial cells are depolarized by acidification and probably contribute to the CO₂ sensitivity of the RTN neurons. ATP is the presumed mediator of this paracrine mechanism (Gourine et al. 2010). Mechanism 3: coupling between RTN neurons via gap junctions or recurrent collaterals (depicted) may amplify the cell autonomous effect of pH on RTN neurons (Fortin and Thoby-Brisson 2009). Mechanism 4: RTN neurons receive input from orexinergic or serotonergic neurons. Subsets of these neurons may respond to changes in brain pH/pCO₂ (Guyenet et al. 2010). Mechanism 5: RTN neurons receive a polysynaptic excitatory input from the carotid bodies (Takakura et al. 2006)