FIGURE 2.

Astrocytes contribute to the modulation of breathing in response to changes in pH and pCO₂. (a) Anatomical organization of the brainstem circuits responsible for breathing. pF_v: ventral parafacial nucleus, also known as RTN: retrotrapezoid nucleus. preBötC: preBötzinger complex. pF: parafacial nucleus. pF_l: lateral parafacial nucleus. pF_v: ventral parafacial nucleus. LRN: lateral reticular nucleus. NA: nucleus ambiguus. preBötC: preBötzinger complex. BötC: Bötzinger complex. rVRG: rostral ventral respiratory group. cVRG: caudal ventral respiratory group. (b) Ca²⁺ response of astrocytes in the pF_v (RTN) to acidification. (c) Response of neurons from the pF_v (RTN) and of phrenic nerve to the optogenetic activation of pF_v (RTN) astrocytes. b and c are adapted from (Gourine et al., 2010), with permission. (d) Hypothetical mechanisms for the regulation of breathing by pF_v (RTN) astrocytes. Astrocytes sense CO₂ increase via CO₂‐sensitive connexin (Cx) hemichannels which directly release ATP. Acidification activates the Na⁺/HCO₃ ⁻ co‐transport (NBC), which in turn activates the Na⁺/Ca²⁺ exchange (NCX). The increase in intracellular Ca²⁺ leads to the Ca²⁺‐dependent vesicular release of ATP. ATP is likely to act on several downstream targets, including neighboring astrocytes, smooth muscle cells, and neurons