Lateral parabrachial FoxP2 neurons regulate respiratory responses to hypercapnia.

About half of the neurons in the parabrachial nucleus (PB) that are activated by CO ₂ are located in the external lateral (el) subnucleus, express calcitonin gene-related peptide (CGRP), and cause forebrain arousal. We report here, in male mice, that most of the remaining CO ₂ -responsive neurons in the adjacent central lateral (PBcl) and Kölliker-Fuse (KF) PB subnuclei express the transcription factor FoxP2 and many of these neurons project to respiratory sites in the medulla. PBcl ^FoxP2 neurons show increased intracellular calcium during wakefulness and REM sleep and in response to elevated CO ₂ during NREM sleep. Photo-activation of the PBcl ^FoxP2 neurons increases respiration, whereas either photo-inhibition of PBcl ^FoxP2 or genetic deletion of PB/KF ^FoxP2 neurons reduces the respiratory response to CO ₂ stimulation without preventing awakening. Thus, augmenting the PBcl/KF ^FoxP2 response to CO ₂ in patients with sleep apnea in combination with inhibition of the PBel ^CGRP neurons may avoid hypoventilation and minimize EEG arousals.
(© 2024. The Author(s).)