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.