Although CGRP neurons in the external lateral parabrachial nucleus
(PBelCGRPneurons) are critical for cortical arousal in response to
hypercapnia, activating them has little effect on respiration. However, deletion of all
Vglut2 expressing neurons in the PBel region suppresses both the respiratory and arousal
response to high CO2. We identified a second population of non-CGRP neurons adjacent to
the PBelCGRPgroup in the central lateral, lateral crescent and
Kölliker-Fuse parabrachial subnuclei that are also activated by CO2 and project to
the motor and premotor neurons that innvervate respiratory sites in the medulla and spinal
cord. We hypothesize that these neurons may in part mediate the respiratory response to
CO2 and that they may express the transcription factor, Fork head Box protein 2 (FoxP2),
which has recently been found in this region. To test this, we examined the role of the
PBFoxP2neurons in respiration and arousal response to CO2, and found that
they show cFos expression in response to CO2 exposure as well as increased intracellular
calcium activity during spontaneous sleep-wake and exposure to CO2. We also found that
optogenetically photo-activating PBFoxP2neurons increases respiration and that
photo-inhibition using archaerhodopsin T (ArchT) reduced the respiratory response to CO2
stimulation without preventing awakening. Our results indicate that PBFoxP2neurons play an important role in the respiratory response to CO2 exposure during NREM
sleep, and indicate that other pathways that also contribute to the response cannot
compensate for the loss of the PBFoxP2neurons. Our findings suggest that
augmentation of the PBFoxP2response to CO2 in patients with sleep apnea in
combination with inhibition of the PBelCGRPneurons may avoid hypoventilation
and minimize EEG arousals.