Brain Circuitry for Arousal from Apnea.

We wanted to understand the brain circuitry that awakens the individual when there is elevated CO or low O (e.g., during sleep apnea or asphyxia). The sensory signals for high CO and low O all converge on the parabrachial nucleus (PB) of the pons, which contains neurons that project to the forebrain. So, we first deleted the vesicular glutamate transporter 2, necessary to load glutamate into synaptic vesicles, from neurons in the PB, and showed that this prevents awakening to high CO or low O We then showed that PB neurons that express calcitonin gene-related peptide (CGRP) show cFos staining during high CO Using CGRP-Cre-ER mice, we expressed the inhibitory opsin archaerhodopsin just in the PB neurons. Photoinhibition of the PB neurons effectively prevented awakening to high CO, as did photoinhibition of their terminals in the basal forebrain, amygdala, and lateral hypothalamus. The PB neurons are a key mediator of the wakening response to apnea.