Abstract
We wanted to understand the brain circuitry that awakens the individual when there is elevated CO2 or low O2 (e.g., during sleep apnea or asphyxia). The sensory signals for high CO2 and low O2 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 CO2 or low O2 We then showed that PB neurons that express calcitonin gene-related peptide (CGRP) show cFos staining during high CO2 Using CGRP-Cre-ER mice, we expressed the inhibitory opsin archaerhodopsin just in the PBCGRP neurons. Photoinhibition of the PBCGRP neurons effectively prevented awakening to high CO2, as did photoinhibition of their terminals in the basal forebrain, amygdala, and lateral hypothalamus. The PBCGRP neurons are a key mediator of the wakening response to apnea.
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