RT Journal Article SR Electronic T1 Analyzing the brainstem circuits for respiratory chemosensitivity in freely moving mice JF bioRxiv FD Cold Spring Harbor Laboratory SP 492041 DO 10.1101/492041 A1 Amol Bhandare A1 Robert Huckstepp A1 Nicholas Dale YR 2018 UL http://biorxiv.org/content/early/2018/12/10/492041.abstract AB The regulated excretion of CO2 during breathing is a key life-preserving homeostatic mechanism. In the rostral medulla oblongata, neurons in two nuclei -the retrotrapezoid nucleus (RTN) and the rostral medullary raphe -have been proposed as central CO2 chemosensors that mediate adaptive changes in breathing. Using synapsin promoter-driven expression of GCaMP6 and head-mounted mini-microscopes, we imaged the Ca2+ activity of RTN and raphe neurons in awake adult mice during inspiration of elevated CO2. 40% of raphe neurons were activated by 3% and 6% inspired CO2. By contrast, only 5% of RTN neurons were activated by CO2. 4% of RTN neurons were inhibited by elevated CO2, and 4% of RTN neurons were coactive with exploratory sniffing. In awake mice it is therefore the serotonergic raphe neurons that are predominant in detecting and mediating the effects of elevated inspired CO2. Neurons of the RTN have heterogeneous roles but make relatively little contribution to this key homeostatic reflex.One sentence summary Neurons of the raphe, but not the retrotrapezoid nucleus, dominate the response to inspiration of elevated CO2 in awake adult mice.