Ventral parafacial inhibitory neurons regulate baseline breathing by a mechanism involving disinhibition
A parafacial region of the medulla called the retrotrapezoid nucleus (RTN) is an important respiratory control center. A group of glutamatergic neurons in this region function as respiratory  chemoreceptors by regulating breathing in response to changes in tissue CO2/H+. Cellular mechanisms underlying this function involve H+-inhibition of TASK2 channels and -activation of  GPR4 receptors. Evidence also suggests the RTN and greater parafacial region functions as a CO2/H+ sensing network where CO2/H+-activated and -inhibited neurons talk to each other through  excitatory and inhibitory interactions. However, contributions of parafacial inhibitory neurons to control of breathing are unknown, and synaptic properties of RTN chemorecpetors have not been  characterized. Here, we show the ventral parafacial region contains parvalbumin (Pvalb), cholecystokinin (CCK), neuron-derived neurotrophic factor (Ndnf) and somatostatin (SST) subtypes of interneurons including a subset strongly inhibited by CO2/H+. We also show that chemosensitive RTN neurons receive tonic inhibitory input under control conditions that is withdrawn in a CO2/H+-dependent manner, and chemogenetic inhibition of ventral parafacial inhibitory neurons increases baseline respiratory activity. These results suggest ventral parafacial inhibitory neurons are important determinants of respiratory activity under baseline conditions when the respiratory system is most prone to failure. Overall design: Examination of cells from ventral parafacial brain slices from two batches of B6 mice