Somatostatin-expressing parafacial neurons are CO 2 /H + sensitive and regulate baseline breathing

• Published in: eLife Vol. 10
• Main Authors: Cleary, Colin M, Milla, Brenda M, Kuo, Fu-Shan, James, Shaun, Flynn, William F, Robson, Paul, Mulkey, Daniel K
• Format: Journal Article
• Language: English
• Published: England 20.05.2021
• Subjects: Animals; Carbon Dioxide - metabolism; Chemoreceptor Cells - metabolism; Disease Models, Animal; Epilepsies, Myoclonic - genetics; Epilepsies, Myoclonic - metabolism; Epilepsies, Myoclonic - physiopathology; Female; Glutamic Acid - metabolism; Hydrogen - metabolism; Intralaminar Thalamic Nuclei - metabolism; Intralaminar Thalamic Nuclei - physiopathology; Lung - innervation; Male; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Transgenic; NAV1.1 Voltage-Gated Sodium Channel - genetics; NAV1.1 Voltage-Gated Sodium Channel - metabolism; Neural Inhibition; Respiration; Somatostatin - genetics; Somatostatin - metabolism; Synaptic Transmission; mouse; neuroscience; chemoreception; disinhibition; retrotrapezoid nucleus
• ISSN: 2050-084X

Glutamatergic neurons in the retrotrapezoid nucleus (RTN) function as respiratory chemoreceptors by regulating breathing in response to tissue CO /H . The RTN and greater parafacial region may also function as a chemosensing network composed of CO /H -sensitive excitatory and inhibitory synaptic interactions. In the context of disease, we showed that loss of inhibitory neural activity in a mouse model of Dravet syndrome disinhibited RTN chemoreceptors and destabilized breathing (Kuo et al., 2019). Despite this, contributions of parafacial inhibitory neurons to control of breathing are unknown, and synaptic properties of RTN neurons have not been characterized. Here, we show the parafacial region contains a limited diversity of inhibitory neurons including somatostatin ( )-, parvalbumin ( )-, and cholecystokinin ( )-expressing neurons. Of these, Sst-expressing interneurons appear uniquely inhibited by CO /H . We also show RTN chemoreceptors receive inhibitory input that is withdrawn in a CO /H -dependent manner, and chemogenetic suppression of parafacial neurons, but not or + neurons, increases baseline breathing. These results suggest -expressing parafacial neurons contribute to RTN chemoreception and respiratory activity.