Somatostatin-expressing parafacial neurons are CO2/H+ sensitive and regulate baseline breathing
- University of Connecticut, United States
- The Jackson Laboratory, United States
Abstract
Glutamatergic neurons in the retrotrapezoid nucleus (RTN) function as respiratory chemoreceptors by regulating breathing in response to tissue CO2/H+. The RTN and greater parafacial region may also function as a chemosensing network composed of CO2/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; 25). 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 (Sst)-, parvalbumin (Pvalb)- and cholecystokinin (Cck)-expressing neurons. Of these, Sst-expressing interneurons appear uniquely inhibited by CO2/H+. We also show RTN chemoreceptors receive inhibitory input that is withdrawn in a CO2/H+-dependent manner, and chemogenetic suppression of Sst+ parafacial neurons, but not Pvalb+ or Cck+ neurons, increases baseline breathing. These results suggest Sst-expressing parafacial neurons contribute to RTN chemoreception and respiratory activity.
Data availability
Raw and processed scRNA-seq data are available through the Gene Expression Omnibus (accession GSE153172) and analysis code is available on GitHub. Analysis of FISH, electrophysiology, and respiratory activity data was done using standard software and no custom code was written.
Article and author information
Author details
Funding
National Institutes of Health (HL104101)
- Daniel K Mulkey
National Institutes of Health (HL137094)
- Daniel K Mulkey
National Institutes of Health (NS099887)
- Daniel K Mulkey
National Institutes of Health (HL142227)
- Colin M Cleary
National Institutes of Health (F31NS120467)
- Brenda M Milla
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures were performed in accordance with National Institutes of Health and University of Connecticut Animal Care and Use Guidelines (protocols A19-048 and A20-016).
Copyright
© 2021, Cleary et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Somatostatin-expressing parafacial neurons are CO2/H+ sensitive and regulate baseline breathing
eLife 10:e60317.
https://doi.org/10.7554/eLife.60317
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