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| Status |
Public on May 12, 2021 |
| Title |
Ventral parafacial inhibitory neurons regulate baseline breathing by a mechanism involving disinhibition |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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 We also show that chemosensitive RTN neurons receive tonic inhibitory input under control conditions that is withdrawn in a CO2/H+-dependent manner, and chemogenetic inhibition of ventral parafacial inhibitory neurons increases baseline respiratory activity.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.
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| Overall design |
Examination of cells from ventral parafacial brain slices from two batches of B6 mice
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| Contributor(s) |
Cleary CM, Kuo F, James SD, Flynn WF, Robson P, Mulkey DK |
| Citation(s) |
34013884, 38548965 |
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| Submission date |
Jun 24, 2020 |
| Last update date |
Apr 05, 2024 |
| Contact name |
William F Flynn |
| Organization name |
The Jackson Laboratory
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| Street address |
10 Discovery Drive
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| City |
Farmington |
| State/province |
CT |
| ZIP/Postal code |
06032 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA641666 |
| SRA |
SRP268680 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE153172_RAW.tar |
65.5 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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