Conditional loss of Engrailed1/2 in Atoh1-derived excitatory cerebellar nuclear neurons impairs eupneic respiration in mice Journal Article
| Authors: | Taylor, A. P.; Lee, A. S.; Goedecke, P. J.; Tolley, E. A.; Joyner, A. L.; Heck, D. H. |
| Article Title: | Conditional loss of Engrailed1/2 in Atoh1-derived excitatory cerebellar nuclear neurons impairs eupneic respiration in mice |
| Abstract: | Evidence for a cerebellar role during cardiopulmonary challenges has long been established, but studies of cerebellar involvement in eupneic breathing have been inconclusive. Here we investigated temporal aspects of eupneic respiration in the Atoh1-En1/2 mouse model of cerebellar neuropathology. Atoh1-En1/2 conditional knockout mice have conditional loss of the developmental patterning genes Engrailed1 and 2 in excitatory cerebellar nuclear neurons, which leads to loss of a subset of medial and intermediate excitatory cerebellar nuclear neurons. A sample of three Atoh1-derived extracerebellar nuclei showed no cell loss in the conditional knockout compared to control mice. We measured eupneic respiration in mutant animals and control littermates using whole-body unrestrained plethysmography and compared the average respiratory rate, coefficient of variation, and the CV2, a measure of intrinsic rhythmicity. Linear regression analyses revealed that Atoh1-En1/2 conditional knockouts have decreased overall variability (p = 0.021; b = −0.045) and increased intrinsic rhythmicity compared to their control littermates (p < 0.001; b = −0.037), but we found no effect of genotype on average respiratory rate (p = 0.064). Analysis also revealed modestly decreased respiratory rates (p = 0.025; b = −0.82), increased coefficient of variation (p = 0.0036; b = 0.060), and increased CV2 in female animals, independent of genotype (p = 0.024; b = 0.026). These results suggest a cerebellar involvement in eupneic breathing by controlling rhythmicity. We argue that the cerebellar involvement in controlling the CV2 of respiration is indicative of an involvement of coordinating respiration with other orofacial rhythms, such as swallowing. © 2021 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd. |
| Keywords: | controlled study; nonhuman; mouse; cerebellum; animal experiment; genotype; gene loss; knockout mouse; plethysmography; cerebellum nucleus; brain nerve cell; breathing; nerve cell stimulation; breathing rate; male; female; article; gene knockout; interpositus nucleus |
| Journal Title: | Genes, Brain and Behavior |
| Volume: | 21 |
| Issue: | 2 |
| ISSN: | 1601-1848 |
| Publisher: | Wiley-Blackwell Publishing, Inc. |
| Date Published: | 2022-01-01 |
| Start Page: | e12788 |
| Language: | English |
| DOI: | 10.1111/gbb.12788 |
| PUBMED: | 35044072 |
| PROVIDER: | scopus |
| PMCID: | PMC8852233 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2022 -- Source: Scopus |
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