Sleep is a universal state of behavioral quiescence in both vertebrates and invertebrates that is controlled by conserved genes. We previously found that AP2 transcription factors control sleep in C. elegans, Drosophila, and mice. Heterozygous deletion of Tfap2b, one of the mammalian AP2 paralogs, reduces sleep in mice. The cell types and mechanisms through which Tfap2b controls sleep in mammals are, however, not known. In mice, Tfap2b acts during early embryonic stages. In this study, we used RNA-seq to measure the gene expression changes in brains of Tfap2b−/− embryos. Our results indicated that genes related to brain development and patterning were differentially regulated. As many sleep-promoting neurons are known to be GABAergic, we measured the expression of GAD1, GAD2 and Vgat genes in different brain areas of adult Tfap2b+/− mice using qPCR. These experiments suggested that GABAergic genes are downregulated in the cortex, brainstem and cerebellum areas, but upregulated in the striatum. To investigate whether Tfap2b controls sleep through GABAergic neurons, we specifically deleted Tfap2b in GABAergic neurons. We recorded the EEG and EMG before and after a 6-h period of sleep deprivation and extracted the time spent in NREM and in REM sleep as well as delta and theta power to assess NREM and REM sleep, respectively. During baseline conditions, Vgat-tfap2b−/− mice exhibited both shortened NREM and REM sleep time and reduced delta and theta power. Consistently, weaker delta and theta power were observed during rebound sleep in the Vgat-tfap2b−/− mice after sleep deprivation. Taken together, the results indicate that Tfap2b in GABAergic neurons is required for normal sleep.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:93499 |
| Date | 06 November 2024 |
| Creators | Hu, Yang, Bringmann, Henrik |
| Publisher | Springer Nature |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2045-2322, 8026, 10.1038/s41598-023-34772-x, info:eu-repo/grantAgreement/European Commission/H2020 | ERC | ERC-STG/637860//SLEEPCONTROL : The mechanism of sleep control through a sleep-active sleep-promoting neuron |
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