Tfap2b acts in GABAergic neurons to control sleep in mice

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Yang Hu - , Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute) (Author)
  • Henrik Bringmann - , Biotechnology Center, Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute) (Author)

Abstract

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.

Details

Original languageEnglish
Article number8026
JournalScientific reports
Volume13
Issue number1
Publication statusPublished - 17 May 2023
Peer-reviewedYes

External IDs

PubMedCentral PMC10192351
Scopus 85159764437
ORCID /0000-0002-7689-8617/work/142658507

Keywords

Keywords

  • Animals, Mice, Electroencephalography, GABAergic Neurons, Mammals, Sleep/physiology, Sleep Deprivation/genetics, Sleep Stages/physiology

Library keywords