Hypocretin neuron-specific transcriptome profiling identifies the sleep modulator Kcnh4a
Name
Yelin-Bekerman-2015-Hypocretin neuron-sp.pdf
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5.29 MB
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Author(s)
Yelin-Bekerman, Laura
Elbaz, Idan
Diber, Alex
Dahary, Dvir
Gibbs-Bar, Liron
Alon, Shahar
Lerer-Goldshtein, Tali
Appelbaum, Lior
Date Issued
October 2015
Journal
eLife
Publisher
eLife Sciences Publications, Ltd.
Citation
Yelin-Bekerman, Laura, Idan Elbaz, Alex Diber, Dvir Dahary, Liron Gibbs-Bar, Shahar Alon, Tali Lerer-Goldshtein, and Lior Appelbaum. “Hypocretin Neuron-Specific Transcriptome Profiling Identifies the Sleep Modulator Kcnh4a.” eLife 4 (October 1, 2015).
Version
Final published version
Abstract
Sleep has been conserved throughout evolution; however, the molecular and neuronal mechanisms of sleep are largely unknown. The hypothalamic hypocretin/orexin (Hcrt) neurons regulate sleep/wake states, feeding, stress, and reward. To elucidate the mechanism that enables these various functions and to identify sleep regulators, we combined fluorescence cell sorting and RNA-seq in hcrt:EGFP zebrafish. Dozens of Hcrt-neuron-specific transcripts were identified and comprehensive high-resolution imaging revealed gene-specific localization in all or subsets of Hcrt neurons. Clusters of Hcrt-neuron-specific genes are predicted to be regulated by shared transcription factors. These findings show that Hcrt neurons are heterogeneous and that integrative molecular mechanisms orchestrate their diverse functions. The voltage-gated potassium channel Kcnh4a, which is expressed in all Hcrt neurons, was silenced by the CRISPR-mediated gene inactivation system. The mutant kcnh4a(kcnh4a-/-) larvae showed reduced sleep time and consolidation, specifically during the night, suggesting that Kcnh4a regulates sleep.
MIT Department
Massachusetts Institute of Technology. Media Laboratory
Program in Media Arts and Sciences (Massachusetts Institute of Technology)
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.7554/eLife.08638
