Hypocretin neuron-specific transcriptome profiling identifies the sleep modulator Kcnh4a
Author(s)
Yelin-Bekerman, Laura; Elbaz, Idan; Diber, Alex; Dahary, Dvir; Gibbs-Bar, Liron; Alon, Shahar; Lerer-Goldshtein, Tali; Appelbaum, Lior; ... Show more Show less![Thumbnail](/bitstream/handle/1721.1/99667/Yelin-Bekerman-2015-Hypocretin%20neuron-sp.pdf.jpg?sequence=4&isAllowed=y)
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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.
Date issued
2015-10Department
Massachusetts Institute of Technology. Media Laboratory; Program in Media Arts and Sciences (Massachusetts Institute of Technology)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
ISSN
2050-084X