Hypocretin neuron-specific transcriptome profiling identifies the sleep modulator Kcnh4a

• DOI: 10.7554/elife.08638
• Publication Date: 2015-10-01T11:35:23Z
• Authors: Laura Yelin-Bekerman; Idan Elbaz; Alex Diber; Dvir Dahary; Liron Gibbs-Bar; Shahar Alon; Tali Lerer-Goldsh...; Lior Appelbaum
• Keywords: Sleep

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, reward. To elucidate mechanism that enables these various functions to identify regulators, we combined fluorescence cell sorting RNA-seq in hcrt:EGFP zebrafish. Dozens Hcrt-neuron–specific transcripts were identified comprehensive high-resolution imaging revealed gene-specific localization all or subsets Hcrt neurons. Clusters genes predicted be regulated by shared transcription factors. These findings show heterogeneous integrative orchestrate their diverse functions. voltage-gated potassium channel Kcnh4a, which is expressed neurons, was silenced CRISPR-mediated gene inactivation system. mutant kcnh4a (kcnh4a-/-) larvae showed reduced time consolidation, specifically during night, suggesting Kcnh4a regulates sleep.