TY - JOUR TI - Hypocretin underlies the evolution of sleep loss in the Mexican cavefish AU - Jaggard, James B AU - Stahl, Bethany A AU - Lloyd, Evan AU - Prober, David A AU - Duboue, Erik R AU - Keene, Alex C A2 - Bronner, Marianne VL - 7 PY - 2018 DA - 2018/02/06 SP - e32637 C1 - eLife 2018;7:e32637 DO - 10.7554/eLife.32637 UR - https://doi.org/10.7554/eLife.32637 AB - The duration of sleep varies dramatically between species, yet little is known about the genetic basis or evolutionary factors driving this variation in behavior. The Mexican cavefish, Astyanax mexicanus, exists as surface populations that inhabit rivers, and multiple cave populations with convergent evolution on sleep loss. The number of Hypocretin/Orexin (HCRT)-positive hypothalamic neurons is increased significantly in cavefish, and HCRT is upregulated at both the transcript and protein levels. Pharmacological or genetic inhibition of HCRT signaling increases sleep in cavefish, suggesting enhanced HCRT signaling underlies the evolution of sleep loss. Ablation of the lateral line or starvation, manipulations that selectively promote sleep in cavefish, inhibit hcrt expression in cavefish while having little effect on surface fish. These findings provide the first evidence of genetic and neuronal changes that contribute to the evolution of sleep loss, and support a conserved role for HCRT in sleep regulation. KW - cavefish KW - sleep KW - Orexin KW - sensory processing KW - metabolism JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -