title: Ectopic expression of melanopsin in orexin/hypocretin neurons enables control of wakefulness of mice in vivo by blue light.
abstract: Melanopsin (OPN4) is a photosensitive G-protein-coupled photopigment and its ectopic expression enables control of neural activity induced by blue light. Here we report that we successfully expressed OPN4 in hypothalamic orexin/hypocretin neurons of double-transgenic mice (orexin-tTA; Bitet-O human OPN4 [hOPN4]/mCherry mice). In the double-transgenic mice, hypothalamic orexin neurons selectively expressed hOPN4 as well as mCherry as a reporter. We conducted slice patch-clamp recordings on hOPN4/mCherry-expressing orexin neurons, which showed long-lasting activation initiated by blue light even after the light was switched off. Optical fiber-guided blue light stimulation in the hypothalamus successfully initiated the electroencephalography pattern that reflects long-lasting wakefulness in the mice in vivo. Taken together, the results indicate that ectopic expression of hOPN4 in orexin neurons enables long-lasting activation of orexin neurons by blue light to control sleep/wakefulness of the mice.
authors.affiliation: Division of Cell Signaling, National Institute for Physiological Sciences, Okazaki, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Tsunematsu
authors.forename: Kenji F
authors.initials: KF
authors.lastname: Tanaka
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yamanaka
authors.forename: Amane
authors.initials: A
authors.lastname: Koizumi
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D062308:Optogenetics / Q000379:methods*; D000068797:Orexins; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017299:Rod Opsins / Q000235:genetics*; D014851:Wakefulness / Q000502:physiology*; D000099210:Melanopsin
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D017299:Rod Opsins; D000099210:Melanopsin