title: Loss of Melanopsin Photoreception and Antagonism of the Histamine H3 Receptor by Ciproxifan Inhibit Light-Induced Sleep in Mice.
abstract: Light has direct effects on sleep and wakefulness causing arousal in diurnal animals and sleep in nocturnal animals. In the present study, we assessed the modulation of light-induced sleep by melanopsin and the histaminergic system by exposing mice to millisecond light flashes and continuous light respectively. First, we show that the induction of sleep by millisecond light flashes is dose dependent as a function of light flash number. We found that exposure to 60 flashes of light occurring once every 60 seconds for 1-h (120-ms of total light over an hour) induced a similar amount of sleep as a continuous bright light pulse. Secondly, the induction of sleep by millisecond light flashes was attenuated in the absence of melanopsin when animals were presented with flashes occurring every 60 seconds over a 3-h period beginning at ZT13. Lastly, the acute administration of a histamine H3 autoreceptor antagonist, ciproxifan, blocked the induction of sleep by a 1-h continuous light pulse during the dark period. Ciproxifan caused a decrease in NREMS delta power and an increase in theta activity during both sleep and wake periods respectively. The data suggest that some form of temporal integration occurs in response to millisecond light flashes, and that this process requires melanopsin photoreception. Furthermore, the pharmacological data suggest that the increase of histaminergic neurotransmission is sufficient to attenuate the light-induced sleep response during the dark period.
authors.affiliation: Department of Biology, Stanford University, Stanford, California, United States of America; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Fanuel
authors.initials: F
authors.lastname: Muindi
authors.affiliation: Department of Biology, Stanford University, Stanford, California, United States of America.
authors.forename: Damien
authors.initials: D
authors.lastname: Colas
authors.affiliation: Department of Biology, Stanford University, Stanford, California, United States of America.
authors.forename: Jesse
authors.initials: J
authors.lastname: Ikeme
authors.affiliation: Department of Biology, Stanford University, Stanford, California, United States of America.
authors.forename: Norman F
authors.initials: NF
authors.lastname: Ruby
authors.affiliation: Department of Biology, Stanford University, Stanford, California, United States of America.
authors.forename: H Craig
authors.initials: HC
authors.lastname: Heller
mesh_terms: D000818:Animals; D004569:Electroencephalography; D004576:Electromyography; D006633:Histamine Antagonists / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D008027:Light; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D018100:Receptors, Histamine H3 / Q000737:chemistry / Q000378:metabolism*; D017299:Rod Opsins / Q000235:genetics / Q000378:metabolism*; D012890:Sleep / Q000187:drug effects* / Q000528:radiation effects; D014851:Wakefulness / Q000187:drug effects / Q000528:radiation effects; D000099210:Melanopsin
chemical_list: D006633:Histamine Antagonists; D007093:Imidazoles; D018100:Receptors, Histamine H3; D017299:Rod Opsins; D000099210:Melanopsin; C115705:ciproxifan