title: Neuronal ensembles sufficient for recovery sleep and the sedative actions of α2 adrenergic agonists.
abstract: Do sedatives engage natural sleep pathways? It is usually assumed that anesthetic-induced sedation and loss of righting reflex (LORR) arise by influencing the same circuitry to lesser or greater extents. For the α2 adrenergic receptor agonist dexmedetomidine, we found that sedation and LORR were in fact distinct states, requiring different brain areas: the preoptic hypothalamic area and locus coeruleus (LC), respectively. Selective knockdown of α2A adrenergic receptors from the LC abolished dexmedetomidine-induced LORR, but not sedation. Instead, we found that dexmedetomidine-induced sedation resembled the deep recovery sleep that follows sleep deprivation. We used TetTag pharmacogenetics in mice to functionally mark neurons activated in the preoptic hypothalamus during dexmedetomidine-induced sedation or recovery sleep. The neuronal ensembles could then be selectively reactivated. In both cases, non-rapid eye movement sleep, with the accompanying drop in body temperature, was recapitulated. Thus, α2 adrenergic receptor-induced sedation and recovery sleep share hypothalamic circuitry sufficient for producing these behavioral states.
authors.affiliation: Department of Life Sciences Imperial College London, South Kensington, SW7 2AZ, U.K.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Life Sciences Imperial College London, South Kensington, SW7 2AZ, U.K.
authors.forename: Valentina
authors.initials: V
authors.lastname: Ferretti
authors.affiliation: Department of Life Sciences Imperial College London, South Kensington, SW7 2AZ, U.K.
authors.forename: İlke
authors.initials: İ
authors.lastname: Güntan
authors.affiliation: Department of Life Sciences Imperial College London, South Kensington, SW7 2AZ, U.K.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moro
authors.affiliation: Department of Life Sciences Imperial College London, South Kensington, SW7 2AZ, U.K.
authors.forename: Eleonora A
authors.initials: EA
authors.lastname: Steinberg
authors.affiliation: Department of Life Sciences Imperial College London, South Kensington, SW7 2AZ, U.K.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Department of Life Sciences Imperial College London, South Kensington, SW7 2AZ, U.K.
authors.forename: Anna Y
authors.initials: AY
authors.lastname: Zecharia
authors.affiliation: Department of Life Sciences Imperial College London, South Kensington, SW7 2AZ, U.K.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yu
authors.affiliation: Institute of Neuroinformatics, University of Zürich/ETH Zürich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland.
authors.forename: Alexei L
authors.initials: AL
authors.lastname: Vyssotski
authors.affiliation: Department of Life Sciences Imperial College London, South Kensington, SW7 2AZ, U.K.
authors.forename: Stephen G
authors.identifier: 0000-0002-0930-7346
authors.initials: SG
authors.lastname: Brickley
authors.affiliation: Department of Life Sciences Imperial College London, South Kensington, SW7 2AZ, U.K.
authors.forename: Raquel
authors.initials: R
authors.lastname: Yustos
authors.affiliation: Department of Life Sciences Imperial College London, South Kensington, SW7 2AZ, U.K.
authors.forename: Zoe E
authors.initials: ZE
authors.lastname: Pillidge
authors.affiliation: Department of Life Sciences Imperial College London, South Kensington, SW7 2AZ, U.K.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Harding
authors.affiliation: Department of Life Sciences Imperial College London, South Kensington, SW7 2AZ, U.K.
authors.forename: William
authors.identifier: 0000-0003-4743-0334
authors.initials: W
authors.lastname: Wisden
authors.affiliation: Department of Life Sciences Imperial College London, South Kensington, SW7 2AZ, U.K.
authors.forename: Nicholas P
authors.identifier: 0000-0003-4874-4212
authors.initials: NP
authors.lastname: Franks
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D054810:Deep Sedation; D020927:Dexmedetomidine / Q000494:pharmacology*; D004569:Electroencephalography; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects* / Q000502:physiology; D007035:Hypothermia / Q000139:chemically induced; D008125:Locus Coeruleus / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010597:Pharmacogenetics; D012890:Sleep / Q000187:drug effects*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine