Neuronal ensembles sufficient for recovery sleep and the sedative actions of alpha(2) adrenergic agonists

作者：Zhang Zhe; Ferretti Valentina; Guentan Ilke; Moro Alessandro; Steinberg Eleonora A; Ye Zhiwen; Zecharia Anna Y; Yu Xiao; Vyssotski Alexei L; Brickley Stephen G; Yustos Raquel; Pillidge Zoe E; Harding Edward C; Wisden William; Franks Nicholas P^*

来源：Nature Neuroscience, 2015, 18(4): 553-+.

DOI：10.1038/nn.3957

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 alpha 2 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 alpha 2A 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, alpha 2 adrenergic receptor-induced sedation and recovery sleep share hypothalamic circuitry sufficient for producing these behavioral states.

• 出版日期2015-4