Optogenetic stimulation of astrocytes in the posterior hypothalamus increases sleep at night in C57BL/6J mice. (16th October 2015)

• Record Type: Journal Article
• Authors: Pelluru, Dheeraj; Konadhode, Roda Rani; Bhat, Narayan R.; Shiromani, Priyattam J.
• Editors: Silver, Rae
• Is Part Of: European journal of neuroscience. Volume 43:Number 10(2016:May)
• Page Start: 1298
• Page End: 1306
• Publication Date: 2015-10-16
• Subjects: channelrhodopsin‐2 -- melanin concentrating hormone -- orexin -- recombinant adenoassociated virus -- REM sleep; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.13074
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: A distributed network of neurons regulates wake, non‐rapid eye movement (NREM) sleep, and REM sleep. However, there are also glia in the brain, and there is growing evidence that neurons and astroglia communicate intimately to regulate behaviour. To identify the effect of optogenetic stimulation of astrocytes on sleep, the promoter for the astrocyte‐specific cytoskeletal protein, glial fibrillary acidic protein (GFAP) was used to direct the expression of channelrhodopsin‐2 (ChR2) and the linked reporter gene, enhanced yellow fluorescent protein (EYFP), in astrocytes. rAAV‐GFAP‐ChR2 (H134R)‐EYFP or rAAV‐GFAP‐EYFP was microinjected (750 nL) into the posterior hypothalamus (bilateral) of mice. Three weeks later baseline sleep was recorded (0 Hz) and 24 h later optogenetic stimulation applied during the first 6 h of the lights‐off period. Mice with ChR2 were given 5, 10 or 30 Hz stimulation for 6 h (10‐ms pulses; 1 mW; 1 min on 4 min off). At least 36 h elapsed between the stimulation periods (5, 10, 30 Hz) and although 0 Hz was always first, the order of the other three stimulation rates was randomised. In mice with ChR2 ( n = 7), 10 Hz, but not 5 or 30 Hz stimulation increased both NREM and REM sleep during the 6‐h period of stimulation. Delta power did not increase. In control mice (no ChR2; n = 5), 10 Hz stimulation had no effect. This study demonstrates that direct stimulation of astrocytes powerfully induces sleep during the active phase of the sleep–wake cycle and underlines the inclusion of astrocytes in network models of sleep–wake regulation. Abstract : Astrocytes in posterior hypothalamus of C57BL/6J mice (n = 7) were transduced with rAAV‐GFAP‐ChR2 (H134R)‐EYFP to express ChR2. When optogenetically stimulated at 10 Hz with blue light (473 nm) during the dark phase (active period), the mice had significant increase in NREM and REM sleep. This underscores the importance of astrocytes in sleep.