The intrinsic microglial molecular clock controls synaptic strength via the circadian expression of cathepsin S

Yoshinori Hayashi, Satoru Koyanagi, Naoki Kusunose, Ryo Okada, Zhou Wu, Hidetoshi Tozaki-Saitoh, Kiyoharu Ukai, Shinichi Kohsaka, Kazuhide Inoue, Shigehiro Ohdo, Hiroshi Nakanishi

Research output: Contribution to journalArticlepeer-review

67 Citations (Scopus)

Abstract

Microglia are thought to play important roles in the maintenance of neuronal circuitry and the regulation of behavior. We found that the cortical microglia contain an intrinsic molecular clock and exhibit a circadian expression of cathepsin S (CatS), a microglia-specific lysosomal cysteine protease in the brain. The genetic deletion of CatS causes mice to exhibit hyperlocomotor activity and removes diurnal variations in the synaptic activity and spine density of the cortical neurons, which are significantly higher during the dark (waking) phase than the light (sleeping) phase. Furthermore, incubation with recombinant CatS significantly reduced the synaptic activity of the cortical neurons. These results suggest that CatS secreted by microglia during the dark-phase decreases the spine density of the cortical neurons by modifying the perisynaptic environment, leading to downscaling of the synaptic strength during the subsequent light-phase. Disruption of CatS therefore induces hyperlocomotor activity due to failure to downscale the synaptic strength.

Original languageEnglish
Article number2744
JournalScientific reports
Volume3
DOIs
Publication statusPublished - 2013

All Science Journal Classification (ASJC) codes

  • General

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