Cerebral capillary blood flow upsurge during REM sleep is mediated by A2a receptors

Chia Jung Tsai, Takeshi Nagata, Chih Yao Liu, Takaya Suganuma, Takeshi Kanda, Takehiro Miyazaki, Kai Liu, Tsuyoshi Saitoh, Hiroshi Nagase, Michael Lazarus, Kaspar E. Vogt, Masashi Yanagisawa, Yu Hayashi

Research output: Contribution to journalArticlepeer-review

Abstract

Sleep is generally viewed as a period of recovery, but how the supply of cerebral blood flow (CBF) changes across sleep/wake states has remained unclear. Here, we directly observe red blood cells (RBCs) within capillaries, where the actual substance exchange between the blood and neurons/glia occurs, by two-photon microscopy. Across multiple cortical areas, average capillary CBF is largely increased during rapid eye movement (REM) sleep, whereas it does not differ between periods of active wakefulness and non-REM sleep. Capillary RBC flow during REM sleep is further elevated following REM sleep deprivation, suggesting that capillary CBF reflects REM sleep pressure. At the molecular level, signaling via adenosine A2a receptors is crucial; in A2a-KO mice, capillary CBF upsurge during REM sleep is dampened, and effects of REM sleep pressure are abolished. These results provide evidence regarding the dynamics of capillary CBF across sleep/wake states and insights to the underlying mechanisms.

Original languageEnglish (US)
Article number109558
JournalCell Reports
Volume36
Issue number7
DOIs
StatePublished - Aug 17 2021
Externally publishedYes

Keywords

  • adenosine A2a receptor knockout mice
  • capillary
  • cerebral blood flow
  • rapid-eye-movement (REM) sleep
  • sleep homeostasis
  • two-photon microscopy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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