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.
Highlights
Mammalian sleep comprises two distinct states, non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep
Capillary Cerebral blood flow (CBF) largely increased during REM sleep, but was comparable between active wakefulness and NREM sleep To analyze the dynamics of capillary CBF in unanesthetized mice, we used 2PM to directly measure the movement of individual red blood cells (RBCs) within capillaries (Figures 1A and 1B)
Evaluation of capillary CBF in the parietal cortex, primary somatosensory cortex, and secondary visual cortex during active wakefulness, NREM sleep, and REM sleep revealed significantly increased capillary CBF in all cortical areas during REM sleep in terms of both the RBC velocity and flow compared with the other stages (Figures 2A– 2C)
Summary
Mammalian sleep comprises two distinct states, non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. In fMRI studies, blood oxygen level-dependent signals, which correlate with increased blood flow, during REM sleep have not yet been strictly compared with other stages, whereas during NREM sleep, they become higher as sleep becomes deeper compared with the awake state (McAvoy et al, 2019). These conflicting findings are likely due to differences in the data processing and normalization procedures used as well as differences in the type of blood vessels that were observed.
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