REM sleep promotes experience-dependent dendritic spine elimination in the mouse cortex

Yanmei Zhou,Wei Li,Marcos G Frank,Yang Bai,Guang Yang,Ruohe Zhao,Cora Sau Wan Lai,Wen-Biao Gan

doi:10.1038/s41467-020-18592-5

Abstract

In many parts of the nervous system, experience-dependent refinement of neuronal circuits predominantly involves synapse elimination. The role of sleep in this process remains unknown. We investigated the role of sleep in experience-dependent dendritic spine elimination of layer 5 pyramidal neurons in the visual (V1) and frontal association cortex (FrA) of 1-month-old mice. We found that monocular deprivation (MD) or auditory-cued fear conditioning (FC) caused rapid spine elimination in V1 or FrA, respectively. MD- or FC-induced spine elimination was significantly reduced after total sleep or REM sleep deprivation. Total sleep or REM sleep deprivation also prevented MD- and FC-induced reduction of neuronal activity in response to visual or conditioned auditory stimuli. Furthermore, dendritic calcium spikes increased substantially during REM sleep, and the blockade of these calcium spikes prevented MD- and FC-induced spine elimination. These findings reveal an important role of REM sleep in experience-dependent synapse elimination and neuronal activity reduction.

Highlights

In many parts of the nervous system, experience-dependent refinement of neuronal circuits predominantly involves synapse elimination
We found that monocular deprivation (MD) significantly increased dendritic spine elimination within
Our results show that rapid eye movement (REM) sleep is critical for MD- and fear conditioning (FC)-induced elimination of dendritic spines in the developing visual and frontal association cortex (FrA), respectively

Summary

Introduction

In many parts of the nervous system, experience-dependent refinement of neuronal circuits predominantly involves synapse elimination. REM sleep deprivation reduces neuronal excitability[20,21], the induction and maintenance of long-term potentiation[22,23,24], as well as ocular dominance plasticity in the developing cat visual cortex[15] Together, these studies support a view that both NREM and REM sleep have important roles in activity- and experience-dependent synaptic plasticity. Recent studies have shown that monocular deprivation (MD) or auditory-cued fear conditioning (FC) significantly increases dendritic spine elimination of layer 5 pyramidal neurons in the developing mouse primary visual cortex (V1) or frontal association cortex (FrA), respectively[29,30] Such experience-dependent dendritic spine elimination likely contributes to changes of neuronal activity in response to visual and auditory inputs[27,31,32]. These findings suggest the important role of REM sleep in experience-dependent synapse elimination, likely via dendritic Ca2+ spike-dependent mechanisms

Methods

Results

Conclusion