Journal Article

Evidence for sleep-dependent synaptic renormalization in mouse pups

de Vivo, Luisa, Nagai, Hirotaka, Nagai, Midori, Spano, Giovanna Maria, Cirelli, Chiara, Nemec, Kelsey Marie, De Wispelaere, Noemi, Marshall, William, Schiereck, Shannon Sandra, Tononi, Giulio, Bellesi, Michele

2019

Overview

In adolescent and adult brains several molecular, electrophysiological, and ultrastructural measures of synaptic strength are higher after wake than after sleep [1, 2]. These results support the proposal that a core function of sleep is to renormalize the increase in synaptic strength associated with ongoing learning during wake, to reestablish cellular homeostasis and avoid runaway potentiation, synaptic saturation, and memory interference [2, 3]. Before adolescence however, when the brain is still growing and many new synapses are forming, sleep is widely believed to promote synapse formation and growth. To assess the role of sleep on synapses early in life, we studied 2-week-old mouse pups (both sexes) whose brain is still undergoing significant developmental changes, but in which sleep and wake are easy to recognize. In two strains (CD-1, YFP-H) we found that pups spend ~50% of the day asleep and show an immediate increase in total sleep duration after a few hours of enforced wake, indicative of sleep homeostasis. In YFP-H pups we then used serial block-face electron microscopy to examine whether the axon-spine interface (ASI), an ultrastructural marker of synaptic strength, changes between wake and sleep. We found that the ASI of cortical synapses (layer 2, motor cortex) was on average 33.9% smaller after sleep relative to after extended wake and the differences between conditions were consistent with multiplicative scaling. Thus, the need for sleep-dependent synaptic renormalization may apply also to the young, pre-weaned cerebral cortex, at least in the superficial layers of the primary motor area.

• Publisher: Oxford University Press
• Subject: Adolescence / Analysis / Animals / Animals, Newborn / Axons - physiology / Basic Science of Sleep and Circadian Rhythms / Brain / Cerebral Cortex - physiology / Dendritic Spines - physiology / Electron microscopy / Electrophysiological Phenomena / Female / Homeostasis / Learning / Male / Mice / Microscopy / Microscopy, Electron / Neuronal Plasticity - physiology / Neurons - physiology / Sleep / Sleep - physiology / Synapses / Synapses - physiology / Wakefulness - physiology