Effects of sleep and waking on the synaptic ultrastructure.

We summarize here several studies performed in our laboratory, mainly using serial block-face scanning electron microscopy (SBEM), to assess how sleep, spontaneous waking and short sleep deprivation affect the size and number of synapses in the cerebral cortex and hippocampus. With SBEM, we reconstructed thousands of cortical and hippocampal excitatory, axospinous synapses and compared the distribution of their size after several hours of sleep relative to several hours of waking. Because stronger synapses are on average also bigger, the goal was to test a prediction of the synaptic homeostasis hypothesis, according to which overall synaptic strength increases during waking, owing to ongoing learning, and needs to be renormalized during sleep, to avoid saturation and to benefit memory consolidation and integration. Consistent with this hypothesis, we found that the size of the axon-spine interface (ASI), a morphological measure of synaptic strength, was on average smaller after sleep, but with interesting differences between primary cortex and the CA1 region of the hippocampus. In two-week-old mouse pups, the decline in ASI size after sleep was larger, and affected more cortical synapses, compared with one-month-old adolescent mice, suggesting that synaptic renormalization during sleep may be especially important during early development. This work is still in progress and other brain areas need to be tested after sleep, acute sleep loss and chronic sleep restriction. Still, the current results show that a few hours of sleep or waking lead to significant changes in synaptic morphology that can be linked to changes in synaptic efficacy. This article is part of the Theo Murphy meeting issue 'Memory reactivation: replaying events past, present and future'.