Effects of sleep and waking on the synaptic ultrastructure

Abstract

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’.

Effects of Severe Sleep Disruption on the Synaptic Ultrastructure of Young Mice

“…We also found that, in primary motor cortex, the ASI was larger in two-week-old mouse pups kept awake for 4-5 hours during the day as compared to siblings allowed to sleep during the same time window . Together, these findings show that the ASI of cortical synapses is larger after wake than after sleep independent of circadian time, both in early development and during adolescence, in line with the synaptic homeostasis hypothesis (Tononi and Cirelli, 2014Cirelli, , 2020.…”

“…Like the latter, the ASI increases with synaptic potentiation (Buchs and Muller, 1996;Cheetham et al, 2014;Desmond and Levy, 1988;Fukazawa et al, 2003). The goal of our experiments was to use the ASI to test the synaptic homeostasis hypothesis of sleep function (Tononi and Cirelli, 2014Cirelli, , 2020. According to this hypothesis, ongoing learning during wake leads to a net increase in synaptic strength in many brain circuits, and sleep is needed to renormalize synaptic weights to save energy, avoid saturation, and benefit memory consolidation and integration.…”

The overfitted brain: Dreams evolved to assist generalization

“…This may include things like tracking changes in dendritic spine morphology during REM, such have been used to track spine morphology changes during sleep to investigate SHY. 157 Notably, the sort of cognitive flexibility and generalization the OBH claims is the purpose of dreams is highly important for workers and those in the armed forces who sometimes operate under sleep deprivation during critical periods, which can lead to increased accident rates, 158 and has a significant monetary annual impact. 159 If it is true that sleep-deprived brains are overfitted, they will be prone to make errors in stereotypical ways.…”

“…This may include things like tracking changes in dendritic spine morphology during REM, such have been used to track spine morphology changes during sleep to investigate SHY. 157 …”

Pills or Sleep Deprivation? Sleep-Deprivation as a Therapeutic Option Intervention in Psychiatry

“…Уровни кортикального серотонина находятся в высоких пределах во время состояния бодрствования, снижаются во время фазы медленного сна и приближаются к нулевым значениям во время фазы REM-сна [193; 194]. Результатами некоторых исследований на животных продемонстрировано, что во время сеанса депривации сна высвобождение серотонина гораздо выше, чем в предшествующий период бодрствования [195]. Одна ночь депривации сна приводит к повышению уровней серотонина и триптофана в плазме у человека [196].…”