Theoretical ReviewSleep function and synaptic homeostasis
Introduction
This paper discusses a novel hypothesis—the synaptic homeostasis hypothesis—which claims that sleep plays a role in the regulation of synaptic weight in the brain.1 The synaptic homeostasis hypothesis can account for several aspects of sleep and its regulation, and makes several specific predictions. In brief, the hypothesis is as follows: (1) Wakefulness is associated with synaptic potentiation in several cortical circuits; (2) Synaptic potentiation is tied to the homeostatic regulation of slow wave activity; (3) Slow wave activity is associated with synaptic downscaling; (4) Synaptic downscaling is tied to the beneficial effects of sleep on neural function and, indirectly, on performance.
A useful way of introducing the synaptic homeostasis hypothesis is to relate it to one of the best-established models of sleep regulation—the two-process model.2 The model distinguishes between the circadian and the homeostatic regulation of sleep propensity. The circadian component (process C) describes how sleep propensity changes during the 24 h. Process C is well understood, both in its mechanisms, centered in the suprachiasmatic nucleus, and in its function, which is to restrict sleep to a time of day that is ecologically appropriate. The homeostatic component (Process S) accumulates exponentially during wakefulness and is discharged when we sleep, also exponentially but with a faster time course (Fig. 1). The time course of Process S was derived from a physiological variable, EEG slow-wave activity (SWA) in the electroencephalogram (EEG) of non rapid eye movement (NREM) sleep. The homeostatic regulation of SWA suggests that it may reflect some restorative aspect of sleep, but what this aspect may be remains unknown.
According to the present hypothesis, Process S describes the process of synaptic homeostasis. Specifically, the curve in Fig. 1 can be interpreted as reflecting how the total amount of synaptic strength in the cerebral cortex (and possibly other brain structures) changes as a function of wakefulness and sleep. Thus, the hypothesis claims that, under normal conditions, total synaptic strength increases during wakefulness and reaches a maximum just before going to sleep. Then, as soon as sleep ensues, total synaptic strength begins to decrease, and reaches a baseline level by the time sleep ends. In addition to claiming a correspondence between the homeostatic Process S and total synaptic strength, the hypothesis proposes specific mechanisms, whereby synaptic strength would increase during wakefulness and decrease during sleep, and suggests why the tight regulation of synaptic strength would be of great importance for the brain.
Section snippets
Synaptic homeostasis: a schematic diagram
The diagram in Fig. 2 presents a simplified version of the main points of the hypothesis. During wakefulness (yellow background), we interact with the environment and acquire information about it. The EEG is activated, and the neuromodulatory milieu (for example, high levels of noradrenaline, NA) favors the storage of information, which occurs largely through long-term potentiation of synaptic strength. This potentiation occurs when the firing of a presynaptic neuron is followed by the
The main claims of the synaptic homeostasis hypothesis
After this schematic depiction of the hypothesis, we now turn to describing its main points in more detail, and to discussing some supporting evidence.
Some implications of the synaptic homeostasis hypothesis
To the extent that the main claims of the synaptic homeostasis hypothesis are justified by the available evidence, they offer a fresh perspective on several aspects of sleep and sleep medicine. In what follows, we will consider some intriguing implications of the hypothesis for neuroimaging studies, and briefly discuss the possibility that a dysregulation of synaptic homeostasis may be implicated in disorders such as insomnia and depression.
Conclusion
In summary, the synaptic homeostasis hypothesis makes four main claims: (1) Wakefulness is associated with synaptic potentiation in several cortical circuits; (2) Synaptic potentiation is tied to the homeostatic regulation of slow wave activity; (3) Slow wave activity is associated with synaptic downscaling; (4) Synaptic downscaling is tied to the beneficial effects of sleep on neural function and, indirectly, on performance. From these claims derive several intriguing possibilities, including
Acknowledgements
Supported by RO1-MH65135
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