Trends in Neurosciences
ReviewSynaptic plasticity in sleep: learning, homeostasis and disease
Introduction
While we all experience sleep, and so believe we know what it is, sleep remains a scientific enigma. A conclusive definition of sleep has eluded researchers and probably will continue to do so until the function of sleep is fully elucidated. Nevertheless, a working description of sleep as an electrophysiologically and behaviorally defined state has been established since the middle of the 20th century 1, 2. In animals with a developed neocortex, including mammals and birds, sleep states are defined by specific patterns of whole-brain activity detected by an electroencephalograph (EEG), along with eye movement electrooculogram (EOG) and muscle tone electromyogram (EMG) patterns. Non-rapid eye movement sleep (NREM) is characterized by high-voltage synchronized slow waves of electrical activity throughout the cortex and is referred to as slow-wave sleep (SWS) in its most synchronized form. Rapid eye movement (REM) sleep is characterized by rapid eye movement, muscle paralysis and low-voltage irregular EEG waves similar to waves observed during wakefulness [3].
During the early 1980s, Irene Tobler extended this definition of sleep using additional behavioral criteria 4, 5, 6: (i) decreased behavioral activity (immobility); (ii) site preference (e.g. bed); (iii) specific posture (e.g. lying); (iv) rapid reversibility (unlike coma); and, most importantly, (v) increased arousal threshold (offline state, no perception of the environment); and (vi) homeostatic control (sleep rebound after sleep deprivation). As of today, using the above criteria, sleep has been documented and studied in a wide range of vertebrates and invertebrates [7] and there is currently no clear evidence of an animal species that does not sleep [8]. The existence of an ancestral sleep state, combined with evidence that prolonged sleep deprivation leads to death in rats [9], fruit flies [10] and humans with fatal familial insomnia [11], strongly supports the hypothesis that sleep function serves a universal physiological need.
Using the above electrophysiological and behavioral criteria, major progress has been made in deciphering the mechanisms regulating sleep and wake states. Brain nuclei, circuits, neurotransmitters and genes involved in sleep–wake regulation and state switch have been identified 12, 13, but the most fundamental question remains: why do we sleep? Diverse theories have been postulated to account for the restorative effect of sleep and the importance of sleep for cognitive performance 14, 15, 16, 17, 18, 19. Sleep probably has multiple functions, but the strongest experimental evidence supports a primary role for sleep in the regulation of brain plasticity and cognition. Sleep deprivation impairs performance in motor and cognitive tasks [20] and sleep strengthens cognitive functions, including visual discrimination [21], motor learning [22] and insight (gaining explicit understanding of an implicit rule) [23]. Evidence has been gathered at the behavioral, neuronal, synaptic and molecular levels indicating that sleep promotes neural plasticity. Recent work in mammalian and non-mammalian models highlights the importance of sleep for synaptic remodeling and homeostasis (Table 1). In this review, we focus on the evidence for the role of sleep in synapse plasticity, a function conserved across animal phyla and critical for learning and memory as well as synaptic function and homeostasis.
Section snippets
Learning, memory and plasticity consolidation
The facilitation of memory retention is the most widely accepted and experimentally supported hypothesis explaining the neuronal need for sleep. Although learning mostly occurs during wake, sleep is of critical importance for memory processes. Sleep greatly enhances both the encoding and consolidation of memory 18, 19, 24. Adequate sleep is necessary, both before and after an event, for that event to be properly encoded and stored in long-term memory 18, 19, 25. Sleep-deprived humans have
The synaptic homeostasis hypothesis
The memory consolidation hypothesis proposes a specific mechanism of synapse modification by which the encoding of memory traces is rendered more efficient through modification of relevant synapses. Recently a new hypothesis, the SHH, has emerged that postulates that sleep globally downscales all synapses to compensate for the net increase in synapse formation and strength during wake 14, 54 (Figure 1a). The SHH assumes that wakefulness causes net cortical synaptic potentiation throughout the
What could be the primary ancestral function of sleep?
The accumulation of evidence linking sleep to synaptic and circuit plasticity in vertebrates and, more recently, invertebrates (Table 1) allows informed speculations about what could be the ancestral and primary role of sleep. Across distantly related animal models, sleep has been shown to have a critical role in at least three main manifestations of circuit plasticity: brain and nervous system development, learning and memory, and synaptic homeostasis. Based on this observation, one convergent
Sleep abnormalities in cognitive disorders and related animal models
Our discussion thus far has focused on the role of sleep as a major organizer of synapse and circuit plasticity in the brain. In this role, sleep acts in synchrony with the circadian rhythm to normalize, modulate and optimize the synaptic function and circuit connectivity of cortical and subcortical neural networks. The dark side of the importance of sleep for synapse and circuit function is that sleep dysfunction is also connected to numerous neurological and neurodevelopment disorders (Table 3
Concluding remarks
Although many questions remain (Box 2), the scientific enigma as to why we sleep is beginning to be unraveled. In the brain, sleep is essential, and this need appears to require a level of synaptic plasticity that is unavailable during wake. This state of plasticity allows for homeostatic optimization of neural networks as well as the replay-based consolidation of specific circuits. Indeed, sleep plasticity appears to be focused not on acquiring new information, but on prioritizing and
Acknowledgment
Our work is supported by the National Institutes of Health (NS062798, DK090065).
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2022, International Journal of PsychophysiologySleep and homeostatic control of plasticity
2022, Handbook of Clinical NeurologyCitation Excerpt :This daily structural and functional increase of synaptic activity is also associated with the modification of gene expression and neurochemical systems that are critical to the induction and maintenance of synaptic potentiation. Therefore, SHY provides a compelling set of testable hypotheses for describing the synaptic changes happening in sleep and during the wake–sleep cycle (Wang et al., 2011). On the other hand, wake time duration regulates the amplitude and duration of SWA: extended wakefulness leads to higher amplitude of the slow waves in NREM sleep with steeper slopes and fewer multi-peak waves (Huber et al., 2000).
Sleep Promotes Downward Firing Rate Homeostasis
2021, NeuronCitation Excerpt :It was thus surprising to find that they have a diametrically opposite dependence upon behavioral state: upward FRH occurs during active waking, whereas downward FRH occurs during sleep. These findings show that upward and downward homeostatic compensation do not operate simultaneously within neuronal circuits and add complexity to the idea that the function of sleep is to provide a window of opportunity for homeostatic plasticity (Wang et al., 2011). SHY proposes that wakefulness drives learning-related increases in synaptic strengths and firing rates, whereas sleep renormalizes activity by downregulating synaptic strengths, a process dependent on activity patterns during NREM sleep (Tononi and Cirelli, 2014).