The facilitation of memory retention is the most widely accepted and experimentally supported hypothesis explaining the neuronal need for sleep. Though learning mostly occurs during wake, sleep is of critical importance for memory processes. Sleep greatly enhances both the encoding and consolidation of memory [18
]. Adequate sleep is necessary, both before and after an event, for that event to be properly encoded and stored in long-term memory [18
]. Sleep-deprived humans have significantly impaired memory retention and degraded performance in memory encoding [26
]. Long periods of sleep are clearly beneficial but gains in memorization performance have also been reported after short sleep periods. Recall of events is stronger and more accurate after daytime nap as brief as a few minutes, as compared to a similar wake period [29
Quality of memory consolidation is not only a function of time spent asleep but can also vary depending on the type of memories, the relevance of the memorized event, and the motivation to remember. Following sleep, procedural memories(i.e. memorization of cognitive and motor skills) have been shown to benefit more than declarative memories (i.e. recollection of experiences and information) [19
]. Further, sleep had a stronger stabilizing effect on memories of tasks or events when there was a conscious effort or an incentive to memorize those. Simply put, conscious learning of a motor task associated with a potential reward generates memories that profit the most from sleep-dependent consolidation in contrast to unconscious and/or unmotivated learning of the same task [19
]. This uneven and contextual influence of sleep on different classes of memories suggests an intriguing possibility that sleep-dependent and sleep-independent plasticity coexist and interact in the circuits and brain regions responsible for encoding and storing the different memory types.
While behavioral observations have shown that sleep as a whole is clearly important for memory consolidation, the roles of the different sleep phases are still being deciphered. Because of its relationship with dreams, REM sleep was first suspected to be critical for memory formation, but most of the EEG studies performed so far have reported that NREM, especially SWS, sleep is critical for memory retention. SWS/NREM sleep deprivation after learning prevents subsequent consolidation and enhancement of memories [19
]. Consistent with this observation, stimulation of slow wave oscillations during sleep enhances the retention of same-day memory traces for next-day retrieval [33
]. Although SWS seems to have a primary role in memory formation, it is still unclear how other sleep phases participate in memory encoding and consolidation. NREM sleep spindles for example have been shown to be important for consolidation [34
] and more recently encoding/learning capabilities [25
]. REM sleep has also been associated with emotion-related memories [18
]. Finally, in opposition to a dichotomous view associating a specific sleep stage with a specific type of memory, it has also been postulated that the sequence in which phases appear in normal sleep, i.e. NREMREM succession, could be more important for optimal consolidation, whatever the memory type, than duration of each stage [35
]. A better understanding of the molecular and physiological mechanisms generating the different sleep stages should shed light on their roles in hippocampal/cortical circuit plasticity and the different types of memory.
An intriguing and important mechanism proposed for sleep’s role in the facilitation of memory consolidation is the replay of memory traces in hippocampal and cortical circuits during sleep (reviewed in [19
]). Firing patterns recorded during wakefulness can be replayed during the following SWS/NREM sleep period [19
] and sometimes REM [38
]. In neurons of the zebra finch song system, replay of patterns of bursts corresponding to singing sequence was observed during sleep [39
]. In rats, neuronal activation patterns recorded during maze learning are recreated during SWS [41
]. The human hippocampus is similarly reactivated during SWS following learning of a spatial task and the strength of this reactivation is associated with fidelity of learning [43
]. Importantly, the reactivation of memories in humans by presenting, during SWS, odor or noise cues that were also present during learning leads to enhanced memory consolidation [44
] and increased resistance of that memory to interference [46
]. During a NREM nap, mental activity related to a spatial memory task is associated with enhanced memory consolidation [38
]. Consistently, reactivation in SWS was correlated to activations of hippocampal and neocortical regions critical to learning and memory [46
]. Interestingly, replay happens during the first 15-30min of sleep, when mammals are in SWS. During this SWS period, reactivated circuits undergo synaptic consolidation according to replay hypothesis, while others could be pruned according to the synaptic homeostasis hypothesis (see below). One could speculate that both hypotheses are not exclusive and that replay mechanisms could be important to protect fragile circuits against global synaptic downscaling.
While these recent reinstatement data are compelling, replay as a sleep-dependent mechanism for memory consolidation still remains to be fully established. Replay has mostly been studied in extensively trained rodents, except in a few cases [47
], and thus, it may also reflect the firing of well-entrained circuitry. Moreover, replay is extremely transient and labile, and only a few studies have successfully investigated its function in memory transfer from the hippocampus to the neocortex (e.g. [48
]). It is important to mention here that replay also occurs during wake, when it can similarly affect learning and memory consolidation [49
]. Reactivation of memories by odorants during sleep and during wake, however, activate different brain regions and elicit very different memory responses. Odor cues that were present during learning activate hippocampal and posterior cortical regions and strengthen object-location memories when presented during sleep, but weaken those memories and activate mainly prefrontal cortical regions when presented during wakefulness [46
]. Clearly, more work needs to be done to uncover the molecular and circuit properties of sleep/wake gating of brain activity and effects of memory reactivation on consolidation.
Consistent with the replay/reactivation studies, sleep is believed to consolidate synaptic connections required for encoding and retention of memories. Currently, the mechanisms underpinning synaptic consolidation during sleep in these hippocampal and cortical memory storage circuits remain unknown. Sleep has, however, already proven to be critical for consolidation of ocular dominance plasticity (ODP), a type of cortical plasticity widespread in mammals and particularly well-studied in cats. In ODP, deprivation of vision in one eye (monocular deprivation, MD) leads to increased rewiring of visual cortex by the non-deprived eye [51
]. Interestingly, when MD is followed by just a few hours of sleep, cortical responses to non-deprived eye stimulation are strengthened [51
]. Further, cortical consolidation was found correlated with the amount of NREM [51
]. This finding suggests that sleep, especially NREM, has a critical function in cortical synaptic remodeling.
More recently, sleep-dependent consolidation in ODP was disrupted when major molecular actors of synaptic potentiation and plasticity such as NMDA receptors NMDARs) and protein kinase A (PKA) were antagonized [53
]. Increased phosphorylation and activation of downstream targets of these pathways [eg. extracellular signal-regulated kinase (ERK), Ca2+
-calmodulin-dependent protein kinase (CaMKII) and the AMPA receptor (AMPAR) GluR1 subunit] were observed only after post-MD sleep [53
]. These data show that sleep can change the strength of neuronal connections and that pathways involved in synaptic plasticity are activated. Furthermore, all these data suggest that synchronous reactivation of behaviorally relevant neural circuits during sleep can mediate meaningful and functionally relevant changes in the brain, and further dissection of the molecular mechanisms underlying these activity states is critical to the understanding of sleep in the consolidation and optimization of brain circuit function.