Sleep and Memory


Current behavioural evidence indicates that sleep plays a central role in memory consolidation. Neural events during post‐learning sleep share key features with both early and late stages of memory consolidation. For example, recent studies have shown neuronal changes during post‐learning sleep which reflect early synaptic changes associated with consolidation, including activation of shared intracellular pathways and modifications of synaptic strength. Sleep may also play a role in later stages of consolidation involving propagation of memory traces throughout the brain. However, to date the precise molecular and physiological aspects of sleep required for this process remain unknown. The behavioural effects of sleep may be mediated by the large‐scale, global changes in neuronal activity, synchrony and intracellular communication that accompany sleep, or by synapse‐specific ‘replay’ of activity patterns associated with prior learning.

Key Concepts:

  • Memory consolidation involves plastic changes at the synaptic and brain‐systems levels; these changes occur over timescales of minutes (synaptic consolidation) to days or months (systems consolidation).

  • Cellular changes occurring during early post‐learning sleep suggest that synaptic consolidation may occur preferentially during sleep.

  • Brain‐imaging and gene expression studies have provided limited evidence that sleep may facilitate the gradual redistribution of memory traces throughout the brain.

  • Sleep may facilitate consolidation through large‐scale changes in neural activity, neurotransmission or gene expression associated with REM and NREM sleep.

  • It remains unclear whether sleep‐dependent consolidation is mediated by permissive (global) or instructive (synapse‐specific) mechanisms.

Keywords: sleep; memory; synaptic plasticity; consolidation; long‐term potentiation; long‐term depression

Figure 1.

Synaptic and systems levels of memory consolidation. In the first hours following acquisition, a memory trace is represented in specific neural circuits (in this example, within the hippocampus, highlighted in grey, a). The memory trace is then gradually integrated into a broader neuronal network, including areas not involved in acquisition (in this example, in the neocortex, b), and distributed over time throughout the neocortex (c). Synaptic consolidation (schematised in d) involves activation of NMDA receptor (NMDA‐R)‐ and kinase‐dependent signalling cascades which promote de novo mRNA and protein synthesis. NMDA‐R activation increases calcium (Ca2+) influx, whereas neurotransmitter‐mediated activation of G‐protein coupled receptors stimulate cyclic adenosine monophosphate (cAMP) production. These intracellular signals in turn promote the phosphorylation‐dependent activation of kinases (e.g. PKA, CaMKII and extracellular signal‐regulated kinase (ERK)) (Wang et al., ). These kinases activate cAMP response‐element binding protein (CREB)‐dependent immediate‐early gene (IEG) expression (e.g. zif268, arc/arg3.1 and c‐fos) (Abel and Lattal, ). Products of these transcripts are then translated, together with additional effectors of synaptic potentiation or depression (e.g. glutamate receptor subunits, BDNF and CaMKII). Systems consolidation (schematised in e) requires subsequent activation of CaMKII and synthetic pathways over a period of days to months (Wang et al., ), as memory traces expand through more broadly distributed brain areas.

Figure 2.

Potential roles of sleep in synaptic and systems consolidation. (a) Representative changes in release of acetylcholine (ACh) and noradrenaline (NA) in the cortex (relative to waking) during REM and NREM sleep. Representative EEG traces for the two sleep states show cortical activity similar to that of waking during REM sleep, and high‐amplitude EEG oscillations – including sleep spindles and slow‐wave activity (SWA) – during NREM sleep. (b) Sequence of events showing the transfer over time of the memory trace from hippocampus to neocortical distributed network (see Figure a–c for detailed description). (c–e) Potential cellular mechanisms underlying sleep facilitation of consolidation. Functions demonstrated to occur specifically during sleep are shown in colour; mechanisms that might be activated in sleep, but not yet proven are indicated with a question mark. Mechanisms that have not been studied with respect to sleep are shown in grey. (c) Mechanisms implicated in sleep facilitation of synaptic consolidation are schematised in a neuron within the circuits activated by prior learning (in this example, a neuron in the hippocampus). NMDA‐R activation during sleep may be necessary for some early forms of consolidation (Gais et al., ), whereas PKA, CaMKII and CREB activation and protein synthesis are correlated with the time‐dependent requirement for sleep in other forms of learning (Bourtchouladze et al., ; Horn, ; Saha and Datta, ). Increased expression of the IEG zif268 occurs during REM sleep following some forms of learning (Ribeiro et al., ), while arc/arg3.1 and c‐fos expression are correlated in time with the requirement for sleep following other learning paradigms (Horn, ; Bock et al., ). (d) The same signalling pathways may be activated in additional neural circuits during subsequent systems consolidation (schematised as a neuron in the neocortex which is synaptically connected with the original hippocampal neuron). Changes in neurotransmission or activity during sleep (e.g. synchronised bursting activity produce by SWA and spindles) could promote intercellular communication between these brain areas (represented by red arrows). During subsequent stages of systems consolidation (e), these same sleep‐dependent mechanisms may promote further expansion of memory traces throughout the neocortex (indicated by red arrows).



Abel T and Lattal KM (2001) Molecular mechanisms of memory acquisition, consolidation and retrieval. Current Opinion in Neurobiology 11: 180–187.

Aton SJ, Seibt J, Dumoulin M et al. (2009) Mechanisms of sleep‐dependent consolidation of cortical plasticity. Neuron 61: 454–466.

Aton SJ, Suresh A, Broussard C and Frank MG (2014) Sleep promotes cortical response potentiation following visual experience. Sleep 37(7): 1163–1170.

Benington JH and Frank MG (2003) Cellular and molecular connections between sleep and synaptic plasticity. Progress in Neurobiology 69: 77–101.

Bock J, Thode C, Hannemann O, Braun K and Darlison MG (2005) Early socio‐emotional experience induces expression of the immediate‐early gene Arc/arg3.1 (activity‐regulated cytoskeleton‐associated protein/activity‐regulated gene) in learning‐relevant brain regions of the newborn chick. Neuroscience 133: 625–633.

Bourtchouladze R, Abel T, Berman N et al. (1998) Different training procedures recruit either one or two critical periods for contextual memory consolidation, each of which requires protein synthesis and PKA. Learning & Memory 5: 365–374.

Brashers‐Krug T, Shadmehr R and Bizzi E (1996) Consolidation in human motor memory. Nature 382: 252–255.

Chauvette S, Seigneur J and Timofeev I (2012) Sleep oscillations in the thalamocortical system induce long‐term neuronal plasticity. Neuron 75: 1105–1113.

Cooke SF and Bear MF (2010) Visual experience induces long‐term potentiation in the primary visual cortex. Journal of Neuroscience 30: 16304–16313.

Czarnecki A, Birtoli B and Ulrich D (2007) Cellular mechanisms of burst firing‐mediated long‐term depression in rat neocortical pyramidal cells. Journal of Physiology 578: 471–479.

Dudai Y (2004) The neurobiology of consolidations, or, how stable is the engram? Annual Review of Psychology 55: 51–86.

Ellenbogen JM, Payne JD and Stickgold R (2006) The role of sleep in declarative memory consolidation: passive, permissive, active or none? Current Opinion in Neurobiology 16: 716–722.

Fischer S, Nitschke MF, Melchert UH, Erdmann C and Born J (2005) Motor memory consolidation in sleep shapes more effective neuronal representations. Journal of Neuroscience 25: 11248–11255.

Frank MG (2012) Erasing synapses in sleep: is it time to be SHY? Neural Plasticity 2012: 1–27.

Frank MG and Benington JH (2006) The role of sleep in memory consolidation and brain plasticity: dream or reality? Neuroscientist 12: 477–488.

Frank MG, Issa NP and Stryker MP (2001) Sleep enhances plasticity in the developing visual cortex. Neuron 30: 275–287.

Frank MG, Jha SK and Coleman T (2006) Blockade of postsynaptic activity in sleep inhibits developmental plasticity in visual cortex. NeuroReport 17: 1459–1463.

Frankland PW, Bontempi B, Talton LE, Kaczmarek L and Silva AJ (2004) The involvement of the anterior cingulate cortex in remote contextual fear memory. Science 304: 881–883.

Gais S, Albouy G, Boly M et al. (2007) Sleep transforms the cerebral trace of declarative memories. Proceedings of the National Academy of Sciences of the USA 104: 18778–18783.

Gais S and Born J (2004) Low acetylcholine during slow‐wave sleep is critical for declarative memory consolidation. Proceedings of the National Academy of Sciences of the USA 101: 2140–2144.

Gais S, Lucas B and Born J (2006) Sleep after learning aids memory recall. Learning & Memory 13: 259–262.

Gais S, Rasch B, Wagner U and Born J (2008) Visual‐procedural memory consolidation during sleep blocked by glutamatergic receptor antagonists. Journal of Neuroscience 28: 5513–5518.

Gottesmann C (1999) The neurophysiology of sleep and waking: intracerebral connections, functioning and ascending influences of the medulla oblongata. Progress in Neurobiology 59: 1–54.

Graves LA, Heller EA, Pack AI and Abel T (2003) Sleep deprivation selectively impairs memory consolidation for contextual fear conditioning. Learning & Memory 10: 168–176.

Hasselmo ME (1999) Neuromodulation: acetylcholine and memory consolidation. Trends in Cognitive Sciences 3: 351–359.

Hoffman KL, Battaglia FP, Harris K et al. (2007) The upshot of up states in the neocortex: from slow oscillations to memory formation. Journal of Neuroscience 27: 11838–11841.

Hoffman KL and McNaughton BL (2002) Coordinated reactivation of distributed memory traces in primate cortex. Science 297: 2070–2073.

Horn G (2004) Pathways of the past: the imprint of memory. Nature Reviews Neuroscience 5: 108–120.

Huber R, Ghilardi MF, Massimini M and Tononi G (2004) Local sleep and learning. Nature 430: 78–81.

Isomura Y, Sirota A, Ozen S et al. (2006) Integration and segregation of activity in entorhinal‐hippocampal subregions by neocortical slow oscillations. Neuron 52: 871–882.

Jackson C, McCabe BJ, Nicol AU et al. (2008) Dynamics of a memory trace: effects of sleep on consolidation. Current Biology 18: 393–400.

Jha SK, Jones BE, Coleman T et al. (2005) Sleep‐dependent plasticity requires cortical activity. Journal of Neuroscience 25: 9266–9274.

Ji D and Wilson MA (2007) Coordinated memory replay in the visual cortex and hippocampus during sleep. Nature Neuroscience 10: 100–107.

Korman M, Doyon J, Doljansky J et al. (2007) Daytime sleep condenses the time course of motor memory consolidation. Nature Neuroscience 10: 1206–1213.

Luczak A, Bartho P, Marguet SL, Buzsaki G and Harris KD (2007) Sequential structure of neocortical spontaneous activity in vivo. Proceedings of the National Academy of Sciences of the USA 104: 347–352.

Mackiewicz M, Shockley KR, Romer MA et al. (2007) Macromolecule biosynthesis – a key function of sleep. Physiological Genomics 31(3): 441–457.

Marshall L, Helgadottir H, Molle M and Born J (2006) Boosting slow oscillations during sleep potentiates memory. Nature 444(7119): 610–613.

Mednick SC, Nakayama K, Cantero JL et al. (2002) The restorative effect of naps on perceptual deterioration. Nature Neuroscience 5: 677–681.

Mioche L and Singer W (1989) Chronic recordings from single sites of kitten striate cortex during experience‐dependent modifications of receptive‐field properties. Journal of Neurophysiology 62: 185–197.

Nishida M and Walker MP (2007) Daytime naps, motor memory consolidation and regionally specific sleep spindles. PLoS One 2: e341.

Ramm P and Smith CT (1990) Rates of cerebral protein synthesis are linked to slow‐wave sleep in the rat. Physiology & Behavior 48: 749–753.

Ribeiro S, Goyal V, Mello CV and Pavlides C (1999) Brain gene expression during REM sleep depends on prior waking experience. Learning & Memory 6: 500–508.

Ribeiro S and Nicolelis MAL (2004) Reverberation, storage, and postsynaptic propagation of memories during sleep. Learning & Memory 11: 686–696.

Rosanova M and Ulrich D (2005) Pattern‐specific associative long‐term potentiation induced by a sleep spindle‐related spike train. Journal of Neuroscience 25: 9398–9405.

Saha S and Datta S (2005) Two‐way active avoidance training‐specific increases in phosphorylated cAMP response element‐binding protein in the dorsal hippocampus, amygdala, and hypothalamus. European Journal of Neuroscience 21: 3403–3414.

Schafe GE, Nadel NV, Sullivan GM, Harris A and LeDoux JE (1999) Memory consolidation for contextual and auditory fear conditioning is dependent on protein synthesis, PKA, and MAP kinase. Learning & Memory 6: 97–110.

Steriade M and Timofeev I (2003) Neuronal plasticity in thalamocortical networks during sleep and waking oscillations. Neuron 37: 563–576.

Sterpenich V, Albouy G, Boly M et al. (2007) Sleep‐related hippocampo‐cortical interplay during emotional memory recollection. PLoS Biology 5: e282.

Stickgold R (2005) Sleep‐dependent memory consolidation. Nature 437: 1272–1278.

Takashima A, Peterson KM, Rutters F et al. (2006) Declarative memory consolidation in humans: a prospective functional magnetic resonance imaging study. Proceedings of the National Academy of Sciences of the USA 103: 756–761.

Tononi G and Cirelli C (2003) Sleep and synaptic homeostasis: a hypothesis. Brain Research Bulletin 62: 143–150.

Tononi G and Cirelli C (2014) Sleep and the price of plasticity: from synaptic and cellular homeostasis to memory consolidation and integration. Neuron 81: 12–34.

Ulloor J and Datta S (2005) Spatio‐temporal activation of cyclic AMP response element‐binding protein, activity‐regulated cytoskeletal‐associated protein and brain‐derived nerve growth factor: a mechanism for pontine‐wave generator activation‐dependent two‐way active‐avoidance memory processing in the rat. Journal of Neurochemistry 95: 418–428.

Wang H, Hu Y and Tsien JZ (2006) Molecular and systems mechanisms of memory consolidation and storage. Progress in Neurobiology 79: 123–135.

Whitlock JR, Heynen AJ, Shuler MG and Bear MF (2006) Learning induces long‐term potentiation in the hippocampus. Science 313: 1093–1097.

Wixted JT (2004) The psychology and neuroscience of forgetting. Annual Review of Psychology 55: 235–269.

Further Reading

Maquet P, Smith C and Stickgold R (eds) (2003) Sleep and Brain Plasticity. Oxford: Oxford University Press.

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Aton, Sara J, Seibt, Julie, and Frank, Marcos G(Aug 2014) Sleep and Memory. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0021395.pub2]