Trends in Neurosciences
Volume 24, Issue 4, 1 April 2001, Pages 237-243
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Review
Sleep and memory: a molecular perspective

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Abstract

This review synthesizes data from behavioral studies examining the role of sleep in memory storage with what is known about the molecular mechanisms of memory consolidation. There are striking similarities in the effects on memory storage of post-training pharmacological manipulations and post-training manipulations of sleep. For example, inhibition of protein synthesis is most effective if it occurs at a time post-training when rapid eye movement (REM) sleep is required for memory consolidation. The neurochemical changes that occur across sleep/wake states, especially the cholinergic changes that occur in the hippocampus during REM sleep, might provide a mechanism by which sleep modulates specific cellular signaling pathways involved in hippocampus-dependent memory storage.

Section snippets

Post-training sleep and memory consolidation

Sleep can be broadly considered as two states: rapid-eye movement (REM) sleep (also referred to as paradoxical sleep) and non-rapid-eye movement (NREM) sleep 2, 3. REM sleep is characterized by a rapid desynchronous cortical electroencephalogram (EEG) with the predominance of a theta rhythm, atonia of postural muscles and bursts of rapid eye movements. By contrast, during NREM sleep, which has several stages, the cortical EEG is slowed overall and progresses from intermittent spindling to a

The molecular basis of long-term memory storage

The behavioral experiments outlined above have led to the conclusion that post-training sleep is important for memory consolidation. One of the defining themes of the study of memory storage is that molecular and biochemical events that occur during the post-training period are crucial for the consolidation of long-term memory 1, 10. Fear conditioning has been particularly important for the elucidation of the molecular basis of memory (see, for example, 19, 20). Fear conditioning is a form of

Cholinergic signaling mechanisms, sleep and memory consolidation

This analysis of the molecular mechanisms of memory consolidation and the role of sleep in memory storage suggests that the effects of REM sleep might be to modulate PKA and protein synthesis-dependent processes within the hippocampus following spatial or contextual training. During REM sleep there is a marked increase of acetylcholine (ACh) in the hippocampus measured with microdialysis 24, and this could be one mechanism by which REM sleep modulates hippocampal function. ACh acts on two broad

Serotonergic signaling mechanisms, sleep and memory consolidation

Another prominent feature of REM sleep is decreased levels of 5-HT (serotonin) in the hippocampus, relative to levels during wake and NREM sleep 45. This reduction in the level of 5-HT might be important for the modulation of hippocampal function by REM sleep. Different subtypes of 5-HT receptors are negatively or positively coupled to adenylyl cyclase, coupled to phospholipase C, or are ligand-gated ion channels 46. Post-training administration of an agonist of the 5-HT1A receptor, which is

Genetic approaches to study the relationship between sleep and memory

Genetic approaches have provided ways to identify the molecular mechanisms underlying biological processes. In mice, the use of reverse genetics to alter specific genes has been crucial for many recent advances in understanding the molecular basis of learning and memory 1. Mice are an ideal model system in which to investigate the molecular basis of sleep and the relationship between sleep and memory consolidation, for several reasons. First, recent experiments have begun to dissect the

Conclusion

One way that sleep might facilitate hippocampus-dependent long-term memory is through its effects on the PKA signaling pathway in the hippocampus during REM sleep. However, sleep is known to affect learning that is mediated by many different neural systems 63. Each neural system must be considered separately when examining molecular mechanisms through which sleep can interact with memory. A focus on hippocampus-dependent tasks provides a way to establish an understanding of the molecular

Acknowledgements

The authors are grateful to J. Hendricks, S. Veasey, K.M. Lattal and N.M. O'Conner-Abel for comments on the manuscript, and C. Lam for assistance with Fig. 4. This work was supported by grants from the NIH to L.G. (5T32 AG-00256), A.P. (5T32 AG-00256) and T.A. (AG-18199, MH-60244), as well as grants from the Whitehall Foundation and the University of Pennsylvania Research Foundation to T.A. T.A. is a John Merck Scholar.

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