Trends in Neurosciences
ReviewSleep and memory: a molecular perspective
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.
References (65)
- et al.
Evidence for a paradoxical sleep window for place learning in the Morris water maze
Physiol. Behav.
(1996) - et al.
Memory trace reactivation in hippocampal and neocortical neuronal ensembles
Curr. Opin. Neurobiol.
(2000) Sleep states, memory processes and synaptic plasticity
Behav. Brain Res.
(1996)Sleep states and learning: a review of the animal literature
Neurosci. Biobehav. Rev.
(1985)Disruptive effects of rapid eye movement sleep deprivation on long-term memory
Physiol. Behav.
(1971)Brief paradoxical sleep deprivation impairs reference, but not working, memory in the radial arm maze task
Neurobiol. Learn. Memory
(1998)- et al.
Learning perceptual skills: behavioral probes into adult cortical plasticity
Curr. Opin. Neurobiol.
(1997) Genetic demonstration of a role for PKA in the late phase of LTP and in hippocampus-based long-term memory
Cell
(1997)- et al.
Hippocampus and context in classical conditioning
Curr. Opin. Neurobiol.
(1999) Microdialysis measurement of cortical and hippocampal acetylcholine release during sleep-wake cycle in freely moving cats
Brain Res.
(1995)