Sleep and memory: a molecular perspective
Trends in NeurosciencesPublished 1 April 2001
Letitia Y. Graves
Citations215
SJR quartileQ1
SJR score4.73
SNIP3.68
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TL;DR
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 to suggest neurochemical changes that occur across sleep/wake states might provide a mechanism by which sleep modulates specific cellular signaling pathways involved in hippocampus-dependent memory storage.
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.
Keywords
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Current Opinion in NeurobiologyHippocampus and context in classical conditioning
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Journal of Biological ChemistryRegulation of purified type I and type II adenylylcyclases by G protein beta gamma subunits.
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Current Opinion in NeurobiologyLearning perceptual skills: behavioral probes into adult cortical plasticity
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The generality of these findings was obtained by depriving mice of REM sleep during the interval between a discrimination training experiment in a black-white T-maze and the subsequent retention test, which showed a temporary retrograde amnesia.
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140 Citations1989Ian Q. Whishaw
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111 Citations1974J. L. Valatx, R. Bugat
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PubMedProlonged increases in paradoxical sleep during and after avoidance-task acquisition.
105 Citations1980Carlyle Smith, Jared W. Young +1 more
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104 Citations1997Carlyle Smith, Gregory M. Rose
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Journal of Biological ChemistryDifferential regulation of cAMP-mediated gene transcription by m1 and m4 muscarinic acetylcholine receptors. Preferential coupling of m4 receptors to Gi alpha-2
69 Citations1994Jacques Migeon, Neil M. Nathanson
The m4 receptor is spontaneously active and can cause constitutive inhibition of adenylyl cyclase that is relieved by atropine treatment, and it is demonstrated that the Gi alpha-2 G-protein alpha subunit preferentially couples the m4 mAChR to inhibition of Adenylate cyclase in JEG-3 cells.
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68 Citations1999Sung Pa Park, Fernando López Rodríguez +4 more
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Physiology & BehaviorA diallel analysis of the genetic underpinnings of mouse sleep
65 Citations1974Joyce K. Friedmann
Animal Learning & BehaviorPosttrial REM sleep: A critical period for consolidation of shuttlebox avoidance
56 Citations1973Chester Pearlman, Ramon Greenbérg
Deprivation of REM sleep for 2 h immediately following shuttlebox avoidance training produced deficient retention at 24 h after initial training, and REM deprivation beginning 2 h after training had no effect.
Canadian Journal of Psychology/Revue Canadienne de PsychologieSome biochemical and behavioural aspects of the paradoxical sleep window.
48 Citations1991Carlyle Smith, Catherine Tenn +1 more
Results suggested that the transmitter ACh plays an important role in learning/memory processes at the PS window.
PubMedFunctional diversity of muscarinic receptor subtypes in cellular signal transduction and growth.
42 Citations1989Avi Ashkenazi, Peralta Eg +3 more
Studies on mAChR regulation of two cellular events involved in cellular growth regulation, the transcription of proto-oncogene c-fos and DNA synthesis, indicate that these events are efficiently activated by those mA ChRs which couple primarily to phospholipase C.
Progress in brain researchChapter 17 Muscarinic receptors and cell signalling
21 Citations1996Konrad Lö ffelholz
This chapter presents various muscarinic receptors belonging to the superfamily of G protein-coupled receptors consisting of seven transmembrane (TM) helices tightly packed in a ring-like structure and arranged in a counter-clockwise fashion.
Pharmacology Biochemistry and BehaviorSleep and serotonin in two strains of Mus musculus
13 Citations1973Merrill M. Mitler, Harry B. Cohen +6 more
The data were interpreted as being generally consistent with the hypothesis of an active serotonergic sleep inducing mechanism in brain, and slow wave sleep may vary negatively with brain stem tryptophan hydroxylase activity, brain stem serotonin level, and cortex tryPTophan level.