INSIGHT REVIEW NATURE Vol 437 27 October 2005 doi 10 1038 nature04286 Sleep dependent memory consolidation Robert Stickgold1 The concept of sleeping on a problem is familiar to most of us But with myriad stages of sleep forms of memory and processes of memory encoding and consolidation sorting out how sleep contributes to memory has been anything but straightforward Nevertheless converging evidence from the molecular to the phenomenological leaves little doubt that offline memory reprocessing during sleep is an important component of how our memories are formed and ultimately shaped Sleep and memory There is more than one type of memory Consider for example the capital of France what you had for dinner last night and how to ride a bicycle All three of these recollections require information that you have learned and stored but they are very different types of memory Multiple memory systems store different classes of memory in different brain regions and quite probably in different formats Memories are most commonly divided into declarative memories which are those that a person can call to mind for example the capital of France or last night s dinner and non declarative memories which are those that are normally used without conscious recollection for example how to ride a bicycle or how to talk your way out of a parking ticket Fig 1 6 Declarative memories are further divided into episodic memories that is memories of specific events such as what you had for dinner last night and semantic memories in other words memories of general information such as the capital of France Non Memory Non declarative Declarative Episodic Semantic Procedural skills Conditioning Nonassociative Priming Figure 1 Categorization of memory systems Awake Sleep stages The question of how sleep might contribute to learning and memory consolidation is an old one In the first century AD the Roman rhetorician Quintilian commenting on the benefits of sleep noted that what could not be repeated at first is readily put together on the following day and the very time which is generally thought to cause forgetfulness is found to strengthen the memory 1 Although this may have been obvious to him it has been less obvious to the research community and until a seminal paper by Karni Sagi and colleagues in 1994 ref 2 the topic received relatively little attention within either the sleep or memory research communities But over the past 10 years the rate of publication of research papers on sleep dependent learning and memory consolidation has increased fivefold3 Evidence supporting sleep dependent memory consolidation has come from a range of molecular cellular physiological and behavioural studies for a review see ref 4 for an opposing view see ref 5 One of the major problems facing this area of research is that the terms sleep memory and memory consolidation all refer to complex phenomena none of which can be treated as a singular event I begin this review by clarifying my use of these terms and then present some of the more convincing evidence from studies of procedural learning in humans I then review more broadly the behavioural evidence for sleep dependent consolidation of perceptual and motor skill procedural memories declarative memories and complex cognitive procedural memories I follow this by outlining converging evidence from molecular cellular neurophysiological brain imaging and dream studies all of which support an important and sometimes essential role for sleep in memory consolidation REM NREM 1 NREM 2 NREM 3 NREM 4 00 00 01 00 02 00 03 00 04 00 05 00 06 00 07 00 Time Figure 2 Categorization of sleep stages declarative memories are also divided into several subcategories such as procedural skills Others in the field use the term memory in a more restricted manner such as limiting it to episodic memories see the commentary by Hobson in this issue p 1254 There is no consensus on what processes should be covered by the term memory consolidation The term memory consolidation originally referred to a process of memory stabilization through which memories become resistant to interference7 8 But after the initial encoding of a sensorimotor experience a series of cellular molecular and systems level alterations develop over time automatically and outside of awareness that stabilize and enhance the initial memory representation converting it into a long lasting and optimally integrated memory These include not only cellular and molecular processes occurring at the local synaptic level but systems level reorganizations of individual memories as well see refs 9 10 for example These additional memory consolidation processes show the greatest evidence of sleep dependence and I include all of them under the umbrella term memory consolidation It is important to note that there is no consensus on how many distinct post encoding processes exist how they should be defined and which should be considered under the rubric of memory consolidation For example memory stabilization cannot be considered absolute because that would mean that other consolidation processes such as enhancement and reorganization of memories would not be possible 1 Department of Psychiatry Harvard Medical School and Centre for Sleep and Cognition Beth Israel Deaconess Medical Centre 330 Brookline Avenue FD 861 Boston Massachusetts 02215 USA 1272 2005 Nature Publishing Group INSIGHT REVIEW NATURE Vol 437 27 October 2005 Visual texture discrimination task a Sleep versus wake b Sleep stage correlation 6 12 18 Improvement ms Improvement ms Improvement ms 0 30 40 Daytime 20 Overnight 10 c Sleep deprivation 30 20 10 24 0 10 0 50 100 150 200 SWS1 REM4 Test interval h Motor sequence learning task d Sleep versus wake 20 e Sleep stage correlation 0 1 2 3 Days 4 7 f Sleep deprivation 40 6 26 24 22 20 AM PM AM Train Retest Sleep AM PM AM 30 20 10 0 25 PM AM PM Train Retest Train Retest Sleep Improvement in rate Sequences 30 s Sequences 30 s 28 45 65 Stage 2 NREM sleep in fourth quarter Sleep Motor adaption learning task g Sleep versus wake h Slow wave activity 12 8 4 0 0 Day Night 48 h j Localization of slow wave activity increase 20 15 10 10 5 185 50 132 0 5 0 10 Sleep Wakefulness 4 2 Rotation no rotation 30 Improvement mean directional error Performance change mean directional error correlation 85 4 Figure 3 Sleep dependent consolidation of procedural memories a c Participants in a visual texture discrimination task show improvement only after posttraining