Low acetylcholine during slow-wave sleep is critical for declarative memory consolidation
Open accessAbstract
The neurotransmitter acetylcholine is considered essential for proper functioning of the hippocampus-dependent declarative memory system, and it represents a major neuropharmacological target for the treatment of memory deficits, such as those in Alzheimer's disease. During slow-wave sleep (SWS), however, declarative memory consolidation is particularly strong, while acetylcholine levels in the hippocampus drop to a minimum. Observations in rats led to the hypothesis that the low cholinergic tone during SWS is necessary for the replay of new memories in the hippocampus and their long-term storage in neocortical networks. However, this low tone should not affect nondeclarative memory systems. In this study, increasing central nervous cholinergic activation during SWS-rich sleep by posttrial infusion of 0.75 mg of the cholinesterase inhibitor physostigmine completely blocked SWS-related consolidation of declarative memories for word pairs in human subjects. The treatment did not interfere with consolidation of a nondeclarative mirror tracing task. Also, physostigmine did not alter memory consolidation during waking, when the endogenous central nervous cholinergic tone is maximal. These findings are in line with predictions that a low cholinergic tone during SWS is essential for declarative memory consolidation.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Increasing cholinergic tone during SWS-rich sleep by physostigmine completely blocked sleep-associated consolidation of word pair memories.
“increasing cholinergic tone during a period of SWS-rich sleep by administration of the cholinesterase inhibitor physostigmine completely blocked the sleep-associated consolidation of word pair memories (FIGURE 6B; Refs.429, 963).”
From About Sleep's Role in Memory (2013) · cites this paper as [429]
Cites
McClelland, J. L., McNaughton, B. L., & O'Reilly, R. C. (1995) · Psychological Review · doi:10.1037/0033-295x.102.3.419 · Cited by 5,256 · see citing works
Two-stage model of memory trace formation: A role for “noisy” brain states
Buzsáki, G. (1989) · Neuroscience · doi:10.1016/0306-4522(89)90423-5 · Cited by 1,709 · see citing works
Memory of sequential experience in the hippocampus during slow wave sleep
Lee, A. K., & Wilson, M. A. (2002) · Neuron · doi:10.1016/s0896-6273(02)01096-6 · Cited by 1,296 · see citing works
Effects of early and late nocturnal sleep on declarative and procedural memory
Plihal, W., & Born, J. (1997) · Journal of Cognitive Neuroscience · doi:10.1162/jocn.1997.9.4.534 · Cited by 1,026 · see citing works
The Neurobiology of Sleep: Genetics, cellular physiology and subcortical networks
Pace-Schott, E. F., & Hobson, J. A. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn895 · Cited by 937 · see citing works
Replay and Time Compression of Recurring Spike Sequences in the Hippocampus
Nádasdy, Z., Hirase, H., Czurkó, A., Csicsvari, J., & Buzsáki, G. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-21-09497.1999 · Cited by 932 · see citing works
Sleep forms memory for finger skills
Fischer, S., Hallschmid, M., Elsner, A. L., & Born, J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.182178199 · Cited by 589 · see citing works
Marrosu, F., Portas, C., Mascia, M. S., Casu, M. A., Fà, M., Giagheddu, M., Imperato, A., & Gessa, G. L. (1995) · Brain Research · doi:10.1016/0006-8993(94)01399-3 · Cited by 480 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Diekelmann, S., & Born, J. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2762 · Cited by 3,760 · see citing works
Self-citationRasch, B., & Born, J. (2013) · Physiological Reviews · doi:10.1152/physrev.00032.2012 · Cited by 2,783 · see citing works
“[Data from Gais and Born (429) and Rasch et al.”
MethodInfluentialSelf-citationThe organization of recent and remote memories
Frankland, P. W., & Bontempi, B. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1607 · Cited by 2,138 · see citing works
Hippocampal sharp wave-ripple: A cognitive biomarker for episodic memory and planning
Buzsáki, G. (2015) · Hippocampus · doi:10.1002/hipo.22488 · Cited by 1,759 · see citing works
Sleep-dependent memory consolidation
Stickgold, R. (2005) · Nature · doi:10.1038/nature04286 · Cited by 1,857 · see citing works
The role of acetylcholine in learning and memory
Hasselmo, M. E. (2006) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2006.09.002 · Cited by 1,693 · see citing works
Control of sleep and wakefulness
Brown, R. E., Basheer, R., McKenna, J. T., Strecker, R. E., & McCarley, R. W. (2012) · Physiological Reviews · doi:10.1152/physrev.00032.2011 · Cited by 1,477 · see citing works
Grouping of brain rhythms in corticothalamic systems
Steriade, M. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2005.10.029 · Cited by 1,296 · see citing works
Sleep-Dependent Learning and Memory Consolidation
Walker, M. P., & Stickgold, R. (2004) · Neuron · doi:10.1016/j.neuron.2004.08.031 · Cited by 1,113 · see citing works
Walker, M. P., & Stickgold, R. (2006) · Annual Review of Psychology · doi:10.1146/annurev.psych.56.091103.070307 · Cited by 1,075 · see citing works
Buzsáki, G. (2005) · Hippocampus · doi:10.1002/hipo.20113 · Cited by 872 · see citing works
Modes and models of forebrain cholinergic neuromodulation of cognition
Hasselmo, M. E., & Sarter, M. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2010.104 · Cited by 733 · see citing works
The contribution of sleep to hippocampus-dependent memory consolidation
Marshall, L., & Born, J. (2007) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2007.09.001 · Cited by 667 · see citing works
The whats and whens of sleep-dependent memory consolidation
Diekelmann, S., Wilhelm, I., & Born, J. (2009) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2008.08.002 · Cited by 566 · see citing works
Transcranial direct current stimulation during sleep improves declarative memory
Marshall, L., Mölle, M., Hallschmid, M., & Born, J. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.2725-04.2004 · Cited by 548 · see citing works
Overlapping memory replay during sleep builds cognitive schemata
Lewis, P. A., & Durrant, S. J. (2011) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2011.06.004 · Cited by 512 · see citing works
Declarative memory consolidation: mechanisms acting during human sleep
Gais, S., & Born, J. (2004) · Learning & Memory · doi:10.1101/lm.80504 · Cited by 536 · see citing works
Self-citationOvernight verbal memory retention correlates with the number of sleep spindles
Clemens, Z., Fabó, D., & Halász, P. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.01.011 · Cited by 405 · see citing works
Ellenbogen, J. M., Hulbert, J. C., Stickgold, R., Dinges, D. F., & Thompson-Schill, S. L. (2006) · Current Biology · doi:10.1016/j.cub.2006.05.024 · Cited by 377 · see citing works
The role of sleep in declarative memory consolidation: passive, permissive, active or none?
Ellenbogen, J. M., Payne, J. D., & Stickgold, R. (2006) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2006.10.006 · Cited by 326 · see citing works
Dreaming of a learning task is associated with enhanced sleep-dependent memory consolidation
Wamsley, E. J., Tucker, M., Payne, J. D., Benavides, J. A., & Stickgold, R. (2010) · Current Biology · doi:10.1016/j.cub.2010.03.027 · Cited by 255 · see citing works
FOGEL, S., SMITH, C., & COTE, K. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2007.02.037 · Cited by 246 · see citing works
Sleep's function in the spontaneous recovery and consolidation of memories.
Drosopoulos, S., Schulze, C., Fischer, S., & Born, J. (2007) · Journal of Experimental Psychology: General · doi:10.1037/0096-3445.136.2.169 · Cited by 230 · see citing works
Self-citationHippocampal-dependent learning requires a functional circadian system
Ruby, N. F., Hwang, C. E., Wessells, C., Fernandez, F., Zhang, P., Sapolsky, R., & Heller, H. C. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808259105 · Cited by 234 · see citing works
Specific basal forebrain-cortical cholinergic circuits coordinate cognitive operations
Záborszky, L., Gombkoto, P., Varsanyi, P., Gielow, M. R., Poe, G., Role, L. W., Ananth, M., Rajebhosale, P., Talmage, D. A., Hasselmo, M. E., et al. (2018) · The Journal of Neuroscience · doi:10.1523/jneurosci.1676-18.2018 · Cited by 202 · see citing works
Scheinost, D., Stoica, T., Saksa, J., Papademetris, X., Constable, R. T., Pittenger, C., & Hampson, M. (2013) · Translational Psychiatry · doi:10.1038/tp.2013.24 · Cited by 201 · see citing works
Slow-wave sleep takes the leading role in memory reorganization
Diekelmann, S., & Born, J. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2762-c2 · Cited by 177 · see citing works
Self-citationSleep and memory in mammals, birds and invertebrates
Vorster, A. P., & Born, J. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.09.020 · Cited by 169 · see citing works
Self-citationTucker, M. A., & Fishbein, W. (2008) · Sleep · doi:10.1093/sleep/31.2.197 · Cited by 171 · see citing works
Co-transmission of acetylcholine and GABA regulates hippocampal states
Takács, V. T., Cserép, C., Schlingloff, D., Pósfai, B., Szőnyi, A., Sos, K. E., Környei, Z., Dénes, Á., Gulyás, A. I., Freund, T. F., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05136-1 · Cited by 169 · see citing works
Kaestner, E. J., Wixted, J. T., & Mednick, S. C. (2013) · Journal of Cognitive Neuroscience · doi:10.1162/jocn_a_00433 · Cited by 149 · see citing works
Sleep and the functional connectome
Picchioni, D., Duyn, J. H., & Horovitz, S. G. (2013) · NeuroImage · doi:10.1016/j.neuroimage.2013.05.067 · Cited by 115 · see citing works
Effects of Cortisol Suppression on Sleep-Associated Consolidation of Neutral and Emotional Memory
Wagner, U., Degirmenci, M., Drosopoulos, S., Perras, B., & Born, J. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.05.008 · Cited by 119 · see citing works
Self-citationDaytime napping: Effects on human direct associative and relational memory
Lau, H., Tucker, M. A., & Fishbein, W. (2010) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2010.02.003 · Cited by 115 · see citing works
Eschenko, O., & Sara, S. J. (2008) · Cerebral Cortex · doi:10.1093/cercor/bhn020 · Cited by 115 · see citing works
Cairney, S. A., Lindsay, S., Sobczak, J. M., Paller, K. A., & Gaskell, M. G. (2016) · SLEEP · doi:10.5665/sleep.5772 · Cited by 93 · see citing works
Contribution of norepinephrine to emotional memory consolidation during sleep
Groch, S., Wilhelm, I., Diekelmann, S., Sayk, F., Gais, S., & Born, J. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.03.006 · Cited by 93 · see citing works
Self-citationKuriyama, K., Soshi, T., & Kim, Y. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.08.015 · Cited by 84 · see citing works
How Aging Affects Sleep-Dependent Memory Consolidation?
Harand, C., Bertran, F., Doidy, F., Guénolé, F., Desgranges, B., Eustache, F., & Rauchs, G. (2012) · Frontiers in Neurology · doi:10.3389/fneur.2012.00008 · Cited by 83 · see citing works
The impact of overnight consolidation upon memory for emotional and neutral encoding contexts
Lewis, P. A., Cairney, S., Manning, L., & Critchley, H. D. (2011) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2011.05.009 · Cited by 79 · see citing works
Rehearsal initiates systems memory consolidation, sleep makes it last
Himmer, L., Schönauer, M., Heib, D. P. J., Schabus, M., & Gais, S. (2019) · Science Advances · doi:10.1126/sciadv.aav1695 · Cited by 70 · see citing works
Self-citationThe sleep benefit in episodic memory: An integrative review and a meta-analysis.
Berres, S., & Erdfelder, E. (2021) · Psychological Bulletin · doi:10.1037/bul0000350 · Cited by 74 · see citing works
Sleep-dependent memory processing
Walker, M. P. (2008) · Harvard Review of Psychiatry · doi:10.1080/10673220802432517 · Cited by 72 · see citing works
Memory Consolidation, The Diurnal Rhythm of Cortisol, And The Nature Of Dreams
Payne, J. D. (2010) · International Review of Neurobiology · doi:10.1016/s0074-7742(10)92006-0 · Cited by 69 · see citing works
Rasch, B., Gais, S., & Born, J. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.6 · Cited by 57 · see citing works
Self-citationKelemen, E., Bahrendt, M., Born, J., & Inostroza, M. (2014) · Hippocampus · doi:10.1002/hipo.22266 · Cited by 43 · see citing works
Bentley, P., Driver, J., & Dolan, R. J. (2009) · Brain · doi:10.1093/brain/awp176 · Cited by 41 · see citing works
KOPASZ, M., LOESSL, B., VALERIUS, G., KOENIG, E., MATTHAEAS, N., HORNYAK, M., KLOEPFER, C., NISSEN, C., RIEMANN, D., & VODERHOLZER, U. (2010) · Journal of Sleep Research · doi:10.1111/j.1365-2869.2009.00742.x · Cited by 37 · see citing works
Central Nervous Insulin Signaling in Sleep-Associated Memory Formation and Neuroendocrine Regulation
Feld, G. B., Wilhem, I., Benedict, C., Rüdel, B., Klameth, C., Born, J., & Hallschmid, M. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.312 · Cited by 36 · see citing works
Self-citationOffline consolidation of procedural skill learning is enhanced by negative emotional content
Javadi, A. H., Walsh, V., & Lewis, P. A. (2011) · Experimental Brain Research · doi:10.1007/s00221-010-2497-7 · Cited by 26 · see citing works
Rauchs, G., Harand, C., Bertran, F., Desgranges, B., & Eustache, F. (2010) · Revue Neurologique · doi:10.1016/j.neurol.2010.03.021 · Cited by 19 · see citing works
Verleger, R., Schuknecht, S.-V., Jaśkowski, P., & Wagner, U. (2008) · Brain and Cognition · doi:10.1016/j.bandc.2008.04.006 · Cited by 15 · see citing works
- Authors
- Gais, S., & Born, J.
- Affiliations
- University of Lübeck (DE)
- Department of Neuroendocrinology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2004-02-06
- Volume
- 101
- Issue
- 7
- Pages
- 2140-2144
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC357065
- OpenAlex
- W2119042170
- Cited by
- 412
- References
- 8
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 9 · 2023: 11 · 2022: 9 · 2021: 14 · 2020: 14 · 2019: 15 · 2018: 26 · 2017: 27 · 2016: 15 · 2015: 15 · 2014: 21 · 2013: 17 · 2012: 31
- FWCI
- 12.93
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Keywords
- acetylcholine, slow-wave sleep, declarative memory consolidation, physostigmine, cholinergic tone, hippocampus, memory replay, mirror tracing, implicit memory, Alzheimer's disease, cholinesterase inhibitors
- MeSH terms
- Acetylcholine, Adolescent, Adult, Cholinesterase Inhibitors, Hippocampus, Humans, Hydrocortisone, Male, Memory, Physostigmine, Mental Recall, Sleep, Wakefulness
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review