Cited by 412Sleep and Wakefulness ResearchMemory and Neural MechanismsMemory Processes and Influences

Low acetylcholine during slow-wave sleep is critical for declarative memory consolidation

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Gais, Steffen, Born, Jan·2004·Proceedings of the National Academy of Sciences

Abstract

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.

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Registry

Crossref · 10.1073/pnas.0305404101

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  • 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]

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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
Published
2004-02-06
Volume
101
Issue
7
Pages
2140-2144
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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

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