Combined Blockade of Cholinergic Receptors Shifts the Brain from Stimulus Encoding to Memory Consolidation
Abstract
High central nervous system levels of acetylcholine (ACh) are commonly regarded as crucial for learning and memory, and a decline in cholinergic neurotransmission is associated with Alzheimer's dementia. However, recent findings revealed exceptions to this rule: The low ACh tone characterizing slow wave sleep (SWS) has proven necessary for consolidation of hippocampus-dependent declarative memories during this sleep stage. Such observations, together with recent models of a hippocampal-neocortical dialogue underlying systems memory consolidation, suggest that high levels of ACh support memory encoding, whereas low levels facilitate consolidation. We tested this hypothesis in human subjects by blocking cholinergic neurotransmission during wakefulness, starting 30 min after learning. Subjects received the muscarinic antagonist scopolamine (4 microg/kg bodyweight intravenously) and the nicotinic antagonist mecamylamine (5 mg orally). Compared to placebo, combined muscarinic and nicotinic receptor blockade significantly improved consolidation of declarative memories tested 10 hr later, but simultaneously impaired acquisition of similar material. Consolidation of procedural memories, which are not dependent on hippocampal functioning, was unaffected. Neither scopolamine nor mecamylamine alone enhanced declarative memory consolidation. Our findings support the notion that ACh acts as a switch between modes of acquisition and consolidation. We propose that the natural shift in centr…
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Blocking cholinergic receptors in waking subjects improved consolidation of declarative memories during wakefulness but decreased ability to encode new information.
“Conversely, blocking cholinergic receptors in waking subjects by simultaneous administration of nicotinic and muscarinic receptor antagonists improved the consolidation of declarative memories during wakefulness, but concomitantly decreased the ability to encode new information (963).”
From About Sleep's Role in Memory (2013) · cites this paper as [963]
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 [963]
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- Authors
- Rasch, B. H., Born, J., & Gais, S.
- Affiliations
- University of Lübeck (DE)
- ORCID
- Rasch, Björn H.
- Venue
- Journal of Cognitive Neuroscience
- Publisher
- MIT Press - Journals
- Published
- 2006-05-01
- Volume
- 18
- Issue
- 5
- Pages
- 793-802
- ISSN
- 0898-929X (ISSN-L)
- 1530-8898
- OpenAlex
- W2168011518
- Cited by
- 137
- References
- 12
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 3 · 2023: 4 · 2022: 8 · 2021: 8 · 2020: 3 · 2019: 7 · 2018: 6 · 2017: 9 · 2016: 7 · 2015: 7 · 2014: 7 · 2013: 3 · 2012: 7
- FWCI
- 4.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cognitive Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- 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, cholinergic neurotransmission, memory consolidation, memory encoding, scopolamine, mecamylamine, muscarinic receptor blockade, declarative memory, procedural memory, hippocampus, slow-wave sleep, cholinergic tone, Alzheimer's disease
- MeSH terms
- Adult, Blood Pressure, Brain, Cholinesterase Inhibitors, Drug Combinations, Emotions, Humans, Hydrocortisone, Male, Mecamylamine, Memory, Neuropsychological Tests, Physostigmine, Psychomotor Performance, Reaction Time, Receptors, Cholinergic, Scopolamine, Wakefulness, Cholinergic Antagonists
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