Combined blockade of cholinergic receptors shifts the brain from stimulus encoding to memory consolidation.

Full 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 central nervous system cholinergic tone from high levels during wakefulness to minimal levels during SWS optimizes declarative memory consolidation during a period with no need for new memory encoding.

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Author information

Author/s: Rasch, Björn H (BH); Born, Jan (J); Gais, Steffen (S);

Affiliation: University of Lübeck, Germany. born(-atsign-)kfg.uni-luebeck.de

Journal and publication information

Publication Type: Clinical Trial; Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

Journal: Journal of cognitive neuroscience (J Cogn Neurosci), published in United States. (Language: eng)

Reference: 2006-May; vol 18 (issue 5) : pp 793-802

Dates: Created 2006/06/13; Completed 2006/09/14; Revised 2006/11/15;

PMID: 16768378, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adult
Blood Pressure - drug effects
Brain - drug effects; physiology
Cholinergic Antagonists - pharmacology
Cholinesterase Inhibitors - pharmacology
Drug Combinations
Emotions - drug effects
Humans
Hydrocortisone - blood
Male

Male
Mecamylamine - pharmacology
Memory - drug effects; physiology
Neuropsychological Tests
Physostigmine - pharmacology
Psychomotor Performance - drug effects
Reaction Time - drug effects
Receptors, Cholinergic - metabolism
Scopolamine - pharmacology
Wakefulness - drug effects

Associated Chemicals: Cholinergic Antagonists (0) ; Cholinesterase Inhibitors (0) ; Drug Combinations (0) ; Receptors, Cholinergic (0) ; Hydrocortisone (50-23-7) ; Scopolamine (51-34-3) ; Physostigmine (57-47-6) ; Mecamylamine (60-40-2)

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