Send to

Choose Destination
Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2140-4. Epub 2004 Feb 6.

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

Author information

Department of Neuroendocrinology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.


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.

Comment in

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center