title: Low acetylcholine during slow-wave sleep is critical for declarative memory consolidation.
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.
authors.affiliation: Department of Neuroendocrinology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. gais@kfg.mu-luebeck.de
authors.forename: Steffen
authors.initials: S
authors.lastname: Gais
authors.forename: Jan
authors.initials: J
authors.lastname: Born
mesh_terms: D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology; D010830:Physostigmine / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
chemical_list: D002800:Cholinesterase Inhibitors; D010830:Physostigmine; D000109:Acetylcholine; D006854:Hydrocortisone