Impaired Off-Line Consolidation of Motor Memories After Combined Blockade of Cholinergic Receptors During REM Sleep-Rich Sleep

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 34; no. 7; pp. 1843 - 1853
• Main Authors: Rasch, Björn, Gais, Steffen, Born, Jan
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2009; Nature Publishing Group
• Subjects: Activity levels. Psychomotricity; Adult; Affect - drug effects; Association Learning - drug effects; Association Learning - physiology; Behavioral Sciences; Biological and medical sciences; Biological Psychology; Blood Pressure - drug effects; Cardiovascular Physiological Phenomena - drug effects; Cholinergic Antagonists - adverse effects; Double-Blind Method; Electroencephalography - drug effects; Eye movements; Fundamental and applied biological sciences. Psychology; Heart Rate - drug effects; Human; Humans; Learning. Memory; Male; Mecamylamine - adverse effects; Medicine; Medicine & Public Health; Memory; Memory Disorders - chemically induced; Memory Disorders - physiopathology; Motor ability; Motor Skills - drug effects; Motor Skills - physiology; Neuropsychological Tests; Neurosciences; Neurosecretory Systems - drug effects; original-article; Pharmacotherapy; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Reaction Time - drug effects; Reaction Time - physiology; Receptors, Cholinergic - physiology; Scopolamine Hydrobromide - adverse effects; Skills; Sleep deprivation; Sleep, REM - drug effects; Sleep, REM - physiology; Vigilance. Attention. Sleep; Young Adult; Basel Switzerland; Switzerland; Germany; mecamylamine; acetylcholine; skill memory; memory consolidation; scopolamine; REM sleep; Human; Hyoscine; Healthy subject; Memory; Rapid eye movement sleep; Mecamylamine; Alkaloid; Anticholinergic agent; Skill; Cholinergic receptor; Consolidation; Neurotransmitter; Acetylcholine
• DOI: 10.1038/npp.2009.6
• ISSN: 0893-133X; 1740-634X

Rapid eye movement (REM) sleep has been considered important for the consolidation of memories, particularly of procedural skills. REM sleep, in contrast to slow-wave sleep (SWS), is hallmarked by the high, wake-like activity of the neurotransmitter acetylcholine (ACh), which promotes certain synaptic plastic processes underlying the formation of memories. Here, we show in healthy young men that off-line consolidation of a motor skill during a period of late sleep with high amounts of REM sleep depends essentially on high cholinergic activity. After a 3-h sleep period during the early night to satisfy the need for SWS, subjects learned a procedural finger sequence tapping task and a declarative word-pair learning task. After learning, they received either placebo or a combination of the muscarinic receptor antagonist scopolamine (4 μg/kg bodyweight, intravenously) and the nicotinic receptor antagonist mecamylamine (5 mg, orally), and then slept for another 3 h, ie, the late nocturnal sleep period, which is dominated by REM sleep. Retrieval was tested the following evening. Combined cholinergic receptor blockade significantly impaired motor skill consolidation, whereas word-pair memory remained unaffected. Additional data show that the impairing effect of cholinergic receptor blockade is specific to sleep-dependent consolidation of motor skill and does not occur during a wake-retention interval. Taken together, these results identify high cholinergic activity during late, REM sleep-rich sleep as an essential factor promoting sleep-dependent consolidation of motor skills.