Impaired off-line consolidation of motor memories after combined blockade of cholinergic receptors during REM sleep-rich sleep.
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 microg/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.
Rasch
Björn
B
Department of Neuroendocrinology, University of Lübeck, Lübeck, Germany.
Gais
Steffen
S
Born
Jan
J
D000328:Adult; D000339:Affect / Q000187:drug effects; D001245:Association Learning / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D018680:Cholinergic Antagonists / Q000009:adverse effects; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008464:Mecamylamine / Q000009:adverse effects; D008569:Memory Disorders / Q000139:chemically induced / Q000503:physiopathology*; D009048:Motor Skills / Q000187:drug effects / Q000502:physiology*; D009483:Neuropsychological Tests; D009490:Neurosecretory Systems / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011950:Receptors, Cholinergic / Q000502:physiology*; D012601:Scopolamine / Q000009:adverse effects; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult
D018680:Cholinergic Antagonists; D011950:Receptors, Cholinergic; D008464:Mecamylamine; D012601:Scopolamine