1. ¹Department of Neuroendocrinology, University of Lübeck, Lübeck, Germany
2. ²Department of Molecular Psychology, University of Basel, Basel, Switzerland

Correspondence: Professor J Born, Department of Neuroendocrinology, University of Lübeck, Ratzeburger Allee 160, Hs 23a, Lübeck D-23538, Germany. Tel: +49 451 500 3639; Fax: +49 451 500 3640; E-mail: born@kfg.mu-luebeck.de; Dr. rer. nat. B Rasch, Department of Molecular Psychology, University of Basel, Missionsstrasse 60/62, 4055 Basel, Switzerland. Tel: +41 61 267 05 91; Fax: +41 61 267 05 87; E-mail: bjoern.rasch@unibas.ch

Received 11 November 2008; Revised 11 December 2008; Accepted 19 December 2008; Published online 4 February 2009.

Abstract

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 g/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.