Gais Steffen, Born Jan
Department of Neuroendocrinology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2140-4. doi: 10.1073/pnas.0305404101. Epub 2004 Feb 6.
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.
神经递质乙酰胆碱被认为对依赖海马体的陈述性记忆系统的正常运作至关重要，并且它是治疗记忆缺陷（如阿尔茨海默病中的记忆缺陷）的主要神经药理学靶点。然而，在慢波睡眠（SWS）期间，陈述性记忆巩固尤为强烈，而海马体中的乙酰胆碱水平降至最低。对大鼠的观察结果提出了这样一个假设，即慢波睡眠期间低胆碱能张力对于海马体中新记忆的重演及其在新皮质网络中的长期存储是必要的。然而，这种低张力不应影响非陈述性记忆系统。在这项研究中，通过试验后注入0.75毫克胆碱酯酶抑制剂毒扁豆碱来增加富含慢波睡眠的睡眠期间的中枢神经胆碱能激活，完全阻断了人类受试者中与慢波睡眠相关的单词对陈述性记忆的巩固。该治疗并未干扰非陈述性镜像追踪任务的巩固。此外，当内源性中枢神经胆碱能张力最大时，毒扁豆碱在清醒期间也不会改变记忆巩固。这些发现与慢波睡眠期间低胆碱能张力对陈述性记忆巩固至关重要的预测一致。
