Jaffard R, Etchamendy N, Desmedt A, Krazem A, Cortes-Torrea C, Marighetto A
Laboratoire de Neurosciences Cognitives, CNRS UMR 5106, Université de Bordeaux 1, Talence, France.
Therapie. 2000 Jul-Aug;55(4):477-85.
The present work was aimed at determining, both at the psychological and at the neurobiological levels, aspects of rodent memory that fall into line with human declarative memory which is known to be selectively impaired in amnesic subjects and during the course of ageing. The ability to compare and to contrast items in memory, and to support inferential use of memories in novel situations (flexibility), were considered to be the two key psychological features of human declarative memory that were altered by both hippocampal lesions and hippocampal dysfunction. Adult and aged mice were trained on learning tasks using two-stage paradigms, the aim of which was to assess memory performance through these two psychological aspects in the same subjects. Results suggest that ageing specifically impairs the ability to both compare and contrast items in memory (declarative/relational memory based on complex associations), without altering memory based on simple S-R associations (procedural memory). Hippocampal lesions in adult mice produced the same dissociation between relational memory (impaired) and procedural memory (spared). Pharmacological experiments showed that, depending on the drug used, the relational memory deficit of aged mice may be selectively reversed (i.e. without changes in procedural memory) and that the behavioural efficacy of certain treatments was shown to parallel their potency in re-establishing normal (i.e. adult) levels of hippocampal plasticity-related mechanisms. Together with previous findings, these results suggest that the storage and use of relational representations would critically depend on the plasticity of hippocampal synapses, which via their connections with cortical areas, would support the storage of associations between perceptual, behavioral and cognitive events.
本研究旨在从心理学和神经生物学层面确定啮齿动物记忆中与人类陈述性记忆相符的方面，已知人类陈述性记忆在失忆症患者及衰老过程中会受到选择性损害。在记忆中比较和对比项目的能力，以及在新情境中支持对记忆进行推理运用（灵活性），被认为是人类陈述性记忆的两个关键心理特征，海马体损伤和海马体功能障碍都会改变这两个特征。成年和老年小鼠通过两阶段范式接受学习任务训练，其目的是在同一实验对象中通过这两个心理方面评估记忆表现。结果表明，衰老会特异性损害在记忆中比较和对比项目的能力（基于复杂关联的陈述性/关系性记忆），而不会改变基于简单刺激-反应关联的记忆（程序性记忆）。成年小鼠的海马体损伤在关系性记忆（受损）和程序性记忆（未受损）之间产生了相同的分离。药理学实验表明，根据所使用的药物，老年小鼠的关系性记忆缺陷可能会被选择性逆转（即程序性记忆无变化），并且某些治疗的行为效果与其在恢复正常（即成年）水平的海马体可塑性相关机制方面的效力平行。与先前的研究结果一起，这些结果表明关系性表征的存储和运用将关键取决于海马体突触的可塑性，海马体突触通过与皮质区域的连接，将支持感知、行为和认知事件之间关联的存储。
