Bidirectional Regulation of Hippocampal Long-Term Synaptic Plasticity and Its Influence on Opposing Forms of Memory

记忆巩固 长时程增强 神经科学 突触可塑性 齿状回 海马结构 海马体 长期记忆 变质塑性 神经元记忆分配 心理学 干涉理论 工作记忆 生物 突触疲劳 认知 兴奋性突触后电位 抑制性突触后电位 生物化学 受体
作者
Gaël Malleret,Juan Marcos Alarcón,Guillaume Martel,Shuichi Takizawa,Svetlana Vronskaya,Deqi Yin,Irene Z. Chen,Eric R. Kandel,Gleb P. Shumyatsky
出处
期刊:The Journal of Neuroscience [Society for Neuroscience]
卷期号:30 (10): 3813-3825 被引量:100
标识
DOI:10.1523/jneurosci.1330-09.2010
摘要

Reference memory characterizes the long-term storage of information acquired through numerous trials. In contrast, working memory represents the short-term acquisition of trial-unique information. A number of studies in the rodent hippocampus have focused on the contribution of long-term synaptic potentiation (LTP) to long-term reference memory. In contrast, little is known about the synaptic plasticity correlates of hippocampal-based components of working memory. Here, we described a mouse with selective expression of a dominant-negative mutant of the regulatory subunit of protein kinase A (PKA) only in two regions of the hippocampus, the dentate gyrus and area CA1. This mouse showed a deficit in several forms of LTP in both hippocampal subregions and a lowered threshold for the consolidation of long-term synaptic depression (LTD). When trained with one trial per day in a water maze task, mutant mice displayed a deficit in consolidation of long-term memory. In contrast, these mice proved to be more flexible after a transfer test and also showed a delay-dependent increased performance in working memory, when repetitive information (proactive interference) was presented. We suggest that through its bidirectional control over synaptic plasticity PKA can regulate opposing forms of memory. The defect in L-LTP disrupts long-term memory consolidation. The persistence of LTD may allow acquisition of new information by restricting the body of previously stored information and suppressing interference.
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