Hippocampal long-term depression is required for the consolidation of spatial memory
Hippocampal long-term depression is required for the consolidation of spatial memory
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DOI：
10.1073/pnas.1008200107
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发表时间：
2010-09-21
影响因子：
11.1
通讯作者：
Wang, Yu Tian
中科院分区：
文献类型：
--
作者：
Ge, Yuan;Dong, Zhifang;Wang, Yu Tian
尽管谷氨酸能传递的N -甲基 - D -天冬氨酸受体（NMDAR）依赖性长时程增强（LTP）和长时程抑制（LTD）是长时程空间记忆的候选机制，但LTP和LTD的确切作用仍知之甚少。在此，我们报道在自由活动的成年大鼠海马CA1区，LTP和LTD分别被NMDAR 2A（GluN2A）和2B亚基（GluN2B）选择性拮抗剂所阻断。这些结果有力地表明，NMDAR亚型选择性拮抗剂是探究LTP和LTD在空间记忆中作用的合适工具。通过莫里斯水迷宫任务，阻断LTP的GluN2A拮抗剂对行为表现的任何方面都没有显著影响，而阻断LTD的GluN2B拮抗剂则损害空间记忆巩固。此外，通过海马内注射一种特异性干扰α - 氨基 - 3 - 羟基 - 5 - 甲基 - 4 - 异恶唑丙酸受体（AMPA受体）内吞作用的短肽来抑制LTD的表达，也诱导出类似的空间记忆缺陷。综上所述，我们的研究结果支持海马CA1区LTD在长时程空间记忆巩固中的功能性需求。
Although NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) and long-term depression (LTD) of glutamatergic transmission are candidate mechanisms for long-term spatial memory, the precise contributions of LTP and LTD remain poorly understood. Here, we report that LTP and LTD in the hippocampal CA1 region of freely moving adult rats were prevented by NMDAR 2A (GluN2A) and 2B subunit (GluN2B) preferential antagonists, respectively. These results strongly suggest that NMDAR subtype preferential antagonists are appropriate tools to probe the roles of LTP and LTD in spatial memory. Using a Morris water maze task, the LTP-blocking GluN2A antagonist had no significant effect on any aspect of performance, whereas the LTD-blocking GluN2B antagonist impaired spatial memory consolidation. Moreover, similar spatial memory deficits were induced by inhibiting the expression of LTD with intrahippocampal infusion of a short peptide that specifically interferes with AMPA receptor endocytosis. Taken together, our findings support a functional requirement of hippocampal CA1 LTD in the consolidation of long-term spatial memory.