A role in learning for SRF:: Deletion in the adult forebrain disrupts LTD and the formation of an immediate memory of a novel context
A role in learning for SRF:: Deletion in the adult forebrain disrupts LTD and the formation of an immediate memory of a novel context
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DOI：
10.1016/j.neuron.2006.03.013
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发表时间：
2006-04-06
期刊：
影响因子：
16.2
通讯作者：
Kandel, ER
中科院分区：
文献类型：
--
作者：
Etkin, A;Alarcón, JM;Kandel, ER
虽然对于长时程增强（LTP）相关变化如何有助于长期记忆的形成已有重要见解，但对于海马体类似长时程抑制（LTD）的变化在学习和记忆存储中的作用却知之甚少。我们描述了一种在成年前脑中缺乏转录因子血清反应因子（SRF）的小鼠。这种小鼠即使在几分钟的时间跨度内也无法对一个新环境形成基于海马体的即时记忆，这导致了在明确空间记忆方面出现严重但有选择性的缺陷。这些动物在长时程抑制的诱导方面也存在障碍，包括由胆碱能激动剂触发的长时程抑制。此外，在基因敲除小鼠中，调节长时程抑制所必需的两个过程——细胞内储存钙的释放和磷酸酶激活的基因表达异常。这些发现表明，海马体要通过类似长时程增强的过程形成联想性空间记忆，它必须首先通过探索和熟悉性学习来学习环境本身，而这需要类似长时程抑制的过程。
Whereas significant insight exists as to how LTP-related changes can contribute to the formation of long-term memory, little is known about the role of hippocampal LTD-like changes in learning and memory storage. We describe a mouse lacking the transcription factor SRF in the adult forebrain. This mouse could not acquire a hippocampus-based immediate memory for a novel context even across a few minute timespan, which led to a profound but selective deficit in explicit spatial memory. These animals were also impaired in the induction of LTD, including LTD triggered by a cholinergic agonist. Moreover, genes regulating two processes essential for LTD-calcium release from intracellular stores and phosphatase activation-were abnormally expressed in knockouts. These findings suggest that for the hippocampus to form associative spatial memories through LTP-like processes, it must first undergo learning of the context per se through exploration and the learning of familiarity, which requires LTD-like processes.