Retrieval of context-associated memory is dependent on the Ca(v)3.2 T-type calcium channel.
Retrieval of context-associated memory is dependent on the Ca(v)3.2 T-type calcium channel.
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DOI：
10.1371/journal.pone.0029384
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Liu IY
中科院分区：
文献类型：
--
作者：
Chen CC;Shen JW;Chung NC;Min MY;Cheng SJ;Liu IY
在所有的电压门控钙通道中，由Cav3.2基因编码的T型钙通道在海马中高度表达，其与情境、时间和空间学习和记忆相关。然而，Cav3.2 T型Ca 2+通道在这些依赖于海马的学习和记忆类型中的具体参与仍不清楚。为了研究该通道在学习和记忆中的功能作用，我们将Cav3.2纯合和杂合敲除小鼠及其野生型同窝小鼠进行了依赖于海马的行为任务，包括微量恐惧条件反射、Morris水迷宫和被动回避。Cav3.2 −/−小鼠在Morris水迷宫和听觉痕迹恐惧条件反射任务中表现正常，但在情境线索的痕迹恐惧条件反射、步下和步下被动回避任务中受损。此外，在WT和Cav3.2 +/−小鼠的海马切片中可以诱导长时程增强（LTP）180分钟，而在Cav3.2 −/−小鼠中LTP仅持续120分钟。为了确定海马结构是否对受损的行为表型负责，我们接下来进行实验以敲低海马中Cav3.2 T型Ca 2+通道的局部功能。输注米贝拉地尔（一种T型通道阻断剂）的野生型小鼠表现出与纯合子敲除小鼠相似的行为。两者合计，我们的研究结果表明，检索上下文相关的记忆依赖于Cav3.2 T型钙通道。
Among all voltage-gated calcium channels, the T-type Ca2+ channels encoded by the Cav3.2 genes are highly expressed in the hippocampus, which is associated with contextual, temporal and spatial learning and memory. However, the specific involvement of the Cav3.2 T-type Ca2+ channel in these hippocampus-dependent types of learning and memory remains unclear. To investigate the functional role of this channel in learning and memory, we subjected Cav3.2 homozygous and heterozygous knockout mice and their wild-type littermates to hippocampus-dependent behavioral tasks, including trace fear conditioning, the Morris water-maze and passive avoidance. The Cav3.2 −/− mice performed normally in the Morris water-maze and auditory trace fear conditioning tasks but were impaired in the context-cued trace fear conditioning, step-down and step-through passive avoidance tasks. Furthermore, long-term potentiation (LTP) could be induced for 180 minutes in hippocampal slices of WTs and Cav3.2 +/− mice, whereas LTP persisted for only 120 minutes in Cav3.2 −/− mice. To determine whether the hippocampal formation is responsible for the impaired behavioral phenotypes, we next performed experiments to knock down local function of the Cav3.2 T-type Ca2+ channel in the hippocampus. Wild-type mice infused with mibefradil, a T-type channel blocker, exhibited similar behaviors as homozygous knockouts. Taken together, our results demonstrate that retrieval of context-associated memory is dependent on the Cav3.2 T-type Ca2+ channel.
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