The L-type voltage-gated calcium channel CaV1.3 mediates consolidation, but not extinction, of contextually conditioned fear in mice
The L-type voltage-gated calcium channel CaV1.3 mediates consolidation, but not extinction, of contextually conditioned fear in mice
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DOI：
10.1101/lm.279006
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发表时间：
2006-09-01
影响因子：
2
通讯作者：
Murphy, Geoffrey G.
中科院分区：
文献类型：
--
作者：
McKinney, Brandon C.;Murphy, Geoffrey G.
用药理学方法证明，巴甫洛夫恐惧条件反射的巩固和消退在一定程度上依赖于L型电压门控钙通道(LVGCC)。虽然这些研究已经成功地将LVGCC与巴甫洛夫恐惧条件反射联系在一起，但它们并没有提供有关特定的LVGCC亚型的信息。在大脑中发现的两种主要的LVGCC亚型(Ca(V)1.2和Ca(V)1.3)都是早期工作中使用的药物操作的靶点。在这项研究中，我们使用了孔形成亚单位(α(1D))Ca(V)1.3基因缺失的小鼠(Ca(V)1.3基因敲除小鼠)来阐明它对巩固和消除条件性恐惧的贡献。我们发现，Ca(V)1.3基因敲除小鼠在巩固情境恐惧条件反射方面表现出显著的损伤。然而，一旦过度训练，Ca(V)1.3基因敲除小鼠的灭绝速度与野生型小鼠相同。我们还发现，在隐藏平台版本的Morris水迷宫上，Ca(V)1.3基因敲除小鼠的表现与野生型小鼠一样好，这表明在Ca(V)1.3基因敲除小鼠中观察到的条件性恐惧的巩固缺陷不太可能是无法编码上下文的结果，而可能反映了无法在上下文和无条件刺激之间建立联系。
Using pharmacological techniques, it has been demonstrated that both consolidation and extinction of Pavlovian fear conditioning are dependent to some extent upon L-type voltage-gated calcium channels (LVGCCs). Although these studies have successfully implicated LVGCCs in Pavlovian fear conditioning, they do not provide information about the specific LVGCC isoform involved. Both of the major LVGCC subtypes found in the brain (Ca(v)1.2 and Ca(v)1.3) are targets of the pharmacological manipulations used in earlier work. In this study, we used mice in which the gene for the pore-forming subunit (alpha(1D)) Ca(v)1.3 was deleted (Ca(v)1.3 knockout mice) to elucidate its contribution to consolidation and extinction of conditioned fear. We find that Ca(v)1.3 knockout mice exhibit significant impairments in consolidation of contextual fear conditioning. However, once sufficiently overtrained, the Ca(v)1.3 knockout mice exhibit rates of extinction that are identical to that observed in wild-type mice. We also find that Ca(v)1.3 knockout mice perform as well as wild-type mice on the hidden platform version of the Morris water maze, suggesting that the consolidation deficit in conditioned fear observed in the Ca(v)1.3 knockout mice is not likely the result of an inability to encode the context, but may reflect an inability to make the association between the context and the unconditioned stimulus.