Overexpression of acid-sensing ion channel 1a in transgenic mice increases acquired fear-related behavior
Overexpression of acid-sensing ion channel 1a in transgenic mice increases acquired fear-related behavior
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DOI：
10.1073/pnas.0308753101
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发表时间：
2004-03-09
影响因子：
11.1
通讯作者：
Welsh, MJ
中科院分区：
文献类型：
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作者：
Wemmie, JA;Coryell, MW;Welsh, MJ
酸敏感离子通道Ia（ASIC1a）在杏仁核复合体和其他与恐惧相关的大脑区域中大量表达。对ASIC1基因被破坏的小鼠的研究表明，ASIC1a可能有助于学习恐惧。为了验证这一假设，我们通过使用泛神经元突触蛋白1启动子来产生过表达人类ASIC1a的小鼠。转基因ASIC1a与内源性小鼠ASIC1a相互作用，并分布到大脑的突触体部分。ASIC1a的转基因表达也使神经元酸诱发的阳离子电流加倍。annygdala表现出突出的表达，过表达ASIC1a增强了恐惧条件反射，获得性焦虑的动物模型。这些数据提出了ASIC1a和H+门控电流可能有助于人类异常恐惧和焦虑症的发展的可能性。
The acid-sensing ion channel la (ASIC1a) is abundantly expressed in the annygdala complex and other brain regions associated with fear. Studies of mice with a disrupted ASIC1 gene suggested that ASIC1a may contribute to learned fear. To test this hypothesis, we generated mice overexpressing human ASIC1a by using the panneuronal synapsin 1 promoter. Transgenic ASIC1a interacted with endogenous mouse ASIC1a and was distributed to the synaptosomal fraction of brain. Transgenic expression of ASIC1a also doubled neuronal acid-evoked cation currents. The annygdala showed prominent expression, and overexpressing ASIC1a enhanced fear conditioning, an animal model of acquired anxiety. These data raise the possibility that ASIC1a and H+-gated currents may contribute to the development of abnormal fear and to anxiety disorders in humans.