在基因敲除小鼠的杏仁核中恢复酸敏感离子通道-1a可挽救恐惧记忆，但不能挽救非条件恐惧反应。
Restoring Acid-sensing ion channel-1a in the amygdala of knock-out mice rescues fear memory but not unconditioned fear responses.
作者信息
Coryell Matthew W, Wunsch Amanda M, Haenfler Jill M, Allen Jason E, McBride Jodi L, Davidson Beverly L, Wemmie John A
机构信息
Neuroscience Program, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
出版信息
J Neurosci. 2008 Dec 17;28(51):13738-41. doi: 10.1523/JNEUROSCI.3907-08.2008.
Abstract
Acid-sensing ion channel-1a (ASIC1a) contributes to multiple fear behaviors, however the site of ASIC1a action in behavior is not known. To explore a specific location of ASIC1a action, we expressed ASIC1a in the basolateral amygdala of ASIC1a-/- mice using viral vector-mediated gene transfer. This rescued context-dependent fear memory, but not the freezing deficit during training or the unconditioned fear response to predator odor. These data pinpoint the basolateral amygdala as the site where ASIC1a contributes to fear memory. They also discriminate fear memory from fear expressed during training and from unconditioned fear. Furthermore, this work illustrates a strategy for identifying discrete brain regions where specific genes contribute to complex behaviors.
摘要
酸敏感离子通道1a（ASIC1a）参与多种恐惧行为，然而ASIC1a在行为中的作用位点尚不清楚。为了探索ASIC1a作用的特定位置，我们使用病毒载体介导的基因转移在ASIC1a基因敲除小鼠的基底外侧杏仁核中表达ASIC1a。这挽救了与情境相关的恐惧记忆，但没有挽救训练期间的僵立缺陷或对捕食者气味的无条件恐惧反应。这些数据确定基底外侧杏仁核是ASIC1a对恐惧记忆起作用的位点。它们还将恐惧记忆与训练期间表现出的恐惧以及无条件恐惧区分开来。此外，这项工作阐明了一种识别特定基因对复杂行为起作用的离散脑区的策略。
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本文引用的文献
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2
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Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16556-61. doi: 10.1073/pnas.0608018103. Epub 2006 Oct 23.
3
Acid-sensing ion channels: advances, questions and therapeutic opportunities.酸敏感离子通道：进展、问题与治疗机遇
Trends Neurosci. 2006 Oct;29(10):578-86. doi: 10.1016/j.tins.2006.06.014. Epub 2006 Aug 7.
4
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Behav Brain Res. 2006 Feb 15;167(1):57-62. doi: 10.1016/j.bbr.2005.08.016. Epub 2005 Oct 6.
5
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6
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7
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8
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9
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