Acid-Sensing Ion Channel 1 Is Localized in Brain Regions with High Synaptic Density and Contributes to Fear Conditioning
Acid-Sensing Ion Channel 1 Is Localized in Brain Regions with High Synaptic Density and Contributes to Fear Conditioning
复制标题
DOI：
10.1523/jneurosci.23-13-05496.2003
复制
发表时间：
2003-07
期刊：
影响因子：
--
通讯作者：
J. Wemmie;C. Askwith;E. Lamani;M. Cassell;J. Freeman;M. Welsh
中科院分区：
文献类型：
--
作者：
J. Wemmie;C. Askwith;E. Lamani;M. Cassell;J. Freeman;M. Welsh
酸敏感离子通道ASIC1有助于海马区突触的可塑性和海马区依赖的空间记忆。为了探讨ASIC1在脑内的作用，我们检测了ASIC1蛋白的分布。令人惊讶的是，尽管ASIC1存在于海马区，但在海马区以外的几个区域中，它的含量要丰富得多。ASIC1主要集中在嗅球肾小球、胡须桶皮质、扣带回、纹状体、伏隔核、杏仁核和小脑皮质等兴奋性突触输入较强的区域。由于杏仁核的ASIC1水平特别高，我们进一步关注了这一区域。我们发现，细胞外酸中毒在杏仁核神经元中引起的电流密度比海马神经元更大，并且破坏ASIC1基因消除了杏仁核中的H+诱发电流。我们还测试了ASIC1对杏仁核依赖行为的影响；ASIC1缺失的小鼠在线索和情景恐惧条件反射方面存在缺陷，但在升高的加迷宫上的基线恐惧是完整的。这些研究表明，ASIC1分布在支持高水平突触可塑性的区域，并参与恐惧条件反射的神经机制。
The acid-sensing ion channel, ASIC1, contributes to synaptic plasticity in the hippocampus and to hippocampus-dependent spatial memory. To explore the role of ASIC1 in brain, we examined the distribution of ASIC1 protein. Surprisingly, although ASIC1 was present in the hippocampal circuit, it was much more abundant in several areas outside the hippocampus. ASIC1 was enriched in areas with strong excitatory synaptic input such as the glomerulus of the olfactory bulb, whisker barrel cortex, cingulate cortex, striatum, nucleus accumbens, amygdala, and cerebellar cortex. Because ASIC1 levels were particularly high in the amygdala, we focused further on this area. We found that extracellular acidosis elicited a greater current density in amygdala neurons than hippocampal neurons and that disrupting the ASIC1 gene eliminated H+-evoked currents in the amygdala. We also tested the effect of ASIC1 on amygdala-dependent behavior; ASIC1-null mice displayed deficits in cue and context fear conditioning, yet baseline fear on the elevated plus maze was intact. These studies suggest that ASIC1 is distributed to regions supporting high levels of synaptic plasticity and contributes to the neural mechanisms of fear conditioning.