ASIC-dependent LTP at multiple glutamatergic synapses in amygdala network is required for fear memory.

ASIC-dependent LTP at multiple glutamatergic synapses in amygdala network is required for fear memory.
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DOI:
10.1038/srep10143
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发表时间:
2015-05-19
期刊:
影响因子:
4.6
通讯作者:
Lien CC
Lien CC
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chiang PH;Chien TC;Chen CC;Yanagawa Y;Lien CC

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人类酸敏感离子通道-1a亚基(ASIC 1a)基因同源基因的遗传变异与惊恐障碍和杏仁核功能障碍相关在ASIC 1a基因敲除小鼠中,恐惧学习和皮质基底外侧杏仁核(BLA)突触的活动诱导的长时程增强(LTP)均受损,表明ASICs在恐惧记忆形成中起关键作用。在这项研究中,我们发现,ASIC的差异表达的杏仁核神经元的人口,和LTP的程度,在各种神经元突触与ASIC的表达水平在突触后神经元。重要的是,选择性删除GABA能细胞(包括杏仁核输出神经元)中的ASIC 1a,消除了这些细胞中的LTP,并减少了恐惧学习,其程度与选择性消除BLA神经元中的ASIC 1a时相同。因此,恐惧学习需要多个杏仁核突触的ASIC依赖性LTP,包括皮质-BLA输入突触和输出神经元上的杏仁核内突触。
Genetic variants in the human ortholog of acid-sensing ion channel-1a subunit (ASIC1a) gene are associated with panic disorder and amygdala dysfunction. Both fear learning and activity-induced long-term potentiation (LTP) of cortico-basolateral amygdala (BLA) synapses are impaired in ASIC1a-null mice, suggesting a critical role of ASICs in fear memory formation. In this study, we found that ASICs were differentially expressed within the amygdala neuronal population, and the extent of LTP at various glutamatergic synapses correlated with the level of ASIC expression in postsynaptic neurons. Importantly, selective deletion of ASIC1a in GABAergic cells, including amygdala output neurons, eliminated LTP in these cells and reduced fear learning to the same extent as that found when ASIC1a was selectively abolished in BLA glutamatergic neurons. Thus, fear learning requires ASIC-dependent LTP at multiple amygdala synapses, including both cortico-BLA input synapses and intra-amygdala synapses on output neurons.
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