Structural and Functional Remodeling of Amygdala GABAergic Synapses in Associative Fear Learning
Structural and Functional Remodeling of Amygdala GABAergic Synapses in Associative Fear Learning
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DOI：
10.1016/j.neuron.2019.08.013
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发表时间：
2019-11-20
期刊：
影响因子：
16.2
通讯作者：
Ferraguti, Francesco
中科院分区：
文献类型：
--
作者：
Kasugai, Yu;Vogel, Elisabeth;Ferraguti, Francesco
联想学习被认为涉及不同形式的活动依赖性突触可塑性。虽然以前的研究主要集中在学习相关的变化发生在兴奋性突触，我们发现，联想学习，如恐惧条件反射，也需要持久的功能和结构可塑性的GABA能突触的锥体神经元的小鼠基底杏仁核。条件性恐惧介导的GABA能突触结构重塑与mIPSC动力学变化和含有α 2亚基的突触苯二氮卓类敏感（BZD）GABA（A）受体部分增加相关，而不改变突触内BZD-GABA（A）受体的分布和总量。这些结构和功能的突触变化部分逆转的灭绝训练。这些发现提供了证据表明，联想学习，如巴甫洛夫恐惧条件反射和消退，塑造抑制性突触来调节活性神经元网络的抑制，这一过程可能会调整杏仁核回路对威胁的反应。
Associative learning is thought to involve different forms of activity-dependent synaptic plasticity. Although previous studies have mostly focused on learning-related changes occurring at excitatory glutamatergic synapses, we found that associative learning, such as fear conditioning, also entails long-lasting functional and structural plasticity of GABAergic synapses onto pyramidal neurons of the murine basal amygdala. Fear conditioning-mediated structural remodeling of GABAergic synapses was associated with a change in mIPSC kinetics and an increase in the fraction of synaptic benzodiazepine-sensitive (BZD) GABA(A) receptors containing the alpha 2 subunit without altering the intrasynaptic distribution and overall amount of BZD-GABA(A) receptors. These structural and functional synaptic changes were partly reversed by extinction training. These findings provide evidence that associative learning, such as Pavlovian fear conditioning and extinction, sculpts inhibitory synapses to regulate inhibition of active neuronal networks, a process that may tune amygdala circuit responses to threats.