Pathway-Selective Adjustment of Prefrontal-Amygdala Transmission during Fear Encoding

Pathway-Selective Adjustment of Prefrontal-Amygdala Transmission during Fear Encoding
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DOI:
10.1523/jneurosci.2664-14.2014
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发表时间:
2014-11-19
影响因子:
5.3
通讯作者:
Clem, Roger L.
Clem, Roger L.
中科院分区:
医学1区
文献类型:
--
作者:
Arruda-Carvalho, Maithe;Clem, Roger L.

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条件恐惧需要基底外侧杏仁核(BLA)和内侧前额叶皮层(mPFC)的神经活动,这两个结构在突触水平上紧密相连。先前的研究表明,mPFC的解剖细分对恐惧的表达和抑制有不同的贡献,并且这种处理的功能输出传递给BLA复合体。然而,mPFC-BLA网络的突触可塑性是否与恐惧记忆编码有关尚不清楚。本研究利用光遗传学和离体电生理学方法揭示了恐惧条件反射对边缘下(IL)和边缘前(PL)皮层投射形成的BLA兴奋性和前馈抑制回路的影响。在幼年小鼠中,这些途径在BLA主神经元中获得等效的兴奋和前馈抑制。然而,恐惧学习导致PL回路中抑制:兴奋平衡的选择性减少,这可归因于AMPA受体功能的突触后增加。这些数据提示了mPFC-BLA传输调节对恐惧记忆编码的通路特异性机制。在条件提示的再参与下,这些修改可能会放大情绪反应。
Conditioned fear requires neural activity in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC), structures that are densely interconnected at the synaptic level. Previous work has suggested that anatomical subdivisions of mPFC make distinct contributions to fear expression and inhibition, and that the functional output of this processing is relayed to the BLA complex. However, it remains unknown whether synaptic plasticity in mPFC-BLA networks contributes to fear memory encoding. Here we use optogenetics and ex vivo electrophysiology to reveal the impact of fear conditioning on BLA excitatory and feedforward inhibitory circuits formed by projections from infralimbic (IL) and prelimbic (PL) cortices. In naive mice, these pathways recruit equivalent excitation and feedforward inhibition in BLA principal neurons. However, fear learning leads to a selective decrease in inhibition: excitation balance in PL circuits that is attributable to a postsynaptic increase in AMPA receptor function. These data suggest a pathway-specific mechanism for fear memory encoding by adjustment of mPFC-BLA transmission. Upon reengagement of PL by conditioned cues, these modifications may serve to amplify emotional responses.