The Fishberg Department of Neuroscience and the Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
The Fishberg Department of Neuroscience and the Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029
J Neurosci. 2014 Nov 19;34(47):15601-9. doi: 10.1523/JNEUROSCI.2664-14.2014.
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.
条件性恐惧需要杏仁基底外侧核（BLA）和内侧前额叶皮层（mPFC）的神经活动，这些结构在突触水平上密集地相互连接。以前的工作表明，mPFC 的解剖细分对恐惧表达和抑制有不同的贡献，并且这种处理的功能输出被传递到 BLA 复合体。然而，目前尚不清楚 mPFC-BLA 网络中的突触可塑性是否有助于恐惧记忆编码。在这里，我们使用光遗传学和离体电生理学来揭示恐惧条件作用对来自下边缘（IL）和前边缘（PL）皮层的投射形成的 BLA 兴奋性和前馈抑制回路的影响。在幼稚小鼠中，这些通路在 BLA 主神经元中募集等效的兴奋和前馈抑制。然而，恐惧学习导致 PL 回路中抑制-兴奋平衡的选择性降低，这归因于 AMPA 受体功能的突触后增加。这些数据表明，通过调整 mPFC-BLA 传递，存在一种特定于通路的恐惧记忆编码机制。在条件线索重新激活 PL 时，这些修饰可能有助于放大情绪反应。
