Role of the mPFC-Amygdala Circuit in Fear Extinction

描述（由申请人提供）：本研究的目的是阐明条件性恐惧消失的机制。由于灭绝被广泛用作治疗焦虑障碍（如创伤后应激障碍（PTSD））的模型，了解其神经相关性无疑将有益于公众健康。皮层对杏仁核的影响被认为是抑制性的，并且抑制了条件恐惧，因此作为杏仁核输出的抑制性控制的模型结构。内侧前额叶皮层（mPFC）可以抑制杏仁核中央核（CEm），这是向下游目标投射产生恐惧反应的主要输出。我们将测试一个模型，该模型假设mpfc介导的CEm抑制可以通过其投射到杏仁核中的一小群gaba能细胞（插层细胞团（ITCs））而发生，然后这些细胞投射到CEm并抑制CEm。ITCs将通过显微注射与μ -阿片受体激动剂结合的皂苷（它们大量表达）来损伤ITCs，并且将测试恐惧条件反射及其灭绝。电生理记录将确定病变是否影响了mPFC对杏仁核输出的抑制驱动。

DESCRIPTION (provided by applicant): The goal of the proposed work is to elucidate the mechanisms underlying extinction of conditioned fear. Since extinction is widely used as a model for the treatment of anxiety disorders such as Post Traumatic Stress Disorder (PTSD), understanding its neural correlates will undoubtedly be beneficial to public health. Cortical influence over the amygdala is known to be inhibitory and [to] suppress conditioned fear, thus serving as the model structure for inhibitory control of amygdala output. The medial prefrontal cortex (mPFC) can inhibit the central nucleus of the amygdala (CEm), which is the main output projecting to downstream targets to produce a fearful response. We will test a model which posits that mPFC-mediated inhibition in the CEm can occur via its projection to small groups of GABAergic cells in the amygdala (the intercalated cell masses (ITCs)), which then project to and inhibit the CEm. ITCs will be lesioned by microinjections of saporin conjugated to an agonist of the mu-opioid receptor (which they abundantly express) and fear conditioning and its extinction will be tested. Electrophysiological recordings will determine whether the lesion has affected the inhibitory drive that the mPFC is known to exert on amygdala output.