Role of the mPFC-Amygdala Circuit in Fear Extinction

描述(申请人提供)：拟议工作的目标是阐明条件性恐惧消退的潜在机制。由于消退被广泛用作治疗创伤后应激障碍(PTSD)等焦虑症的模型，了解其神经关联无疑将有利于公众健康。众所周知，皮质对杏仁核的影响是抑制和抑制条件性恐惧的，因此可以作为杏仁核输出抑制控制的模型结构。内侧前额叶皮质(MPFC)可以抑制杏仁中央核(CEM)，这是投射到下游靶点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在CEM中的抑制可以通过其投射到杏仁核中的GABA能细胞(插层细胞团)，然后投射到CEM并抑制CEM而发生。通过微量注射与mu型阿片受体激动剂(它们大量表达)结合的皂苷，将损害iTCs，并将测试恐惧条件反射及其消退。电生理记录将确定病变是否影响了已知的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.