Role of the mPFC-Amygdala Circuit in Fear Extinction

mPFC-杏仁核回路在恐惧消退中的作用

• 批准号: 7057610
• 负责人: EKATERINA LIKHTIK
• 金额: $ 3.9万
• 依托单位: RUTGERS THE STATE UNIV OF NJ NEWARK
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7057610
• 关键词: amygdala; anxiety disorders; behavior test; behavioral /social science research tag; behavioral extinction; biotin; disease /disorder model; electrophysiology; experimental brain lesion; fear; gamma aminobutyrate; immunotoxicity; interneurons; laboratory rat; memory; microinjections; neural information processing; neuropsychology; operant conditionings; opioid receptor; predoctoral investigator; prefrontal lobe /cortex

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.

描述（由申请人提供）：拟议工作的目标是阐明条件性恐惧消失的机制。由于灭绝被广泛用作治疗创伤后应激障碍（PTSD）等焦虑症的模型，了解其神经相关性无疑将有益于公众健康。众所周知，皮质对杏仁核的影响是抑制性的，可以抑制条件性恐惧，因此可以作为杏仁核输出抑制控制的模型结构。内侧前额叶皮层（mPFC）可以抑制杏仁核中央核（CEm），这是投射到下游目标以产生可怕反应的主要输出。我们将测试一个模型，该模型假设 CEm 中 mPFC 介导的抑制可以通过其投射到杏仁核中的一小群 GABA 能细胞（嵌入细胞团 (ITC)）而发生，然后投射到并抑制 CEm。通过显微注射与 mu-阿片受体激动剂（它们大量表达）结合的皂草素，ITC 会受到损害，并且将测试恐惧调节及其消退。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力。