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）：拟议工作的目的是阐明条件恐惧的灭绝机制。由于灭绝被广泛用作治疗诸如创伤后应激障碍（PTSD）等焦虑症的模型，因此理解其神经相关性无疑将对公共卫生有益。已知对杏仁核的皮质影响是抑制性的，并且[]抑制条件的恐惧，从而充当抑制杏仁核输出的模型结构。内侧前额叶皮层（MPFC）可以抑制杏仁核（CEM）的中央核，这是向下游靶标投射的主要输出，以产生可怕的反应。我们将测试一个模型，该模型假设MPFC介导的CEM中的抑制作用可以通过投影到杏仁核（ITCS）中的少量GABA能细胞（ITC）中，然后投影并抑制CEM。 ITC将通过与Mu-Apioid受体的激动剂相结合（它们丰富地表达）的激动剂的显微注射来使ITC生存，并将测试恐惧调节及其灭绝。电生理记录将确定病变是否影响了MPFC已知会在杏仁核输出上施加的抑制驱动。