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Neural Mechanisms in the Medial Amygdala Underlying Aggression

内侧杏仁核潜在攻击性的神经机制

基本信息

批准号：
9151037
负责人：
Jacob Nordman
金额：
--
依托单位：
U.S. NATIONAL INSTITUTE OF MENTAL HEALTH
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-10-01 至 2019-10-01
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9151037
关键词：
Aggressive behavior Amygdaloid structure Anger Automobile Driving Award Behavioral Binding Cell Nucleus Chemosensitization Data Disease Dorsal Electrophysiology (science)FOS gene Fellowship Frequencies Funding Future Genetic Glutamates Goals Lead Medial Mediating Mental disorders Modification Neurologic Neurons Outcome Partner in relationship Patients Physiological Population Post-Traumatic Stress Disorders Prevention Protocols documentation Psychopathology Reporting Research Research Personnel Resources Rodent Role Serotonin Signal Transduction Social Behavior Social Interaction Societies Symptoms Synapses Techniques Testing Therapeutic United States National Institutes of Health Violence associated symptom base cell type common symptom design emotion regulation in vivo innovation insight neuromechanism novel strategies optogenetics psychopathic personality relating to nervous system sensor social synaptic depression synaptic function

项目摘要

PROJECT SUMMARY/ABSTRACT Aggression and violence are common symptoms of many psychiatric disorders, but the underlying mechanisms that lead to their expression remain largely unknown. The amygdala is a key region involved in the regulation of emotion and has been implicated as a primary locus of psychopathology. The medial amygdala (MeA) is a major subdivision of the amygdala and is an important modulator of aggression and violence. Previous studies have shown that high-frequency stimulation of neurons at the MeA can enhance aggression during future social encounters, producing a phenomenon called aggression priming. The precise mechanism by which the medial amygdala mediates aggression and its role in psychiatric illness, however, requires further elucidation. The goal of this PRAT fellowship proposal is to define the role of the MeA in aggression. My preliminary results show that glutamatergic neurons within the MeA respond to stimulation in a frequency-dependent manner and that the MeA can regulate expressions of aggression and violence during a social interaction test. My central hypothesis is that potentiation of glutamatergic synapses at the MeA can prime aggression, leading to an increase in aggression and violence during social interaction. Firstly, I plan to determine whether high-frequency photostimulation (HFPS) using optogenetics can induce aggression priming during a social interaction test. I will test whether HFPS induces synaptic potentiation at the MeA using in vivo electrophysiology and whether synaptic potentiation is responsible for aggressive behavior by depotentiating synapses after HFPS using low-frequency photostimulation, a known protocol for inducing depression of synaptic activity. Secondly I will determine the role of serotonin in MeA regulated aggression by stimulating dorsal raphe projections, a primary locus of serotonergic neurons, at the MeA using optogenetics. Finally I will confirm the role of serotonin in MeA regulated aggression using genetic modifications to the serotonin releasing machinery in vivo and specialized sensors designed to detect serotonin binding at the MeA. The successful completion of this proposal will have a positive translational impact because preventative therapeutic strategies targeting the MeA can potentially be developed to curb excessive aggression and violence associated with psychiatric disorders based on the findings of the proposed research.

项目总结/摘要攻击和暴力是许多精神疾病的常见症状，但导致其表达的潜在机制在很大程度上仍然未知。杏仁核是参与情绪调节的关键区域，并且被认为是精神病理学的主要位点。内侧杏仁核（MeA）是杏仁核的一个主要分支，是攻击和暴力的重要调制器。先前的研究表明，对MeA神经元的高频刺激可以增强未来社会交往中的攻击性，产生一种称为攻击启动的现象。然而，内侧杏仁核介导攻击性的确切机制及其在精神疾病中的作用还需要进一步阐明。这个普拉奖学金提案的目标是定义MeA在攻击中的作用。我的初步研究结果表明，MeA内的神经元对刺激的反应频率依赖性的方式和MeA可以调节表达的侵略和暴力在社会互动测试。我的中心假设是，MeA的突触增强可以引发攻击，导致社会交往中攻击和暴力的增加。首先，我计划确定使用光遗传学的高频光刺激（HFPS）是否可以在社交互动测试中诱导攻击启动。我将测试是否HFPS诱导突触增强在MeA使用体内电生理学和突触增强是否是负责攻击性行为通过去增强突触后HFPS使用低频光刺激，一个已知的协议，用于诱导抑郁症的突触活动。其次，我将确定5-羟色胺在MeA调节的侵略刺激中缝背核的预测，一个主要的位点，在MeA使用光遗传学。最后，我将确认5-羟色胺在MeA调节的侵略中的作用，使用基因修饰的5-羟色胺释放机器在体内和专门的传感器，旨在检测5-羟色胺结合在MeA。这项提案的成功完成将产生积极的转化影响，因为根据拟议研究的结果，可以制定针对MeA的预防性治疗策略，以遏制与精神疾病相关的过度攻击和暴力。