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.

项目摘要/摘要侵略性和暴力是许多精神疾病的常见症状，但是导致其表达的基本机制在很大程度上是未知的。杏仁核是参与情感调节的关键区域，并被牵涉到心理病理学的主要根源。内侧杏仁核（MEA）是杏仁核的主要细分，是侵略性和暴力的重要调节剂。先前的研究表明，在MEA上对神经元的高频刺激可以在未来的社会遭遇中增强侵略性，从而产生一种称为侵略性启动的现象。但是，内侧杏仁核介导侵略性及其在精神病疾病中的作用的确切机制需要进一步阐明。该PRAT奖学金提案的目的是确定MEA在侵略中的作用。我的初步结果表明，MEA内的谷氨酸能神经元以频率依赖性的方式对刺激做出反应，并且MEA可以在社交交互测试中调节侵略和暴力的表达。我的中心假设是，在MEA处的谷氨酸能突触增强可以侵略，从而导致社交互动期间的侵略性和暴力增加。首先，我计划确定使用光遗传学的高频光刺激（HFP）是否可以在社交互动测试中诱导攻击性启动。我将测试HFP是否使用体内电生理学在MEA诱导MEA突触增强，以及突触增强是否是通过使用低频光刺激（一种已知的用于诱导突触活动抑制抑郁症的方案）在HFPS后通过将HFPS定位突触来造成攻击行为的。其次，我将使用光遗传学在MEA在MEA上刺激脑部Raphe投影（羟色胺能神经元的主要原点），确定5-羟色胺在MEA调节攻击中的作用。最后，我将使用对体内的5-羟色胺释放机械和专门的传感器的遗传修饰来证实5-羟色胺在MEA调节攻击中的作用，旨在检测MEA处的5-羟色胺结合。该提案的成功完成将产生积极的翻译影响，因为针对MEA的预防性治疗策略可能有可能根据拟议研究的发现来遏制与精神疾病相关的过度侵略和暴力。