Dynamics of neural ensembles in emotional stress

情绪压力下神经系统的动态

• 批准号: 8093285
• 负责人: EHUD KAPLAN
• 金额: $ 33.74万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-11 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8093285
• 关键词: Address; Affect; Aggressive behavior; Amplifiers; Anesthesia procedures; Animal Behavior; Animal Model; Animals; Area; Behavior; Behavior Control; Behavioral; Brain; Brain Part; Cell physiology; Cells; Computers; Control Animal; Data; Disease; Drug Addiction; Effectiveness; Electrodes; Emotional Stress; Emotional disorder; Evolution; Future; Genetic; Health; In Vitro; Individual; Knowledge; Lead; Light; Measures; Mediator of activation protein; Mental Depression; Methods; Molecular; Monitor; Mus; Neurons; Nucleus Accumbens; Outcome; Pathway Analysis; Pattern; Pharmaceutical Preparations; Pharmacotherapy; Phenotype; Population; Predisposition; Prefrontal Cortex; Property; Protocols documentation; Psychotropic Drugs; Research; Research Personnel; Seeds; Social Interaction; Stress; Testing; Time; Ventral Tegmental Area; Wireless Technology; Work; cellular pathology; cost; design; directed attention; functional group; in vivo; insight; mesolimbic system; relating to nervous system; research study; social

DESCRIPTION (provided by applicant): Emotional stress affects millions of people, and is a major health-related expense in the US. Despite great advances in our knowledge of the molecular, cellular and genetic factors that are involved, precious little is known about the effects of emotional stress on the neuronal circuits and ensembles that are the mediators between the cellular pathologies and the dysfunctional behavior. Recent advances have made it possible, for the first time, to record simultaneously from many neurons in one (or several) brain areas, and to apply new analysis methods to such data. These advances are now poised to produce new insights into the network's dynamical behavior. We propose to record simultaneously from many neurons in those parts of the mammalian brain that have been shown to be involved in emotional stress and drug addiction, which include the Ventral Tegmental Area (VTA), Prefrontal Cortex (PFC) and Nucleus Accumbens (NAc). The recordings will be carried out in mice that have been subjected to the behavioral protocol of social defeat (SD), which is used as an animal model for emotional stress, and which results in two distinct behavioral phenotypes, called resilient and susceptible. We shall compare the effect of SD on the dynamical behavior and interactions among the neural populations in these two behavioral phenotypes, to test the hypothesis that SD induces (or is at least correlated with) changes in the dynamical network properties of the mesolimbic system. This research differs from most of the previous work in this area in combining 3 crucial features: 1) It focuses not on individual neurons, but on the dynamical behavior and interactions within the relevant brain networks; 2) It is related to the behavioral state of the animal, and 3) It will be carried out in vivo, rather than in vitro. It will therefore provide new information, not currently available, about the neuronal ensembles that occupy a critical intermediate brain level, between single neurons and whole animal behavior. It will thus shed new light on the brain mechanisms that are involved in emotional stress, and will provide new ways to assess the effectiveness of drugs. PUBLIC HEALTH RELEVANCE: We plan to use modern methods of network analysis to investigate the hypothesis that emotional stress is caused by changes in the dynamical behavior of neuronal groups in specific parts of the brain. After being exposed to aggressive behavior from other mice, some mice show signs of emotional stress, while others remain resilient. We shall compare the network properties of the stressed and resilient mice to discover how the emotional stress changes the group behavior of their neuronal ensembles.

描述（由申请人提供）：情绪压力影响数百万人，是美国一项主要的健康相关费用。尽管我们对所涉及的分子、细胞和遗传因素的了解取得了巨大进步，但我们对情绪压力对神经元回路和神经元群的影响知之甚少，而神经元回路和神经元群是细胞病理学和功能失调行为之间的中介。最近的进展首次使得同时记录一个（或多个）大脑区域中的许多神经元成为可能，并对这些数据应用新的分析方法。这些进步现在有望为网络的动态行为带来新的见解。 我们建议同时记录哺乳动物大脑中那些已被证明与情绪压力和药物成瘾有关的部分的许多神经元，其中包括腹侧被盖区（VTA）、前额皮质（PFC）和伏隔核（NAc）。这些记录将在接受社交失败（SD）行为协议的小鼠中进行，该协议被用作情绪压力的动物模型，并导致两种不同的行为表型，称为弹性和易感性。我们将比较 SD 对这两种行为表型中神经群体之间的动态行为和相互作用的影响，以检验 SD 诱导（或至少相关）中脑边缘系统动态网络特性变化的假设。 这项研究与该领域之前的大多数工作不同，它结合了三个关键特征：1）它不关注单个神经元，而是关注相关大脑网络内的动态行为和相互作用； 2）与动物的行为状态有关，3）将在体内进行，而不是体外。因此，它将提供目前无法获得的关于神经元群的新信息，这些神经元群占据单个神经元和整个动物行为之间的关键中间大脑水平。因此，它将为涉及情绪压力的大脑机制提供新的线索，并将提供评估药物有效性的新方法。 公共健康相关性：我们计划使用现代网络分析方法来研究以下假设：情绪压力是由大脑特定部位神经元群动态行为的变化引起的。在受到其他小鼠的攻击行为后，一些小鼠表现出情绪压力的迹象，而另一些小鼠则保持弹性。我们将比较压力小鼠和弹性小鼠的网络特性，以发现情绪压力如何改变其神经元群的群体行为。