Dynamics of neural ensembles in emotional stress

描述（由申请人提供）：情绪压力影响着数百万人，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、细胞和遗传因素的认识有了很大的进步，但对情绪压力对神经元回路和神经元集合的影响知之甚少，而神经元回路和神经元集合是细胞病理和功能失调行为之间的中介。最近的进展使人们有可能第一次同时记录一个（或几个）大脑区域的许多神经元，并将新的分析方法应用于这些数据。这些进展现在准备对网络的动态行为产生新的见解。 我们建议同时记录哺乳动物大脑中与情绪应激和药物成瘾有关的部分的许多神经元，这些部分包括大脑被盖区（VTA），前额叶皮层（PFC）和伏隔核（NAc）。这些记录将在经历了社交失败（SD）行为协议的小鼠中进行，SD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的神经群体之间的动态行为和相互作用的影响，以检验SD诱导中脑边缘系统的动态网络特性变化（或至少与之相关）的假设。 这项研究与该领域以前的大多数工作不同，它结合了3个关键特征：1）它关注的不是单个神经元，而是相关大脑网络内的动态行为和相互作用; 2）它与动物的行为状态有关; 3）它将在体内进行，而不是体外。因此，它将提供新的信息，目前还没有，关于神经元的合奏，占据了一个关键的中间脑水平，单个神经元和整个动物行为之间。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。 公共卫生相关性：我们计划使用网络分析的现代方法来研究这一假设，即情绪压力是由大脑特定部位神经元群的动力学行为变化引起的。在暴露于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集合的群体行为。

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.