Dynamics of neural ensembles in emotional stress

描述(由申请者提供)：情绪压力影响着数百万人，在美国是一项与健康相关的主要支出。尽管我们对其中涉及的分子、细胞和遗传因素的知识有了很大的进步，但对情绪应激对神经元回路和神经系统的影响知之甚少，而神经回路和神经系统是细胞病理和功能失调行为之间的中介。最近的进展第一次使同时记录一个(或几个)大脑区域的多个神经元成为可能，并将新的分析方法应用于这些数据。这些进展现在有望对该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那些被证明与情绪应激和药物成瘾有关的部分的许多神经元，包括腹侧被盖区(VTA)、前额叶皮质(PFC)和伏核(NAC)。录音将在经历了社会失败(SD)行为协议的小鼠身上进行，这种行为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。我们将比较SD对这两种行为表型中神经种群的动态行为和相互作用的影响，以检验SD诱导(或至少与之相关)中边缘系统动态网络属性变化的假设。这项研究与这一领域的大多数以前的工作不同之处在于结合了三个关键特征：1)它不关注单个神经元，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，而不是在体外进行。因此，它将提供目前无法获得的关于神经元集合的新信息，这些神经元集合占据了大脑中单个神经元和整个动物行为之间的关键中间水平。因此，它将为涉及情绪压力的大脑机制提供新的线索，并将为评估药物的有效性提供新的方法。 与公共健康相关：我们计划使用现代网络分析方法来调查这一假设，即情绪应激是由大脑特定部分神经元组的动态行为变化引起的。在接触到其他老鼠的攻击性行为后，一些老鼠表现出情绪压力的迹象，而另一些老鼠则保持着韧性。我们将比较应激小鼠和弹性小鼠的网络特性，以发现情绪应激如何改变它们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.