How social behavior changes the brain

描述(申请人提供)：物理和社会环境塑造了所有动物从出生到成年的行为，产生的影响包括大脑的生理、细胞和分子变化。这项研究的长期目标是了解社交互动如何在行为、电路、神经元和基因水平上产生大脑变化。由于社会地位是社会制度中无处不在的元素，而社会地位可以极大地影响个人的生活质量，我们将分析地位的变化如何改变大脑结构和功能。我们将继续使用定义明确的硬骨鱼 FISH模型系统，我们在模拟自然事件的受控实验室条件下操纵动物的社会地位，并测量识别出的神经元的细胞和分子后果。我们之前已经证明，仅社会环境就可以使这些神经元的体积扩大或缩小约8倍，它们的树突范围和相互联系严重依赖于社会地位。我们将使用新的、互补的方法来发现行为是如何导致大脑中的这些变化的。1)我们将收集单个已识别神经元的内容，这些神经元在社会地位上升时对社会信号表现出较大的反应。我们将对这些神经元在社会进化过程中产生的基因转录本进行测序，并确定这些基因转录本，以确定导致神经元大小和连接性变化的基因表达模式的后遗症。我们将使用尖端的生物信息学工具分析转录，以确定导致大脑变化的分子表达架构。这一新的信息将揭示细胞和生理变化的分子基础及其在状态变化过程中的个体发育。2)我们将确定状态敏感神经元之间的功能变化和联系，以确定它们如何随着等级的社会信号而变化。我们研究的神经元必须整合社会和生理输入，使我们能够通过利用动物的两种极端表型-高状态和低状态以及动物在这些状态之间的转换来识别控制它们的路径。社会上升具有不同于社会血统的行为和分子特征，我们将利用这些特征来理解潜在控制机制的差异。我们知道，正在研究的神经元的功能在高状态动物中不同，在高状态动物中，它们同步发射，而在低状态动物中，它们异步发射。我们将确定在蜂窝和网络级别上解释这些不同功能的机制。优势等级是动物社会的核心组织机制，地位控制资源的获取，影响生存、健康和繁殖。然而，关于社会等级如何在生物学上改变大脑和行为，人们知之甚少。这里提出的实验结果应该为揭示指示状态的社会信号可以改变脊椎动物大脑细胞和电路的机制提供洞察力。由于社会地位在大多数物种中类似地调节社会行为，我们的结果将为理解这些强大的社会信号如何影响大脑提供有用的信息，这最终将对改善公共健康至关重要。

DESCRIPTION (provided by applicant): Physical and social environments shape the behavior of all animals from prenatal life through adulthood, producing effects that include physiological, cellular and molecular changes in the brain. The long-term objective of this research is to understand how social interactions produce changes in the brain at the level of behavior, circuitry, neurons and genes. Since social rank is a ubiquitous element in social systems and rank position can dramatically influence the quality of an individual's life, we will analyze how changes in status alter brain structure and function. We will continue using a well-defined teleost fish model system in which we manipulate the social status of animals under controlled laboratory conditions mimicking natural events and measure the cellular and molecular consequences in identified neurons. We have previously shown that the social environment alone can cause these neurons to enlarge or shrink ca. 8-fold in volume and that their dendritic extent and interconnections depend critically on social status. We will use novel, complementary approaches to discover how behavior causes these changes in the brain. 1) We will collect the contents of the single identified neurons that show a large response to social signals as they ascend in social status. We will sequence the gene transcripts produced in these neurons during social ascent and identify the gene transcripts to identify the sequelae of gene expression patterns responsible for changes in neuronal size and connectivity. We will analyze the transcripts using cutting edge bioinformatic tools to identify the architecture of molecular expression that causes changes in the brain. This novel information will reveal the molecular underpinnings of cellular and physiological changes and its ontogeny during status change. 2) We will identify functional changes and connections among the status sensitive neurons to identify how they change in response to social signals of rank. The neurons we study must integrate social and physiological inputs allowing us to identify pathways that control them by exploiting animals in their two extreme phenotypes, high status and low status as well as animals during transitions between these states. Social ascent has behavioral and molecular signatures distinct from social descent that we will use to understand the differences in the underlying mechanisms of control. We know that the neurons under study differ in their function between high status animals where they fire synchronously while in low status animals where they fire asynchronously. We will identify the mechanisms that account for these different functions at the cellular and network levels. Dominance hierarchies are a central organizing mechanism for animal societies and status is known to regulate access to resources and impact survival, health, and reproduction. Yet little is known about how social rank acts biologically to alter the brain and behavior. The results from the experiments proposed here should provide insights into mechanisms through which social signals that indicate status can change cells and circuits in vertebrate brains. Since social status regulates social behavior similarly in most species, our results will provide useful information for understanding how such potent social signals influence the brain that will ultimately be important for improving public health.