Ontogeny of sociality in a mouse model

描述(申请人提供)：社会性是一种行为维度，它使生物体与他人，特别是与自己物种的其他成员联系在一起，并提供代表群体隶属、配偶选择、父母行为、信息交换和利他主义等现象的所有重要互动。社会性既存在于个体层面，也存在于群体层面，两者都有一个既可分离又相互关联的发展过程。这项拟议的研究旨在定义和确定小鼠的社会性的开始，小鼠是为美国国立卫生研究院路线图服务的主要“模式”哺乳动物。我们提出了一项研究计划，将使用观察性、经验性、生理学、基因组和神经内分泌方法来识别幼鼠幼崽首次表达社会反应的时间，它们的社会行为是如何针对其他小鼠的，以及管理个人和群体行为的规则。拟议研究的具体目标包括：为C57品系的实验室小鼠建立一套代表其早期社会行为的群体和个人现象；创建关于个人和群体新陈代谢努力的参数基础数据，以便将接触行为的生理(特别是热)影响与非热、社会联系分开。在整个研究过程中，我们还将引用选定的基因工程(“敲除”)小鼠来测试关于皮肤温度感觉和中枢催产素在子女行为形成和表达中的作用的具体假设。我们将分析个体发展中的社会性，特别是嗅觉偏好的发展，这些偏好会对个体做出特定的孝顺反应。新的“嗅觉同位素”将被用来发现发育决定因素，这些决定因素来自与母亲和幼崽在巢中的特定经历。这些构成了对自然经验如何在行为发展中充当学习机制的探讨。最后，我们将提供C57母鼠母体行为的全局和具体测量，因为这些数据和它们的方法是完整分析遗传和其他对发育的实验贡献所必需的，因为这些操纵中的许多可以通过改变母体行为来操作。将研究母亲对基因改变的猫砂和个体的反应，以检验这些想法。公共卫生相关性：这项拟议研究的重要性将首先体现在它将社会行为的客观和定量指标与大脑中基因表达和内分泌过程的现代知识联系起来。老鼠模型中的这种联系将为测试多种形式的精神疾病的治疗提供必要的研究工具，例如自闭症谱系障碍和精神分裂症，这些疾病涉及社会过程和社会反应的根本中断。

DESCRIPTION (provided by applicant): Sociality is the dimension of behavior that brings organisms into association with others, especially other members of one's species and affords all the vital interactions that represent phenomena such group affiliation, mate choice, parental behaviors, information exchange, and altruism. Sociality exists on the level of the individual and on the level of the group, and each has a separable, but interrelated development. The proposed research is designed to define and identify the onset of sociality in Mus musculus, the major "model" mammal serving the NIH Roadmap. We propose a program of research that will employ observational, experiential, physiological, genomic and neuroendrocrine approaches to recognizing when social responses are first expressed by infant mouse pups, how their social behavior becomes directed at other mice, and the rules that govern individual and group behavior. The Specific Aims of the proposed research include: establishing for the C57 strain of laboratory mouse, a set of group and individual phenomena that represent their early social behaviors; creating parametric, foundation data on metabolic effort by individuals and groups so that physiological (especially thermal) effects of contact behavior can be separated from non-thermal, social affiliations. Throughout the research, we will also invoke selected genetically-engineered ("knock out") mice to both test specific hypotheses concerning the roles of cutaneous temperature sensation and the central oxytocin in the formation and expression of filial behavior. Sociality in individual development will be analyzed, especially the development of olfactory preferences that make specific individual's filial responses. Novel "olfactory isotopes" will be used to discover the developmental determinants that derive from specific experiences in the nest with mother and littermates. These constitute probes into how natural experiences serve as learning mechanisms in behavioral development. Finally, we will provide both global and specific measures of maternal behavior in the C57 mother mouse, for these data and their methods are needed for complete analyses of genetic and other experimental contributions to development, since many of these manipulations can operate by altering in maternal behavior. Maternal responses to genomically-altered litters and individuals will be studied to test these ideas. PUBLIC HEALTH RELEVANCE: The importance of the proposed research will be seen first in its contribution to linking objective and quantitative metrics of social behavior to modern knowledge of gene expression and endocrine processes in the brain. This linkage in a mouse model will provide a needed research tool for testing treatments for the many forms of mental illness, such as the autism spectrum disorders and schizophrenia, that involve fundamental disruptions in social processes and social responses.