Metrics and tools for phenotyping sociality and development in animal models

描述（由申请人提供）： 影响数百万人的主要精神疾病，如精神分裂症和自闭症谱系障碍，有一个共同的症状，即受影响的人对社会线索没有适应性反应。这种统一的特征有助于人们关注理解社会性的行为、基因组、神经和发育基础的重要性，因为这些是这些毁灭性疾病表现的基础。现代生物医学方法来识别，分析和治疗这些疾病需要动物模型，而SBIR第一阶段的建议提出了一种新的方法来行为表型，揭示了小鼠社会性的发生和发展，并可以识别偏离正常发育。传统上，行为表型使用分类的措施，如探索，睡眠，焦虑，喂养，侵略等，我们的方法背离了这一传统，而是使用运动学措施的个人在一组上下文中。我们监控连续参数，如活动/不活动、位置、联系人、组大小和配置。我们有研究群体行为和群体中个体行为的实验室基础;现在可以将方法从实验室转移到市场。星星企业在设计和建造自动化、控制良好的啮齿动物栖息地（用于航天研究）方面有着出色的历史，并且可以将这种专长与其对小鼠和大鼠行为发育的知识联合收割机结合起来。我们将创建一个受控的测试环境，在该环境中，通过摄像机观察8、12和16日龄的幼鼠组。插件程序将自动分析20分钟的数字化视频样本，以检测社会性的开始，识别组中个体之间耦合活动的发展外观，并通过组作为单位显示的聚集体形成模式。还将在个体水平上对组进行分析。这些组和个体数据将使用更传统的表型分析方法与相同小鼠作为独立的青春期前青少年和成年小鼠的行为数据相关。因此，我们既可以开发我们的新方法，又可以将它们与传统指标进行交叉验证。最后，我们将进一步证明这些方法的灵敏度，功率和实际应用，通过使用它们与突变小鼠含有基因工程敲除缺陷已知影响社会性。公共卫生相关性：准确评估行为和社会性的发展对于开发和使用人类行为和精神障碍的动物模型至关重要。我们开发的行为协议和工具将促进行为障碍动物模型的创建，并在整个发展过程中对社会性进行准确可靠的测量，这将服务于心理健康研究界，包括实验室，制药和生物技术部门。 公共卫生相关性： 使用一种新的行为测量方法，我们将创建一种设备（硬件和软件），使科学家能够快速评估实验室小鼠是否正在发展正常的社会行为。这种生物医学评估工具是研究和治疗自闭症和精神分裂症等疾病的迫切需要，这些疾病涉及对社会线索反应的改变。

DESCRIPTION (provided by applicant): Major mental illnesses such as schizophrenia and the Autism Spectrum Disorder, which affect millions of people, share a common symptom, the afflicted people do not respond adaptively to social cues. This unifying feature has helped call attention to the importance of understanding the behavioral, genomic, neural, and developmental foundations of sociality, for these are the substrates on which these devastating diseases are manifested. Modern biomedical approaches to recognizing, analyzing, and remediating such disorders require animal models, and this SBIR Phase I proposal presents a novel approach to behavioral phenotyping that reveals the onset and development of sociality in mice, and can recognize deviations from normal development. Traditionally, behavioral phenotyping uses categorical measures, such as exploration, sleep, anxiety, feeding, aggression, etc. Our approach departs from this tradition and instead uses kinematic measures of individuals in a group context. We monitor continuous parameters such as activity/inactivity, position, contact, group size and configuration. We have the laboratory foundation for studying group behavior and individuals' behavior in the group; it is now possible to move the approach from the lab to the marketplace. Star Enterprises has an excellent history in designing and building automated, well-controlled habitats for rodents (used in spaceflight research) and can combine that expertise with its knowledge of behavioral development in mice and rats. We will create a controlled testing environment in which groups of infant mice are observed by video camera at 8-, 12-, and 16- days of age. Plug-in programs will automatically analyze 20-min digitized video samples to detect the onset of sociality, recognizing the developmental appearance of coupled activity among the individuals in the group, and by patterns of aggregon formation shown by the group as unit. Groups will also be analyzed at the level of the individual. These group and individual data will be correlated to behavioral data of the same mice as independent, pre-pubertal juveniles and as adults, using more traditional phenotyping measures. Thus, we can both develop our new methods and cross-validate them with conventional indices. Finally, we will further demonstrate the sensitivity, power, and practical application of these methods by using them with mutant mice containing genetically-engineered knock-out deficits known to affect sociality. PUBLIC HEALTH RELEVANCE: Accurately assessing the development of behavior and sociality is critical in developing and using animal models for human behavioral and mental disorders. The behavioral protocols and tools we develop will facilitate the creation of behavioral-disorder animal models and make possible accurate and reliable measures of sociality throughout development, which will serve the mental health research community, including the laboratory, pharmaceutical, and biotechnology sectors. PUBLIC HEALTH RELEVANCE: Using a novel approach to behavioral measurement, we will create an apparatus (hardware and software) that will enable scientists to rapidly assess whether laboratory mice are developing normal social behavior. Such biomedical assessment tools are urgently needed for studying and remediating illnesses such as autism and schizophrenia that involve alterations in responses to social cues.