Metrics and tools for phenotyping sociality and development in animal models

动物模型中社会性和发育表型分析的指标和工具

基本信息

批准号：
8126581
负责人：
JEFFREY R ALBERTS
金额：
$ 16.85万
依托单位：
STAR ENTERPRISES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-15 至 2013-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8126581
关键词：
Adolescent Adult Affect Age Aggressive behavior Animal Model Animal Testing Animals Anxiety Appearance Attention Behavior Behavior Disorders Behavior assessment Behavioral Biotechnology Breeding Central Nervous System Diseases Communities Computer software Coupled Cues Data Development Disease Drug Industry Economics Effectiveness Engineering Environment Foundations Goals Habitats Home environment House mice Human Image Individual Infant Infant Behavior Java Knock-out Knowledge Laboratories Link Measurement Measures Memory Mental Health Mental disorders Methods Metric Monitor Mus Mutant Strains Mice Oxytocin Pattern Pharmacologic Substance Phase Phenotype Plug-in Positioning Attribute Preclinical Drug Evaluation Protocols documentation Rattus Recording of previous events Research Rodent Sampling Schizophrenia Screening procedure Sleep Small Business Innovation Research Grant Social Behavior Social Development Space Flight Staging Symptoms Testing United States National Aeronautics and Space Administration Weaning autism spectrum disorder behavior test behavioral genomics design feeding indexing innovation kinematics mouse model mutant novel novel strategies open source practical application programs prototype relating to nervous system response social tool

项目摘要

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.

描述（由申请人提供）：影响数百万人的精神分裂症和自闭症谱系障碍等主要精神疾病有一个共同的症状，即患者无法对社会线索做出适应性反应。这种统一的特征有助于引起人们对理解社会性的行为、基因组、神经和发育基础的重要性的关注，因为这些是这些毁灭性疾病显现的基础。识别、分析和治疗此类疾病的现代生物医学方法需要动物模型，而这项 SBIR 第一阶段提案提出了一种新的行为表型分析方法，可以揭示小鼠社交性的发生和发展，并可以识别正常发育的偏差。传统上，行为表型分析使用分类测量，例如探索、睡眠、焦虑、进食、攻击性等。我们的方法背离了这一传统，而是使用群体环境中个体的运动学测量。我们监控连续参数，例如活动/不活动、位置、接触、群体规模和配置。我们拥有研究群体行为和群体中个体行为的实验室基础；现在可以将该方法从实验室转移到市场。 Star Enterprises 在设计和建造自动化、控制良好的啮齿类动物栖息地（用于航天研究）方面拥有悠久的历史，并且可以将其专业知识与小鼠和大鼠的行为发育知识相结合。我们将创建一个受控测试环境，在其中通过摄像机观察 8、12 和 16 天龄的幼鼠组。插件程序将自动分析 20 分钟的数字化视频样本，以检测社交性的开始，识别群体中个体之间耦合活动的发展表现，以及以群体为单位显示的聚合形成模式。还将在个人层面上对群体进行分析。使用更传统的表型分析方法，将这些组和个体数据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联。因此，我们既可以开发新方法，又可以与传统指数进行交叉验证。最后，我们将通过将这些方法用于含有已知会影响社交性的基因工程敲除缺陷的突变小鼠，进一步证明这些方法的敏感性、功效和实际应用。公共卫生相关性：准确评估行为和社交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，并在整个发育过程中实现准确可靠的社会性测量，这将为心理健康研究界（包括实验室、制药和生物技术领域）服务。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。迫切需要这种生物医学评估工具来研究和治疗自闭症和精神分裂症等涉及对社会线索反应改变的疾病。