NEUROPHYSIOLOGY DATABASE OF INBRED MUTANT STRAINS

对小鼠近交系中确定的基因突变进行神经感觉评估是大脑和行为遗传分析的重要组成部分，也是评估药物治疗反应的关键工具。该项目的具体目标是开发和实施快速、高通量的电生理调查方法和一个开放的电子参考数据库，该数据库包含对自交系和突变体的标准化神经生理评估，包括清醒和行为小鼠的表面皮质脑电图、深度记录海马脑电图、视觉诱发电位和脑干听觉诱发电位。具体目标包括：1)技术组件，涉及开发用于慢性植入的更轻重量，更高电极密度的硬膜外和深度电极阵列。目前的技术将通过实施非创伤性、灵活的零插入力微连接器和校准的、特定区域的放置而得到加强。电生理数据将以数字方式采集，并结合分屏数字视频，实现通过互联网快速显示和在线共享的程序。2)定量数据分析组件，包括应用自发皮质电图和平均诱发电位的光谱和拓扑分析来编目自交系。3)表型筛选标准组成部分：将进行多参数研究，以评估与昼夜节律、一天中的时间和重复采样相关的变异性；年龄与行为状态；并表征技术工件，以优化所有基础和诱发数据样本的可重复性和有效性。4)教学部分：所有的技术将被标准化，定量分析和筛选的方法将被详细说明，并传播给所有NIH诱变中心和其他实验室采用。5)科学数据库和信息学组件：所有近交系的原始和分析数据的存储和检索将存储在一个开放的参考数据库中，可以通过互联网上的专门网站访问，并发布总结结果。在验证之后，针对个别研究者筛选的特定突变体的数据将在研究后不久获得同意。来自多个中心的自交系和定义突变的参考数据将在一个公共访问数据库中启动，允许实验室随后存储、检索甚至重新分析来自所有中心筛选的小鼠的参考数据。将与其他数据库创建超链接。该项目将提供规范性数据框架，用于比较近亲繁殖小鼠品系和定义基因突变的电生理、行为和实验药理学。

Neurosensory evaluation of defined gene mutations in inbred strains of mice is an essential component of the genetic analysis of brain and behavior, and a critical tool in assessing responses to pharmacological treatment. The specific aims of this project are to develop and implement rapid, high-throughput electrophysiologic survey methods and an open electronic reference database containing standardized neurophysiological evaluation of inbred strains and mutants, including surface cortical EEG, depth-recorded hippocampal EEG, visual evoked potentials, and brainstem auditory evoked potentials, in awake and behaving mice. The specific aims include: 1) A technological component, involving development of lighter-weight, higher- electrode density epidural and depth electrode arrays for chronic implantation. Current techniques will be enhanced by implementation of non-traumatic, flexible zero-insertion force microconnectors and calibrated, region-specific placement. Electrophysiological data will be acquired digitally, combined with split-screen digital video, and programs to rapidly display and share online over the internet will be implemented. 2) A quantitative data analysis component, involving application of spectral and topological analysis of spontaneous electrocorticograms and averaged evoked potentials to catalog inbred strains. 3) A phenotypic screening standards component: Multi-parametric studies will be performed to assess variability related to diurnal rhythm, time of day, and repeated sampling; age and behavioral state; and characterization of technical artifacts in order to optimize reproducibility and validation of all basal and evoked data samples. 4) An instructional component: all technqiues will be standardized and methods for quantitative analysis and screening will be fully detailed and disseminated for adoption by all NIH mutagenesis centers and other laboratories. 5) A scientific database and informatics component: Storage and retrieval of all raw and analyzed data on inbred strains will be deposited in an open reference database accessible from a dedicated website over the Internet, and summary results published. Following validation, data on specific mutants screened for individual investigators will be available by consent shortly after study. The reference data on inbred strains and defined mutants from multiple centers will be initiated in a common access database, allowing laboratories to subsequently deposit, retrieve, and even reanalyze reference data from mice screened by all centers. Hyperlinks will be created with other databases. This project will provide the framework for normative data to be used for comparative electrophysiological, behavioral and experimental pharmacology on inbred mouse strains and defined gene mutations.