Highthroughput analysis of behavior for CNS applications

描述（由申请人提供）：本申请是针对SBIR征集中NIMH研究主题、神经科学和基础行为科学而提交的。该项目的目标是利用我们在小鼠行为药理学方面的专业知识，开发智能立方体，一种自动化的高通量行为，神经和生理分析系统，以缓解精神科药物和新突变体靶点发现和表征的瓶颈。智能立方体将包括创新的类似机器人的硬件和机器学习算法，以捕获和整合行为和生理状态。Smart Cube将以一个大型药理学数据库为中心，包括抗精神病药、抗焦虑药和其他已证明对人类有效的药物的药物概况，并将配备最先进的生物信息学，以提供新药治疗潜力的快速和准确的指标。智能立方体将促进当前的行为研究，药物发现，目标验证和快速表征突变小鼠的靶基因操作和诱变的努力。该快速通道提案的第一阶段将开发SmartCube，以自动分类小鼠行为，表征近系小鼠在不同药物干预（包括抗焦虑药和抗精神病药）影响下的行为反应，并在不受约束的小鼠中开发一种集成的无创心电图，该心电图将与自动行为分析同时运行。该提案的第二阶段，包括在随附的申请中，将进一步开发SmartCube功能，以自动分类行为，区分药物档案，并将开发Smart Base，一个大型药物档案集合，及其相关的生物信息学工具，以执行复杂的数据挖掘。

DESCRIPTION (provided by applicant): This application is submitted in response to the NIMH research topic, neuroscience and basic behavioral science in the SBIR solicitation. The goal of this project is to alleviate the bottleneck in psychiatric drug and target discovery and characterization of novel mutants by using our expertise in behavioral pharmacology in mice to develop Smart cube, an automated high-throughput system of behavioral, neurological and physiological analysis. Smart cube will comprise innovative robotic-like hardware, and machine-learning algorithms to capture and integrate behavioral and physiological states. Smart Cube will be centered around a large pharmacological database comprised of drug profiles of antipsychotics, anxiolytics and other drugs of proven efficacy in humans and will be equipped with state of the art bioinformatics to provide rapid and accurate indices of the therapeutic potential of novel drugs. Smart cube will facilitate current behavioral research, drug discovery, target validation and fast characterization of mutant mice from target gene manipulation and mutagenesis efforts. Phase I of this Fast Track proposal will develop SmartCube to automatically classify mouse behavior, to characterize the behavioral response of inbred strains of mice under the influence of different pharmacological interventions covering anxiolytic and antipsychotic drugs and to develop an integrated non-invasive ECG in unrestrained mice, which will run simultaneously with the automated analysis of behavior. Phase II of this proposal, included in the accompanying application, will further develop SmartCube capabilities to automatically classify behaviors, discriminate between drug profiles and will develop Smart Base, a large collection of drug profiles, and its associated bioinformatic tools to perform sophisticated data mining. Commercial Value: There is a great need to improve data collection and analysis of drug candidates and mutants. By providing a substantial increase in the throughput of behavioral testing (about 100 fold), and normative data with accompanying bioinformatic tools, the Smart cube system will facilitate current behavioral research (by performing known standard models faster and more reliably), CNS novel drug discovery (by screening whole drug libraries) and CNS target validation (by quickly characterizing novel mutant mice). Smart Base, with its cumulative normative data in inbred mice will have great impact and value.