HIGHTHROUGHPUT ANALYSIS OF BEHAVIOR FOR CNS APPLICATIONS

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.