An innovative instrument cluster for the integrative behavioral analysis of mouse mutants with perturbed neuronal connectivity

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Project Summary/Abstract: This S10 SIFAR grant application seeks funds to acquire an integrated instrument cluster to allow the sensitive, reliable, and unbiased neurobehavioral phenotyping of a range of mouse mutants from five major users modeling neurodegenerative conditions. These conditions arise from gene mutations in glial cells resulting in aberrant myelination and axon degeneration. The synergistic instrument cluster from Noldus Information Technology comprises the Noldus CatWalk XT, the Noldus ErasmusLadder, and the Noldus EthoVision XT open-field analysis system with custom configuration for simultaneous observation of up to eight animals. The CatWalk XT is a highly sensitive video-based automated gait analysis tool quantifying spatiotemporal characteristics of gait patterns along with paw print intensities and ambulatory velocities of mice. The ErasmusLadder is an automated system for the assessment of balance, coordination and locomotor capacity in mice. The EthoVision XT open-field video-tracking system allows automated monitoring and statistical analysis of activity, numerous ambulatory parameters, and stereotypic behavior in freely moving mice in batch-acquisition mode. The five investigators currently use conventional neurobehavioral methods (e.g., ink-based footprint, rotarod, pole-climb analysis) that are particularly laborious, susceptible to artefacts, prone to high variability, inherently subjective, and distressing to animals. The complementary instrument cluster will minimize these shortcomings, while in parallel increasing throughput via the automation and computerization of data acquisition. The equipment will also synergize with another instrument cluster accessible to the investigators for the specific analysis of sensory impairment. All instruments together will allow the investigators to comprehensively study sensorimotor alterations in their neurodegenerative mouse disease models. This will allow for the identification of more reliable neurobehavioral biomarkers, which will facilitate the measurement of disease progression and comparision of treatment groups. The base grant projects that support this proposal will greatly benefit from the additional capabilities of the tripartite instrument cluster as well as from enhanced rigor, reproducibility, and transparency.