Integrated Gait and Pose Analysis Utilizing Computer Vision for Parkinsonian Behavioral Phenotyping in Mice

Area of Science:

• Neuroscience
• Biomedical Engineering
• Animal Models

Background:

• Synucleinopathies, including Parkinson's disease, exhibit motor symptoms that manifest late in disease progression.
• Early, subclinical circuit dysfunction occurs before overt parkinsonism, necessitating sensitive preclinical motor endpoints.
• The mThy1-α-synuclein line 61 (L61-Tg) mouse model displays progressive synucleinopathy and early circuit dysfunction.

Purpose of the Study:

• To develop and validate objective, sensitive motor endpoints for preclinical synucleinopathy research.
• To integrate CatWalk XT gait analysis with markerless pose estimation for comprehensive motor phenotyping.
• To assess the utility of combined gait and pose analysis in detecting early motor deficits in L61-Tg mice.

Main Methods:

• Utilized an integrated pipeline combining CatWalk XT gait analysis and DeepLabCut markerless pose estimation on videos from L61-Tg and non-transgenic mice.
• Assessed two cohorts of mice at 12 and 18 months of age.
• Quantified mediolateral instability using tail-base lateral position variance and analyzed hind base of support.

Main Results:

• L61-Tg mice showed significantly increased tail-base lateral variance at both 12 and 18 months.
• CatWalk analysis identified six genotype-dependent gait parameters at 12 months and a progressive increase in hind base of support at 18 months.
• Both hind base of support and tail-base lateral instability provided high discrimination between genotypes and demonstrated synergistic effects.

Conclusions:

• The combined gait and pose estimation strategy offers scalable and interpretable endpoints for preclinical Parkinson-like phenotyping.
• This integrated approach enhances the sensitivity and objectivity of motor endpoint assessment in synucleinopathy models.
• The findings support the use of this pipeline for early detection of motor deficits and for evaluating therapeutic interventions in Parkinson's disease research.