Abnormal whisker movements in the 3xTg-AD mouse model of Alzheimer's disease.

Alzheimer's disease is the most frequent form of dementia in elderly people. The triple transgenic (3xTg-AD) mouse model of Alzheimer's Disease is important in biomedical research as these mice develop both neuropathological and behavioural phenotypes. However, their behavioural phenotype is variable, with findings depending on the specific task, as well as the age and sex of the mice. Whisker movements show motor, sensory and cognitive deficits in mouse models of neurodegenerative disease. Therefore, we examined whisker movements in 3, 12.5 and 17-month-old female 3xTg-AD mice and their B6129S/F2 wildtype controls. Mice were filmed using a high-speed video camera (500 fps) in an open arena during a novel object exploration task. Genotype and age differences were found in mice exploring the arena prior to object contact. Prior to whisker contact, the 3-month-old 3xTg-AD mice had smaller whisker angles compared with the wildtype controls, suggesting an early motor phenotype in these mice. Pre-contact mean angular position at 3 months and whisking amplitude at 17 months of age differed between the 3xTg-AD and wildtype mice. During object contact 3xTg-AD mice did not reduce whisker spread as frequently as the wildtype mice at 12.5 and 17 months, which may suggest sensory or attentional deficits. We show that whisker movements are a powerful behavioural measurement tool for capturing behavioural deficits in mouse models that show complex phenotypes, such as the 3xTg-AD mouse model.

Recommendations for measuring whisker movements and locomotion in mice with sensory, motor and cognitive deficits.

BACKGROUND: Previous studies have measured whisker movements and locomotion to characterise mouse models of neurodegenerative disease. However, these studies have always been completed in isolation, and do not involve standardized procedures for comparisons across multiple mouse models and background strains. NEW METHOD: We present a standard method for conducting whisker movement and locomotion studies, by carrying out qualitative scoring and quantitative measurement of whisker movements from high-speed video footage of mouse models of Amyotrophic Lateral Sclerosis, Huntington's disease, Parkinson's disease, Alzheimer's disease, Cerebellar Ataxia, Somatosensory Cortex Development and Ischemic stroke. RESULTS: Sex, background strain, source breeder and genotype all affected whisker movements. All mouse models, apart from Parkinson's disease, revealed differences in whisker movements during locomotion. R6/2 CAG250 Huntington's disease mice had the strongest behavioural phenotype. Robo3R3-5-CKO and RIM-DKOSert mouse models have abnormal somatosensory cortex development and revealed significant changes in whisker movements during object exploration. COMPARISON WITH EXISTING METHOD(S): Our results have good agreement with past studies, which indicates the robustness and reliability of measuring whisking. We recommend that differences in whisker movements of mice with motor deficits can be captured in open field arenas, but that mice with impairments to sensory or cognitive functioning should also be filmed investigating objects. Scoring clips qualitatively before tracking will help to structure later analyses. CONCLUSIONS: Studying whisker movements provides a quantitative measure of sensing, motor control and exploration. However, the effect of background strain, sex and age on whisker movements needs to be better understood.

Description and validation of the LocoWhisk system: Quantifying rodent exploratory, sensory and motor behaviours.

BACKGROUND: Previous studies have demonstrated that analysing whisker movements and locomotion allows us to quantify the behavioural consequences of sensory, motor and cognitive deficits in rodents. Independent whisker and feet trackers exist but there is no fully-automated, open-source software and hardware solution, that measures both whisker movements and gait. NEW METHOD: We present the LocoWhisk arena and new accompanying software (ARTv2) that allows the automatic detection and measurement of both whisker and gait information from high-speed video footage. RESULTS: We demonstrate the new whisker and foot detector algorithms on high-speed video footage of freely moving small mammals, and show that whisker movement and gait measurements collected in the LocoWhisk arena are similar to previously reported values in the literature. COMPARISON WITH EXISTING METHOD(S): We demonstrate that the whisker and foot detector algorithms, are comparable in accuracy, and in some cases significantly better, than readily available software and manual trackers. CONCLUSION: The LocoWhisk system enables the collection of quantitative data from whisker movements and locomotion in freely behaving rodents. The software automatically records both whisker and gait information and provides added statistical tools to analyse the data. We hope the LocoWhisk system and software will serve as a solid foundation from which to support future research in whisker and gait analysis.