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PLoS Biol. 2019 Jun 27;17(6):e3000346. doi: 10.1371/journal.pbio.3000346. eCollection 2019 Jun.

Fully automated leg tracking of Drosophila neurodegeneration models reveals distinct conserved movement signatures.

Author information

1
Bioinformatics Institute, Agency for Science, Technology and Research, Singapore.
2
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore.
3
Duke-NUS Graduate Medical School, Neuroscience and Behavioural Disorders, Singapore.
4
National University of Singapore, Department of Biological Sciences, Singapore.
5
National Neuroscience Institute, Singapore General Hospital, Singapore.
6
Singapore Institute for Neurotechnology (SiNAPSE), Singapore.
7
National University of Singapore, Department of Psychology, Singapore.
8
Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta, Canada.

Abstract

Some neurodegenerative diseases, like Parkinsons Disease (PD) and Spinocerebellar ataxia 3 (SCA3), are associated with distinct, altered gait and tremor movements that are reflective of the underlying disease etiology. Drosophila melanogaster models of neurodegeneration have illuminated our understanding of the molecular mechanisms of disease. However, it is unknown whether specific gait and tremor dysfunctions also occur in fly disease mutants. To answer this question, we developed a machine-learning image-analysis program, Feature Learning-based LImb segmentation and Tracking (FLLIT), that automatically tracks leg claw positions of freely moving flies recorded on high-speed video, producing a series of gait measurements. Notably, unlike other machine-learning methods, FLLIT generates its own training sets and does not require user-annotated images for learning. Using FLLIT, we carried out high-throughput and high-resolution analysis of gait and tremor features in Drosophila neurodegeneration mutants for the first time. We found that fly models of PD and SCA3 exhibited markedly different walking gait and tremor signatures, which recapitulated characteristics of the respective human diseases. Selective expression of mutant SCA3 in dopaminergic neurons led to a gait signature that more closely resembled those of PD flies. This suggests that the behavioral phenotype depends on the neurons affected rather than the specific nature of the mutation. Different mutations produced tremors in distinct leg pairs, indicating that different motor circuits were affected. Using this approach, fly models can be used to dissect the neurogenetic mechanisms that underlie movement disorders.

Conflict of interest statement

The authors have declared that no competing interests exist.

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