A locomotor assay reveals deficits in heterozygous Parkinson's disease model and proprioceptive mutants in adult Drosophila

被引:25
作者
Aggarwal, Aman [1 ,2 ]
Reichert, Heinrich [3 ]
VijayRaghavan, K. [1 ]
机构
[1] Tata Inst Fundamental Res, Natl Ctr Biol Sci, Bangalore 560065, Karnataka, India
[2] Manipal Acad Higher Educ, Manipal 576104, Karnataka, India
[3] Univ Basel, Biozentrum, CH-4056 Basel, Switzerland
关键词
Drosophila; climbing; locomotion; Parkinson's; geotaxis; GRAVITY; GEOTAXIS; BEHAVIOR; GENETICS;
D O I
10.1073/pnas.1807456116
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Severe locomotor impairment is a common phenotype of neurode-generative disorders such as Parkinson's disease (PD). Drosophila models of PD, studied for more than a decade, have helped in understanding the interaction between various genetic factors, such as parkin and PINK1, in this disease. To characterize locomotor behavioral phenotypes for these genes, fly climbing assays have been widely used. While these simple current assays for locomotor defects in Drosophila mutants measure some locomotor phenotypes well, it is possible that detection of subtle changes in behavior is important to understand the manifestation of locomotor disorders. We introduce a climbing behavior assay which provides such fine-scale behavioral data and tests this proposition for the Drosophila model. We use this inexpensive, fully automated assay to quantitatively characterize the climbing behavior at high parametric resolution in 3 contexts. First, we characterize wild-type flies and uncover a hitherto unknown sexual dimorphism in climbing behavior. Second, we study climbing behavior of heterozygous mutants of genes implicated in the fly PD model and reveal previously unreported prominent locomotor defects in some of these heterozygous fly lines. Finally, we study locomotor defects in a homozygous proprioceptory mutation (Trp-gamma(1)) known to affect fine motor control in Drosophila. Moreover, we identify aberrant geotactic behavior in Trp-gamma(1) mutants, thereby opening up a finer assay for geotaxis and its genetic basis. Our assay is therefore a cost-effective, general tool for measuring locomotor behaviors of wild-type and mutant flies in fine detail and can reveal subtle motor defects.
引用
收藏
页码:24830 / 24839
页数:10
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