A hallmark of many neurodegenerative diseases is progressive locomotive impairment. Animal models for movement have previously been used to study the foraging patterns of ants, seabirds and butterflies but are also studied for a plethora of diseases, including Parkinson’s disease, Alzheimer’s disease, Amyotrophic lateral sclerosis, and Fragile X syndrome. Given the genetic origin of many of these disorders, Drosophila melanogaster has proven to be a powerful model system in many cases. While studying the locomotion of adult flies is feasible, we use larval phenotypes to characterize mutations because of the simplicity of their movement patterns. Larvae also have the advantage over adults in that they allow for the study of diseases that are lethal before adulthood. We develop high throughput and sensitive methods to quantitatively describe larval crawling behavior without the need for setting ad hoc thresholds or imposing models. By tracking crawling larvae from wild-type strains and models of the Fragile-X mental retardation as well as Alzheimer’s disease models we were able to show that the mutants exhibit impaired crawling and that the magnitude of impaired crawling correlates with the severity of the mutation for the phenotypes that we quantify.

We are currently developing new methods to more fully describe larval crawling. While we studied models of neuronal disorders, the methods we develop lend themselves to characterizing locomotion in other diseases, especially in cases where the mutation leads to lethality at the pupal or adult stages, as well as locomotion in the presence of external cues. Further, the high throughput and sensitivity of the methods make them suitable for drug as well as genetic screens.