Multimodal behavioral aging profiles in Drosophila models of human neurodegenerative diseases

Abstract

Neurodegenerative diseases are highly disruptive, and they play critical roles in end of life behavior. Much of the literature on neurodegenerative disease focuses on biochemical and physiological decline with age, but fails to rigorously categorize the vast set of behavioral changes that occur. In order to gain a more complete understanding of neurodegeneration, we use a data-driven approach to construct a space that describes the complete set of behaviors demonstrated by Drosophila melanogaster. By examining differences in the types of behaviors and rate of aging in three neurodegenerative models, we observe non-monotonic aging profiles that differ across the mutants. Closer examination of individual behaviors in these profiles indicates that behaviors do not necessarily covary with age, nor are they affected by each neurodegenerative disease in the same manner. This finding emphasizes the importance of studying nuanced behavioral change at a more granular level, since neurodegeneration gives rise to non-monotonic behavioral aging profiles that show distinct modular patterns.