Semi-mobile C. elegans electrotaxis assay for movement screening and neural monitoring of Parkinson’s disease models

Abstract

Microfluidic-based electrotaxis assay is a quantitative movement phenotyping technique for behavioral studies on Caenorhabditis (C.) elegans which is currently space-consuming and limited for cell imaging. To address these limitations and show applications in Parkinson’s Disease (PD) studies, we introduce a novel microfluidic device to investigate the electrotaxis of semi-mobile C. elegans and image them immediately after the behavioral assay. The device consisted of an electrotaxis screening channel integrated with a perpendicular tapered microchannel that was used for worm tail or head trapping for electrotaxis screening and full-body immobilization for neuron imaging. Semi-mobile C. elegans with trapped tails demonstrated electrotaxis orientation towards the cathode. Interestingly, the response of head-trapped worms was also with the tail towards the cathode, implying the involvement of the mid-body to tail sensory neurons in electrotaxis. Moreover, semi-mobile C. elegans electrotaxis assay time is 3-folds shorter and 20-folds less space-consuming, compared to our freely moving assay. This makes the technique amenable to parallelization for the design of multi-worm electrotaxis and neuronal screening devices. For biological application to PD studies, we showed that human α-synuclein protein accumulation or exposure to neurotoxin 6-OHDA affected the electrotaxis phenotypes of semi-mobile worms. Moreover, L-DOPA rescued the electrotaxis of 6-OHDA exposed worms. The above behavioral effects of 6-OHDA and L-DOPA corresponded well with the degeneration of dopaminergic neurons and rescue of dopamine transmission, confirmed by on-chip fluorescent imaging. Our technique can be used for PD pathology studies and potentially for other neurobehavioral disorders modeled in C. elegans.