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Discovery of molecular targets or compounds that alter neuronal function can lead to therapeutic advances that ameliorate age-related neurodegenerative pathologies. Currently, there is a lack of  in vivo  screening technologies for the discovery of compounds that affect the age-dependent neuronal physiology. Here, we present a high-throughput, microfluidic-based assay for automated manipulation and on-chip monitoring and analysis of stimulus-evoked calcium responses of intact  C. elegans  at various life stages. First, we successfully applied our technology to quantify the effects of aging and age-related genetic and chemical factors in the calcium transients of the ASH sensory neuron. We then performed a large-scale screen of a library of 107 FDA-approved compounds to identify hits that prevented the age-dependent functional deterioration of ASH. The robust performance of our assay makes it a valuable tool for future high-throughput applications based on  in vivo  functional imaging.

An automated compound screening for anti-aging effects on the function of C. elegans sensory neurons