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MOTONEURON SYNAPTIC CURRENTS IN A DROSOPHILA SEIZURE MUTANT: COMPOSITIONAL ANALYSIS OF SPONTANEOUS RHYTHMIC CURRENT SYNAPTIC INPUT**

Abstract

Neuronal action potentials are generated by sodium channels, whose mutations underlie some forms of epilepsy. In the fruit fly (Drosophila), experimental and computational studies showed a relationship between sodium channels and seizure tendency in the family of seizure-sensitive mutants. In these studies, fly motoneurons were studied in isolation, though their synaptic inputs from premotor interneurons also varied between wildtype and mutant animals. Here, we aim to analyze spontaneous rhythmic current (SRC) inputs to these neurons to quantify their changes. We reproduced statistical analyses of each individual fly’s SRC peak widths and heights, as well as the intervals between SRCs, which found substantial differences between the CantonS wildtype and bang senseless (bss) mutant fruit flies. This study investigates underlying mechanism(s) of SRC generation that may cause these differences. We hypothesize that each SRC peak is caused by multiple excitatory postsynaptic currents (EPSCs) aggregating on the postsynaptic membrane. We aimed to characterize the properties of SRC generation via these underlying EPSCs. We first performed an exploratory qualitative analysis of the data to identify candidate SRCs for further quantitative analysis. For each SRC peak, we counted the number of apparent EPSCs, measured their magnitude, onset time, and time between EPSCs. Distributions of these metrics were compared between wildtype and mutants, and differences in mean values and variability were observed. We are searching for recurring patterns in the bss mutant that are distinct from wildtype fruit flies. Understanding these patterns can tell us about changes of circuit anatomy in mutants, including synaptic localization, morphology, strengths, and presynaptic action potential timing. In summary, it will help us understand synaptic contribution to seizure tendency in motor circuits, and allow further investigation of synaptic mechanisms by combining experimental and computational approaches.

Acknowledgements

Carlo Giachello and Richard Baines from University of Manchester, UK, provided the experimental data used in this work. GGC VPASA Seed Fund awarded to CG paid for student assistants who performed the work. We thank SST for paying for poster printing costs.

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