Distinctions among electroconvulsion- and proconvulsant-induced seizure discharges and native motor patterns during flight and grooming: Quantitative spike pattern analysis in Drosophila flight muscles

Abstract

In Drosophila, high-frequency electrical stimulation across the brain triggers a highly stereotypic repertoire of spasms known as electroconvulsive seizures (ECS). The distinctive ECS spiking discharges manifest across the nervous system and can be stably assessed throughout the seizure repertoire in the large indirect flight muscles (DLMs). ECS discharges in DLMs have been extensively used to monitor seizure activities, notably in stress ( bang)-sensitive mutants. However, the relationships between ECS-spike patterns and native motor programs, including flight and grooming, are not known and their similarities and distinctions remain to be characterized. We employed quantitative spike pattern analyses including: 1) overall firing frequency, 2) spike timing between contralateral fibers, and 3) short-term variability in spike interval regularity (CV2) and instantaneous firing frequency (ISI-1) to reveal distinctions amongst ECS discharges, flight and grooming motor patterns. We then examined DLM firing phenotypes in well-established mutants in excitatory cholinergic (Cha), inhibitory GABAergic (Rdl) and electrical (ShakB) synaptic transmission. The results provide an initial glimpse on the vulnerability of individual motor patterns to perturbations of respective synaptic transmission systems. We found marked alterations of ECS discharge spike patterns in terms of either seizure threshold, spike frequency or spiking regularity. In contrast, no gross alterations during grooming and only a minor reduction of firing frequency during Rdl mutant flight were observed, suggesting a role for GABAergic modulation of flight motor programs. Picrotoxin (PTX), a known pro-convulsant that inhibits GABAA receptors, induced DLM seizure patterns that displayed some features, e.g. left-right coordination and ISI-1 range, that could be found in flight or grooming, but distinct from ECS discharges. Our results indicate that these quantitative techniques may be employed to reveal overlooked relationships among aberrant motor patterns and native DLM motor programs in genetic and pharmacological analyses of underlying cellular and neural circuit function.