Steady-State Visually Evoked Potentials as Readouts for Abnormal GSK3β Activity in Drosophila

Abstract

Glycogen synthase kinase 3{beta} (GSK3{beta}) is important in neuronal development and maintenance, acting as a key regulator by controlling a broad range of cellular processes. The effects of its dysregulation range from impairments in axonal transport and energy metabolism to synapse formation and neuronal plasticity. However, how such cellular defects link to neuronal dysfunction is less well studied despite the links between GSK3{beta} and various neurological conditions, such as Alzheimers and Parkinsons diseases, mood disorders and autism. Here we used a steady-state visually evoked potential (SSVEP) assay with Drosophila to measure the effect of altering GSK3{beta} expression on neuronal function. We recorded SSVEPs from flies that expressed constitutively active or inactive (kinase-dead) variants of GSK3{beta} and showed that the visual responses of these flies differed from those of controls. This was indicated by increased response latency and reduced photoreceptor maximum response (Rmax). Importantly, multivariate pattern classification can distinguish between over- and inactive GSK3{beta} conditions. Taken together, we show that SSVEPs provide a powerful tool for future studies to link the molecular and cellular functions of GSK3{beta} with their effects on neuronal function. Furthermore, we introduce a monitoring protocol that ensures the quality of datasets to support future fly SSVEP experiments.