Role(s) Of Pannexin1A/B In The Physiology Of The Zebrafish Visual System

Panx1 proteins are glycosylated integral membrane channels with unique conduction properties, functioning as an ATP channel and non-selective ion channel in different physiological pathways. In zebrafish, the mammalian Panx1 ohnologues, Panx1a and Panx1b, have distinct tissue expression patterns. We previously demonstrated that in the retina, Panx1a is localized in the horizontal cell layer and the ON/OFF ganglion cell layer, while Panx1b protein is present in the horizontal cell layer, ganglion cell layer, and in the end-feet of the Muller glia astrocytes. Here we investigated the optic flow response in the Panx1a-/- and Panx1b-/- 6dpf larvae utilizing molecular, systems, and behavioral assays. The RNA-seq analysis revealed broad regulation of genes involved in axon guidance, retinal axon guidance, astrocytes, axons, dendrites, and synapse, confirmed by RT-qPCR in the 3dpf and 6dpf Panx1a-/- and Panx1b-/-. We demonstrate that Panx1a-/- and Panx1b-/- display an inability to make a leftward and rightward directional motion in low light contrast conditions when exposed to the left and right moving gratings. We also show how the strategic localization of Panx1a and Panx1b in the habenula region modulates visually guided behavior. Lastly, Panx1a-/- and Panx1b-/- demonstrate the inability to generate functional saccades and display ocular motor deficiencies linked to potential neurological disorders. These findings suggest that Panx1 modulates the axonal growth in axon guidance pathfinding and together are interconnected to the habenula region, leading to synaptic plasticity of the retinal neural circuitry, and regulating visually guided locomotion in the zebrafish larvae.