Abstract

Pannexin 1 (Panx1) forms ATP-permeable membrane channels that play roles in the nervous system. The analysis of roles in both standard and pathological conditions benefits from a model organism with rapid development and early onset of behaviors. Such a model was developed by ablating the zebrafish panx1a gene using TALEN technology. Here, RNA-seq analysis of 6 days post fertilization larvae were confirmed by Real-Time PCR and paired with testing visual-motor behavior and in vivo electrophysiology. Results demonstrated that loss of panx1a specifically affected the expression of gene classes representing the development of the visual system and visual processing. Abnormal swimming behavior in the dark and the expression regulation of pre-and postsynaptic biomarkers suggested changes in dopaminergic signaling. Indeed, altered visuomotor behavior in the absence of functional Panx1a was evoked through D1/D2-like receptor agonist treatment and rescued with the D2-like receptor antagonist Haloperidol. Local field potentials recorded from superficial areas of the optic tectum receiving input from the retina confirmed abnormal responses to visual stimuli, which resembled treatments with a dopamine receptor agonist or pharmacological blocking of Panx1a. We conclude that Panx1a functions are relevant at a time point when neuronal networks supporting visual-motor functions undergo modifications preparing for complex behaviors of freely swimming fish.

Highlights

  • Pannexin 1 (Panx1) forms ATP-permeable membrane channels that play roles in the nervous system

  • In vivo electrophysiological recording of local field potentials (LOF) from the larval optic tectum in a region receiving input from the retina demonstrated that the dynamic transition from low to higher-frequency brain waves in light and darkness was compromised in panx1a−/− larvae

  • The four base pair deletion caused a frameshift at amino acid 195, resulting in a premature stop codon leading to truncated 201-amino-acid protein, lacking most of the 416 amino acid long Panx1a protein sequence including two transmembrane regions and the entire carboxyterminal domain (Fig. 1e)

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Summary

Introduction

Pannexin 1 (Panx1) forms ATP-permeable membrane channels that play roles in the nervous system. The analysis of roles in both standard and pathological conditions benefits from a model organism with rapid development and early onset of behaviors Such a model was developed by ablating the zebrafish panx1a gene using TALEN technology. In vivo electrophysiological recording of local field potentials (LOF) from the larval optic tectum in a region receiving input from the retina demonstrated that the dynamic transition from low to higher-frequency brain waves in light and darkness was compromised in panx1a−/− larvae. This phenotype was reproduced by pharmacological blocking of Panx1a, or by treatment with the D1/D2 receptor agonist apomorphine. This research delivers a novel association between Panx1a in the integration of sensory-motor behavior through modulation of dopaminergic signaling

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