Visuomotor deficiency in panx1a knockout zebrafish is linked to dopaminergic signaling

Sci Rep. 2020 Jun 12;10(1):9538. doi: 10.1038/s41598-020-66378-y.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Connexins / metabolism*
  • Dopamine / metabolism*
  • Dopamine D2 Receptor Antagonists / pharmacology
  • Haloperidol / pharmacology
  • Larva / drug effects
  • Larva / metabolism
  • Neurons / drug effects
  • Neurons / metabolism*
  • Receptors, Dopamine D2 / metabolism
  • Retina / drug effects
  • Retina / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Superior Colliculi / drug effects
  • Superior Colliculi / metabolism
  • Swimming / physiology
  • Vision, Ocular / drug effects
  • Vision, Ocular / physiology*
  • Zebrafish / metabolism*
  • Zebrafish Proteins / metabolism*

Substances

  • Connexins
  • Dopamine D2 Receptor Antagonists
  • Receptors, Dopamine D2
  • Zebrafish Proteins
  • panx1a protein, zebrafish
  • Haloperidol
  • Dopamine