Effects of Constitutive and Acute Connexin 36 Deficiency on Brain-Wide Susceptibility to PTZ-Induced Neuronal Hyperactivity

Title: Effects of Constitutive and Acute Connexin 36 Deficiency on Brain-Wide Susceptibility to PTZ-Induced Neuronal Hyperactivity

Journal: Front. Mol. Neurosci., (2021) 13:587978

Link: https://doi.org/10.3389/fnmol.2020.587978

Comments:

Connexins are transmembrane proteins in the hemichannels that facilitate the intercellular communication across the gap junctions. The authors utilized mitogen-activated protein kinase (MAP) mapping to quantify neuronal activity across the whole brain to understand the brain region, dose and exposure time dependent relationship of PTZ based seizure model of zebrafish. MAP based neuronal activity marker uses immunostaining of total extracellular signal-regulated kinase (tERK) and phosphorylated ERK (pERK). pERK was an interesting approach and has quick onset of expression when compared to the traditional method using immediate early gene expression like c-Fos which takes longer induction time of around 2 hours. Using cx35.5 mutant zebrafish (which shows complete loss of the Cx35.5 isoforms of Connexin 36 (Cx36) and a significant reduction in the three other Cx36 isoforms) the authors showed altered susceptibility to PTZ-induced neuronal hyperactivity in a region-specific manner. This work supports the possibility that Cx36, a key structural component of the electrical synapse could be a potential target for therapeutic intervention in seizure.