Cells (Nov 2022)

The Long-Term Pannexin 1 Ablation Produces Structural and Functional Modifications in Hippocampal Neurons

  • Carolina Flores-Muñoz,
  • Francisca García-Rojas,
  • Miguel A. Pérez,
  • Odra Santander,
  • Elena Mery,
  • Stefany Ordenes,
  • Javiera Illanes-González,
  • Daniela López-Espíndola,
  • Arlek M. González-Jamett,
  • Marco Fuenzalida,
  • Agustín D. Martínez,
  • Álvaro O. Ardiles

DOI
https://doi.org/10.3390/cells11223646
Journal volume & issue
Vol. 11, no. 22
p. 3646

Abstract

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Enhanced activity and overexpression of Pannexin 1 (Panx1) channels contribute to neuronal pathologies such as epilepsy and Alzheimer’s disease (AD). The Panx1 channel ablation alters the hippocampus’s glutamatergic neurotransmission, synaptic plasticity, and memory flexibility. Nevertheless, Panx1-knockout (Panx1-KO) mice still retain the ability to learn, suggesting that compensatory mechanisms stabilize their neuronal activity. Here, we show that the absence of Panx1 in the adult brain promotes a series of structural and functional modifications in the Panx1-KO hippocampal synapses, preserving spontaneous activity. Compared to the wild-type (WT) condition, the adult hippocampal neurons of Panx1-KO mice exhibit enhanced excitability, a more complex dendritic branching, enhanced spine maturation, and an increased proportion of multiple synaptic contacts. These modifications seem to rely on the actin–cytoskeleton dynamics as an increase in the actin polymerization and an imbalance between the Rac1 and the RhoA GTPase activities were observed in Panx1-KO brain tissues. Our findings highlight a novel interaction between Panx1 channels, actin, and Rho GTPases, which appear to be relevant for synapse stability.

Keywords