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

Flores-Munoz, Carolina; Garcia-Rojas, Francisca; Perez, Miguel A.; Santander, Odra; Mery, Elena; Ordenes, Stefany; Illanes-Gonzalez, Javiera; Lopez-Espindola, Daniela; Gonzalez-Jamett, Arlek M.; Fuenzalida, Marco; Martinez, Agustin D.; Ardiles, Alvaro O.


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.

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Título según WOS: ID WOS:000887170300001 Not found in local WOS DB
Título de la Revista: CELLS
Volumen: 11
Número: 22
Editorial: MDPI
Fecha de publicación: 2022


Notas: ISI