Integrins Bidirectionally Regulate the Efficacy of Inhibitory Synaptic Transmission and Control GABAergic Plasticity
Grzegorz Wiera, Patrycja Brzdąk, Anna Maria Lech, Katarzyna Lebida, Jadwiga Jabłońska, Przemysław Gmerek, Jerzy W. Mozrzymas
Abstract
Epilepsy, schizophrenia, and anxiety are just a few medical conditions associated with dysfunctional inhibitory synaptic transmission. GABAergic synapses are known for their extraordinary susceptibility to modulation by endogenous factors and exogenous pharmacological agents. We describe here that integrins, adhesion proteins, play a key role in the modulation of inhibitory synaptic transmission. Specifically, we show that interference with integrin-dependent adhesion results in a variety of effects on the amplitude and frequency of GABAergic mIPSCs. Activation of β3 subunit-containing integrins induces inhibitory long-term depression, whereas the inhibition of β1 subunit-containing integrins induces iLTP. Our results unveil an important mechanism controlling synaptic inhibition, which opens new avenues into the usage of integrin-aimed pharmaceuticals as modulators of GABAergic synapses.