Altered Hippocampal Synaptic Potentiation in P2X4Knock-Out Mice

Abstract

P2X₄ purinergic receptors are calcium-permeable, ATP-activated ion channels. In the CA1 area of the hippocampus, they are located at the subsynaptic membrane somewhat peripherally to AMPA receptors. The possible role of P2X₄ receptors has been difficult to elucidate because of the lack of selective antagonists. Here we report the generation of a P2X₄ receptor knock-out mouse and show that long-term potentiation (LTP) at Schaffer collateral synapses is reduced relative to that in wild-type mice. Ivermectin, which selectively potentiates currents at P2X₄, was found to increase LTP in wild-type mice but had no effect in P2X₄ knock-out mice. We suggest that calcium entry through subsynaptic P2X₄ receptors during high-frequency stimulation contributes to synaptic strengthening.