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The Journal of Neuroscience, August 30, 2006, 26(35):9006-9009; doi:10.1523/JNEUROSCI.2370-06.2006

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Brief Communications
Altered Hippocampal Synaptic Potentiation in P2X₄ Knock-Out Mice

Joan A. Sim,¹ Séverine Chaumont,² Jihoon Jo,³ Lauriane Ulmann,² Mark T. Young,¹ Kwangwook Cho,³ Gary Buell,⁴ R. Alan North,¹ and Francois Rassendren²

¹Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom, ²Department of Molecular Pharmacology, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5203, Institut National de la Santé et de la Recherche Médicale, Unité 661, Universités Montpellier 1 et 2, Montpelier 34396, France, ³Department of Biomedical Sciences, University of Sheffield, Sheffield S10 2TN, United Kingdom, and ⁴GlaxoWellcome Biomedical Research Institute, Plan-les-Ouates, Geneva 1228, Switzerland

Correspondence should be addressed to R. Alan North, Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK. Email: r.a.north{at}manchester.ac.uk

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.

Key words: LTP; P2X₄; knock-out; mice; hippocampus; ivermectin

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Received June 5, 2006; revised July 20, 2006; accepted July 20, 2006.

Correspondence should be addressed to R. Alan North, Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK. Email: r.a.north{at}manchester.ac.uk

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