title: ATP P2X receptors downregulate AMPA receptor trafficking and postsynaptic efficacy in hippocampal neurons.
abstract: P2X receptors (P2XRs) are ATP-gated cation channels widely expressed in the brain where they mediate action of extracellular ATP released by neurons or glia. Although purinergic signaling has multiple effects on synaptic transmission and plasticity, P2XR function at brain synapses remains to be established. Here, we show that activation of postsynaptic P2XRs by exogenous ATP or noradrenaline-dependent glial release of endogenous ATP decreases the amplitude of miniature excitatory postsynaptic currents and AMPA-evoked currents in cultured hippocampal neurons. We also observed a P2X-mediated depression of field potentials recorded in CA1 region from brain slices. P2X2Rs trigger dynamin-dependent internalization of AMPA receptors (AMPARs), leading to reduced surface AMPARs in dendrites and at synapses. AMPAR alteration required calcium influx through opened ATP-gated channels and phosphatase or CamKII activities. These findings indicate that postsynaptic P2XRs play a critical role in regulating the surface expression of AMPARs and thereby regulate the synaptic strength.
authors.affiliation: Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France.
authors.forename: Johan-Till
authors.initials: JT
authors.lastname: Pougnet
authors.affiliation: Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Toulme
authors.affiliation: Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Martinez
authors.affiliation: Université de Bordeaux, Institut Interdisciplinaire des Neurosciences, UMR 5297, 33000 Bordeaux, France; CNRS, Institut Interdisciplinaire des Neurosciences, UMR 5297, 33000 Bordeaux, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Choquet
authors.affiliation: Université de Bordeaux, Institut Interdisciplinaire des Neurosciences, UMR 5297, 33000 Bordeaux, France; CNRS, Institut Interdisciplinaire des Neurosciences, UMR 5297, 33000 Bordeaux, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Hosy
authors.affiliation: Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France. Electronic address: eric.boue-grabot@u-bordeaux.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Boué-Grabot
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D055369:Miniature Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D058469:Receptors, Purinergic P2X / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D018091:Receptors, AMPA; D058469:Receptors, Purinergic P2X; D000255:Adenosine Triphosphate