title: A critical role for VEGF and VEGFR2 in NMDA receptor synaptic function and fear-related behavior.
abstract: Vascular endothelial growth factor (VEGF) is known to be required for the action of antidepressant therapies but its impact on brain synaptic function is poorly characterized. Using a combination of electrophysiological, single-molecule imaging and conditional transgenic approaches, we identified the molecular basis of the VEGF effect on synaptic transmission and plasticity. VEGF increases the postsynaptic responses mediated by the N-methyl-D-aspartate type of glutamate receptors (GluNRs) in hippocampal neurons. This is concurrent with the formation of new synapses and with the synaptic recruitment of GluNR expressing the GluN2B subunit (GluNR-2B). VEGF induces a rapid redistribution of GluNR-2B at synaptic sites by increasing the surface dynamics of these receptors within the membrane. Consistently, silencing the expression of the VEGF receptor 2 (VEGFR2) in neural cells impairs hippocampal-dependent synaptic plasticity and consolidation of emotional memory. These findings demonstrated the direct implication of VEGF signaling in neurons via VEGFR2 in proper synaptic function. They highlight the potential of VEGF as a key regulator of GluNR synaptic function and suggest a role for VEGF in new therapeutic approaches targeting GluNR in depression.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1028, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5292, Lyon, France.|Claude Bernard University Lyon 1, Lyon, France.|Neurooncology and Neuroinflammation, Lyon Neuroscience Research Center, Lyon, France.
authors.forename: P
authors.initials: P
authors.lastname: De Rossi
authors.affiliation: Institute of Cell Biology and Neuroscience and BMLS, Goethe University Frankfurt, Frankfurt, Germany.|Max Planck Institute for Brain Research, Frankfurt, Germany.|Focus Program Translational Neurosciences, University of Mainz, Mainz, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Harde
authors.affiliation: Interdisciplinary Institute for Neuroscience, Unité Mixte de Recherche 5297, Université de Bordeaux, Bordeaux, France.|Interdisciplinary Institute for Neuroscience, UMR 5297, Centre National de la Recherche Scientifique, Bordeaux, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Dupuis
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1028, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5292, Lyon, France.|Claude Bernard University Lyon 1, Lyon, France.|Neurooncology and Neuroinflammation, Lyon Neuroscience Research Center, Lyon, France.
authors.forename: L
authors.initials: L
authors.lastname: Martin
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1028, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5292, Lyon, France.|Claude Bernard University Lyon 1, Lyon, France.|Neurooncology and Neuroinflammation, Lyon Neuroscience Research Center, Lyon, France.
authors.forename: N
authors.initials: N
authors.lastname: Chounlamountri
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1028, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5292, Lyon, France.|Claude Bernard University Lyon 1, Lyon, France.|Neurooncology and Neuroinflammation, Lyon Neuroscience Research Center, Lyon, France.
authors.forename: M
authors.initials: M
authors.lastname: Bardin
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1028, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5292, Lyon, France.|Claude Bernard University Lyon 1, Lyon, France.|Neurooncology and Neuroinflammation, Lyon Neuroscience Research Center, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Watrin
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1028, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5292, Lyon, France.|Claude Bernard University Lyon 1, Lyon, France.|Functional Neurogenomics and Optogenetics, Lyon Neuroscience Research Center, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Benetollo
authors.affiliation: Grenoble Institute of Neurosciences, Grenoble, France.|INSERM U836, Microscopy and Electron Microscopy Platform, Grenoble, France.
authors.forename: K
authors.initials: K
authors.lastname: Pernet-Gallay
authors.affiliation: Institute of Physiology, University Medical Center, University of Mainz, Mainz, Germany.
authors.forename: H J
authors.initials: HJ
authors.lastname: Luhmann
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1028, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5292, Lyon, France.|Claude Bernard University Lyon 1, Lyon, France.|Neuro-Oncology Department, Hospices Civils de Lyon, Hôpital Neurologique, Lyon, France.
authors.forename: J
authors.initials: J
authors.lastname: Honnorat
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1028, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5292, Lyon, France.|Claude Bernard University Lyon 1, Lyon, France.|Forgetting and Cortical Dynamics, Lyon Neuroscience Research Center, Lyon, France.
authors.forename: G
authors.initials: G
authors.lastname: Malleret
authors.affiliation: Interdisciplinary Institute for Neuroscience, Unité Mixte de Recherche 5297, Université de Bordeaux, Bordeaux, France.|Interdisciplinary Institute for Neuroscience, UMR 5297, Centre National de la Recherche Scientifique, Bordeaux, France.
authors.forename: L
authors.initials: L
authors.lastname: Groc
authors.affiliation: Institute of Cell Biology and Neuroscience and BMLS, Goethe University Frankfurt, Frankfurt, Germany.|Max Planck Institute for Brain Research, Frankfurt, Germany.|Focus Program Translational Neurosciences, University of Mainz, Mainz, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Acker-Palmer
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1028, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5292, Lyon, France.|Claude Bernard University Lyon 1, Lyon, France.|Forgetting and Cortical Dynamics, Lyon Neuroscience Research Center, Lyon, France.
authors.forename: P A
authors.initials: PA
authors.lastname: Salin
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1028, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5292, Lyon, France.|Claude Bernard University Lyon 1, Lyon, France.|Neurooncology and Neuroinflammation, Lyon Neuroscience Research Center, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Meissirel
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D018929:Cell Culture Techniques; D019706:Excitatory Postsynaptic Potentials; D005239:Fear; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D021122:Protein Subunits; D017470:Receptors, Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism* / Q000502:physiology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism* / Q000502:physiology
chemical_list: D021122:Protein Subunits; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C000592875:Kdr protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2