A critical role for VEGF and VEGFR2 in NMDA receptor synaptic function and fear-related behavior

P. De Rossi, E. Harde, J. P. Dupuis, L. Martin, N. Chounlamountri, M. Bardin, C. Watrin, C. Benetollo, K. Pernet-Gallay, H. J. Luhmann, J. Honnorat, G. Malleret, L. Groc, A. Acker-Palmer, P. A. Salin, C. Meissirel

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1768-1780
Number of pages13
JournalMolecular Psychiatry
Volume21
Issue number12
DOIs
StatePublished - Dec 1 2016
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

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