6533b861fe1ef96bd12c5a5a
RESEARCH PRODUCT
A critical role for VEGF and VEGFR2 in NMDA receptor synaptic function and fear-related behavior
M. BardinM. BardinLaurent GrocLaurent GrocNaura ChounlamountriNaura ChounlamountriJulien P. DupuisJulien P. DupuisClaire BenetolloClaire BenetolloClaire MeissirelClaire MeissirelLaurent MartinLaurent MartinPaul-antoine SalinPaul-antoine SalinPaul-antoine SalinK. Pernet-gallayP. De RossiP. De RossiChantal WatrinChantal WatrinGaël MalleretGaël MalleretGaël MalleretHeiko J. LuhmannJérôme HonnoratJérôme HonnoratAmparo Acker-palmerAmparo Acker-palmerAmparo Acker-palmerEva HardeEva HardeEva Hardesubject
Vascular Endothelial Growth Factor A0301 basic medicine[SDV]Life Sciences [q-bio]Cell Culture TechniquesNonsynaptic plasticityBiologyNeurotransmissionHippocampusReceptors N-Methyl-D-AspartateSynaptic TransmissionMice03 medical and health sciencesCellular and Molecular Neuroscience0302 clinical medicinePostsynaptic potentialAnimalsddc:610Molecular BiologyComputingMilieux_MISCELLANEOUSNeuronsNeuronal PlasticityBehavior AnimalGlutamate receptorExcitatory Postsynaptic PotentialsKinase insert domain receptorFearVascular Endothelial Growth Factor Receptor-2Protein SubunitsPsychiatry and Mental health030104 developmental biologySynaptic fatigueReceptors GlutamateSynapsesSynaptic plasticityNMDA receptorOriginal ArticleNeuroscience030217 neurology & neurosurgerydescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-12-01 |