TY  - JOUR
A1  - De Rossi, Pierre
A1  - Harde, Eva
A1  - Dupuis, Julien P.
A1  - Martin, Laurent
A1  - Chounlamountri, Naura
A1  - Bardin, Manon
A1  - Watrin, Chantal
A1  - Benetollo, Claire
A1  - Pernet-Gallay, Karin
A1  - Luhmann, Heiko
A1  - Honnorat, Jérôme
A1  - Malleret, Gael
A1  - Groc, Laurent
A1  - Acker-Palmer, Amparo
A1  - Salin, Paul Antoine
A1  - Meissirel, Claire
T1  - A critical role for VEGF and VEGFR2 in NMDA receptor synaptic function and fear-related behavior
T2  - Molecular psychiatry
N2  - 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.
Y1  - 2016
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/43929
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-439296
N1  - This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if thematerial is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
VL  - 21
SP  - 1768
EP  - 1780
PB  - Springer Nature
ER  -