Glutamate controls vessel-associated migration of GABA interneurons from the pial migratory route via NMDA receptors and endothelial protease activation

Cellular and Molecular Life Sciences : CMLS
Cécile LégerBruno J Gonzalez

Abstract

During cortex development, fine interactions between pyramidal cells and migrating GABA neurons are required to orchestrate correct positioning of interneurons, but cellular and molecular mechanisms are not yet clearly understood. Functional and age-specific expression of NMDA receptors by neonate endothelial cells suggests a vascular contribution to the trophic role of glutamate during cortical development. Associating functional and loss-of-function approaches, we found that glutamate stimulates activity of the endothelial proteases MMP-9 and t-PA along the pial migratory route (PMR) and radial cortical microvessels. Activation of MMP-9 was NMDAR-dependent and abrogated in t-PA-/- mice. Time-lapse recordings revealed that glutamate stimulated migration of GABA interneurons along vessels through an NMDAR-dependent mechanism. In Gad67-GFP mice, t-PA invalidation and in vivo administration of an MMP inhibitor impaired positioning of GABA interneurons in superficial cortical layers, whereas Grin1 endothelial invalidation resulted in a strong reduction of the thickness of the pial migratory route, a marked decrease of the glutamate-induced MMP-9-like activity along the PMR and a depopulation of interneurons in superficial cortical...Continue Reading

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Citations

Aug 6, 2020·Journal of Clinical Medicine·Vianney GilardStéphane Marret
Dec 2, 2020·Acta Neuropathologica Communications·Florent MarguetAnnie Laquerrière
Jun 3, 2021·Current Opinion in Neurobiology·Blanca PegueraAmparo Acker-Palmer

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Datasets Mentioned

BETA
GM6001
GM6001-treated

Methods Mentioned

BETA
transgenic
FCS
mechanical dissociation
PCRs
PCR
electrophoresis
laser capture microdissection
zymography

Software Mentioned

Leica LAS AF Lite
ImageJ
biostatistic Prism
Leica MM AF
INTERVISION
GraphPad
AutoQuant X 3
Filament
Explora Nova Mercator
maze

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