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Accelerated Experience-Dependent Pruning of Cortical Synapses in Ephrin-A2 Knockout Mice

Accelerated Experience-Dependent Pruning of Cortical Synapses in Ephrin-A2 Knockout Mice

Authors :
Xinzhu Yu
Yi Zuo
Lu Chen
Ada Xin Yee
Gordon X. Wang
Xiang Li
Anthony Gilmore
Tonghui Xu
Stephen J. Smith
Source :
Neuron, vol 80, iss 1
Publication Year :
2013
Publisher :
Elsevier BV, 2013.

Abstract

SummaryRefinement of mammalian neural circuits involves substantial experience-dependent synapse elimination. Using in vivo two-photon imaging, we found that experience-dependent elimination of postsynaptic dendritic spines in the cortex was accelerated in ephrin-A2 knockout (KO) mice, resulting in fewer adolescent spines integrated into adult circuits. Such increased spine removal in ephrin-A2 KOs depended on activation of glutamate receptors, as blockade of the N-methyl-D-aspartate (NMDA) receptors eliminated the difference in spine loss between wild-type and KO mice. We also showed that ephrin-A2 in the cortex colocalized with glial glutamate transporters, which were significantly downregulated in ephrin-A2 KOs. Consistently, glial glutamate transport was reduced in ephrin-A2 KOs, resulting in an accumulation of synaptic glutamate. Finally, inhibition of glial glutamate uptake promoted spine elimination in wild-type mice, resembling the phenotype of ephrin-A2 KOs. Together, our results suggest that ephrin-A2 regulates experience-dependent, NMDA receptor-mediated synaptic pruning through glial glutamate transport during maturation of the mouse cortex.

Details

ISSN :
08966273
Volume :
80
Database :
OpenAIRE
Journal :
Neuron
Accession number :
edsair.doi.dedup.....c35bc274f40da27df3d3e17bc693f842
Full Text :
https://doi.org/10.1016/j.neuron.2013.07.014