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

Xinzhu Yu, Gordon Wang, Anthony Gilmore, Ada Xin Yee, Xiang Li, Tonghui Xu, Stephen J. Smith, Lu Chen, Yi Zuo

Research output: Contribution to journalArticlepeer-review

Abstract

Refinement of mammalian neural circuits involves substantial experience-dependent synapse elimination. Using invivo 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

Original languageEnglish (US)
Pages (from-to)64-71
Number of pages8
JournalNeuron
Volume80
Issue number1
DOIs
StatePublished - Oct 2 2013
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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