Accelerated experience-dependent pruning of cortical synapses in ephrin-A2 knockout mice

Neuron. 2013 Oct 2;80(1):64-71. doi: 10.1016/j.neuron.2013.07.014. Epub 2013 Oct 2.


Refinement 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Transport System X-AG / metabolism
  • Animals
  • Brain / growth & development
  • Dendritic Spines / metabolism
  • Ephrin-A2 / deficiency
  • Ephrin-A2 / genetics*
  • Excitatory Postsynaptic Potentials / genetics
  • Mice
  • Mice, Knockout
  • Neuroglia / metabolism*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synapses / metabolism*
  • Synaptic Transmission / physiology


  • Amino Acid Transport System X-AG
  • Ephrin-A2
  • Receptors, N-Methyl-D-Aspartate