First Author | Yu X | Year | 2013 |
Journal | Neuron | Volume | 80 |
Issue | 1 | Pages | 64-71 |
PubMed ID | 24094103 | Mgi Jnum | J:201801 |
Mgi Id | MGI:5515814 | Doi | 10.1016/j.neuron.2013.07.014 |
Citation | Yu X, et al. (2013) Accelerated experience-dependent pruning of cortical synapses in ephrin-A2 knockout mice. Neuron 80(1):64-71 |
abstractText | 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. |