Glial ephrin-A3 regulates hippocampal dendritic spine morphology and glutamate transport

被引:162
作者
Carmona, Maria A. [1 ]
Murai, Keith K. [2 ]
Wang, Lei [1 ]
Roberts, Amanda J. [3 ]
Pasquale, Elena B. [1 ,4 ]
机构
[1] Burnham Inst Med Res, La Jolla, CA 92037 USA
[2] McGill Univ, Ctr Hlth, Montreal Gen Hosp, Dept Neurol & Neurosurg,Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada
[3] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA
[4] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
基金
美国国家卫生研究院;
关键词
glial glutamate transporters; hippocampus-dependent learning; neuron-glia communication; perisynaptic glial processes; LOCALIZATION; PHARMACOLOGY; PLASTICITY; RECEPTORS; SYNAPSES; GEOMETRY; EPILEPSY; DISEASE; INJURY; BRAIN;
D O I
10.1073/pnas.0903328106
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Increasing evidence indicates the importance of neuron-glia communication for synaptic function, but the mechanisms involved are not fully understood. We reported that the EphA4 receptor tyrosine kinase is in dendritic spines of pyramidal neurons of the adult hippocampus and regulates spine morphology. We now show that the ephrin-A3 ligand, which is located in the perisynaptic processes of astrocytes, is essential for maintaining EphA4 activation and normal spine morphology in vivo. Ephrin-A3-knockout mice have spine irregularities similar to those observed in EphA4knockout mice. Remarkably, loss of ephrin-A3 or EphA4 increases the expression of glial glutamate transporters. Consistent with this, glutamate transport is elevated in ephrin-A3-null hippocampal slices whereas Eph-dependent stimulation of ephrin-A3 signaling inhibits glutamate transport. Furthermore, some forms of hippocampus-dependent learning are impaired in the ephrin-A-3knockout mice. Our results suggest that the interaction between neuronal EphA4 and glial ephrin-A3 bidirectionally controls synapse morphology and glial glutamate transport, ultimately regulating hippocampal function.
引用
收藏
页码:12524 / 12529
页数:6
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