Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 30, Pages 12524-12529Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0903328106
Keywords
glial glutamate transporters; hippocampus-dependent learning; neuron-glia communication; perisynaptic glial processes
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Funding
- National Institutes of Health [HD025938]
- Sanford Children's Health Research Center
- Fundacion Espanola para la Ciencia y la Tecnologia
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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.
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