REGULATION OF HIPPOCAMPAL SYNAPTIC PLASTICITY BY THE TYROSINE KINASE RECEPTOR, REK7 EPHA5, AND ITS LIGAND, AL-1/EPHRIN-A5/

The Eph-related tyrosine kinase receptor, REK7/EphA5, mediates the eff ects of AL-1/Ephrin-A5 and related ligands and is involved in the guid ance of retinal, cortical, and hippocampal axons during development. T he continued expression of REK7/EphA5 in the adult brain, in particula r in areas associated with a high degree of synaptic plasticity such a s the hippocampus, raises the question of its function in the mature n ervous system. In this report we examined the role of REK7/EphA5 in sy naptic remodeling by asking if agents that either block or activate RE K7/EphA5 affect synaptic strength in hippocampal slices from adult mou se brain. We show that a REK7/EphA5 antagonist, soluble REK7/EphA5-IgG , impairs the induction of long-term potentiation (LTP) without affect ing other synaptic parameters such as normal synaptic transmission or paired-pulse facilitation. In contrast, perfusion with AL-1/Ephrin-A5- IgG, an activator of REK7/EphA5, induces a sustained increase in norma l synaptic transmission that partially mimics LTP. The sustained eleva tion of normal synaptic transmission could be attributable to a longla sting binding of the AL-1/Ephrin-A5-IgG; to the endogenous REK7/EphA5 receptor, as revealed by immunohistochemistry. Furthermore, maximal el ectrical induction of LTP occludes the potentiating effects of subsequ ent treatment with AL-1/Ephrin-A5-IgG. Taken together these results im plicate REK7/EphA5 in the regulation of synaptic plasticity in the mat ure hippocampus and suggest that REK7/EphA5 activation is recruited in the LTP induced by tetanization.