Regulation of Hippocampal Synaptic Plasticity by the Tyrosine Kinase Receptor, REK7/EphA5, and its Ligand, AL-1/Ephrin-A5
Regulation of Hippocampal Synaptic Plasticity by the Tyrosine Kinase Receptor, REK7/EphA5, and its Ligand, AL-1/Ephrin-A5
复制标题
酪氨酸激酶受体 REK7/EphA5 及其配体 AL-1/Ephrin-A5 对海马突触可塑性的调节
DOI：
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发表时间：
1998
影响因子：
3.5
通讯作者：
I. Caras
中科院分区：
文献类型：
--
作者：
Wei;N. Shinsky;M. Armanini;P. Moran;J;J. Mendoza;H. Phillips;J. Winslow;I. Caras
Eph相关的酪氨酸激酶受体，REK7/EPHA5，介导AL-1/EPhin-A5和相关配体的作用，并参与视网膜、皮质和海马轴突的发育指导。REK7/EPHA5在成人大脑中的持续表达，特别是在与高度突触可塑性相关的区域，如海马体，提出了它在成熟神经系统中的功能问题。在这篇报道中，我们研究了REK7/EPHA5在突触重构中的作用，方法是研究阻断或激活REK7/EPHA5的药物是否影响成年小鼠海马片的突触强度。我们发现，REK7/EPHA5拮抗剂，可溶性REK7/EPHA5-IgG，在不影响其他突触参数(如正常突触传递或成对脉冲促进)的情况下，削弱了长时程增强(LTP)的诱导。相反，用REK7/EPHA5的激活剂AL-1/Ephin-A5-IgG灌流，可诱导部分模拟LTP的正常突触传递持续增加。免疫组织化学显示，正常突触传递的持续增加可能归因于AL-1/Ephin-A5-Ig G与内源性REK7/EPHA5受体的长期结合。此外，LTP的最大电诱导阻断了AL-1/Ephin-A5-Ig G后续治疗的增强效果。综上所述，这些结果提示REK7/EPHA5参与了成熟海马区突触可塑性的调节，并提示REK7/EPHA5的激活在强直刺激诱导的LTP中被招募。
The Eph-related tyrosine kinase receptor, REK7/EphA5, mediates the effects of AL-1/Ephrin-A5 and related ligands and is involved in the guidance of retinal, cortical, and hippocampal axons during development. The continued expression of REK7/EphA5 in the adult brain, in particular in areas associated with a high degree of synaptic plasticity such as the hippocampus, raises the question of its function in the mature nervous system. In this report we examined the role of REK7/EphA5 in synaptic remodeling by asking if agents that either block or activate REK7/EphA5 affect synaptic strength in hippocampal slices from adult mouse brain. We show that a REK7/EphA5 antagonist, soluble REK7/EphA5-IgG, impairs the induction of long-term potentiation (LTP) without affecting 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 normal synaptic transmission that partially mimics LTP. The sustained elevation of normal synaptic transmission could be attributable to a long-lasting binding of the AL-1/Ephrin-A5-IgG to the endogenous REK7/EphA5 receptor, as revealed by immunohistochemistry. Furthermore, maximal electrical induction of LTP occludes the potentiating effects of subsequent treatment with AL-1/Ephrin-A5-IgG. Taken together these results implicate REK7/EphA5 in the regulation of synaptic plasticity in the mature hippocampus and suggest that REK7/EphA5 activation is recruited in the LTP induced by tetanization.
影响因子：
56.9
作者：
GRANT, SGN;ODELL, TJ;KANDEL, ER
通讯作者：
KANDEL, ER