Loss of cadherin-11 adhesion receptor enhances plastic changes in hippocampal synapses and modifies behavioral responses

Loss of cadherin-11 adhesion receptor enhances plastic changes in hippocampal synapses and modifies behavioral responses
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DOI:
10.1006/mcne.2000.0849
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发表时间:
2000-06-01
影响因子:
3.5
通讯作者:
Hayakawa, Y
Hayakawa, Y
中科院分区:
医学3区
文献类型:
--
作者:
Manabe, T;Togashi, H;Hayakawa, Y

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钙粘蛋白组织中央突触中突触前膜和突触后膜之间的对称连接。其中之一,钙粘蛋白-11(cad 11),在大脑边缘系统中表达,在海马体中表达最强。海马的免疫组化研究表明,cad 11蛋白密集分布在其突触神经元区,在培养的海马神经元,其分布往往重叠的突触素,偶尔也与GluR 1在棘。为了评估cad 11在突触形成和/或功能中的作用,我们分析了cad 11缺陷小鼠的大脑。在这些小鼠中,海马CA 1区的长时程增强(LTP)出乎意料地增强; LTP饱和水平增加。在行为测试中,突变小鼠表现出与恐惧或焦虑相关的反应减少。这些结果表明,cad 11介导的连接可能调节突触的功效,限制其动态变化在一个有限的范围内,或者这些连接所需的正常发展的海马突触组织。
Cadherins organize symmetrical junctions between the pre- and postsynaptic membranes in central synapses. One of them, cadherin-11 (cad11), is expressed in the limbic system of the brain, most strongly in the hippocampus. Immunohistochemical studies of the hippocampus showed that cad11 proteins were densely distributed in its synaptic neuropil zones; in cultured hippocampal neurons, their distribution often overlapped with that of synaptophysin, and also occasionally with that of GluR1 at spines. To assess the role of cad11 in synaptic formation and/or function, we analyzed brains of cad11-deficient mice. In these mice, long-term potentiation (LTP) in the CA1 region of the hippocampus was, unexpectedly, enhanced; and the level of LTP saturation was increased. In behavioral tests, the mutant mice showed reduced fear- or anxiety-related responses. These results suggest that the cad11-mediated junctions may modulate synaptic efficacy, confining its dynamic changes to a limited range, or these junctions are required for normal development of synaptic organization in the hippocampus.