Tissue plasminogen activator contributes to the late phase of LTP and to synaptic growth in the hippocampal mossy fiber pathway

Tissue plasminogen activator contributes to the late phase of LTP and to synaptic growth in the hippocampal mossy fiber pathway
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DOI:
10.1016/s0896-6273(00)80597-8
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发表时间:
1998-10-01
期刊:
影响因子:
16.2
通讯作者:
Kandel, ER
Kandel, ER
中科院分区:
医学1区
文献类型:
--
作者:
Baranes, D;Lederfein, D;Kandel, ER

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组织型纤溶酶原激活物(tPA)的表达在突触可塑性的活动依赖性形式期间增加。我们已经发现,tPA抑制剂抑制的长时程增强(L-LTP)诱导的毛喉素或强直刺激在海马苔藓纤维和Schaffer侧支通路的晚期。此外,tPA的应用增强由单次破伤风诱导的L-LTP。暴露在培养中的颗粒细胞毛喉素分泌的tPA,苔藓纤维轴突的伸长,并形成新的,活跃的突触前静脉曲张邻接的树突状簇的谷氨酸受体R1的结果。这些结构变化被tPA抑制剂阻断,并通过应用tPA诱导。因此,tPA可能在L-LTP的产生中起关键作用,特别是在突触生长中。
The expression of tissue plasminogen activator (tPA) is increased during activity-dependent forms of synaptic plasticity. We have found that inhibitors of tPA inhibit the late phase of long-term potentiation (L-LTP) induced by either forskolin or tetanic stimulation in the hippocampal mossy fiber and Schaffer collateral pathways. Moreover, application of tPA enhances L-LTP induced by a single tetanus. Exposure of granule cells in culture to forskolin results in secretion of tPA, elongation of mossy fiber axons, and formation of new, active presynaptic varicosities contiguous to dendritic clusters of the glutamate receptor R1. These structural changes are blocked by tPA inhibitors and induced by application of tPA. Thus, tPA may be critically involved in the production of L-LTP and specifically in synaptic growth.