Baranes D, Lederfein D, Huang Y Y, Chen M, Bailey C H, Kandel E R
Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Neuron. 1998 Oct;21(4):813-25. doi: 10.1016/s0896-6273(00)80597-8.
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.
组织型纤溶酶原激活物（tPA）的表达在依赖活动的突触可塑性形式中会增加。我们发现，tPA抑制剂可抑制海马苔藓纤维和Schaffer侧支通路中由福斯克林或强直刺激诱导的晚期长时程增强（L-LTP）。此外，应用tPA可增强单次强直刺激诱导的L-LTP。培养的颗粒细胞暴露于福斯克林会导致tPA分泌、苔藓纤维轴突延长以及形成与谷氨酸受体R1的树突簇相邻的新的、活跃的突触前膨体。这些结构变化被tPA抑制剂阻断，并由应用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。
