Mice lacking the gene encoding tissue-type plasminogen activator show a selective interference with late-phase long-term potentiation in both Schaffer collateral and mossy fiber pathways
Mice lacking the gene encoding tissue-type plasminogen activator show a selective interference with late-phase long-term potentiation in both Schaffer collateral and mossy fiber pathways
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DOI：
10.1073/pnas.93.16.8699
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发表时间：
1996-08-06
影响因子：
11.1
通讯作者：
Carmeliet, P
中科院分区：
文献类型：
--
作者：
Huang, YY;Bach, ME;Carmeliet, P
组织型纤溶酶原激活物（t-PA）基因是一种即时反应基因，位于CREB-1和其他组成型表达转录因子的下游，在海马长时程增强（L-LTP）晚期被诱导。切除t-PA基因的小鼠（t-PA（-/-））没有表现出明显的解剖学、电生理学、感觉或运动异常，但表现出在Schaffer侧支-CA 1和杂乱纤维-CA 3通路中海马切片中L-LTP的选择性降低，t-PA（-/-）小鼠也表现出cAMP类似物和D1/D5激动剂的增强作用降低。相比之下，这些小鼠的海马依赖性学习和记忆没有受到影响，而在双向主动回避（一种纹状体依赖性任务）上的表现却受到了损害。这些结果提供了遗传学证据，t-PA是一个下游效应基因的重要L-LTP，并表明，在CA 1和CA 3的L-LTP的适度损害不会导致海马依赖的行为表型。
The gene encoding tissue-type plasminogen activator (t-PA) is an immediate response gene, downstream from CREB-1 and other constitutively expressed transcription factors, which is induced in the hippocampus during the late phase of long-term potentiation (L-LTP). Mice in which the t-PA gene has been ablated (t-PA(-/-)) showed no gross anatomical, electrophysiological, sensory, or motor abnormalities but manifest a selective reduction in L-LTP in hippocampal slices in both the Schaffer collateral-CA1 and messy fiber-CA3 pathways, t-PA(-/-) mice also exhibit reduced potentiation by cAMP analogs and D1/D5 agonists. By contrast, hippocampal-dependent learning and memory were not affected in these mice, whereas performance was impaired on two-way active avoidance, a striatum-dependent task. These results provide genetic evidence that t-PA is a downstream effector gene important for L-LTP and show that modest impairment of L-LTP in CA1 and CA3 does not result in hippocampus-dependent behavioral phenotypes.