O'Dell T J, Kandel E R, Grant S G
Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, New York, New York 10032.
Nature. 1991 Oct 10;353(6344):558-60. doi: 10.1038/353558a0.
Long-term potentiation (LTP) in the hippocampus is thought to contribute to memory formation. In the Ca1 region, LTP requires the NMDA (N-methyl-D-aspartate) receptor-dependent influx of Ca2+ and activation of serine and threonine protein kinases. Because of the high amount of protein tyrosine kinases in hippocampus and cerebellum, two regions implicated in learning and memory, we examined the possible additional requirement of tyrosine kinase activity in LTP. We first examined the specificity in brain of five inhibitors of tyrosine kinase and found that two of them, lavendustin A and genistein, showed substantially greater specificity for tyrosine kinase from hippocampus than for three serine-threonine kinases: protein kinase A, protein kinase C, and Ca2+/calmodulin kinase II. Lavendustin A and genistein selectively blocked the induction of LTP when applied in the bath or injected into the postsynaptic cell. By contrast, the inhibitors had no effect on the established LTP, on normal synaptic transmission, or on the neurotransmitter actions attributable to the actions of protein kinase A or protein kinase C. These data suggest that tyrosine kinase activity could be required postsynaptically for long-term synaptic plasticity in the hippocampus. As Ca2+ calmodulin kinase II or protein kinase C seem also to be required, the tyrosine kinases could participate postsynaptically in a kinase network together with serine and threonine kinases.
海马体中的长时程增强（LTP）被认为有助于记忆形成。在海马体CA1区，LTP需要NMDA（N-甲基-D-天冬氨酸）受体依赖的Ca2+内流以及丝氨酸和苏氨酸蛋白激酶的激活。由于海马体和小脑这两个与学习和记忆有关的区域中存在大量蛋白酪氨酸激酶，我们研究了LTP中酪氨酸激酶活性可能的额外需求。我们首先检测了五种酪氨酸激酶抑制剂在脑中的特异性，发现其中两种，拉文达ustin A和染料木黄酮，对海马体酪氨酸激酶的特异性比对三种丝氨酸-苏氨酸激酶（蛋白激酶A、蛋白激酶C和Ca2+/钙调蛋白激酶II）的特异性高得多。当通过浴槽给药或注入突触后细胞时，拉文达ustin A和染料木黄酮选择性地阻断了LTP的诱导。相比之下，这些抑制剂对已建立的LTP、正常突触传递或归因于蛋白激酶A或蛋白激酶C作用的神经递质作用没有影响。这些数据表明，酪氨酸激酶活性可能是海马体长时程突触可塑性的突触后所需条件。由于似乎也需要Ca2+钙调蛋白激酶II或蛋白激酶C，酪氨酸激酶可能在突触后与丝氨酸和苏氨酸激酶一起参与激酶网络。
