Satoh M, Watanabe S
Department of Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Nihon Yakurigaku Zasshi. 1993 Sep;102(3):225-34. doi: 10.1254/fpj.102.225.
The physiological characteristics and significance of long-term potentiation in the hippocampus were summarized. In particular, it was pointed out that different mechanisms are involved in the production of hippocampal LTP between the mossy fiber-CA3 system and other systems such as Schaffer collateral-CA1, fimbrial fiber-CA3 and commissural/associational fiber-CA3. Furthermore, the epsilon-subspecies of protein kinase C (PKC) was demonstrated to be exclusively located at the presynaptic terminals in the hippocampus and activated by arachidonic acid, and this enzyme is suggested to be involved in the production of LTP through a phosphorylation of GAP-43, while the gamma-subspecies of PKC may be postsynaptically involved in LTP through an activation of NMDAR1. The production of LTP in the hippocampus is facilitated by many factors such as epidermal growth factor, fibroblast growth factors, somatostatin, M1 receptor agonists and many drugs like anirasetam, bifemelane, idebenone, indeloxazine and vinpocetine, but inhibited by M2-receptor agonists, scopolamine and midazolam. In addition to electrophysiological methods, LTP-like phenomena in 2-deoxyglucose uptake and leucine incorporation can be detected. These LTP phenomena in several animal models will be useful as indices for evaluating facilitatory actions of various compounds on learning/memory functions.
总结了海马体中长期增强的生理特征及意义。特别指出,苔藓纤维 - CA3系统与其他系统(如谢弗侧支 - CA1、穹窿纤维 - CA3和联合/联络纤维 - CA3)之间,海马体LTP产生涉及不同机制。此外,蛋白激酶C(PKC)的ε亚型被证明仅位于海马体的突触前终末,并可被花生四烯酸激活,该酶被认为通过对GAP - 43的磷酸化参与LTP的产生,而PKC的γ亚型可能通过激活NMDAR1在突触后参与LTP。海马体中LTP的产生受多种因素促进,如表皮生长因子、成纤维细胞生长因子、生长抑素、M1受体激动剂以及许多药物(如阿尼西坦、双苯美伦、艾地苯醌、茚洛秦和长春西汀),但受M2受体激动剂、东莨菪碱和咪达唑仑抑制。除电生理方法外,还可检测到2 - 脱氧葡萄糖摄取和亮氨酸掺入中的LTP样现象。几种动物模型中的这些LTP现象,将作为评估各种化合物对学习/记忆功能促进作用的指标。