Roles of Presynaptic Protein, complexins : in Long-term Potentiation and Learning

1)我们已经获得了复合蛋白II敲除小鼠，并试图制造复合蛋白I敲除小鼠，但失败了。复合蛋白I和II双基因敲除小鼠已由其他小组制备。他们认为复合蛋白是神经递质快速释放所必需的。2)复合蛋白II敲除显示海马LTP降低（Eur. J. Neurosci. 11：2359-2366，1999）。为了了解复合蛋白II在LTP中的作用，我们进一步研究了海马CA 1-LTP。在强直刺激后评估LTP的幅度。在野生型中，幅度随着强直刺激的频率（10、30、100 Hz）而逐渐增长，但在敲除中，没有观察到这种频率依赖性增加。这表明复合蛋白II可能参与强直刺激期间的快速释放（Jpn. J. Pharmcol. 84：179-187，2000）。3)行为实验已经完成。复杂蛋白II基因敲除小鼠在水迷宫、新环境下自由活动和MK 801处理下的活动均未见异常。我们进一步分析了应激条件下的行为和LTP。4)在一项人类研究中，精神分裂症海马中复合蛋白II的表达减少。因此，我们和不列颠哥伦比亚省大学精神病学小组检测了精神分裂症和双相情感障碍患者中复合蛋白的表达。复杂蛋白I在精神分裂症的前额叶皮层中显著减少（Molec. Psych.：（in press））.如前所述，精神分裂症患者海马中的复合蛋白II明显减少（已提交）。这些结果提示复合素可能参与了该病的发病过程。

1) We have already got complexin II knockout mice and tried to make complexin I knockout mice but failed. Complexin I and II double knockout mice have been made by other group. They suggests that complexin is necessary for fast release of neurotransmitter. 2) Complexin II knockout showed a reduction of hippocampal LTP (Eur. J. Neurosci. 11 : 2359-2366, 1999). To know how complexin II is involved in LTP, We further studied hippocampal CA1-LTP. The magnitude of LTP was evaluated after the tetanic stimulation. In the wild types, the magnitude gradually grew with the frequency of the tetanic stimulation (10, 30, 100 Hz), but in the knockout, such a frequency-dependent increase was not observed. This suggest that complexin II may be involved in the fast release during the tetanic stimulation (Jpn. J. Pharmcol. 84 : 179-187, 2000). 3) Behavior experiments have been done. Complexin II knockout mice did not show an abnormality in the analyzes of water-maze, free locomotion in a novel environment, and that under the treatment with MK801. We further intend to analyze behavior and LTP under stress-condition. 4) In a human study, complexin II expression is reduced in the schizophrenia hippocampus. So we and the group of Psychiatry in the Univ. of British Columbia examined the complexin expression in the patients of schizophrenia and bipolar disease. Complexin I was significantly reduced in the prefrontal cortex of schizophrenia (Molec. Psych. : (in press)). And as reported before, complexin II was clearly decreased in the schizophrenia hippocampus (submitted). These results suggest that complexin may be involved in the onset of the desease.