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

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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.