Mitsuyama Fuyuki, Niimi Gen, Kato Kunio, Hirosawa Kazushige, Mikoshiba Katsuhiko, Okuya Masato, Karagiozov Kostadin, Kato Yoko, Kanno Tetsuo, Sanoe Hirotoshi, Koide Tadashi
Department of Neurosurgery, Fujita Health University, Aichi, Japan.
Ital J Anat Embryol. 2008 Jan-Mar;113(1):17-27.
It is now well accepted that the trafficking of AMPA receptors to the postsynaptic plasma membrane plays an essential role in long-term potentiation at the hippocampal Schaffer collateral synapses on CA1 pyramidal cells, but the motor mechanism of trafficking is unknown. We suspected that this trafficking of AMPA receptors during long-term potentiation may be carried out along microtubules by their motors. To ascertain this hypothesis, we light- and electron-microscopically studied the distribution of microtubules in dendrites of CA1 neurons of non-stimulated and stimulated rat hippocampal slices by using very strong tetanic stimulation for inducing long-term potentiation. As a result, we observed the following changes: 1. In immunofluorescence for microtubules and IP3 receptor using ultrathin-cryosections, linear signals of microtubules in main dendritic shafts were changed into fragmented. 2. Many spotty signals of microtubules emerged at the peripheral area of dendrites. Electron-microscopically, there was redistribution of microtubules in dendritic spines and dendritic shafts, and the thickening of post-synaptic density. 3. Many microtubules concentrated to thickened postsynaptic density in spines and new ones emerged, going to spines from dendritic shafts. These results strongly suggest that new tracks of microtubules from cell bodies to the stimulated postsynaptic membranes were produced after tetanic stimulation during long-term potentiation. This newly produced microtubules between stimulated postsynaptic membranes and the cell body must be the most promising candidate of the track for the trafficking of AMPA receptors to the stimulated postsynaptic plasma membrane.
目前已广泛接受的观点是,AMPA受体向突触后质膜的转运在海马CA1锥体细胞上的Schaffer侧支突触的长时程增强中起着至关重要的作用,但转运的分子机制尚不清楚。我们推测,长时程增强过程中AMPA受体的这种转运可能是由其分子沿着微管进行的。为了验证这一假设,我们通过使用非常强的强直刺激诱导长时程增强,对未刺激和刺激的大鼠海马切片的CA1神经元树突中的微管分布进行了光学显微镜和电子显微镜研究。结果,我们观察到以下变化:1. 在使用超薄冷冻切片对微管和IP3受体进行免疫荧光检测时,主树突干中微管的线性信号变成了片段化。2. 在树突的周边区域出现了许多微管的斑点状信号。电子显微镜观察发现,树突棘和树突干中的微管发生了重新分布,突触后致密部增厚。3. 许多微管集中到棘突中增厚的突触后致密部,并且有新的微管出现,从树突干伸向棘突。这些结果强烈表明,在长时程增强过程中的强直刺激后,产生了从细胞体到受刺激突触后膜的新的微管轨道。这种在受刺激突触后膜和细胞体之间新产生的微管必定是AMPA受体向受刺激突触后质膜转运的最有希望的轨道候选者。