Study on the mechanism of brain plasticity

脑可塑性机制研究

基本信息

批准号：
07044281
负责人：
MIYAMOTO Eishichi
金额：
$ 3.78万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07044281/
关键词：
Hippocampus Synaptic long-term potentiation Learning Memory Glutamate receptor Ca^<2+>mobilization CaM kinase II Protein phospatases Endogenous substrates 転写因子

项目摘要

High-frequency stimulation of afferents to certain synapses causes long-lasting potentiation of synaptic transmission efficacy in the hippocampus. This phenomenon is called long-term potentiation (LTP), which is a possible model for a cellular mechanism for learning and memory in vertebrate brain. Since the discovery of LTP,the molecular mechanisms responsible for the neurophysiological phenomena have been investigated in the hippocampus. Ca^<2+>-dependent protein kinases, especially, Ca^<2+>/calmodulin-dependent protein kinase II (CaM kinase II) is implicated in the induction of LTP in the hippocampus.The present project elucidated the following findings 1) Application of high but not low frequency stimulation to tow groups of afferents in the CA1 region of ^<32>P-labeled slices resulted in autophosphorylation of CaM kinase IIalpha and beta subunits as well asphosphorylation of synapsin I and microtubule-associated protein 2 (MAP2) which are localized in the presynaptic and post-synap … More tic neurons, respectively. 2) The phosphorylation site of synapsin I was site II during LTP induction, which is the site phosphorylated by CaM kinase II.It indicates that activated CaM kinase II during LTP induction phosphorylates certain substrates in neurons. 3) Autophosphorylation of CaM kinase II and phosphorylation of synapsin I and MAP2 were inhibited by addition of AP5 which is an NMDA glutamate receptor antagonists. 4) Addition of calmidazolilum, a calmodulin antagonist, inhibited not only LTP induction, but also autophosphorylation of CaM kinase II alpha and beta subunits and phosphorylation of synapsin I and MAP2.5) Immunoblotting analysis revealed that LTP induction was associated with an increase in the amount of CaM kinase II beta subunit in the CA1 region. 6) Calyculin A-sensitive protein phosphatase activity decreased during LTP induction in association with phosphorylation of the regulatory subunit of protein phosphatase 2A.In vitro experiments revealed that the phosphorylation of the regulatory subunit of protein phosphatase 2A inhibit the activity of the enzyme. Less

高频刺激某些突触的传入会导致海马中突触传递效率的长期增强。这种现象称为长期增强（LTP），这是用于脊椎动物大脑学习和记忆的细胞机制的可能模型。自从发现LTP以来，已经在海马中研究了负责神经生理现象的分子机制。 Ca^<2+> - 依赖性蛋白激酶，尤其是Ca^<2+>/钙调蛋白依赖性蛋白激酶II（CAM激酶II）在海马中的LTP诱导中暗示。目前的项目阐明了以下发现1）在高频刺激中，但在Ca1 efferents中的应用不低，但在Ca1 efferents中的应用不低，但在Ca1 efferents中的应用不低。 CAM激酶IIALPHA和β亚基的自磷酸化以及突触素I和微管相关蛋白2（MAP2）的磷酸化分别定位于突触前和突触后……更为tic的神经元中。 2）突触素I的磷酸化位点是LTP诱导期间的位点II，这是CAM激酶II磷酸化的位点磷酸化。这表明LTP诱导期间活性CAM激酶II磷酸化在神经元中的某些底物。 3）CAM激酶II的自磷酸化和突触蛋白I和MAP2的磷酸化被添加的AP5抑制，AP5是NMDA谷氨酸受体拮抗剂。 4）添加Calmazolium是一种钙调蛋白拮抗剂，不仅抑制了LTP的诱导，而且还抑制了CAM激酶IIα和β亚基的自磷酸化以及突触I和MAP2.5）免疫印迹分析的磷酸化以及LTP诱导的磷酸化表明，LTP诱导与CAM Kinase II BEAS量增加了CABASE SUBUNIT的增加相关。 6）在LTP诱导过程中，钙蛋白A敏感的蛋白磷酸酶活性与蛋白质磷酸酶2A的调节亚基的磷酸化相关性下降。在体外实验表明，蛋白质磷酸酶2a的调节亚基的磷酸化磷酸化蛋白2a的调节亚基抑制了enzeme的活性。较少的