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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导致海马突触传递效能的持久增强。这种现象被称为长期增强（LTP），它可能是脊椎动物大脑学习和记忆的细胞机制的模型。自LTP被发现以来，有关海马神经生理现象的分子机制已被研究。Ca^<2+>依赖性蛋白激酶，特别是Ca^<2+>/钙调素依赖性蛋白激酶II （CaM激酶II）与海马LTP的诱导有关。结果表明：1)高而非低频率刺激两组神经传入事件在^<32> p标记片的CA1区导致CaM激酶ii α和β亚基的自磷酸化，以及突触前和突触后神经元突触素I和微管相关蛋白2 （MAP2）的磷酸化。2) LTP诱导时synapsin I的磷酸化位点为II位点，是CaM激酶II磷酸化的位点。这表明在LTP诱导过程中活化的CaM激酶II使神经元中的某些底物磷酸化。3)添加NMDA谷氨酸受体拮抗剂AP5可抑制CaM kinase II的自磷酸化、synapsin I和MAP2的磷酸化。4)钙调素拮抗剂calmidazolilum的加入不仅抑制了LTP的诱导，还抑制了CaM kinase II α和β亚基的自磷酸化以及synapsin I和MAP2.5的磷酸化。免疫印迹分析显示，LTP的诱导与CA1区域CaM kinase II β亚基的数量增加有关。6)在LTP诱导过程中，Calyculin a敏感蛋白磷酸酶活性降低与蛋白磷酸酶2A调控亚基磷酸化有关。体外实验表明，蛋白磷酸酶2A调控亚基的磷酸化抑制了酶的活性。少