Study on the mechanism of brain plasticity

对某些突触的传入神经的高频刺激引起海马中突触传递功效的持久增强。这种现象被称为长时程增强（LTP），这是脊椎动物大脑学习和记忆细胞机制的一个可能模型。自从LTP被发现以来，人们一直在研究海马中引起这种神经生理现象的分子机制。本研究通过对大鼠海马LTP的研究，阐明了钙依赖性蛋白激酶，尤其是钙/钙调蛋白依赖性蛋白激酶Ⅱ（CaM kinase Ⅱ）参与海马LTP的诱导，并阐明了以下结果：（1）高频刺激大鼠海马CA 1区的两组传入纤维，而非低频刺激<32>。标记的切片导致CaM激酶II α和β亚基的自磷酸化，以及突触蛋白I和微管相关蛋白2（MAP 2）的磷酸化，它们位于突触前和突触后 关于我们 抽搐神经元，分别。2)突触蛋白I在LTP诱导过程中的磷酸化位点为位点II，即CaM激酶II磷酸化位点，表明LTP诱导过程中激活的CaM激酶II磷酸化神经元中的某些底物。3)加入NMDA谷氨酸受体拮抗剂AP 5可抑制CaM激酶II的自磷酸化以及突触蛋白I和MAP 2的磷酸化。4)加入钙调素拮抗剂calmidazolilum不仅抑制LTP的诱导，而且抑制CaM激酶II α和β亚基的自磷酸化以及突触蛋白I和MAP 2的磷酸化。5）免疫印迹分析显示，LTP的诱导与CA 1区CaM激酶II β亚基的量增加有关。6)在LTP诱导过程中，Calyculin A敏感性蛋白磷酸酶活性降低，这与蛋白磷酸酶2A调节亚基的磷酸化有关;体外实验表明，蛋白磷酸酶2A调节亚基的磷酸化抑制了该酶的活性。少

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