Study on the mechanism of brain plasticity

高频刺激某些突触的传入会导致海马区突触传递效能的持久增强。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的细胞机制的可能模型。自从LTP被发现以来，海马区神经生理现象的分子机制一直被研究。钙依赖的蛋白激酶，尤其是钙调素依赖的蛋白激酶II参与了海马长时程增强的诱导。本项目阐明了以下发现：1)对突触前和突触后…区的两组传入施加高频而非低频刺激，导致定位于突触前和突触后的突触蛋白I和微管相关蛋白2的自动磷酸化。分别是更多的抽动神经元。2)LTP诱导过程中突触素I的磷酸化位点为位点II，提示LTP诱导过程中激活的CaM激酶II可磷酸化神经元中的某些底物。3)加入NMDA谷氨酸受体拮抗剂AP5后，CaM激酶II的自磷酸化、突触素I和MAP2的磷酸化均受到抑制。4)钙调素拮抗剂卡米达唑仑不仅能抑制LTP的诱导，而且还能抑制CaM激酶IIα和β亚基的自磷酸化以及突触素I和MAP2.5的磷酸化。6)在LTP诱导过程中，Calyculin A敏感的蛋白磷酸酶活性下降，与蛋白磷酸酶2 A调节亚基的磷酸化有关。体外实验表明，蛋白磷酸酶2 A调节亚基的磷酸化抑制了该酶的活性。较少

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