双向突触可塑性诱导与维持的调控机制模型  

Modeling for CREB-Mediated Induction and Maintenance Mechanism of Bidirectional Synaptic Plasticity

作　　者：陈炜 张广辉 CHENG Wei;ZHANG Guang-hui(Human Resource Department,Hebei Agricultural University,Baoding Hebei 071001,China;School of Information Science and Technology,Hebei Agricultural University,Baoding Hebei 071001,China)

机构地区：[1]河北农业大学人事处,河北保定071001 [2]河北农业大学信息科学与技术学院,河北保定071001

出　　处：《计算机仿真》2022年第3期391-395,共5页Computer Simulation

基　　金：河北农业大学引进人才专项(YJ201953);河北省教育厅高校基本科研业务费专项(KY201903)。

摘　　要：神经元突触可塑性是大脑记忆形成与存储的重要生理模型,核内转录因子cAMP反应结合蛋白CREB在其诱导与维持中具有重要调控作用。针对目前CREB调控神经元突触可塑行为的分子信号转导机制尚不清晰的问题,采用数学建模与数值仿真相结合的方法,通过整合神经元膜上突触活动、突触信号在细胞质中的级联反应传递、激发型与抑制型CREB介导的基因转录以及新合成蛋白对NMDA膜受体的反馈调控,建立了一个从神经元膜到核的分子信号转导计算模型。通过数值仿真,探究了模型的动力学特性,表明在不同的突触刺激频率域下,CREB介导的分子信号转导系统呈现出静息、长时程增强和长时程抑制三种可塑性形态,由此得出结论,激发型与抑制型CREB对神经元生化级联反应的有序调控是神经元双向突触可塑性诱导与维持的导向机制之一。Neuronal synaptic plasticity is an important physiological model in the research of memory formation and storage.The transcription factor cAMP response element-binding(CREB)is crucial for the induction and maintenance of synaptic plasticity.However,it is not clear how CREB regulars the synaptic plasticity at present.In order to reveal the biochemical mechanism,mathematical modeling and numerical simulation are combined.The proposed calculational model integrates four sets of biochemical cascades from neuronal membrane to nucleus,which consists of the synaptic activities on neuronal membrane,transduction of synaptic signal in the cytoplasm,gene transcription mediated by excitatory and inhibitory CREB,and feedback regulation of protein synthesis for NMDA receptor.Through solving the calculational model numerically,the dynamic characteristics of the model are explored qualitatively and three types of plasticity states are shown when executing different stimulation frequencies:resting,long-term potentiation and long-term depression.Therefore,it is concluded that the biochemical cascades mediated by excitatory and inhibitory CREB are one of the oriented mechanisms for inducing and maintaining bidirectional synaptic plasticity.

关 键 词：长时程增强 长时程抑制 建模与仿真 

分 类 号：Q42[生物学—神经生物学] Q811[生物学—生理学]