突触后膜AMPA受体输运机制的理论研究

Theoretical study on postsynaptic membrane AMAPR trafficking

突触可塑性是大脑学习和记忆的基础.AMPA受体是中枢神经系统快速兴奋性突触传递主要的特异性受体,研究AMPA受体在突触后膜上如何迁移运动,可明确突触传递强度的生物物理基础.AMPA受体位于突触后膜的突触致密区,在突触区域以及突触外之间的区域输运.本研究建立了AMPA受体的动态输运模型,并且探讨AMPA受体在突触后3个区域中数量与跃迁概率之间的关系.通过数学解析求解方程组的稳定解和特征根发现,AMPA受体在PSD、ESM和细胞内部3个部位的稳态数量,数学解析结果与数值结果相一致,并且不依赖于初始分布.特征根的数学解析解可以表达为各跃迁概率的函数,其大小决定系统演化的时间尺度.我们的模型对于进一步研究调控AMPA受体上下膜的钙离子依赖的化学信号通路,以及介导突触强度变化的作用机制提供了理论基础.

Synaptic plasticity is the physical basis of learning and memory.AMPA receptor mediates fast excitatory neurotransmission in the CNS,therefore it is important to understand how postsynaptic AMPA receptors migrate during formation of synaptic plasticity.AMPAR can transfer among 3regions of the postsynaptic membrane,post-synaptic density,extra-synaptic membrane,and dendritic cytosol.A,mathematic model for dynamic AMPAR trafficking was built to investigate AMPAR distribution in each compartment with varied rates for exocytosis,hopping and endocytosis.Analytical solution for equilibrium distribution and eigenvalue can be written as functions of rate parameters.Dynamics of AMPAR distribution in computer simulation was found to be consistent with analytical solutions,to be regulated by exocytosis,endocytosis and hopping.In addition,eigenvalues of dynamic equations determine the timescales of AMPAR evolution,which are regulated by rate parameters.The model provides some theoretical basis to investigate calcium-dependent regulation of exocytosis and endocytosis and synaptic plasticity.