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首页> 外文期刊>Journal of Computational Neuroscience >Modeling the role of lateral membrane diffusion in AMPA receptor trafficking along a spiny dendrite
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Modeling the role of lateral membrane diffusion in AMPA receptor trafficking along a spiny dendrite

机译：模拟侧向膜扩散在AMPA受体沿着多刺树突的运输中的作用

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AMPA receptor trafficking in dendritic spines is emerging as a major postsynaptic mechanism for the expression of plasticity at glutamatergic synapses. AMPA receptors within a spine are in a continuous state of flux, being exchanged with local intracellular pools via exo/endocytosis and with the surrounding dendrite via lateral membrane diffusion. This suggests that one cannot treat a single spine in isolation. Here we present a model of AMPA receptor trafficking between multiple dendritic spines distributed along the surface of a dendrite. Receptors undergo lateral diffusion within the dendritic membrane, with each spine acting as a spatially localized trap where receptors can bind to scaffolding proteins or be internalized through endocytosis. Exocytosis of receptors occurs either at the soma or at sites local to dendritic spines via constitutive recycling from intracellular pools. We derive a reaction-diffusion equation for receptor trafficking that takes into account these various processes. Solutions of this equation allow us to calculate the distribution of synaptic receptor numbers across the population of spines, and hence determine how lateral diffusion contributes to the strength of a synapse. A number of specific results follow from our modeling and analysis. (1) Lateral membrane diffusion alone is insufficient as a mechanism for delivering AMPA receptors from the soma to distal dendrites. (2) A source of surface receptors at the soma tends to generate an exponential-like distribution of receptors along the dendrite, which has implications for synaptic democracy. (3) Diffusion mediates a heterosynaptic interaction between spines so that local changes in the constitutive recycling of AMPA receptors induce nonlocal changes in synaptic strength. On the other hand, structural changes in a spine following long term potentiation or depression have a purely local effect on synaptic strength. (4) A global change in the rates of AMPA receptor exo/endocytosis is unlikely to be the sole mechanism for homeostatic synaptic scaling. (5) The dynamics of AMPA receptor trafficking occurs on multiple timescales and varies according to spatial location along the dendrite. Understanding such dynamics is important when interpreting data from inactivation experiments that are used to infer the rate of relaxation to steady-state.
机译：树突状棘突中的AMPA受体运输正在成为在谷氨酸能突触中表达可塑性的主要突触后机制。脊柱内的AMPA受体处于连续的流量状态，通过胞外/内吞作用与局部细胞内池交换，并通过横向膜扩散与周围的树突交换。这表明一个人不能孤立地对待一根脊柱。在这里，我们提出了一个AMPA受体运输模型之间分布在沿树突表面的多个树突棘之间的模型。受体在树突状膜内进行侧向扩散，每个脊柱都充当一个空间定位的陷阱，在此处受体可以与支架蛋白结合或通过内吞作用被内化。受体的胞吐作用发生在体细胞或树突棘的局部位置，通过细胞内池的组成性循环发生。我们推导了考虑到这些不同过程的受体运输反应扩散方程。该方程式的解使我们能够计算整个脊椎种群中突触受体数量的分布，从而确定横向扩散如何促进突触的强度。我们的建模和分析得出了许多具体结果。 （1）仅横向膜扩散不足以作为将AMPA受体从躯体传递至远端树突的机制。 （2）躯体表面受体的来源倾向于沿着树突生成受体的指数状分布，这对突触民主具有影响。 （3）扩散介导了棘突之间的异质突触相互作用，因此AMPA受体组成性循环的局部变化会引起突触强度的非局部变化。另一方面，长期增强或抑制后脊柱的结构变化仅对突触强度产生局部影响。 （4）AMPA受体胞外/内吞率的总体变化不太可能是稳态突触定标的唯一机制。 （5）AMPA受体运输的动力学发生在多个时间尺度上，并根据枝晶的空间位置而变化。在解释用于推断弛豫速率到稳态的灭活实验的数据时，了解这种动力学非常重要。

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