Unified quantitative model of AMPA receptor trafficking at synapses

被引:86
作者
Czoendoer, Katalin [1 ,2 ]
Mondin, Magali [1 ,2 ]
Garcia, Mikael [1 ,2 ]
Heine, Martin [3 ]
Frischknecht, Renato [3 ]
Choquet, Daniel [1 ,2 ]
Sibarita, Jean-Baptiste [1 ,2 ]
Thoumine, Olivier R. [1 ,2 ]
机构
[1] Univ Bordeaux, Interdisciplinary Inst Neurosci, F-33000 Bordeaux, France
[2] CNRS, Interdisciplinary Inst Neurosci, F-33000 Bordeaux, France
[3] Leibniz Inst Neurobiol, D-39118 Magdeburg, Germany
关键词
glutamate receptor; scaffold molecules; synaptic plasticity; theoretical model; diffusion/trapping; LONG-TERM POTENTIATION; HIPPOCAMPAL-NEURONS; DENDRITIC SPINES; SYNAPTIC-TRANSMISSION; GLUTAMATE RECEPTORS; INDIVIDUAL SYNAPSES; LATERAL DIFFUSION; EXOCYTOSIS; ENDOCYTOSIS; PLASTICITY;
D O I
10.1073/pnas.1109818109
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Trafficking of AMPA receptors (AMPARs) plays a key role in synaptic transmission. However, a general framework integrating the two major mechanisms regulating AMPAR delivery at post-synapses (i.e., surface diffusion and internal recycling) is lacking. To this aim, we built a model based on numerical trajectories of individual AMPARs, including free diffusion in the extrasynaptic space, confinement in the synapse, and trapping at the postsynaptic density (PSD) through reversible interactions with scaffold proteins. The AMPAR/scaffold kinetic rates were adjusted by comparing computer simulations to single-particle tracking and fluorescence recovery after photobleaching experiments in primary neurons, in different conditions of synapse density and maturation. The model predicts that the steady-state AMPAR number at synapses is bidirectionally controlled by AMPAR/scaffold binding affinity and PSD size. To reveal the impact of recycling processes in basal conditions and upon synaptic potentiation or depression, spatially and temporally defined exocytic and endocytic events were introduced. The model predicts that local recycling of AMPARs close to the PSD, coupled to short-range surface diffusion, provides rapid control of AMPAR number at synapses. In contrast, because of long-range diffusion limitations, extrasynaptic recycling is intrinsically slower and less synapse-specific. Thus, by discriminating the relative contributions of AMPAR diffusion, trapping, and recycling events on spatial and temporal bases, this model provides unique insights on the dynamic regulation of synaptic strength.
引用
收藏
页码:3522 / 3527
页数:6
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