Unified quantitative model of AMPA receptor trafficking at synapses

K. Czondor, M. Mondin, M. Garcia, M. Heine, R. Frischknecht, D. Choquet, J.-B. Sibarita, O. R. Thoumine
Proceedings of the National Academy of Sciences. 2012-02-13; 109(9): 3522-3527
DOI: 10.1073/pnas.1109818109

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1. Proc Natl Acad Sci U S A. 2012 Feb 28;109(9):3522-7. doi:
10.1073/pnas.1109818109. Epub 2012 Feb 13.

Unified quantitative model of AMPA receptor trafficking at synapses.

Czöndör K(1), Mondin M, Garcia M, Heine M, Frischknecht R, Choquet D, Sibarita
JB, Thoumine OR.

Author information:
(1)Interdisciplinary Institute for Neuroscience, University of Bordeaux, F-33000
Bordeaux, France.

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 postsynapses (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.

DOI: 10.1073/pnas.1109818109
PMCID: PMC3295262
PMID: 22331885 [Indexed for MEDLINE]

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