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Regulation of AMPA receptor lateral movements



An essential feature in the modulation of the efficacy of synaptic transmission is rapid changes in the number of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors at post-synaptic sites on neurons1,2,3,4. Regulation of receptor endo- and exocytosis has been shown to be involved in this process5,6,7,8,9,10,11,12,13,14. Whether regulated lateral diffusion of receptors in the plasma membrane also participates in receptor exchange to and from post-synaptic sites remains unknown. We analysed the lateral mobility of native AMPA receptors containing the glutamate receptor subunit GluR2 in rat cultured hippocampal neurons, using single-particle tracking and video microscopy. Here we show that AMPA receptors alternate within seconds between rapid diffusive and stationary behaviour. During maturation of neurons, stationary periods increase in frequency and length, often in spatial correlation with synaptic sites. Raising intracellular calcium, a central element in synaptic plasticity, triggers rapid receptor immobilization and local accumulation on the neuronal surface. We suggest that calcium influx prevents AMPA receptors from diffusing, and that lateral receptor diffusion to and from synaptic sites acts in the rapid and controlled regulation of receptor numbers at synapses.

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This work was supported by grants from the Centre National de la Recherche Scientifique and the Conseil Régional d'Aquitaine. A.J.B. was supported by the Fondation pour la Recherche Médicale and an EC (European Commission) Marie Curie Training fellowship. We thank P. Osten for his gift of GluR2–GFP cDNA, A. Benmerah for the gift of the Esp15–GFP cDNA, and R.-M. Mège for the gift of anti-N-Cam. We thank P. Ascher for his support during early phases of this work; C. Mulle, A. Hémar and L. Cognet for their comments on the manuscript; and F. Rossignol for cultures of hippocampal neurons.

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Competing interests

The authors declare that they have no competing financial interests.

Correspondence to Daniel Choquet.

Supplementary information

  1. Legends to supplementary movies 1 - 3 (DOC 20 kb)

  2. Supplementary movie 1 - GluR2 (AVI 3687 kb)

  3. Supplementary movie 2 - GluR-FLASH (AVI 3626 kb)

  4. Supplementary movie 3 - GluR2-Doublebeads (AVI 4133 kb)

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Further reading

Figure 1: Lateral mobility of GluR2 decreases during neuronal maturation.
Figure 2: GluR2 stops reversibly at synaptic sites.
Figure 3: Spontaneous neuronal activity modulates GluR2 mobility.
Figure 4: Local rises in intracellular calcium decrease GluR2 mobility and accumulate GluR2.


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