Changes in synaptic structure underlie the developmental speeding of AMPA receptor-mediated EPSCs

被引:98
作者
Cathala, L
Holderith, NB
Nusser, Z
DiGregorio, DA
Cull-Candy, SG
机构
[1] UCL, Dept Pharmacol, London WC1E 6BT, England
[2] Univ Paris 05, CNRS, UMR 8118, F-75006 Paris, France
[3] Hungarian Acad Sci, Inst Expt Med, Lab Cellular Neurophysiol, H-1083 Budapest, Hungary
基金
英国惠康基金;
关键词
D O I
10.1038/nn1534
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
At many excitatory and inhibitory synapses throughout the nervous system, postsynaptic currents become faster as the synapse matures, primarily owing to changes in receptor subunit composition. The origin of the developmental acceleration of AMPA receptor (AMPAR)-mediated excitatory postsynaptic currents (EPSCs) remains elusive. We used patch-clamp recordings, electron microscopic immunogold localization of AMPARs, partial three-dimensional reconstruction of the neuropil and numerical simulations of glutamate diffusion and AMPAR activation to examine the factors underlying the developmental speeding of miniature EPSCs in mouse cerebellar granule cells. We found that the main developmental change that permits submillisecond transmission at mature synapses is an alteration in the glutamate concentration waveform as experienced by AMPARs. This can be accounted for by changes in the synaptic structure and surrounding neuropil, rather than by a change in AMPAR properties. Our findings raise the possibility that structural alterations could be a general mechanism underlying the change in the time course of AMPAR-mediated synaptic transmission.
引用
收藏
页码:1310 / 1318
页数:9
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