title: Changes in synaptic structure underlie the developmental speeding of AMPA receptor-mediated EPSCs.
abstract: 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.
authors.affiliation: [1] Department of Pharmacology, University College London, UK.
authors.forename: Laurence
authors.initials: L
authors.lastname: Cathala
authors.forename: Noemi B
authors.initials: NB
authors.lastname: Holderith
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Nusser
authors.forename: David A
authors.initials: DA
authors.lastname: DiGregorio
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Cull-Candy
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001569:Benzodiazepines / Q000494:pharmacology; D002531:Cerebellum / Q000166:cytology* / Q000254:growth & development; D004307:Dose-Response Relationship, Radiation; D004553:Electric Conductivity; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018698:Glutamic Acid / Q000378:metabolism; D021621:Imaging, Three-Dimensional / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008959:Models, Neurological; D009412:Nerve Fibers / Q000000981:diagnostic imaging / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques / Q000379:methods; D018091:Receptors, AMPA / Q000502:physiology* / Q000648:ultrastructure; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology*; D013696:Temperature; D014463:Ultrasonography
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D001569:Benzodiazepines; C079692:GYKI 53655; D018698:Glutamic Acid; D007736:Kynurenic Acid