title: Spillover of glutamate onto synaptic AMPA receptors enhances fast transmission at a cerebellar synapse.
abstract: Diffusion of glutamate from the synaptic cleft can activate high-affinity receptors, but is not thought to contribute to fast AMPA receptor-mediated transmission. Here, we show that single AMPA receptor EPSCs at the cerebellar mossy fiber-granule cell connection are mediated by both direct release of glutamate and rapid diffusion of glutamate from neighboring synapses. Immunogold localization revealed that AMPA receptors are located exclusively in postsynaptic densities, indicating that spillover of glutamate occurs between synaptic contacts. Spillover currents contributed half the synaptic charge and exhibited little trial-to-trial variability. We propose that spillover of glutamate improves transmission efficacy by both increasing the amplitude and duration of the EPSP and reducing fluctuations arising from the probabilistic nature of transmitter release.
authors.affiliation: Department of Physiology, University College London, Gower Street, London WC1E 6BT, United Kingdom.
authors.forename: David A
authors.initials: DA
authors.lastname: DiGregorio
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Nusser
authors.forename: R Angus
authors.initials: RA
authors.lastname: Silver
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002525:Cerebellar Cortex / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D007150:Immunohistochemistry; D007736:Kynurenic Acid / Q000494:pharmacology; D008854:Microscopy, Electron; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology*; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology*; D013997:Time Factors
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D018698:Glutamic Acid; D007736:Kynurenic Acid; C104722:glutamate receptor ionotropic, AMPA 2