title: Spike-driven glutamate electrodiffusion triggers synaptic potentiation via a homer-dependent mGluR-NMDAR link.
abstract: Electric fields of synaptic currents can influence diffusion of charged neurotransmitters, such as glutamate, in the synaptic cleft. However, this phenomenon has hitherto been detected only through sustained depolarization of large principal neurons, and its adaptive significance remains unknown. Here, we find that in cerebellar synapses formed on electrically compact granule cells, a single postsynaptic action potential can retard escape of glutamate released into the cleft. This retardation boosts activation of perisynaptic group I metabotropic glutamate receptors (mGluRs), which in turn rapidly facilitates local NMDA receptor currents. The underlying mechanism relies on a Homer-containing protein scaffold, but not GPCR- or Ca(2+)-dependent signaling. Through the mGluR-NMDAR interaction, the coincidence between a postsynaptic spike and glutamate release triggers a lasting enhancement of synaptic transmission that alters the basic integrate-and-spike rule in the circuitry. Our results thus reveal an electrodiffusion-driven synaptic memory mechanism that requires high-precision coincidence detection suitable for high-fidelity circuitries.
authors: UCL Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors: Sergiy
authors: S
authors: Sylantyev
authors: Leonid P
authors: LP
authors: Savtchenko
authors: Yaroslav
authors: Y
authors: Ermolyuk
authors: Piotr
authors: P
authors: Michaluk
authors: Dmitri A
authors: DA
authors: Rusakov
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000494:pharmacology; D001703:Biophysics; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D000072233:Homer Scaffolding Proteins; D006801:Humans; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000235:genetics; D046529:Microscopy, Electron, Transmission; D008959:Models, Neurological; D009010:Monte Carlo Method; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D011810:Quinoxalines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D018709:Statistics, Nonparametric; D013569:Synapses / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D016704:Synapsins / Q000235:genetics / Q000378:metabolism; D014162:Transfection / Q000379:methods; D000097573:Red Fluorescent Protein
chemical_list: D001224:Aspartic Acid; D002352:Carrier Proteins; D018683:Excitatory Amino Acid Agents; D018698:Glutamic Acid; D049452:Green Fluorescent Proteins; D000072233:Homer Scaffolding Proteins; D008164:Luminescent Proteins; D011810:Quinoxalines; D034741:RNA, Small Interfering; D018094:Receptors, Metabotropic Glutamate; D016704:Synapsins; D000097573:Red Fluorescent Protein; C120673:benzyloxyaspartate; C104077:metabotropic glutamate receptor type 1; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
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