title: Electric fields due to synaptic currents sharpen excitatory transmission.
abstract: The synaptic response waveform, which determines signal integration properties in the brain, depends on the spatiotemporal profile of neurotransmitter in the synaptic cleft. Here, we show that electrophoretic interactions between AMPA receptor-mediated excitatory currents and negatively charged glutamate molecules accelerate the clearance of glutamate from the synaptic cleft, speeding up synaptic responses. This phenomenon is reversed upon depolarization and diminished when intracleft electric fields are weakened through a decrease in the AMPA receptor density. In contrast, the kinetics of receptor-mediated currents evoked by direct application of glutamate are voltage-independent, as are synaptic currents mediated by the electrically neutral neurotransmitter GABA. Voltage-dependent temporal tuning of excitatory synaptic responses may thus contribute to signal integration in neural circuits.
authors: 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: Yin-Ping
authors: YP
authors: Niu
authors: Anton I
authors: AI
authors: Ivanov
authors: Thomas P
authors: TP
authors: Jensen
authors: Dimitri M
authors: DM
authors: Kullmann
authors: Min-Yi
authors: MY
authors: Xiao
authors: Dmitri A
authors: DA
authors: Rusakov
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003712:Dendrites / Q000502:physiology; D004058:Diffusion; D004151:Dipeptides / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials; D018698:Glutamic Acid / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009010:Monte Carlo Method; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018079:Receptors, GABA / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D004151:Dipeptides; D011810:Quinoxalines; D018091:Receptors, AMPA; D018079:Receptors, GABA; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C028929:gamma-glutamylglycine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D008274:Magnesium