Electric fields due to synaptic currents sharpen excitatory transmission.
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.
Sylantyev
Sergiy
S
Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK.
Savtchenko
Leonid P
LP
Niu
Yin-Ping
YP
Ivanov
Anton I
AI
Jensen
Thomas P
TP
Kullmann
Dimitri M
DM
Xiao
Min-Yi
MY
Rusakov
Dmitri A
DA
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
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