Journal
SCIENCE
Volume 319, Issue 5871, Pages 1845-1849Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1154330
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Funding
- MRC [G0400627, G0600368, G116/147] Funding Source: UKRI
- Medical Research Council [G0400627(76527), G0400627, G0400627(71256), G0600368, G0600368(77987), G116/147] Funding Source: Medline
- Wellcome Trust [071179] Funding Source: Medline
- Medical Research Council [G0601943B, G0600368, G116/147, G0400627] Funding Source: researchfish
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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.
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