Slow AMPAR Synaptic Transmission Is Determined by Stargazin and Glutamate Transporters

Hsin Wei Lu, Timothy S. Balmer, Gabriel E. Romero, Laurence Trussell

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

AMPARs mediate the briefest synaptic currents in the brain by virtue of their rapid gating kinetics. However, at the mossy fiber-to-unipolar brush cell synapse in the cerebellum, AMPAR-mediated EPSCs last for hundreds of milliseconds, and it has been proposed that this time course reflects slow diffusion from a complex synaptic space. We show that upon release of glutamate, synaptic AMPARs were desensitized by transmitter by >90%. As glutamate levels subsequently fell, recovery of transmission occurred due to the presence of the AMPAR accessory protein stargazin that enhances the AMPAR response to low levels of transmitter. This gradual increase in receptor activity following desensitization accounted for the majority of synaptic transmission at this synapse. Moreover, the amplitude, duration, and shape of the synaptic response was tightly controlled by plasma membrane glutamate transporters, indicating that clearance of synaptic glutamate during the slow EPSC is dictated by an uptake process. Glutamate receptors that normally participate in rapid synaptic signaling can also create ultra-slow signals. Lu et al. show that slow signals require TARP accessory subunits to glutamate receptors as well as tight control of glutamate time course mediated by transporters.

Original languageEnglish (US)
JournalNeuron
DOIs
StateAccepted/In press - 2017

ASJC Scopus subject areas

  • Neuroscience(all)

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