Spillover of glutamate onto synaptic AMPA receptors enhances fast transmission at a cerebellar synapse

Neuron. 2002 Aug 1;35(3):521-33. doi: 10.1016/s0896-6273(02)00787-0.

Abstract

Diffusion of glutamate from the synaptic cleft can activate high-affinity receptors, but is not thought to contribute to fast AMPA receptor-mediated transmission. Here, we show that single AMPA receptor EPSCs at the cerebellar mossy fiber-granule cell connection are mediated by both direct release of glutamate and rapid diffusion of glutamate from neighboring synapses. Immunogold localization revealed that AMPA receptors are located exclusively in postsynaptic densities, indicating that spillover of glutamate occurs between synaptic contacts. Spillover currents contributed half the synaptic charge and exhibited little trial-to-trial variability. We propose that spillover of glutamate improves transmission efficacy by both increasing the amplitude and duration of the EPSP and reducing fluctuations arising from the probabilistic nature of transmitter release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Animals
  • Cell Differentiation / physiology
  • Cerebellar Cortex / growth & development
  • Cerebellar Cortex / metabolism*
  • Cerebellar Cortex / ultrastructure
  • Dendrites / metabolism
  • Dendrites / ultrastructure
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • Glutamic Acid / metabolism*
  • Glutamic Acid / pharmacology
  • Immunohistochemistry
  • Kynurenic Acid / pharmacology
  • Microscopy, Electron
  • Nerve Fibers / drug effects
  • Nerve Fibers / metabolism*
  • Nerve Fibers / ultrastructure
  • Organ Culture Techniques
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism*
  • Presynaptic Terminals / ultrastructure
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / drug effects
  • Reaction Time / physiology*
  • Receptors, AMPA / drug effects
  • Receptors, AMPA / metabolism*
  • Receptors, AMPA / ultrastructure
  • Synaptic Membranes / drug effects
  • Synaptic Membranes / metabolism
  • Synaptic Membranes / ultrastructure
  • Synaptic Transmission / physiology*
  • Time Factors

Substances

  • Excitatory Amino Acid Antagonists
  • Receptors, AMPA
  • Glutamic Acid
  • Kynurenic Acid
  • glutamate receptor ionotropic, AMPA 2