The glial glutamate transporter GLT-1 is localized both in the vicinity of and at distance from axon terminals in the rat cerebral cortex

Neuroscience. 2001;108(1):51-9. doi: 10.1016/s0306-4522(01)00375-x.

Abstract

Glutamate transporter-1 (GLT-1) is responsible for the largest proportion of glutamate transport in the brain and the density of GLT-1 molecules inserted in the plasma membrane is highest in regions of high demand. Previous electron microscopic studies in the hippocampus and cerebellum have shown that GLT-1 is concentrated both in the vicinity of and at considerable distance from the synaptic cleft [Chaudry et al., Neuron 15 (1995) 711-721], but little is known about its distribution in the neocortex. We therefore studied the spatial relationships between elements expressing the presynaptic marker synaptophysin and those containing GLT-1 in the rat cerebral cortex using confocal microscopy. Preliminary studies confirmed that GLT-1 positive puncta were exclusively astrocytic processes; moreover, they showed that in most cases GLT-1 positive processes either completely surrounded asymmetric synapses or had no apparent relationship with synapses; occasionally, they were apposed to terminals containing pleomorphic vesicles. In sections double-labeled for GLT-1 and synaptophysin, codistribution analysis revealed that 61.2% of pixels detecting fluorescent emission for GLT-1 immunoreactivity overlapped with pixels detecting synaptophysin. The percentages of GLT-1/synaptophysin codistribution were significantly different from controls. In sections double-labeled for GLT-1 and the vesicular GABA transporter, codistribution analysis revealed that 27% of pixels detecting GLT-1 overlapped with those revealing the vesicular GABA transporter.The remarkable 'synaptic' localization of GLT-1 provides anatomical support for the hypothesis that in the cerebral cortex GLT-1 contributes to shaping fast, point-to-point, excitatory synaptic transmission. Moreover, the considerable fraction of GLT-1 immunoreactivity localized at sites distant from axon terminals supports the notion that glutamate spillout occurs also in the intact brain and suggests that 'extrasynaptic' GLT-1 regulates the diffusion of glutamate escaped from the cleft.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / ultrastructure
  • Excitatory Amino Acid Transporter 2 / metabolism*
  • Fluorescent Antibody Technique
  • Immunoenzyme Techniques
  • Microscopy, Confocal
  • Neuroglia / metabolism*
  • Presynaptic Terminals / metabolism*
  • Rats
  • Synapses / metabolism
  • Synaptophysin / metabolism
  • Tissue Distribution

Substances

  • Excitatory Amino Acid Transporter 2
  • Synaptophysin

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