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Publication : The role of glial glutamate transporters in maintaining the independent operation of juvenile mouse cerebellar parallel fibre synapses.

First Author  Marcaggi P Year  2003
Journal  J Physiol Volume  552
Issue  Pt 1 Pages  89-107
PubMed ID  12878755 Mgi Jnum  J:105257
Mgi Id  MGI:3614584 Doi  10.1113/jphysiol.2003.044263
Citation  Marcaggi P, et al. (2003) The role of glial glutamate transporters in maintaining the independent operation of juvenile mouse cerebellar parallel fibre synapses. J Physiol 552(Pt 1):89-107
abstractText  There is controversy over the extent to which glutamate released at one synapse can escape from the synaptic cleft and affect receptors at other synapses nearby, thereby compromising the synapse-specificity of information transmission. Here we show that the glial glutamate transporters GLAST and GLT-1 limit the activation of Purkinje cell AMPA receptors produced by glutamate diffusion between parallel fibre synapses in the cerebellar cortex of juvenile mice. For a single stimulus to the cerebellar molecular layer of wild-type mice, increasing the number of activated parallel fibres prolonged the parallel fibre EPSC, demonstrating an interaction between different synapses. Knocking out GLAST, or blocking GLT-1 in the absence of GLAST, prolonged the EPSC when many parallel fibres were stimulated but not when few were stimulated. When spatially separated parallel fibres were activated by granular layer stimulation, the EPSC prolongation produced by stimulating more fibres or reducing glutamate transport was greatly reduced. Thus, GLAST and GLT-1 curtail the EPSC produced by a single stimulus only when many nearby fibres are simultaneously activated. However when trains of stimuli were applied, even to a small number of parallel fibres, knocking out GLAST or blocking GLT-1 in the absence of GLAST greatly prolonged and enhanced the AMPA receptor-mediated current. These results show that glial cell glutamate transporters allow neighbouring synapses to operate more independently, and control the postsynaptic response to high frequency bursts of action potentials.
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