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Patterned expression of Purkinje cell glutamate transporters controls synaptic plasticity

Abstract

Glutamate transporters are responsible for clearing synaptically released glutamate from the extracellular space. If expressed at high enough densities, transporters can prevent activation of extrasynaptic receptors by rapidly lowering glutamate concentrations to insignificant levels. We find that synaptic activation of metabotropic glutamate receptors expressed by Purkinje cells is prevented in regions of rat cerebellum where the density of the glutamate transporter EAAT4 is high. The consequences of metabotropic receptor stimulation, including activation of a depolarizing conductance, cannabinoid-mediated presynaptic inhibition and long-term depression, are also limited in Purkinje cells expressing high levels of EAAT4. We conclude that neuronal uptake sites must be overwhelmed by glutamate to activate perisynaptic metabotropic glutamate receptors. Regional differences in glutamate transporter expression affect the degree of metabotropic glutamate receptor activation and therefore regulate synaptic plasticity.

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Figure 1: Purkinje cell location predicts transporter number and occupancy following climbing fiber activation.
Figure 2: Release probability is not dependent on Purkinje cell location.
Figure 3: Purkinje cell location predicts transporter number following parallel fiber (PF) activation.
Figure 4: Parallel fiber (PF)–Purkinje cell mGluR currents depend on Purkinje cell location.
Figure 5: Purkinje cell mGluR sensitivity does not depend on cell location.
Figure 6: Regional differences in mGluR-mediated synaptic plasticity.

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Acknowledgements

We thank the members of the Jahr lab, L.O. Wadiche and A.V. Tzingounis for comments and suggestions during this project. Supported by NS40056 (C.E.J.).

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Correspondence to Craig E Jahr.

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Wadiche, J., Jahr, C. Patterned expression of Purkinje cell glutamate transporters controls synaptic plasticity. Nat Neurosci 8, 1329–1334 (2005). https://doi.org/10.1038/nn1539

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