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.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Analysis of Variance
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Animals
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Animals, Newborn
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Aspartic Acid / pharmacology
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Calcium / pharmacology
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Cannabinoids / pharmacology
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Cerebellum / cytology*
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Dose-Response Relationship, Drug
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Drug Interactions
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Excitatory Amino Acid Agonists / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Amino Acid Transporter 4 / metabolism*
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Excitatory Postsynaptic Potentials / physiology
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Excitatory Postsynaptic Potentials / radiation effects
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology*
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Glutamic Acid / metabolism
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In Vitro Techniques
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Long-Term Synaptic Depression / drug effects
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Long-Term Synaptic Depression / physiology
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Membrane Potentials / radiation effects
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Methoxyhydroxyphenylglycol / analogs & derivatives
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Methoxyhydroxyphenylglycol / pharmacology
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Neuronal Plasticity / physiology*
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Patch-Clamp Techniques / methods
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Purkinje Cells / physiology*
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Quinoxalines / pharmacology
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Rats
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Synapses / metabolism*
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology
Substances
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Cannabinoids
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Excitatory Amino Acid Agonists
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Excitatory Amino Acid Antagonists
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Excitatory Amino Acid Transporter 4
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Quinoxalines
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Slc1a6 protein, rat
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benzyloxyaspartate
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2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
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Aspartic Acid
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Glutamic Acid
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Methoxyhydroxyphenylglycol
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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Calcium
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3,4-dihydroxyphenylglycol