Abstract
We studied the roles of mGlu2/3 receptors (mGlu2/3) in glutamatergic transmission at corticostriatal synapses in mice brain slices. Perfusion of the selective mGlu2/3 agonists LY354740 and L-CCG1 caused the long term depression (LTD) of evoked synaptic responses. Photonic and electronic microscopy showed mGlu2/3 on axonal fibers and glial processes but not on striatal dendrites. mGlu2/3-LTD was independent of synaptic activity and insensitive to specific antagonists of dopamine D1, D2, GABA(B), N-methyl-D-aspartate or adenosine A1 receptors. Manipulation of the cAMP/protein kinase A cascade had no effect on the mGlu2/3-LTD. In contrast, MEK1-2 inhibitors reduced both mGlu2/3 initial depression and LTD suggesting the involvement of the mitogen activated kinase pathway in mGlu2/3-LTD.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenergic Antagonists / pharmacology
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Animals
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Cerebral Cortex / drug effects
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Cerebral Cortex / metabolism*
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Cerebral Cortex / ultrastructure
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Dendrites / drug effects
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Dendrites / metabolism
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Dendrites / ultrastructure
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Dopamine Antagonists / pharmacology
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Excitatory Amino Acid Agonists / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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Fluorescent Antibody Technique
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GABA Antagonists / pharmacology
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Glutamic Acid / metabolism*
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MAP Kinase Kinase 1
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Male
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Mice
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Mice, Inbred C57BL
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Microscopy, Electron
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Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinase Kinases / metabolism
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Neostriatum / drug effects
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Neostriatum / metabolism*
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Neostriatum / ultrastructure
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Neural Inhibition / drug effects
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Neural Inhibition / physiology*
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Neural Pathways / drug effects
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Neural Pathways / metabolism*
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Neural Pathways / ultrastructure
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Neuroglia / drug effects
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Neuroglia / metabolism
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Neuroglia / ultrastructure
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / physiology
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Presynaptic Terminals / drug effects
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Presynaptic Terminals / metabolism*
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Presynaptic Terminals / ultrastructure
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein Serine-Threonine Kinases / metabolism
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Receptors, Metabotropic Glutamate / drug effects
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Receptors, Metabotropic Glutamate / metabolism*
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
Substances
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Adrenergic Antagonists
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Dopamine Antagonists
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Excitatory Amino Acid Agonists
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Excitatory Amino Acid Antagonists
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GABA Antagonists
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Receptors, Metabotropic Glutamate
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metabotropic glutamate receptor 2
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Glutamic Acid
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Protein Serine-Threonine Kinases
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Cyclic AMP-Dependent Protein Kinases
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MAP Kinase Kinase 1
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Map2k1 protein, mouse
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Mitogen-Activated Protein Kinase Kinases