Abstract
1. Depolarization-induced suppression of inhibition (DSI) is a form of synaptic plasticity which involves a retrograde messenger. We have performed experiments in Purkinje cells of rat cerebellar slices to determine the nature of this messenger. 2. DSI is mimicked by 2-(2,3-dicarboxycyclopropyl)-glycine (DCG-IV), a specific agonist of group II metabotropic glutamate receptors (mGluRs). 3. DSI is reduced if transmitter release is inhibited by saturating doses of DCG-IV. 4. Both DSI and DCG-IV-induced inhibition are inhibited by L-2-amino-3-phosphonopropionic acid (L-AP3), a drug which interferes with several subtypes of mGluRs. 5. DSI is reduced if synaptic activity is enhanced by application of forskolin. 6. We propose that glutamate or a glutamate-like substance is the retrograde messenger implicated in DSI, and that the inhibition resulting from presynaptic glutamate binding is mediated by a decrease in the presynaptic concentration of cAMP.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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2-Amino-5-phosphonovalerate / pharmacology
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Alanine / analogs & derivatives
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Alanine / pharmacology
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Animals
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Benzoates / pharmacology
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Colforsin / pharmacology
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Cyclopropanes / pharmacology
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Electrophysiology
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Excitatory Amino Acid Antagonists / pharmacology
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Glutamic Acid / physiology*
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Glycine / analogs & derivatives
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Glycine / pharmacology
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Interneurons / chemistry
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Interneurons / physiology*
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Kinetics
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Presynaptic Terminals / chemistry
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Presynaptic Terminals / physiology
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Purkinje Cells / chemistry
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Purkinje Cells / physiology*
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Purkinje Cells / ultrastructure
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Quinoxalines / pharmacology
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Rats
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Receptors, Metabotropic Glutamate / agonists
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Receptors, Metabotropic Glutamate / antagonists & inhibitors
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Receptors, Metabotropic Glutamate / physiology
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Synapses / chemistry
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Synapses / drug effects
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Synapses / physiology
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology*
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Tetrodotoxin / pharmacology
Substances
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Benzoates
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Cyclopropanes
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Excitatory Amino Acid Antagonists
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Quinoxalines
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Receptors, Metabotropic Glutamate
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2-amino-3-phosphonopropionic acid
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2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
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alpha-methyl-4-carboxyphenylglycine
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2-(2,3-dicarboxycyclopropyl)glycine
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Colforsin
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Glutamic Acid
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Tetrodotoxin
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2-Amino-5-phosphonovalerate
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Alanine
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Glycine