Abstract
Brain functions are based on the dynamic interaction of excitatory and inhibitory inputs. Spillover of glutamate from excitatory synapses may diffuse to and modulate nearby inhibitory synapses. By recording unitary inhibitory postsynaptic currents (uIPSCs) from cell pairs in CA1 of the hippocampus, we demonstrated that low concentrations of Kainate receptor (KAR) agonists increased the success rate (P(s)) of uIPSCs, whereas high concentrations of KAR agonists depressed GABAergic synapses. Ambient glutamate released by basal activities or stimulation of the stratum radiatum increases the efficacy of GABAergic synapses by activating presynaptic KARs, which facilitate Ca(2+)-dependent GABA release. The results suggest that glutamate released from excitatory synapses may also function as an intermediary between excitatory and inhibitory synapses to protect overexcitation of local circuits.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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2-Amino-5-phosphonovalerate / pharmacology
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6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
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Animals
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Benzoates / pharmacology
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Benzodiazepines / pharmacology
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Enzyme Inhibitors / pharmacology
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Evoked Potentials / drug effects
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Evoked Potentials / physiology*
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Excitatory Amino Acid Antagonists / pharmacology*
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology*
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Glycine / analogs & derivatives
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Glycine / pharmacology
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Hippocampus / drug effects
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Hippocampus / physiology*
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In Vitro Techniques
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Interneurons / drug effects
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Interneurons / physiology
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Kainic Acid / pharmacology*
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Neurons / drug effects
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Neurons / physiology*
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Protein Kinase C / metabolism
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Pyramidal Cells / drug effects
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Pyramidal Cells / physiology*
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Quinoxalines / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, Kainic Acid / agonists
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Receptors, Kainic Acid / physiology*
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Staurosporine / pharmacology
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Synapses / drug effects
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Synapses / physiology*
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Tetradecanoylphorbol Acetate / pharmacology
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Tetrodotoxin / pharmacology
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gamma-Aminobutyric Acid / physiology*
Substances
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Benzoates
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Enzyme Inhibitors
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Excitatory Amino Acid Antagonists
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Quinoxalines
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Receptors, Kainic Acid
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2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
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Benzodiazepines
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alpha-methyl-4-carboxyphenylglycine
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Tetrodotoxin
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gamma-Aminobutyric Acid
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6-Cyano-7-nitroquinoxaline-2,3-dione
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2-Amino-5-phosphonovalerate
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talampanel
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Cyclic AMP-Dependent Protein Kinases
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Protein Kinase C
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Staurosporine
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Tetradecanoylphorbol Acetate
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Kainic Acid
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Glycine