Modulation of GABAergic signaling among interneurons by metabotropic glutamate receptors.
Synapses between hippocampal interneurons are an important potential target for modulatory influences that could affect overall network behavior. We report that the selective group III metabotropic receptor agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4) depresses GABAergic transmission to interneurons more than to pyramidal neurons. The L-AP4-induced depression is accompanied by changes in trial-to-trial variability and paired-pulse depression that imply a presynaptic site of action. Brief trains of stimuli in Schaffer collaterals also depress GABAergic transmission to interneurons. This depression persists when GABA(B) receptors are blocked, is enhanced by blocking glutamate uptake, and is abolished by the group III metabotropic receptor antagonist (alpha-methylserine-O-phosphate (MSOP). The results imply that GABAergic transmission among interneurons is modulated by glutamate spillover from excitatory afferent terminals.
Semyanov
A
A
University Department of Clinical Neurology, Institute of Neurology, University College London, United Kingdom.
Kullmann
D M
DM
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D006168:Guinea Pigs; D006624:Hippocampus / Q000502:physiology; D066298:In Vitro Techniques; D007395:Interneurons / Q000737:chemistry / Q000502:physiology*; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D009433:Neural Inhibition / Q000502:physiology; D011422:Propionates / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
C114785:2-amino-4-phosphono-propinate; D018691:Excitatory Amino Acid Antagonists; D011422:Propionates; D011810:Quinoxalines; D018094:Receptors, Metabotropic Glutamate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D018698:Glutamic Acid; C020889:dihydrokainic acid; D005680:gamma-Aminobutyric Acid; D015763:2-Amino-5-phosphonovalerate; D007608:Kainic Acid