title: Presynaptic AMPA and kainate receptors increase the size of GABAergic terminals and enhance GABA release.
abstract: In the developing cerebellum, NMDA receptors promote the maturation of axonal terminals of inhibitory interneurons. We compared the effects of AMPA/kainate receptor agonists in cultured cerebellar cells from GAD65-eGFP mice. Both AMPA and kainate augmented granule cell survival without affecting interneurons. The action of kainate was blocked by an AMPA but not by a NMDA receptor antagonist, suggesting AMPA receptor involvement. AMPA and kainate increased the size of the GABAergic terminals and the action of kainate was insensitive to NMDA blockers. Whole cell recordings in granule neurons revealed that chronic treatment for 5 days with kainate as well as NMDA decreased AMPA receptor expression while interneuronal kainate receptors were depressed by kainate treatment. Acute kainate application increased mIPSCs frequency in both granule neurons and interneurons and this effect was only partially blocked by an AMPA receptor antagonist. In contrast to what was reported for NMDA, chronic treatment with kainate induced a significant decrease of the basal mIPSCs frequency but increased the acute action of kainate on mIPSCs. Direct recordings from presynaptic GABAergic terminals suggest that AMPA and kainate receptors are present in developing GABAergic terminals and their activation affects the size of GABAergic terminals and spontaneous GABA release.
authors.affiliation: Department of Physiology and Biophysics, Georgetown University School of Medicine, Washington, DC 20007, USA.
authors.forename: Mónica L
authors.initials: ML
authors.lastname: Fiszman
authors.forename: Ferenc
authors.initials: F
authors.lastname: Erdélyi
authors.forename: Gábor
authors.initials: G
authors.lastname: Szabó
authors.forename: Stefano
authors.initials: S
authors.lastname: Vicini
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001569:Benzodiazepines / Q000494:pharmacology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000528:radiation effects; D007395:Interneurons / Q000166:cytology* / Q000187:drug effects; D007608:Kainic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D018091:Receptors, AMPA / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D001569:Benzodiazepines; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D005968:Glutamate Decarboxylase; D049452:Green Fluorescent Proteins; D007608:Kainic Acid; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D005680:gamma-Aminobutyric Acid; C061950:GYKI 52466; C401141:glutamate decarboxylase 2