Assessing the role of GLUK5 and GLUK6 at hippocampal mossy fiber synapses.
It has been suggested recently that presynaptic kainate receptors (KARs) are involved in short-term and long-term synaptic plasticity at hippocampal mossy fiber synapses. Using genetic deletion and pharmacology, we here assess the role of GLU(K5) and GLU(K6) in synaptic plasticity at hippocampal mossy fiber synapses. We found that the kainate-induced facilitation was completely abolished in the GLU(K6)-/- mice, whereas it was unaffected in the GLU(K5)-/-. Consistent with this finding, synaptic facilitation was reduced in the GLU(K6)(-/-) and was normal in the GLU(K5)-/-. In agreement with these results and ruling out any compensatory effects in the genetic deletion models, application of the GLU(K5)-specific antagonist LY382884 [(3S,4aR,6S,8aR)-6-(4-carboxyphenyl)methyl-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid] did not affect short-term and long-term synaptic plasticity at the hippocampal mossy fiber synapses. We therefore conclude that the facilitatory effects of kainate on mossy fiber synaptic transmission are mediated by GLU(K6)-containing KARs.
Breustedt
Jörg
J
Neurowissenschaftliches Forschungszentrum, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany.
Schmitz
Dietmar
D
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D003521:Cyclopropanes / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D017353:Gene Deletion; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D007555:Isoxazoles / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D018092:Kainic Acid Receptors / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D000097806:GluK2 Kainate Receptor
D015763:2-Amino-5-phosphonovalerate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000600:Amino Acids, Dicarboxylic; D001569:Benzodiazepines; D003521:Cyclopropanes; D005998:Glycine; D007546:Isoquinolines; D007555:Isoxazoles; D007608:Kainic Acid; D011188:Potassium; D011422:Propionates; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor; C400802:LY382884; C081662:alpha-amino-3-hydroxy-5-tert-butyl-4-isoxazolepropionate; C079692:GYKI 53655; C082313:2-(2,3-dicarboxycyclopropyl)glycine; C035261:(alpha-carboxycyclopropyl)glycine