ly382884 and alpha-amino-3-hydroxy-5-tert-butyl-4-isoxazolepropionate

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.

Topics: 2-Amino-5-phosphonovalerate; 6-Cyano-7-nitroquinoxaline-2,3-dione; Amino Acids, Dicarboxylic; Animals; Benzodiazepines; Cyclopropanes; Excitatory Postsynaptic Potentials; Gene Deletion; GluK2 Kainate Receptor; Glycine; Isoquinolines; Isoxazoles; Kainic Acid; Mice; Mice, Knockout; Mossy Fibers, Hippocampal; Neuronal Plasticity; Patch-Clamp Techniques; Potassium; Propionates; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Kainic Acid; Synaptic Transmission

Kainate receptors are involved in a variety of synaptic functions in the CNS including the regulation of excitatory synaptic transmission. Previously we described the depressant action of the GLU(K5) selective agonist (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid (ATPA) on synaptic transmission in the Schaffer collateral-commissural pathway of rat hippocampal slices. In the present study we report several new features of the actions of ATPA at this synapse. Firstly, the effectiveness of ATPA is developmentally regulated. Secondly, the effects of ATPA decline during prolonged or repeated applications. Thirdly, the effects of ATPA are not mediated indirectly via activation of GABA(A), GABA(B), muscarinic or adenosine A(1) receptors. Fourthly, elevating extracellular Ca(2+) from 2 to 4 mM antagonises the effects of ATPA. Some differences between the actions of ATPA and kainate on synaptic transmission in the Schaffer collateral-commissural pathway are also noted.

Topics: Animals; Excitatory Postsynaptic Potentials; Hippocampus; In Vitro Techniques; Isoquinolines; Isoxazoles; Propionates; Pyramidal Cells; Rats; Rats, Wistar; Receptors, Kainic Acid; Synaptic Transmission