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The Journal of Neuroscience, November 10, 2004, 24(45):10093-10098; doi:10.1523/JNEUROSCI.3078-04.2004

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Cellular/Molecular
Assessing the Role of GLU_K5 and GLU_K6 at Hippocampal Mossy Fiber Synapses

Jörg Breustedt and Dietmar Schmitz

Neurowissenschaftliches Forschungszentrum, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany

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.

Key words: hippocampus; kainate receptors; long-term potentiation; mossy fiber synapses; short-term potentiation; synaptic plasticity

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Received July 28, 2004; revised September 13, 2004; accepted September 13, 2004.

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