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Kainate receptors are involved in synaptic plasticity

A Corrigendum to this article was published on 25 January 2001

Abstract

The ability of synapses to modify their synaptic strength in response to activity is a fundamental property of the nervous system and may be an essential component of learning and memory1. There are three classes of ionotropic glutamate receptor, namely NMDA (N-methyl-D-aspartate), AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid) and kainate receptors2; critical roles in synaptic plasticity have been identified for two of these. Thus, at many synapses in the brain, transient activation of NMDA receptors leads to a persistent modification in the strength of synaptic transmission mediated by AMPA receptors3,4. Here, to determine whether kainate receptors5,6,7 are involved in synaptic plasticity, we have used a new antagonist, LY382884 ((3S, 4aR, 6S, 8aR)-6-((4-carboxyphenyl)methyl-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid), which antagonizes kainate receptors at concentrations that do not affect AMPA or NMDA receptors. We find that LY382884 is a selective antagonist at neuronal kainate receptors containing the GluR5 subunit. It has no effect on long-term potentiation (LTP) that is dependent on NMDA receptors but prevents the induction of mossy fibre LTP, which is independent of NMDA receptors. Thus, kainate receptors can act as the induction trigger for long-term changes in synaptic transmission.

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Figure 1: LY382884 is a selective GluR5 kainate receptor antagonist.
Figure 2: LY382884 as an antagonist in rat hippocampal slices.
Figure 3: LY382884 specifically blocks the induction of mossy fibre LTP.
Figure 4: LY382884 does not affect forskolin-induced LTP.
Figure 5: Kynurenate and CNQX block the induction of mossy fibre LTP.

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Acknowledgements

We thank B. Anderson for providing the data acquisition software (http://www. ltp-program.com). This work was supported by the MRC. I.S. is a postdoc of the FWO-Vlaanderen, Belgium.

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Bortolotto, Z., Clarke, V., Delany, C. et al. Kainate receptors are involved in synaptic plasticity. Nature 402, 297–301 (1999). https://doi.org/10.1038/46290

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