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Developmental and activity- dependent regulation of kainate receptors at thalamocortical synapses

Nature volume 400, pages 569–573 (1999)Cite this article

Abstract

Most of the fast excitatory synaptic transmission in the mammalian brain is mediated by ionotrophic glutamate receptors, of which there are three subtypes: AMPA (α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate), NMDA (N -methyl-D-aspartate) and kainate. Although kainate-receptor subunits (GluR5–7, KA1 and 2) are widely expressed in the mammalian central nervous system1,2, little is known about their function. The development of pharmacological agents that distinguish between AMPA and kainate receptors has now allowed the functions of kainate receptors to be investigated3,4. The modulation of synaptic transmission by kainate receptors5,6,7 and their synaptic activation8,9,10,11,12,13,14 in a variety of brain regions have been reported. The expression of kainate receptor subunits is developmentally regulated1,2 but their role in plasticity and development is unknown. Here we show that developing thalamocortical synapses express postsynaptic kainate receptors as well as AMPA receptors; however, the two receptor subtypes do not co-localize. During the critical period for experience-dependent plasticity, the kainate-receptor contribution to transmission decreases; a similar decrease occurs when long-term potentiation is induced in vitro. This indicates that during development there is activity-dependent regulation of the expression of kainate receptors at thalamocortical synapses.

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Figure 1: KAR-mediated synaptic transmission at developing thalamocortical synapses.
Figure 2: KAR-mediated EPSCs can be evoked in the absence of an AMPAR component.
Figure 3: AMPAR-mediated spontaneous EPSCs do not have a KAR component.
Figure 4: Slow spontaneous EPSCs with similar kinetics and pharmacology to evoked kainate EPSCs coexist with AMPAR-mediated SEPSCs.
Figure 5: The KAR component of thalamocortical transmission decreases during the critical period.
Figure 6: LTP induction causes a rapid reduction in the KAR component of EPSCs.

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Acknowledgements

We thank G. Collingridge, V. Clarke, R. Chittajallu, S.Braithwaite and J. Crabtree for advice and comments; W. W. Anderson for providing the data acquisition software; and D. Lodge (Eli Lilly and Co.) for supplying the GYKI 53655. This work was supported by the Wellcome Trust.

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  1. Department of Anatomy, MRC Centre for Synaptic Plasticity, University of Bristol, Bristol, BS8 1TD, UK

    Fleur L. Kidd & John T. R. Isaac

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Kidd, F., Isaac, J. Developmental and activity- dependent regulation of kainate receptors at thalamocortical synapses. Nature 400, 569–573 (1999). https://doi.org/10.1038/23040

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