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Synaptic activation of kainate receptors on hippocampal interneurons

Nature Neuroscience volume 1, pages 479–486 (1998)Cite this article

Abstract

Although kainate receptor activation has been known to evoke epileptiform activity, little is known about the role of kainate receptors in synaptic transmission. Here we report that kainate (KA) receptors are present on interneurons and, when activated, cause a large increase in the frequency of spontaneous inhibitory postsynaptic currents (IPSCs) driven by action potentials. Stimulation of excitatory afferents generates a pharmacologically identifiable synaptic current mediated by KA receptors in interneurons. This synaptic current is similar to that mediated by AMPA receptors in its response to short stimulus trains, current–voltage relations and coefficient of variation, but it is much smaller in peak amplitude and much slower. KA application also considerably depresses evoked IPSCs. This depression seems to be in large part an indirect consequence of the repetitive firing evoked by the activation of the interneuronal somatic/dendritic KA receptors.

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Figure 1: KA receptor activation increases the frequency of TTX-sensitive sIPSCs.
Figure 2: Kainate receptor activation depolarizes interneurons and increases interneuronal spiking rate.
Figure 3: EPSCs in interneurons, but not in pyramidal cells, have a KA receptor-mediated component.
Figure 4: EPSCAMPA and EPSCKA in interneurons have different pharmacological properties but similar release properties.
Figure 5: Current–voltage relations of the EPSCAMPA and EPSCKA are similar.
Figure 6: The stimulus-evoked monosynaptic IPSC on pyramidal cells is rapidly and reversibly reduced by KA receptor activation.
Figure 7: KA receptor activation has no effect on miniature IPSCs in TTX.
Figure 8: The KA-induced depression of stimulus-evoked IPSCs results from the KA-induced increase in interneuronal spiking.

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Acknowledgements

We thank members of the Nicoll-Malenka lab for discussions, D. Selig for providing on-line data acquisition software and H. Czerwonka for secretarial support. M.F. is supported by an NIH postdoctoral training grant in Neuroscience (T32NS07067). R.A.N. is a member of the Keck Center for Integrative Neuroscience and the Silvio Conte Center for Neuroscience Research. R.C.M. is a member of the Center for Neurobiology and Psychiatry, and the Center for the Neurobiology of Addiction. R.A.N. is supported by grants from the NIH. R.C.M. is supported by grants from the NIH, HFSP, and an Investigator Award from the McKnight Endowment Fund for Neuroscience.

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Authors and Affiliations

  1. Departments of Cellular and Molecular, Pharmacology University of California, San Francisco, 94143, California, USA

    M. Frerking & R. A. Nicoll

  2. Department of Physiology, University of California, San Francisco, 94143, California, USA

    R. C. Malenka & R. A. Nicoll

  3. Department of Psychiatry, University of California, San Francisco, 94143, California, USA

    R. C. Malenka

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  1. M. Frerking
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Correspondence to R. A. Nicoll.

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Frerking, M., Malenka, R. & Nicoll, R. Synaptic activation of kainate receptors on hippocampal interneurons . Nat Neurosci 1, 479–486 (1998). https://doi.org/10.1038/2194

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