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Kainate-receptor-mediated sensory synaptic transmission in mammalian spinal cord

Nature volume 397, pages 161–164 (1999)Cite this article

Abstract

Glutamate, the major excitatory neurotransmitter in the central nervous system, activates three different receptors that directly gate ion channels, namely receptors for AMPA (α-amino-3-hydroxy-5-methyl isoxozole propionic acid), NMDA (N-methyl-D-aspartate), and kainate, a structural analogue of glutamate. The contribution of AMPA and NMDA receptors to synaptic transmission and plasticity is well established1. Recent work on the physiological function of kainate receptors has focused on the hippocampus2, where repetitive activation of the mossy-fibre pathway generates a slow, kainate-receptor-mediated excitatory postsynaptic current (EPSC)3,4,5. Here we show that high-intensity single-shock stimulation (of duration 200 microseconds) of primary afferent sensory fibres produces a fast, kainate-receptor-mediated EPSC in the superficial dorsal horn of the spinal cord. Activation of low-threshold afferent fibres generates typical AMPA-receptor-mediated EPSCs only, indicating that kainate receptors may be restricted to synapses formed by high-threshold nociceptive (pain-sensing) and thermoreceptive primary afferent fibres. Consistent with this possibility, kainate-receptor-mediated EPSCs are blocked by the analgesic µ-opiate-receptor agonist Damgo and spinal blockade of both kainate and AMPA receptors produces antinociception. Thus, spinal kainate receptors contribute to transmission of somatosensory inputs from the periphery to the brain.

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Figure 1: AMPA- and NMDA-receptor antagonists produce incomplete block of primary afferent EPSCs.
Figure 2: Kainate-receptor-mediated synaptic transmission.
Figure 3: Kainate-receptor-mediated currents in spinal cultured neurons and a slice.
Figure 4: Kainate receptors reside at synapses receiving high-threshold afferents.
Figure 5: Kainate receptors contribute to ascending sensory transmission.

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Acknowledgements

We thank D. Leander for GYKI 53655. This work was supported in part by grants from NIDA (to M.Z.) and NINDS (to J.E.H.) of the NIH.

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Authors and Affiliations

  1. Departments of Anesthesiology, St Louis, 63110, Missouri, USA

    Ping Li, Susan J. Kim, Amelita A. Calejesan & Min Zhuo

  2. Departments of Cell Biology and Physiology, St Louis, 63110, Missouri, USA

    Timothy J. Wilding & James E. Huettner

  3. Departments of Anatomy and Neurobiology, Washington University in St Louis, St Louis, 63110, Missouri, USA

    Min Zhuo

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Correspondence to Min Zhuo.

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Li, P., Wilding, T., Kim, S. et al. Kainate-receptor-mediated sensory synaptic transmission in mammalian spinal cord. Nature 397, 161–164 (1999). https://doi.org/10.1038/16469

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