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Synaptic activation of AMPA receptors inhibits GABA release from cerebellar interneurons

Nature Neuroscience volume 3, pages 551–558 (2000)Cite this article

Abstract

A single neurotransmitter elicits diverse physiological responses through activation of multiple receptor subtypes and/or heterosynaptic interactions involving distinct synaptic targets. We found that a typical excitatory transmitter released from the climbing fiber (CF) in the cerebellar cortex not only excited Purkinje cells directly but also presynaptically inhibited GABAergic transmission from interneurons converging on the same Purkinje cells. Both homosynaptic and heterosynaptic actions of the CF transmitter (possibly glutamate) were mediated by activation of AMPA receptors. Dual AMPA receptor-mediated functions of excitation and disinhibition may ensure transmission of cerebellar CF signals controlling sensorimotor coordination.

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Figure 1: Repetitive activation of the CF inhibits GABAergic transmission on to rat cerebellar PCs.
Figure 2: Stimulus frequency, intensity and number dependency, and time course of CF stimulation-induced inhibition of GABAergic IPSCs.
Figure 3: The amplitude but not the frequency of GABA receptor-mediated sIPSC decreased after the CF repetitive stimulation.
Figure 4: Presynaptic nature of the CF-induced inhibition of cerebellar GABAergic transmission.
Figure 5: Inhibitory effect of CF conditioning stimulation on BC action current-triggered IPSCs determined by double recordings from a BC–PC pair.
Figure 6: Effects of ionotropic and metabotropic glutamate receptor antagonists and a modulator of AMPA receptors on the CF-induced inhibition of GABAA IPSCs.
Figure 7: Pharmacology for testing possible involvement of mGluR2/3 and intracellular messengers in the CF-induced inhibition of GABAergic transmission.
Figure 8: Effects of AMPA, an ionotropic GluR agonist, on the GABAA IPSC and specific enhancement of the AMPA effect by CYZ, an inhibitor of AMPA receptor desensitization.

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Acknowledgements

We thank N. Bowery, T. Murakoshi, H. Suzuki and K. Yoshioka for comments on the manuscript and D. Lodge at Eli Lilly and Fujisawa Pharmaceutical for the gifts of GYKI 53655 and FK506, respectively.

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Authors and Affiliations

  1. Laboratory of Molecular Neurobiology, Mitsubishi Kasei Institute of Life Sciences and CREST (Japan Science and Technology), 11 Minamiooya, Machida-shi, Tokyo, 194-8511, Japan

    Shin'Ichiro Satake, Fumihito Saitow, Junko Yamada & Shiro Konishi

  2. Department of Applied Biology, Faculty of Textile Science, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, 606-8585, Japan

    Junko Yamada

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  1. Shin'Ichiro Satake
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Correspondence to Shiro Konishi.

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Satake, S., Saitow, F., Yamada, J. et al. Synaptic activation of AMPA receptors inhibits GABA release from cerebellar interneurons. Nat Neurosci 3, 551–558 (2000). https://doi.org/10.1038/75718

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