Ablation of cerebellar Golgi cells disrupts synaptic integration involving GABA inhibition and NMDA receptor activation in motor coordination
Watanabe D, Inokawa H, Hashimoto K, Suzuki N, Kano M, Shigemoto R, Hirano T, Toyama K, Kaneko S, Yokoi M, Moriyoshi K, Suzuki M, Kobayashi K, Nagatsu T, Kreitman R, Pastan I, Nakanishi S. 1998. Ablation of cerebellar Golgi cells disrupts synaptic integration involving GABA inhibition and NMDA receptor activation in motor coordination. Cell. 95(1), 17–27.
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Journal Article
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| English
Scopus indexed
Author
Watanabe, Dai;
Inokawa, Hitoshi;
Hashimoto, Kouichi;
Suzuki, Noboru;
Kano, Masanobu;
Shigemoto, RyuichiISTA 
;
Hirano, Tomoo;
Toyama, Keisuke;
Kaneko, Satoshi;
Yokoi, Mineto;
Moriyoshi, Koki;
Suzuki, Misao
All
;
Hirano, Tomoo;
Toyama, Keisuke;
Kaneko, Satoshi;
Yokoi, Mineto;
Moriyoshi, Koki;
Suzuki, Misao
All
Abstract
The role of inhibitory Golgi cells in cerebellar function was investigated by selectively ablating Golgi cells expressing human interleukin-2 receptor α subunit in transgenic mice, using the immunotoxin- mediated cell targeting technique. Golgi cell disruption caused severe acute motor disorders. These mice showed gradual recovery but retained a continuing inability to perform compound movements. Optical and electrical recordings combined with immunocytological analysis indicated that elimination of Golgi cells not only reduces GABA-mediated inhibition but also attenuates functional NMDA receptors in granule cells. These results demonstrate that synaptic integration involving both GABA inhibition and NMDA receptor activation is essential for compound motor coordination. Furthermore, this integration can adapt after Golgi cell elimination so as not to evoke overexcitation by the reduction of NMDA receptors.
Publishing Year
Date Published
1998-10-02
Journal Title
Cell
Acknowledgement
We thank Kumlesh K Dev for careful reading of this manuscript, Peter Somogyi and Hirohide Sawada for invaluable advice, and Akira Uesugi for photographic assistance. This work was supported in part by research grants from the Ministry of Education, Science and Culture of Japan. the Sankyo Foundation. the Yamanouchi Founda-tion. the Biomolecular Engineering Research Institute, CREST and the International Resource Program of the National Cancer Institute.
Volume
95
Issue
1
Page
17 - 27
ISSN
IST-REx-ID
Cite this
Watanabe D, Inokawa H, Hashimoto K, et al. Ablation of cerebellar Golgi cells disrupts synaptic integration involving GABA inhibition and NMDA receptor activation in motor coordination. Cell. 1998;95(1):17-27. doi:10.1016/S0092-8674(00)81779-1
Watanabe, D., Inokawa, H., Hashimoto, K., Suzuki, N., Kano, M., Shigemoto, R., … Nakanishi, S. (1998). Ablation of cerebellar Golgi cells disrupts synaptic integration involving GABA inhibition and NMDA receptor activation in motor coordination. Cell. Cell Press. https://doi.org/10.1016/S0092-8674(00)81779-1
Watanabe, Dai, Hitoshi Inokawa, Kouichi Hashimoto, Noboru Suzuki, Masanobu Kano, Ryuichi Shigemoto, Tomoo Hirano, et al. “Ablation of Cerebellar Golgi Cells Disrupts Synaptic Integration Involving GABA Inhibition and NMDA Receptor Activation in Motor Coordination.” Cell. Cell Press, 1998. https://doi.org/10.1016/S0092-8674(00)81779-1.
D. Watanabe et al., “Ablation of cerebellar Golgi cells disrupts synaptic integration involving GABA inhibition and NMDA receptor activation in motor coordination,” Cell, vol. 95, no. 1. Cell Press, pp. 17–27, 1998.
Watanabe D, Inokawa H, Hashimoto K, Suzuki N, Kano M, Shigemoto R, Hirano T, Toyama K, Kaneko S, Yokoi M, Moriyoshi K, Suzuki M, Kobayashi K, Nagatsu T, Kreitman R, Pastan I, Nakanishi S. 1998. Ablation of cerebellar Golgi cells disrupts synaptic integration involving GABA inhibition and NMDA receptor activation in motor coordination. Cell. 95(1), 17–27.
Watanabe, Dai, et al. “Ablation of Cerebellar Golgi Cells Disrupts Synaptic Integration Involving GABA Inhibition and NMDA Receptor Activation in Motor Coordination.” Cell, vol. 95, no. 1, Cell Press, 1998, pp. 17–27, doi:10.1016/S0092-8674(00)81779-1.
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