Ablation of Cerebellar Golgi Cells Disrupts Synaptic Integration Involving GABA Inhibition and NMDA Receptor Activation in Motor Coordination

• Published in: Cell 1998-10, Vol.95 (1), p.17-27
• Main Authors: Watanabe, Dai, Inokawa, Hitoshi, Hashimoto, Kouichi, Suzuki, Norimitsu, Kano, Masanobu, Shigemoto, Ryuichi, Hirano, Tomoo, Toyama, Keisuke, Kaneko, Satoshi, Yokoi, Mineto, Moriyoshi, Koki, Suzuki, Misao, Kobayashi, Kazuto, Nagatsu, Toshiharu, Kreitman, Robert J, Pastan, Ira, Nakanishi, Shigetada
• Format: Article
• Language: English
• Subjects: Animals; Cerebellum - cytology; Cerebellum - metabolism; Cerebellum - physiology; Exotoxins - metabolism; Exotoxins - pharmacology; gamma-Aminobutyric Acid - metabolism; Gene Expression - drug effects; Humans; Immunotoxins - metabolism; Immunotoxins - pharmacology; Mice; Mice, Transgenic; Motor Activity; Receptors, Interleukin-2 - genetics; Receptors, Interleukin-2 - metabolism; Receptors, N-Methyl-D-Aspartate - metabolism; Synaptic Transmission - physiology
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(00)81779-1

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.