ABLATION OF CEREBELLAR GOLGI CELLS DISRUPTS SYNAPTIC INTEGRATION INVOLVING GABA INHIBITION AND NMDA RECEPTOR ACTIVATION IN MOTOR COORDINATION

The role of inhibitory Golgi cells in cerebellar function was investig ated by selectively ablating Golgi cells expressing human interleukin- 2 receptor alpha subunit in transgenic mice, using the immunotoxin-med iated cell targeting technique. Golgi cell disruption caused severe ac ute motor disorders. These mice showed gradual recovery but retained a continuing inability to perform compound movements. Optical and elect rical recordings combined with immunocytological analysis indicated th at elimination of Golgi cells not only reduces GABA-mediated inhibitio n but also attenuates functional NMDA receptors in granule cells. Thes e results demonstrate that synaptic integration involving both GABA in hibition 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 NMD A receptors.