トランスジェニックマウスによる小脳神経回路の解析

抄録

In the cerebellar circuit, Golgi cells receive inputs from granule cells and in turn terminate their axons on granule cell dendrites. Since Golgi cells are the only element that controls the activity of granule cells, Golgi cells are thought to play an important role in information processing via feedback mechanisms.First we investigated the role of Golgi cells by selective ablation using the immunotoxin-mediated cell targeting technique. The elimination of Golgi cells caused severe acute motor disorders. These mice gradually recovered but retained a continuing difficulty in performing fine movements. Electrophysiological analyses indicated that disruption of Golgi cells not only eliminates GABA-mediated inhibition but also attenuates functional NMDA receptors in granule cells. These results demonstrate that synaptic integration involving GABA inhibition and NMDA receptor activation is essential for motor coordination. Next we investigated the synaptic mechanisms of postsynaptic metabotropic glutamate receptor subtype 2 (mGluR2) on Golgi cell dendrites, using whole-cell patch-clamp recording of green fluorescent protein-positive Golgi cells of wild-type and mGluR2-deficient mice. Postsynaptic mGluR2 was activated by glutamate released from granule cells and hyperpolarized Golgi cells via G protein-coupled inwardly rectifying K channels. This hyperpolarization induced long-lasting silencing of Golgi cells, the duration and extents of which were dependent on stimulus strengths. Postsynaptic mGluR2 thus senses inputs from granule cells and plays a pivotal role in spatiotemporal modulation of mossy fiber-granule cell transmission. [J Physiol Sci. 2006;56 Suppl:S21]