Cheron G, Servais L, Dan B
Laboratory of Neurophysiology and Movement Biomechanics, Université Libre de Bruxelles, CP640, 50 Av F Roosevelt, Brussels, Belgium.
Neuroscience. 2008 Apr 22;153(1):1-19. doi: 10.1016/j.neuroscience.2008.01.074. Epub 2008 Feb 19.
The role of the cerebellum has been increasingly recognized not only in motor control but in sensory, cognitive and emotional learning and regulation. Purkinje cells, being the sole output from the cerebellar cortex, occupy an integrative position in this network. Plasticity at this level is known to critically involve calcium signaling. In the last few years, electrophysiological study of genetically engineered mice has demonstrated the topical role of several genes encoding calcium-binding proteins (calretinin, calbindin, parvalbumin). Specific inactivation of these genes results in the emergence of a fast network oscillation (ca. 160 Hz) throughout the cerebellar cortex in alert animals, associated with ataxia. This oscillation is produced by synchronization of Purkinje cells along the parallel fiber beam. It behaves as an electrophysiological arrest rhythm, being blocked by sensorimotor stimulation. Pharmacological manipulations showed that the oscillation is blocked by GABA(A) and NMDA antagonists as well as gap junction blockers. This cerebellar network oscillation has also been documented in mouse models of human conditions with complex developmental cerebellar dysfunction, such as Angelman syndrome and fetal alcohol syndrome. Recent evidence suggests a relationship between fast oscillation and cerebellar long term depression (LTD). This may have major implications for future therapeutic targeting.
小脑的作用不仅在运动控制方面，而且在感觉、认知和情感学习与调节方面越来越受到认可。浦肯野细胞作为小脑皮质的唯一输出，在这个网络中占据着整合的位置。已知这个层面的可塑性关键涉及钙信号传导。在过去几年中，对基因工程小鼠的电生理研究已经证明了几个编码钙结合蛋白（钙视网膜蛋白、钙结合蛋白、小白蛋白）的基因的局部作用。这些基因的特异性失活会导致警觉动物的整个小脑皮质出现快速网络振荡（约160赫兹），并伴有共济失调。这种振荡是由浦肯野细胞沿平行纤维束同步产生的。它表现为一种电生理静息节律，可被感觉运动刺激阻断。药理学操作表明，这种振荡可被GABA(A)和NMDA拮抗剂以及缝隙连接阻滞剂阻断。在患有复杂发育性小脑功能障碍的人类疾病的小鼠模型中，如天使综合征和胎儿酒精综合征，也记录到了这种小脑网络振荡。最近的证据表明快速振荡与小脑长时程抑制（LTD）之间存在关联。这可能对未来的治疗靶点具有重要意义。
