Cerebellar network plasticity: from genes to fast oscillation.
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.
Cheron
G
G
Laboratory of Neurophysiology and Movement Biomechanics, Université Libre de Bruxelles, CP640, 50 Av F Roosevelt, Brussels, Belgium. gcheron@ulb.ac.be
Servais
L
L
Dan
B
B
D000200:Action Potentials / Q000235:genetics; D000818:Animals; D001683:Biological Clocks / Q000235:genetics*; D020013:Calcium Signaling / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000235:genetics; D002525:Cerebellar Cortex / Q000502:physiology*; D002526:Cerebellar Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D051379:Mice; D009415:Nerve Net / Q000502:physiology*; D009433:Neural Inhibition / Q000235:genetics; D009473:Neuronal Plasticity / Q000235:genetics*; D013997:Time Factors
D002135:Calcium-Binding Proteins