Physiology of the cerebellum.

The cerebellum is a central brain structure deeply integrated into major loops with the cerebral cortex, brainstem, and spinal cord. The cerebellum shows a complex regional organization consisting of modules with sagittal orientation. The cerebellum takes part in motor control and its lesions cause a movement incoordination syndrome called ataxia. Recent observations also imply involvement of the cerebellum in cognition and executive control, with an impact on pathologies like dyslexia and autism. The cerebellum operates as a forward controller learning to predict the precise timing of correlated events. The physiologic mechanisms of cerebellar functioning are still the object of intense research. The signals entering the cerebellum through the mossy fibers are processed in the granular layer and transmitted to Purkinje cells, while a collateral pathway activates the deep cerebellar nuclei (DCN). Purkinje cells in turn inhibit DCN, so that the cerebellar cortex operates as a side loop controlling the DCN. Learning is now known to occur through synaptic plasticity at multiple synapses in the granular layer, molecular layer, and DCN, extending the original concept of the Motor Learning Theory that predicted a single form of plasticity at the synapse between parallel fibers and Purkinje cells under the supervision of climbing fibers deriving from the inferior olive. Coordination derives from the precise regulation of timing and gain in the different cerebellar modules. The investigation of cerebellar dynamics using advanced physiologic recordings and computational models is now providing new clues on how the cerebellar network performs its internal computations.