The mystery of the cerebellum: clues from experimental and clinical observations

Abstract

The cerebellum has a striking homogeneous cytoarchitecture and participates in both motor and non-motor domains. Indeed, a wealth of evidence from neuroanatomical, electrophysiological, neuroimaging and clinical studies has substantially modified our traditional view on the cerebellum as a sole calibrator of sensorimotor functions. Despite the major advances of the last four decades of cerebellar research, outstanding questions remain regarding the mechanisms and functions of the cerebellar circuitry. We discuss major clues from both experimental and clinical studies, with a focus on rodent models in fear behaviour, on the role of the cerebellum in motor control, on cerebellar contributions to timing and our appraisal of the pathogenesis of cerebellar tremor. The cerebellum occupies a central position to optimize behaviour, motor control, timing procedures and to prevent body oscillations. More than ever, the cerebellum is now considered as a major actor on the scene of disorders affecting the CNS, extending from motor disorders to cognitive and affective disorders. However, the respective roles of the mossy fibres, the climbing fibres, cerebellar cortex and cerebellar nuclei remains unknown or partially known at best in most cases. Research is now moving towards a better definition of the roles of cerebellar modules and microzones. This will impact on the management of cerebellar disorders.

Keywords: Anatomy; Cerebellum; Cognition; Fear; History; Motor; Timing; Tremor.

Fig. 1

Cerebellum detects similarities and discordances between predicted and actual sequences of events. The incoming sensation activate a microcomplex especially via activation of mossy fibres (MFs). Selected bands of Purkinje neurons are activated, resulting in a sculpting of patterns in the cerebellar nuclei. In case of discrepancy between actual signals and expected sequence, the forward model is recalibrated via activation of the climbing fibres (CFs) of the olivo-cerebellar tract. Right panel: schematic representation of the cerebellar circuitry. Parallel fibres emerging from granule cells (in orange) generate simple spikes (S. Sp.) at the level of Purkinje neurons (in black). Purkinje neurons target cerebellar nuclei neurons (in green). The activation of the inferior olivary complex (in blue) triggers a complex spike in the cerebellar cortex