Organizational principles and microcircuitry of the cerebellum

The cerebellum is known to influence motor behavior and to enable smooth, coordinated movements. Recent evidence also suggests that the cerebellum contributes to non-motor behavior, including components of cognition and regulation of affective state. This review summarizes the organization and circuitry of the cerebellum as a basis for understanding newly emerging concepts about the function of this neuronal system. The cerebellum consists of several divisions with separate functions. One region is associated with the vestibular system and another with brainstem and spinal cord. A third region, the cerebrocerebellum, has extensive interconnections with cerebral cortex and is likely to be involved in motor coordination and regulation of non-motor behavior. The cerebellar cortex is made up of radial modules of interconnected neurons. The Purkinje cell is the principle integrating neuron and focal point of each module. Other neuron types include the granule cell and three inhibitory interneurons. The Purkinje cell integrates excitatory inputs from climbing and parallel fibers, while its axon modulates activity of neurons in the deep nuclei, which represents the final outflow from cerebellum to other parts of the brain. Cerebellar circuitry exhibits a strong parasagittal organization based on climbing fiber input and the distributions of neuronal proteins and neuronal vulnerability to insults. The combination of this parasagittal circuitry with the mediolateral course of parallel fibers results in a Cartesian coordinate system which is likely to be a crucial factor in its signal processing function. Although numerous details of cerebellar microcircuitry, synaptic transmission and signal transduction have been determined, the functional contribution of cerebellar signalling to brain function remains highly enigmatic.