Neural circuits of the cerebellum: hypothesis for function.

The rapid growth of cerebellar research is going to clarify several aspects of cellular and circuit physiology. However, the concepts about cerebellar mechanisms of function are still largely related to clinical observations and to models elaborated before the last discoveries appeared. In this paper, the major issues are revisited, suggesting that previous concepts can now be refined and modified. The cerebellum is fundamentally involved in timing and in controlling the ordered and precise execution of motor sequences. The fast reaction of the cerebellum to the inputs is sustained by specific cellular mechanisms ensuring precision on the millisecond scale. These include burst-burst reconversion in the granular layer and instantaneous frequency modulation on the 100-Hz band in Purkinje and deep cerebellar nuclei cells. Precisely timed signals can be used for perceptron operations in Purkinje cells and to establish appropriate correlations with climbing fiber signals inducing learning at parallel fiber synapses. In the granular layer, plasticity turns out to be instrumental to timing, providing a conceptual solution to the discrepancy between cerebellar learning and timing. The granular layer sub-circuit can be tuned by long-term synaptic plasticity and synaptic inhibition to delay the incoming signals over a 100-ms range. For longer sequences, large circuit sections can be entrained into coherent activity in 100-ms cycles. These dynamic aspects, which have not been accounted for by original theories, could in fact represent the essence of cerebellar functioning. It is suggested that the cerebellum can, in this way, operate the realignment of temporally incongruent signals, allowing their binding and pattern recognition in Purkinje cells. The demonstration of these principles, their behavioral relevance and their relationship with internal model theories represent a challenge for future cerebellar research.