Neural Circuits of the Cerebellum: Hypothesis for Function

Abstract

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.

The cerebellum for jocks and nerds alike

“…There is increasing evidence that the time delays required to create opposing signals might be generated by the mossy fiber-granule cell circuitry in the mammalian cerebellum. Long term plasticity at the mossy fiber—granule cell synapse can delay incoming signals for up to 100 ms, or even longer when larger sections of the circuitry are entrained (D'Angelo, 2011). Similar delays are generated in cerebellar-like structures involving the mossy fibers, granule cells and unipolar brush cells (Kennedy et al, 2014).…”

Fast convergence of learning requires plasticity between inferior olive and deep cerebellar nuclei in a manipulation task: a closed-loop robotic simulation

“…Although this mechanism supports the core process of error-correction in the motor learning theory and subsequent derivations, this same mechanism alone can only account for limited aspects of biological learning. A new spectrum of possibilities was opened by the discovery on multiple forms of synaptic plasticity (Hansel et al, 2001; Evans, 2007; Ohtsuki et al, 2009; D'Angelo, 2011; Gao et al, 2012). A recent model has shown that plasticity at deep-cerebellar nuclei (DCN) synapses can indeed account for learning on multiple time scales and for generalization (Garrido et al, 2013a).…”

Repetitive TMS on Left Cerebellum Affects Impulsivity in Borderline Personality Disorder: A Pilot Study

“…Additionally, the cerebellum is critical for revealing differences between predictions elaborated by the cortex and the stimuli conveyed by the senses. Thus, dysfunction of the cortico-cerebellar circuits may affect the detection of novelty and impair attention switching (D’Angelo, 2011). These complex functions (sensory prediction and novelty detection) seem to be impaired in BPD patients and are widely described by clinicians.…”