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Studies on the olivo-cerebellar system have rapidly advanced over the past decade, leading to new insight in the structural and functional properties of its synapses, neurons, intrinsic circuits, and connectivity with the rest of the brain. As in many other fields of neuroscience, it is becoming more and more appropriate to try to bring our understanding at the level of individual synapses and neurons to that of ensemble activity, circuits, and behavior. This Editorial aims to facilitate this process by ordering the 26 contributions of this special issue of Frontiers in Brain Microcircuits Series from studies on the development and structure of synaptic contacts to those on the function of local microcircuits and network plasticity as well as the olivo-cerebellar system as a whole. More specifically, we highlight here the main points of the chapters on development, circuit organization and structural plasticity of various types of neurons in the olivo-cerebellar system (A); the chapters on their basic activity and synaptic plasticity (B); the chapters on the relevance of the emerging network patterns in the olivo-cerebellar system (C); the chapters on current high-level theories of motor learning (D); and the chapters on the overall role of the olivo-cerebellar system in the integration of sensorimotor control and cognition (E).

The cerebellum refines the accuracy and timing of motor performance. How it encodes information to perform these functions is a major topic of interest. We performed whole cell and extracellular recordings of Purkinje cells (PCs) and cerebellar nuclei neurons (CNs) in vivo, while activating PCs with light in transgenic mice. We show for the first time that graded activation of PCs translates into proportional CN inhibition and induces rebound activity in CNs, which is followed by graded motor contractions timed to the cessation of the stimulus. Moreover, activation of PC ensembles led to disinhibition of climbing fiber activity, which coincided with rebound activity in CNs. Our data indicate that cessation of concerted activity in ensembles of PCs can regulate both timing and strength of movements via control of rebound activity in CNs.

Cerebellar granule cells (GrCs) convey information from mossy fibers (MFs) to Purkinje cells (PCs) via their parallel fibers (PFs). MF to GrC signaling allows transmission of frequencies up to 1 kHz and GrCs themselves can also fire bursts of action potentials with instantaneous frequencies up to 1 kHz. So far, in the scientific literature no evidence has been shown that these high-frequency bursts also exist in awake, behaving animals. More so, it remains to be shown whether such high-frequency bursts can transmit temporally coded information from MFs to PCs and/or whether these patterns of activity contribute to the spatiotemporal filtering properties of the granule cell layer. Here, we show that, upon sensory stimulation both in un-anesthetized rabbits and mice, GrCs can show bursts that consist of tens of spikes at instantaneous frequencies over 800 Hz. In vitro recordings from individual GrC-PC pairs following high-frequency stimulation revealed an overall low initial release probability of ~0.17. Nevertheless, high-frequency burst activity induced a short-lived facilitation to ensure signaling within the first few spikes, which was rapidly followed by a reduction in transmitter release to prevent immediate postsynaptic saturation. The facilitation rate among individual GrC-PC pairs was heterogeneously distributed and could be classified as either ‘reluctant’ or ‘responsive’ according to their release characteristics. Despite the variety of efficacy at individual connections, grouped activity in GrCs resulted in a linear relationship between PC response and PF burst duration at frequencies up to 300 Hz allowing rate coding to persist at the network level. Together, these findings support the hypothesis that the cerebellar granular layer acts as a spatiotemporal filter between MF input and PC output (D’Angelo and De Zeeuw, 2009).

Climbing fibers (CFs) originating in the inferior olive (IO) constitute one of the main inputs to the cerebellum. In the mammalian cerebellar cortex each of them climbs into the dendritic tree of up to ten Purkinje cells where they make hundreds of synaptic contacts and elicit the so-called all-or-none complex spikes controlling the output. While it has been proven that CFs contact molecular layer interneurons (MLIs) via spillover mechanisms, it remains to be elucidated to what extent CFs contact the main type of interneuron in the granular layer, i.e. the Golgi cells (GoCs). This issue is particularly relevant, because direct contacts would imply that CFs can also control computations at the input stage of the cerebellar cortical network. Here, we performed a systematic morphological investigation of labeled CFs and GoCs at the light microscopic level following their path and localization through the neuropil in both the granular and molecular layer. Whereas the appositions of CFs to Purkinje cells, stellate cells and basket cells in the molecular layer were prominent and numerous, those to cell-bodies and dendrites of GoCs in both the granular layer and molecular layer were virtually absent. Our results argue against the functional significance of direct synaptic contacts between CFs and interneurons at the input stage, but support those at the output stage.