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Background Climbing fibers (CFs) innervate Purkinje cells (PCs) with 1:1 relationship to ensure proper cerebellar function. Although CFs abnormally extend into the parallel fiber domain of PC dendrites in essential tremor (ET), the architecture of CFs in relation to PCs has yet to be investigated in detail. Objective The aim of this work was to study the architecture of CFs in relation to PCs in ET. Methods The number of PC somas and PC dendrites that a single CF crossed was quantified in the postmortem cerebellum of 15 ET cases and 15 control cases. Results In ET, CFs crossed a greater number of PC somas and PC dendrites than in control cases, raising the possibility that there is abnormal CF wiring onto the PCs. Interestingly, the increase in CF-PC crossings positively correlated with tremor severity. Conclusions Patients with ET have increased CF crossings on PC dendrites. This abnormal architectural arrangement may contribute to synchronous brain activity and tremor. © 2021 International Parkinson and Movement Disorder Society.

Existing knowledge of the cerebellar microcircuitry structure and physiology allows a rather detailed description of what it in itself can and cannot do. Combined with a known mapping of different cerebellar regions to afferent systems and motor output target structures, there are several constraints that can be used to describe how specific components of the cerebellar microcircuitry may work during sensorimotor control. In fact, as described in this review, the major factor that hampers further progress in understanding cerebellar function is the limited insights into the circuitry-level function of the targeted motor output systems and the nature of the information in the mossy fiber afferents. The cerebellar circuitry in itself is here summarized as a gigantic associative memory element, primarily consisting of the parallel fiber synapses, whereas most other circuitry components, including the climbing fiber system, primarily has the role of maintaining activity balance in the intracerebellar and extracerebellar circuitry. The review explores the consistency of this novel interpretational framework with multiple diverse observations at the synaptic and microcircuitry level within the cerebellum.

Objectives Functional neuroimaging and voxel-based morphometry studies have confirmed the important role of the cerebellum in motor behavior. However, little is known about the relationship between cerebellar gray (GMv) and white matter (WMv) volume and manual motor performance in aging individuals. This study aims to quantify the relationship between cerebellar tissue volume and manual motor performance. Experimental design To gain more insight into cerebellar function and how it relates to the role of the primary motor cortex (M1), we related cerebellar GMv, WMv, and M1v to manual motor performance in 217 healthy older individuals. Left and right cerebellar GMv and WMv, and M1v were obtained using FreeSurfer. The following motor measures were obtained: grip force, tapping speed, bimanual visuomotor coordination, and manual dexterity. Principal observations Significant positive relationships were observed between cerebellar GMv and WMv and grip strength, right cerebellar WMv and right-hand tapping speed, right cerebellar WMv and dexterity, M1v and grip strength, and right M1v and left-hand dexterity, though effect sizes were small. Conclusions Our results show that cerebellar GMv and WMv are differently associated with manual motor performance. These associations partly overlap with the brain-behavior associations between M1 and manual motor performance. Not all observed associations were lateralized (i.e., ipsilateral cerebellar and contralateral M1v associations with motor performance), which could point to age-related neural dedifferentiation. The current study provides new insights in the role of the cerebellum in manual motor performance. In consideration of the small effect sizes replication studies are needed to validate these results. Hum Brain Mapp 36:2352–2363, 2015. © 2015 Wiley Periodicals, Inc.

In the late 1970s, Wally Welker and his colleagues published a series of papers describing the first high-resolution physiological maps of tactile mossy fiber projections to the granule cell layer of the rat. Over the subsequent decade, his laboratory continued to explore the implications of these results for cerebellar connectivity and function while also extending the basic mapping results to a number of additional mammalian species. In each case, the maps revealed several surprising features, including a dominance of tactile (cutaneous inputs), robust short latency responses from the sensory periphery, and a fractured patchy somatotopic organization of receptive fields. This paper summarizes the major results of these micromapping experiments and reconsiders their implications for cerebellar function in light of more recent experimental data. The paper also explores the relationship between these fundamental discoveries and Wally Welker's theory-neutral approach to experimental science.

Complex spike synchrony is thought to be a key feature of how inferior olive climbing fibre afferents make their vital contribution to cerebellar function. However, little is known about whether the other major cerebellar input, the mossy fibres (which generate simple spikes within Purkinje cells, PCs), exhibit a similar synchrony in impulse timing. We have used a multi-microelectrode system to record simultaneously from two or more PCs in the posterior lobe of the ketamine/xylazine-anaesthetized rat to examine the relationship between complex spike and simple spike synchrony in PC pairs located mainly in the A2 and C1 zones in crus II and the paramedian lobule. PC pairs displaying correlations in the occurrence of their complex spikes (coupled PCs) were usually located in the same zone and were also more likely to exhibit correlations in the timing of their spontaneous simple spikes and associated pauses in activity. In coupled PCs, synchrony in both complex spike and simple spike activity was enhanced and the relative timing in the occurrence of complex spikes could be altered by peripheral stimulation. We conclude that the functional coupling between PC pairs in their complex spike and simple spike activity can be significantly modified by sensory inputs, and that mechanisms besides electrotonic coupling are involved in generating PC synchrony. Synchronous activity in multiple PCs converging onto the same cerebellar nuclear cells is likely to have a significant impact on cerebellar output that could form important timing signals to orchestrate coordinated movements.

Hereditary episodic ataxia (EA) syndromes are rare monogenic disorders that are phenotypically and genetically heterogeneous. The number of identified EA phenotypes is expanding. So far, mutations have been identified in four genes, all coding for membrane proteins including ion channels and transporters. The study of EA has illuminated previously unrecognized but important roles of ion channels and transporters in cerebellar function. This review summarizes recent advances and focuses on practical approaches in the diagnosis and treatment of episodic ataxia.

Objective: Structural, biochemical, and functional cerebellar abnormalities occur in individuals with or at-risk for developing bipolar disorder (BD), but the clinical implications of these abnormalities are unknown. The present study examined cerebellar function in youths who were at familial risk for BD by comparing ataxia battery scores of youths with a bipolar parent to those of healthy youths. Methods: Trained raters administered an ataxia battery, consisting of three tasks, to children (aged 8–12 years) with at least one parent with BD type I (BDI) who themselves did not have BDI (at-risk or AR group, n = 21) and healthy comparison children (aged 8–12 years) with parents free of DSM-IV Axis I psychopathology (HC group, n = 23). Results: AR youths performed worse than HC youths on the Sharpened Romberg test (subjects standing heel-to-toe) and standing on one foot with eyes open (p

The very special intrinsic connectivity of the cerebellar cortex plays but a minor role in present-day theories of cerebellar function, and it is hardly used as a source of inspiration for experiments. It is argued here that a direct translation of structure into physiological relations inescapably leads to some propositions about cerebellar function that could be tested experimentally.

Fishes, in general, have several advantages as vertebrate models for basic brain function. They are phylogenetically closer than mammals to the basic vertebrate blueprint and thus allow behavioural and neurological studies of fundamental brain systems without the interaction of more recently evolved functions. Further, the absence of a highly developed telencephalon allows ready access to many structures without cerebral interference. A disadvantage of working with most fishes is, however, the relatively small size of the brain that often hinders or precludes the use of many standard neurological techniques. In contrast, a group of chondrichthians, the stingrays, Dasyatoidea, has a brain size rivaling mammalian rodent models. Of particular interest to our research, stingrays, like mammals, have a large, complex, three-lobed cerebellum. However, in the yellow stingray these lobes are completely separated. Thus, the lobes can be individually manipulated to examine behavioural correlates of specific lobes. For example, ablation of the centre lobe (also known as anterior caudal lobule) causes a fixed-pattern hyperactivity. Yellow stingrays are abundant in many areas, they are hardy, and tolerate anaesthesia and the surgical procedures well. A more complete elucidation of cerebellar function awaits further physical and pharmacological ablative studies but the potential for these animals as vertebrate models of cerebellar-controlled behaviour is clear.

The sections in this article are: 1 Introduction 1.1 Concepts of Cerebellar Function 1.2 Localization in the Cerebellum: Functional Anatomy 2 What Aspects of Movements are Controlled? 2.1 Overview 2.2 Classification of Movements 2.3 A Frame of Reference 2.4 Cerebellar Control 2.5 Muscle Tone and Force 3 Microanatomy 3.1 Fundamental Cerebellar Circuit 3.2 Summary: Microanatomy 4 Cellular Roles in Cerebellar Function 4.1 Discharge Properties 4.2 Relation of Discharge to Behavioral Events 5 General Summary 5.1 What Aspects of Movements Are Controlled by the Cerebellum? 5.2 What Are the Roles of the Individual Cells Within the Cerebellar Circuit?

No cerebellifugel fiber connections which reach farther forward than the midbrain were found.