| 1. |
- Apps, Richard, et al.
(author)
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Cerebellar Modules and Their Role as Operational Cerebellar Processing Units
- 2018
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In: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4222. ; 17:5, s. 654-682
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Journal article (peer-reviewed)abstract
- The compartmentalization of the cerebellum into modules is often used to discuss its function. What, exactly, can be considered a module, how do they operate, can they be subdivided and do they act individually or in concert are only some of the key questions discussed in this consensus paper. Experts studying cerebellar compartmentalization give their insights on the structure and function of cerebellar modules, with the aim of providing an up-to-date review of the extensive literature on this subject. Starting with an historical perspective indicating that the basis of the modular organization is formed by matching olivocorticonuclear connectivity, this is followed by consideration of anatomical and chemical modular boundaries, revealing a relation between anatomical, chemical, and physiological borders. In addition, the question is asked what the smallest operational unit of the cerebellum might be. Furthermore, it has become clear that chemical diversity of Purkinje cells also results in diversity of information processing between cerebellar modules. An additional important consideration is the relation between modular compartmentalization and the organization of the mossy fiber system, resulting in the concept of modular plasticity. Finally, examination of cerebellar output patterns suggesting cooperation between modules and recent work on modular aspects of emotional behavior are discussed. Despite the general consensus that the cerebellum has a modular organization, many questions remain. The authors hope that this joint review will inspire future cerebellar research so that we are better able to understand how this brain structure makes its vital contribution to behavior in its most general form.
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| 2. |
- Bengtsson, Fredrik, et al.
(author)
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Cerebellar control of the inferior olive.
- 2006
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In: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4230. ; 5:1, s. 7-14
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Research review (peer-reviewed)abstract
- A subpopulation of neurones in the cerebellar nuclei projects to the inferior olive, the source of the climbing fibre input to the cerebellum. This nucleo-olivary projection follows the zonal and, probably also, the microzonal arrangement of the cerebellum so that closed loops are formed between the neurones in the olive, the cerebellar cortex and the nuclei. The nucleo-olivary pathway is GABAergic, but several investigators argue that its main effect is to regulate electrotonic coupling between cells in the inferior olive rather than inhibit the olive. However, there is now strong evidence that the nucleo-olivary fibres do inhibit the olive. Three functions have been suggested for this inhibition: (i) feedback control of background activity in Purkinje cells, (ii) feedback control of learning, and (iii) gating of olivary input in general. Evidence is consistent with (i) and (ii). Activity in the nucleo-olivary pathway suppresses both synaptic transmission and background activity in the olive. When learned blink responses develop, the blink related part of the olive is inhibited while blinks are produced. When the nucleo-olivary pathway is interrupted, there is a corresponding increase in complex spike discharge in Purkinje cells followed by a strong suppression of simple spike firing. Stimulation of the pathway has the opposite results. It is concluded that the nucleo-olivary fibres are inhibitory and that they form a number of independent feedback loops, each one specific for a microcomplex, that regulate cerebellar learning as well as spontaneous activity in the olivo-cerebellar circuit.
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| 3. |
- Caligiore, Daniele, et al.
(author)
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Consensus Paper: Towards a Systems-Level View of Cerebellar Function: the Interplay Between Cerebellum, Basal Ganglia, and Cortex.
- 2016
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In: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4230.
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Journal article (peer-reviewed)abstract
- Despite increasing evidence suggesting the cerebellum works in concert with the cortex and basal ganglia, the nature of the reciprocal interactions between these three brain regions remains unclear. This consensus paper gathers diverse recent views on a variety of important roles played by the cerebellum within the cerebello-basal ganglia-thalamo-cortical system across a range of motor and cognitive functions. The paper includes theoretical and empirical contributions, which cover the following topics: recent evidence supporting the dynamical interplay between cerebellum, basal ganglia, and cortical areas in humans and other animals; theoretical neuroscience perspectives and empirical evidence on the reciprocal influences between cerebellum, basal ganglia, and cortex in learning and control processes; and data suggesting possible roles of the cerebellum in basal ganglia movement disorders. Although starting from different backgrounds and dealing with different topics, all the contributors agree that viewing the cerebellum, basal ganglia, and cortex as an integrated system enables us to understand the function of these areas in radically different ways. In addition, there is unanimous consensus between the authors that future experimental and computational work is needed to understand the function of cerebellar-basal ganglia circuitry in both motor and non-motor functions. The paper reports the most advanced perspectives on the role of the cerebellum within the cerebello-basal ganglia-thalamo-cortical system and illustrates other elements of consensus as well as disagreements and open questions in the field.
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| 4. |
- Devita, Maria, et al.
(author)
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The Role of Cognitive Reserve in Protecting Cerebellar Volumes of Older Adults with mild Cognitive Impairment
- 2024
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In: Cerebellum. - 1473-4222 .- 1473-4230.
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Journal article (peer-reviewed)abstract
- The present study aims to investigate the relationship between cerebellar volumes and cognitive reserve in individuals with Mild Cognitive Impairment (MCI). A description of proxies of cerebellar cognitive reserve in terms of different volumes across lobules is also provided. 36 individuals with MCI underwent neuropsychological (MoCA, MMSE, Clock test, CRIq) assessment and neuroimaging acquisition with magnetic resonance imaging at 3 T. Simple linear correlations were applied between cerebellar volumes and cognitive measures. Multiple linear regression models were then used to estimate standardized regression coefficients and 95% confidence intervals. Simple linear correlations between cerebellar lobules volumes and cognitive features highlighted a significant association between CRIq_Working activity and specific motor cerebellar volumes: Left_V (ρ = 0.40, p = 0.02), Right_V (r = 0.42, p = 0.002), Vermis_VIIIb (ρ = 0.47, p = 0.003), Left_X (ρ = -0.46, p = 0.002) and Vermis_X (r = 0.35, p = 0.03). Furthermore, CRIq_Working activity scores correlated with certain cerebellar lobules implicated in cognition: Left_Crus_II, Vermis VIIb, Left_IX. MMSE was associated only with the Right_VIIB volume (r = 0.35, p = 0.02), while Clock Drawing Test scores correlated with both Left_Crus_I and Right_Crus_I (r = -0.42 and r = 0.42, p = 0.02, respectively). This study suggests that a higher cognitive reserve is associated with specific cerebellar lobule volumes and that Working activity may play a predominant role in this association. These findings contribute to the understanding of the relationship between cerebellar volumes and cognitive reserve, highlighting the potential modulatory role of Working activity on cerebellum response to cognitive decline.
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| 5. |
- Eftekhari, Sajedeh, et al.
(author)
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Localization of CGRP Receptor Components, CGRP, and Receptor Binding Sites in Human and Rhesus Cerebellar Cortex.
- 2013
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In: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4230. ; 12:6, s. 937-949
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Journal article (peer-reviewed)abstract
- The cerebellum is classically considered to be mainly involved in motor processing, but studies have suggested several other functions, including pain processing. Calcitonin-gene-related peptide (CGRP) is a neuropeptide involved in migraine pathology, where there is elevated release of CGRP during migraine attacks and CGRP receptor antagonists have antimigraine efficacy. In the present study, we examined CGRP and CGRP receptor binding sites and protein expression in primate cerebellar cortex. Additionally, mRNA expression of the CGRP receptor components, calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1), was examined. In addition, expression of procalcitonin was studied. We observed high [(3)H]MK-3207 (CGRP receptor antagonist) binding densities in the molecular layer of rhesus cerebellar cortex; however, due to the limit of resolution of the autoradiographic image the exact cellular localization could not be determined. Similarly, [(125)I]CGRP binding was observed in the molecular layer and Purkinje cell layer of human cerebellum. CLR and RAMP1 mRNA was expressed within the Purkinje cell layer and some expression was found in the molecular layer. Immunofluorescence revealed expression of CGRP, CLR, and RAMP1 in the Purkinje cells and in cells in the molecular layer. Procalcitonin was found in the same localization. Recent research in the biology of cerebellum indicates that it may have a role in nociception. For the first time we have identified CGRP and CGRP receptor binding sites together with CGRP receptor expression through protein and mRNA localization in primate cerebellar cortex. These results point toward a functional role of CGRP in cerebellum. Further efforts are needed to evaluate this.
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| 6. |
- Ekerot, Carl-Fredrik, et al.
(author)
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Parallel fiber receptive fields: a key to understanding cerebellar operation and learning.
- 2003
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In: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4230. ; 2:2, s. 101-109
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Journal article (peer-reviewed)abstract
- In several theories of the function of the cerebellum in motor control, the mossy-fiber-parallel fiber input has been suggested to provide information used in the control of ongoing movements whereas the role of climbing fibers is to induce plastic changes of parallel fiber (PF) synapses on Purkinje cells. From studies of climbing fibers during the last few decades, we have gained detailed knowledge about the zonal and microzonal organization of the cerebellar cortex and the information carried by climbing fibers. However, properties of the PF input to Purkinje cells and inhibitory interneurones have been largely unknown. The present review, which focuses on the C3 zone of the cerebellar anterior lobe, will present and discuss recent data of the cutaneous PF input to Purkinje cells, interneurons and Golgi cells as well as novel forms of PF plasticity
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| 7. |
- Ekerot, Carl-Fredrik, et al.
(author)
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Synaptic Integration in Cerebellar Granule Cells
- 2008
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In: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4230. ; 7:4, s. 539-541
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Journal article (peer-reviewed)abstract
- To understand the function of cerebellar granule cells, we need detailed knowledge about the information carried by their afferent mossy fibers and how this information is integrated by the granule cells. Recently, we made whole cell recordings from granule cells in the non-anesthetized, decerebrate cats. All recordings were made in the forelimb area of the C3 zone for which the afferent and efferent connections and functional organization have been investigated in detail. Major findings of the study were that the mossy fiber input to single granule cells was modality- and receptive field-specific and that simultaneous activity in two and usually more of the afferent mossy fibers were required to activate the granule cell spike. The high threshold for action potentials and the convergence of afferents with virtually identical information suggest that an important function of granule cells is to increase the signal-to-noise ratio of the mossy fiber-parallel fiber information. Thus a high-sensitivity, noisy mossy fiber input is transformed by the granule cell to a high-sensitivity, low-noise signal.
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| 8. |
- Gorcenco, Sorina, et al.
(author)
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Patients’ Perspective in Hereditary Ataxia
- 2022
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In: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4222.
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Journal article (peer-reviewed)abstract
- Hereditary ataxia represents a heterogeneous group of rare disorders with the chronic progression of motor symptoms that often become debilitating. Many forms include additional neurological, cognitive, or other symptoms. Most of these disorders lack specific treatment. We aimed to investigate aspects of patients’ quality of life, experiences, and expectations. Patients with a diagnosis of hereditary ataxia were identified from our center’s diagnostic register, direct referrals, and from a patient organization. We designed a questionnaire with 32 multiple-choice or open-ended questions on disability and impairment of daily life activities, the perceived effect of symptomatic and supportive therapies, coping strategies, and how they used and experienced various sources of information about their neurological disease. We also included the EQ-5D-3L quality-of-life instrument. Results were analyzed statistically for gender, age, and groups with and without a genetic diagnosis, and were compared to published data from the general population. Seventy-five patients returned the questionnaire. Patients reported considerable disease-related disability and impairment and had significantly lower quality-of-life scores than the general population. Physiotherapy and support from family or friends were important for patients’ overall well-being. Patients with a genetic diagnosis had a lower average age at onset and felt more well-informed about their disease than patients without a genetic diagnosis. Patients used internet sources but relied primarily on their doctors to obtain information about their disease. Our study provides insights into hereditary ataxia patients’ experiences that can lead to improvements in medical and nursing care for these patients.
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| 9. |
- Jirenhed, Dan-Anders, et al.
(author)
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Are Purkinje Cell Pauses Drivers of Classically Conditioned Blink Responses?
- 2016
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In: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4230. ; 15:4, s. 526-534
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Research review (peer-reviewed)abstract
- Several lines of evidence show that classical or Pavlovian conditioning of blink responses depends on the cerebellum. Recordings from cerebellar Purkinje cells that control the eyelid and the conditioned blink show that during training with a conditioning protocol, a Purkinje cell develops a pause response to the conditional stimulus. This conditioned cellular response has many of the properties that characterise the overt blink. The present paper argues that the learned Purkinje cell pause response is the memory trace and main driver of the overt conditioned blink and that it explains many well-known behavioural phenomena.
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| 10. |
- Jirenhed, Dan-Anders, et al.
(author)
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Learning Stimulus Intervals – Adaptive Timing of Conditioned Purkinje Cell Responses
- 2011
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In: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4230. ; 10:Online March 17, 2011, s. 523-535
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Journal article (peer-reviewed)abstract
- Classical conditioning of motor responses, such as the eyeblink response, is an experimental model of associative learning and of adaptive timing of movements. A conditioned blink will have its maximum amplitude near the expected onset of the unconditioned blink-eliciting stimulus and it adapts to changes in the interval between the conditioned and unconditioned stimuli. Previous studies have shown that an eyeblink conditioning protocol can make cerebellar Purkinje cells learn to pause in response to the conditioned stimulus. According to the cerebellar cortical conditioning model, this conditioned Purkinje cell response drives the overt blink. If so, the model predicts that the temporal properties of the Purkinje cell response reflect the overt behaviour. To test this prediction, in vivo recordings of Purkinje cell activity were performed in decerebrate ferrets during conditioning, using direct stimulation of cerebellar mossy and climbing fibre afferents as conditioned and unconditioned stimuli. The results show that Purkinje cells not only develop a change in responsiveness to the conditioned stimulus. They also learn a particular temporal response profile where the timing, not only of onset and maximum but also of offset, is determined by the temporal interval between the conditioned and unconditioned stimuli.
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