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Synapses
Published in Nassir H. Sabah, Neuromuscular Fundamentals, 2020
Internalization of AMPARs occurs by a different mechanism in cerebellar Purkinje cells but leads to LTD just the same. The circuitry of the cerebellar cortex is described in detail in Section 12.2.4. Purkinje cells have two types of excitatory inputs – from climbing fibers and from parallel fibers. A climbing fiber makes 500–1000 synapses on the main dendritic branches of the Purkinje cell, so that a climbing fiber AP results in intense depolarization of the dendrites. The synapses of parallel fibers, on the other hand, are found on fine dendrites and on dendritic spines. Paired activation of the two inputs at a low frequency of about 1 Hz gave some mixed results in cerebellar slice experiments. When climbing fiber activation followed parallel fiber activation by 250 ms, LTD of the parallel fiber synapses was observed with 100 paired stimuli. The depression was still about 25%, 30 minutes after stimulation. There was no LTD when the interval between stimulations was reduced to 125 ms or when climbing fiber activation preceded parallel fiber activation by 250 ms. When the number of pairings was increased to 600, LTD was observed at the four intervals tested (250 ms, 125 ms, 0, –250 ms, that is, CF activation preceding PF activation in the latter case). Moreover, it was found that a strong activation of parallel fibers on their own could induce LTD through elevation of postsynaptic Ca2+ levels.
Three-Dimensional Upper Limb Movements in Cerebellar Ataxia
Published in Michael Fetter, Thomas Haslwanter, Hubert Misslisch, Douglas Tweed, Three-Dimensional Kinematics of Eye, Head and Limb Movements, 2020
Helge Topka, Jürgen Konczak, K. Schneider, J. Dichgans
While these studies unequivocally show that cerebellar dysfunction disorders even simple single-joint movements, recent anatomical and physiological data have prompted the notion that the cerebellum may specifically play a role in controlling movements of adjacent joints and thus in the coordination of multijoint movements (Goodkin et al., 1993; Thach et al., 1992). In his recent review, Thach (1992) reevaluated the current knowledge of cerebellar cortical anatomy and physiology and pointed out that the architecture of the cerebellar cortex could indeed provide an ideal neuroanatomical basis for monitoring and coordinating multijoint limb movements. In particular, the existence of a roughly somatotopical organization of the cerebellar nuclei and associated cerebellar cortical areas and the spatial organization of parallel fiber beams within that somatotopic pattern are thought to represent the neuroanatomical basis of cerebellar involvement in the coordination of movement. In theory, the spatial orientation of the parallel fiber beams which is in parallel to the myotome representation within each of the cerebellar nuclei and the considerable length of parallel fibers would allow for the parallel fibers to influence motions of several adjacent joints, hereby providing intersegmental coordination of a multi-joint movement.
David Coutnay Marr (1945–1980)s
Published in Andrew P. Wickens, Key Thinkers in Neuroscience, 2018
It was against this backdrop that Marr began his theorising. In 1964, Giles Brindley had pointed out that the convergence of excitatory parallel and climbing fibres onto Purkinje cells implied the existence of Hebbian synapses.2 More specifically, he reasoned: if the activity of the parallel and climbing fibres was synchronised, then the synapses between the parallel fibres and the Purkinje cells would become strengthened – fulfilling Hebb’s criteria for the occurrence of neural plasticity (i.e. learning). This also implicated the cerebellum in the learning of new motor skills. Marr extended this idea by proposing that each climbing fibre conveyed an instruction from the cerebral cortex to the Purkinje cell regarding an elemental movement (such as a fine digit movement or limb action). At the same time, the parallel fibre input to the Purkinje cell was seen as providing information about the situational context in which the climbing fibre fired. This meant, according to Marr, during the learning of a new skill, each Purkinje cell began to recognise the contexts in which the action was appropriate. And, ultimately, this led to a situation where once a movement had been learned, the context alone could be enough to fire the Purkinje cell and its elemental action. Thus, the movement became automated. It was also a theory that placed the memory of skilled motor behaviour, at least in part, in the synapses located between the parallel fibres and the Purkinje cells.
Vision Beyond Vision: Lessons Learned from Amblyopia
Published in Journal of Binocular Vision and Ocular Motility, 2023
What is the neural mechanism that accounts for these deficits? To answer this question, we need to understand the anatomy and physiology of the cerebellum.36,37 In the cerebellar cortex, the Purkinje cells are the only output cells. They receive two major inputs. The first input comes from parallel fibers, which carry information from many different sites in the brainstem and spinal cord, including visual, vestibular, proprioceptive, tactile, and auditory signals. The second input comes from climbing fibers in the form of a “teaching signal” derived from retinal errors. We postulate that in amblyopia, because of spatiotemporal uncertainty, the visual signals are “noisy,” degrading the teaching signal from the climbing fibers to the Purkinje cells, which may explain the deficits in motor control and adaptation we found in patients with amblyopia.
Mechanisms of COVID-19-induced cerebellitis
Published in Current Medical Research and Opinion, 2022
Mohammad Banazadeh, Sepehr Olangian-Tehrani, Melika Sharifi, Mohammadreza Malek-Ahmadi, Farhad Nikzad, Nooria Doozandeh-Nargesi, Alireza Mohammadi, Gary J. Stephens, Mohammad Shabani
The cerebellum is intimately involved in motor control, and cerebellar injuries result in the condition of movement incoordination known as ataxia. In addition to its role in cognition and executive control, the cerebellum influences diseases such as dyslexia and autism—the cerebellum functions as a forward controller that predicts the precise timing of related events through learning. The physiologic processes underlying cerebellar function continue to be the subject of intensive study. Signals entering the cerebellum via mossy fibers are processed in the granular layer and delivered to Purkinje cells, whilst a collateral channel stimulates the deep cerebellar nuclei (DCN). In turn, Purkinje cells inhibit DCN; therefore, the cerebellar cortex functions as a side-loop regulating DCN. It is now known that learning occurs through synaptic plasticity at multiple synapses in the granular layer, molecular layer, and DCN, expanding the original concept of the Motor Learning Theory, which predicted a single form of plasticity at the synapse between excitatory parallel fibers and Purkinje cells under the supervision of climbing fibers originating from the inferior olive. The precise modulation of timing and gain in the many cerebellar modules is the source of coordination11.
Current challenges in the pathophysiology, diagnosis, and treatment of paroxysmal movement disorders
Published in Expert Review of Neurotherapeutics, 2021
Cécile Delorme, Camille Giron, David Bendetowicz, Aurélie Méneret, Louise-Laure Mariani, Emmanuel Roze
Patients with monoallelic proline-rich transmembrane protein 2 (PRRT2) mutations typically have PKD. Interestingly, the rare patients with biallelic PRRT2 mutations are prone to develop a combination of episodic ataxia and prolonged episodes of paroxysmal dyskinesia[22]. Some of them also have obvious cerebellar atrophy. These observations support a critical role of the cerebellum in the pathogenesis of PRRT2-associated paroxysmal dyskinesia. The PRRT2 protein is highly expressed in the cerebellum, although it is also present in the cerebral cortex and other brain regions, including the basal ganglia [23]. PRRT2 knock-out mice have complex motor episodes comprising paroxysmal dyskinesia, which are associated with a higher excitatory strength at parallel fiber-Purkinje cell synapses during high-frequency stimulation[23]. In another mouse model, the selective silencing of PRRT2 in cerebellar granule cells is sufficient to induce paroxysmal dyskinesia and is associated with an irregular firing of Purkinje cells [24]. PRRT2 is expressed in the granular cells but not Purkinje cells of the cerebellar cortex and its expression is presynaptic in the molecular layer containing the axons of the granular cells [25]. An alteration of the synaptic transmission at the level of the parallel fibers-Purkinje cells synapses may account for the abnormal cerebellar output likely involved in paroxysmal dyskinesia.