Cerebellum from Fundamentals to Translational App

Authors: Mario Manto Peter Mariën

Publish Date: 2016/01/07

Volume: 15, Issue: 1, Pages: 1-4

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Abstract

In terms of cerebellar research and ataxiology a most fascinating period is currently going on Numerous academic groups are now focusing their innovative research on the socalled little brain hidden at the bottom of our brain Indeed its unique anatomical features make the cerebellum a wonderful window to address major questions about the central nervous system The seventh international symposium of the SRC was held in Brussels at the Palace of Academies from May 8 to 10 2015 The main goal of this dense symposium was to gather in a 2day meeting senior researchers of exceptional scientific quality and talented junior scientists from all over the world working in the multidisciplinary field of cerebellar research Fundamental and clinical researchers shared the latest knowledge and developments in this rapidly growing field New ideas addressed in a variety of inspiring talks provoked a vivid debate Advances in genetics development electrophysiology neuroimaging neurocognition and affect as well as in the cerebellar ataxias and the controversies on the roles and functions of the cerebellum were presented The Ferdinando Rossi lecture and the keynote lecture were delivered by Jan Voogd and Chris De Zeeuw respectively Contacts between researchers of different neuroscientific disciplines established a robust basis for novel trends and promising new cooperations between researchers and their centers spread all over the worldThe cerebellum is particularly vulnerable to malformations and disruptions since it develops from the early embryonic period to the first postnatal years In the first thematic session devoted to congenital and developmental aspects of the cerebellum and cerebellar pathology Roy Sillitoe addressed novel genetic mouse models that might become very relevant for cerebellar disorders Nori Koibuchi subsequently discussed the important links between hormones and cerebellar development with an emphasis on thyroid hormones and their physiological action Andrea Poretti explained the critical importance of pre and postnatal imaging in the diagnosis of congenital and developmental disorders of the cerebellum 1The second session of the symposium dealt with electrophysiological aspects of the cerebellum from its cells to its networks It is well established that the cerebellar nuclei play a central role because they represent the sole output of cerebellar circuitry Eric Lang presented novel findings on the effects of complex spikes on cerebellar nuclei discharges 2 Clear evidence was provided of synchrony as a mechanism by which complex spikes tune the electrophysiological patterns in cerebellar nuclei In his talk Egidio DAngelo addressed the advances in our understanding of the electrophysiological properties of the cerebellar cortex Abigail Person discussed the sensorimotor integrative mechanisms in the mammalian cerebellum Finally Chris De Zeeuw presented a talk focusing on the mechanisms of the plasticity of the cerebellar networks starting from the anatomy to the electrophysiologyAdvances in the neuroimaging of the cerebellum were presented in the third thematic session Anna Letizia Allegra Mascaro showed how researchers can take advantage of the optical techniques to assess the anatomy the plasticity and various functions of the cerebellum 3 Detailed 3D reconstructions of cerebellar axons represent an example of the recent advances made in this rapidly growing field of research Dagmar Timmann presented stateoftheart MRI methods to characterize structural alterations of the cerebellum 4 These methods represent powerful diagnostic tools Gülin Οz discussed the scope and limits of magnetic resonance spectroscopy MRS of the cerebellum She demonstrated that MRS detects parallel neurochemical alterations in patients and mouse models of SCA prior to structural MRI changes and before overt pathology is observedThe fourth session of the symposium was dedicated to cerebellar disorders Nicolas Dupré presented an overview of the clinical neurophysiological genetic and neuroimaging characteristics of the autosomal recessive cerebellar ataxias The nonataxic presentations of adolescent or adultonset dominant ataxias were reviewed by Elsdon Storey 5 Both nervous system visual symptoms deafness neuropathy movement disorders neuropsychiatric presentations and nonnervous system features were discussed Elan Louis provided a framework for the pathogenesis of essential tremor on the basis of recent findings showing a major involvement of the cerebellar cortex To close the fourth session Jerôme Honnorat discussed the fundamental mechanisms of the immune cerebellar ataxiasThe fifth session of the symposium addressed the role of the cerebellum in neurocognition affect and social behaviour Jeremy Schmahmann presented converging evidence from clinical anatomical and functional neuroimaging studies demonstrating that the cerebellum is a major player in the modulation of a variety of cognitive and affective operations The constellation of the neuropsychological and behavioralaffective deficits linked to cerebellar pathology is now coined Schmahmann’s syndrome 6 Dennis Schutter discussed the links between cerebellar circuitry and mood disorders 7 He discussed the anatomical basis for a role of the cerebellum in reward and homeostatic regulation Catherine Stoodley provided an overview of clinical and functional neuroimaging findings in a number of neurodevelopmental disorders in which the cerebellum is crucially implicated including developmental dyslexia attention deficit hyperactivity disorder ADHD and autism spectrum disorders ASD 8 The disruption of specific cerebellocerebral circuits in each disorder is now hypothesizedThe sixth session covered the field of therapeutic approaches to cerebellar pathology A great need exists for effective medications in cerebellar ataxias in order to alleviate symptoms and improve the quality of life of the patients Katharina Feil presented an update on the pharmacological treatments of cerebellar ataxias and nystagmus in particular therapies with 4aminopyridines 4AP acetazolamide chlorzoxazone and acetyldlleucine 9 A number of ongoing randomized placebocontrolled trials were presented Neuromodulation of the cerebellum by means of tDCS and TMS is a novel and steadily growing field in the therapeutic approaches to cerebellar pathology Alberto Priori showed how the activity of the cerebellum can be modulated noninvasively with the goal of improving levodopainduced dyskinesias in Parkinson’s disease 10 As highlighted by Jan Cendelin great hope exists that neurotransplantations will soon represent a viable therapeutical strategy Studies in mutant mice are very encouraging and further experiments are needed to jump successfully to human trials in the near future 11 Bingwen Soong discussed in his talk the dominant ataxias with a focus on TGM6 as a novel causative gene of SCA35 and its clinical features SCA35 was identified as a relatively rare subtype of ADCA clinically characterized by cerebellar ataxia corticospinal tract signs hand tremors and EPS The perturbation of the protein stability and transglutaminase activity as well as sensitisation of cells to apoptosis by increasing the activities of caspases were identified as the pathomechanisms underlying SCA35

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