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https://www.readbyqxmd.com/read/28439779/searching-for-an-internal-representation-of-stimulus-kinematics-in-the-response-of-ventral-paraflocculus-purkinje-cells
#1
Pablo M Blazquez, GyuTae Kim, Tatyana A Yakusheva
Motor control theories propose that the central nervous system builds internal representations of the motion of both our body and external objects. These representations, called forward models, are essential for accurate motor control. For instance, to produce a precise reaching movement to catch a flying ball, the central nervous system must build predictions of the current and future states of both the arm and the ball. Accumulating evidence suggests that the cerebellar cortex contains a forward model of an individual's body movement...
April 24, 2017: Cerebellum
https://www.readbyqxmd.com/read/28436840/a-parametric-computational-model-of-the-action-potential-of-pacemaker-cells
#2
Weiwei Ai, Nitish Patel, Partha Roop, Avinash Malik, Sidharta Andalam, Eugene Yip, Nathan Allen, Mark Trew
OBJECTIVE: A flexible, efficient and verifiable pacemaker cell model is essential to the design of real-time virtual hearts that can be used for closed-loop validation of cardiac devices. A new parametric model of pacemaker action potential is developed to address this need. METHODS: The action potential phases are modeled using hybrid automaton (HA) with one piecewise-linear continuous variable. The model can capture ratedependent dynamics, such as action potential duration (APD) restitution, conduction velocity (CV) restitution, and overdrive suppression by incorporating non-linear update functions...
April 24, 2017: IEEE Transactions on Bio-medical Engineering
https://www.readbyqxmd.com/read/28435670/type-1-metabotropic-glutamate-receptor-signaling-in-cerebellar-purkinje-cells-in-health-and-disease
#3
REVIEW
Masanobu Kano, Takaki Watanabe
The cerebellum is a brain structure involved in coordination, control, and learning of movements, as well as certain aspects of cognitive function. Purkinje cells are the sole output neurons from the cerebellar cortex and therefore play crucial roles in the overall function of the cerebellum. The type-1 metabotropic glutamate receptor (mGluR1) is a key "hub" molecule that is critically involved in the regulation of synaptic wiring, excitability, synaptic response, and synaptic plasticity of Purkinje cells. In this review, we aim to highlight how mGluR1 controls these events in Purkinje cells...
2017: F1000Research
https://www.readbyqxmd.com/read/28433554/catheter-ablation-to-prevent-sudden-cardiac-death
#4
Josef Kautzner, Petr Peichl
Since ventricular arrhythmias are a common cause of sudden cardiac death (SCD), treatment for ventricular arrhythmias is the target area of interest in research field. Among different means to prevent ventricular arrhythmias, catheter ablation (CA) has emerged as an effective therapeutic method. CA can decrease the likelihood of SCD in the following arrhythmia categories: 1) idiopathic ventricular fibrillation (VF) that is usually triggered by premature ventricular beats originating in the Purkinje fibres; 2) VF in subjects with structural heart disease, especially after myocardial infarction, that is triggered by premature ventricular beats from surviving Purkinje fibres; 3) Brugada syndrome in which modification of an epicardial substrate in the right ventricular outflow tract might be the most promising strategy; 4) recurrent monomorphic ventricular tachycardias in the setting of structural heart disease; 5) ventricular preexcitation in which CA appears to be a method of choice in high risk patients, regardless of the presence or absence of symptoms...
April 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28429218/modification-of-calcium-activated-chloride-currents-in-cerebellar-purkinje-neurons
#5
E A Vikhareva, V L Zamoyski, V V Grigoriev
The whole-cell voltage clamp technique was employed to record the total ionic currents in rat cerebellar Purkinje neurons. When intrapipette solution contained 120 mM KCl, replacement of the standard external physiological saline with Na-free solution resulted in appearance of inward tail current after the end of the depolarizing pulse. When intrapipette potassium ions were replaced for cesium ones, the tail currents were observed even in the presence of normal Na(+) concentration (140 mM) in the external solution...
April 21, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28425471/nonspecific-synaptic-plasticity-improves-the-recognition-of-sparse-patterns-degraded-by-local-noise
#6
Karen Safaryan, Reinoud Maex, Neil Davey, Rod Adams, Volker Steuber
Many forms of synaptic plasticity require the local production of volatile or rapidly diffusing substances such as nitric oxide. The nonspecific plasticity these neuromodulators may induce at neighboring non-active synapses is thought to be detrimental for the specificity of memory storage. We show here that memory retrieval may benefit from this non-specific plasticity when the applied sparse binary input patterns are degraded by local noise. Simulations of a biophysically realistic model of a cerebellar Purkinje cell in a pattern recognition task show that, in the absence of noise, leakage of plasticity to adjacent synapses degrades the recognition of sparse static patterns...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424594/overexpression-of-human-sod1-leads-to-discrete-defects-in-the-cerebellar-architecture-in-the-mouse
#7
Pegah Afshar, Niloufar Ashtari, Xiaodan Jiao, Maryam Rahimi-Balaei, Xiaosha Zhang, Behzad Yaganeh, Marc R Del Bigio, Jiming Kong, Hassan Marzban
The human superoxide dismutase 1 (SOD1) gene is responsible for neutralizing supercharged oxygen radicals within the cell. Mutation in SOD1 gene causes amyotrophic lateral sclerosis (ALS). Recent studies have shown involvement of the cerebellum in ALS, although the cerebellar contribution in SOD1 transgenic mice remains unclear. Using immunohistopathology, we investigated the Purkinje cell phenotype in the vermis of the SOD1 transgenic mice cerebellum. Calbindin 1 (Calb1) and three well-known zone and stripe markers, zebrin II, HSP25, and PLCβ4 have been used to explore possible alteration in zone and stripe...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28423317/loss-of-nav%C3%AE-4-mediated-regulation-of-sodium-currents-in-adult-purkinje-neurons-disrupts-firing-and-impairs-motor-coordination-and-balance
#8
Joseph L Ransdell, Edward Dranoff, Brandon Lau, Wan-Lin Lo, David L Donermeyer, Paul M Allen, Jeanne M Nerbonne
The resurgent component of voltage-gated Na(+) (Nav) currents, INaR, has been suggested to provide the depolarizing drive for high-frequency firing and to be generated by voltage-dependent Nav channel block (at depolarized potentials) and unblock (at hyperpolarized potentials) by the accessory Navβ4 subunit. To test these hypotheses, we examined the effects of the targeted deletion of Scn4b (Navβ4) on INaR and on repetitive firing in cerebellar Purkinje neurons. We show here that Scn4b(-/-) animals have deficits in motor coordination and balance and that firing rates in Scn4b(-/-) Purkinje neurons are markedly attenuated...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28413823/long-term-predictive-and-feedback-encoding-of-motor-signals-in-the-simple-spike-discharge-of-purkinje-cells
#9
Laurentiu S Popa, Martha L Streng, Timothy J Ebner
Most hypotheses of cerebellar function emphasize a role in real-time control of movements. However, the cerebellum's use of current information to adjust future movements and its involvement in sequencing, working memory, and attention argues for predicting and maintaining information over extended time windows. The present study examines the time course of Purkinje cell discharge modulation in the monkey (Macaca mulatta) during manual, pseudo-random tracking. Analysis of the simple spike firing from 183 Purkinje cells during tracking reveals modulation up to 2 s before and after kinematics and position error...
March 2017: ENeuro
https://www.readbyqxmd.com/read/28409694/immunohistochemical-localization-of-irisin-in-mole-rats-spalax-leucodon
#10
F M Gür, S Timurkaan, M H Yalcin, A Girgin, B Gençer Tarakçı
Irisin was first identified in skeletal muscle cells. It is an exercise protein that is secreted into the circulation; it causes conversion of white adipose tissue to brown adipose tissue. We investigated irisin immunoreactivity in mole rat (Spalax leucodon) tissues. We examined cerebellum, pituitary, heart, liver, pancreas, spleen, uterus, kidney and striated muscle in female adult mole rats. Tissues were processed, embedded in paraffin, sectioned at 5 μm and stained immunohistochemically for irisin. Irisin immunostaining was detected in the cytoplasm of stained cells; the cytoplasm of Purkinje cells was unstained...
April 14, 2017: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/28405024/antisense-oligonucleotide-therapy-for-spinocerebellar-ataxia-type-2
#11
Daniel R Scoles, Pratap Meera, Matthew D Schneider, Sharan Paul, Warunee Dansithong, Karla P Figueroa, Gene Hung, Frank Rigo, C Frank Bennett, Thomas S Otis, Stefan M Pulst
There are no disease-modifying treatments for adult human neurodegenerative diseases. Here we test RNA-targeted therapies in two mouse models of spinocerebellar ataxia type 2 (SCA2), an autosomal dominant polyglutamine disease. Both models recreate the progressive adult-onset dysfunction and degeneration of a neuronal network that are seen in patients, including decreased firing frequency of cerebellar Purkinje cells and a decline in motor function. We developed a potential therapy directed at the ATXN2 gene by screening 152 antisense oligonucleotides (ASOs)...
April 20, 2017: Nature
https://www.readbyqxmd.com/read/28392471/expression-of-mutant-disc1-in-purkinje-cells-increases-their-spontaneous-activity-and-impairs-cognitive-and-social-behaviors-in-mice
#12
Alexey V Shevelkin, Chantelle E Terrillion, Bagrat N Abazyan, Tymoteusz J Kajstura, Yan A Jouroukhin, Gay L Rudow, Juan C Troncoso, David J Linden, Mikhail V Pletnikov
In addition to motor function, the cerebellum has been implicated in cognitive and social behaviors. Various structural and functional abnormalities of Purkinje cells (PCs) have been observed in schizophrenia and autism. As PCs express the gene Disrupted-In-Schizophrenia-1 (DISC1), and DISC1 variants have been associated with neurodevelopmental disorders, we evaluated the role of DISC1 in cerebellar physiology and associated behaviors using a mouse model of inducible and selective expression of a dominant-negative, C-terminus truncated human DISC1 (mutant DISC1) in PCs...
April 6, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28389475/movement-rate-is-encoded-and-influenced-by-widespread-coherent-activity-of-cerebellar-molecular-layer-interneurons
#13
Michael A Gaffield, Jason M Christie
Inhibition from molecular layer interneurons (MLIs) is thought to play an important role in cerebellar function by sharpening the precision of Purkinje cell spike output. Yet the coding features of MLIs during behavior are poorly understood. To study MLI activity, we used in vivo Ca(2+) imaging in head-fixed mice during the performance of a rhythmic motor behavior, licking during water consumption. MLIs were robustly active during lick-related movement across a lobule-specific region of the cerebellum showing high temporal correspondence within their population...
April 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28388629/a-tubulin-alpha-8-mouse-knockout-model-indicates-a-likely-role-in-spermatogenesis-but-not-in-brain-development
#14
Christine P Diggle, Isabel Martinez-Garay, Zoltan Molnar, Martin H Brinkworth, Ed White, Ewan Fowler, Ruth Hughes, Bruce E Hayward, Ian M Carr, Christopher M Watson, Laura Crinnion, Aruna Asipu, Ben Woodman, P Louise Coletta, Alexander F Markham, T Neil Dear, David T Bonthron, Michelle Peckham, Ewan E Morrison, Eamonn Sheridan
Tubulin alpha 8 (Tuba8) is the most divergent member of the highly conserved alpha tubulin family, and uniquely lacks two key post-translational modification sites. It is abundantly expressed in testis and muscle, with lower levels in the brain. We previously identified homozygous hypomorphic TUBA8 mutations in human subjects with a polymicrogyria (PMG) syndrome, suggesting its involvement in development of the cerebral cortex. We have now generated and characterized a Tuba8 knockout mouse model. Homozygous mice were confirmed to lack Tuba8 protein in the testis, but did not display PMG and appeared to be neurologically normal...
2017: PloS One
https://www.readbyqxmd.com/read/28387450/severe-demyelination-in-a-patient-with-a-late-infantile-form-of-niemann-pick-disease-type-c
#15
Tsuyoshi Kodachi, Shizuko Matsumoto, Masashi Mizuguchi, Hitoshi Osaka, Nobuyuki Kanai, Eiji Nanba, Kousaku Ohno, Takanori Yamagata
Niemann-Pick disease type C (NPC) is a cholesterol storage disease caused by defective cellular cholesterol transportation. The onset and progression of NPC are variable, and autopsy findings have mainly been reported for the adult and juvenile forms of this disease. Here we report the clinical and pathological findings from a 9-year-old female patient with the late infantile form of NPC due to NPC1 gene mutation. She had notable splenomegaly at 4 months of age. She lost the ability to speak at 18 months of age...
April 7, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28386581/paraneoplastic-cerebellar-degeneration-in-a-patient-with-a-primary-fallopian-tube-adenocarcinoma-a-case-report-and-brief-review
#16
Mario Campero, Alberto E Selman
We describe a 65-year-old woman with subacute cerebellar syndrome expressed as severe ataxia, and the presence of anti Purkinje cell antibodies (Anti-Yo). A small adnexal mass was only evident on PET CT with the pathological feature of fallopian tube adenocarcinoma. Anti-Yo antibodies have been strongly associated with paraneoplastic cerebellar degeneration, and nearly always associated to ovarian adenocarcinomas. Few cases have been reported in which this paraneoplastic syndrome has been related to fallopian tube adenocarcinoma...
May 2017: Gynecologic Oncology Reports
https://www.readbyqxmd.com/read/28374839/genetic-silencing-of-olivocerebellar-synapses-causes-dystonia-like-behaviour-in-mice
#17
Joshua J White, Roy V Sillitoe
Theories of cerebellar function place the inferior olive to cerebellum connection at the centre of motor behaviour. One possible implication of this is that disruption of olivocerebellar signalling could play a major role in initiating motor disease. To test this, we devised a mouse genetics approach to silence glutamatergic signalling only at olivocerebellar synapses. The resulting mice had a severe neurological condition that mimicked the early-onset twisting, stiff limbs and tremor that is observed in dystonia, a debilitating movement disease...
April 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28373570/effects-of-systemic-multiexon-skipping-with-peptide-conjugated-morpholinos-in-the-heart-of-a-dog-model-of-duchenne-muscular-dystrophy
#18
Yusuke Echigoya, Akinori Nakamura, Tetsuya Nagata, Nobuyuki Urasawa, Kenji Rowel Q Lim, Nhu Trieu, Dharminder Panesar, Mutsuki Kuraoka, Hong M Moulton, Takashi Saito, Yoshitsugu Aoki, Patrick Iversen, Peter Sazani, Ryszard Kole, Rika Maruyama, Terry Partridge, Shin'ichi Takeda, Toshifumi Yokota
Duchenne muscular dystrophy (DMD) is a lethal genetic disorder caused by an absence of the dystrophin protein in bodywide muscles, including the heart. Cardiomyopathy is a leading cause of death in DMD. Exon skipping via synthetic phosphorodiamidate morpholino oligomers (PMOs) represents one of the most promising therapeutic options, yet PMOs have shown very little efficacy in cardiac muscle. To increase therapeutic potency in cardiac muscle, we tested a next-generation morpholino: arginine-rich, cell-penetrating peptide-conjugated PMOs (PPMOs) in the canine X-linked muscular dystrophy in Japan (CXMDJ) dog model of DMD...
April 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28366372/rotational-stability-of-2-intraocular-lenses-with-an-identical-design-and-different-materials
#19
Petra Draschl, Nino Hirnschall, Nikolaus Luft, Sandra Schuschitz, Jörg Wiesinger, Karl Rigal, Oliver Findl
PURPOSE: To evaluate the rotational stability of nontoric intraocular lenses (IOLs) of the same design and different materials. SETTING: Vienna Institute for Research in Ocular Surgery, Department of Ophthalmology, Hanusch Hospital, Vienna, Austria. DESIGN: Prospective randomized case series. METHODS: This study included cataract patients with a corneal astigmatism of less than 1.75 diopters measured with the IOLMaster 500...
February 2017: Journal of Cataract and Refractive Surgery
https://www.readbyqxmd.com/read/28364185/cerebellar-pathology-in-familial-vs-sporadic-essential-tremor
#20
Elan D Louis, Sheng-Han Kuo, Jie Wang, William J Tate, Ming-Kai Pan, Geoffrey C Kelly, Jesus Gutierrez, Etty P Cortes, Jean-Paul G Vonsattel, Phyllis L Faust
Familial and sporadic essential tremor (ET) cases differ in several respects. Whether they differ with respect to cerebellar pathologic changes has yet to be studied. We quantified a broad range of postmortem features (Purkinje cell (PC) counts, PC axonal torpedoes, a host of associated axonal changes, heterotopic PCs, and hairy basket ratings) in 60 ET cases and 30 controls. Familial ET was defined using both liberal criteria (n = 27) and conservative criteria (n = 20). When compared with controls, ET cases had lower PC counts, more torpedoes, more heterotopic PCs, a higher hairy basket rating, an increase in PC axonal collaterals, an increase in PC thickened axonal profiles, and an increase in PC axonal branching...
March 31, 2017: Cerebellum
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