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Purkinje fibre

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https://www.readbyqxmd.com/read/28795396/synaptic-excitation-by-climbing-fibre-collaterals-in-the-cerebellar-nuclei-of-juvenile-and-adult-mice
#1
Marion Najac, Indira M Raman
The inferior olive conveys instructive signals to the cerebellum that drive sensorimotor learning. Inferior olivary neurons transmit their signals via climbing fibres, which powerfully excite Purkinje cells, evoking complex spikes and depressing parallel fibre synapses. Additionally, however, these climbing fibres send collaterals to the cerebellar nuclei (CbN). In vivo and in vitro data suggest that climbing fibre collateral excitation is weak in adult mice, raising the question of whether the primary role of this pathway may be developmental...
August 10, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28794450/serial-processing-of-kinematic-signals-by-cerebellar-circuitry-during-voluntary-whisking
#2
Susu Chen, George J Augustine, Paul Chadderton
Purkinje cells (PCs) in Crus 1 represent whisker movement via linear changes in firing rate, but the circuit mechanisms underlying this coding scheme are unknown. Here we examine the role of upstream inputs to PCs-excitatory granule cells (GCs) and inhibitory molecular layer interneurons-in processing of whisking signals. Patch clamp recordings in GCs reveal that movement is accompanied by changes in mossy fibre input rate that drive membrane potential depolarisation and high-frequency bursting activity at preferred whisker angles...
August 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28677370/neuronal-vacuolation-and-spinocerebellar-degeneration-associated-with-altered-neurotransmission
#3
Aggeliki Giannakopoulou
<i>Inherited neurodegenerative disorders are debilitating diseases that occur across different species, such as the domestic dog (Canis lupus familiaris), and many are caused by mutations in the same genes as corresponding human conditions. In the present study, we report an inherited neurodegenerative condition, termed 'neuronal vacuolation and spinocerebellar degeneration' (NVSD) which affects neonatal or young dogs, mainly Rottweilers, which recently has been linked with the homozygosity for the RAB3GAP1:c...
2017: Folia Neuropathologica
https://www.readbyqxmd.com/read/28634887/aberrant-connections-between-climbing-fibres-and-purkinje-cells-induce-alterations-in-the-timing-of-an-instrumental-response-in-the-rat
#4
Lorena Gaytán-Tocavén, Miguel Ángel López-Vázquez, Miguel Ángel Guevara, María Esther Olvera-Cortés
Cerebellar participation in timing and sensory-motor sequences has been supported by several experimental and clinical studies. A relevant role of the cerebellum in timing of conditioned responses in the range of milliseconds has been demonstrated, but less is known regarding the role of the cerebellum in supra-second timing of operant responses. A dissociated role of the cerebellum and striatum in timing in the millisecond and second range had been reported, respectively. The climbing fibre-Purkinje cell synapse is crucial in timing models; thus, the aberrant connection between these cellular elements is a suitable model for evaluating the contribution of the cerebellum in timing in the supra-second range...
June 20, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28513836/facilitation-of-mossy-fibre-driven-spiking-in-the-cerebellar-nuclei-by-the-synchrony-of-inhibition
#5
Yeechan Wu, Indira M Raman
KEY POINTS: Large premotor neurons of the cerebellar nuclei (CbN cells) integrate synaptic inhibition from Purkinje neurons and synaptic excitation from mossy fibres to generate cerebellar output. We find that mossy fibre inputs to CbN cells generate unitary AMPA receptor EPSCs of ∼1 nS that decay in ∼1 ms and mildly voltage-dependent NMDA receptor EPSCs of ∼0.6 nS that decay in ∼7 ms. A few hundred mossy fibres active at a few tens of spikes s(-1) must converge on CbN cells to generate physiological CbN spike rates (∼60 spikes s(-1) ) during convergent inhibition from spontaneously active Purkinje cells...
August 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28495974/long-term-depression-of-intrinsic-excitability-accompanied-by-the-synaptic-depression-in-the-cerebellar-purkinje-cells
#6
Hyun Geun Shim, Dong Cheol Jang, Jaegeon Lee, Geehoon Chung, Sukchan Lee, Yong Gyu Kim, Da Eun Jeon, Sang Jeong Kim
Long-term depression (LTD) at parallel fibres (PF) to cerebellar Purkinje cells (PC) synapse is implicated in the output of PC, the sole output of the cerebellar cortex. Besides the synaptic plasticity, intrinsic excitability is also one of the components which determines the PC output. Although long-term potentiation of intrinsic excitability (LTP-IE) has been suggested, it has yet to be investigated how PF-PC LTD modifies intrinsic excitability of PC. Here, we show that pairing of the PF and climbing fibre (CF) for PF-PC LTD induction evokes long-term depression of intrinsic excitability (LTD-IE) in the cerebellar PCs from male C57BL/6 mice...
May 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28433554/catheter-ablation-to-prevent-sudden-cardiac-death
#7
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/27832106/the-effect-of-a-novel-highly-selective-inhibitor-of-the-sodium-calcium-exchanger-ncx-on-cardiac-arrhythmias-in-in-vitro-and-in-vivo-experiments
#8
Zsófia Kohajda, Nikolett Farkas-Morvay, Norbert Jost, Norbert Nagy, Amir Geramipour, András Horváth, Richárd S Varga, Tibor Hornyik, Claudia Corici, Károly Acsai, Balázs Horváth, János Prorok, Balázs Ördög, Szilvia Déri, Dániel Tóth, Jouko Levijoki, Piero Pollesello, Tuula Koskelainen, Leena Otsomaa, András Tóth, István Baczkó, István Leprán, Péter P Nánási, Julius Gy Papp, András Varró, László Virág
BACKGROUND: In this study the effects of a new, highly selective sodium-calcium exchanger (NCX) inhibitor, ORM-10962 were investigated on cardiac NCX current, Ca2+ transients, cell shortening and in experimental arrhythmias. The level of selectivity of the novel inhibitor on several major transmembrane ion currents (L-type Ca2+ current, major repolarizing K+ currents, late Na+ current, Na+/K+ pump current) was also determined. METHODS: Ion currents in single dog ventricular cells (cardiac myocytes; CM), and action potentials in dog cardiac multicellular preparations were recorded utilizing the whole-cell patch clamp and standard microelectrode techniques, respectively...
2016: PloS One
https://www.readbyqxmd.com/read/27716829/analysis-of-microstructure-of-the-cardiac-conduction-system-based-on-three-dimensional-confocal-microscopy
#9
Daniel Romero, Oscar Camara, Frank Sachse, Rafael Sebastian
The specialised conducting tissues present in the ventricles are responsible for the fast distribution of the electrical impulse from the atrio-ventricular node to regions in the subendocardial myocardium. Characterisation of anatomical features of the specialised conducting tissues in the ventricles is highly challenging, in particular its most distal section, which is connected to the working myocardium via Purkinje-myocardial junctions. The goal of this work is to characterise the architecture of the distal section of the Purkinje network by differentiating Purkinje cells from surrounding tissue, performing a segmentation of Purkinje fibres at cellular scale, and mathematically describing its morphology and interconnections...
2016: PloS One
https://www.readbyqxmd.com/read/27661463/improved-hybrid-gpu-algorithm-for-solving-cardiac-electrophysiology-problems-on-purkinje-networks
#10
M Lange, S Palamara, T Lassila, C Vergara, A Quarteroni, A F Frangi
Cardiac Purkinje fibers provide an important pathway to the coordinated contraction of the heart. We present a numerical algorithm for the solution of electrophysiology problems across the Purkinje network that is efficient enough to be used in in silico studies on realistic Purkinje networks with physiologically detailed models of ion exchange at the cell membrane. The algorithm is on the basis of operator splitting and is provided with 3 different implementations: pure CPU, hybrid CPU/GPU, and pure GPU. Compared to our previous work, we modify the explicit gap junction term at network bifurcations to improve its mathematical consistency...
September 23, 2016: International Journal for Numerical Methods in Biomedical Engineering
https://www.readbyqxmd.com/read/27651000/spatiotemporal-dynamics-of-lesion-induced-axonal-sprouting-and-its-relation-to-functional-architecture-of-the-cerebellum
#11
Matasha Dhar, Joshua M Brenner, Kenji Sakimura, Masanobu Kano, Hiroshi Nishiyama
Neurodegenerative lesions induce sprouting of new collaterals from surviving axons, but the extent to which this form of axonal remodelling alters brain functional structure remains unclear. To understand how collateral sprouting proceeds in the adult brain, we imaged post-lesion sprouting of cerebellar climbing fibres (CFs) in mice using in vivo time-lapse microscopy. Here we show that newly sprouted CF collaterals innervate multiple Purkinje cells (PCs) over several months, with most innervations emerging at 3-4 weeks post lesion...
September 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27586811/cathepsin-l-coexists-with-cytotoxic-t-lymphocyte-antigen-2-alpha-in-distinct-regions-of-the-mouse-brain
#12
Claudius Luziga, Bui Thi To Nga, Gabriel Mbassa, Yoshimi Yamamoto
Cathepsins B and L are two prominent members of cystein proteases with broad substrate specificity and are known to be involved in the process of intra- and extra-cellular protein degradation and turnover. The propeptide region of cathepsin L is identical to Cytotoxic T-lymphocyte antigen-2α (CTLA-2α) discovered in mouse activated T-cells and mast cells. CTLA-2α exhibits selective inhibitory activities against papain and cathepsin L. We previously demonstrated the distribution pattern of the CTLA-2α protein in mouse brain by immunohistochemistry, describing that it is preferentially localized within nerve fibre bundles than neuronal cell bodies...
September 2016: Acta Histochemica
https://www.readbyqxmd.com/read/27581745/dysfunctional-cerebellar-purkinje-cells-contribute-to-autism-like-behaviour-in-shank2-deficient-mice
#13
Saša Peter, Michiel M Ten Brinke, Jeffrey Stedehouder, Claudia M Reinelt, Bin Wu, Haibo Zhou, Kuikui Zhou, Henk-Jan Boele, Steven A Kushner, Min Goo Lee, Michael J Schmeisser, Tobias M Boeckers, Martijn Schonewille, Freek E Hoebeek, Chris I De Zeeuw
Loss-of-function mutations in the gene encoding the postsynaptic scaffolding protein SHANK2 are a highly penetrant cause of autism spectrum disorders (ASD) involving cerebellum-related motor problems. Recent studies have implicated cerebellar pathology in the aetiology of ASD. Here we evaluate the possibility that cerebellar Purkinje cells (PCs) represent a critical locus of ASD-like pathophysiology in mice lacking Shank2. Absence of Shank2 impairs both PC intrinsic plasticity and induction of long-term potentiation at the parallel fibre to PC synapse...
September 1, 2016: Nature Communications
https://www.readbyqxmd.com/read/27571910/double-trouble-para-neoplastic-anti-pca-2-and-crmp-5-mediated-small-fibre-neuropathy-followed-by-chorea-associated-with-small-cell-lung-cancer-and-evolving-radiological-features
#14
Waqar Waheed, James Boyd, Farrah Khan, Sharon L Mount, Neil M Borden, Rup Tandan
Patients with Purkinje cell cytoplasmic autoantibody type 2 (PCA-2) and collapsin response-mediator protein-5 (CRMP-5) autoantibody can present with multifocal elements of encephalomyeloneuropathy. Except for an anecdotal report, case descriptions of paraneoplastic small fibre neuropathy are lacking. We report paraneoplastic small fibre neuropathy followed by chorea associated with small cell lung cancer. A man aged 57 years with a 35 pack-year smoking history presented with painless subacute paresthesia and weight fluctuation...
August 29, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27543770/ultrastructural-pathology-of-human-peritumoural-oedematous-cerebellar-cortex
#15
O J Castejón
Cerebellar cortical biopsies of the peritumoural region of seven patients with cerebellar haemangioma, mesencephalic meningioma, cerebellopontine astrocytoma, cerebellopontine meningioma, and medulloblastoma of cerebellar vermis were examined by means of conventional transmission electron microscopy. Granule cells showed oedematous cytoplasm and mitochondria. Swollen Golgi cells exhibited lipofuscin granules and intranuclear inclusions. Both neuron cell types displayed swollen dendritic digits synapsing with afferent mossy fibre endings...
2016: Folia Neuropathologica
https://www.readbyqxmd.com/read/27531396/transient-cerebellar-alterations-during-development-prior-to-obvious-motor-phenotype-in-a-mouse-model-of-spinocerebellar-ataxia-type-6
#16
Sriram Jayabal, Lovisa Ljungberg, Alanna J Watt
KEY POINTS: Spinocerebellar ataxia type 6 (SCA6) is a midlife-onset neurodegenerative disease caused by a CACNA1A mutation; CACNA1A is also implicated in cerebellar development. We have previously shown that when disease symptoms are present in midlife in SCA6(84Q/84Q) mice, cerebellar Purkinje cells spike with reduced rate and precision. In contrast, we find that during postnatal development (P10-13), SCA6(84Q/84Q) Purkinje cells spike with elevated rate and precision. Although surplus climbing fibres are linked to ataxia in other mouse models, we found surplus climbing fibre inputs on developing (P10-13) SCA6(84Q/84Q) Purkinje cells when motor deficits were not detected...
February 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/27530255/posterior-cerebellar-purkinje-cells-in-an-sca5-sparca1-mouse-model-are-especially-vulnerable-to-the-synergistic-effect-of-loss-of-%C3%AE-iii-spectrin-and-glast
#17
Emma M Perkins, Daumante Suminaite, Yvonne L Clarkson, Sin Kwan Lee, Alastair R Lyndon, Jeffrey D Rothstein, David J A Wyllie, Kohichi Tanaka, Mandy Jackson
Clinical phenotypes of spinocerebellar ataxia type-5 (SCA5) and spectrin-associated autosomal recessive cerebellar ataxia type-1 (SPARCA1) are mirrored in mice lacking β-III spectrin (β-III(-/-)). One function of β-III spectrin is the stabilization of the Purkinje cell-specific glutamate transporter EAAT4 at the plasma membrane. In β-III(-/-) mice EAAT4 levels are reduced from an early age. In contrast levels of the predominant cerebellar glutamate transporter GLAST, expressed in Bergmann glia, only fall progressively from 3 months onwards...
August 15, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27518800/regional-regulation-of-purkinje-cell-dendritic-spines-by-integrins-and-eph-ephrins
#18
Tristan G Heintz, Richard Eva, James W Fawcett
Climbing fibres and parallel fibres compete for dendritic space on Purkinje cells in the cerebellum. Normally, climbing fibres populate the proximal dendrites, where they suppress the multiple small spines typical of parallel fibres, leading to their replacement by the few large spines that contact climbing fibres. Previous work has shown that ephrins acting via EphA4 are a signal for this change in spine type and density. We have used an in vitro culture model in which to investigate the ephrin effect on Purkinje cell dendritic spines and the role of integrins in these changes...
2016: PloS One
https://www.readbyqxmd.com/read/27440721/progressive-impairment-of-cerebellar-mglur-signalling-and-its-therapeutic-potential-for-cerebellar-ataxia-in-spinocerebellar-ataxia-type-1-model-mice
#19
Anton N Shuvaev, Nobutake Hosoi, Yamato Sato, Dai Yanagihara, Hirokazu Hirai
KEY POINTS: Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disease caused by a gene defect, leading to movement disorder such as cerebellar ataxia. It remains largely unknown which functional defect contributes to the cerebellar ataxic phenotype in SCA1. In this study, we report progressive dysfunction of metabotropic glutamate receptor (mGluR) signalling, which leads to smaller slow synaptic responses, reduced dendritic Ca(2+) signals and impaired synaptic plasticity at cerebellar synapses, in the early disease stage of SCA1 model mice...
January 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/27163479/a-generalised-method-to-estimate-the-kinetics-of-fast-ca-2-currents-from-ca-2-imaging-experiments
#20
Karima Ait Ouares, Nadia Jaafari, Marco Canepari
BACKGROUND: Fast Ca(2+) imaging using low-affinity fluorescent indicators allows tracking Ca(2+) neuronal influx at high temporal resolution. In some systems, where the Ca(2+)-bound indicator is linear with Ca(2+) entering the cell, the Ca(2+) current has same kinetics of the fluorescence time derivative. In other systems, like cerebellar Purkinje neuron dendrites, the time derivative strategy fails since fluorescence kinetics is affected by Ca(2+) binding proteins sequestering Ca(2+) from the indicator...
August 1, 2016: Journal of Neuroscience Methods
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