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Purkinje fibre

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
M Lange, S Palamara, T Lassila, C Vergara, A Quarteroni, A F Frangi
Cardiac Purkinje fibres 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 based on operator splitting and is provided with three 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 in order to improve its mathematical consistency...
September 23, 2016: International Journal for Numerical Methods in Biomedical Engineering
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
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...
August 29, 2016: Acta Histochemica
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...
2016: Nature Communications
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
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
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...
August 17, 2016: Journal of Physiology
Emma M Perkins, Daumante Suminaite, Yvonne L Clarkson, Sin Kwan Lee, Alastair R Lyndon, Jeffrey D Rothstein, David Ja 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 stabilisation 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
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
Anton N Shuvaev, Nobutake Hosoi, Yamato Sato, Dai Yanagihara, Hirokazu Hirai
Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disease that presents with cerebellar ataxia and motor learning defects. Previous studies have indicated that the pathology of SCA1, as well as other ataxic diseases, is related to signalling pathways mediated by the metabotropic glutamate receptor type 1 (mGluR1), which is indispensable for proper motor coordination and learning. However, the functional contribution of mGluR signalling to SCA1 pathology is unclear. In the present study, we show that SCA1 model mice develop a functional impairment of mGluR signalling which mediates slow synaptic responses, dendritic Ca(2+) signals and short- and long-term synaptic plasticity at parallel fibre (PF)-Purkinje cell (PC) synapses in a progressive manner from the early disease stage (5 postnatal weeks) prior to PC death...
July 21, 2016: Journal of Physiology
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
Suma Priya Sudarsana Devi, James R Howe, Céline Auger
KEY POINTS: Purkinje cells of the cerebellum receive ∼180,000 parallel fibre synapses, which have often been viewed as a homogeneous synaptic population and studied using single action potentials. Many parallel fibre synapses might be silent, however, and granule cells in vivo fire in bursts. Here, we used trains of stimuli to study parallel fibre inputs to Purkinje cells in rat cerebellar slices. Analysis of train EPSCs revealed two synaptic components, phase 1 and 2. Phase 1 is initially large and saturates rapidly, whereas phase 2 is initially small and facilitates throughout the train...
July 1, 2016: Journal of Physiology
M Gesek, I Otrocka-DomagaŁa, R SokóŁ, K PaŹdzior-Czapula, B D Lambert, A M WiŚniewska, M Żechowicz, M Mikiewicz, P Korzeniowska
The aim of this study was to analyse the morphological lesion pattern of the heart of broiler chickens (Cobb 500, Hubbard F15 and Ross 308) during fattening with no clinical signs of disease and to determine the most susceptible period for the occurrence of morphological lesions. The most frequently diagnosed lesions in each genetic line were degeneration of the fibres with vacuolation, congestion of cardiac muscle, oedema and vacuolisation of the Purkinje cells. The highest numbers of morphological lesions were observed on d 38, 31 and 10 of life...
April 2016: British Poultry Science
Jue Li, Sunil Jit Logantha, Joseph Yanni, Xue Cai, Halina Dobrzynski, George Hart, Mark R Boyett
This study used one-dimensional computer simulation to investigate the influence of heart failure on action potential conduction through the left Purkinje fibres to the left ventricle. The study was based on a rabbit model of left ventricular heart failure caused by volume and pressure overload. To simulate the effect of heart failure, we began with models of the healthy rabbit Purkinje fibre action potential and healthy left ventricular (endocardial) action potential. In the absence of ionic current measurements from failing rabbit Purkinje fibres, we assumed that changes in ionic currents mirrored changes in ion channel expression (measured at the messenger RNA level): ionic conductances were adjusted based on changes in expression of the relevant ion channels...
2015: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
Natsumi Ageta-Ishihara, Maya Yamazaki, Kohtarou Konno, Hisako Nakayama, Manabu Abe, Kenji Hashimoto, Tomoki Nishioka, Kozo Kaibuchi, Satoko Hattori, Tsuyoshi Miyakawa, Kohichi Tanaka, Fathul Huda, Hirokazu Hirai, Kouichi Hashimoto, Masahiko Watanabe, Kenji Sakimura, Makoto Kinoshita
The small GTPase-effector proteins CDC42EP1-5/BORG1-5 interact reciprocally with CDC42 or the septin cytoskeleton. Here we show that, in the cerebellum, CDC42EP4 is exclusively expressed in Bergmann glia and localizes beneath specific membrane domains enwrapping dendritic spines of Purkinje cells. CDC42EP4 forms complexes with septin hetero-oligomers, which interact with a subset of glutamate transporter GLAST/EAAT1. In Cdc42ep4(-/-) mice, GLAST is dissociated from septins and is delocalized away from the parallel fibre-Purkinje cell synapses...
2015: Nature Communications
Romain Ly, Guy Bouvier, German Szapiro, Haydn M Prosser, Andrew D Randall, Masanobu Kano, Kenji Sakimura, Philippe Isope, Boris Barbour, Anne Feltz
KEY POINTS: At the parallel fibre-Purkinje cell glutamatergic synapse, little or no Ca(2+) entry takes place through postsynaptic neurotransmitter receptors, although postsynaptic calcium increases are clearly involved in the synaptic plasticity. Postsynaptic voltage-gated Ca(2+) channels therefore constitute the sole rapid postsynaptic Ca(2+) signalling mechanism, making it essential to understand how they contribute to the synaptic signalling. Using a selective T-type calcium channel antagonist, we describe a T-type component of the EPSC that is activated by the AMPA receptor-mediated depolarization of the spine and thus will contribute to the local calcium dynamics...
February 15, 2016: Journal of Physiology
Thomas Hof, Laurent Sallé, Laurent Coulbault, Romain Richer, Joachim Alexandre, René Rouet, Alain Manrique, Romain Guinamard
KEY POINTS: The transient receptor potential melastatin 4 (TRPM4) inhibitor 9-phenanthrol reduces action potential duration in rabbit Purkinje fibres but not in ventricle. TRPM4-like single channel activity is observed in isolated rabbit Purkinje cells but not in ventricular cells. The TRPM4-like current develops during the notch and early repolarization phases of the action potential in Purkinje cells. ABSTRACT: Transient receptor potential melastatin 4 (TRPM4) Ca(2+)-activated non-selective cation channel activity has been recorded in cardiomyocytes and sinus node cells from mammals...
January 15, 2016: Journal of Physiology
Norbert Nagy, Tamás Szél, Norbert Jost, András Tóth, Julius Gy Papp, András Varró
Data obtained from canine cardiac electrophysiology studies are often extrapolated to the human heart. However, it has been previously demonstrated that because of the lower density of its K(+) currents, the human ventricular action potential has a less extensive repolarization reserve. Since the relevance of canine data to the human heart has not yet been fully clarified, the aim of the present study was to determine for the first time the action potentials of undiseased human Purkinje fibres (PFs) and to compare them directly with those of dog PFs...
September 2015: Canadian Journal of Physiology and Pharmacology
Nico Angliker, Michael Burri, Mariana Zaichuk, Jean-Marc Fritschy, Markus A Rüegg
The mammalian target of rapamycin (mTOR) is a key regulator of cellular growth which associates with other proteins to form two multi-protein complexes called mTORC1 and mTORC2. Dysregulation of mTORC1 signalling in brain is implicated in neuropathological conditions such as autism spectrum or neurodegenerative disorders. Accordingly, allosteric mTOR inhibitors are currently in clinical trials for the treatment of such disorders. Here, we ablated either mTORC1 or mTORC2 conditionally in Purkinje cells of the mouse cerebellum to dissect their role in the development, function and survival of these neurons...
October 2015: European Journal of Neuroscience
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