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Sample records for cascade mediates cerebellar

  1. Cerebellar vermis H₂ receptors mediate fear memory consolidation in mice.

    Science.gov (United States)

    Gianlorenço, A C L; Riboldi, A M; Silva-Marques, B; Mattioli, R

    2015-02-01

    Histaminergic fibers are present in the molecular and granular layers of the cerebellum and have a high density in the vermis and flocullus. Evidence supports that the cerebellar histaminergic system is involved in memory consolidation. Our recent study showed that histamine injections facilitate the retention of an inhibitory avoidance task, which was abolished by pretreatment with an H2 receptor antagonist. In the present study, we investigated the effects of intracerebellar post training injections of H1 and H2 receptor antagonists as well as the selective H2 receptor agonist on fear memory consolidation. The cerebellar vermi of male mice were implanted with guide cannulae, and after three days of recovery, the inhibitory avoidance test was performed. Immediately after a training session, animals received a microinjection of the following histaminergic drugs: experiment 1, saline or chlorpheniramine (0.016, 0.052 or 0.16 nmol); experiment 2, saline or ranitidine (0.57, 2.85 or 5.07 nmol); and experiment 3, saline or dimaprit (1, 2 or 4 nmol). Twenty-four hours later, a retention test was performed. The data were analyzed using one-way analysis of variance (ANOVA) and Duncan's tests. Animals microinjected with chlorpheniramine did not show any behavioral effects at the doses that we used. Intra-cerebellar injection of the H2 receptor antagonist ranitidine inhibited, while the selective H2 receptor agonist dimaprit facilitated, memory consolidation, suggesting that H2 receptors mediate memory consolidation in the inhibitory avoidance task in mice.

  2. Similar cation channels mediate protection from cerebellar exitotoxicity by exercise and inheritance.

    Science.gov (United States)

    Ben-Ari, Shani; Ofek, Keren; Barbash, Shahar; Meiri, Hanoch; Kovalev, Eugenia; Greenberg, David Samuel; Soreq, Hermona; Shoham, Shai

    2012-03-01

    Exercise and inherited factors both affect recovery from stroke and head injury, but the underlying mechanisms and interconnections between them are yet unknown. Here, we report that similar cation channels mediate the protective effect of exercise and specific genetic background in a kainate injection model of cerebellar stroke. Microinjection to the cerebellum of the glutamatergic agonist, kainate, creates glutamatergic excito\\xE2\\x80\\x90toxicity characteristic of focal stroke, head injury or alcoholism. Inherited protection and prior exercise were both accompanied by higher cerebellar expression levels of the Kir6.1 ATP-dependent potassium channel in adjacent Bergmann glia, and voltage-gated KVbeta2 and cyclic nucleotide-gated cation HCN1 channels in basket cells. Sedentary FVB/N and exercised C57BL/6 mice both expressed higher levels of these cation channels compared to sedentary C57BL/6 mice, and were both found to be less sensitive to glutamate toxicity. Moreover, blocking ATP-dependent potassium channels with Glibenclamide enhanced kainate-induced cell death in cerebellar slices from the resilient sedentary FVB/N mice. Furthermore, exercise increased the number of acetylcholinesterase-positive fibres in the molecular layer, reduced cerebellar cytokine levels and suppressed serum acetylcholinesterase activity, suggesting anti-inflammatory protection by enhanced cholinergic signalling. Our findings demonstrate for the first time that routine exercise and specific genetic backgrounds confer protection from cerebellar glutamatergic damages by similar molecular mechanisms, including elevated expression of cation channels. In addition, our findings highlight the involvement of the cholinergic anti-inflammatory pathway in insult-inducible cerebellar processes. These mechanisms are likely to play similar roles in other brain regions and injuries as well, opening new venues for targeted research efforts.

  3. The p53 inhibitor MDM2 facilitates Sonic Hedgehog-mediated tumorigenesis and influences cerebellar foliation.

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    Reem Malek

    Full Text Available Disruption of cerebellar granular neuronal precursor (GNP maturation can result in defects in motor coordination and learning, or in medulloblastoma, the most common childhood brain tumor. The Sonic Hedgehog (Shh pathway is important for GNP proliferation; however, the factors regulating the extent and timing of GNP proliferation, as well as GNP differentiation and migration are poorly understood. The p53 tumor suppressor has been shown to negatively regulate the activity of the Shh effector, Gli1, in neural stem cells; however, the contribution of p53 to the regulation of Shh signaling in GNPs during cerebellar development has not been determined. Here, we exploited a hypomorphic allele of Mdm2 (Mdm2(puro, which encodes a critical negative regulator of p53, to alter the level of wild-type MDM2 and p53 in vivo. We report that mice with reduced levels of MDM2 and increased levels of p53 have small cerebella with shortened folia, reminiscent of deficient Shh signaling. Indeed, Shh signaling in Mdm2-deficient GNPs is attenuated, concomitant with decreased expression of the Shh transducers, Gli1 and Gli2. We also find that Shh stimulation of GNPs promotes MDM2 accumulation and enhances phosphorylation at serine 166, a modification known to increase MDM2-p53 binding. Significantly, loss of MDM2 in Ptch1(+/- mice, a model for Shh-mediated human medulloblastoma, impedes cerebellar tumorigenesis. Together, these results place MDM2 at a major nexus between the p53 and Shh signaling pathways in GNPs, with key roles in cerebellar development, GNP survival, cerebellar foliation, and MB tumorigenesis.

  4. Differential Modulation of GABAA Receptors Underlies Postsynaptic Depolarization- and Purinoceptor-Mediated Enhancement of Cerebellar Inhibitory Transmission: A Non-Stationary Fluctuation Analysis Study

    Science.gov (United States)

    Ono, Yumie; Saitow, Fumihito; Konishi, Shiro

    2016-01-01

    Cerebellar GABAergic inhibitory transmission between interneurons and Purkinje cells (PCs) undergoes a long-lasting enhancement following different stimulations, such as brief depolarization or activation of purinergic receptors of postsynaptic PCs. The underlying mechanisms, however, are not completely understood. Using a peak-scaled non-stationary fluctuation analysis, we therefore aimed at characterizing changes in the electrophysiological properties of GABAA receptors in PCs of rat cerebellar cortex during depolarization-induced “rebound potentiation (RP)” and purinoceptor-mediated long-term potentiation (PM-LTP), because both RP and PM-LTP likely depend on postsynaptic mechanisms. Stimulation-evoked inhibitory postsynaptic currents (eIPSCs) were recorded from PCs in neonatal rat cerebellar slices. Our analysis showed that postsynaptic membrane depolarization induced RP of eIPSCs in association with significant increase in the number of synaptic GABAA receptors without changing the channel conductance. By contrast, bath application of ATP induced PM-LTP of eIPSCs with a significant increase of the channel conductance of GABAA receptors without affecting the receptor number. Pretreatment with protein kinase A (PKA) inhibitors, H-89 and cAMPS-Rp, completely abolished the PM-LTP. The CaMKII inhibitor KN-62 reported to abolish RP did not alter PM-LTP. These results suggest that the signaling mechanism underlying PM-LTP could involve ATP-induced phosphorylation of synaptic GABAA receptors, thereby resulting in upregulation of the channel conductance by stimulating adenylyl cyclase-PKA signaling cascade, possibly via activation of P2Y11 purinoceptor. Thus, our findings reveal that postsynaptic GABAA receptors at the interneuron-PC inhibitory synapses are under the control of two distinct forms of long-term potentiation linked with different second messenger cascades. PMID:26930485

  5. Cell Division Mode Change Mediates the Regulation of Cerebellar Granule Neurogenesis Controlled by the Sonic Hedgehog Signaling

    OpenAIRE

    Rong Yang; Minglei Wang; Jia Wang; Xingxu Huang; Ru Yang; Wei-Qiang Gao

    2015-01-01

    Summary Symmetric and asymmetric divisions are important for self-renewal and differentiation of stem cells during neurogenesis. Although cerebellar granule neurogenesis is controlled by sonic hedgehog (SHH) signaling, whether and how this process is mediated by regulation of cell division modes have not been determined. Here, using time-lapse imaging and cell culture from neuronal progenitor-specific and differentiated neuron-specific reporter mouse lines (Math1-GFP and Dcx-DsRed) and Patche...

  6. Organic Photocatalytic Cyclization of Polyenes: A Visible-Light-Mediated Radical Cascade Approach.

    Science.gov (United States)

    Yang, Zhongbo; Li, Han; Zhang, Long; Zhang, Ming-Tian; Cheng, Jin-Pei; Luo, Sanzhong

    2015-10-12

    A visible-light-mediated, organic photocatalytic stereoselective radical cascade cyclization of polyprenoids is described. The desired cascade cyclization products are achieved in good yields and high stereoselectivities with eosin Y as photocatalyst in hexafluoro-2-propanol. The catalyst system is also suitable for 1,3-dicarbonyl compounds, which require only catalytic amounts of LiBr to promote the formation of the corresponding enols.

  7. Cell Division Mode Change Mediates the Regulation of Cerebellar Granule Neurogenesis Controlled by the Sonic Hedgehog Signaling

    Directory of Open Access Journals (Sweden)

    Rong Yang

    2015-11-01

    Full Text Available Symmetric and asymmetric divisions are important for self-renewal and differentiation of stem cells during neurogenesis. Although cerebellar granule neurogenesis is controlled by sonic hedgehog (SHH signaling, whether and how this process is mediated by regulation of cell division modes have not been determined. Here, using time-lapse imaging and cell culture from neuronal progenitor-specific and differentiated neuron-specific reporter mouse lines (Math1-GFP and Dcx-DsRed and Patched+/− mice in which SHH signaling is activated, we find evidence for the existence of symmetric and asymmetric divisions that are closely associated with progenitor proliferation and differentiation. While activation of the SHH pathway enhances symmetric progenitor cell divisions, blockade of the SHH pathway reverses the cell division mode change in Math1-GFP;Dcx-DsRed;Patched+/− mice by promoting asymmetric divisions or terminal neuronal symmetric divisions. Thus, cell division mode change mediates the regulation of cerebellar granule neurogenesis controlled by SHH signaling.

  8. Purinergic P2X7 receptors mediate cell death in mouse cerebellar astrocytes in culture.

    Science.gov (United States)

    Salas, Elvira; Carrasquero, Luz María G; Olivos-Oré, Luis A; Bustillo, Diego; Artalejo, Antonio R; Miras-Portugal, Maria Teresa; Delicado, Esmerilda G

    2013-12-01

    The brain distribution and functional role of glial P2X7 receptors are broader and more complex than initially anticipated. We characterized P2X7 receptors from cerebellar astrocytes at the molecular, immunocytochemical, biophysical, and cell physiologic levels. Mouse cerebellar astrocytes in culture express mRNA coding for P2X7 receptors, which is translated into P2X7 receptor protein as proven by Western blot analysis and immunocytochemistry. Fura-2 imaging showed cytosolic calcium responses to ATP and the synthetic analog 3'-O-(4-benzoyl)benzoyl-ATP (BzATP) exhibited two components, namely an initial transient and metabotropic component followed by a sustained one that depended on extracellular calcium. This latter component, which was absent in astrocytes from P2X7 receptor knockout mice (P2X7 KO), was modulated by extracellular Mg(2+), and was sensitive to Brilliant Blue G (BBG) and 3-(5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl)methyl pyridine (A438079) antagonism. BzATP also elicited inwardly directed nondesensitizing whole-cell ionic currents that were reduced by extracellular Mg(2+) and P2X7 antagonists (BBG and calmidazolium). In contrast to that previously reported in rat cerebellar astrocytes, sustained BzATP application induced a gradual increase in membrane permeability to large cations, such as N-methyl-d-glucamine and 4-[3-methyl-2(3H)-benzoxazolylidene)-methyl]-1-[3-(triethylammonio)propyl]diiodide, which ultimately led to the death of mouse astrocytes. Cerebellar astrocyte cell death was prevented by BBG but not by calmidazolium, removal of extracellular calcium, or treatment with the caspase-3 inhibitor, benzyloxycarbonyl-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethylketone, thus suggesting a necrotic-type mechanism of cell death. Since this cellular response was not observed in astrocytes from P2X7 KO mice, this study suggests that stimulation of P2X7 receptor may convey a cell death signal to cerebellar astrocytes in a species-specific manner.

  9. mGluR1-mediated excitation of cerebellar GABAergic interneurons requires both G protein-dependent and Src-ERK1/2-dependent signaling pathways.

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    Hideo Kubota

    Full Text Available Stimulation of type I metabotropic glutamate receptors (mGluR1/5 in several neuronal types induces slow excitatory responses through activation of transient receptor potential canonical (TRPC channels. GABAergic cerebellar molecular layer interneurons (MLIs modulate firing patterns of Purkinje cells (PCs, which play a key role in cerebellar information processing. MLIs express mGluR1, and activation of mGluR1 induces an inward current, but its precise intracellular signaling pathways are unknown. We found that mGluR1 activation facilitated spontaneous firing of mouse cerebellar MLIs through an inward current mediated by TRPC1 channels. This mGluR1-mediated inward current depends on both G protein-dependent and -independent pathways. The nonselective protein tyrosine kinase inhibitors genistein and AG490 as well as the selective extracellular signal-regulated kinase 1/2 (ERK1/2 inhibitors PD98059 and SL327 suppressed the mGluR1-mediated current responses. Following G protein blockade, the residual mGluR1-mediated inward current was significantly reduced by the selective Src tyrosine kinase inhibitor PP2. In contrast to cerebellar PCs, GABAB receptor activation in MLIs did not alter the mGluR1-mediated inward current, suggesting that there is no cross-talk between mGluR1 and GABAB receptors in MLIs. Thus, activation of mGluR1 facilitates firing of MLIs through the TRPC1-mediated inward current, which depends on not only G protein-dependent but also Src-ERK1/2-dependent signaling pathways, and consequently depresses the excitability of cerebellar PCs.

  10. Cerebellar Mutism

    OpenAIRE

    1994-01-01

    Of a series of 15 children operated for cerebellar tumor at University Hospital Rotterdam-Dijkzigt, The Netherlands, 5 developed “cerebellar mutism” and subsequent dysarthria after surgery, and 2 had mild speech problems.

  11. Anti-Yo Mediated Paraneoplastic Cerebellar Degeneration Associated with Pseudobulbar Affect in a Patient with Breast Cancer

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    Allison N. Martin

    2017-01-01

    Full Text Available Paraneoplastic cerebellar degeneration (PCD is a rare anti-Yo mediated paraneoplastic syndromes rarely that is infrequently associated with breast cancer. We present a case of a 52-year-old female presenting with diplopia, gait instability, dysarthria, dysphagia, nystagmus, and, most notably, new onset paroxysmal episodes of uncontrollable crying concerning for pseudobulbar affect (PBA. Serologic testing showed anti-Yo antibodies. The patient was found to have stage IIIA breast cancer as the inciting cause of the paraneoplastic syndrome. The patient was treated with neoadjuvant chemotherapy, modified radical mastectomy, adjuvant Herceptin, and pertuzumab. She was given IVIG for paraneoplastic syndrome, antidepressants, and dextromethorphan-quinidine (Nuedexta, the first FDA-approved therapy for PBA. With multimodality therapy, she demonstrated significant improvement in neurologic and mood symptoms associated with PCD and PBA.

  12. Anti-Yo Mediated Paraneoplastic Cerebellar Degeneration Associated with Pseudobulbar Affect in a Patient with Breast Cancer

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    Martin, Allison N.; Jones, David E.; Brenin, David R.; Lapides, David A.

    2017-01-01

    Paraneoplastic cerebellar degeneration (PCD) is a rare anti-Yo mediated paraneoplastic syndromes rarely that is infrequently associated with breast cancer. We present a case of a 52-year-old female presenting with diplopia, gait instability, dysarthria, dysphagia, nystagmus, and, most notably, new onset paroxysmal episodes of uncontrollable crying concerning for pseudobulbar affect (PBA). Serologic testing showed anti-Yo antibodies. The patient was found to have stage IIIA breast cancer as the inciting cause of the paraneoplastic syndrome. The patient was treated with neoadjuvant chemotherapy, modified radical mastectomy, adjuvant Herceptin, and pertuzumab. She was given IVIG for paraneoplastic syndrome, antidepressants, and dextromethorphan-quinidine (Nuedexta), the first FDA-approved therapy for PBA. With multimodality therapy, she demonstrated significant improvement in neurologic and mood symptoms associated with PCD and PBA.

  13. Lack of connexin43-mediated Bergmann glial gap junctional coupling does not affect cerebellar long-term depression, motor coordination, or eyeblink conditioning

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    Mika Tanaka

    2008-04-01

    Full Text Available Bergmann glial cells are specialized astrocytes in the cerebellum. In the mature cerebellar molecular layer, Bergmann glial processes are closely associated with Purkinje cells, enclosing Purkinje cell dendritic synapses with a glial sheath. There is intensive gap junctional coupling between Bergmann glial processes, but their significance in cerebellar functions is not known. Connexin43 (Cx43, a major component of astrocytic gap junction channels, is abundantly expressed in Bergmann glial cells. To examine the role of Cx43-mediated gap junctions between Bergmann glial cells in cerebellar functions, we generated Cx43 conditional knockout mice with the S100b-Cre transgenic line (Cx43fl/fl:S100b-Cre, which exhibited a significant loss of Cx43 in the Bergmann glial cells and astrocytes in the cerebellum with a postnatal onset. The Cx43fl/fl:S100b-Cre mice had normal cerebellar architecture. Although gap junctional coupling between the Bergmann glial cells measured by spreading of microinjected Lucifer yellow was virtually abolished in Cx43fl/fl:S100b-Cre mice, electrophysiologic analysis revealed that cerebellar long-term depression could be induced and maintained normally in thier cerebellar slices. In addition, at the behavioral level, Cx43fl/fl:S100b-Cre mice had normal motor coordination in the rotarod task and normal conditioned eyelid response. Our findings suggest that Cx43-mediated gap junctional coupling between Bergmann glial cells is not necessary for the neuron-glia interactions required for cerebellum-dependent motor coordination and motor learning.

  14. Horseradish Peroxidase-Mediated, Iodide-Catalyzed Cascade Reaction for Plasmonic Immunoassays.

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    Xianyu, Yunlei; Chen, Yiping; Jiang, Xingyu

    2015-11-01

    This report outlines an enzymatic cascade reaction for signal transduction and amplification for plasmonic immunoassays by using horseradish peroxidase (HRP)-mediated aggregation of gold nanoparticles (AuNPs). HRP-catalyzed oxidation of iodide and iodide-catalyzed oxidation of cysteine is employed to modulate the plasmonic signals of AuNPs. It agrees well with the current immunoassay platforms and allows naked-eye readout with enhanced sensitivity, which holds great promise for applications in resource-constrained settings.

  15. Alteration of AMPA Receptor-Mediated Synaptic Transmission by Alexa Fluor 488 and 594 in Cerebellar Stellate Cells.

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    Maroteaux, Matthieu; Liu, Siqiong June

    2016-01-01

    The fluorescent dyes, Alexa Fluor 488 and 594 are commonly used to visualize dendritic structures and the localization of synapses, both of which are critical for the spatial and temporal integration of synaptic inputs. However, the effect of the dyes on synaptic transmission is not known. Here we investigated whether Alexa Fluor dyes alter the properties of synaptic currents mediated by two subtypes of AMPA receptors (AMPARs) at cerebellar stellate cell synapses. In naive mice, GluA2-lacking AMPAR-mediated synaptic currents displayed an inwardly rectifying current-voltage (I-V) relationship due to blockade by cytoplasmic spermine at depolarized potentials. We found that the inclusion of 100 µm Alexa Fluor dye, but not 10 µm, in the pipette solution led to a gradual increase in the amplitude of EPSCs at +40 mV and a change in the I-V relationship from inwardly rectifying to more linear. In mice exposed to an acute stress, AMPARs switched to GluA2-containing receptors, and 100 µm Alexa Fluor 594 did not alter the I-V relationship of synaptic currents. Therefore, a high concentration of Alexa Fluor dye changed the I-V relationship of EPSCs at GluA2-lacking AMPAR synapses.

  16. The complement cascade as a mediator of tissue growth and regeneration.

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    Rutkowski, Martin J; Sughrue, Michael E; Kane, Ari J; Ahn, Brian J; Fang, Shanna; Parsa, Andrew T

    2010-11-01

    Recent evidence has demonstrated that the complement cascade is involved in a variety of physiologic and pathophysiologic processes in addition to its role as an immune effector. Research in a variety of organ systems has shown that complement proteins are direct participants in maintenance of cellular turnover, healing, proliferation and regeneration. As a physiologic housekeeper, complement proteins maintain tissue integrity in the absence of inflammation by disposing of cellular debris and waste, a process critical to the prevention of autoimmune disease. Developmentally, complement proteins influence pathways including hematopoietic stem cell engraftment, bone growth, and angiogenesis. They also provide a potent stimulus for cellular proliferation including regeneration of the limb and eye in animal models, and liver proliferation following injury. Here, we describe the complement cascade as a mediator of tissue growth and regeneration.

  17. Light-mediated cascaded locking of multiple nano-optomechanical oscillators

    CERN Document Server

    Gil-Santos, Eduardo; Baker, Christophe; Goetschy, Arthur; Hease, William; Gomez, Carmen; Lemaître, Aristide; Leo, Giuseppe; Ciuti, Cristiano; Favero, Ivan

    2016-01-01

    Collective phenomena emerging from non-linear interactions between multiple oscillators, such as synchronization and frequency locking, find applications in a wide variety of fields. Optomechanical resonators, which are intrinsically non-linear, combine the scientific assets of mechanical devices with the possibility of long distance controlled interactions enabled by travelling light. Here we demonstrate light-mediated frequency locking of three distant nano-optomechanical oscillators positioned in a cascaded configuration. The oscillators, integrated on a chip along a coupling waveguide, are optically driven with a single laser and oscillate at gigahertz frequency. Despite an initial frequency disorder of hundreds of kilohertz, the guided light locks them all with a clear transition in the optical output. The experimental results are described by Langevin equations, paving the way to scalable cascaded optomechanical configurations.

  18. Color-Tunable Resonant Photoluminescence and Cavity-Mediated Multistep Energy Transfer Cascade.

    Science.gov (United States)

    Okada, Daichi; Nakamura, Takashi; Braam, Daniel; Dao, Thang Duy; Ishii, Satoshi; Nagao, Tadaaki; Lorke, Axel; Nabeshima, Tatsuya; Yamamoto, Yohei

    2016-07-26

    Color-tunable resonant photoluminescence (PL) was attained from polystyrene microspheres doped with a single polymorphic fluorescent dye, boron-dipyrrin (BODIPY) 1. The color of the resonant PL depends on the assembling morphology of 1 in the microspheres, which can be selectively controlled from green to red by the initial concentration of 1 in the preparation process of the microspheres. Studies on intersphere PL propagation with multicoupled microspheres, prepared by micromanipulation technique, revealed that multistep photon transfer takes place through the microspheres, accompanying energy transfer cascade with stepwise PL color change. The intersphere energy transfer cascade is direction selective, where energy donor-to-acceptor down conversion direction is only allowed. Such cavity-mediated long-distance and multistep energy transfer will be advantageous for polymer photonics device application.

  19. Neural correlates of cerebellar-mediated timing during finger tapping in children with fetal alcohol spectrum disorders

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    Lindie du Plessis

    2015-01-01

    Conclusions: The four cerebellar areas activated by the controls more during rhythmic than non-rhythmic tapping have been implicated in the production of timed responses in several previous studies. These data provide evidence linking binge-like drinking during pregnancy to poorer function in cerebellar regions involved in timing and somatosensory processing needed for complex tasks requiring precise timing.

  20. Are wolves saving Yellowstone's aspen? A landscape-level test of a behaviorally mediated trophic cascade.

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    Kauffman, Matthew J; Brodie, Jedediah F; Jules, Erik S

    2010-09-01

    Behaviorally mediated trophic cascades (BMTCs) occur when the fear of predation among herbivores enhances plant productivity. Based primarily on systems involving small-bodied predators, BMTCs have been proposed as both strong and ubiquitous in natural ecosystems. Recently, however, synthetic work has suggested that the existence of BMTCs may be mediated by predator hunting mode, whereby passive (sit-and-wait) predators have much stronger effects than active (coursing) predators. One BMTC that has been proposed for a wide-ranging active predator system involves the reintroduction of wolves (Canis lupus) to Yellowstone National Park, USA, which is thought to be leading to a recovery of trembling aspen (Populus tremuloides) by causing elk (Cervus elaphus) to avoid foraging in risky areas. Although this BMTC has been generally accepted and highly popularized, it has never been adequately tested. We assessed whether wolves influence aspen by obtaining detailed demographic data on aspen Stands using tree rings and by monitoring browsing levels in experimental elk exclosures arrayed across a gradient of predation risk for three years. Our study demonstrates that the historical failure of aspen to regenerate varied widely among stands (last recruitment year ranged from 1892 to 1956), and our data do not indicate an abrupt cessation of recruitment. This pattern of recruitment failure appears more consistent with a gradual increase in elk numbers rather than a rapid behavioral shift in elk foraging following wolf extirpation. In addition, our estimates of relative survivorship of young browsable aspen indicate that aspen are not currently recovering in Yellowstone, even in the presence of a large wolf population. Finally, in an experimental test of the BMTC hypothesis we found that the impacts of elk browsing on aspen demography are not diminished in sites where elk are at higher risk of predation by wolves. These findings suggest the need to further evaluate how trophic

  1. Acute cerebellar ataxia

    Science.gov (United States)

    Cerebellar ataxia; Ataxia - acute cerebellar; Cerebellitis; Post-varicella acute cerebellar ataxia; PVACA ... Acute cerebellar ataxia in children, especially younger than age 3, may occur several weeks after an illness caused by a virus. ...

  2. A posttranslational modification cascade involving p38, Tip60, and PRAK mediates oncogene-induced senescence.

    Science.gov (United States)

    Zheng, Hui; Seit-Nebi, Alim; Han, Xuemei; Aslanian, Aaron; Tat, John; Liao, Rong; Yates, John R; Sun, Peiqing

    2013-06-06

    Oncogene-induced senescence is an important tumor-suppressing defense mechanism. However, relatively little is known about the signaling pathway mediating the senescence response. Here, we demonstrate that a multifunctional acetyltransferase, Tip60, plays an essential role in oncogenic ras-induced senescence. Further investigation reveals a cascade of posttranslational modifications involving p38, Tip60, and PRAK, three proteins that are essential for ras-induced senescence. Upon activation by ras, p38 induces the acetyltransferase activity of Tip60 through phosphorylation of Thr158; activated Tip60 in turn directly interacts with and induces the protein kinase activity of PRAK through acetylation of K364 in a manner that depends on phosphorylation of both Tip60 and PRAK by p38. These posttranslational modifications are critical for the prosenescent function of Tip60 and PRAK, respectively. These results have defined a signaling pathway that mediates oncogene-induced senescence, and identified posttranslational modifications that regulate the enzymatic activity and biological functions of Tip60 and PRAK.

  3. L-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade

    KAUST Repository

    Jourdain, P.

    2016-02-19

    Converging experimental data indicate a neuroprotective action of L-Lactate. Using Digital Holographic Microscopy, we observe that transient application of glutamate (100 μM; 2 min) elicits a NMDA-dependent death in 65% of mouse cortical neurons in culture. In the presence of L-Lactate (or Pyruvate), the percentage of neuronal death decreases to 32%. UK5099, a blocker of the Mitochondrial Pyruvate Carrier, fully prevents L-Lactate-mediated neuroprotection. In addition, L-Lactate-induced neuroprotection is not only inhibited by probenicid and carbenoxolone, two blockers of ATP channel pannexins, but also abolished by apyrase, an enzyme degrading ATP, suggesting that ATP produced by the Lactate/Pyruvate pathway is released to act on purinergic receptors in an autocrine/paracrine manner. Finally, pharmacological approaches support the involvement of the P2Y receptors associated to the PI3-kinase pathway, leading to activation of KATP channels. This set of results indicates that L-Lactate acts as a signalling molecule for neuroprotection against excitotoxicity through coordinated cellular pathways involving ATP production, release and activation of a P2Y/KATP cascade.

  4. Asymmetric Formation of Bridged Benzoxazocines through an Organocatalytic Multicomponent Dienamine-Mediated One-Pot Cascade

    DEFF Research Database (Denmark)

    Ransborg, Lars Krogager; Overgaard, Mette Kiilerich; Hejmanowska, Joanna;

    2014-01-01

    An organocatalytic one-pot cascade leading to the stereoselective formation of novel bridged benzoxazocines is presented. The developed methodology is based on the first example of a γ-selective-Mannich-initiated cascade reaction and allows for direct annulation of the bridged benzoxazocines by i...

  5. A respiratory chain controlled signal transduction cascade in the mitochondrial intermembrane space mediates hydrogen peroxide signaling.

    Science.gov (United States)

    Patterson, Heide Christine; Gerbeth, Carolin; Thiru, Prathapan; Vögtle, Nora F; Knoll, Marko; Shahsafaei, Aliakbar; Samocha, Kaitlin E; Huang, Cher X; Harden, Mark Michael; Song, Rui; Chen, Cynthia; Kao, Jennifer; Shi, Jiahai; Salmon, Wendy; Shaul, Yoav D; Stokes, Matthew P; Silva, Jeffrey C; Bell, George W; MacArthur, Daniel G; Ruland, Jürgen; Meisinger, Chris; Lodish, Harvey F

    2015-10-20

    Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) govern cellular homeostasis by inducing signaling. H2O2 modulates the activity of phosphatases and many other signaling molecules through oxidation of critical cysteine residues, which led to the notion that initiation of ROS signaling is broad and nonspecific, and thus fundamentally distinct from other signaling pathways. Here, we report that H2O2 signaling bears hallmarks of a regular signal transduction cascade. It is controlled by hierarchical signaling events resulting in a focused response as the results place the mitochondrial respiratory chain upstream of tyrosine-protein kinase Lyn, Lyn upstream of tyrosine-protein kinase SYK (Syk), and Syk upstream of numerous targets involved in signaling, transcription, translation, metabolism, and cell cycle regulation. The active mediators of H2O2 signaling colocalize as H2O2 induces mitochondria-associated Lyn and Syk phosphorylation, and a pool of Lyn and Syk reside in the mitochondrial intermembrane space. Finally, the same intermediaries control the signaling response in tissues and species responsive to H2O2 as the respiratory chain, Lyn, and Syk were similarly required for H2O2 signaling in mouse B cells, fibroblasts, and chicken DT40 B cells. Consistent with a broad role, the Syk pathway is coexpressed across tissues, is of early metazoan origin, and displays evidence of evolutionary constraint in the human. These results suggest that H2O2 signaling is under control of a signal transduction pathway that links the respiratory chain to the mitochondrial intermembrane space-localized, ubiquitous, and ancient Syk pathway in hematopoietic and nonhematopoietic cells.

  6. The Neuroprotective Effect of Lithium in cannabinoid Dependence is Mediated through Modulation of Cyclic AMP, ERK1/2 and GSK-3β Phosphorylation in Cerebellar Granular Neurons of Rat

    Science.gov (United States)

    Rahimi, Hamid Reza; Ghahremani, Mohammad Hossein; Dehpour, Ahmad Reza; Sharifzadeh, Mohammad; Ejtemaei-Mehr, Shahram; Razmi, Ali; Ostad, Seyed Nasser

    2015-01-01

    Lithium (Li), a glycogen synthase kinase-3β (GSK-3β) inhibitor, has used to attenuate the cannabinoid-induced dependence/withdrawal signs, but molecular mechanisms related to this are unclear. Recent studies indicate the involvement of upstream extracellular signal kinase1/2 (ERK1/2) and downstream GSK-3β pathways in the development of cannabinoid-induced dependence. This is mediated through cannabinoid receptor 1 (CB1) enriched in cerebellar granular neurons (CGNs). Accordingly, the present study aimed to investigate the mechanism of modulatory/neuroprotective effects of Li on a cannabinoid agonist (WIN 55,212-2 (WIN))-induced dependence, through quantitative analysis of some involved proteins such as ERK1/2, GSK-3β and related signaling pathways including their phosphorylated forms; and cAMP level as the other molecular mechanisms leading to dependence, in CGNs model. The CGNs were prepared from 7-day-old Wistar rat pup in a 12-well plate, pretreated with Li (1mM) and an ERK1/2 inhibitor SL327 (SL, 10 µM). The WIN (1 µM) was added 30 minutes prior to treatment and AM251 (AM, 1 µM), as a cannabinoid antagonist was co-treated with WIN. The cAMP level, as an indicator of cannabinoid-induced dependence, was measured by ELISA following forskolin (FSK) stimulation. Western blot analyses determined the phosphorylated forms of ERK1/2 (p-ERK1/2), GSK-3β (p-GSK-3β) as well as their total expressions in various treatment times and doses in CGNs. WIN alone could down regulate the cAMP/p-ERK1/2 cascade compared to AM treatment. However, P-GSK-3β was up-regulated with Li and WIN or with SL and Li pretreatment to AM-induced cellular response, which was the highest 60 minutes after CGNs exposure. Results further suggested the potential role of Li pretreatment to diminish the development of cannabinoid-induced dependence/neuronal injury through possible mechanisms of modulating the cAMP/p-ERK1/2 cascade independent of p-GSK-3β signaling pathway in-vitro. PMID:26664379

  7. Cyclization–endoperoxidation cascade reactions of dienes mediated by a pyrylium photoredox catalyst

    Directory of Open Access Journals (Sweden)

    Nathan J. Gesmundo

    2014-06-01

    Full Text Available Triarylpyrylium salts were employed as single electron photooxidants to catalyze a cyclization–endoperoxidation cascade of dienes. The transformation is presumed to proceed via the intermediacy of diene cation radicals. The nature of the diene component was investigated in this context to determine the structural requirements necessary for successful reactivity. Several unique endoperoxide structures were synthesized in yields up to 79%.

  8. ORGANOCOPPER-MEDIATED TWO-COMPONENT SN2'-SUBSTITUTION CASCADE TOWARDS N-FUSED HETEROCYCLES*

    OpenAIRE

    Chernyak, D.; Gevorgyan, V.

    2012-01-01

    Organocuprates efficiently undergo reaction with heterocyclic propargyl mesylates at low temperature to produce N-fused heterocycles. The copper reagent plays a "double duty" in this cascade transformation, which proceeds through an SN2'-substitution followed by a consequent cycloisomerization step.

  9. ORGANOCOPPER-MEDIATED TWO-COMPONENT SN2'-SUBSTITUTION CASCADE TOWARDS N-FUSED HETEROCYCLES.

    Science.gov (United States)

    Chernyak, D; Gevorgyan, V

    2012-03-01

    Organocuprates efficiently undergo reaction with heterocyclic propargyl mesylates at low temperature to produce N-fused heterocycles. The copper reagent plays a "double duty" in this cascade transformation, which proceeds through an SN2'-substitution followed by a consequent cycloisomerization step.

  10. Viral mediated redirection of NEMO/IKKγ to autophagosomes curtails the inflammatory cascade.

    Directory of Open Access Journals (Sweden)

    Patricia M Fliss

    2012-02-01

    Full Text Available The early host response to viral infections involves transient activation of pattern recognition receptors leading to an induction of inflammatory cytokines such as interleukin-1β (IL-1β and tumor necrosis factor α (TNFα. Subsequent activation of cytokine receptors in an autocrine and paracrine manner results in an inflammatory cascade. The precise mechanisms by which viruses avert an inflammatory cascade are incompletely understood. Nuclear factor (NF-κB is a central regulator of the inflammatory signaling cascade that is controlled by inhibitor of NF-κB (IκB proteins and the IκB kinase (IKK complex. In this study we show that murine cytomegalovirus inhibits the inflammatory cascade by blocking Toll-like receptor (TLR and IL-1 receptor-dependent NF-κB activation. Inhibition occurs through an interaction of the viral M45 protein with the NF-κB essential modulator (NEMO, the regulatory subunit of the IKK complex. M45 induces proteasome-independent degradation of NEMO by targeting NEMO to autophagosomes for subsequent degradation in lysosomes. We propose that the selective and irreversible degradation of a central regulatory protein by autophagy represents a new viral strategy to dampen the inflammatory response.

  11. Label-free electrochemical nucleic acid biosensing by tandem polymerization and cleavage-mediated cascade target recycling and DNAzyme amplification.

    Science.gov (United States)

    Liu, Shufeng; Gong, Hongwei; Wang, Yanqun; Wang, Li

    2016-03-15

    Owing to the intrinsic importance of nucleic acid as bio-targets, the achievement of its simple and sensitive detection with high confidence is very essential for biological studies and diagnostic purposes. Herein, a label-free, isothermal, and ultrasensitive electrochemical detection of target DNA was developed by using a tandem polymerization and cleavage-mediated cascade target recycling and DNAzyme releasing amplification strategy. Upon sensing of the nucleic acid analyte for the assembled hairpin-like probe DNA on the electrode, the DNA polymerase guided the target recycling and simultaneously triggered the lambda exonuclease cleavage, accompanied by the cascade recycling of the released new complementary strand and the amplified liberation of the G-rich sequence of the HRP-mimicking DNAzyme. The electrocatalytic reduction of H2O2 by the generated hemin/G-quadruplex DNAzyme was used for the signal readout and further amplification toward target response. Such tandem functional operation by DNA polymerase, lambda exonuclease and DNAzyme endows the developed biosensor with a high sensitivity and also a high confidence. A low detection limit of 5 fM with an excellent selectivity toward target DNA could be achieved. It also exhibits the distinct advantages of simplicity in probe design and biosensor fabrication, and label-free electrochemical detection, thus may offer a promising avenue for the applications in disease diagnosis and clinical biomedicine.

  12. BF3 x Et2O-mediated cascade cyclizations: synthesis of schweinfurthins F and G.

    Science.gov (United States)

    Mente, Nolan R; Neighbors, Jeffrey D; Wiemer, David F

    2008-10-17

    The total synthesis of the natural stilbene (+)-schweinfurthin G (8) has been accomplished through a sequence based on an efficient cationic cascade cyclization. This cascade process is initiated by Lewis acid promoted ring opening of an epoxide and terminated through a novel reaction with a phenolic oxygen "protected" as its MOM ether. Several Lewis acids have been examined for their ability to induce this new reaction, and BF3 x Et2O was found to be the most effective. The only major byproduct under these conditions was one where the expected secondary alcohol was found as its MOM ether derivative (e.g., 30). While this byproduct could be converted to the original target compound through hydrolysis, it also could be employed as a protected alcohol to allow preparation of a benzylic phosphonate (43) without dehydration of the secondary alcohol. The resulting phosphonate was employed in a Horner-Wadsworth-Emmons condensation with an aldehyde representing the right half of the target compounds, an approach complementary to previous studies based on condensation of a right-half phosphonate and a left-half aldehyde.

  13. Cascaded plasmon-plasmon coupling mediated energy transfer across stratified metal-dielectric nanostructures

    Science.gov (United States)

    Golmakaniyoon, Sepideh; Hernandez-Martinez, Pedro Ludwig; Demir, Hilmi Volkan; Sun, Xiao Wei

    2016-01-01

    Surface plasmon (SP) coupling has been successfully applied to nonradiative energy transfer via exciton-plasmon-exciton coupling in conventionally sandwiched donor-metal film-acceptor configurations. However, these structures lack the desired efficiency and suffer poor photoemission due to the high energy loss. Here, we show that the cascaded exciton-plasmon-plasmon-exciton coupling in stratified architecture enables an efficient energy transfer mechanism. The overlaps of the surface plasmon modes at the metal-dielectric and dielectric-metal interfaces allow for strong cross-coupling in comparison with the single metal film configuration. The proposed architecture has been demonstrated through the analytical modeling and numerical simulation of an oscillating dipole near the stratified nanostructure of metal-dielectric-metal-acceptor. Consistent with theoretical and numerical results, experimental measurements confirm at least 50% plasmon resonance energy transfer enhancement in the donor-metal-dielectric-metal-acceptor compared to the donor-metal-acceptor structure. Cascaded plasmon-plasmon coupling enables record high efficiency for exciton transfer through metallic structures. PMID:27698422

  14. Predation risk, elk, and aspen: tests of a behaviorally mediated trophic cascade in the Greater Yellowstone Ecosystem.

    Science.gov (United States)

    Winnie, John A

    2012-12-01

    Aspen in the Greater Yellowstone Ecosystem are hypothesized to be recovering from decades of heavy browsing by elk due to a behaviorally mediated trophic cascade (BMTC). Several authors have suggested that wolves interact with certain terrain features, creating places of high predation risk at fine spatial scales, and that elk avoid these places, which creates refugia for plants. This hypothesized BMTC could release aspen from elk browsing pressure, leading to a patchy recovery in places of high risk. I tested whether four specific, hypothesized fine-scale risk factors are correlated with changes in current elk browsing pressure on aspen, or with aspen recruitment since wolf reintroduction, in the Daly Creek drainage in Yellowstone National Park, and near two aspen enclosures outside of the park boundary. Aspen were not responding to hypothesized fine-scale risk factors in ways consistent with the current BMTC hypothesis.

  15. Proton feedback mediates the cascade of color-opponent signals onto H3 horizontal cells in goldfish retina.

    Science.gov (United States)

    Kamiji, Nilton L; Yamamoto, Kazunori; Hirasawa, Hajime; Yamada, Masahiro; Usui, Shiro; Kurokawa, Makoto

    2012-04-01

    It has been postulated that horizontal cells (HCs) send feedback signals onto cones via a proton feedback mechanism, which generates the center-surround receptive field of bipolar cells, and color-opponent signals in many non-mammalian vertebrates. Here we used a strong pH buffer, HEPES, to reduce extracellular proton concentration changes and so determine whether protons mediate color-opponent signals in goldfish H3 (triphasic) HCs. Superfusion with 10mM HEPES-fortified saline elicited depolarization of H3 HCs' dark membrane potential and enhanced hyperpolarizing responses to blue stimuli, but suppressed both depolarization by yellow and orange and hyperpolarization by red stimuli. The response components suppressed by HEPES resembled the inverse of spectral responses of H2 (biphasic) HCs. These results are consistent with the Stell-Lightfoot cascade model, in which the HEPES-suppressed component of H3 HCs was calculated using light responses recorded experimentally in H1 (monophasic) and H2 HCs. Selective suppression of long- or long-+middle-wavelength cone signals by long-wavelength background enhanced the responses to short-wavelength stimuli. These results suggest that HEPES inhibited color opponent signals in H3 HCs, in which the source of opponent-color signals is primarily a feedback from H2 HCs and partly from H1 HCs onto short-wavelength cones, probably mediated by protons.

  16. A component of retinal light adaptation mediated by the thyroid hormone cascade.

    Directory of Open Access Journals (Sweden)

    Diana E Bedolla

    Full Text Available Analysis with DNA-microrrays and real time PCR show that several genes involved in the thyroid hormone cascade, such as deiodinase 2 and 3 (Dio2 and Dio3 are differentially regulated by the circadian clock and by changes of the ambient light. The expression level of Dio2 in adult rats (2-3 months of age kept continuously in darkness is modulated by the circadian clock and is up-regulated by 2 fold at midday. When the diurnal ambient light was on, the expression level of Dio2 increased by 4-8 fold and a consequent increase of the related protein was detected around the nuclei of retinal photoreceptors and of neurons in inner and outer nuclear layers. The expression level of Dio3 had a different temporal pattern and was down-regulated by diurnal light. Our results suggest that DIO2 and DIO3 have a role not only in the developing retina but also in the adult retina and are powerfully regulated by light. As the thyroid hormone is a ligand-inducible transcription factor controlling the expression of several target genes, the transcriptional activation of Dio2 could be a novel genomic component of light adaptation.

  17. Cerebellar transcranial direct current stimulation effects on saccade adaptation

    NARCIS (Netherlands)

    E. Avila (Eric); J.N. van der Geest (Jos); S. Kengne Kamga (Sandra); M.C. Verhage (M. Claire); O. Donchin (Opher); M.A. Frens (Maarten)

    2015-01-01

    textabstractSaccade adaptation is a cerebellar-mediated type of motor learning in which the oculomotor system is exposed to repetitive errors. Different types of saccade adaptations are thought to involve distinct underlying cerebellar mechanisms. Transcranial direct current stimulation (tDCS) induc

  18. Mitochondria-cytochrome C-caspase-9 cascade mediates isorhamnetin-induced apoptosis.

    Science.gov (United States)

    Lee, Hyo-Jung; Lee, Hyo-Jeong; Lee, Eun-Ok; Ko, Seong-Gyu; Bae, Hyun-Soo; Kim, Cheol-Ho; Ahn, Kyoo-Seok; Lu, Junxuan; Kim, Sung-Hoon

    2008-11-08

    Isorhamnetin is a flavanoid present in plants of the Polygonaceae family and is also an immediate metabolite of quercetin in mammals. Since the plasma level of isorhamnetin is maintained longer than quercetin, isorhamnetin may be a key metabolite to mediate the anti-tumor effect of quercetin. In the present study, we investigated the apoptotic mechanism of isorhamnetin in Lewis lung cancer (LLC) cells in vitro and established its in vivo anti-cancer efficacy. In cell culture, isorhamnetin significantly increased DNA fragmentation, and TUNEL positive apoptotic bodies and sub-G(1) apoptotic population in time- and dose-dependent manners. Western blot analyses revealed increased cleavage of caspase-3, and caspase-9 and PARP and increased cytosolic cytochrome C in isorhamnetin-treated cells. These events were accompanied by a reduced mitochondrial potential. Apoptosis was blocked by a general caspase inhibitor or the specific inhibitor of caspase-3 or -9. These in vitro results support mitochondria-dependent caspase activation to mediate isorhamnetin-induced apoptosis. Furthermore, an animal study revealed for the first time that isorhamnetin given by i.p. injection at a dose that is at least one order of magnitude lower than quercetin significantly suppressed the weights of tumors excised from LLC bearing mice. The in vivo anti-tumor efficacy was accompanied by increased TUNEL-positive and cleaved-caspase-3-positive tumor cells. Our data therefore support isorhamnetin as an active anti-cancer metabolite of quercetin in part through caspase-mediated apoptosis.

  19. Bilateral otogenic cerebellar abscesses.

    Directory of Open Access Journals (Sweden)

    Nadkarni T

    1993-01-01

    Full Text Available An unusual presentation of bilateral otogenic cerebellar abscesses observed in two of our patients is reported. Both gave a history of otorrhoea, fever, headache, vomiting and had bilateral cerebellar signs and conductive hearing loss. The abscesses were detected on computerised tomography. X-rays revealed bilateral mastoiditis. The therapy followed was excision of abscesses, mastoidectomy and antibiotic therapy.

  20. Iatrogenic postoperative cerebellar cyst.

    Science.gov (United States)

    Sharif, Robin; Moscovici, Samuel; Wygoda, Marc; Eliahou, Ruth; Spektor, Sergey

    2016-12-01

    Cerebellar cyst is a known but uncommon entity. It is congenital in most cases, or may develop after brain parenchyma injuries or interventions. To our knowledge, de novo cerebellar cyst after extra-axial tumor excision, has not been described in the literature. We present the first reported case of a de novo cerebellar cyst developing in a 70-year-old woman following retrosigmoid craniotomy for vestibular schwannoma excision, and discuss the possible causes. Following cyst fenestration, there was no clinical or radiological evidence of a residual cyst.

  1. Cerebellar vermis plays a causal role in visual motion discrimination.

    Science.gov (United States)

    Cattaneo, Zaira; Renzi, Chiara; Casali, Stefano; Silvanto, Juha; Vecchi, Tomaso; Papagno, Costanza; D'Angelo, Egidio

    2014-09-01

    Cerebellar patients have been found to show deficits in visual motion discrimination, suggesting that the cerebellum may play a role in visual sensory processing beyond mediating motor control. Here we show that triple-pulse online transcranial magnetic stimulation (TMS) over cerebellar vermis but not over the cerebellar hemispheres significantly impaired motion discrimination. Critically, the interference caused by vermis TMS on motion discrimination did not depend on an indirect effect of TMS over nearby visual areas, as demonstrated by a control experiment in which TMS over V1 but not over cerebellar vermis significantly impaired orientation discrimination. These findings demonstrate the causal role of the cerebellar vermis in visual motion processing in neurologically normal participants.

  2. Cerebellar anatomy as applied to cerebellar microsurgical resections

    Directory of Open Access Journals (Sweden)

    Alejandro Ramos

    2012-06-01

    Full Text Available OBJECTIVE: To define the anatomy of dentate nucleus and cerebellar peduncles, demonstrating the surgical application of anatomic landmarks in cerebellar resections. METHODS: Twenty cerebellar hemispheres were studied. RESULTS: The majority of dentate nucleus and cerebellar peduncles had demonstrated constant relationship to other cerebellar structures, which provided landmarks for surgical approaching. The lateral border is separated from the midline by 19.5 mm in both hemispheres. The posterior border of the cortex is separated 23.3 mm from the posterior segment of the dentate nucleus; the lateral one is separated 26 mm from the lateral border of the nucleus; and the posterior segment of the dentate nucleus is separated 25.4 mm from the posterolateral angle formed by the junction of lateral and posterior borders of cerebellar hemisphere. CONCLUSIONS: Microsurgical anatomy has provided important landmarks that could be applied to cerebellar surgical resections.

  3. Myeloid differentiation primary response gene 88-leukotriene B4 receptor 2 cascade mediates lipopolysaccharide-potentiated invasiveness of breast cancer cells.

    Science.gov (United States)

    Park, Geun-Soo; Kim, Jae-Hong

    2015-03-20

    Inflammation and local inflammatory mediators are inextricably linked to tumor progression through complex pathways in the tumor microenvironment. Lipopolysaccharide (LPS) exposure to tumor cells has been suggested to promote tumor invasiveness and metastasis. However, the detailed signaling mechanism involved has not been elucidated. In this study, we showed that LPS upregulated the expression of leukotriene B4 receptor-2 (BLT2) and the synthesis of BLT2 ligands in MDA-MB-231 and MDA-MB-435 breast cancer cells, thereby promoting invasiveness. BLT2 depletion with siRNA clearly attenuated LPS-induced invasiveness. In addition, we demonstrated that myeloid differentiation primary response gene 88 (MyD88) lies upstream of BLT2 in LPS-potentiated invasiveness and that this 'MyD88-BLT2' cascade mediates activation of NF-κB and the synthesis of IL-6 and IL-8, which are critical for the invasiveness and aggression of breast cancer cells. LPS-driven metastasis of MDA-MB-231 cells was also markedly suppressed by the inhibition of BLT2. Together, our results demonstrate, for the first time, that LPS potentiates the invasiveness and metastasis of breast cancer cells via a 'MyD88-BLT2'-linked signaling cascade.

  4. Cerebellar endocannabinoids: retrograde signaling from purkinje cells.

    Science.gov (United States)

    Marcaggi, Païkan

    2015-06-01

    The cerebellar cortex exhibits a strikingly high expression of type 1 cannabinoid receptor (CB1), the cannabinoid binding protein responsible for the psychoactive effects of marijuana. CB1 is primarily found in presynaptic elements in the molecular layer. While the functional importance of cerebellar CB1 is supported by the effect of gene deletion or exogenous cannabinoids on animal behavior, evidence for a role of endocannabinoids in synaptic signaling is provided by in vitro experiments on superfused acute rodent cerebellar slices. These studies have demonstrated that endocannabinoids can be transiently released by Purkinje cells and signal at synapses in a direction opposite to information transfer (retrograde). Here, following a description of the reported expression pattern of the endocannabinoid system in the cerebellum, I review the accumulated in vitro data, which have addressed the mechanism of retrograde endocannabinoid signaling and identified 2-arachidonoylglycerol as the mediator of this signaling. The mechanisms leading to endocannabinoid release, the effects of CB1 activation, and the associated synaptic plasticity mechanisms are discussed and the remaining unknowns are pointed. Notably, it is argued that the spatial specificity of this signaling and the physiological conditions required for its induction need to be determined in order to understand endocannabinoid function in the cerebellar cortex.

  5. Cerebellar Hypoplasia and Autism

    OpenAIRE

    1989-01-01

    The size of the cerebellar hemisphere and vermal lobules was measured in ten autistic and eight normal control subjects at the Neuropsychology Research Laboratory, Children’s Hospital Research Center, and the Departments of Neurosciences and Radiology, School of Medicine, University of California at San Diego, LaJolla.

  6. Genetics Home Reference: lissencephaly with cerebellar hypoplasia

    Science.gov (United States)

    ... Conditions lissencephaly with cerebellar hypoplasia lissencephaly with cerebellar hypoplasia Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description Lissencephaly with cerebellar hypoplasia (LCH) affects brain development, resulting in the brain ...

  7. Etk/Bmx mediates expression of stress-induced adaptive genes VEGF, PAI-1, and iNOS via multiple signaling cascades in different cell systems.

    Science.gov (United States)

    Chau, Cindy H; Clavijo, Carlos A; Deng, Hong-Tao; Zhang, Qunzhou; Kim, Kwang-Jin; Qiu, Yun; Le, Anh D; Ann, David K

    2005-08-01

    We recently showed that Etk/Bmx, a member of the Tec family of nonreceptor protein tyrosine kinases, promotes tight junction formation during chronic hypoxic exposure and augments normoxic VEGF expression via a feedforward mechanism. Here we further characterized Etk's role in potentiating hypoxia-induced gene expression in salivary epithelial Pa-4 cells. Using transient transfection in conditionally activated Etk (DeltaEtk:ER) cells, we demonstrated that Etk enhances hypoxia-response element-dependent reporter activation in normoxia and hypoxia. This Etk-driven reporter activation is ameliorated by treatment with wortmannin or LFM-A13. Using lentivirus-mediated gene delivery and small interfering RNA, we provided direct evidence that hypoxia leads to transient Etk and Akt activation and hypoxia-mediated Akt activation is Etk dependent. Northern blot analyses confirmed that Etk activation led to induction of steady-state mRNA levels of endogenous VEGF and plasminogen activator inhibitor (PAI)-1, a hallmark of hypoxia-mediated gene regulation. We also demonstrated that Etk utilizes a phosphatidylinositol 3-kinase/Akt pathway to promote reporter activation driven by NF-kappaB, another oxygen-sensitive transcription factor, and to augment cytokine-induced inducible nitric oxide synthase expression in endothelial cells. To establish the clinical relevance of Etk-induced, hypoxia-mediated gene regulation, we examined Etk expression in keloid, which has elevated VEGF and PAI-1. We found that Etk is overexpressed in keloid (but not normal skin) tissues. The differential steady-state Etk protein levels were further confirmed in primary fibroblast cultures derived from these tissues, suggesting an Etk role in tissue fibrosis. Our results provide further understanding of Etk function within multiple signaling cascades to govern adaptive cytoprotection against extracellular stress in different cell systems, salivary epithelial cells, brain endothelial cells, and dermal

  8. Mitogen-activated protein kinase kinase 5 (MKK5)-mediated signalling cascade regulates expression of iron superoxide dismutase gene in Arabidopsis under salinity stress.

    Science.gov (United States)

    Xing, Yu; Chen, Wei-hua; Jia, Wensuo; Zhang, Jianhua

    2015-09-01

    Superoxide dismutases (SODs) are involved in plant adaptive responses to biotic and abiotic stresses but the upstream signalling process that modulates their expression is not clear. Expression of two iron SODs, FSD2 and FSD3, was significantly increased in Arabidopsis in response to NaCl treatment but blocked in transgenic MKK5-RNAi plant, mkk5. Using an assay system for transient expression in protoplasts, it was found that mitogen-activated protein kinase kinase 5 (MKK5) was also activated in response to salt stress. Overexpression of MKK5 in wild-type plants enhanced their tolerance to salt treatments, while mkk5 mutant exhibited hypersensitivity to salt stress in germination on salt-containing media. Moreover, another kinase, MPK6, was also involved in the MKK5-mediated iron superoxide dismutase (FSD) signalling pathway in salt stress. The kinase activity of MPK6 was totally turned off in mkk5, whereas the activity of MPK3 was only partially blocked. MKK5 interacted with the MEKK1 protein that was also involved in the salt-induced FSD signalling pathway. These data suggest that salt-induced FSD2 and FSD3 expressions are influenced by MEKK1 via MKK5-MPK6-coupled signalling. This MAP kinase cascade (MEKK1, MKK5, and MPK6) mediates the salt-induced expression of iron superoxide dismutases.

  9. Falls in degenerative cerebellar ataxias

    NARCIS (Netherlands)

    van de Warrenburg, Bart P C; Steijns, Janneke A G; Munneke, Marten; Kremer, Berry P H; Bloem, Bastiaan R

    2005-01-01

    We retrospectively and prospectively assessed the frequency and characteristics of falls in patients with degenerative cerebellar ataxias. The results show that falls occur very frequently in patients with degenerative cerebellar ataxias and that these falls are serious and often lead to injuries or

  10. Activation of Nrf2 Reduces UVA-Mediated MMP-1 Upregulation via MAPK/AP-1 Signaling Cascades: The Photoprotective Effects of Sulforaphane and Hispidulin

    Science.gov (United States)

    Chaiprasongsuk, Anyamanee; Lohakul, Jinaphat; Soontrapa, Kitipong; Sampattavanich, Somponnat; Akarasereenont, Pravit

    2017-01-01

    UVA irradiation plays a role in premature aging of the skin through triggering oxidative stress-associated stimulation of matrix metalloproteinase-1 (MMP-1) responsible for collagen degradation, a hallmark of photoaged skin. Compounds that can activate nuclear factor E2-related factor 2 (Nrf2), a transcription factor regulating antioxidant gene expression, should therefore serve as effective antiphotoaging agents. We investigated whether genetic silencing of Nrf2 could relieve UVA-mediated MMP-1 upregulation via activation of mitogen-activated protein kinase (MAPK)/activator protein 1 (AP-1) signaling using human keratinocyte cell line (HaCaT). Antiphotoaging effects of hispidulin (HPD) and sulforaphane (SFN) were assessed on their abilities to activate Nrf2 in controlling MMP-1 and collagen expressions in association with phosphorylation of MAPKs (extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38), c-Jun, and c-Fos, using the skin of BALB/c mice subjected to repetitive UVA irradiation. Our findings suggested that depletion of Nrf2 promoted both mRNA expression and activity of MMP-1 in the UVA-irradiated HaCaT cells. Treatment of Nrf2 knocked-down HaCaT cells with MAPK inhibitors significantly suppressed UVA-induced MMP-1 and AP-1 activities. Moreover, pretreatment of the mouse skin with HPD and SFN, which could activate Nrf2, provided protective effects against UVA-mediated MMP-1 induction and collagen depletion in correlation with the decreased levels of phosphorylated MAPKs, c-Jun, and c-Fos in the mouse skin. In conclusion, Nrf2 could influence UVA-mediated MMP-1 upregulation through the MAPK/AP-1 signaling cascades. HPD and SFN may therefore represent promising antiphotoaging candidates. PMID:28011874

  11. Socioeconomic status and the cerebellar grey matter volume. Data from a well-characterised population sample.

    Science.gov (United States)

    Cavanagh, Jonathan; Krishnadas, Rajeev; Batty, G David; Burns, Harry; Deans, Kevin A; Ford, Ian; McConnachie, Alex; McGinty, Agnes; McLean, Jennifer S; Millar, Keith; Sattar, Naveed; Shiels, Paul G; Tannahill, Carol; Velupillai, Yoga N; Packard, Chris J; McLean, John

    2013-12-01

    The cerebellum is highly sensitive to adverse environmental factors throughout the life span. Socioeconomic deprivation has been associated with greater inflammatory and cardiometabolic risk, and poor neurocognitive function. Given the increasing awareness of the association between early-life adversities on cerebellar structure, we aimed to explore the relationship between early life (ESES) and current socioeconomic status (CSES) and cerebellar volume. T1-weighted MRI was used to create models of cerebellar grey matter volumes in 42 adult neurologically healthy males selected from the Psychological, Social and Biological Determinants of Ill Health study. The relationship between potential risk factors, including ESES, CSES and cerebellar grey matter volumes were examined using multiple regression techniques. We also examined if greater multisystem physiological risk index-derived from inflammatory and cardiometabolic risk markers-mediated the relationship between socioeconomic status (SES) and cerebellar grey matter volume. Both ESES and CSES explained the greatest variance in cerebellar grey matter volume, with age and alcohol use as a covariate in the model. Low CSES explained additional significant variance to low ESES on grey matter decrease. The multisystem physiological risk index mediated the relationship between both early life and current SES and grey matter volume in cerebellum. In a randomly selected sample of neurologically healthy males, poorer socioeconomic status was associated with a smaller cerebellar volume. Early and current socioeconomic status and the multisystem physiological risk index also apparently influence cerebellar volume. These findings provide data on the relationship between socioeconomic deprivation and a brain region highly sensitive to environmental factors.

  12. Sleep disorders in cerebellar ataxias

    Directory of Open Access Journals (Sweden)

    José L. Pedroso

    2011-04-01

    Full Text Available Cerebellar ataxias comprise a wide range of etiologies leading to central nervous system-related motor and non-motor symptoms. Recently, a large body of evidence has demonstrated a high frequency of non-motor manifestations in cerebellar ataxias, specially in autosomal dominant spinocerebellar ataxias (SCA. Among these non-motor dysfunctions, sleep disorders have been recognized, although still under or even misdiagnosed. In this review, we highlight the main sleep disorders related to cerebellar ataxias focusing on REM sleep behavior disorder (RBD, restless legs syndrome (RLS, periodic limb movement in sleep (PLMS, excessive daytime sleepiness (EDS, insomnia and sleep apnea.

  13. Smad4-Shh-Nfic signaling cascade-mediated epithelial-mesenchymal interaction is crucial in regulating tooth root development.

    Science.gov (United States)

    Huang, Xiaofeng; Xu, Xun; Bringas, Pablo; Hung, Yee Ping; Chai, Yang

    2010-05-01

    Transforming growth factor beta (TGF-beta)/bone morphogenetic protein (BMP) signaling is crucial for regulating epithelial-mesenchymal interaction during organogenesis, and the canonical Smad pathway-mediated TGF-beta/BMP signaling plays important roles during development and disease. During tooth development, dental epithelial cells, known as Hertwig's epithelial root sheath (HERS), participate in root formation following crown development. However, the functional significance of HERS in regulating root development remains unknown. In this study we investigated the signaling mechanism of Smad4, the common Smad for TGF-beta/BMP signaling, in HERS in regulating root development. Tissue-specific inactivation of Smad4 in HERS results in abnormal enamel and dentin formation in K14-Cre;Smad4(fl/fl) mice. HERS enlarges but cannot elongate to guide root development without Smad4. At the molecular level, Smad4-mediated TGF-beta/BMP signaling is required for Shh expression in HERS and Nfic (nuclear factor Ic) expression in the cranial neural crest (CNC)-derived dental mesenchyme. Nfic is crucial for root development, and loss of Nfic results in a CNC-derived dentin defect similar to the one of K14-Cre;Smad4(fl/fl) mice. Significantly, we show that ectopic Shh induces Nfic expression in dental mesenchyme and partially rescues root development in K14-Cre;Smad4(fl/fl) mice. Taken together, our study has revealed an important signaling mechanism in which TGF-beta/BMP signaling relies on a Smad-dependent mechanism in regulating Nfic expression via Shh signaling to control root development. The interaction between HERS and the CNC-derived dental mesenchyme may guide the size, shape, and number of tooth roots.

  14. Ultrasensitive detection of single nucleotide polymorphism in human mitochondrial DNA utilizing ion-mediated cascade surface-enhanced Raman spectroscopy amplification.

    Science.gov (United States)

    Shi, Muling; Zheng, Jing; Tan, Yongjun; Tan, Guixiang; Li, Jishan; Li, Yinhui; Li, Xia; Zhou, Zhiguang; Yang, Ronghua

    2015-03-01

    Although surface-enhanced Raman spectroscopy (SERS) has been featured by high sensitivity, additional signal enhancement is still necessary for trace amount of biomolecules detection. In this paper, a SERS amplified approach, featuring "ions-mediated cascade amplification (IMCA)", was proposed by utilizing the dissolved silver ions (Ag(+)) from silver nanoparticles (AgNPs). We found that using Ag(+) as linkage agent can effectively control the gaps between neighboring 4-aminobenzenethiol (4-ABT) encoded gold nanoparticles (AuNPs@4-ABT) to form "hot spots" and thus produce SERS signal output, in which the SERS intensity was proportional to the concentration of Ag(+). Inspired by this finding, the IMCA was utilized for ultrasensitive detection of single nucleotide polymorphism in human mitochondrial DNA (16189T → C). Combining with the DNA ligase reaction, each target DNA binding event could successfully cause one AgNP introduction. By detecting the dissolved Ag(+) from AgNPs using IMCA, low to 3.0 × 10(-5) fm/μL targeted DNA can be detected, which corresponds to extractions from 200 nL cell suspension containing carcinoma pancreatic β-cell lines from diabetes patients. This IMCA approach is expected to be a universal strategy for ultrasensitive detection of analytes and supply valuable information for biomedical research and clinical early diagnosis.

  15. Mangiferin attenuates diabetic nephropathy by inhibiting oxidative stress mediated signaling cascade, TNFα related and mitochondrial dependent apoptotic pathways in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Pal, Pabitra Bikash; Sinha, Krishnendu; Sil, Parames C

    2014-01-01

    Oxidative stress plays a crucial role in the progression of diabetic nephropathy in hyperglycemic conditions. It has already been reported that mangiferin, a natural C-glucosyl xanthone and polyhydroxy polyphenol compound protects kidneys from diabetic nephropathy. However, little is known about the mechanism of its beneficial action in this pathophysiology. The present study, therefore, examines the detailed mechanism of the beneficial action of mangiferin on STZ-induced diabetic nephropathy in Wister rats as the working model. A significant increase in plasma glucose level, kidney to body weight ratio, glomerular hypertrophy and hydropic changes as well as enhanced nephrotoxicity related markers (BUN, plasma creatinine, uric acid and urinary albumin) were observed in the experimental animals. Furthermore, increased oxidative stress related parameters, increased ROS production and decreased the intracellular antioxidant defenses were detected in the kidney. Studies on the oxidative stress mediated signaling cascades in diabetic nephropathy demonstrated that PKC isoforms (PKCα, PKCβ and PKCε), MAPKs (p38, JNK and ERK1/2), transcription factor (NF-κB) and TGF-β1 pathways were involved in this pathophysiology. Besides, TNFα was released in this hyperglycemic condition, which in turn activated caspase 8, cleaved Bid to tBid and finally the mitochorndia-dependent apoptotic pathway. In addition, oxidative stress also disturbed the proapoptotic-antiapoptotic (Bax and Bcl-2) balance and activated mitochorndia-dependent apoptosis via caspase 9, caspase 3 and PARP cleavage. Mangiferin treatment, post to hyperglycemia, successfully inhibited all of these changes and protected the cells from apoptotic death.

  16. Patterns of top-down control in a seagrass ecosystem: could a roving apex predator induce a behaviour-mediated trophic cascade?

    Science.gov (United States)

    Burkholder, Derek A; Heithaus, Michael R; Fourqurean, James W; Wirsing, Aaron; Dill, Lawrence M

    2013-11-01

    1. The loss of large-bodied herbivores and/or top predators has been associated with large-scale changes in ecosystems around the world, but there remain important questions regarding the contexts in which such changes are most likely and the mechanisms through which they occur, particularly in marine ecosystems. 2. We used long-term exclusion cages to examine the effects of large grazers (sea cows, Dugong dugon; sea turtles Chelonia mydas) on seagrass community structure, biomass and nutrient dynamics. Experiments were conducted in habitats with high risk of predation (interior of shallow banks) and lower risk (edges of banks) to elucidate whether nonconsumptive (risk) effects of tiger sharks (Galeocerdo cuvier), a roving predator, structure herbivore impacts on seagrasses. 3. In lower-risk habitats, excluding large herbivores resulted in increased leaf length for Cymodocea angustata and Halodule uninervis. C. angustata shoot densities nearly tripled when released from herbivory, while H. uninervis nearly disappeared from exclusion cages over the course of the study. 4. We found no support for the hypothesis that grazing increases seagrass nutrient content. Instead, phosphorus content was higher in seagrasses within exclosures. This pattern is consistent with decreased light availability in the denser C. angustata canopies that formed in exclosures, and may indicate that competition for light led to the decrease in H. uninervis. 5. Impacts of large grazers were consistent with a behaviour-mediated trophic cascade (BMTC) initiated by tiger sharks and mediated by risk-sensitive foraging by large grazers. 6, Our results suggest that large-bodied grazers likely played important roles in seagrass ecosystem dynamics historically and that roving predators are capable of initiating a BMTC. Conservation efforts in coastal ecosystems must account for such interactions or risk unintended consequences.

  17. Rho/ROCK signal cascade mediates asymmetric dimethylarginine-induced vascular smooth muscle cells migration and phenotype change.

    Science.gov (United States)

    Zhou, Yi-ming; Lan, Xi; Guo, Han-bin; Zhang, Yan; Ma, Li; Cao, Jian-biao

    2014-01-01

    Asymmetric dimethylarginine (ADMA) induces vascular smooth muscle cells (VSMCs) migration. VSMC phenotype change is a prerequisite of migration. RhoA and Rho-kinase (ROCK) mediate migration of VSMCs. We hypothesize that ADMA induces VSMC migration via the activation of Rho/ROCK signal pathway and due to VSMCs phenotype change. ADMA activates Rho/ROCK signal pathway that interpreted by the elevation of RhoA activity and phosphorylation level of a ROCK substrate. Pretreatment with ROCK inhibitor, Y27632 completely reverses the induction of ADMA on ROCK and in turn inhibits ADMA-induced VSMCs migration. When the Rho/ROCK signal pathway has been blocked by pretreatment with Y27632, the induction of ERK signal pathway by ADMA is completely abrogated. Elimination of ADMA via overexpression of dimethylarginine dimethylaminohydrolase 2 (DDAH2) and L-arginine both blocks the effects of ADMA on the activation of Rho/ROCK and extra cellular signal-regulated kinase (ERK) in VSMCs. The expression of differentiated phenotype relative proteins was reduced and the actin cytoskeleton was disassembled by ADMA, which were blocked by Y27632, further interpreting that ADMA inducing VSMCs migration via Rho/ROCK signal pathway is due to its effect on the VSMCs phenotype change. Our present study may help to provide novel insights into the therapy and prevention of atherosclerosis.

  18. Learning Cascading

    CERN Document Server

    Covert, Michael

    2015-01-01

    This book is intended for software developers, system architects and analysts, big data project managers, and data scientists who wish to deploy big data solutions using the Cascading framework. You must have a basic understanding of the big data paradigm and should be familiar with Java development techniques.

  19. Complex partial seizures: cerebellar metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Theodore, W.H.; Fishbein, D.; Deitz, M.; Baldwin, P.

    1987-07-01

    We used positron emission tomography (PET) with (/sup 18/F)2-deoxyglucose to study cerebellar glucose metabolism (LCMRglu) and the effect of phenytoin (PHT) in 42 patients with complex partial seizures (CPS), and 12 normal controls. Mean +/- SD patient LCMRglu was 6.9 +/- 1.8 mg glucose/100 g/min (left = right), significantly lower than control values of 8.5 +/- 1.8 (left, p less than 0.006), and 8.3 +/- 1.6 (right, p less than 0.02). Only four patients had cerebellar atrophy on CT/MRI; cerebellar LCMRglu in these was 5.5 +/- 1.5 (p = 0.054 vs. total patient sample). Patients with unilateral temporal hypometabolism or EEG foci did not have lateralized cerebellar hypometabolism. Patients receiving phenytoin (PHT) at the time of scan and patients with less than 5 years total PHT exposure had lower LCMRglu, but the differences were not significant. There were weak inverse correlations between PHT level and cerebellar LCMRglu in patients receiving PHT (r = -0.36; 0.05 less than p less than 0.1), as well as between length of illness and LCMRglu (r = -0.22; 0.05 less than p less than 0.1). Patients with complex partial seizures have cerebellar hypometabolism that is bilateral and due only in part to the effect of PHT.

  20. Exposure to extremely low-frequency electromagnetic fields modulates Na+ currents in rat cerebellar granule cells through increase of AA/PGE2 and EP receptor-mediated cAMP/PKA pathway.

    Directory of Open Access Journals (Sweden)

    Yan-Lin He

    Full Text Available Although the modulation of Ca(2+ channel activity by extremely low-frequency electromagnetic fields (ELF-EMF has been studied previously, few reports have addressed the effects of such fields on the activity of voltage-activated Na(+ channels (Na(v. Here, we investigated the effects of ELF-EMF on Na(v activity in rat cerebellar granule cells (GCs. Our results reveal that exposing cerebellar GCs to ELF-EMF for 10-60 min significantly increased Na(v currents (I(Na by 30-125% in a time- and intensity-dependent manner. The Na(v channel steady-state activation curve, but not the steady-state inactivation curve, was significantly shifted (by 5.2 mV towards hyperpolarization by ELF-EMF stimulation. This phenomenon is similar to the effect of intracellular application of arachidonic acid (AA and prostaglandin E(2 (PGE(2 on I(Na in cerebellar GCs. Increases in intracellular AA, PGE(2 and phosphorylated PKA levels in cerebellar GCs were observed following ELF-EMF exposure. Western blottings indicated that the Na(V 1.2 protein on the cerebellar GCs membrane was increased, the total expression levels of Na(V 1.2 protein were not affected after exposure to ELF-EMF. Cyclooxygenase inhibitors and PGE(2 receptor (EP antagonists were able to eliminate this ELF-EMF-induced increase in phosphorylated PKA and I(Na. In addition, ELF-EMF exposure significantly enhanced the activity of PLA(2 in cerebellar GCs but did not affect COX-1 or COX-2 activity. Together, these data demonstrate for the first time that neuronal I(Na is significantly increased by ELF-EMF exposure via a cPLA2 AA PGE(2 EP receptors PKA signaling pathway.

  1. ApoE4-Driven Accumulation of Intraneuronal Oligomerized Aβ42 following Activation of the Amyloid Cascade In Vivo Is Mediated by a Gain of Function

    Directory of Open Access Journals (Sweden)

    Lia Zepa

    2011-01-01

    Full Text Available Activating the amyloid cascade by inhibiting the Aβ-degrading enzyme neprilysin in targeted replacement mice, which express either apoE4 or apoE3, results in the specific accumulation of oligomerized Aβ42 in hippocampal CA1 neurons of the apoE4 mice. We presently investigated the extent to which the apoE4-driven accumulation of Aβ42 and the resulting mitochondrial pathology are due to either gain or loss of function. This revealed that inhibition of neprilysin for one week triggers the accumulation of Aβ42 in hippocampal CA1 neurons of the apoE4 mice but not of either the corresponding apoE3 mice or apoE-deficient mice. At 10 days, Aβ42 also accumulated in the CA1 neurons of the apoE-deficient mice but not in those of the apoE3 mice. Mitochondrial pathology, which in the apoE4 mice is an early pathological consequence following inhibition of neprilyisn, also occurs in the apoE-deficient but not in the apoE3 mice and the magnitude of this effect correlates with the levels of accumulated Aβ42 and oligomerized Aβ42 in these mice. These findings suggest that the rate-limiting step in the pathological effects of apoE4 on CA1 neurons is the accumulation of intracellular oligomerized Aβ42 which is mediated via a gain of function property of apoE4.

  2. Mangiferin attenuates diabetic nephropathy by inhibiting oxidative stress mediated signaling cascade, TNFα related and mitochondrial dependent apoptotic pathways in streptozotocin-induced diabetic rats.

    Directory of Open Access Journals (Sweden)

    Pabitra Bikash Pal

    Full Text Available Oxidative stress plays a crucial role in the progression of diabetic nephropathy in hyperglycemic conditions. It has already been reported that mangiferin, a natural C-glucosyl xanthone and polyhydroxy polyphenol compound protects kidneys from diabetic nephropathy. However, little is known about the mechanism of its beneficial action in this pathophysiology. The present study, therefore, examines the detailed mechanism of the beneficial action of mangiferin on STZ-induced diabetic nephropathy in Wister rats as the working model. A significant increase in plasma glucose level, kidney to body weight ratio, glomerular hypertrophy and hydropic changes as well as enhanced nephrotoxicity related markers (BUN, plasma creatinine, uric acid and urinary albumin were observed in the experimental animals. Furthermore, increased oxidative stress related parameters, increased ROS production and decreased the intracellular antioxidant defenses were detected in the kidney. Studies on the oxidative stress mediated signaling cascades in diabetic nephropathy demonstrated that PKC isoforms (PKCα, PKCβ and PKCε, MAPKs (p38, JNK and ERK1/2, transcription factor (NF-κB and TGF-β1 pathways were involved in this pathophysiology. Besides, TNFα was released in this hyperglycemic condition, which in turn activated caspase 8, cleaved Bid to tBid and finally the mitochorndia-dependent apoptotic pathway. In addition, oxidative stress also disturbed the proapoptotic-antiapoptotic (Bax and Bcl-2 balance and activated mitochorndia-dependent apoptosis via caspase 9, caspase 3 and PARP cleavage. Mangiferin treatment, post to hyperglycemia, successfully inhibited all of these changes and protected the cells from apoptotic death.

  3. Cognition and Emotion in Cerebellar Disorders

    Science.gov (United States)

    ... cerebral cortical “association” areas important for thought, reasoning, motivation, memory and feelings. Damage to the non-motor ... tolerance. Psychosocial interaction may be impaired, particularly in children with cerebellar damage. Dementia is uncommon in cerebellar ...

  4. Cascading Cosmology

    CERN Document Server

    Agarwal, Nishant; Khoury, Justin; Trodden, Mark

    2009-01-01

    We develop a fully covariant, well-posed 5D effective action for the 6D cascading gravity brane-world model, and use this to study cosmological solutions. We obtain this effective action through the 6D decoupling limit, in which an additional scalar degree mode, \\pi, called the brane-bending mode, determines the bulk-brane gravitational interaction. The 5D action obtained this way inherits from the sixth dimension an extra \\pi self-interaction kinetic term. We compute appropriate boundary terms, to supplement the 5D action, and hence derive fully covariant junction conditions and the 5D Einstein field equations. Using these, we derive the cosmological evolution induced on a 3-brane moving in a static bulk. We study the strong- and weak-coupling regimes analytically in this static ansatz, and perform a complete numerical analysis of our solution. Although the cascading model can generate an accelerating solution in which the \\pi field comes to dominate at late times, the presence of a critical singularity prev...

  5. Language Impairment in Cerebellar Ataxia

    NARCIS (Netherlands)

    van Gaalen, Judith; de Swart, Bert J. M.; Oostveen, Judith; Knuijt, Simone; van de Warrenburg, Bart P. C.; Kremer, Berry (H. ) P. H.

    2014-01-01

    Background: Several studies have suggested that language impairment can be observed in patients with cerebellar pathology. The aim of this study was to investigate language performance in patients with spinocerebellar ataxia type 6 (SCA6). Methods: We assessed speech and language in 29 SCA6 patients

  6. Cerebellar Zones: A Personal History

    NARCIS (Netherlands)

    J. Voogd (Jan)

    2011-01-01

    textabstractCerebellar zones were there, of course, before anyone noticed them. Their history is that of young people, unhindered by preconceived ideas, who followed up their observations with available or new techniques. In the 1960s of the last century, the circumstances were fortunate because thr

  7. Cerebellar arteriovenous malformations in children

    Energy Technology Data Exchange (ETDEWEB)

    Griffiths, P.D. [Sheffield Univ. (United Kingdom). Acad. Dept. of Radiol.; Blaser, S.; Armstrong, D.; Chuang, S.; Harwood-Nash, D. [Division of Neuroradiology, The Hospital for Sick Children and University of Toronto, Toronto (Canada); Humphreys, R.P. [Division of Neurosurgery, The Hospital for Sick Children and University of Toronto, Toronto (Canada)

    1998-05-01

    We review the presentation, imaging findings and outcome in 18 children with cerebellar arteriovenous malformations (AVM). This group is of particular interest because of the reported poor outcome despite modern imaging and neurosurgical techniques. All children had CT and 15 underwent catheter angiography at presentation. Several of the children in the latter part of the study had MRI. Of the 18 children, 17 presented with a ruptured AVM producing intracranial haemorrhage. The remaining child presented with temporal lobe epilepsy and was shown to have temporal, vermian and cerebellar hemisphere AVM. This child had other stigmata of Osler-Weber-Rendu syndrome. Three other children had pre-existing abnormalities of possible relevance. One had a vascular malformation of the cheek and mandible, one a documented chromosomal abnormality and another a midline cleft upper lip and palate. Six of the 17 children with a ruptured cerebellar AVM died within 7 days of the ictus. Vascular pathology other than an AVM was found in 10 of the 14 children with a ruptured cerebellar AVM who had angiography: 4 intranidal aneurysms, 5 venous aneurysms and 2 cases of venous outflow obstruction (one child having both an aneurysm and obstruction). The severity of clinical presentation was directly related to the size of the acute haematoma, which was a reasonable predictor of outcome. (orig.) With 4 figs., 4 tabs., 23 refs.

  8. Defects in the CAPN1 Gene Result in Alterations in Cerebellar Development and Cerebellar Ataxia in Mice and Humans

    Directory of Open Access Journals (Sweden)

    Yubin Wang

    2016-06-01

    Full Text Available A CAPN1 missense mutation in Parson Russell Terrier dogs is associated with spinocerebellar ataxia. We now report that homozygous or heterozygous CAPN1-null mutations in humans result in cerebellar ataxia and limb spasticity in four independent pedigrees. Calpain-1 knockout (KO mice also exhibit a mild form of ataxia due to abnormal cerebellar development, including enhanced neuronal apoptosis, decreased number of cerebellar granule cells, and altered synaptic transmission. Enhanced apoptosis is due to absence of calpain-1-mediated cleavage of PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1, which results in inhibition of the Akt pro-survival pathway in developing granule cells. Injection of neonatal mice with the indirect Akt activator, bisperoxovanadium, or crossing calpain-1 KO mice with PHLPP1 KO mice prevented increased postnatal cerebellar granule cell apoptosis and restored granule cell density and motor coordination in adult mice. Thus, mutations in CAPN1 are an additional cause of ataxia in mammals, including humans.

  9. Cerebellar ataxia and functional genomics : Identifying the routes to cerebellar neurodegeneration

    NARCIS (Netherlands)

    Smeets, C J L M; Verbeek, D S

    2014-01-01

    Cerebellar ataxias are progressive neurodegenerative disorders characterized by atrophy of the cerebellum leading to motor dysfunction, balance problems, and limb and gait ataxia. These include among others, the dominantly inherited spinocerebellar ataxias, recessive cerebellar ataxias such as Fried

  10. Cerebellar deficits and hyperactivity in mice lacking Smad4.

    Science.gov (United States)

    Zhou, Yong-Xing; Zhao, Mingrui; Li, Dan; Shimazu, Kazuhiro; Sakata, Kazuko; Deng, Chu-Xia; Lu, Bai

    2003-10-24

    Smad4 is a central mediator of TGF-beta signals, which are known to play essential roles in many biological processes. Using a Cre-loxP approach to overcome early embryonic lethality, we have studied functions of TGF-beta/Smad4 signals in the central nervous system (CNS). No obvious deficits were detected in mice carrying the targeted disruption of Smad4 in the CNS. The overall morphology of the hippocampus appeared normal. There was no change in the proliferation of neuronal precursor cells, nor in several forms of synaptic plasticity. In contrast, deletion of Smad4 resulted in a marked decrease in the number of cerebellar Purkinje cells and parvalbumin-positive interneurons. Accompanied by the abnormality in the cerebellum, mutant mice also exhibited significantly increased vertical activity. Thus, our study reveals an unexpected role for Smad4 in cerebellar development and in the control of motor function.

  11. Nonsurgical cerebellar mutism (anarthria) in two children.

    Science.gov (United States)

    Mewasingh, Leena D; Kadhim, Hazim; Christophe, Catherine; Christiaens, Florence J; Dan, Bernard

    2003-01-01

    Cerebellar mutism (anarthria) is a well-described complication of posterior fossa tumor resection. It is accompanied by a characteristic behavior including irritability and autistic features. This syndrome is typically reversible within days to months. Underlying pathophysiology is unknown. We describe two children who presented with a similar clinical finding after nonsurgical cerebellar involvement, hemolytic-uremic syndrome in one and cerebellitis in the other. Postmortem pathologic findings in the first patient indicated cerebellar ischemic necrosis. Single-photon emission computed tomography in the second patient revealed diffuse cerebellar hypoperfusion with no supratentorial abnormalities, refuting a phenomenon of diaschisis between cerebellar and frontal connections. These findings confirm that this clinical syndrome may occur in a nonsurgical, nontraumatic context. They are consistent with recent integrative hypotheses explaining cerebellar anarthria.

  12. Crossed cerebral - cerebellar diaschisis : MRI evaluation.

    Directory of Open Access Journals (Sweden)

    Chakravarty A

    2002-07-01

    Full Text Available MRI, done later in life, in two patients with infantile hemiplegia syndrome showed significant volume loss in the cerebellar hemisphere contralateral to the side of the affected cerebrum. The cerebellar volume loss seemed to correlate with the degree of volume loss in the contralateral cerebral hemisphere. These observations provide morphological evidence of the phenomenon of crossed cerebral-cerebellar diaschisis (CCD. Functional neuroimaging studies in support of the concept of CCD has been critically reviewed.

  13. Autosomal recessive cerebellar ataxias : the current state of affairs

    NARCIS (Netherlands)

    Vermeer, S.; van de Warrenburg, B. P. C.; Willemsen, M. A. A. P.; Cluitmans, M.; Scheffer, H.; Kremer, B. P.; Knoers, N. V. A. M.

    2011-01-01

    Among the hereditary ataxias, autosomal recessive cerebellar ataxias (ARCAs) encompass a diverse group of rare neurodegenerative disorders in which a cerebellar syndrome is the key clinical feature. The clinical overlap between the different cerebellar ataxias, the occasional atypical phenotypes, an

  14. Genetics Home Reference: VLDLR-associated cerebellar hypoplasia

    Science.gov (United States)

    ... Conditions VLDLR-associated cerebellar hypoplasia VLDLR-associated cerebellar hypoplasia Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description VLDLR -associated cerebellar hypoplasia is an inherited condition that affects the development ...

  15. [Peripheral neuropathies associated with hereditary cerebellar ataxias].

    Science.gov (United States)

    Anheim, M; Tranchant, C

    2011-01-01

    Inherited cerebellar ataxias constitute a complicated and heterogeneous group of neurodegenerative disorders affecting the cerebellum and/or spinocerebellar tract, spinal cord and peripheral nerves. A peripheral neuropathy is frequently seen in inherited cerebellar ataxias although it rarely reveals the disease. Moreover, the peripheral neuropathy is helpful for the diagnostic procedure and contributes to the functional prognosis of the disease. Thus, electroneuromyography is essential in the algorithm for the diagnosis of inherited cerebellar ataxias, as well as brain MRI (looking especially for cerebellar atrophy) and the assessment of several biomarkers (alpha-foetoprotein, vitamin E, albumin, LDL cholesterol, lactic acid, phytanic acid).

  16. MAPK Cascades in Guard Cell Signal Transduction

    Science.gov (United States)

    Lee, Yuree; Kim, Yun Ju; Kim, Myung-Hee; Kwak, June M.

    2016-01-01

    Guard cells form stomata on the epidermis and continuously respond to endogenous and environmental stimuli to fine-tune the gas exchange and transpirational water loss, processes which involve mitogen-activated protein kinase (MAPK) cascades. MAPKs form three-tiered kinase cascades with MAPK kinases and MAPK kinase kinases, by which signals are transduced to the target proteins. MAPK cascade genes are highly conserved in all eukaryotes, and they play crucial roles in myriad developmental and physiological processes. MAPK cascades function during biotic and abiotic stress responses by linking extracellular signals received by receptors to cytosolic events and gene expression. In this review, we highlight recent findings and insights into MAPK-mediated guard cell signaling, including the specificity of MAPK cascades and the remaining questions. PMID:26904052

  17. MAPK cascades in guard cell signal transduction

    Directory of Open Access Journals (Sweden)

    Yuree eLee

    2016-02-01

    Full Text Available Guard cells form stomata on the epidermis and continuously respond to endogenous and environmental stimuli to fine-tune the gas exchange and transpirational water loss, processes which involve mitogen-activated protein kinase (MAPK cascades. MAPKs form three-tiered kinase cascades with MAPK kinases and MAPK kinase kinases, by which signals are transduced to the target proteins. MAPK cascade genes are highly conserved in all eukaryotes, and they play crucial roles in myriad developmental and physiological processes. MAPK cascades function during biotic and abiotic stress responses by linking extracellular signals received by receptors to cytosolic events and gene expression. In this review, we highlight recent findings and insights into MAPK-mediated guard cell signaling, including the specificity of MAPK cascades and the remaining questions.

  18. Blue to near-IR energy transfer cascade within a dye-doped polymer matrix, mediated by a photochromic molecular switch.

    Science.gov (United States)

    Dryza, Viktoras; Smith, Trevor A; Bieske, Evan J

    2016-02-21

    The spectroscopic properties of a poly(methyl methacrylate) matrix doped with a coumarin dye, a cyanine dye, and a photochromic spiropyran dye have been investigated. Before UV irradiation of the matrix, excitation of the coumarin dye results in minimal energy transfer to the cyanine dye. The energy transfer is substantially enhanced following UV irradiation of the matrix, which converts the colourless spiropyran isomer to the coloured merocyanine isomer, which then acts as an intermediate bridge by accepting energy from the coumarin dye and then donating energy to the cyanine dye. This demonstration of a switchable energy transfer cascade should help initiate new research directions in molecular photonics.

  19. The clinical presentation of preterm cerebellar haemorrhage

    NARCIS (Netherlands)

    G.M. Ecury-Goossen (Ginette); J. Dudink (Jeroen); M. Leguin (Maarten); M. Feijen-Roon (Monique); S. Horsch (Sandra); P. Govaert (Paul)

    2010-01-01

    textabstractThe objective of this study was to evaluate clinical symptoms and findings on cranial ultrasound (CUS) in preterm infants with cerebellar haemorrhage through retrospective analysis of all preterm infants with a postnatal CUS or MRI diagnosis of cerebellar haemorrhage admitted in a tertia

  20. Cellular and Molecular Basis of Cerebellar Development

    Directory of Open Access Journals (Sweden)

    Salvador eMartinez

    2013-06-01

    Full Text Available Historically, the molecular and cellular mechanisms of cerebellar development were investigated through structural descriptions and studying spontaneous mutations in animal models and humans. Advances in experimental embryology, genetic engineering and neuroimaging techniques render today the possibility to approach the analysis of molecular mechanisms underlying histogenesis and morphogenesis of the cerebellum by experimental designs. Several genes and molecules were identified to be involved in the cerebellar plate regionalization, specification and differentiation of cerebellar neurons, as well as the establishment of cellular migratory routes and the subsequent neuronal connectivity. Indeed, pattern formation of the cerebellum requires the adequate orchestration of both key morphogenetic signals, arising from distinct brain regions, and local expression of specific transcription factors. Thus, the present review wants to revisit and discuss these morphogenetic and molecular mechanisms taking place during cerebellar development in order to understand causal processes regulating cerebellar cytoarchitecture, its highly topographically ordered circuitry and its role in brain function.

  1. Cerebellar stroke-manifesting as mania

    Directory of Open Access Journals (Sweden)

    Venkatesan Jagadesan

    2014-01-01

    Full Text Available Secondary mania resulting from cerebral Cortex are described commonly. But secondary mania produced by cerebellar lesions are relatively uncommon. This case report describes a patient who developed cerebellar stoke and manic features simultaneously. 28 years old male developed giddiness and projectile vomiting. Then he would lie down for about an hour only to find that he could not walk. He became quarrelsome. His Psycho motor activities and speech were increased. He was euphoric and was expressing grandiose ideas. Bender Gestalt Test showed signs of organicity. Score in Young mania relating scale was 32; productivity was low in Rorschach. Neurological examination revealed left cerebellar signs like ataxia and slurring of speech. Computed tomography of brain showed left cerebellar infarct. Relationship between Psychiatric manifestations and cerebellar lesion are discussed.

  2. The bihemispheric posterior inferior cerebellar artery

    Energy Technology Data Exchange (ETDEWEB)

    Cullen, Sean P. [Brigham and Women' s Hospital and Children' s Hospital, Department of Radiology and Neurosurgery, Boston, MA (United States); Ozanne, Augustin; Alvarez, Hortensia; Lasjaunias, Pierre [Service de Neuroradiologie Diagnostic et Therapeutique, Hopital de Bicetre-Universite Paris-sud Orsay (France)

    2005-11-01

    Rarely, a solitary posterior inferior cerebellar artery (PICA) will supply both cerebellar hemispheres. We report four cases of this variant. We present a retrospective review of clinical information and imaging of patients undergoing angiography at our institution to identify patients with a bihemispheric PICA. There were four patients: three males and one female. One patient presented with a ruptured arteriovenous malformation, and one with a ruptured aneurysm. Two patients had normal angiograms. The bihemispheric PICA was an incidental finding in all cases. The bihemispheric vessel arose from the dominant left vertebral artery, and the contralateral posterior inferior cerebellar artery was absent or hypoplastic. In all cases, contralateral cerebellar supply arose from a continuation of the ipsilateral PICA distal to the choroidal point and which crossed the midline dorsal to the vermis. We conclude that the PICA may supply both cerebellar hemispheres. This rare anatomic variant should be considered when evaluating patients with posterior fossa neurovascular disease. (orig.)

  3. Altered cerebellar feedback projections in Asperger syndrome.

    Science.gov (United States)

    Catani, Marco; Jones, Derek K; Daly, Eileen; Embiricos, Nitzia; Deeley, Quinton; Pugliese, Luca; Curran, Sarah; Robertson, Dene; Murphy, Declan G M

    2008-07-15

    It has been proposed that the biological basis of autism spectrum disorder includes cerebellar 'disconnection'. However, direct in vivo evidence in support of this is lacking. Here, the microstructural integrity of cerebellar white matter in adults with Asperger syndrome was studied using diffusion tensor magnetic resonance tractography. Fifteen adults with Asperger syndrome and 16 age-IQ-gender-matched healthy controls underwent diffusion tensor magnetic resonance imaging. For each subject, tract-specific measurements of mean diffusivity and fractional anisotropy were made within the inferior, middle, superior cerebellar peduncles and short intracerebellar fibres. No group differences were observed in mean diffusivity. However, people with Asperger syndrome had significantly lower fractional anisotropy in the short intracerebellar fibres (pAsperger syndrome. The localised abnormalities in the main cerebellar outflow pathway may prevent the cerebral cortex from receiving those cerebellar feedback inputs necessary for a successful adaptive social behaviour.

  4. Role of synchronous activation of cerebellar purkinje cell ensembles in multi-joint movement control

    NARCIS (Netherlands)

    T.M. Hoogland (Tycho); J.R. de Gruijl (Jornt); L. Witter (Laurens); M.I. Canto (Marcia Irene); C.I. de Zeeuw (Chris)

    2015-01-01

    textabstractIt is a longstanding question in neuroscience how elaborate multi-joint movements are coordinated coherently. Microzones of cerebellar Purkinje cells (PCs) are thought to mediate this coordination by controlling the timing of particular motor domains. However, it remains to be elucidated

  5. Role of Synchronous Activation of Cerebellar Purkinje Cell Ensembles in Multi-joint Movement Control

    NARCIS (Netherlands)

    Hoogland, Tycho M; De Gruijl, Jornt R; Witter, Laurens; Canto, Cathrin B; De Zeeuw, Chris I

    2015-01-01

    It is a longstanding question in neuroscience how elaborate multi-joint movements are coordinated coherently. Microzones of cerebellar Purkinje cells (PCs) are thought to mediate this coordination by controlling the timing of particular motor domains. However, it remains to be elucidated to what ext

  6. Imaging calcium waves in cerebellar Bergmann glia.

    Science.gov (United States)

    Beierlein, Michael

    2013-01-01

    This protocol describes methods for recording synaptically evoked Ca(2+) waves from individual Bergmann glia (BG) in slices of cerebellar cortex. Unlike protoplasmic, star-shaped astrocytes, whose thin processes pose a serious challenge to stable Ca(2+) measurements, BG are large radial cells, with several main processes that run over distances of several hundred micrometers toward the pia and ensheathe thousands of parallel fiber (PF) synapses. Stimulation of PF synapses with brief bursts can trigger long-lasting Ca(2+) responses in BG processes, which can be reliably recorded using a cooled charge-coupled device (CCD) camera. This protocol was developed to enable measurements of Ca(2+) waves in individual BG loaded with a high-affinity Ca(2+) indicator such as Fura-2 for up to 2 h. Because BG recorded in slices rarely display spontaneous (i.e., tetrodotoxin [TTX]-sensitive) or intrinsic Ca(2+) transients, Ca(2+) waves can be evoked repeatedly and reliably, which permits quantitative studies using pharmacological tools. Fluorescence measurements obtained using CCD technology offer a straightforward means of characterizing the mechanisms and potential functional consequences of widespread and long-lasting, store-mediated Ca(2+) increases in astrocytes.

  7. Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy

    DEFF Research Database (Denmark)

    Winkelmann, Juliane; Lin, Ling; Schormair, Barbara

    2012-01-01

    Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN) is characterized by late onset (30-40 years old) cerebellar ataxia, sensory neuronal deafness, narcolepsy-cataplexy and dementia. We performed exome sequencing in five individuals from three ADCA-DN kindreds and identified DNMT.......GLY605Ala mutation was subsequently identified. Narcolepsy and deafness were the first symptoms to appear in all pedigrees, followed by ataxia. DNMT1 is a widely expressed DNA methyltransferase maintaining methylation patterns in development, and mediating transcriptional repression by direct binding...

  8. The role of Kv3-type potassium channels in cerebellar physiology and behavior.

    Science.gov (United States)

    Joho, Rolf H; Hurlock, Edward C

    2009-09-01

    Different subunits of the Kv3 subfamily of voltage-gated potassium (Kv) channels (Kv3.1-Kv3.4) are expressed in distinct neuronal subpopulations in the cerebellum. Behavioral phenotypes in Kv3-null mutant mice such as ataxia with prominent hypermetria and heightened alcohol sensitivity are characteristic of cerebellar dysfunction. Here, we review how the unique biophysical properties of Kv3-type potassium channels, fast activation and fast deactivation that enable cerebellar neurons to generate brief action potentials at high frequencies, affect firing patterns and influence cerebellum-mediated behavior.

  9. Effects of cerebellar transcranial alternating current stimulation on motor cortex excitability and motor function.

    Science.gov (United States)

    Naro, Antonino; Bramanti, Alessia; Leo, Antonino; Manuli, Alfredo; Sciarrone, Francesca; Russo, Margherita; Bramanti, Placido; Calabrò, Rocco Salvatore

    2017-01-07

    The cerebellum regulates several motor functions through two main mechanisms, the cerebellum-brain inhibition (CBI) and the motor surround inhibition (MSI). Although the exact cerebellar structures and functions involved in such processes are partially known, Purkinje cells (PC) and their surrounding interneuronal networks may play a pivotal role concerning CBI and MSI. Cerebellar transcranial alternating current stimulation (tACS) has been proven to shape specific cerebellar components in a feasible, safe, effective, and non-invasive manner. The aim of our study was to characterize the cerebellar structures and functions subtending CBI and MSI using a tACS approach. Fifteen healthy individuals underwent a cerebellar tACS protocol at 10, 50, and 300 Hz, or a sham-tACS over the right cerebellar hemisphere. We measured the tACS aftereffects on motor-evoked potential (MEP) amplitude, CBI induced by tACS (tiCBI) at different frequencies, MSI, and hand motor task performance. None of the participants had any side effect related to tACS. After 50-Hz tACS, we observed a clear tiCBI-50Hz weakening (about +30%, p  0.6). Our preliminary data suggest that PC may represent the last mediator of tiCBI and that the surrounding interneuronal network may have an important role in updating MSI, tiCBI, and M1 excitability during tonic muscle contraction, by acting onto the PC. The knowledge of these neurophysiological issues offers new cues to design innovative, non-invasive neuromodulation protocols to shape cerebellar-cerebral functions.

  10. Effects of ethanol and NAP on cerebellar expression of the neural cell adhesion molecule L1.

    Directory of Open Access Journals (Sweden)

    Devon M Fitzgerald

    Full Text Available The neural cell adhesion molecule L1 is critical for brain development and plays a role in learning and memory in the adult. Ethanol inhibits L1-mediated cell adhesion and neurite outgrowth in cerebellar granule neurons (CGNs, and these actions might underlie the cerebellar dysmorphology of fetal alcohol spectrum disorders. The peptide NAP potently blocks ethanol inhibition of L1 adhesion and prevents ethanol teratogenesis. We used quantitative RT-PCR and Western blotting of extracts of cerebellar slices, CGNs, and astrocytes from postnatal day 7 (PD7 rats to investigate whether ethanol and NAP act in part by regulating the expression of L1. Treatment of cerebellar slices with 20 mM ethanol, 10(-12 M NAP, or both for 4 hours, 24 hours, and 10 days did not significantly affect L1 mRNA and protein levels. Similar treatment for 4 or 24 hours did not regulate L1 expression in primary cultures of CGNs and astrocytes, the predominant cerebellar cell types. Because ethanol also damages the adult cerebellum, we studied the effects of chronic ethanol exposure in adult rats. One year of binge drinking did not alter L1 gene and protein expression in extracts from whole cerebellum. Thus, ethanol does not alter L1 expression in the developing or adult cerebellum; more likely, ethanol disrupts L1 function by modifying its conformation and signaling. Likewise, NAP antagonizes the actions of ethanol without altering L1 expression.

  11. Cerebellar Involvement in Ataxia and Generalized Epilepsy

    NARCIS (Netherlands)

    L. Kros (Lieke)

    2015-01-01

    markdownabstract__Abstract__ The work described in this thesis was performed in order to elucidate the role of different cerebellar modules in ataxia and generalized epilepsy using various techniques including in vivo electrophysiology, optogenetics, pharmacological interventions, immunohistology a

  12. Synchrony and neural coding in cerebellar circuits

    Directory of Open Access Journals (Sweden)

    Abigail L Person

    2012-12-01

    Full Text Available The cerebellum regulates complex movements and is also implicated in cognitive tasks, and cerebellar dysfunction is consequently associated not only with movement disorders, but also with conditions like autism and dyslexia. How information is encoded by specific cerebellar firing patterns remains debated, however. A central question is how the cerebellar cortex transmits its integrated output to the cerebellar nuclei via GABAergic synapses from Purkinje neurons. Possible answers come from accumulating evidence that subsets of Purkinje cells synchronize their firing during behaviors that require the cerebellum. Consistent with models predicting that coherent activity of inhibitory networks has the capacity to dictate firing patterns of target neurons, recent experimental work supports the idea that inhibitory synchrony may regulate the response of cerebellar nuclear cells to Purkinje inputs, owing to the interplay between unusually fast inhibitory synaptic responses and high rates of intrinsic activity. Data from multiple laboratories lead to a working hypothesis that synchronous inhibitory input from Purkinje cells can set the timing and rate of action potentials produced by cerebellar nuclear cells, thereby relaying information out of the cerebellum. If so, then changing spatiotemporal patterns of Purkinje activity would allow different subsets of inhibitory neurons to control cerebellar output at different times. Here we explore the evidence for and against the idea that a synchrony code defines, at least in part, the input-output function between the cerebellar cortex and nuclei. We consider the literature on the existence of simple spike synchrony, convergence of Purkinje neurons onto nuclear neurons, and intrinsic properties of nuclear neurons that contribute to responses to inhibition. Finally, we discuss factors that may disrupt or modulate a synchrony code and describe the potential contributions of inhibitory synchrony to other motor

  13. Cerebellar mutism: review of the literature

    DEFF Research Database (Denmark)

    Gudrunardottir, Thora; Sehested, Astrid; Juhler, Marianne;

    2011-01-01

    Cerebellar mutism is a common complication of posterior fossa surgery in children. This article reviews current status with respect to incidence, anatomical substrate, pathophysiology, risk factors, surgical considerations, treatment options, prognosis and prevention.......Cerebellar mutism is a common complication of posterior fossa surgery in children. This article reviews current status with respect to incidence, anatomical substrate, pathophysiology, risk factors, surgical considerations, treatment options, prognosis and prevention....

  14. Gene regulation by MAP kinase cascades

    DEFF Research Database (Denmark)

    Fiil, Berthe Katrine; Petersen, Klaus; Petersen, Morten

    2009-01-01

    Mitogen-activated protein kinase (MAPK) cascades are signaling modules that transduce extracellular stimuli to a range of cellular responses. Research in yeast and metazoans has shown that MAPK-mediated phosphorylation directly or indirectly regulates the activity of transcription factors. Plant ...

  15. Bilateral Cerebellar Cortical Dysplasia without Other Malformations: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Jung Seok; Ahn Kook Jin; Kim, Jee Young; Lee, Sun Jin; Park, Jeong Mi [Catholic University Yeouido St. Mary' s Hospital, College of Medicine, Seoul (Korea, Republic of)

    2010-06-15

    Recent advances in MRI have revealed congenital brain malformations and subtle developmental abnormalities of the cerebral and cerebellar cortical architecture. Typical cerebellar cortical dysplasia as a newly categorized cerebellar malformation, has been seen in patients with Fukuyama congenital muscular dystrophy. Cerebellar cortical dysplasia occurs at the embryonic stage and is often observed in healthy newborns. It is also incidentally and initially detected in adults without symptoms. To the best of our knowledge, cerebellar dysplasia without any related disorders is very rare. We describe the MRI findings in one patient with disorganized foliation of both cerebellar hemispheres without a related disorder or syndrome

  16. Changes in the cerebellar and cerebro-cerebellar circuit in type 2 diabetes.

    Science.gov (United States)

    Fang, Peng; An, Jie; Tan, Xin; Zeng, Ling-Li; Shen, Hui; Qiu, Shijun; Hu, Dewen

    2017-01-11

    Currently, 422 million adults suffer from diabetes worldwide, leading to tremendous disabilities and a great burden to families and society. Functional and structural MRIs have demonstrated that patients with type 2 diabetes mellitus (T2DM) exhibit abnormalities in brain regions in the cerebral cortex. However, the changes of cerebellar anatomical connections in diabetic patients remains unclear. In the current study, diffusion tensor imaging deterministic tractography and statistical analysis were employed to investigate abnormal cerebellar anatomical connections in diabetic patients. This is the first study to investigate the altered cerebellar anatomical connectivity in T2DM patients. Decreased anatomical connections were found in the cerebellar and cerebro-cerebellar circuits of T2DM patients, providing valuable new insights into the potential neuro-pathophysiology of diabetes-related motor and cognitive deficits.

  17. Delineating the cortico-striatal-cerebellar network in implicit motor sequence learning.

    Science.gov (United States)

    Tzvi, Elinor; Münte, Thomas F; Krämer, Ulrike M

    2014-07-01

    Theoretical models and experimental evidence suggest that cortico-striatal-cerebellar networks play a crucial role in mediating motor sequence learning. However, how these different regions interact in order to mediate learning is less clear. In the present fMRI study, we used dynamic causal modeling to investigate effective connectivity within the cortico-striatal-cerebellar network while subjects performed a serial reaction time task. Using Bayesian model selection and family wise inference, we show that the cortico-cerebellar loop had higher model evidence than the cortico-striatal loop during motor learning. We observed significant negative modulatory effects on the connections from M1 to cerebellum bilaterally during learning. The results suggest that M1 causes the observed decrease in activity in the cerebellum as learning progresses. The current study stresses the significant role that the cerebellum plays in motor learning as previously suggested by fMRI studies in healthy subjects as well as behavioral studies in patients with cerebellar dysfunction. These results provide important insight into the neural mechanisms underlying motor learning.

  18. The depletion of ATM inhibits colon cancer proliferation and migration via B56γ2-mediated Chk1/p53/CD44 cascades.

    Science.gov (United States)

    Liu, Rui; Tang, Jiajia; Ding, Chaodong; Liang, Weicheng; Zhang, Li; Chen, Tianke; Xiong, Yan; Dai, Xiaowei; Li, Wenfeng; Xu, Yunsheng; Hu, Jin; Lu, Liting; Liao, Wanqin; Lu, Xincheng

    2017-04-01

    Ataxia-telangiectasia mutated (ATM) protein kinase is a major guardian of genomic stability, and its well-established function in cancer is tumor suppression. Here, we report an oncogenic role of ATM. Using two isogenic sets of human colon cancer cell lines that differed only in their ATM status, we demonstrated that ATM deficiency significantly inhibits cancer cell proliferation, migration, and invasion. The tumor-suppressive function of ATM depletion is not modulated by the compensatory activation of ATR, but it is associated with B56γ2-mediated Chk1/p53/CD44 signaling pathways. Under normal growth conditions, the depletion of ATM prevents B56γ2 ubiquitination and degradation, which activates PP2A-mediated Chk1/p53/p21 signaling pathways, leading to senescence and cell cycle arrest. CD44 was validated as a novel ATM target based on its ability to rescue cell migration and invasion defects in ATM-depleted cells. The activation of p53 induced by ATM depletion suppresses CD44 transcription, thus resulting in epithelial-mesenchymal transition (EMT) and cell migration suppression. Our study suggests that ATM has tumorigenic potential in post-formed colon neoplasia, and it supports ATM as an appealing target for improving cancer therapy.

  19. Cascade quantum teleportation

    Institute of Scientific and Technical Information of China (English)

    ZHOU Nan-run; GONG Li-hua; LIU Ye

    2006-01-01

    In this letter a cascade quantum teleportation scheme is proposed. The proposed scheme needs less local quantum operations than those of quantum multi-teleportation. A quantum teleportation scheme based on entanglement swapping is presented and compared with the cascade quantum teleportation scheme. Those two schemes can effectively teleport quantum information and extend the distance of quantum communication.

  20. Purkinje cell activity in the cerebellar anterior lobe after rabbit eyeblink conditioning

    Science.gov (United States)

    Green, John T.; Steinmetz, Joseph E.

    2005-01-01

    The cerebellar anterior lobe may play a critical role in the execution and proper timing of learned responses. The current study was designed to monitor Purkinje cell activity in the rabbit cerebellar anterior lobe after eyeblink conditioning, and to assess whether Purkinje cells in recording locations may project to the interpositus nucleus. Rabbits were trained in an interstimulus interval discrimination procedure in which one tone signaled a 250-msec conditioned stimulus-unconditioned stimulus (CS-US) interval and a second tone signaled a 750-msec CS-US interval. All rabbits showed conditioned responses to each CS with mean onset and peak latencies that coincided with the CS-US interval. Many anterior lobe Purkinje cells showed significant learning-related activity after eyeblink conditioning to one or both of the CSs. More Purkinje cells responded with inhibition than with excitation to CS presentation. In addition, when the firing patterns of all conditioning-related Purkinje cells were pooled, it appeared that the population showed a pattern of excitation followed by inhibition during the CS-US interval. Using cholera toxin-conjugated horseradish peroxidase, Purkinje cells in recording areas were found to project to the interpositus nucleus. These data support previous studies that have suggested a role for the anterior cerebellar cortex in eyeblink conditioning as well as models of cerebellar-mediated CR timing that postulate that Purkinje cell activity inhibits conditioned response (CR) generation during the early portion of a trial by inhibiting the deep cerebellar nuclei and permits CR generation during the later portion of a trial through disinhibition of the cerebellar nuclei. PMID:15897252

  1. Excitatory effect of histamine on neuronal activity of rat cerebellar fastigial nucleus in vitro

    Institute of Scientific and Technical Information of China (English)

    TANG Biao; ZHANG Jun; LI HongZhao; ZHU JingNing; WANG JianJun

    2007-01-01

    The cerebellar fastigial nucleus (FN) holds an important role in motor control and body balance. Previous studies have revealed that the nucleus is innervated by direct hypothalamocerebellar histaminergic fibers. However, the functional role of histaminergic projection in cerebellar FN has never been established. In this study, we investigated the effect of histamine on neuronal firing of cerebellar FN by using slice preparations. Sixty-five FN cells were recorded from 47 cerebellar slices, and a vast majority of the cells responded to histamine stimulation with an excitatory response (58/65, 89.2%). Perfusing slices with low-Ca2+/high-Mg2+ medium did not block the histamine-induced excitation (n=10), supporting a direct postsynaptic action of histamine on the cells. Furthermore, the excitatory effect of histamine on FN neurons was not blocked by selective histamine H1 receptor antagonist triprolidine (n=15) or chlorpheniramine (n=10), but was effectively suppressed by ranitidine (n=15), a highly selective histamine H2 receptor antagonist. On the other hand, highly selective histamine H2 receptor agonist dimaprit (n=20) instead of histamine H1 receptor agonist 2-pyridylethylamine (n=16) mimicked the excitatory effect of histamine on FN neurons. The dimaprit-induced FN neuronal excitation was effectively antagonized by selective histamine H2 receptor antagonist ranitidine (n=13) but not influenced by selective histamine H1 receptor antagonist triprolidine (n=15). These results demonstrate that histamine excites cerebellar FN cells via the histamine H2 receptor mechanism and suggest that the hypothalamocerebellar histaminergic fibers may modulate cerebellar FN-mediated sensorimotor integration through their excitatory innervations on FN neurons.

  2. Metabolic anatomy of paraneoplastic cerebellar degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, N.E.; Posner, J.B.; Sidtis, J.J.; Moeller, J.R.; Strother, S.C.; Dhawan, V.; Rottenberg, D.A.

    1988-06-01

    Eleven patients with acquired cerebellar degeneration (10 of whom had paraneoplastic cerebellar degeneration (PCD)) were evaluated using neuropsychological tests and /sup 18/F-fluorodeoxyglucose/positron emission tomography to (1) quantify motor, cognitive, and metabolic abnormalities; (2) determine if characteristic alterations in the regional cerebral metabolic rate for glucose (rCMRGlc) are associated with PCD; and (3) correlate behavioral and metabolic measures of disease severity. Eighteen volunteer subjects served as normal controls. Although some PCD neuropsychological test scores were abnormal, these results could not, in general, be dissociated from the effects of dysarthria and ataxia. rCMRGlc was reduced in patients with PCD (versus normal control subjects) in all regions except the brainstem. Analysis of patient and control rCMRGlc data using a mathematical model of regional metabolic interactions revealed two metabolic pattern descriptors, SSF1 and SSF2, which distinguished patients with PCD from normal control subjects; SSF2, which described a metabolic coupling between cerebellum, cuneus, and posterior temporal, lateral frontal, and paracentral cortex, correlated with quantitative indices of cerebellar dysfunction. Our inability to document substantial intellectual impairment in 7 of 10 patients with PCD contrasts with the 50% incidence of dementia in PCD reported by previous investigators. Widespread reductions in PCD rCMRGlc may result from the loss of cerebellar efferents to thalamus and forebrain structures, a reverse cerebellar diaschisis.

  3. Genetics Home Reference: autosomal recessive cerebellar ataxia type 1

    Science.gov (United States)

    ... Genetics Home Health Conditions ARCA1 autosomal recessive cerebellar ataxia type 1 Enable Javascript to view the expand/ ... Open All Close All Description Autosomal recessive cerebellar ataxia type 1 ( ARCA1 ) is a condition characterized by ...

  4. Landmark based shape analysis for cerebellar ataxia classification and cerebellar atrophy pattern visualization

    Science.gov (United States)

    Yang, Zhen; Abulnaga, S. Mazdak; Carass, Aaron; Kansal, Kalyani; Jedynak, Bruno M.; Onyike, Chiadi; Ying, Sarah H.; Prince, Jerry L.

    2016-03-01

    Cerebellar dysfunction can lead to a wide range of movement disorders. Studying the cerebellar atrophy pattern associated with different cerebellar disease types can potentially help in diagnosis, prognosis, and treatment planning. In this paper, we present a landmark based shape analysis pipeline to classify healthy control and different ataxia types and to visualize the characteristic cerebellar atrophy patterns associated with different types. A highly informative feature representation of the cerebellar structure is constructed by extracting dense homologous landmarks on the boundary surfaces of cerebellar sub-structures. A diagnosis group classifier based on this representation is built using partial least square dimension reduction and regularized linear discriminant analysis. The characteristic atrophy pattern for an ataxia type is visualized by sampling along the discriminant direction between healthy controls and the ataxia type. Experimental results show that the proposed method can successfully classify healthy controls and different ataxia types. The visualized cerebellar atrophy patterns were consistent with the regional volume decreases observed in previous studies, but the proposed method provides intuitive and detailed understanding about changes of overall size and shape of the cerebellum, as well as that of individual lobules.

  5. Transplantation of cerebellar neural stem cells improves motor coordination and neuropathology in Machado-Joseph disease mice.

    Science.gov (United States)

    Mendonça, Liliana S; Nóbrega, Clévio; Hirai, Hirokazu; Kaspar, Brian K; Pereira de Almeida, Luís

    2015-02-01

    Machado-Joseph disease is a neurodegenerative disease without effective treatment. Patients with Machado-Joseph disease exhibit significant motor impairments such as gait ataxia, associated with multiple neuropathological changes including mutant ATXN3 inclusions, marked neuronal loss and atrophy of the cerebellum. Thus, an effective treatment of symptomatic patients with Machado-Joseph disease may require cell replacement, which we investigated in this study. For this purpose, we injected cerebellar neural stem cells into the cerebellum of adult Machado-Joseph disease transgenic mice and assessed the effect on the neuropathology, neuroinflammation mediators and neurotrophic factor levels and motor coordination. We found that upon transplantation into the cerebellum of adult Machado-Joseph disease mice, cerebellar neural stem cells differentiate into neurons, astrocytes and oligodendrocytes. Importantly, cerebellar neural stem cell transplantation mediated a significant and robust alleviation of the motor behaviour impairments, which correlated with preservation from Machado-Joseph disease-associated neuropathology, namely reduction of Purkinje cell loss, reduction of cellular layer shrinkage and mutant ATXN3 aggregates. Additionally, a significant reduction of neuroinflammation and an increase of neurotrophic factors levels was observed, indicating that transplantation of cerebellar neural stem cells also triggers important neuroprotective effects. Thus, cerebellar neural stem cells have the potential to be used as a cell replacement and neuroprotective approach for Machado-Joseph disease therapy.

  6. A probabilistic atlas of the cerebellar white matter

    NARCIS (Netherlands)

    Baarsen, K.M. van; Kleinnijenhuis, M.; Jbabdi, S.; Sotiropoulos, S.N.; Grotenhuis, J.A.; Cappellen van Walsum, A.M. van

    2016-01-01

    Imaging of the cerebellar cortex, deep cerebellar nuclei and their connectivity are gaining attraction, due to the important role the cerebellum plays in cognition and motor control. Atlases of the cerebellar cortex and nuclei are used to locate regions of interest in clinical and neuroscience studi

  7. Rhythmic finger tapping reveals cerebellar dysfunction in essential tremor

    NARCIS (Netherlands)

    Buijink, A. W. G.; Broersma, M.; van der Stouwe, A. M. M.; van Wingen, G. A.; Groot, P. F. C.; Speelman, J. D.; Maurits, N. M.; van Rootselaar, A. F.

    2015-01-01

    Introduction: Cerebellar circuits are hypothesized to play a central role in the pathogenesis of essential tremor. Rhythmic finger tapping is known to strongly engage the cerebellar motor circuitry. We characterize cerebellar and, more specifically, dentate nucleus function, and neural correlates of

  8. 21 CFR 882.5820 - Implanted cerebellar stimulator.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implanted cerebellar stimulator. 882.5820 Section... (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5820 Implanted cerebellar stimulator. (a) Identification. An implanted cerebellar stimulator is a device used to...

  9. Global dysrhythmia of cerebro-basal ganglia-cerebellar networks underlies motor tics following striatal disinhibition.

    Science.gov (United States)

    McCairn, Kevin W; Iriki, Atsushi; Isoda, Masaki

    2013-01-09

    Motor tics, a cardinal symptom of Tourette syndrome (TS), are hypothesized to arise from abnormalities within cerebro-basal ganglia circuits. Yet noninvasive neuroimaging of TS has previously identified robust activation in the cerebellum. To date, electrophysiological properties of cerebellar activation and its role in basal ganglia-mediated tic expression remain unknown. We performed multisite, multielectrode recordings of single-unit activity and local field potentials from the cerebellum, basal ganglia, and primary motor cortex using a pharmacologic monkey model of motor tics/TS. Following microinjections of bicuculline into the sensorimotor putamen, periodic tics occurred predominantly in the orofacial region, and a sizable number of cerebellar neurons showed phasic changes in activity associated with tic episodes. Specifically, 64% of the recorded cerebellar cortex neurons exhibited increases in activity, and 85% of the dentate nucleus neurons displayed excitatory, inhibitory, or multiphasic responses. Critically, abnormal discharges of cerebellar cortex neurons and excitatory-type dentate neurons mostly preceded behavioral tic onset, indicating their central origins. Latencies of pathological activity in the cerebellum and primary motor cortex substantially overlapped, suggesting that aberrant signals may be traveling along divergent pathways to these structures from the basal ganglia. Furthermore, the occurrence of tic movement was most closely associated with local field potential spikes in the cerebellum and primary motor cortex, implying that these structures may function as a gate to release overt tic movements. These findings indicate that tic-generating networks in basal ganglia mediated tic disorders extend beyond classical cerebro-basal ganglia circuits, leading to global network dysrhythmia including cerebellar circuits.

  10. Paraneoplastic cerebellar dysfunction in Hodgkin's lymphoma

    Directory of Open Access Journals (Sweden)

    Kazi Sazzad Manir

    2015-01-01

    Full Text Available Paraneoplastic cerebellar degeneration (PCD is a rare presentation of Hodgkin's Lymphoma (HL manifests as acute/sub-acute nature. We report a case of 21 yr old male presented with acute cerebellar signs along with underlying HL.MRI brain was normal. CSF study was unremarkable. Patient was treated with six cycles of chemotherapy followed by radiotherapy. Neurological manifestations remarkably improved along with complete resolution of underlying HL. Anti-cancer therapy of underlying HL is the main strategy of treating associated PCD.

  11. MAP Kinase Cascades in Plant Innate Immunity

    Directory of Open Access Journals (Sweden)

    Magnus Wohlfahrt Rasmussen

    2012-07-01

    Full Text Available Plant mitogen-activated protein kinase (MAPK cascades generally transduce extracellular stimuli into cellular responses. These stimuli include the perception of pathogen-associated molecular patterns (PAMPs by host transmembrane pattern recognition receptors (PRRs which trigger MAPK-dependent innate immune responses. In the model Arabidopsis, molecular genetic evidence implicates a number of MAPK cascade components in PAMP signaling, and in responses to immunity-related phytohormones such as ethylene, jasmonate and salicylate. In a few cases, cascade components have been directly linked to the transcription of target genes or to the regulation of phytohormone synthesis. Thus MAPKs are obvious targets for bacterial effector proteins and are likely guardees of resistance (R proteins, which mediate defense signaling in response to the action of effectors, or effector-triggered immunity (ETI. This mini-review discusses recent progress in this field with a focus on the Arabidopsis MAPKs MPK3, 4, 6 and 11 in their apparent pathways.

  12. Depletion of polyamines prevents the neurotrophic activity of the GABA-agonist THIP in cultured rat cerebellar granule cells

    DEFF Research Database (Denmark)

    Abraham, J H; Hansen, Gert Helge; Seiler, N

    1993-01-01

    Effects of polyamine depletion by alpha-difluoromethylornithine (DFMO) were studied on the GABA-agonist mediated enhancement of the morphological development of cultured rat cerebellar granule cells. An increase in the number of neurite extending cells and in the cytoplasmic density of organelles...... endoplasmic reticulum, Golgi apparatus and different types of vesicles was prevented by the exposure to DFMO....

  13. Distributed cerebellar plasticity implements generalized multiple-scale memory components in real-robot sensorimotor tasks

    Directory of Open Access Journals (Sweden)

    Claudia eCasellato

    2015-02-01

    Full Text Available The cerebellum plays a crucial role in motor learning and it acts as a predictive controller. Modeling it and embedding it into sensorimotor tasks allows us to create functional links between plasticity mechanisms, neural circuits and behavioral learning. Moreover, if applied to real-time control of a neurorobot, the cerebellar model has to deal with a real noisy and changing environment, thus showing its robustness and effectiveness in learning. A biologically inspired cerebellar model with distributed plasticity, both at cortical and nuclear sites, has been used. Two cerebellum-mediated paradigms have been designed: an associative Pavlovian task and a vestibulo-ocular reflex, with multiple sessions of acquisition and extinction and with different stimuli and perturbation patterns. The cerebellar controller succeeded to generate conditioned responses and finely tuned eye movement compensation, thus reproducing human-like behaviors. Through a productive plasticity transfer from cortical to nuclear sites, the distributed cerebellar controller showed in both tasks the capability to optimize learning on multiple time-scales, to store motor memory and to effectively adapt to dynamic ranges of stimuli.

  14. GAD Antibody-Associated Late-Onset Cerebellar Ataxia in Two Female Siblings

    Directory of Open Access Journals (Sweden)

    Joseph Kuchling

    2014-11-01

    Full Text Available Background: Anti-glutamic acid decarboxylase antibody (GAD-ab-associated cerebellar ataxia is a rare neurological disorder characterized by cerebellar symptoms concomitant with high GAD-ab levels in serum and cerebrospinal fluid (CSF. Case Report: We report on 2 female siblings (aged 74 and 76 years presenting with gradual progression of rotational vertigo, gait ataxia and vertical diplopia, continuously progressing for 6 months and 6 years, respectively. Autoimmune laboratory examinations showed remarkably increased serum and CSF GAD-ab levels. Their medical histories revealed late-onset type 1 diabetes mellitus (T1DM and other concomitant autoimmune disorders (Grave's disease, Hashimoto's thyroiditis. Cerebral MRI and laboratory examinations were unremarkable. The diagnosis of GAD-ab-associated cerebellar ataxia with particular brainstem involvement was established in both women. After the exclusion of an underlying malignancy, immunosuppressive therapy has been initiated in both patients, which resulted in stabilization in one and in clinical improvement in the other patient. Discussion: The unique association of autoantibody-mediated cerebellar ataxia and late-onset T1DM in 2 siblings with similar clinical and paraclinical phenotypes strengthens the concept that hereditary factors might play a relevant role also in autoimmune diseases so far considered to be sporadic. Moreover, the occurrence of continuous vertical diplopia broadens the clinical spectrum of GAD-ab-associated neurological syndromes.

  15. Cerebellar atrophy is frequently associated with non-paraneoplastic sensory neuronopathy

    Directory of Open Access Journals (Sweden)

    Alfredo Damasceno

    2011-08-01

    Full Text Available Sensory neuronopathies (SN are peripheral nervous system disorders associated with degeneration of dorsal root ganglion neurons. Despite the evidence of a defective proprioceptive sensory input in SN,the prominent gait and truncal ataxia raises the question of a concomitant involvement of the cerebellum. OBJECTIVE: To evaluate cerebellar atrophy in SN. METHOD: We analyzed MRI-based volumetry of anterior lobe (paleocerebellum and total cerebellum in patients with non-paraneoplastic chronic SN and compared to age- and gender-matched controls. RESULTS: Cerebellum and anterior lobe MRI volumetry were performed in 20 patients and nine controls. Mean anterior lobe and cerebellar volume were not statistically different. Three patients (15%, however, had an abnormal anterior lobe and cerebellar volume index (values outside 2.5 standard deviations. One of them also had a specific atrophy of the anterior lobe. All these patients had infectious or dysimmune associated SN. CONCLUSION: Cerebellar atrophy is infrequently associated with SN, but can be found in some patients with SN related to infectious or immune mediated conditions. It can be more prominent in the anterior lobe and may contribute to the ataxia seen in these patients.

  16. Non-progressive cerebellar ataxia and previous undetermined acute cerebellar injury: a mysterious clinical condition

    Directory of Open Access Journals (Sweden)

    Wladimir Bocca Vieira de Rezende Pinto

    2015-01-01

    Full Text Available Cerebellar ataxias represent a wide group of neurological diseases secondary to dysfunctions of cerebellum or its associated pathways, rarely coursing with acute-onset acquired etiologies and chronic non-progressive presentation. We evaluated patients with acquired non-progressive cerebellar ataxia that presented previous acute or subacute onset. Clinical and neuroimaging characterization of adult patients with acquired non-progressive ataxia were performed. Five patients were identified with the phenotype of acquired non-progressive ataxia. Most patients presented with a juvenile to adult-onset acute to subacute appendicular and truncal cerebellar ataxia with mild to moderate cerebellar or olivopontocerebellar atrophy. Establishing the etiology of the acute triggering events of such ataxias is complex. Non-progressive ataxia in adults must be distinguished from hereditary ataxias.

  17. Non-progressive cerebellar ataxia and previous undetermined acute cerebellar injury: a mysterious clinical condition

    Directory of Open Access Journals (Sweden)

    Wladimir Bocca Vieira de Rezende Pinto

    2015-10-01

    Full Text Available Cerebellar ataxias represent a wide group of neurological diseases secondary to dysfunctions of cerebellum or its associated pathways, rarely coursing with acute-onset acquired etiologies and chronic non-progressive presentation. We evaluated patients with acquired non-progressive cerebellar ataxia that presented previous acute or subacute onset. Clinical and neuroimaging characterization of adult patients with acquired non-progressive ataxia were performed. Five patients were identified with the phenotype of acquired non-progressive ataxia. Most patients presented with a juvenile to adult-onset acute to subacute appendicular and truncal cerebellar ataxia with mild to moderate cerebellar or olivopontocerebellar atrophy. Establishing the etiology of the acute triggering events of such ataxias is complex. Non-progressive ataxia in adults must be distinguished from hereditary ataxias.

  18. Case of subacute cerebellar degeneration associated with pleocytosis and cerebellar swelling shown in computed tomography scanning

    Energy Technology Data Exchange (ETDEWEB)

    Yoshino, Hiide; Anezaki, Toshiharu; Takashima, Noriko; Inuzuka, Takashi; Miyatake, Tadashi

    1988-02-01

    A 44 year old woman was healthy until January 3, 1986, when she had headache. On January 9, she developed gait ataxia and dysarthria. Cerebellar ataxia worsened rapidly. Aftar a week she could not sit without support and her consciousness was disturbed. Corticosteroid was administrated and consciousness proved alert, but cerebellar ataxia and dysarthria remained unchanged. The patient was found carcinoma of the lung in August 1986. Characteristic features of clinical and laboratory findings of this patient are acute progression, cerebrospinal fluid pleocytosis of 1,064/3 cells (860 mononuclear cell, 204 polymorphonuclear cell), and cerebellar swelling shown in computed tomography scanning. Though the mechanism of acute cerebellar degeneration is still uncertained, inflammatory process was supported to exist in cerebellum of this case.

  19. Cerebellar Hypoplasia and Dysmorphia in Neurofibromatosis Type 1.

    Science.gov (United States)

    Toelle, Sandra P; Poretti, Andrea; Weber, Peter; Seute, Tatjana; Bromberg, Jacoline E C; Scheer, Ianina; Boltshauser, Eugen

    2015-12-01

    Unidentified bright objects (UBO) and tumors are well-known cerebellar abnormalities in neurofibromatosis type 1 (NF1). Literature reports on malformative cerebellar anomalies in neurofibromatosis type 1 (NF1), however, are scant. We retrospectively studied the clinical and neuroimaging findings of 5 patients with NF1 (4 females, age 6 to 29 years at last follow-up) and cerebellar anomalies. Cerebellar symptoms on neurological examination were mild or even not evident whereas learning disabilities were more or less pronounced in four patients. Two patients had cerebellar hypoplasia (diffusely enlarged cerebellar interfoliar spaces) and three cerebellar dysmorphias involving mainly one cerebellar hemisphere. In NF1, malformative cerebellar anomalies are rare (estimated prevalence of about 1%), but most likely underestimated and easily overlooked, because physicians tend to focus on more prevalent, obvious, and well-known findings such as optic pathway gliomas, other tumors, and UBO. This kind of cerebellar anomaly in NF1 has most likely a malformative origin, but the exact pathogenesis is unknown. The individual clinical significance is difficult to determine. We suggest that cerebellar anomalies should be systematically evaluated in neuroimaging studies of NF1 patients.

  20. Climbing fiber signaling and cerebellar gain control

    NARCIS (Netherlands)

    G. Ohtsuki (Gen); C. Piochon (Claire); C.R.W. Hansel (Christian)

    2009-01-01

    textabstractThe physiology of climbing fiber signals in cerebellar Purkinje cells has been studied since the early days of electrophysiology. Both the climbing fiber-evoked complex spike and the role of climbing fiber activity in the induction of long-term depression (LTD) at parallel fiber-Purkinje

  1. Crossed cerebellar diaschisis in ischemic stroke

    DEFF Research Database (Denmark)

    Meneghetti, G; Vorstrup, S; Mickey, B

    1984-01-01

    depression was evident in five patients with severe hemispheric low flow areas, which correlated with large, hypodense lesions on the computerized tomographic scan. In a sixth patient with a small, deep infarct, a transient crossed cerebellar low flow was observed, while the clinical symptoms persisted...... in the infarcted hemisphere, in which a period of relative hyperemia is frequently seen....

  2. Improving cerebellar segmentation with statistical fusion

    Science.gov (United States)

    Plassard, Andrew J.; Yang, Zhen; Prince, Jerry L.; Claassen, Daniel O.; Landman, Bennett A.

    2016-03-01

    The cerebellum is a somatotopically organized central component of the central nervous system well known to be involved with motor coordination and increasingly recognized roles in cognition and planning. Recent work in multiatlas labeling has created methods that offer the potential for fully automated 3-D parcellation of the cerebellar lobules and vermis (which are organizationally equivalent to cortical gray matter areas). This work explores the trade offs of using different statistical fusion techniques and post hoc optimizations in two datasets with distinct imaging protocols. We offer a novel fusion technique by extending the ideas of the Selective and Iterative Method for Performance Level Estimation (SIMPLE) to a patch-based performance model. We demonstrate the effectiveness of our algorithm, Non- Local SIMPLE, for segmentation of a mixed population of healthy subjects and patients with severe cerebellar anatomy. Under the first imaging protocol, we show that Non-Local SIMPLE outperforms previous gold-standard segmentation techniques. In the second imaging protocol, we show that Non-Local SIMPLE outperforms previous gold standard techniques but is outperformed by a non-locally weighted vote with the deeper population of atlases available. This work advances the state of the art in open source cerebellar segmentation algorithms and offers the opportunity for routinely including cerebellar segmentation in magnetic resonance imaging studies that acquire whole brain T1-weighted volumes with approximately 1 mm isotropic resolution.

  3. Ultrasonically detectable cerebellar haemorrhage in preterm infants.

    LENUS (Irish Health Repository)

    McCarthy, Lisa Kenyon

    2011-07-01

    To determine the frequency and pattern of cerebellar haemorrhage (CBH) on routine cranial ultrasound (cUS) imaging in infants of ≤32 weeks gestation, and to investigate how extremely preterm infants with CBH differ from those with severe intraventricular haemorrhage (IVH).

  4. Cerebellar liponeurocytoma: a case-report

    Directory of Open Access Journals (Sweden)

    K.V. Sreedhar Babu

    Full Text Available Cerebellar liponeurocytoma is a rare cerebellar neoplasm of adults with advanced neuronal / neurocytic and focal lipomatous differentiation, a low proliferative potential and a favorable clinical prognosis corresponding to World Health Organization grade I or II. Only a few cases have been described in the literature (approximately 20 cases by different names. A 48-years old female, presented with history of headache and dizziness associated with neck pain; restricted neck movements, drop attacks and occasional regurgitation of food since one year. Magnetic resonance imaging disclosed a right cerebellar mass lesion. Gross total resec- tion of the tumour was accomplished through a suboccipital craniotomy. The excised tissue was diagnosed as cerebellar liponeurocytoma, a rare entity, based on histopathological examination and immunohistochemistry. The morphological appearance of this neoplasm can be confused with that of oligodendroglioma, neurocytoma, ependymoma, medulloblastoma, solid hemangioblastoma and metastatic carcinomas etc., with unpredictable prognosis, which require postoperative radiotherapy, hence the importance of accurately diagnosing this rare neoplasm. This tumour should be added to the differential diagnosis of mass lesions of the posterior fossa.

  5. Cerebellar cortical inhibition and classical eyeblink conditioning.

    Science.gov (United States)

    Bao, Shaowen; Chen, Lu; Kim, Jeansok J; Thompson, Richard F

    2002-02-01

    The cerebellum is considered a brain structure in which memories for learned motor responses (e.g., conditioned eyeblink responses) are stored. Within the cerebellum, however, the relative importance of the cortex and the deep nuclei in motor learning/memory is not entirely clear. In this study, we show that the cerebellar cortex exerts both basal and stimulus-activated inhibition to the deep nuclei. Sequential application of a gamma-aminobutyric acid type A receptor (GABA(A)R) agonist and a noncompetitive GABA(A)R antagonist allows selective blockade of stimulus-activated inhibition. By using the same sequential agonist and antagonist methods in behaving animals, we demonstrate that the conditioned response (CR) expression and timing are completely dissociable and involve different inhibitory inputs; although the basal inhibition modulates CR expression, the conditioned stimulus-activated inhibition is required for the proper timing of the CR. In addition, complete blockade of cerebellar deep nuclear GABA(A)Rs prevents CR acquisition. Together, these results suggest that different aspects of the memories for eyeblink CRs are encoded in the cerebellar cortex and the cerebellar deep nuclei.

  6. Perinatal Cerebellar Injury in Human and Animal Models

    Directory of Open Access Journals (Sweden)

    Valerie Biran

    2012-01-01

    Full Text Available Cerebellar injury is increasingly recognized through advanced neonatal brain imaging as a complication of premature birth. Survivors of preterm birth demonstrate a constellation of long-term neurodevelopmental deficits, many of which are potentially referable to cerebellar injury, including impaired motor functions such as fine motor incoordination, impaired motor sequencing and also cognitive, behavioral dysfunction among older patients. This paper reviews the morphogenesis and histogenesis of the human and rodent developing cerebellum, and its more frequent injuries in preterm. Most cerebellar lesions are cerebellar hemorrhage and infarction usually leading to cerebellar abnormalities and/or atrophy, but the exact pathogenesis of lesions of the cerebellum is unknown. The different mechanisms involved have been investigated with animal models and are primarily hypoxia, ischemia, infection, and inflammation Exposure to drugs and undernutrition can also induce cerebellar abnormalities. Different models are detailed to analyze these various disturbances of cerebellar development around birth.

  7. Cascade Organic Solar Cells

    KAUST Repository

    Schlenker, Cody W.

    2011-09-27

    We demonstrate planar organic solar cells consisting of a series of complementary donor materials with cascading exciton energies, incorporated in the following structure: glass/indium-tin-oxide/donor cascade/C 60/bathocuproine/Al. Using a tetracene layer grown in a descending energy cascade on 5,6-diphenyl-tetracene and capped with 5,6,11,12-tetraphenyl- tetracene, where the accessibility of the π-system in each material is expected to influence the rate of parasitic carrier leakage and charge recombination at the donor/acceptor interface, we observe an increase in open circuit voltage (Voc) of approximately 40% (corresponding to a change of +200 mV) compared to that of a single tetracene donor. Little change is observed in other parameters such as fill factor and short circuit current density (FF = 0.50 ± 0.02 and Jsc = 2.55 ± 0.23 mA/cm2) compared to those of the control tetracene-C60 solar cells (FF = 0.54 ± 0.02 and Jsc = 2.86 ± 0.23 mA/cm2). We demonstrate that this cascade architecture is effective in reducing losses due to polaron pair recombination at donor-acceptor interfaces, while enhancing spectral coverage, resulting in a substantial increase in the power conversion efficiency for cascade organic photovoltaic cells compared to tetracene and pentacene based devices with a single donor layer. © 2011 American Chemical Society.

  8. Eph receptors are involved in the activity-dependent synaptic wiring in the mouse cerebellar cortex.

    Directory of Open Access Journals (Sweden)

    Roberta Cesa

    Full Text Available Eph receptor tyrosine kinases are involved in many cellular processes. In the developing brain, they act as migratory and cell adhesive cues while in the adult brain they regulate dendritic spine plasticity. Here we show a new role for Eph receptor signalling in the cerebellar cortex. Cerebellar Purkinje cells are innervated by two different excitatory inputs. The climbing fibres contact the proximal dendritic domain of Purkinje cells, where synapse and spine density is low; the parallel fibres contact the distal dendritic domain, where synapse and spine density is high. Interestingly, Purkinje cells have the intrinsic ability to generate a high number of spines over their entire dendritic arborisations, which can be innervated by the parallel fibres. However, the climbing fibre input continuously exerts an activity-dependent repression on parallel fibre synapses, thus confining them to the distal Purkinje cell dendritic domain. Such repression persists after Eph receptor activation, but is overridden by Eph receptor inhibition with EphA4/Fc in neonatal cultured cerebellar slices as well as mature acute cerebellar slices, following in vivo infusion of the EphA4/Fc inhibitor and in EphB receptor-deficient mice. When electrical activity is blocked in vivo by tetrodotoxin leading to a high spine density in Purkinje cell proximal dendrites, stimulation of Eph receptor activation recapitulates the spine repressive effects of climbing fibres. These results suggest that Eph receptor signalling mediates the repression of spine proliferation induced by climbing fibre activity in Purkinje cell proximal dendrites. Such repression is necessary to maintain the correct architecture of the cerebellar cortex.

  9. A probabilistic atlas of the cerebellar white matter.

    Science.gov (United States)

    van Baarsen, K M; Kleinnijenhuis, M; Jbabdi, S; Sotiropoulos, S N; Grotenhuis, J A; van Cappellen van Walsum, A M

    2016-01-01

    Imaging of the cerebellar cortex, deep cerebellar nuclei and their connectivity are gaining attraction, due to the important role the cerebellum plays in cognition and motor control. Atlases of the cerebellar cortex and nuclei are used to locate regions of interest in clinical and neuroscience studies. However, the white matter that connects these relay stations is of at least similar functional importance. Damage to these cerebellar white matter tracts may lead to serious language, cognitive and emotional disturbances, although the pathophysiological mechanism behind it is still debated. Differences in white matter integrity between patients and controls might shed light on structure-function correlations. A probabilistic parcellation atlas of the cerebellar white matter would help these studies by facilitating automatic segmentation of the cerebellar peduncles, the localization of lesions and the comparison of white matter integrity between patients and controls. In this work a digital three-dimensional probabilistic atlas of the cerebellar white matter is presented, based on high quality 3T, 1.25mm resolution diffusion MRI data from 90 subjects participating in the Human Connectome Project. The white matter tracts were estimated using probabilistic tractography. Results over 90 subjects were symmetrical and trajectories of superior, middle and inferior cerebellar peduncles resembled the anatomy as known from anatomical studies. This atlas will contribute to a better understanding of cerebellar white matter architecture. It may eventually aid in defining structure-function correlations in patients with cerebellar disorders.

  10. A toolbox to visually explore cerebellar shape changes in cerebellar disease and dysfunction

    Science.gov (United States)

    Abulnaga, S. Mazdak; Yang, Zhen; Carass, Aaron; Kansal, Kalyani; Jedynak, Bruno M.; Onyike, Chiadi U.; Ying, Sarah H.; Prince, Jerry L.

    2016-03-01

    The cerebellum plays an important role in motor control and is also involved in cognitive processes. Cerebellar function is specialized by location, although the exact topographic functional relationship is not fully understood. The spinocerebellar ataxias are a group of neurodegenerative diseases that cause regional atrophy in the cerebellum, yielding distinct motor and cognitive problems. The ability to study the region-specific atrophy patterns can provide insight into the problem of relating cerebellar function to location. In an effort to study these structural change patterns, we developed a toolbox in MATLAB to provide researchers a unique way to visually explore the correlation between cerebellar lobule shape changes and function loss, with a rich set of visualization and analysis modules. In this paper, we outline the functions and highlight the utility of the toolbox. The toolbox takes as input landmark shape representations of subjects' cerebellar substructures. A principal component analysis is used for dimension reduction. Following this, a linear discriminant analysis and a regression analysis can be performed to find the discriminant direction associated with a specific disease type, or the regression line of a specific functional measure can be generated. The characteristic structural change pattern of a disease type or of a functional score is visualized by sampling points on the discriminant or regression line. The sampled points are used to reconstruct synthetic cerebellar lobule shapes. We showed a few case studies highlighting the utility of the toolbox and we compare the analysis results with the literature.

  11. Hereditary spastic paraplegia with cerebellar ataxia

    DEFF Research Database (Denmark)

    Nielsen, J E; Johnsen, B; Koefoed, P

    2004-01-01

    Complex forms of hereditary spastic paraplegia (HSP) are rare and usually transmitted in an autosomal recessive pattern. A family of four generations with autosomal dominant hereditary spastic paraplegia (AD-HSP) and a complex phenotype with variably expressed co-existing ataxia, dysarthria...... in those individuals who were clinically affected by a complex phenotype consisting of HSP and cerebellar ataxia. Other features noted in this kindred including epilepsy, cognitive impairment, depression, and migraine did not segregate with the HSP phenotype or mutation, and therefore the significance...... relatively decreased regional cerebral blood flow in most of the cerebellum. We conclude that this kindred demonstrates a considerable overlap between cerebellar ataxia and spastic paraplegia, emphasizing the marked clinical heterogeneity of HSP associated with spastin mutations....

  12. An update on Spino-cerebellar ataxias

    Directory of Open Access Journals (Sweden)

    Banashree Mondal

    2013-01-01

    Full Text Available The dominantly inherited ataxias, also known as Spino-cerebellar ataxias (SCAs, are rapidly expanding entities. New mutations are being identified at remarkable regularity. Recent awareness of molecular abnormalities in SCAs has addressed some of the long sought questions, but gaps in knowledge still exist. Three major categories of SCAs, according to molecular mechanisms, have evolved over recent few years: Polyglutamate expansion ataxia, non-coding zone repeat ataxia, and ataxia due to conventional mutation. Using the fulcrum of these mechanisms, the article provides an update of SCAs. Shared and specific clinical features, genetic abnormalities, and possible links between molecular abnormalities and cerebellar degeneration have been discussed. Emphasis has been placed on the mechanisms of polyglutamate toxicity.

  13. Cerebellar Dysfunction in a Patient with HIV.

    Science.gov (United States)

    Gonzalez-Ibarra, Fernando; Abdul, Waheed; Eivaz-Mohammadi, Sahar; Foscue, Christopher; Gongireddy, Srinivas; Syed, Amer

    2014-01-01

    A 50-year-old AIDS patient with a CD4 T-cell count of 114/mm(3) was admitted with cerebellar symptoms of left CN XI weakness, wide-based gait with left-sided dysmetria, abnormal heel-knee-shin test, and dysdiadochokinesia. MRI showed region of hyperintensity in the left inferior cerebellar hemisphere involving the cortex and underlying white matter. Serological tests for HSV1, HSV2, and syphilis were negative. Her CSF contained high protein content and a WBC of 71/mm(3), predominantly lymphocytes. The CSF was also negative for cryptococcal antigen and VDRL. CSF culture did not grow microbes. CSF PCR assay was negative for HSV1 and HSV2 but was positive for JC virus (1,276 copies). The most likely diagnosis is granule cell neuronopathy (GCN), which can only be definitively confirmed with biopsy and immunohistochemistry.

  14. Molecular mechanisms governing competitive synaptic wiring in cerebellar Purkinje cells.

    Science.gov (United States)

    Watanabe, Masahiko

    2008-03-01

    Cerebellar Purkinje cells (PCs) play a principal role in motor coordination and motor learning. To fulfill these functions, PCs receive and integrate two types of excitatory inputs, climbing fiber (CF) and parallel fiber (PF). CFs are projection axons from the inferior olive, and convey error signals to PCs. On the other hand, PFs are T-shaped axons of cerebellar granule cells, and convey sensory and motor information carried through the pontocerebellar and spinocerebellar mossy fiber pathways. The most remarkable feature of PC circuits is the highly territorial innervation by these two excitatory afferents. A single climbing CF powerfully and exclusively innervates proximal PC dendrites, whereas hundreds of thousands of PFs innervate distal PC dendrites. Recent studies using gene-manipulated mice have been elucidating that the PC circuitry is formed and maintained by molecular mechanisms that fuel homosynaptic competition among CFs and heterosynaptic competition between CFs and PFs. GluRdelta2 (a PC-specific glutamate receptor) and precerebellin or Cbln1 (a granule cell-derived secretory protein) cooperatively work for selective strengthening of PF-PC synapses, and prevent excessive distal extension of CFs that eventually causes multiple innervation at distal dendrites. In contrast, P/Q-type Ca2+ channels, which mediate Ca2+ influx upon CF activity, selectively strengthen the innervation by a single main CF, and expel PFs and other CFs from proximal dendrites that it innervates. Therefore, we now understand that owing to these mechanisms, territorial innervation by CFs and PFs is properly structured and mono-innervation by CFs is established. Several key issues for future study are also discussed.

  15. Hereditary spastic paraplegia with cerebellar ataxia

    DEFF Research Database (Denmark)

    Nielsen, J E; Johnsen, B; Koefoed, P

    2004-01-01

    Complex forms of hereditary spastic paraplegia (HSP) are rare and usually transmitted in an autosomal recessive pattern. A family of four generations with autosomal dominant hereditary spastic paraplegia (AD-HSP) and a complex phenotype with variably expressed co-existing ataxia, dysarthria...... relatively decreased regional cerebral blood flow in most of the cerebellum. We conclude that this kindred demonstrates a considerable overlap between cerebellar ataxia and spastic paraplegia, emphasizing the marked clinical heterogeneity of HSP associated with spastin mutations....

  16. Memory consolidation in the cerebellar cortex.

    Directory of Open Access Journals (Sweden)

    Daniel O Kellett

    Full Text Available Several forms of learning, including classical conditioning of the eyeblink, depend upon the cerebellum. In examining mechanisms of eyeblink conditioning in rabbits, reversible inactivations of the control circuitry have begun to dissociate aspects of cerebellar cortical and nuclear function in memory consolidation. It was previously shown that post-training cerebellar cortical, but not nuclear, inactivations with the GABAA agonist muscimol prevented consolidation but these findings left open the question as to how final memory storage was partitioned across cortical and nuclear levels. Memory consolidation might be essentially cortical and directly disturbed by actions of the muscimol, or it might be nuclear, and sensitive to the raised excitability of the nuclear neurons following the loss of cortical inhibition. To resolve this question, we simultaneously inactivated cerebellar cortical lobule HVI and the anterior interpositus nucleus of rabbits during the post-training period, so protecting the nuclei from disinhibitory effects of cortical inactivation. Consolidation was impaired by these simultaneous inactivations. Because direct application of muscimol to the nuclei alone has no impact upon consolidation, we can conclude that post-training, consolidation processes and memory storage for eyeblink conditioning have critical cerebellar cortical components. The findings are consistent with a recent model that suggests the distribution of learning-related plasticity across cortical and nuclear levels is task-dependent. There can be transfer to nuclear or brainstem levels for control of high-frequency responses but learning with lower frequency response components, such as in eyeblink conditioning, remains mainly dependent upon cortical memory storage.

  17. Cascaded Poisson processes

    Science.gov (United States)

    Matsuo, Kuniaki; Saleh, Bahaa E. A.; Teich, Malvin Carl

    1982-12-01

    We investigate the counting statistics for stationary and nonstationary cascaded Poisson processes. A simple equation is obtained for the variance-to-mean ratio in the limit of long counting times. Explicit expressions for the forward-recurrence and inter-event-time probability density functions are also obtained. The results are expected to be of use in a number of areas of physics.

  18. Computed tomography in hypertensive cerebellar hemorrhage

    Energy Technology Data Exchange (ETDEWEB)

    Nose, T.; Maki, Y.; Ono, Y.; Yoshizawa, T.; Tsuboi, K. (Tsukuba Univ., Sakura, Ibaraki (Japan))

    1981-11-01

    Fourteen cases of cerebellar hemorrhage were analysed from the point of CT-scan, and the following results were obtained. 1. The number of cases of cerebellar hemorrhage forms 4.4% of that of total intracranial hemorrhage. 2. Most of the cerebellar hematomas extend upward. Downward extension is rare. 3. In acute dead cases hematomas are 5 cm or more in diameter and lie over bilateral hemispheres with the extension to third or fourth ventricles in CT-scans. 4. Slowly progressive cases are detriorated by the secondary hydrocephalus. 5. In mild cases hematomas are 3cm or less in diameter on CT-scans and the hematoma evacuation is not indicated for these cases. 6. The shunt operation alone is sufficient for the life saving of the slowly progressive cases, but the hematoma evacuation is indicated in these cases if the functional prognosis is taken into consideration. 7. Immediate hematoma evacuation together with the ventricular drainage is considered to be effective for the life saving of the acute fulminant cases.

  19. An integrator circuit in cerebellar cortex.

    Science.gov (United States)

    Maex, Reinoud; Steuber, Volker

    2013-09-01

    The brain builds dynamic models of the body and the outside world to predict the consequences of actions and stimuli. A well-known example is the oculomotor integrator, which anticipates the position-dependent elasticity forces acting on the eye ball by mathematically integrating over time oculomotor velocity commands. Many models of neural integration have been proposed, based on feedback excitation, lateral inhibition or intrinsic neuronal nonlinearities. We report here that a computational model of the cerebellar cortex, a structure thought to implement dynamic models, reveals a hitherto unrecognized integrator circuit. In this model, comprising Purkinje cells, molecular layer interneurons and parallel fibres, Purkinje cells were able to generate responses lasting more than 10 s, to which both neuronal and network mechanisms contributed. Activation of the somatic fast sodium current by subthreshold voltage fluctuations was able to maintain pulse-evoked graded persistent activity, whereas lateral inhibition among Purkinje cells via recurrent axon collaterals further prolonged the responses to step and sine wave stimulation. The responses of Purkinje cells decayed with a time-constant whose value depended on their baseline spike rate, with integration vanishing at low ( 30 per s). The model predicts that the apparently fast circuit of the cerebellar cortex may control the timing of slow processes without having to rely on sensory feedback. Thus, the cerebellar cortex may contain an adaptive temporal integrator, with the sensitivity of integration to the baseline spike rate offering a potential mechanism of plasticity of the response time-constant.

  20. The microvasculature of the human cerebellar meninges.

    Science.gov (United States)

    Nonaka, Hiroko; Akima, Michiko; Hatori, Tsutomu; Nagayama, Tadashi; Zhang, Zean; Ihara, Fumie

    2002-12-01

    The vascular architecture of the human cerebellar meninges was investigated. The surface meninges were poor in vasculature. In the sulci, the meninges were highly vascular but had few capillaries. The venous blood vessels gave long side branches at right angles to the parent vessels in a cruciform pattern, running horizontally along the cerebellar sulci. They were situated at the origin of the secondary or tertiary sulci. Anastomoses between these horizontal branches gave a crosshatched appearance. Short branches often extended to the bases of the sulci, terminating in T-shaped bifurcations with numerous tiny branches, like the roots of a tree. The arteries ran perpendicular to venous branches which were parallel to each other exclusively along the sagittal plane. These arteries bifurcated to straddle the horizontally running veins at the origin of the secondary or tertiary sulci. They gave off many small branches like teeth of a fork from each artery in the secondary or tertiary sulci after they bifurcated to straddle the venous branches and penetrated the cerebellar cortex at the bases of sulci. These fork-like ramifications in the bases of the sulci were most likely responsible for the ready development of pronounced ischemic state. They might also play an important role in the occurrence of ischemic damage at the bases of sulci in cases of severe generalized ischemia.

  1. Emotional disorders in patients with cerebellar damage – case studies

    OpenAIRE

    Siuda, Katarzyna; Chrobak, Adrian Andrzej; Starowicz-Filip, Anna; Tereszko,Anna; Dudek, Dominika

    2014-01-01

    Aim: Growing number of research shows the role of the cerebellum in the regulation of affect. Lesions of the cerebellum can lead to emotional disregulation, a significant part of the Cerebellar Cognitive Affective Syndrome. The aim of this article is to analyze the most recent studies concerning the cerebellar participation in emotional reactions and to present three cases: two female and one male who suffered from cerebellar damage and presented post-traumatic affective and personality chang...

  2. Cerebro-cerebellar circuits in autism spectrum disorder.

    Science.gov (United States)

    D'Mello, Anila M; Stoodley, Catherine J

    2015-01-01

    The cerebellum is one of the most consistent sites of abnormality in autism spectrum disorder (ASD) and cerebellar damage is associated with an increased risk of ASD symptoms, suggesting that cerebellar dysfunction may play a crucial role in the etiology of ASD. The cerebellum forms multiple closed-loop circuits with cerebral cortical regions that underpin movement, language, and social processing. Through these circuits, cerebellar dysfunction could impact the core ASD symptoms of social and communication deficits and repetitive and stereotyped behaviors. The emerging topography of sensorimotor, cognitive, and affective subregions in the cerebellum provides a new framework for interpreting the significance of regional cerebellar findings in ASD and their relationship to broader cerebro-cerebellar circuits. Further, recent research supports the idea that the integrity of cerebro-cerebellar loops might be important for early cortical development; disruptions in specific cerebro-cerebellar loops in ASD might impede the specialization of cortical regions involved in motor control, language, and social interaction, leading to impairments in these domains. Consistent with this concept, structural, and functional differences in sensorimotor regions of the cerebellum and sensorimotor cerebro-cerebellar circuits are associated with deficits in motor control and increased repetitive and stereotyped behaviors in ASD. Further, communication and social impairments are associated with atypical activation and structure in cerebro-cerebellar loops underpinning language and social cognition. Finally, there is converging evidence from structural, functional, and connectivity neuroimaging studies that cerebellar right Crus I/II abnormalities are related to more severe ASD impairments in all domains. We propose that cerebellar abnormalities may disrupt optimization of both structure and function in specific cerebro-cerebellar circuits in ASD.

  3. Acute bilateral cerebellar infarction in the territory of the medial branches of posterior inferior cerebellar arteries.

    Science.gov (United States)

    Gurer, G; Sahin, G; Cekirge, S; Tan, E; Saribas, O

    2001-10-01

    The most frequent type of cerebellar infarcts involved the posterior inferior cerebellar artery (PICA) and superior cerebellar artery territories but bilateral involvement of lateral or medial branches of PICA is extremely rare. In this report, we present a 55-year-old male who admitted to hospital with vomiting, nausea and dizziness. On examination left-sided hemiparesia and ataxic gait were detected. Infarct on bilateral medial branch of PICA artery territories was found out with cranial magnetic resonance imaging (MRI) technique and 99% stenosis of the left vertebral artery was found out with digital subtraction arteriography. The patient was put on heparin treatment. After 3 weeks, his complaints and symptoms had disappeared except for mild gait ataxia.

  4. Integrated Broadband Quantum Cascade Laser

    Science.gov (United States)

    Mansour, Kamjou (Inventor); Soibel, Alexander (Inventor)

    2016-01-01

    A broadband, integrated quantum cascade laser is disclosed, comprising ridge waveguide quantum cascade lasers formed by applying standard semiconductor process techniques to a monolithic structure of alternating layers of claddings and active region layers. The resulting ridge waveguide quantum cascade lasers may be individually controlled by independent voltage potentials, resulting in control of the overall spectrum of the integrated quantum cascade laser source. Other embodiments are described and claimed.

  5. Cerebellar ataxia as the presenting manifestation of Lyme disease.

    Science.gov (United States)

    Arav-Boger, Ravit; Crawford, Thomas; Steere, Allen C; Halsey, Neal A

    2002-04-01

    A 7-year-old boy from suburban Baltimore who presented with cerebellar ataxia and headaches was found by magnetic resonance imaging to have multiple cerebellar enhancing lesions. He had no history of tick exposure. He was initially treated with steroids for presumptive postinfectious encephalitis. Lyme disease was diagnosed 10 weeks later after arthritis developed. Testing of the cerebrospinal fluid obtained at the time cerebellar ataxia was diagnosed revealed intrathecal antibody production to Borrelia burgdorferi. Treatment with intravenous antibiotics led to rapid resolution of persistent cerebellar findings.

  6. Pitch discrimination in cerebellar patients: evidence for a sensory deficit.

    Science.gov (United States)

    Parsons, Lawrence M; Petacchi, Augusto; Schmahmann, Jeremy D; Bower, James M

    2009-12-15

    In the last two decades, a growing body of research showing cerebellar involvement in an increasing number of nonmotor tasks and systems has prompted an expansion of speculations concerning the function of the cerebellum. Here, we tested the predictions of a hypothesis positing cerebellar involvement in sensory data acquisition. Specifically, we examined the effect of global cerebellar degeneration on primary auditory sensory function by means of a pitch discrimination task. The just noticeable difference in pitch between two tones was measured in 15 healthy controls and in 15 high functioning patients afflicted with varying degrees of global cerebellar degeneration caused by hereditary, idiopathic, paraneoplastic, or postinfectious pancerebellitis. Participants also performed an auditory detection task assessing sustained attention, a test of verbal auditory working memory, and an audiometric test. Patient pitch discrimination thresholds were on average five and a half times those of controls and were proportional to the degree of cerebellar ataxia assessed independently. Patients and controls showed normal hearing thresholds and similar performance in control tasks in sustained attention and verbal auditory working memory. These results suggest there is an effect of cerebellar degeneration on primary auditory function. The findings are consistent with other recent demonstrations of cerebellar-related sensory impairments, and with robust cerebellar auditorily evoked activity, confirmed by quantitative meta-analysis, across a range of functional neuroimaging studies dissociated from attention, motor, affective, and cognitive variables. The data are interpreted in the context of a sensory hypothesis of cerebellar function.

  7. A new cascadic multigrid

    Institute of Scientific and Technical Information of China (English)

    SHI; Zhongci

    2001-01-01

    [1]Bornemann, F., Deuflhard, P., The cascadic multigrid method for elliptic problems, Numer. Math., 996, 75: 35.[2]Bornemann, F., Deuflhard, P., The cascadic multigrid method, The Eighth International Conference on Domain Decomposition Methods for Partial Differential Equations (eds. Glowinski, R., Periaux, J., Shi, Z. et al.), New York: John Wiley and Sons, 997.[3]Bornemann, F., Krause, R., Classical and cascadic multigrid-methodogical comparison, Proceedings of the 9th International Conference on Domain Decomposition (eds. Bjorstad, P., Espedal, M., Keyes, D.), New York: John Wiley and Sons, 998.[4]Shaidurov, V., Some estimates of the rate of convergence for the cascadic conjugate gradient method, Comp. Math. Applic., 996, 3: 6.[5]Shi, Z., Xu, X., Cascadic multigrid method for the second order elliptic problem, East-West J. Numer. Math., 998, 6: 309.[6]Shi, Z., Xu, X., Cascadic multigrid for elliptic problems, East-West J. Numer. Math., 999, 7: 99.[7]Shi, Z., Xu, X., Cascadic multigrid method for the plate bending problem, East-West J. Numer. Math., 998, 6: 37.[8]Braess, D., Dahmen, W., A cascade multigrid algorithm for the Stokes equations, Number. Math., 999, 82: 79.[9]Shi, Z., Xu, X., Cascadic multigrid for parabolic problems, J. Comput. Math., 2000, 8: 450.[10]Ciarlet, P.,The Finite Element Method for Elliptic Problems, Amsterdam: North-Holland, 978.[11]Zienkiewicz, O. C., The Finite Element Method, 3rd. ed., London: McGraw-Hill, 977.[12]Powell, M. J. D., Sabin, M. A., Piecewise quadratic approximations on triangles, ACM Trans. Mat. Software, 977, 3: 36.[13]Xu, J., The auxiliary space method and optimal multigrid precondition techniques for unstructured grids, Computing, 996, 56: 25.[14]Bank, R., Dupont, T., An optimal order process for solving finite element equations, Math. Comput., 980, 36: 35.[15]Brenner, S., Convergence of nonconforming multigrid methods without full elliptic regularity, Math

  8. Changes in cerebellar activity and inter-hemispheric coherence accompany improved reading performance following Quadrato Motor Training

    Directory of Open Access Journals (Sweden)

    Tal Dotan Ben-Soussan

    2014-05-01

    Full Text Available Dyslexia is a multifactorial reading deficit that involves multiple brain systems. Among other theories, it has been suggested that cerebellar dysfunction may be involved in dyslexia. This theory has been supported by findings from anatomical and functional imaging. A possible rationale for cerebellar involvement in dyslexia could lie in the cerebellum’s role as an oscillator, producing synchronized activity within neuronal networks including sensorimotor networks critical for reading. If these findings are causally related to dyslexia, a training regimen that enhances cerebellar oscillatory activity should improve reading performance. We examined the cognitive and neural effects of Quadrato Motor Training (QMT, a structured sensorimotor training program that involves sequencing of motor responses based on verbal commands. Twenty-two adult Hebrew readers (12 dyslexics and 10 controls were recruited for the study. Using Magnetoencephalography (MEG, we measured changes in alpha power and coherence following QMT in a within-subject design. Reading performance was assessed pre- and post-training using a comprehensive battery of behavioral tests. Our results demonstrate improved performance on a speeded reading task following one month of intensive QMT in both the dyslexic and control groups. Dyslexic participants, but not controls, showed significant increase in cerebellar oscillatory alpha power following training. In addition, across both time points, inter-hemispheric alpha coherence was higher in the dyslexic group compared to the control group. In conclusion, the current findings suggest that the combination of motor and language training embedded in QMT increases cerebellar oscillatory activity in dyslexics and improves reading performance. These results support the hypothesis that the cerebellum plays a role in skilled reading, and begin to unravel the underlying mechanisms that mediate cerebellar contribution in cognitive and neuronal

  9. Information cascade on networks

    Science.gov (United States)

    Hisakado, Masato; Mori, Shintaro

    2016-05-01

    In this paper, we discuss a voting model by considering three different kinds of networks: a random graph, the Barabási-Albert (BA) model, and a fitness model. A voting model represents the way in which public perceptions are conveyed to voters. Our voting model is constructed by using two types of voters-herders and independents-and two candidates. Independents conduct voting based on their fundamental values; on the other hand, herders base their voting on the number of previous votes. Hence, herders vote for the majority candidates and obtain information relating to previous votes from their networks. We discuss the difference between the phases on which the networks depend. Two kinds of phase transitions, an information cascade transition and a super-normal transition, were identified. The first of these is a transition between a state in which most voters make the correct choices and a state in which most of them are wrong. The second is a transition of convergence speed. The information cascade transition prevails when herder effects are stronger than the super-normal transition. In the BA and fitness models, the critical point of the information cascade transition is the same as that of the random network model. However, the critical point of the super-normal transition disappears when these two models are used. In conclusion, the influence of networks is shown to only affect the convergence speed and not the information cascade transition. We are therefore able to conclude that the influence of hubs on voters' perceptions is limited.

  10. Thyroid hormone promotes transient nerve growth factor synthesis in rat cerebellar neuroblasts.

    Science.gov (United States)

    Charrasse, S; Jehan, F; Confort, C; Brachet, P; Clos, J

    1992-01-01

    Primary cultures of cerebellum from 5-day-old rats indicated that proliferating neuroblasts synthesize and release nerve growth factor (NGF). Since NGF promotes DNA synthesis in these cells, our findings demonstrate that the early developing cerebellum is a suitable physiological model for studying the autocrine mitogenic action of NGF. Thyroid deficiency led to a greater reduction in the NGF content of the cerebellum than of the olfactory bulbs or hippocampus. Cerebellar NGF mRNA was also very sensitive to hormone deprivation. Physiological amounts of thyroid hormone stimulated both the mitotic activity and NGF production of cultured cerebellar neuroblasts. A lack of thyroid hormone is known to markedly alter cell formation in the cerebellum where postnatal neurogenesis is highly significant, in contrast to the olfactory bulbs and hippocampus. Taken together, these results suggest that the hormonal control of cell formation in the cerebellum is, at least partly, mediated by the autocrine mitogenic action of NGF. The thyroid hormone could temporally regulate the transient NGF synthesis by cerebellar neuroblasts directly and/or through its ontogenetic action, and hence all the NGF-dependent trophic effects.

  11. The 5-HT7 receptor triggers cerebellar long-term synaptic depression via PKC-MAPK.

    Science.gov (United States)

    Lippiello, Pellegrino; Hoxha, Eriola; Speranza, Luisa; Volpicelli, Floriana; Ferraro, Angela; Leopoldo, Marcello; Lacivita, Enza; Perrone-Capano, Carla; Tempia, Filippo; Miniaci, Maria Concetta

    2016-02-01

    The 5-HT7 receptor (5-HT7R) mediates important physiological effects of serotonin, such as memory and emotion, and is emerging as a therapeutic target for the treatment of cognitive disorders and depression. Although previous studies have revealed an expression of 5-HT7R in cerebellum, particularly at Purkinje cells, its functional role and signaling mechanisms have never been described. Using patch-clamp recordings in cerebellar slices of adult mice, we investigated the effects of a selective 5-HT7R agonist, LP-211, on the main plastic site of the cerebellar cortex, the parallel fiber-Purkinje cell synapse. Here we show that 5-HT7R activation induces long-term depression of parallel fiber-Purkinje cell synapse via a postsynaptic mechanism that involves the PKC-MAPK signaling pathway. Moreover, a 5-HT7R antagonist abolished the expression of PF-LTD, produced by pairing parallel fiber stimulation with Purkinje cell depolarization; whereas, application of a 5-HT7R agonist impaired LTP induced by 1 Hz parallel fiber stimulation. Our results indicate for the first time that 5-HT7R exerts a fine regulation of cerebellar bidirectional synaptic plasticity that might be involved in cognitive processes and neuropsychiatric disorders involving the cerebellum.

  12. From Cerebellar Activation and Connectivity to Cognition: A Review of the Quadrato Motor Training

    Directory of Open Access Journals (Sweden)

    Tal Dotan Ben-Soussan

    2015-01-01

    Full Text Available The importance of the cerebellum is increasingly recognized, not only in motor control but also in cognitive learning and function. Nevertheless, the relationship between training-induced cerebellar activation and electrophysiological and structural changes in humans has yet to be established. In the current paper, we suggest a general model tying cerebellar function to cognitive improvement, via neuronal synchronization, as well as biochemical and anatomical changes. We then suggest that sensorimotor training provides an optimal paradigm to test the proposed model and review supporting evidence of Quadrato Motor Training (QMT, a sensorimotor training aimed at increasing attention and coordination. Subsequently, we discuss the possible mechanisms through which QMT may exert its beneficial effects on cognition (e.g., increased creativity, reflectivity, and reading, focusing on cerebellar alpha activity as a possible mediating mechanism allowing cognitive improvement, molecular and anatomical changes. Using the example of QMT research, this paper emphasizes the importance of investigating whole-body sensorimotor training paradigms utilizing a multidisciplinary approach and its implications to healthy brain development.

  13. Drug-induced cerebellar ataxia: a systematic review

    NARCIS (Netherlands)

    Gaalen, J. van; Kerstens, F.G.; Maas, R.P.P.W.M.; Harmark, L.; Warrenburg, B.P.C. van de

    2014-01-01

    BACKGROUND AND OBJECTIVES: Cerebellar ataxia can be induced by a large number of drugs. We here conducted a systemic review of the drugs that can lead to cerebellar ataxia as an adverse drug reaction (ADR). METHODS: We performed a systematic literature search in Pubmed (1966 to January 2014) and EMB

  14. Cerebellar pleomorphic xanthoastrocytoma in a patient with neurofibromatosis type 1

    Energy Technology Data Exchange (ETDEWEB)

    Naidich, M.J.; Walker, M.T.; Han, G. [Northwestern University Feinberg School of Medicine, Department of Radiology, Chicago, Illinois (United States); Northwestern Memorial Hospital, Chicago, IL (United States); Gottardi-Littell, N.R. [Northwestern Memorial Hospital, Chicago, IL (United States); Northwestern University Feinberg School of Medicine, Department of Pathology, Chicago, Illinois (United States); Chandler, J.P. [Northwestern Memorial Hospital, Chicago, IL (United States); Northwestern University Feinberg School of Medicine, Department of Neurological Surgery, Chicago, Illinois (United States)

    2004-10-01

    We describe a case of cerebellar pleomorphic xanthoastrocytoma (PXA) occurring in a patient with neurofibromatosis type 1 (NF1). The histomorphology of this uncommon glial (astrocytic) neoplasm is discussed. The occurrence of this tumor within the posterior fossa is extremely rare. To our knowledge, this is the first reported case of a cerebellar PXA in a patient with NF1. (orig.)

  15. Excitatory Cerebellar Nucleocortical Circuit Provides Internal Amplification during Associative Conditioning

    NARCIS (Netherlands)

    Gao, Zhenyu; Proietti-Onori, Martina; Lin, Zhanmin; Ten Brinke, Michiel M; Boele, Henk-Jan; Potters, Jan-Willem; Ruigrok, Tom J H; Hoebeek, Freek E; De Zeeuw, Chris I

    2016-01-01

    Closed-loop circuitries between cortical and subcortical regions can facilitate precision of output patterns, but the role of such networks in the cerebellum remains to be elucidated. Here, we characterize the role of internal feedback from the cerebellar nuclei to the cerebellar cortex in classical

  16. Cerebellar cortical infarct cavities and vertebral artery disease

    Energy Technology Data Exchange (ETDEWEB)

    Cocker, Laurens J.L. de [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Kliniek Sint-Jan Radiologie, Brussels (Belgium); Compter, A.; Kappelle, L.J.; Worp, H.B. van der [University Medical Center Utrecht, Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, Utrecht (Netherlands); Luijten, P.R.; Hendrikse, J. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands)

    2016-09-15

    Cerebellar cortical infarct cavities are a newly recognised entity associated with atherothromboembolic cerebrovascular disease and worse physical functioning. We aimed to investigate the relationship of cerebellar cortical infarct cavities with symptomatic vertebrobasilar ischaemia and with vascular risk factors. We evaluated the MR images of 46 patients with a recent vertebrobasilar TIA or stroke and a symptomatic vertebral artery stenosis ≥50 % from the Vertebral Artery Stenting Trial (VAST) for the presence of cerebellar cortical infarct cavities ≤1.5 cm. At inclusion in VAST, data were obtained on age, sex, history of vertebrobasilar TIA or stroke, and vascular risk factors. Adjusted risk ratios were calculated with Poisson regression analyses for the relation between cerebellar cortical infarct cavities and vascular risk factors. Sixteen out of 46 (35 %) patients showed cerebellar cortical infarct cavities on the initial MRI, and only one of these 16 patients was known with a previous vertebrobasilar TIA or stroke. In patients with symptomatic vertebrobasilar ischaemia, risk factor profiles of patients with cerebellar cortical infarct cavities were not different from patients without these cavities. Cerebellar cortical infarct cavities are seen on MRI in as much as one third of patients with recently symptomatic vertebral artery stenosis. Since patients usually have no prior history of vertebrobasilar TIA or stroke, cerebellar cortical infarct cavities should be added to the spectrum of common incidental brain infarcts visible on routine MRI. (orig.)

  17. Molecular markers of neuronal progenitors in the embryonic cerebellar anlage.

    Science.gov (United States)

    Morales, Daniver; Hatten, Mary E

    2006-11-22

    The cerebellum, like the cerebrum, includes a nuclear structure and an overlying cortical structure. Experiments in the past decade have expanded knowledge beyond the traditional function of the cerebellum to include critical roles in motor learning and memory and sensory discrimination. The initial steps in cerebellar development depend on inductive signaling involving FGF and Wnt proteins produced at the mesencephalic/metencephalic boundary. To address the issue of how individual cerebellar cell fates within the cerebellar territory are specified, we examined the expression of transcription factors, including mammalian homologues of LIM homeodomain-containing proteins, basic helix-loop-helix proteins, and three amino acid loop-containing proteins. The results of these studies show that combinatorial codes of transcription factors define precursors of the cerebellar nuclei, and both Purkinje cells and granule neurons of the cerebellar cortex. Examination of gene expression patterns in several hundred lines of Egfp-BAC (bacterial artificial chromosome) transgenic mice in the GENSAT Project revealed numerous genes with restricted expression in cerebellar progenitor populations, including genes specific for cerebellar nuclear precursors and Purkinje cell precursors. In addition, we identified patterns of gene expression that link granule and Purkinje cells to their precerebellar nuclei. These results identify molecular pathways that offer new insights on the development of the nuclear and cortical structures of the cerebellum, as well as components of the cerebellar circuitry.

  18. New evidence for the cerebellar involvement in personality traits.

    Science.gov (United States)

    Picerni, Eleonora; Petrosini, Laura; Piras, Fabrizio; Laricchiuta, Daniela; Cutuli, Debora; Chiapponi, Chiara; Fagioli, Sabrina; Girardi, Paolo; Caltagirone, Carlo; Spalletta, Gianfranco

    2013-01-01

    Following the recognition of its role in sensory-motor coordination and learning, the cerebellum has been involved in cognitive, emotional, and even personality domains. This study investigated the relationships between cerebellar macro- and micro-structural variations and temperamental traits measured by Temperament and Character Inventory (TCI). High resolution T1-weighted, and Diffusion Tensor Images of 100 healthy subjects aged 18-59 years were acquired by 3 Tesla Magnetic Resonance scanner. In multiple regression analyses, cerebellar Gray Matter (GM) or White Matter (WM) volumes, GM Mean Diffusivity (MD), and WM Fractional Anisotropy (FA) were used as dependent variables, TCI scores as regressors, gender, age, and education years as covariates. Novelty Seeking scores were associated positively with the cerebellar GM volumes and FA, and negatively with MD. No significant association between Harm Avoidance, Reward Dependence or Persistence scores and cerebellar structural measures was found. The present data put toward a cerebellar involvement in the management of novelty.

  19. Electrophysiological Monitoring of Injury ProgressionIn the Rat Cerebellar Cortex

    Directory of Open Access Journals (Sweden)

    Gokhan eOrdek

    2014-10-01

    Full Text Available The changes of excitability in affected neural networks can be used as a marker to study the temporal course of traumatic brain injury (TBI. The cerebellum is an ideal platform to study brain injury mechanisms at the network level using the electrophysiological methods. Within its crystalline morphology, the cerebellar cortex contains highly organized topographical subunits that are defined by two main inputs, the climbing and mossy fibers. Here we demonstrate the use of cerebellar evoked potentials (EPs mediated through these afferent systems for monitoring the injury progression in a rat model of fluid percussion injury (FPI. A mechanical tap on the dorsal hand was used as a stimulus, and EPs were recorded from the paramedian lobule (PML of the posterior cerebellum via multi-electrode arrays (MEA. Post-injury evoked response amplitudes (EPAs were analyzed on a daily basis for one week and compared with pre-injury values. We found a trend of consistently decreasing EPAs in all nine animals, losing as much as 72±4% of baseline amplitudes measured before the injury. Notably, our results highlighted two particular time windows; the first 24 hours of injury in the acute period and day-3 to day-7 in the delayed period where the largest drops (~50% and 24% were observed in the EPAs. In addition, cross-correlations of spontaneous signals between electrode pairs declined (from 0.47±0.1 to 0.35±0.04, p<0.001 along with the EPAs throughout the week of injury. In support of the electrophysiological findings, immunohistochemical analysis at day-7 post-injury showed detectable Purkinje cell loss at low FPI pressures and more with the largest pressures used. Our results suggest that sensory evoked potentials recorded from the cerebellar surface can be a useful technique to monitor the course of cerebellar injury and identify the phases of injury progression even at mild levels.

  20. Disorganized foliation of unilateral cerebellar hemisphere as cerebellar cortical dysplasia in patients with recurrent seizures: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Hye Jin [Dept. of Radiology, Haeundae Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of)

    2013-09-15

    We present a rare case of abnormal foliation for one cerebellar hemisphere on MR imaging, showing vertically-oriented folia. Foliation of contralateral cerebellar hemisphere and other structures in the posterior fossa were normal, and the patient has no neurologic deficits. This rare and unique abnormality is considered a kind of developmental error of the cerebellum.

  1. Acute ethanol exposure inhibits silencing of cerebellar Golgi cell firing induced by granule cell axon input

    Directory of Open Access Journals (Sweden)

    Paolo eBotta

    2014-02-01

    Full Text Available Golgi cells (GoCs are specialized interneurons that provide inhibitory input to granule cells in the cerebellar cortex. GoCs are pacemaker neurons that spontaneously fire action potentials, triggering spontaneous inhibitory postsynaptic currents in granule cells and also contributing to the generation tonic GABAA receptor-mediated currents in granule cells. In turn, granule cell axons provide feedback glutamatergic input to GoCs. It has been shown that high frequency stimulation of granule cell axons induces a transient pause in GoC firing in a type 2-metabotropic glutamate receptor (mGluR2-dependent manner. Here, we investigated the effect ethanol on the pause of GoC firing induced by high frequency stimulation of granule cell axons. GoC electrophysiological recordings were performed in parasagittal cerebellar vermis slices from postnatal day 23 to 26 rats. Loose-patch cell-attached recordings revealed that ethanol (40 mM reversibly decreases the pause duration. An antagonist of mGluR2 reduced the pause duration but did not affect the effect of ethanol. Whole-cell voltage-clamp recordings showed that currents evoked by an mGluR2 agonist were not significantly affected by ethanol. Perforated-patch experiments in which hyperpolarizing and depolarizing currents were injected into GoCs demonstrated that there is an inverse relationship between spontaneous firing and pause duration. Slight inhibition of the Na+/K+ pump mimicked the effect of ethanol on pause duration. In conclusion, ethanol reduces the granule cell axon-mediated feedback mechanism by reducing the input responsiveness of GoCs. This would result in a transient increase of GABAA receptor-mediated inhibition of granule cells, limiting information flow at the input stage of the cerebellar cortex.

  2. Cerebellar ependymal cyst in a dog.

    Science.gov (United States)

    Wyss-Fluehmann, G; Konar, M; Jaggy, A; Vandevelde, M; Oevermann, A

    2008-11-01

    An 11-week-old, male, Staffordshire Bull Terrier had a history of generalized ataxia and falling since birth. The neurologic findings suggested a localization in the cerebellum. Magnetic resonance imaging of the brain was performed. In all sequences the area of the cerebellum was almost replaced by fluid isointense to cerebrospinal fluid. A complete necropsy was performed after euthanasia. Histologically, the lesion was characterized by extensive loss of cerebellar tissue in both hemispheres and vermis. Toward the surface of the cerebellar defect, the cavity was confined by ruptured and folded membranes consisting of a layer of glial fibrillary acidic (GFAP)-positive glial cells covered multifocally by epithelial cells. Some of these cells bore apical cilia and were cytokeratin and GFAP negative, supporting their ependymal origin. The histopathologic features of our case are consistent with the diagnosis of an ependymal cyst. Its glial and ependymal nature as demonstrated by histopathologic and immunohistochemical examination differs from arachnoid cysts, which have also been reported in dogs. The origin of these cysts remains controversial, but it has been suggested that they develop during embryogenesis subsequent to sequestration of developing neuroectoderm. We speculate that the cyst could have been the result of a pre- or perinatal, possibly traumatic, insult because hemorrhage, and tissue destruction had occurred. To our knowledge, this is the first description of an ependymal cyst in the veterinary literature.

  3. Remote cerebellar hemorrhage after lumbar spinal surgery

    Energy Technology Data Exchange (ETDEWEB)

    Cevik, Belma [Baskent University Faculty of Medicine, Department of Radiology, Fevzi Cakmak Cad. 10. sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: belmac@baskent-ank.edu.tr; Kirbas, Ismail; Cakir, Banu; Akin, Kayihan; Teksam, Mehmet [Baskent University Faculty of Medicine, Department of Radiology, Fevzi Cakmak Cad. 10. sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)

    2009-04-15

    Background: Postoperative remote cerebellar hemorrhage (RCH) as a complication of lumbar spinal surgery is an increasingly recognized clinical entity. The aim of this study was to determine the incidence of RCH after lumbar spinal surgery and to describe diagnostic imaging findings of RCH. Methods: Between October 1996 and March 2007, 2444 patients who had undergone lumbar spinal surgery were included in the study. Thirty-seven of 2444 patients were scanned by CT or MRI due to neurologic symptoms within the first 7 days of postoperative period. The data of all the patients were studied with regard to the following variables: incidence of RCH after lumbar spinal surgery, gender and age, coagulation parameters, history of previous arterial hypertension, and position of lumbar spinal surgery. Results: The retrospective study led to the identification of two patients who had RCH after lumbar spinal surgery. Of 37 patients who had neurologic symptoms, 29 patients were women and 8 patients were men. CT and MRI showed subarachnoid hemorrhage in the folia of bilateral cerebellar hemispheres in both patients with RCH. The incidence of RCH was 0.08% among patients who underwent lumbar spinal surgery. Conclusion: RCH is a rare complication of lumbar spinal surgery, self-limiting phenomenon that should not be mistaken for more ominous pathologic findings such as hemorrhagic infarction. This type of bleeding is thought to occur secondary to venous infarction, but the exact pathogenetic mechanism is unknown. CT or MRI allowed immediate diagnosis of this complication and guided conservative management.

  4. Vestibular and cerebellar contribution to gaze optimality.

    Science.gov (United States)

    Sağlam, Murat; Glasauer, Stefan; Lehnen, Nadine

    2014-04-01

    Patients with chronic bilateral vestibular loss have large gaze variability and experience disturbing oscillopsia, which impacts physical and social functioning, and quality of life. Gaze variability and oscillopsia in these patients are attributed to a deficient vestibulo-ocular reflex, i.e. impaired online feedback motor control. Here, we assessed whether the lack of vestibular input also affects feed-forward motor learning, i.e. the ability to choose optimal movement parameters that minimize variability during active movements such as combined eye-head gaze shifts. A failure to learn from practice and reshape feed-forward motor commands in response to sensory error signals to achieve appropriate movements has been proposed to explain dysmetric gaze shifts in patients with cerebellar ataxia. We, therefore, assessed the differential roles of both sensory vestibular information and the cerebellum in choosing optimal movement kinematics. We have previously shown that, in the course of several gaze shifts, healthy subjects adjust the motor command to minimize endpoint variability also when movements are experimentally altered by an increase in the head moment of inertia. Here, we increased the head inertia in five patients with chronic complete bilateral vestibular loss (aged 45.4±7.1 years, mean±standard deviation), nine patients with cerebellar ataxia (aged 56.7±12.6 years), and 10 healthy control subjects (aged 39.7±6.3 years) while they performed large (75° and 80°) horizontal gaze shifts towards briefly flashed targets in darkness and, using our previous optimal control model, compared their gaze shift parameters to the expected optimal movements with increased head inertia. Patients with chronic bilateral vestibular loss failed to update any of the gaze shift parameters to the new optimum with increased head inertia. Consequently, they displayed highly variable, suboptimal gaze shifts. Patients with cerebellar ataxia updated some movement parameters to

  5. Period-doubling cascades galore

    OpenAIRE

    Sander, Evelyn; Yorke, James A.

    2009-01-01

    The appearance of numerous period-doubling cascades is among the most prominent features of {\\bf parametrized maps}, that is, smooth one-parameter families of maps $F:R \\times {\\mathfrak M} \\to {\\mathfrak M}$, where ${\\mathfrak M}$ is a smooth locally compact manifold without boundary, typically $R^N$. Each cascade has infinitely many period-doubling bifurcations, and it is typical to observe -- such as in all the examples we investigate here -- that whenever there are any cascades, there are...

  6. Inferring Network Structure from Cascades

    CERN Document Server

    Ghonge, Sushrut

    2016-01-01

    Many physical, biological and social phenomena can be described by cascades taking place on a network. Often, the activity can be empirically observed, but not the underlying network of interactions. In this paper we solve the dynamics of general cascade processes. We then offer three topological inversion methods to infer the structure of any directed network given a set of cascade arrival times. Our forward and inverse formulas hold for a very general class of models where the activation probability of a node is a generic function of its degree and the number of its active neighbors. We report high success rates for synthetic and real networks, for 5 different cascade models.

  7. Plant MAPK cascades: Just rapid signaling modules?

    KAUST Repository

    Boudsocq, Marie

    2015-08-27

    © 2015 Taylor & Francis Group, LLC. Abscisic acid (ABA) is a major phytohormone mediating important stress-related processes. We recently unveiled an ABA-activated MAPK signaling module constituted of MAP3K17/18-MKK3-MPK1/2/7/14. Unlike classical rapid MAPK activation, we showed that the activation of the new MAPK module is delayed and relies on the MAP3K protein synthesis. In this addendum, we discuss the role of this original and unexpected activation mechanism of MAPK cascades which suggests that MAPKs can regulate both early and longterm plant stress responses.

  8. Information cascade on networks

    CERN Document Server

    Hisakado, Masato

    2015-01-01

    In this paper, we discuss a voting model by considering three different kinds of networks: a random graph, the Barab\\'{a}si-Albert(BA) model, and a fitness model. A voting model represents the way in which public perceptions are conveyed to voters. Our voting model is constructed by using two types of voters--herders and independents--and two candidates. Independents conduct voting based on their fundamental values; on the other hand, herders base their voting on the number of previous votes. Hence, herders vote for the majority candidates and obtain information relating to previous votes from their networks. We discussed the difference between the phases on which the networks depend. Two kinds of phase transitions, an information cascade transition and a super-normal transition, were identified. The first of these is a transition between a state in which most voters make the correct choices and a state in which most of them are wrong. The second is a transition of convergence speed. The information cascade t...

  9. Energy Cascades in MHD

    Science.gov (United States)

    Alexakis, A.

    2009-04-01

    Most astrophysical and planetary systems e.g., solar convection and stellar winds, are in a turbulent state and coupled to magnetic fields. Understanding and quantifying the statistical properties of magneto-hydro-dynamic (MHD) turbulence is crucial to explain the involved physical processes. Although the phenomenological theory of hydro-dynamic (HD) turbulence has been verified up to small corrections, a similar statement cannot be made for MHD turbulence. Since the phenomenological description of Hydrodynamic turbulence by Kolmogorov in 1941 there have been many attempts to derive a similar description for turbulence in conducting fluids (i.e Magneto-Hydrodynamic turbulence). However such a description is going to be based inevitably on strong assumptions (typically borrowed from hydrodynamics) that do not however necessarily apply to the MHD case. In this talk I will discuss some of the properties and differences of the energy and helicity cascades in turbulent MHD and HD flows. The investigation is going to be based on the analysis of direct numerical simulations. The cascades in MHD turbulence appear to be a more non-local process (in scale space) than in Hydrodynamics. Some implications of these results to turbulent modeling will be discussed

  10. An Algebraic Approach to Signaling Cascades with n Layers

    DEFF Research Database (Denmark)

    Feliu, Elisenda; Knudsen, Michael; Andersen, Lars Nørvang;

    2011-01-01

    Posttranslational modification of proteins is key in transmission of signals in cells. Many signaling pathways contain several layers of modification cycles that mediate and change the signal through the pathway. Here, we study a simple signaling cascade consisting of n layers of modification...

  11. Contribution of cerebellar sensorimotor adaptation to hippocampal spatial memory.

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste Passot

    Full Text Available Complementing its primary role in motor control, cerebellar learning has also a bottom-up influence on cognitive functions, where high-level representations build up from elementary sensorimotor memories. In this paper we examine the cerebellar contribution to both procedural and declarative components of spatial cognition. To do so, we model a functional interplay between the cerebellum and the hippocampal formation during goal-oriented navigation. We reinterpret and complete existing genetic behavioural observations by means of quantitative accounts that cross-link synaptic plasticity mechanisms, single cell and population coding properties, and behavioural responses. In contrast to earlier hypotheses positing only a purely procedural impact of cerebellar adaptation deficits, our results suggest a cerebellar involvement in high-level aspects of behaviour. In particular, we propose that cerebellar learning mechanisms may influence hippocampal place fields, by contributing to the path integration process. Our simulations predict differences in place-cell discharge properties between normal mice and L7-PKCI mutant mice lacking long-term depression at cerebellar parallel fibre-Purkinje cell synapses. On the behavioural level, these results suggest that, by influencing the accuracy of hippocampal spatial codes, cerebellar deficits may impact the exploration-exploitation balance during spatial navigation.

  12. Fatal remote cerebellar hemorrhage after supratentorial unruptured aneurysm surgery in patient with previous cerebellar infarction

    Science.gov (United States)

    Koh, Eun-Jeong; Park, Jung-Soo

    2017-01-01

    Abstract Rationale: Remote cerebellar hemorrhage (RCH) is a rare complication of supratentorial and spinal surgeries, seldom requiring intervention but occasionally causing significant morbidity or even mortality. Although a number of theories have been proposed, the exact pathophysiology of RCH remains incompletely understood. Patient concerns: We present a 62-year-old patient with RCH encountered following surgical clipping of an unruptured middle cerebral artery bifurcation aneurysm in a patient with previous cerebellar infarction. Lessons: It is extremely rare, but sometimes, RCH can be life-threatening. It is necessary to check the patient's general condition, underlying diseases and medical history. And controlled drainage of the CSF seems to be most important. Arachnoidplasty may be a consideration and the position of the drain string might have to be carefully determined. PMID:28121936

  13. Lissencephaly with brainstem and cerebellar hypoplasia and congenital cataracts.

    Science.gov (United States)

    Abumansour, Iman S; Wrogemann, Jens; Chudley, Albert E; Chodirker, Bernard N; Salman, Michael S

    2014-06-01

    Classical lissencephaly may be associated with cerebellar hypoplasia and when significant cerebellar abnormalities occur, defects in proteins encoded by TUBA1A, RELN, and very-low-density lipoprotein receptor (VLDLR) genes have been reported. We present a neonate with a severe neurologic phenotype associated with hypotonia, oropharyngeal incoordination that required a gastric tube for feeding, intractable epilepsy, and congenital cataracts. Her brain magnetic resonance imaging (MRI) showed classical lissencephaly, ventriculomegaly, absent corpus callosum, globular and vertical hippocampi, and severe cerebellar and brainstem hypoplasia. She died at 6 weeks of age. No specific molecular diagnosis was made. This likely represents a previously undescribed genetic lissencephaly syndrome.

  14. Occurrence of crossed cerebellar diaschisis in cerebrovascular disease

    Energy Technology Data Exchange (ETDEWEB)

    Biersack, H.J.; Hartmann, A.; Friedrich, G.; Froescher, M.; Reichmann, K.; Reske, S.N.; Knopp, R.

    1984-10-01

    In 31 patients with completed stroke (n = 30) or PRIND (n = 1) a brain SPECT with /sup 123/I-labeled amphetamines was performed. In 14 (= 45%) of the respective patients - suffering from long-lasting hemiplegia - crossed cerebellar diaschisis was present. The interval between onset of the disease and time of examination varied between 1 week and 7 years. On the other hand, patients without crossed cerebellar diaschisis did not, with one exception, suffer from hemiplegia. It is likely that this phenomenon is caused by the reduction of spino-cerebellar stimuli due to the paresis of the respective extremities.

  15. Cerebral venous thrombosis presenting with cerebellar ataxia and cortical blindness.

    Science.gov (United States)

    Ben Sassi, Samia; Mizouni, Habiba; Nabli, Fatma; Kallel, Lamia; Kefi, Mounir; Hentati, Fayçal

    2010-01-01

    Venous infarction in the cerebellum has been reported only rarely, probably because of the abundant venous collateral drainage in this region. Bilateral occipital infarction is a rare cause of visual loss in cerebral venous thrombosis. We describe a 50-year-old woman with a history of ulcerative colitis who developed acute cerebellar ataxia and cortical blindness. She had bilateral cerebellar and occipital lesions related to sigmoid venous thrombosis and achieved complete recovery with anticoagulation therapy. Cerebral venous thrombosis should be considered in cases of simultaneous cerebellar and occipital vascular lesions.

  16. Hereditary Cerebellar Ataxias: A Korean Perspective

    Directory of Open Access Journals (Sweden)

    Ji Sun Kim

    2015-05-01

    Full Text Available Hereditary ataxia is a heterogeneous disorder characterized by progressive ataxia combined with/without peripheral neuropathy, extrapyramidal symptoms, pyramidal symptoms, seizure, and multiple systematic involvements. More than 35 autosomal dominant cerebellar ataxias have been designated as spinocerebellar ataxia, and there are 55 recessive ataxias that have not been named systematically. Conducting genetic sequencing to confirm a diagnosis is difficult due to the large amount of subtypes with phenotypic overlap. The prevalence of hereditary ataxia can vary among countries, and estimations of prevalence and subtype frequencies are necessary for planning a diagnostic strategy in a specific population. This review covers the various hereditary ataxias reported in the Korean population with a focus on the prevalence and subtype frequencies as the clinical characteristics of the various subtypes.

  17. Classically conditioned postural reflex in cerebellar patients.

    Science.gov (United States)

    Kolb, F P; Lachauer, S; Maschke, M; Timmann, D

    2004-09-01

    The aim of the current study was to compare postural responses to repetitive platform-evoked perturbations in cerebellar patients with those of healthy subjects using a classical conditioning paradigm. The perturbations consisted of tilting of the platform (unconditioned stimulus: US) at random time intervals, preceded by an auditory signal that represented the conditioning stimulus (CS). Physiological reactions were recorded biomechanically by measuring the vertical ground forces, yielding the center of vertical pressure (CVP), and electrophysiologically by EMG measurements of the main muscle groups of both legs. The recording session consisted of a control section with US-alone trials, a testing section with paired stimuli and a brief final section with US-alone trials. Healthy control subjects were divided into those establishing conditioned responses (CR) in all muscles tested (strategy I) and those with CR in the gastrocnemius muscles only (strategy II), suggesting an associative motor-related process is involved. Patients with a diffuse, non-localized disease were almost unable to establish CR. This was also true for a patient with a focal surgical lesion with no CR on the affected side but who, simultaneously, showed an essentially normal CR incidence on the intact side. During US-alone trials healthy controls exhibited a remarkable decay of the UR amplitude due to a non-associative motor-related process such as habituation. The decay was most prominent in the paired trials section. In contrast, patients showed no significant differences in the UR amplitude throughout the entire recording session. Analysis of the CVP supported the electrophysiological findings, showing CR in the controls only. The differences between the responses of control subjects and those of the cerebellar patients imply strongly that the cerebellum is involved critically in controlling associative and non-associative motor-related processes.

  18. Cascade Distillation System Development

    Science.gov (United States)

    Callahan, Michael R.; Sargushingh, Miriam; Shull, Sarah

    2014-01-01

    NASA's Advanced Exploration Systems (AES) Life Support System (LSS) Project is chartered with de-veloping advanced life support systems that will ena-ble NASA human exploration beyond low Earth orbit (LEO). The goal of AES is to increase the affordabil-ity of long-duration life support missions, and to re-duce the risk associated with integrating and infusing new enabling technologies required to ensure mission success. Because of the robust nature of distillation systems, the AES LSS Project is pursuing develop-ment of the Cascade Distillation Subsystem (CDS) as part of its technology portfolio. Currently, the system is being developed into a flight forward Generation 2.0 design.

  19. Interband cascade lasers

    Science.gov (United States)

    Vurgaftman, I.; Weih, R.; Kamp, M.; Meyer, J. R.; Canedy, C. L.; Kim, C. S.; Kim, M.; Bewley, W. W.; Merritt, C. D.; Abell, J.; Höfling, S.

    2015-04-01

    We review the current status of interband cascade lasers (ICLs) emitting in the midwave infrared (IR). The ICL may be considered the hybrid of a conventional diode laser that generates photons via electron-hole recombination, and an intersubband-based quantum cascade laser (QCL) that stacks multiple stages for enhanced current efficiency. Following a brief historical overview, we discuss theoretical aspects of the active region and core designs, growth by molecular beam epitaxy, and the processing of broad-area, narrow-ridge, and distributed feedback (DFB) devices. We then review the experimental performance of pulsed broad area ICLs, as well as the continuous-wave (cw) characteristics of narrow ridges having good beam quality and DFBs producing output in a single spectral mode. Because the threshold drive powers are far lower than those of QCLs throughout the λ = 3-6 µm spectral band, ICLs are increasingly viewed as the laser of choice for mid-IR laser spectroscopy applications that do not require high output power but need to be hand-portable and/or battery operated. Demonstrated ICL performance characteristics to date include threshold current densities as low as 106 A cm-2 at room temperature (RT), cw threshold drive powers as low as 29 mW at RT, maximum cw operating temperatures as high as 118 °C, maximum cw output powers exceeding 400 mW at RT, maximum cw wallplug efficiencies as high as 18% at RT, maximum cw single-mode output powers as high as 55 mW at RT, and single-mode output at λ = 5.2 µm with a cw drive power of only 138 mW at RT.

  20. Unsteady turbulence cascades

    Science.gov (United States)

    Goto, Susumu; Vassilicos, J. C.

    2016-11-01

    We have run a total of 311 direct numerical simulations (DNSs) of decaying three-dimensional Navier-Stokes turbulence in a periodic box with values of the Taylor length-based Reynolds number up to about 300 and an energy spectrum with a wide wave-number range of close to -5 /3 power-law dependence at the higher Reynolds numbers. On the basis of these runs, we have found a critical time when (i) the rate of change of the square of the integral length scale turns from increasing to decreasing, (ii) the ratio of interscale energy flux to high-pass filtered turbulence dissipation changes from decreasing to very slowly increasing in the inertial range, (iii) the signature of large-scale coherent structures disappears in the energy spectrum, and (iv) the scaling of the turbulence dissipation changes from the one recently discovered in DNSs of forced unsteady turbulence and in wind tunnel experiments of turbulent wakes and grid-generated turbulence to the classical scaling proposed by G. I. Taylor [Proc. R. Soc. London, Ser. A 151, 421 (1935), 10.1098/rspa.1935.0158] and A. N. Kolmogorov [Dokl. Akad. Nauk SSSR 31, 538 (1941)]. Even though the customary theoretical basis for this Taylor-Kolmogorov scaling is a statistically stationary cascade where large-scale energy flux balances dissipation, this is not the case throughout the entire time range of integration in all our DNS runs. The recently discovered dissipation scaling can be reformulated physically as a situation in which the dissipation rates of the small and large scales evolve together. We advance two hypotheses that may form the basis of a theoretical approach to unsteady turbulence cascades in the presence of large-scale coherent structures.

  1. Cerebellar giant cell glioblastoma multiforme in an adult

    Directory of Open Access Journals (Sweden)

    Sudhansu Sekhar Mishra

    2014-01-01

    Full Text Available Cerebellar glioblastoma multiforme (GBM is a rare tumor that accounts for only 1% of all cases of GBM and its giant cell variant is even much rarely encountered in adults. A case of cerebellar giant cell GBM managed at our institution reporting its clinical presentation, radiological and histological findings, and treatment instituted is described. In conjunction, a literature review, including particular issues, clinical data, advances in imaging studies, pathological characteristics, treatment options, and the behavior of such malignant tumor is presented. It is very important for the neurosurgeon to make the differential diagnosis between the cerebellar GBM, and other diseases such as metastasis, anaplastic astrocytomas, and cerebellar infarct because their treatment modalities, prognosis, and outcome are different.

  2. Bilateral cerebellar activation in unilaterally challenged essential tremor

    Directory of Open Access Journals (Sweden)

    Marja Broersma

    2016-01-01

    Conclusions: Our results expand on previous findings of bilateral cerebellar involvement in ET. We have identified specific areas in the bilateral somatomotor regions of the cerebellum: lobules V, VI and VIII.

  3. Cerebellar infarct patterns: The SMART-Medea study

    Directory of Open Access Journals (Sweden)

    Laurens J.L. De Cocker, MD

    2015-01-01

    Conclusions: Small cerebellar infarcts proved to be much more common than larger infarcts, and preferentially involved the cortex. Small cortical infarcts predominantly involved the posterior lobes, showed sparing of subcortical white matter and occurred in characteristic topographic patterns.

  4. Anomalous cerebellar anatomy in Chinese children with dyslexia

    Directory of Open Access Journals (Sweden)

    Ying-Hui eYang

    2016-03-01

    Full Text Available The cerebellar deficit hypothesis for developmental dyslexia (DD claims that cerebellar dysfunction causes the failures in the acquisition of visuomotor skills and automatic reading and writing skills. In people with dyslexia in the alphabetic languages, the abnormal activation and structure of the right or bilateral cerebellar lobes have been identified. Using a typical implicit motor learning task, however, one neuroimaging study demonstrated the left cerebellar dysfunction in Chinese children with dyslexia. In the present study, using voxel-based morphometry, we found decreased gray matter volume in the left cerebellum in Chinese children with dyslexia relative to age-matched controls. The positive correlation between reading performance and regional gray matter volume suggests that the abnormal structure in the left cerebellum is responsible for reading disability in Chinese children with dyslexia.

  5. Cerebellar blood flow in methylmercury poisoning (Minamata disease)

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, K.; Korogi, Y.; Tomiguchi, S.; Takahashi, M. [Dept. of Radiology, Kumamoto University School of Medicine (Japan); Okajima, T. [Dept. of Neurology, Johnan Hospital, Maihara, Johnan-mochi (Japan); Sato, H. [Dept. of Neurology, Minamata City General Hospital and Medical Centre (Japan)

    2001-04-01

    We looked at regional cerebellar blood flow in patients with Minamata disease (MD) using technetium-99 m ethyl cysteinate dimer (99m-Tc-ECD). We carried out single-photon emission computed tomography (SPECT) on 15 patients with MD (eight men, seven women, aged 51-78 years, mean 70.5 years) and 11 control subjects (eight men, three women, aged 62-80 years, mean 72.5 years). Regional blood flow was measured in the superior, middle, and inferior portions of the cerebellar hemispheres, and the frontal, temporal and occipital cerebral lobes. The degree of cerebellar atrophy was assessed on MRI. There were significant differences in regional blood flow in all parts of the cerebellum between patients and control, but no significant decrease was observed in the cerebrum. Blood flow was lower in the inferior cerebellum than in the other parts. Even in patients without cerebellar atrophy, flow was significantly decreased regional blood flow in the inferior part. (orig.)

  6. Cerebellar blood flow in methylmercury poisoning (Minamata disease).

    Science.gov (United States)

    Itoh, K; Korogi, Y; Tomiguchi, S; Takahashi, M; Okajima, T; Sato, H

    2001-04-01

    We looked at regional cerebellar blood flow in patients with Minamata disease (MD) using technetium-99m ethyl cysteinate dimer (99m-Tc-ECD). We carried out single-photon emission computed tomography (SPECT) on 15 patients with MD (eight men, seven women, aged 51-78 years, mean 70.5 years) and 11 control subjects (eight men, three women, aged 62-80 years, mean 72.5 years). Regional blood flow was measured in the superior, middle, and inferior portions of the cerebellar hemispheres, and the frontal, temporal and occipital cerebral lobes. The degree of cerebellar atrophy was assessed on MRI. There were significant differences in regional blood flow in all parts of the cerebellum between patients and control, but no significant decrease was observed in the cerebrum. Blood flow was lower in the inferior cerebellum than in the other parts. Even in patients without cerebellar atrophy, flow was significantly decreased regional blood flow in the inferior part.

  7. Cerebellar transcranial direct current stimulation in neurological disease

    OpenAIRE

    Ferrucci, Roberta; Bocci, Tommaso; Cortese, Francesca; Ruggiero, Fabiana; Priori, Alberto

    2016-01-01

    Several studies have highlighted the therapeutic potential of transcranial direct current stimulation (tDCS) in patients with neurological diseases, including dementia, epilepsy, post-stroke dysfunctions, movement disorders, and other pathological conditions. Because of this technique’s ability to modify cerebellar excitability without significant side effects, cerebellar tDCS is a new, interesting, and powerful tool to induce plastic modifications in the cerebellum. In this report, we review...

  8. Oxidative Stress in Autism: Elevated Cerebellar 3-nitrotyrosine Levels

    Directory of Open Access Journals (Sweden)

    Elizabeth M. Sajdel-Sulkowska

    2008-01-01

    Full Text Available It has been suggested that oxidative stress and/or mercury compounds play an important role in the pathophysiology of autism. This study compared for the first time the cerebellar levels of the oxidative stress marker 3-nitrotyrosine (3-NT, mercury (Hg and the antioxidant selenium (Se levels between control and autistic subjects. Tissue homogenates were prepared in the presence of protease inhibitors from the frozen cerebellar tissue of control (n=10; mean age, 15.5 years; mean PMI, 15.5 hours and autistic (n=9; mean age 12.1 years; mean PMI, 19.3 hours subjects. The concentration of cerebellar 3-NT, determined by ELISA, in controls ranged from 13.69 to 49.04 pmol g-1 of tissue; the concentration of 3-NT in autistic cases ranged from 3.91 to 333.03 pmol g-1 of tissue. Mean cerebellar 3-NT was elevated in autism by 68.9% and the increase was statistically significant (p=0.045. Cerebellar Hg, measured by atomic absorption spectrometry ranged from 0.9 to 35 pmol g-1 tissue in controls (n=10 and from 3.2 to 80.7 pmol g-1 tissue in autistic cases (n=9; the 68.2% increase in cerebellar Hg was not statistically significant. However, there was a positive correlation between cerebellar 3-NT and Hg levels (r=0.7961, p=0.0001. A small decrease in cerebellar Se levels in autism, measured by atomic absorption spectroscopy, was not statistically significant but was accompanied by a 42.9% reduction in the molar ratio of Se to Hg in the autistic cerebellum. While preliminary, the results of the present study add elevated oxidative stress markers in brain to the growing body of data reflecting greater oxidative stress in autism.

  9. Proprioceptive Localization Deficits in People With Cerebellar Damage.

    Science.gov (United States)

    Weeks, Heidi M; Therrien, Amanda S; Bastian, Amy J

    2017-04-01

    It has been hypothesized that an important function of the cerebellum is predicting the state of the body during movement. Yet, the extent of cerebellar involvement in perception of limb state (i.e., proprioception, specifically limb position sense) has yet to be determined. Here, we investigated whether patients with cerebellar damage have deficits when trying to locate their hand in space (i.e., proprioceptive localization), which is highly important for everyday movements. By comparing performance during passive robot-controlled and active self-made multi-joint movements, we were able to determine that some cerebellar patients show improved precision during active movement (i.e., active benefit), comparable to controls, whereas other patients have reduced active benefit. Importantly, the differences in patient performance are not explained by patient diagnosis or clinical ratings of impairment. Furthermore, a subsequent experiment confirmed that active deficits in proprioceptive localization occur during both single-joint and multi-joint movements. As such, it is unlikely that localization deficits can be explained by the multi-joint coordination deficits occurring after cerebellar damage. Our results suggest that cerebellar damage may cause varied impairments to different elements of proprioceptive sense. It follows that proprioceptive localization should be adequately accounted for in clinical testing and rehabilitation of people with cerebellar damage.

  10. Relationship between the cerebellar function and cerebellar atrophy in Minamata disease. Investigations using body balance analyzer and MR imaging method

    Energy Technology Data Exchange (ETDEWEB)

    Okajima, Toru [Johnan Hospital, Minami, Kumamoto (Japan); Ikeda, Osamu; Sannomiya, Kunihiro; Korogi, Yukinori; Uchino, Makoto

    1995-11-01

    Interrelations between the cerebellar function and cerebellar atrophy were studied in the cases with Minamata disease and spinocerebellar degeneration and in the healthy subjects. For evaluation of the cerebellar function, the statokinesigraph (SKG) was recorded and the shifting length (L-SKG) and moving area (A-SKG) of postural sway were obtained using body balance analyzer. Cerebellar atrophy was evaluated by the rostrocaudal and ventrodorsal diameters of whole vermis and the total area of upper and lower parts (area-UL) of vermis on the midsagittal plane of MR imaging. It was disclosed that there was significant correlation between the L-SKG and the measurement of rostrocaudal diameter as well as the area-UL of vermis through the patients with Minamata disease and the healthy subjects. When added the patients with spinocerebellar degeneration, the significant correlation was not obtainable probably because of the progressive processes of the disease. (author).

  11. Human-induced trophic cascades along the fecal detritus pathway.

    Directory of Open Access Journals (Sweden)

    Elizabeth Nichols

    Full Text Available Human presence and activity in tropical forest is thought to exert top-down regulation over the various 'green-world' pathways of plant-based foodwebs. However, these effects have never been explored for the 'brown-world' pathways of fecal-detritus webs. The strong effects of humans on tropical game mammals are likely to indirectly influence fecal detritivores (including Scarabaeine dung beetles, with subsequent indirect impacts on detrivore-mediated and plant-facilitating detrital processes. Across a 380-km gradient of human influence in the western Brazilian Amazon, we conducted the first landscape-level assessment of human-induced cascade effects on the fecal detritus pathway, by coupling data on human impact, game mammal and detritivore community structure, and rate measurements of a key detritus process (i.e. dung beetle-mediated secondary seed dispersal. We found evidence that human impact indirectly influences both the diversity and biomass of fecal detritivores, but not detritivore-mediated processes. Cascade strength varied across detritivore groups defined by species' traits. We found smaller-bodied dung beetles were at higher risk of local decline in areas of human presence, and that body size was a better predictor of cascade structure than fecal resource manipulation strategy. Cascade strength was also stronger in upland, unflooded forests, than in seasonally flooded forests. Our results suggest that the impact of human activity in tropical forest on fecal-detritus food web structure is mediated by both species' traits and habitat type. Further research will be required to determine the conditions under which these cascade effects influence fecal-detritus web function.

  12. Cascade Mountain Range in Oregon

    Science.gov (United States)

    Sherrod, David R.

    2016-01-01

    The Cascade mountain system extends from northern California to central British Columbia. In Oregon, it comprises the Cascade Range, which is 260 miles long and, at greatest breadth, 90 miles wide (fig. 1). Oregon’s Cascade Range covers roughly 17,000 square miles, or about 17 percent of the state, an area larger than each of the smallest nine of the fifty United States. The range is bounded on the east by U.S. Highways 97 and 197. On the west it reaches nearly to Interstate 5, forming the eastern margin of the Willamette Valley and, farther south, abutting the Coast Ranges. 

  13. Cerebellar Ataxia and Glutamic Acid Decarboxylase Antibodies

    Science.gov (United States)

    Ariño, Helena; Gresa-Arribas, Nuria; Blanco, Yolanda; Martínez-Hernández, Eugenia; Sabater, Lidia; Petit-Pedrol, Mar; Rouco, Idoia; Bataller, Luis; Dalmau, Josep O.; Saiz, Albert; Graus, Francesc

    2016-01-01

    IMPORTANCE Current clinical and immunologic knowledge on cerebellar ataxia (CA) with glutamic acid decarboxylase 65 antibodies (GAD65-Abs) is based on case reports and small series with short-term follow-up data. OBJECTIVE To report the symptoms, additional antibodies, prognostic factors, and long-term outcomes in a cohort of patients with CA and GAD65-Abs. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study and laboratory investigations at a center for autoimmune neurologic disorders among 34 patients with CA and GAD65-Abs, including 25 with long-term follow-up data (median, 5.4 years; interquartile range, 3.1-10.3 years). MAIN OUTCOMES AND MEASURES Analysis of clinicoimmunologic features and predictors of response to immunotherapy. Immunochemistry on rat brain, cultured neurons, and human embryonic kidney cells expressing GAD65, GAD67, α1-subunit of the glycine receptor, and a repertoire of known cell surface autoantigens were used to identify additional antibodies. Twenty-eight patients with stiff person syndrome and GAD65-Abs served as controls. RESULTS The median age of patients was 58 years (range, 33-80 years); 28 of 34 patients (82%) were women. Nine patients (26%) reported episodes of brainstem and cerebellar dysfunction or persistent vertigo several months before developing CA. The clinical presentation was subacute during a period of weeks in 13 patients (38%). Nine patients (26%) had coexisting stiff person syndrome symptoms. Systemic organ-specific autoimmunities (type 1 diabetes mellitus and others) were present in 29 patients (85%). Twenty of 25 patients with long-term follow-up data received immunotherapy (intravenous immunoglobulin in 10 and corticosteroids and intravenous immunoglobulin or other immunosuppressors in 10), and 7 of them (35%) improved. Predictors of clinical response included subacute onset of CA (odds ratio [OR], 0.50; 95% CI, 0.25-0.99; P = .047) and prompt immunotherapy (OR, 0.98; 95% CI, 0.96-0.99; P = .01). Similar

  14. Cascade Product of Permutation Groups

    OpenAIRE

    Egri-Nagy, Attila; Nehaniv, Chrystopher L.

    2013-01-01

    We define the cascade product of permutation groups as an external product, an explicit construction of substructures of the iterated wreath product that are much smaller than the full wreath product. This construction is essential for computational implementations of algebraic hierarchical decompositions of finite automata. We show how direct, semidirect, and wreath products and group extensions can all be expressed as cascade products, and analyse examples of groups that can be constructed ...

  15. Low Noise Interband Cascade Photodetectors

    Science.gov (United States)

    2012-02-28

    National Laboratories, Zhaobing Tian, Zhihua Cai, R. T. Hinkey, L. Li, Tetsuya D. Mishima , Michael B. Santos, and Matthew B. Johnson at the...Phys. 107, No. 5, 054514 (2010). 2. R. Q. Yang, Z. Tian, J. F. Klem, T. D. Mishima , M. B. Santos, and M. B. Johnson, “Interband cascade photovoltaic...2012). 4. Z. Tian, Z. Cai, R. Q. Yang, T. D. Mishima , M. B. Santos, M. B. Johnson, and J. F. Klem, “Interband Cascade Infrared Photodetectors

  16. Are longer cascades more stable?

    OpenAIRE

    2004-01-01

    Yes, they are. We consider data from experimental cascade games that were run in different laboratories, and find uniformly that subjects are more willing to follow the crowd, the bigger the crowd is �although the decision makers who are added to the crowd should in theory simply follow suit and hence reveal no information. This correlation of length and strength of cascades appears consistently across games with different parameters and different choice sets for the subjects. ...

  17. Aeroelasticity in Turbomachine-Cascades.

    Science.gov (United States)

    1982-11-10

    STABLE -180 UNSTABLE -360 ’ - ’ - -180 0. 󈧖O DIAGRAM 3 AERODYNAMIC LIFT (OENT)COEFFICIENTI AND PHASE LEADS IN DEPENDANCE OF FLOM GUANTATIES AND CASCADE...ABL -0.8 0.0 -5 0. -5 DIAGRAM ’. AERODYNAMIC NORK AND DAMPING COEFFICIENTS (FOR A RIGID NOTION) IN DEPENDANCE OF FLOW OURNTATIES AND CASCADE GEOMETRY...coefficients on blades + blade vibration + vizualization in the transonic flow domain (Schlieren) + instability dependance on flow conditions, blade

  18. Cascading Gravity is Ghost Free

    CERN Document Server

    de Rham, Claudia; Tolley, Andrew J

    2010-01-01

    We perform a full perturbative stability analysis of the 6D cascading gravity model in the presence of 3-brane tension. We demonstrate that for sufficiently large tension on the (flat) 3-brane, there are no ghosts at the perturbative level, consistent with results that had previously only been obtained in a specific 5D decoupling limit. These results establish the cascading gravity framework as a consistent infrared modification of gravity.

  19. Electrophysiological mapping of novel prefrontal - cerebellar pathways

    Directory of Open Access Journals (Sweden)

    Thomas C Watson

    2009-08-01

    Full Text Available Whilst the cerebellum is predominantly considered a sensorimotor control structure, accumulating evidence suggests that it may also subserve non motor functions during cognition. However, this possibility is not universally accepted, not least because the nature and pattern of links between higher cortical structures and the cerebellum are poorly characterized. We have therefore used in vivo electrophysiological methods in anaesthetized rats to directly investigate connectivity between the medial prefrontal cortex (prelimbic subdivision, PrL and the cerebellum. Stimulation of deep layers of PrL evoked distinct field potentials in the cerebellar cortex with a mean latency to peak of approximately 35ms. These responses showed a well-defined topography, and were maximal in lobule VII of the contralateral vermis (a known oculomotor centre; they were not attenuated by local anesthesia of the overlying M2 motor cortex, though M2 stimulation did evoke field potentials in lobule VII with a shorter latency. Single-unit recordings showed that prelimbic cortical stimulation elicits complex spikes in lobule VII Purkinje cells, indicating transmission via a previously undescribed cerebro-olivocerebellar pathway. Our results therefore establish a physiological basis for communication between PrL and the cerebellum. The role(s of this pathway remain to be resolved, but presumably relate to control of eye movements and/or distributed networks associated with integrated prefrontal cortical functions.

  20. Sudden stopping in patients with cerebellar ataxia.

    Science.gov (United States)

    Serrao, Mariano; Conte, Carmela; Casali, Carlo; Ranavolo, Alberto; Mari, Silvia; Di Fabio, Roberto; Perrotta, Armando; Coppola, Gianluca; Padua, Luca; Monamì, Stefano; Sandrini, Giorgio; Pierelli, Francesco

    2013-10-01

    Stopping during walking, a dynamic motor task frequent in everyday life, is very challenging for ataxic patients, as it reduces their gait stability and increases the incidence of falls. This study was conducted to analyse the biomechanical characteristics of upper and lower body segments during abrupt stopping in ataxic patients in order to identify possible strategies used to counteract the instability in the sagittal and frontal plane. Twelve patients with primary degenerative cerebellar ataxia and 12 age- and sex-matched healthy subjects were studied. Time-distance parameters, dynamic stability of the centre of mass, upper body measures and lower joint kinematic and kinetic parameters were analysed. The results indicate that ataxic patients have a great difficulty in stopping abruptly during walking and adopt a multi-step stopping strategy, occasionally with feet parallel, to compensate for their inability to coordinate the upper body and to generate a well-coordinated lower limb joint flexor-extensor pattern and appropriate braking forces for progressively decelerating the progression of the body in the sagittal plane. A specific rehabilitation treatment designed to improve the ability of ataxic patients to transform unplanned stopping into planned stopping, to coordinate upper body and to execute an effective flexion-extension pattern of the hip and knee joints may be useful in these patients in order to improve their stopping performance and prevent falls.

  1. Acid-sensitive channel inhibition prevents fetal alcohol spectrum disorders cerebellar Purkinje cell loss.

    Science.gov (United States)

    Ramadoss, Jayanth; Lunde, Emilie R; Ouyang, Nengtai; Chen, Wei-Jung A; Cudd, Timothy A

    2008-08-01

    Ethanol is now considered the most common human teratogen. Educational campaigns have not reduced the incidence of ethanol-mediated teratogenesis, leading to a growing interest in the development of therapeutic prevention or mitigation strategies. On the basis of the observation that maternal ethanol consumption reduces maternal and fetal pH, we hypothesized that a pH-sensitive pathway involving the TWIK-related acid-sensitive potassium channels (TASKs) is implicated in ethanol-induced injury to the fetal cerebellum, one of the most sensitive targets of prenatal ethanol exposure. Pregnant ewes were intravenously infused with ethanol (258+/-10 mg/dl peak blood ethanol concentration) or saline in a "3 days/wk binge" pattern throughout the third trimester. Quantitative stereological analysis demonstrated that ethanol resulted in a 45% reduction in the total number of fetal cerebellar Purkinje cells, the cell type most sensitive to developmental ethanol exposure. Extracellular pH manipulation to create the same degree and pattern of pH fall caused by ethanol (manipulations large enough to inhibit TASK 1 channels), resulted in a 24% decrease in Purkinje cell number. We determined immunohistochemically that TASK 1 channels are expressed in Purkinje cells and that the TASK 3 isoform is expressed in granule cells of the ovine fetal cerebellum. Pharmacological blockade of both TASK 1 and TASK 3 channels simultaneous with ethanol effectively prevented any reduction in fetal cerebellar Purkinje cell number. These results demonstrate for the first time functional significance of fetal cerebellar two-pore domain pH-sensitive channels and establishes them as a potential therapeutic target for prevention of ethanol teratogenesis.

  2. The cerebellar nodulus/uvula integrates otolith signals for the translational vestibulo-ocular reflex.

    Directory of Open Access Journals (Sweden)

    Mark F Walker

    Full Text Available BACKGROUND: The otolith-driven translational vestibulo-ocular reflex (tVOR generates compensatory eye movements to linear head accelerations. Studies in humans indicate that the cerebellum plays a critical role in the neural control of the tVOR, but little is known about mechanisms of this control or the functions of specific cerebellar structures. Here, we chose to investigate the contribution of the nodulus and uvula, which have been shown by prior studies to be involved in the processing of otolith signals in other contexts. METHODOLOGY/PRINCIPAL FINDINGS: We recorded eye movements in two rhesus monkeys during steps of linear motion along the interaural axis before and after surgical lesions of the cerebellar uvula and nodulus. The lesions strikingly reduced eye velocity during constant-velocity motion but had only a small effect on the response to initial head acceleration. We fit eye velocity to a linear combination of head acceleration and velocity and to a dynamic mathematical model of the tVOR that incorporated a specific integrator of head acceleration. Based on parameter optimization, the lesion decreased the gain of the pathway containing this new integrator by 62%. The component of eye velocity that depended directly on head acceleration changed little (gain decrease of 13%. In a final set of simulations, we compared our data to the predictions of previous models of the tVOR, none of which could account for our experimental findings. CONCLUSIONS/ SIGNIFICANCE: Our results provide new and important information regarding the neural control of the tVOR. Specifically, they point to a key role for the cerebellar nodulus and uvula in the mathematical integration of afferent linear head acceleration signals. This function is likely to be critical not only for the tVOR but also for the otolith-mediated reflexes that control posture and balance.

  3. Alcohol Impairs Long-Term Depression at the Cerebellar Parallel Fiber–Purkinje Cell Synapse

    Science.gov (United States)

    Belmeguenai, Amor; Botta, Paolo; Weber, John T.; Carta, Mario; De Ruiter, Martijn; De Zeeuw, Chris I.; Valenzuela, C. Fernando; Hansel, Christian

    2008-01-01

    Acute alcohol consumption causes deficits in motor coordination and gait, suggesting an involvement of cerebellar circuits, which play a role in the fine adjustment of movements and in motor learning. It has previously been shown that ethanol modulates inhibitory transmission in the cerebellum and affects synaptic transmission and plasticity at excitatory climbing fiber (CF) to Purkinje cell synapses. However, it has not been examined thus far how acute ethanol application affects long-term depression (LTD) and long-term potentiation (LTP) at excitatory parallel fiber (PF) to Purkinje cell synapses, which are assumed to mediate forms of cerebellar motor learning. To examine ethanol effects on PF synaptic transmission and plasticity, we performed whole cell patch-clamp recordings from Purkinje cells in rat cerebellar slices. We found that ethanol (50 mM) selectively blocked PF–LTD induction, whereas it did not change the amplitude of excitatory postsynaptic currents at PF synapses. In contrast, ethanol application reduced voltage-gated calcium currents and type 1 metabotropic glutamate receptor (mGluR1)–dependent responses in Purkinje cells, both of which are involved in PF–LTD induction. The selectivity of these effects is emphasized by the observation that ethanol did not impair PF–LTP and that PF–LTP could readily be induced in the presence of the group I mGluR antagonist AIDA or the mGluR1a antagonist LY367385. Taken together, these findings identify calcium currents and mGluR1-dependent signaling pathways as potential ethanol targets and suggest that an ethanol-induced blockade of PF–LTD could contribute to the motor coordination deficits resulting from alcohol consumption. PMID:18922952

  4. Ethanol-Induced Cerebellar Ataxia: Cellular and Molecular Mechanisms.

    Science.gov (United States)

    Dar, M Saeed

    2015-08-01

    The cerebellum is an important target of ethanol toxicity given that cerebellar ataxia is the most consistent physical manifestation of acute ethanol consumption. Despite the significance of the cerebellum in ethanol-induced cerebellar ataxia (EICA), the cellular and molecular mechanisms underlying EICA are incompletely understood. However, two important findings have shed greater light on this phenomenon. First, ethanol-induced blockade of cerebellar adenosine uptake in rodent models points to a role for adenosinergic A1 modulation of EICA. Second, the consistent observation that intracerebellar administration of nicotine in mice leads to antagonism of EICA provides evidence for a critical role of cerebellar nitric oxide (NO) in EICA reversal. Based on these two important findings, this review discusses the potential molecular events at two key synaptic sites (mossy fiber-granule cell-Golgi cell (MGG synaptic site) and granule cell parallel fiber-Purkinje cell (GPP synaptic site) that lead to EICA. Specifically, ethanol-induced neuronal NOS inhibition at the MGG synaptic site acts as a critical trigger for Golgi cell activation which leads to granule cell deafferentation. Concurrently, ethanol-induced inhibition of adenosine uptake at the GPP synaptic site produces adenosine accumulation which decreases glutamate release and leads to the profound activation of Purkinje cells (PCs). These molecular events at the MGG and GPP synaptic sites are mutually reinforcing and lead to cerebellar dysfunction, decreased excitatory output of deep cerebellar nuclei, and EICA. The critical importance of PCs as the sole output of the cerebellar cortex suggests normalization of PC function could have important therapeutic implications.

  5. Abnormal cerebellar volume in acute and remitted major depression.

    Science.gov (United States)

    Depping, Malte S; Wolf, Nadine D; Vasic, Nenad; Sambataro, Fabio; Hirjak, Dusan; Thomann, Philipp A; Wolf, Robert C

    2016-11-01

    Abnormal cortical volume is well-documented in patients with major depressive disorder (MDD), but cerebellar findings have been heterogeneous. It is unclear whether abnormal cerebellar structure relates to disease state or medication. In this study, using structural MRI, we investigated cerebellar volume in clinically acute (with and without psychotropic treatment) and remitted MDD patients. High-resolution structural MRI data at 3T were obtained from acute medicated (n=29), acute unmedicated (n=14) and remitted patients (n=16). Data from 29 healthy controls were used for comparison purposes. Cerebellar volume was investigated using cerebellum-optimized voxel-based analysis methods. Patients with an acute MDD episode showed increased volume of left cerebellar area IX, and this was true for both medicated and unmedicated individuals (pvolume. In remitted, but not in acutely ill patients, area IX volume was significantly associated with measures of depression severity, as assessed by the Hamilton Depression Rating Scale (HAMD). In addition, area IX volume in remitted patients was significantly related to the duration of antidepressant treatment. In acutely ill patients, no significant relationships were established using clinical variables, such as HAMD, illness or treatment duration and number of depressive episodes. The data suggest that cerebellar area IX, a non-motor region that belongs to a large-scale brain functional network with known relevance to core depressive symptom expression, exhibits abnormal volume in patients independent of clinical severity or medication. Thus, the data imply a possible trait marker of the disorder. However, given bilaterality and an association with clinical scores at least in remitted patients, the current findings raise the possibility that cerebellar volume may be reflective of successful treatment as well.

  6. Cerebellar cognitive affective syndrome CCAS – a case report

    Directory of Open Access Journals (Sweden)

    Starowicz-Filip, Anna

    2013-09-01

    Full Text Available Aim. The aim of the study was to describe a case of the patient with cerebellar cognitive affective syndrome CCAS, characterize the role of cerebellum in the regulation of cognitive functions and present theprocedure of neuropsychological diagnosis useful in indicating the specific cognitive and emotional problems in patients with cerebellar damage.Case report. A 41- year old man with an ischemic cerebellar stroke of its right hemisphere manifested the neuropsychological symptoms typical for the frontal damage: euphoric mood, disorganized behavior,lack of criticism and mental plasticity, tendency to shorten the personal distance, problems with mistake correction. In neuropsychological diagnosis we used following methods: Raven Progressive Matrices Test, Mini Mental Stage Examination (MMSE, Trail Making Test, Wisconsin Card Sorting Test, Stroop Interference Test, Word Fluency Test, Auditory Verbal Learning Test by Łuria, Benton Visual Retention Test, Digit Span.Results. Analyzing the obtained results we observed the significant decrease of all executive functions: planning, abstract thinking, cognitive flexibility, adaptation to new situations as well as memory impairments and changes in emotional and behavioral state similar to frontal syndrome. The whole of impairments including the typical cerebellar symptoms (ataxia, dysarthria, dysmetria,hypotonia create the cerebellar cognitive affective syndrome CCAS with leading role of dysexecutive syndrome.Conclusions. The cerebellum takes part in the regulation of cognitive functions. The cerebellar damages can imitate the emotional- cognitive problems of patients after frontal damages what additionally stress the functional link between these two brain structures. Patient’s with cerebellar damages should have neuropsychological and neuropsychiatric diagnosis and care.

  7. A cerebellar neuroprosthetic system: computational architecture and in vivo experiments

    Directory of Open Access Journals (Sweden)

    Ivan eHerreros Alonso

    2014-05-01

    Full Text Available Emulating the input-output functions performed by a brain structure opens the possibility for developing neuro-prosthetic systems that replace damaged neuronal circuits. Here, we demonstrate the feasibility of this approach by replacing the cerebellar circuit responsible for the acquisition and extinction of motor memories. Specifically, we show that a rat can undergo acquisition, retention and extinction of the eye-blink reflex even though the biological circuit responsible for this task has been chemically inactivated via anesthesia. This is achieved by first developing a computational model of the cerebellar microcircuit involved in the acquisition of conditioned reflexes and training it with synthetic data generated based on physiological recordings. Secondly, the cerebellar model is interfaced with the brain of an anesthetized rat, connecting the model's inputs and outputs to afferent and efferent cerebellar structures. As a result, we show that the anesthetized rat, equipped with our neuro-prosthetic system, can be classically conditioned to the acquisition of an eye-blink response. However, non-stationarities in the recorded biological signals limit the performance of the cerebellar model. Thus, we introduce an updated cerebellar model and validate it with physiological recordings showing that learning becomes stable and reliable. The resulting system represents an important step towards replacing lost functions of the central nervous system via neuro-prosthetics, obtained by integrating a synthetic circuit with the afferent and efferent pathways of a damaged brain region. These results also embody an early example of science-based medicine, where on the one hand the neuro-prosthetic system directly validates a theory of cerebellar learning that informed the design of the system, and on the other one it takes a step towards the development of neuro-prostheses that could recover lost learning functions in animals and, in the longer term

  8. Cerebellar development in the absence of Gbx function in zebrafish.

    Science.gov (United States)

    Su, Chen-Ying; Kemp, Hilary A; Moens, Cecilia B

    2014-02-01

    The midbrain-hindbrain boundary (MHB) is a well-known organizing center during vertebrate brain development. The MHB forms at the expression boundary of Otx2 and Gbx2, mutually repressive homeodomain transcription factors expressed in the midbrain/forebrain and anterior hindbrain, respectively. The genetic hierarchy of gene expression at the MHB is complex, involving multiple positive and negative feedback loops that result in the establishment of non-overlapping domains of Wnt1 and Fgf8 on either side of the boundary and the consequent specification of the cerebellum. The cerebellum derives from the dorsal part of the anterior-most hindbrain segment, rhombomere 1 (r1), which undergoes a distinctive morphogenesis to give rise to the cerebellar primordium within which the various cerebellar neuron types are specified. Previous studies in the mouse have shown that Gbx2 is essential for cerebellar development. Using zebrafish mutants we show here that in the zebrafish gbx1 and gbx2 are required redundantly for morphogenesis of the cerebellar primordium and subsequent cerebellar differentiation, but that this requirement is alleviated by knocking down Otx. Expression of fgf8, wnt1 and the entire MHB genetic program is progressively lost in gbx1-;gbx2- double mutants but is rescued by Otx knock-down. This rescue of the MHB genetic program depends on rescued Fgf signaling, however the rescue of cerebellar primordium morphogenesis is independent of both Gbx and Fgf. Based on our findings we propose a revised model for the role of Gbx in cerebellar development.

  9. Interband Cascade Photovoltaic Cells

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Rui Q. [Univ. of Oklahoma, Norman, OK (United States); Santos, Michael B. [Univ. of Oklahoma, Norman, OK (United States); Johnson, Matthew B. [Univ. of Oklahoma, Norman, OK (United States)

    2014-09-24

    In this project, we are performing basic and applied research to systematically investigate our newly proposed interband cascade (IC) photovoltaic (PV) cells [1]. These cells follow from the great success of infrared IC lasers [2-3] that pioneered the use of quantum-engineered IC structures. This quantum-engineered approach will enable PV cells to efficiently convert infrared radiation from the sun or other heat source, to electricity. Such cells will have important applications for more efficient use of solar energy, waste-heat recovery, and power beaming in combination with mid-infrared lasers. The objectives of our investigations are to: achieve extensive understanding of the fundamental aspects of the proposed PV structures, develop the necessary knowledge for making such IC PV cells, and demonstrate prototype working PV cells. This research will focus on IC PV structures and their segments for utilizing infrared radiation with wavelengths from 2 to 5 μm, a range well suited for emission by heat sources (1,000-2,000 K) that are widely available from combustion systems. The long-term goal of this project is to push PV technology to longer wavelengths, allowing for relatively low-temperature thermal sources. Our investigations address material quality, electrical and optical properties, and their interplay for the different regions of an IC PV structure. The tasks involve: design, modeling and optimization of IC PV structures, molecular beam epitaxial growth of PV structures and relevant segments, material characterization, prototype device fabrication and testing. At the end of this program, we expect to generate new cutting-edge knowledge in the design and understanding of quantum-engineered semiconductor structures, and demonstrate the concepts for IC PV devices with high conversion efficiencies.

  10. Communication Scheme via Cascade Chaotic Systems

    Institute of Scientific and Technical Information of China (English)

    HUA Chang-Chun; GUAN Xin-Ping

    2004-01-01

    @@ A new chaotic communication scheme is constructed. Different from the existing literature, cascade chaotic systems are employed. Two cascade modes are considered. First, we investigate the input to state cascade mode;cascade systems between different kinds of chaotic systems are considered. Then the parameter cascade case of chaotic system is studied. Under the different cases, the corresponding receivers are designed, which can succeed in recovering the former emitted signal. Simulations are performed to verify the validity of the proposed main results.

  11. Upregulation of cortico-cerebellar functional connectivity after motor learning.

    Science.gov (United States)

    Mehrkanoon, Saeid; Boonstra, Tjeerd W; Breakspear, Michael; Hinder, Mark; Summers, Jeffery J

    2016-03-01

    Interactions between the cerebellum and primary motor cortex are crucial for the acquisition of new motor skills. Recent neuroimaging studies indicate that learning motor skills is associated with subsequent modulation of resting-state functional connectivity in the cerebellar and cerebral cortices. The neuronal processes underlying the motor-learning-induced plasticity are not well understood. Here, we investigate changes in functional connectivity in source-reconstructed electroencephalography (EEG) following the performance of a single session of a dynamic force task in twenty young adults. Source activity was reconstructed in 112 regions of interest (ROIs) and the functional connectivity between all ROIs was estimated using the imaginary part of coherence. Significant changes in resting-state connectivity were assessed using partial least squares (PLS). We found that subjects adapted their motor performance during the training session and showed improved accuracy but with slower movement times. A number of connections were significantly upregulated after motor training, principally involving connections within the cerebellum and between the cerebellum and motor cortex. Increased connectivity was confined to specific frequency ranges in the mu- and beta-bands. Post hoc analysis of the phase spectra of these cerebellar and cortico-cerebellar connections revealed an increased phase lag between motor cortical and cerebellar activity following motor practice. These findings show a reorganization of intrinsic cortico-cerebellar connectivity related to motor adaptation and demonstrate the potential of EEG connectivity analysis in source space to reveal the neuronal processes that underpin neural plasticity.

  12. Development of the cerebellar cortex in the mouse

    Institute of Scientific and Technical Information of China (English)

    Xiangshu Cheng; Jin Du; Dongming Yu; Qiying Jiang; Yanqiu Hu; Lei Wang; Mingshan Li; Jinbo Deng

    2011-01-01

    The cerebellum is a highly conserved structure in the central nervous system of vertebrates, and is involved in the coordination of voluntary motor behavior. Supporting this function, the cerebellar cortex presents a layered structure which requires precise spatial and temporal coordination of proliferation, migration, differentiation, and apoptosis events. The formation of the layered structure in the developing cerebellum remains unclear. The present study investigated the development of the cerebellar cortex. The results demonstrate that the primordium of the cerebellum comprises the ependymal, mantle, and marginal layers at embryonic day 12 (E12). Subsequently, the laminated cerebellar cortex undergoes cell proliferation, differentiation, and migration, and at about postnatal day 0 (P0), the cerebellar cortex presents an external granular layer, a molecular layer, a Purkinje layer, and an internal granular layer. The external granular layer is thickest at P6/7 and disappears at P20. From P0 to P30, the internal granular cells and the Purkinje cells gradually differentiate and develop until maturity. Apoptotic neurons are evident in the layered structure in the developing cerebellar cortex. The external granular layer disappears gradually because of cell migration and apoptosis. The cells of the other layers primarily undergo differentiation, development, and apoptosis.

  13. Thalamic, brainstem, and cerebellar glucose metabolism in the hemiplegic monkey

    Energy Technology Data Exchange (ETDEWEB)

    Shimoyama, I.; Dauth, G.W.; Gilman, S.; Frey, K.A.; Penney, J.B. Jr.

    1988-12-01

    Unilateral ablation of cerebral cortical areas 4 and 6 of Brodmann in the macaque monkey results in a contralateral hemiplegia that resolves partially with time. During the phase of dense hemiplegia, local cerebral metabolic rate for glucose (1CMRG1c) is decreased significantly in most of the thalamic nuclei ipsilateral to the ablation, and there are slight contralateral decreases. The lCMRGlc is reduced bilaterally in most of the brainstem nuclei and bilaterally in the deep cerebellar nuclei, but only in the contralateral cerebellar cortex. During the phase of partial motor recovery, lCMRGlc is incompletely restored in many of the thalamic nuclei ipsilateral to the ablation and completely restored in the contralateral nuclei. In the brainstem and deep cerebellar nuclei, poor to moderate recovery occurs bilaterally. Moderate recovery occurs in the contralateral cerebellar cortex. The findings demonstrate that a unilateral cerebral cortical lesion strongly affects lCMRGlc in the thalamus ipsilaterally and in the cerebellar cortex contralaterally, but in the brainstem bilaterally. Partial recovery of lCMRGlc accompanies the progressive motor recovery. The structures affected include those with direct, and also those with indirect, connections to the areas ablated.

  14. Cerebellar network plasticity: from genes to fast oscillation.

    Science.gov (United States)

    Cheron, G; Servais, L; Dan, B

    2008-04-22

    The role of the cerebellum has been increasingly recognized not only in motor control but in sensory, cognitive and emotional learning and regulation. Purkinje cells, being the sole output from the cerebellar cortex, occupy an integrative position in this network. Plasticity at this level is known to critically involve calcium signaling. In the last few years, electrophysiological study of genetically engineered mice has demonstrated the topical role of several genes encoding calcium-binding proteins (calretinin, calbindin, parvalbumin). Specific inactivation of these genes results in the emergence of a fast network oscillation (ca. 160 Hz) throughout the cerebellar cortex in alert animals, associated with ataxia. This oscillation is produced by synchronization of Purkinje cells along the parallel fiber beam. It behaves as an electrophysiological arrest rhythm, being blocked by sensorimotor stimulation. Pharmacological manipulations showed that the oscillation is blocked by GABA(A) and NMDA antagonists as well as gap junction blockers. This cerebellar network oscillation has also been documented in mouse models of human conditions with complex developmental cerebellar dysfunction, such as Angelman syndrome and fetal alcohol syndrome. Recent evidence suggests a relationship between fast oscillation and cerebellar long term depression (LTD). This may have major implications for future therapeutic targeting.

  15. Rapid signaling actions of environmental estrogens in developing granule cell neurons are mediated by estrogen receptor ß.

    Science.gov (United States)

    Le, Hoa H; Belcher, Scott M

    2010-12-01

    Estrogenic endocrine disrupting chemicals (EDCs) constitute a diverse group of man-made chemicals and natural compounds derived from plants and microbial metabolism. Estrogen-like actions are mediated via the nuclear hormone receptor activity of estrogen receptor (ER)α and ERβ and rapid regulation of intracellular signaling cascades. Previous study defined cerebellar granule cell neurons as estrogen responsive and that granule cell precursor viability was developmentally sensitive to estrogens. In this study experiments using Western blot analysis and pharmacological approaches have characterized the receptor and signaling modes of action of selective and nonselective estrogen ligands in developing cerebellar granule cells. Estrogen treatments were found to briefly increase ERK1/2-phosphorylation and then cause prolonged depression of ERK1/2 activity. The sensitivity of granule cell precursors to estrogen-induced cell death was found to require the integrated activation of membrane and intracellular ER signaling pathways. The sensitivity of granule cells to selective and nonselective ER agonists and a variety of estrogenic and nonestrogenic EDCs was also examined. The ERβ selective agonist DPN, but not the ERα selective agonist 4,4',4'-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol or other ERα-specific ligands, stimulated cell death. Only EDCs with selective or nonselective ERβ activities like daidzein, equol, diethylstilbestrol, and bisphenol A were observed to induce E2-like neurotoxicity supporting the conclusion that estrogen sensitivity in granule cells is mediated via ERβ. The presented results also demonstrate the utility of estrogen sensitive developing granule cells as an in vitro assay for elucidating rapid estrogen-signaling mechanisms and to detect EDCs that act at ERβ to rapidly regulate intracellular signaling.

  16. Cerebellar hemorrhage after embolization of ruptured vertebral dissecting aneurysm proximal to PICA including parent artery

    Directory of Open Access Journals (Sweden)

    Akira Tamase

    2014-01-01

    Full Text Available Background: Some complications related to vertebral artery occlusion by endovascular technique have been reported. However, cerebellar hemorrhage after vertebral artery occlusion in subacute phase is rare. In this report, we describe a patient who showed cerebellar hemorrhage during hypertensive therapy for vasospasm after embolization of a vertebral dissecting aneurysm. Case Description: A 56-year-old female with a ruptured vertebral dissecting aneurysm proximal to the posterior inferior cerebellar artery developed cerebellar hemorrhage 15 days after embolization of the vertebral artery, including the dissected site. In this patient, the preserved posterior inferior cerebellar artery fed by retrograde blood flow might have been hemodynamically stressed during hypertensive and antiplatelet therapies for subarachnoid hemorrhage, resulting in cerebellar hemorrhage. Conclusion: Although cerebellar hemorrhage is not prone to occur in the nonacute stage of embolization of the vertebral artery, it should be taken into consideration that cerebellar hemorrhage may occur during hypertensive treatment.

  17. Mitotic Events in Cerebellar Granule Progenitor Cells that Expand Cerebellar Surface Area Are Critical for Normal Cerebellar Cortical Lamination in Mice

    Science.gov (United States)

    Chang, Joshua C.; Leung, Mark; Gokozan, Hamza Numan; Gygli, Patrick Edwin; Catacutan, Fay Patsy; Czeisler, Catherine; Otero, José Javier

    2015-01-01

    Late embryonic and postnatal cerebellar folial surface area expansion promotes cerebellar cortical cytoarchitectural lamination. We developed a streamlined sampling scheme to generate unbiased estimates of murine cerebellar surface area and volume using stereological principles. We demonstrate that during the proliferative phase of the external granule layer (EGL) and folial surface area expansion, EGL thickness does not change and thus is a topological proxy for progenitor self-renewal. The topological constraints indicate that during proliferative phases, migration out of the EGL is balanced by self-renewal. Progenitor self-renewal must, therefore, include mitotic events yielding either 2 cells in the same layer to increase surface area (β-events) and mitotic events yielding 2 cells, with 1 cell in a superficial layer and 1 cell in a deeper layer (α-events). As the cerebellum grows, therefore, β-events lie upstream of α-events. Using a mathematical model constrained by the measurements of volume and surface area, we could quantify inter-mitotic times for β-events on a per-cell basis in post-natal mouse cerebellum. Furthermore, we found that loss of CCNA2, which decreases EGL proliferation and secondarily induces cerebellar cortical dyslamination, shows preserved α-type events. Thus, CCNA2-null cerebellar granule progenitor cells are capable of self-renewal of the EGL stem cell niche; this is concordant with prior findings of extensive apoptosis in CCNA2-null mice. Similar methodologies may provide another layer of depth to the interpretation of results from stereological studies. PMID:25668568

  18. Synaptically released neurotransmitter fails to desensitize postsynaptic GABA(A) receptors in cerebellar cultures.

    Science.gov (United States)

    Mellor, J R; Randall, A D

    2001-05-01

    GABA concentration jump experiments performed on membrane patches predict that postsynaptic GABA(A) receptors will become desensitized following the release of the contents of a single GABA-containing synaptic vesicle. To examine this we used a single synaptic bouton stimulation technique to directly examine whether postsynaptic GABA(A) receptors in cultured cerebellar granule cells exhibit transmitter-induced desensitization. In a large number of recordings, no evidence was found for desensitization of postsynaptic GABA(A) receptors by vesicularly released transmitter. This was the case even when as many as 40 vesicles were released from a single bouton within 1.5 s. In addition, postsynaptic depolarization and application of the benzodiazepine flunitrazepam, manipulations previously shown to enhance desensitization of GABA(A) receptors, failed to unmask transmitter-induced desensitization. In contrast, a single 2- to 3-s application of a high concentration of exogenous GABA was able to depress synaptic responsiveness for up to 70 s. Furthermore, pharmacological depletion of GABA eliminated inhibitory synaptic communication, suggesting that GABA is the transmitter and the desensitization-resistant inhibitory postsynaptic currents are not mediated by a "nondesensitizing" ligand such as beta-alanine. Overall our data indicate that a specific desensitization-resistant population of GABA(A) receptors are present at postsynaptic sites on cultured cerebellar granule cells.

  19. Early maternal deprivation in rats induces gender-dependent effects on developing hippocampal and cerebellar cells.

    Science.gov (United States)

    Llorente, Ricardo; Gallardo, Meritxell López; Berzal, Alvaro Llorente; Prada, Carmen; Garcia-Segura, Luis Miguel; Viveros, María-Paz

    2009-05-01

    Adult animals submitted to a single prolonged episode of maternal deprivation [24h, postnatal day 9-10] show behavioral alterations that resemble specific symptoms of schizophrenia. According to the neurodevelopmental theory, these behavioral deficits might be mediated by detrimental neurodevelopmental processes that might be associated, at least partially, with stress-induced corticosterone responses. In order to address this hypothesis, we have focused on the hippocampus and cerebellar cortex, two brain regions that show high density of glucocorticoid receptors, and analyzed possible neuronal and glial alterations by immunohistochemical techniques. To evaluate the presence of degenerated neurons we used Fluoro-Jade-C (FJ-C) staining and for the study of astrocytes we employed glial fibrillary acidic protein (GFAP). Within control animals, females showed significantly more GFAP positive cells than males and a trend towards more FJ-C positive cells. Maternal deprivation induced neuronal degeneration and astroglial changes in the hippocampus and cerebellar cortex of neonatal rats that, in general, were more marked in males. This differential effect may be attributable to a greater vulnerability of males to this kind of early environmental insult and/or to sex-dependent differences in the onset and/or progression of the effects. The present experimental procedure may be instrumental in elucidating sex-dependent mechanisms of neurodevelopmental psychiatric disorders with a basis in early environmental insults.

  20. The Gs-linked receptor GPR3 inhibits the proliferation of cerebellar granule cells during postnatal development.

    Directory of Open Access Journals (Sweden)

    Shigeru Tanaka

    Full Text Available BACKGROUND: During postnatal murine and rodent cerebellar development, cerebellar granule precursors (CGP gradually stop proliferating as they differentiate after migration to the internal granule layer (IGL. Molecular events that govern this program remain to be fully elucidated. GPR3 belongs to a family of Gs-linked receptors that activate cyclic AMP and are abundantly expressed in the adult brain. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the role of this orphan receptor in CGP differentiation, we determined that exogenous GPR3 expression in rat cerebellar granule neurons partially antagonized the proliferative effect of Sonic hedgehog (Shh, while endogenous GPR3 inhibition by siRNA stimulated Shh-induced CGP proliferation. In addition, exogenous GPR3 expression in CGPs correlated with increased p27/kip expression, while GPR3 knock-down led to a decrease in p27/kip expression. In wild-type mice, GPR3 expression increased postnatally and its expression was concentrated in the internal granular layer (IGL. In GPR3 -/- mice, the IGL was widened with increased proliferation of CGPs, as measured by bromodeoxyuridine incorporation. Cell cycle kinetics of GPR3-transfected medulloblastoma cells revealed a G0/G1 block, consistent with cell cycle exit. CONCLUSIONS/SIGNIFICANCE: These results thus indicate that GPR3 is a novel antiproliferative mediator of CGPs in the postnatal development of murine cerebellum.

  1. Cascaded-cladding-pumped cascaded Raman fiber amplifier.

    Science.gov (United States)

    Jiang, Huawei; Zhang, Lei; Feng, Yan

    2015-06-01

    The conversion efficiency of double-clad Raman fiber laser is limited by the cladding-to-core area ratio. To get high conversion efficiency, the inner-cladding-to-core area ratio has to be less than about 8, which limits the brightness enhancement. To overcome the problem, a cascaded-cladding-pumped cascaded Raman fiber laser with multiple-clad fiber as the Raman gain medium is proposed. A theoretical model of Raman fiber amplifier with multiple-clad fiber is developed, and numerical simulation proves that the proposed scheme can improve the conversion efficiency and brightness enhancement of cladding pumped Raman fiber laser.

  2. Cerebellar Development and Autism Spectrum Disorder in Tuberous Sclerosis Complex.

    Science.gov (United States)

    Sundberg, Maria; Sahin, Mustafa

    2015-12-01

    Approximately 50% of patients with the genetic disease tuberous sclerosis complex present with autism spectrum disorder. Although a number of studies have investigated the link between autism and tuberous sclerosis complex, the etiology of autism spectrum disorder in these patients remains unclear. Abnormal cerebellar function during critical phases of development could disrupt functional processes in the brain, leading to development of autistic features. Accordingly, the authors review the potential role of cerebellar dysfunction in the pathogenesis of autism spectrum disorder in tuberous sclerosis complex. The authors also introduce conditional knockout mouse models of Tsc1 and Tsc2 that link cerebellar circuitry to the development of autistic-like features. Taken together, these preclinical and clinical investigations indicate the cerebellum has a profound regulatory role during development of social communication and repetitive behaviors.

  3. An unusual cause of adult onset cerebellar ataxia with hypogonadism

    Directory of Open Access Journals (Sweden)

    Menon Ramshekhar

    2009-01-01

    Full Text Available We report an unusual case of sporadic adult onset cerebellar ataxia with hypogonadism. A 40-year-old unmarried man presented with progressive ataxia and dysarthria along with complaints of non-development of secondary sexual characteristics and erectile dysfunction. There were complaints of intermittent diarrhea. Clinical examination revealed a pan-cerebellar syndrome with features of hypoandrogenism. No eye movement abnormalities were evident. There were signs of malabsorption. Investigations confirmed the presence of auto-antibodies found in celiac disease, and a duodenal biopsy confirmed the same. Hypoandrogenism was postulated to be due to hypergonadotropic hypogonadism which has been mentioned in a few patients of celiac disease. However, the pattern seen in our patient was of a hypogonadotropic hypogonadism. This is probably secondary to an autoimmune hypophysitis seen in some patients in the absence of other clinical manifestations. Autoantibody testing should be a diagnostic necessity in any adult with a sporadic cerebellar ataxia.

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  7. File list: ALL.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

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  8. File list: His.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: Oth.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. File list: DNS.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  11. File list: DNS.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. File list: ALL.Neu.05.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  13. File list: Pol.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  14. File list: Pol.Neu.20.AllAg.Cerebellar_Cortex [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  15. File list: Unc.Neu.10.AllAg.Cerebellar_Cortex [Chip-atlas[Archive

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  16. File list: InP.Neu.05.AllAg.Cerebellar_Cortex [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. File list: His.Neu.20.AllAg.Cerebellar_Cortex [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  18. File list: Pol.Neu.10.AllAg.Cerebellar_Cortex [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  19. File list: ALL.Neu.50.AllAg.Cerebellar_Cortex [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: ALL.Neu.20.AllAg.Cerebellar_Cortex [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  2. File list: Oth.Neu.10.AllAg.Cerebellar_Cortex [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  3. File list: Oth.Neu.50.AllAg.Cerebellar_Cortex [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  4. File list: His.Neu.05.AllAg.Cerebellar_Cortex [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: Unc.Neu.50.AllAg.Cerebellar_Cortex [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  6. File list: ALL.Neu.10.AllAg.Cerebellar_Cortex [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  7. File list: Oth.Neu.20.AllAg.Cerebellar_Cortex [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  8. File list: InP.Neu.20.AllAg.Cerebellar_Cortex [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: ALL.Neu.05.AllAg.Cerebellar_Cortex [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.05.AllAg.Cerebellar_Cortex mm9 All antigens Neural Cerebellar Cortex SRX112...18103 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.05.AllAg.Cerebellar_Cortex.bed ...

  10. File list: Oth.Neu.05.AllAg.Cerebellar_Cortex [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  11. File list: NoD.Neu.05.AllAg.Cerebellar_Cortex [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. File list: Pol.Neu.50.AllAg.Cerebellar_Cortex [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.50.AllAg.Cerebellar_Cortex mm9 RNA polymerase Neural Cerebellar Cortex SRX0...62942,SRX143820,SRX685286,SRX685285 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.50.AllAg.Cerebellar_Cortex.bed ...

  13. File list: His.Neu.10.AllAg.Cerebellar_Cortex [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.10.AllAg.Cerebellar_Cortex mm9 Histone Neural Cerebellar Cortex SRX323779,S...45,SRX1318089,SRX1318093,SRX1318090,SRX1318091,SRX1318094 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.10.AllAg.Cerebellar_Cortex.bed ...

  14. File list: NoD.Neu.50.AllAg.Cerebellar_Cortex [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Neu.50.AllAg.Cerebellar_Cortex mm9 No description Neural Cerebellar Cortex http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Neu.50.AllAg.Cerebellar_Cortex.bed ...

  15. File list: Pol.Neu.05.AllAg.Cerebellar_Cortex [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.05.AllAg.Cerebellar_Cortex mm9 RNA polymerase Neural Cerebellar Cortex SRX0...62942,SRX143820,SRX685285,SRX685286 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.05.AllAg.Cerebellar_Cortex.bed ...

  16. File list: Unc.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. File list: His.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.10.AllAg.Cerebellar_granule_neurons mm9 Histone Neural Cerebellar granule n...eurons http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.10.AllAg.Cerebellar_granule_neurons.bed ...

  18. File list: His.Neu.05.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.05.AllAg.Cerebellar_granule_neurons mm9 Histone Neural Cerebellar granule n...eurons http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.05.AllAg.Cerebellar_granule_neurons.bed ...

  19. File list: His.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: Pol.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: Unc.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Neu.50.AllAg.Cerebellar_granule_neurons mm9 Unclassified Neural Cerebellar gran...ule neurons http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.50.AllAg.Cerebellar_granule_neurons.bed ...

  2. File list: Oth.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Neu.20.AllAg.Cerebellar_granule_neurons mm9 TFs and others Neural Cerebellar gran...ule neurons http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.20.AllAg.Cerebellar_granule_neurons.bed ...

  3. File list: ALL.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.10.AllAg.Cerebellar_granule_neurons mm9 All antigens Neural Cerebellar gran...ule neurons SRX685882,SRX685880,SRX685883,SRX685885,SRX685877,SRX685878 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.10.AllAg.Cerebellar_granule_neurons.bed ...

  4. File list: Oth.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Neu.50.AllAg.Cerebellar_granule_neurons mm9 TFs and others Neural Cerebellar gran...ule neurons http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.50.AllAg.Cerebellar_granule_neurons.bed ...

  5. File list: Oth.Neu.05.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Neu.05.AllAg.Cerebellar_granule_neurons mm9 TFs and others Neural Cerebellar gran...ule neurons http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.05.AllAg.Cerebellar_granule_neurons.bed ...

  6. File list: Pol.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.10.AllAg.Cerebellar_granule_neurons mm9 RNA polymerase Neural Cerebellar gran...ule neurons http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.10.AllAg.Cerebellar_granule_neurons.bed ...

  7. File list: Unc.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Neu.10.AllAg.Cerebellar_granule_neurons mm9 Unclassified Neural Cerebellar gran...ule neurons http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.10.AllAg.Cerebellar_granule_neurons.bed ...

  8. File list: DNS.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. Cerebellar diaschisis in pontine infractions: a report of five cases

    Energy Technology Data Exchange (ETDEWEB)

    Tsuda, Yoshiyasu [Kagawa Medical School (Japan). Second Dept. of Internal Medicine; Ayada, Yoshihide [Kagawa Medical School (Japan). Second Dept. of Internal Medicine; Izumi, Yoshinari [Kagawa Medical School (Japan). Second Dept. of Internal Medicine; Ichihara, Sin-Ichiro [Kagawa Medical School (Japan). Second Dept. of Internal Medicine; Hosomi, Naohisa [Kagawa Medical School (Japan). Second Dept. of Internal Medicine; Ohkawa, Motoomi [Kagawa Medical School (Japan). Dept. of Radiology; Matsuo, Hirohide [Kagawa Medical School (Japan). Second Dept. of Internal Medicine

    1995-05-01

    We evaluate regional cerebral and cerebellar perfusion to prove the occurrence and follow the persistence of crossed cerebellar diaschisis in infratentorial pontine infarction. Six consecutive patients exhibiting mild hemiparetic symptoms or a heavy feeling in the head (mean age 65 years; four women, two men) and diagnosed as having pontine infarction by magnetic resonance imaging were sugjected to evaluation. Lesions due to infarction were located at the upper basis pontis in five partients and the upper tegmentum pontis in one, and medially at the paramedian portion in four and laterally in two. Regional cerebral and cerebellar perfusion was evaluated semiquantitatively by iodine-123 N-isopropyl-p-iodoamphetamine (IMP) single-photon emission tomography (SPET); this was done during the acute stage in five cases (mean time after onset: 0.7 months) and during the chronic stage in three (mean time after onset: 14.8 months) Significant asymmetry in cerebellar perfusion, which was reduced in the contralateral or ipsilateral cerebellar hemisphere, was demonstrated semiquantitatively in four cases during the acute stage and in one during the chronic stage, as compared with normal controls. This asymmetry continued to the chronic stage (6.5 and 33.0 months) in two cases, while no patient showed any significant asymmetries in cerebral perdusion in any region of interest in either SPET study. The pontine lesion may damage the pyramidal tract and corticocerebellar pathway, and interruption of the cerebrocerebellar pontine circuits may be regarded as the cause of the crossed cerebellar diaschisis observed in five of the six reported patients with pontine infarction. (orig.)

  10. Cerebellar substrates for error correction in motor conditioning.

    Science.gov (United States)

    Gluck, M A; Allen, M T; Myers, C E; Thompson, R F

    2001-11-01

    The authors evaluate a mapping of Rescorla and Wagner's (1972) behavioral model of classical conditioning onto the cerebellar substrates for motor reflex learning and illustrate how the limitations of the Rescorla-Wagner model are just as useful as its successes for guiding the development of new psychobiological theories of learning. They postulate that the inhibitory pathway that returns conditioned response information from the cerebellar interpositus nucleus back to the inferior olive is the neural basis for the error correction learning proposed by Rescorla and Wagner (Gluck, Myers, & Thompson, 1994; Thompson, 1986). The authors' cerebellar model expects that behavioral processes described by the Rescorla-Wagner model will be localized within the cerebellum and related brain stem structures, whereas behavioral processes beyond the scope of the Rescorla-Wagner model will depend on extracerebellar structures such as the hippocampus and related cortical regions. Simulations presented here support both implications. Several novel implications of the authors' cerebellar error-correcting model are described including a recent empirical study by Kim, Krupa, and Thompson (1998), who verified that suppressing the putative error correction pathway should interfere with the Kamin (1969) blocking effect, a behavioral manifestation of error correction learning. The authors also discuss the model's implications for understanding the limits of cerebellar contributions to associative learning and how this informs our understanding of hippocampal function in conditioning. This leads to a more integrative view of the neural substrates of conditioning in which the authors' real-time circuit-level model of the cerebellum can be viewed as a generalization of the long-term memory module of Gluck and Myers' (1993) trial-level theory of cerebellar-hippocampal interaction in motor conditioning.

  11. Emotional disorders in patients with cerebellar damage – case studies

    Directory of Open Access Journals (Sweden)

    Siuda, Katarzyna

    2014-04-01

    Full Text Available Aim: Growing number of research shows the role of the cerebellum in the regulation of affect. Lesions of the cerebellum can lead to emotional disregulation, a significant part of the Cerebellar Cognitive Affective Syndrome. The aim of this article is to analyze the most recent studies concerning the cerebellar participation in emotional reactions and to present three cases: two female and one male who suffered from cerebellar damage and presented post-traumatic affective and personality change. Method: The patients’ neuropsychological examination was performed with Raven’s Progressive Matrices Test – standard version, Trial Making Test, Wisconsin Card Sorting Test, Auditory Verbal Learning Test by Łuria, Benton Visual Retention Test, Verbal Fluency Test, Stroop Interference Test, Attention and Perceptivity Test (Test Uwagi i Spostrzegawczości TUS, Frontal Behavioral Inventory (FBI. Results: The review of the literature suggest cerebellar participation, especially teh vermis and paravermial regions, in the detection, integration and filtration of emotional information and in regulation of autonomic emotional responses. In the described patients we observed: oversensitivity, irritability, impulsivity and self-neglect. The man and the woman with right-sided lesions presented similar symptoms: rigidity of thought, stubbornness, lack of criticism, jocular and inappropriate behavior. The woman with left-sided cerebellar lesion was adynamic, apathic and passive, she presented emotional blunting, social isolation, lack of interests and motivation, general cognitive slowdown. Conclusions: Both the analyzed research and the described cases indicate the connection between the cerebellum and emotion regulation. The symptoms presented by the described patients were most probably a consequence of damaged cerebellar projections to subcortical structures (the limbic system and frontal areas. The diversification of symptoms depending on the localization

  12. Autoregressive cascades on random networks

    Science.gov (United States)

    Iyer, Srikanth K.; Vaze, Rahul; Narasimha, Dheeraj

    2016-04-01

    A network cascade model that captures many real-life correlated node failures in large networks via load redistribution is studied. The considered model is well suited for networks where physical quantities are transmitted, e.g., studying large scale outages in electrical power grids, gridlocks in road networks, and connectivity breakdown in communication networks, etc. For this model, a phase transition is established, i.e., existence of critical thresholds above or below which a small number of node failures lead to a global cascade of network failures or not. Theoretical bounds are obtained for the phase transition on the critical capacity parameter that determines the threshold above and below which cascade appears or disappears, respectively, that are shown to closely follow numerical simulation results.

  13. Toxic effects of TiO2 nanoparticles in primary cultured rat sertoli cells are mediated via a dysregulated Ca(2+) /PKC/p38 MAPK/NF-κB cascade.

    Science.gov (United States)

    Ye, Lingqun; Hong, Fashui; Ze, Xiao; Li, Lingjuan; Zhou, Yaoming; Ze, Yuguan

    2017-02-11

    Although numerous studies have demonstrated that titanium dioxide nanoparticles (TiO2 NPs) can be accumulated in various animal organs and can cause toxicity, there is currently only limited data regarding reproductive toxicity especially on the toxic mechanisms of TiO2 NPs in Sertoli cells. In order to investigate the mechanism of reproductive toxicity, primary cultured rat Sertoli cells were exposed to 5, 15, or 30 μg/mL TiO2 NPs for 24 h, and TiO2 NPs internalization, expression of PKC (p-PKC) and p38 MAPK (p-p38 MAPK) as well as calcium homeostasis were examined. Our findings demonstrated that TiO2 NPs crossed the membrane into the cytoplasm or nucleus, and significantly suppressed cell viability of primary cultured rat Sertoli cells in a concentration-dependent manner. Furthermore, immunological dysfunction caused by TiO2 NPs was involved in the increased expression of NF-κB, TNF-α, and IL-1β, and decreased IκB expression. TiO2 NPs significantly decreased Ca(2+) -ATPase and Ca(2+) /Mg(2+) -ATPase activity and enhanced intracellular Ca(2+) levels, and up-regulated the expression of p-PKC and p-p38 MAPK in a dose-dependent manner in primary cultured rat Sertoli cells. Taken together, these findings indicate that TiO2 NPs may induce immunological dysfunction of primary cultured rat Sertoli cells by stimulating the Ca(2+) /PKC/p38 MAPK cascade, which triggers NF-κB activation and ultimately induces the expression of inflammatory cytokines in primary cultured rat Sertoli cells. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2017.

  14. Choline Uptake by Glomerular Synapses Isolated from Bovine Cerebellar Vermis.

    Science.gov (United States)

    1986-01-01

    28 034 UNCLASSIFIED -7t. holing uptake by glomerular aynapaea isolated from bovine cerebellar venni - . 1) N1 IrRRIAN.E L NfISINndwr EtIIOMAS86 .t...w. -%FAt~Jr~a~etn 0,oAAM TX78215-5301 IL’SAJ) A-xpid ( kaolin 22nd. 19W5) hh.lhoac-anln uplake -ainalnnn 177 DIOMIDICAL DmIVIIN,~ F-5’. . Brain...Research. 366 (1986) 401-404 401 Elsevier BRE 21387 Choline uptake by glomerular synapses isolated from bovine cerebellar vermis D.M. TERRIAN, E.L

  15. Inside the Thompson laboratory during the "cerebellar years" and the continuing cerebellar story.

    Science.gov (United States)

    Lavond, D G; Wikgren, J; Nokia, M S

    2011-02-01

    This paper is based on the talk by one of the authors (DL) given at the symposium for the retirement of RF Thompson (RF Thompson: A bridge between 20th and 21st century neuroscience). We first make some informal observations of the historical times and research conditions in the Thompson laboratory when the cerebellum was found to play a critical role in eye lid classical conditioning, the "cerebellar years". These conditions influenced our collaborative international program on the phenomenon known as "transfer of training" or "savings". Our research shows that the appearance of "savings" is an artifact of the order of testing, and depends upon the functioning of the contralateral interpositus nucleus (IPN) in a way that is complementary to the role of the IPN in normal eyelid classical conditioning.

  16. Postural Ataxia in Cerebellar Downbeat Nystagmus: Its Relation to Visual, Proprioceptive and Vestibular Signals and Cerebellar Atrophy

    Science.gov (United States)

    Helmchen, Christoph; Kirchhoff, Jan-Birger; Göttlich, Martin; Sprenger, Andreas

    2017-01-01

    Background The cerebellum integrates proprioceptive, vestibular and visual signals for postural control. Cerebellar patients with downbeat nystagmus (DBN) complain of unsteadiness of stance and gait as well as blurred vision and oscillopsia. Objectives The aim of this study was to elucidate the differential role of visual input, gaze eccentricity, vestibular and proprioceptive input on the postural stability in a large cohort of cerebellar patients with DBN, in comparison to healthy age-matched control subjects. Methods Oculomotor (nystagmus, smooth pursuit eye movements) and postural (postural sway speed) parameters were recorded and related to each other and volumetric changes of the cerebellum (voxel-based morphometry, SPM). Results Twenty-seven patients showed larger postural instability in all experimental conditions. Postural sway increased with nystagmus in the eyes closed condition but not with the eyes open. Romberg’s ratio remained stable and was not different from healthy controls. Postural sway did not change with gaze position or graviceptive input. It increased with attenuated proprioceptive input and on tandem stance in both groups but Romberg’s ratio also did not differ. Cerebellar atrophy (vermal lobule VI, VIII) correlated with the severity of impaired smooth pursuit eye movements of DBN patients. Conclusions Postural ataxia of cerebellar patients with DBN cannot be explained by impaired visual feedback. Despite oscillopsia visual feedback control on cerebellar postural control seems to be preserved as postural sway was strongest on visual deprivation. The increase in postural ataxia is neither related to modulations of single components characterizing nystagmus nor to deprivation of single sensory (visual, proprioceptive) inputs usually stabilizing stance. Re-weighting of multisensory signals and/or inappropriate cerebellar motor commands might account for this postural ataxia. PMID:28056109

  17. Dyslexic Children Show Atypical Cerebellar Activation and Cerebro-Cerebellar Functional Connectivity in Orthographic and Phonological Processing.

    Science.gov (United States)

    Feng, Xiaoxia; Li, Le; Zhang, Manli; Yang, Xiujie; Tian, Mengyu; Xie, Weiyi; Lu, Yao; Liu, Li; Bélanger, Nathalie N; Meng, Xiangzhi; Ding, Guosheng

    2017-04-01

    Previous neuroimaging studies have found atypical cerebellar activation in individuals with dyslexia in either motor-related tasks or language tasks. However, studies investigating atypical cerebellar activation in individuals with dyslexia have mostly used tasks tapping phonological processing. A question that is yet unanswered is whether the cerebellum in individuals with dyslexia functions properly during orthographic processing of words, as growing evidence shows that the cerebellum is also involved in visual and spatial processing. Here, we investigated cerebellar activation and cerebro-cerebellar functional connectivity during word processing in dyslexic readers and typically developing readers using tasks that tap orthographic and phonological codes. In children with dyslexia, we observed an abnormally higher engagement of the bilateral cerebellum for the orthographic task, which was negatively correlated with literacy measures. The greater the reading impairment was for young dyslexic readers, the stronger the cerebellar activation was. This suggests a compensatory role of the cerebellum in reading for children with dyslexia. In addition, a tendency for higher cerebellar activation in dyslexic readers was found in the phonological task. Moreover, the functional connectivity was stronger for dyslexic readers relative to typically developing readers between the lobule VI of the right cerebellum and the left fusiform gyrus during the orthographic task and between the lobule VI of the left cerebellum and the left supramarginal gyrus during the phonological task. This pattern of results suggests that the cerebellum compensates for reading impairment through the connections with specific brain regions responsible for the ongoing reading task. These findings enhance our understanding of the cerebellum's involvement in reading and reading impairment.

  18. Preserved Glucose Metabolism of Deep Cerebellar Nuclei in a Case of Multiple System Atrophy with Predominant Cerebellar Ataxia: F-18 Fluorodeoxyglucose Positron Emission Tomography Study

    Directory of Open Access Journals (Sweden)

    Oh Dae Kwon

    2010-10-01

    Full Text Available The cerebellar glucose metabolism of multiple system atrophy with predominant cerebellar ataxia (MSA-C is known to be decreased but is not defined among areas of cerebellum. We encountered a 54-year-old man who developed dizziness and progressive ataxia followed by urinary incontinence and orthostatic hypotension, all of those symptoms progressed relentlessly and the symptoms responded poorly to levodopa therapy. Visual analysis and statistical parametric mapping analysis of F-18 fluorodeoxyglucose positron emission tomography showed hypometabolism of both cerebellar hemisphere, severe at cortical area, and pons. There was clear sparing of deep cerebellar nuclei. Our report, as we know, shows the first case of preserved glucose metabolism of deep cerebellar nuclei relative to cerebellar cortex in an MSA-C patient.

  19. Calcium as a trigger for cerebellar long-term synaptic depression.

    Science.gov (United States)

    Finch, Elizabeth A; Tanaka, Keiko; Augustine, George J

    2012-09-01

    Cerebellar long-term depression (LTD) is a form of long-term synaptic plasticity that is triggered by calcium(Ca2+) signals in the postsynaptic Purkinje cell. This Ca2+comes both from IP3-mediated release from intracellular Ca2+ stores, as well as from Ca2+ influx through voltage-gated Ca2+ channels. The Ca2+ signal that triggers LTD occurs locally within dendritic spines and is due to supralinear summation of signals coming from these two Ca2+ sources. The properties of this postsynaptic Ca2+signal can explain several features of LTD, such as its associativity, synapse specificity, and dependence on thetiming of synaptic activity, and can account for the slow kinetics of LTD expression. Thus, from a Ca2+ signaling perspective, LTD is one of the best understood forms of synaptic plasticity.

  20. Interneuron- and GABAA receptor-specific inhibitory synaptic plasticity in cerebellar Purkinje cells

    Science.gov (United States)

    He, Qionger; Duguid, Ian; Clark, Beverley; Panzanelli, Patrizia; Patel, Bijal; Thomas, Philip; Fritschy, Jean-Marc; Smart, Trevor G.

    2015-07-01

    Inhibitory synaptic plasticity is important for shaping both neuronal excitability and network activity. Here we investigate the input and GABAA receptor subunit specificity of inhibitory synaptic plasticity by studying cerebellar interneuron-Purkinje cell (PC) synapses. Depolarizing PCs initiated a long-lasting increase in GABA-mediated synaptic currents. By stimulating individual interneurons, this plasticity was observed at somatodendritic basket cell synapses, but not at distal dendritic stellate cell synapses. Basket cell synapses predominantly express β2-subunit-containing GABAA receptors; deletion of the β2-subunit ablates this plasticity, demonstrating its reliance on GABAA receptor subunit composition. The increase in synaptic currents is dependent upon an increase in newly synthesized cell surface synaptic GABAA receptors and is abolished by preventing CaMKII phosphorylation of GABAA receptors. Our results reveal a novel GABAA receptor subunit- and input-specific form of inhibitory synaptic plasticity that regulates the temporal firing pattern of the principal output cells of the cerebellum.

  1. White Matter Microstructural Organization Is Higher with Age in Adult Superior Cerebellar Peduncles.

    Science.gov (United States)

    Kanaan, Richard A; Allin, Matthew; Picchioni, Marco M; Shergill, Sukhwinder S; McGuire, Philip K

    2016-01-01

    Using diffusion tensor imaging, we conducted an exploratory investigation of the relationship between white matter tract microstructure and age in 200 healthy adult subjects using tract-based spatial statistics (TBSS). Though most tracts showed the slight decline in microstructural organization with age widely noted, in both superior cerebellar peduncles (SCP) it correlated positively with age, a result not previously reported. We confirmed this by using an alternative method, and by repeating our TBSS analysis in an additional sample of 133 healthy adults. In exploring this surprising result we considered the possibility that this might arise from the continual cognitive and motor refinement that is enacted in the cerebellum: we found that tract microstructure in both SCPs was also strongly correlated with IQ, again in contrast with all other tracts, and its relationship with age mediated by IQ, as a training model would predict.

  2. White matter microstructural organisation is higher with age in adult Superior Cerebellar Peduncles alone

    Directory of Open Access Journals (Sweden)

    Richard eKanaan

    2016-04-01

    Full Text Available Using diffusion tensor imaging, we conducted an exploratory investigation of the relationship between white matter tract microstructure and age in 200 healthy subjects using tract-based spatial statistics (TBSS. Though most tracts showed the slight decline widely noted, microstructural organization in both superior cerebellar peduncles (SCP correlated positively with age, a result not previously reported. We confirmed this by using an alternative method, and by repeating our TBSS analysis in an additional sample of 133 healthy subjects. In exploring this surprising result we considered the possibility that this might arise from the continual cognitive and motor refinement that is enacted in the cerebellum: we found that tract microstructure in both SCPs was also strongly correlated with IQ, again in contrast with all other tracts, and its relationship with age mediated by IQ, as a training model would predict.

  3. Unsteady transonic flow in cascades

    Science.gov (United States)

    Surampudi, S. P.; Adamczyk, J. J.

    1984-01-01

    There is a need for methods to predict the unsteady air loads associated with flutter of turbomachinery blading at transonic speeds. The results of such an analysis in which the steady relative flow approaching a cascade of thin airfoils is assumed to be transonic, irrotational, and isentropic is presented. The blades in the cascade are allowed to undergo a small amplitude harmonic oscillation which generates a small unsteady flow superimposed on the existing steady flow. The blades are assumed to oscillate with a prescribed motion of constant amplitude and interblade phase angle. The equations of motion are obtained by linearizing about a uniform flow the inviscid nonheat conducting continuity and momentum equations. The resulting equations are solved by employing the Weiner Hopf technique. The solution yields the unsteady aerodynamic forces acting on the cascade at Mach number equal to 1. Making use of an unsteady transonic similarity law, these results are compared with the results obtained from linear unsteady subsonic and supersonic cascade theories. A parametric study is conducted to find the effects of reduced frequency, solidity, stagger angle, and position of pitching axis on the flutter.

  4. Azobenzene-functionalized cascade molecules

    DEFF Research Database (Denmark)

    Archut, A.; Vogtle, F.; De Cola, L.;

    1998-01-01

    Cascade molecules bearing up to 32 azobenzene groups in the periphery have been prepared from poly(propylene imine) dendrimers and N-hydroxysuccinimide esters. The dendritic azobenzene species show similar isomerization properties as the corresponding azobenzene monomers. The all-E azobenzene...

  5. CASCADE: Introducing AI into CBT.

    Science.gov (United States)

    Hendley, R. J.; Jurascheck, N.

    1992-01-01

    Discusses changes in training requirements of commerce and industry in the United Kingdom and describes a project, CASCADE, that was developed to investigate and implement the introduction of artificial intelligence (AI) techniques into computer-based training (CBT). An overview of pilot projects in higher education settings is provided. (eight…

  6. Applications of cascade multilevel inverters

    Institute of Scientific and Technical Information of China (English)

    彭方正; 钱照明

    2003-01-01

    Cascade multilevel inverters have been developed for electric utility applications. A cascade M-level inverter consists of (M-1)/2 H-bridges in which each bridge's dc voltage is supported by its own dc capacitor. The new inverter can: (1) generate almost sinusoidal waveform voltage while only switching one time per fundamental cycle; (2) dispense with multi-pulse inverters' transformers used in conventional utility interfaces and static var compensators; (3) enables direct parallel or series transformer-less connection to medium- and high-voltage power systems. In short, the cascade inverter is much more efficient and suitable for utility applications than traditional multi-pulse and pulse width modulation (PWM) inverters. The authors have experimentally demonstrated the superiority of the new inverter for power supply, (hybrid) electric vehicle (EV) motor drive, reactive power (var) and harmonic compensation. This paper summarizes the features, feasibility, and control schemes of the cascade inverter for utility applications including utility interface of renewable energy, voltage regulation, var compensation, and harmonic filtering in power systems. Analytical, simulated, and experimental results demonstrated the superiority of the new inverters.

  7. Applications of cascade multilevel inverters

    Institute of Scientific and Technical Information of China (English)

    彭方正; 钱照明

    2003-01-01

    Cascade multilevel inverters have been developed for electric utility applications. A cascade M-level inverter consists of (M-1)/2 H-bridges in which each bridge's dc voltage is supported by its own de ca-pacitor. The new inverter can : ( 1 ) generate almost sinusoidal waveform voltage while only switching one timeper fundamental cycle ; (2) dispense with multi-pulse inverters' transformers used in conventional utility in-terfaces and static var compensators; (3) enables direct parallel or series transformer-less connection to medium- and high-voltage power systems. In short, the cascade inverter is much more efficient and suitable for utility applications than traditional multi-pulse and pulse width modulation (PWM) inverters. The authors have experimentally demonstrated the superiority of the new inverter for power supply, (hybrid) electric vehicle (EV) motor drive, reactive power (var) and harmonic compensation. This paper summarizes the features,feasibility, and control schemes of the cascade inverter for utility applications including utility interface of renewable energy, voltage regulation, var compensation, and harmonic filtering in power systems. Analytical,simulated, and experimental results demonstrated the superiority of the new inverters.

  8. Cascade Support Vector Machines with Dimensionality Reduction

    Directory of Open Access Journals (Sweden)

    Oliver Kramer

    2015-01-01

    Full Text Available Cascade support vector machines have been introduced as extension of classic support vector machines that allow a fast training on large data sets. In this work, we combine cascade support vector machines with dimensionality reduction based preprocessing. The cascade principle allows fast learning based on the division of the training set into subsets and the union of cascade learning results based on support vectors in each cascade level. The combination with dimensionality reduction as preprocessing results in a significant speedup, often without loss of classifier accuracies, while considering the high-dimensional pendants of the low-dimensional support vectors in each new cascade level. We analyze and compare various instantiations of dimensionality reduction preprocessing and cascade SVMs with principal component analysis, locally linear embedding, and isometric mapping. The experimental analysis on various artificial and real-world benchmark problems includes various cascade specific parameters like intermediate training set sizes and dimensionalities.

  9. Role of Calcium in Cerebellar Learning and Function

    NARCIS (Netherlands)

    Z. Gao (Zhenyu)

    2011-01-01

    textabstractThe cerebellum, which means little brain in Latin, occupies most of the posterior cranial fossa and connects with the dorsal brainstem (Kandel et al., 2000). The cerebellar cortex is one of the most foliated brain structures, which accounts for 10% of the total volume and over half of th

  10. Reevaluating the Role of LTD in Cerebellar Motor Learning

    NARCIS (Netherlands)

    M. Schonewille (Martijn); Z. Gao (Zhenyu); H.J. Boele (Henk-Jan); M.F. Vinueza Veloz (Maria); W.E. Amerika; A. Šimek (Antonia); M.T.G. Jeu (Marcel); J. Steinberg (Jordan); K. Takamiya (Kogo); F.E. Hoebeek (Freek); D. Linden (David); R. Huganir (Richard); C.I. de Zeeuw (Chris)

    2011-01-01

    textabstractLong-term depression at parallel fiber-Purkinje cell synapses (PF-PC LTD) has been proposed to be required for cerebellar motor learning. To date, tests of this hypothesis have sought to interfere with receptors (mGluR1) and enzymes (PKC, PKG, or αCamKII) necessary for induction of PF-PC

  11. Cerebellar Control of Locomotion in Health and Disease

    NARCIS (Netherlands)

    M.F. Vinueza Veloz (Maria)

    2015-01-01

    markdownabstract__Abstract__ Modern neuroscience is paving the way for new insight into cerebellar functions including the control of cognitive, autonomic and emotional processes. Yet, how the cerebellum contributes to complex motor behaviors, such as locomotion, is still only partially understood.

  12. Is a Cerebellar Deficit the Underlying Cause of Reading Disabilities?

    Science.gov (United States)

    Irannejad, Shahrzad; Savage, Robert

    2012-01-01

    This study investigated whether children with dyslexia differed in their performance on reading, phonological, rapid naming, motor, and cerebellar-related tasks and automaticity measures compared to reading age (RA)-matched and chronological age (CA)-matched control groups. Participants were 51 children attending mainstream English elementary…

  13. Very Preterm Birth, Cerebellar Development and Neuropsychological Outcome in Adolescence

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2008-06-01

    Full Text Available Cerebellar volumes were measured on structural MRI at adolescence and adulthood in 65 preterm individuals (born before 33 weeks’ gestation, and a term-born comparison group, in a study at King’s College, Great Ormond Street Hospital, and University College, London; and Seoul National University College of Medicine, Korea.

  14. Early Cerebellar Network Shifting in Spinocerebellar Ataxia Type 6.

    Science.gov (United States)

    Falcon, M I; Gomez, C M; Chen, E E; Shereen, A; Solodkin, A

    2016-07-01

    Spinocerebellar ataxia 6 (SCA6), an autosomal dominant degenerative disease, is characterized by diplopia, gait ataxia, and incoordination due to severe progressive degeneration of Purkinje cells in the vestibulo- and spinocerebellum. Ocular motor deficits are common, including difficulty fixating on moving objects, nystagmus and disruption of smooth pursuit movements. In presymptomatic SCA6, there are alterations in saccades and smooth-pursuit movements. We sought to assess functional and structural changes in cerebellar connectivity associated with a visual task, hypothesizing that gradual changes would parallel disease progression. We acquired functional magnetic resonance imaging and diffusion tensor imaging data during a passive smooth-pursuit task in 14 SCA6 patients, representing a range of disease duration and severity, and performed a cross-sectional comparison of cerebellar networks compared with healthy controls. We identified a shift in activation from vermis in presymptomatic individuals to lateral cerebellum in moderate-to-severe cases. Concomitantly, effective connectivity between regions of cerebral cortex and cerebellum was at its highest in moderate cases, and disappeared in severe cases. Finally, we noted structural differences in the cerebral and cerebellar peduncles. These unique results, spanning both functional and structural domains, highlight widespread changes in SCA6 and compensatory mechanisms associated with cerebellar physiology that could be utilized in developing new therapies.

  15. Long-Term Sequelae after Cerebellar Astrocytoma Surgery

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2004-05-01

    Full Text Available The long-term effects on neurologic, neuropsychological, and behavioral functioning in a consecutive series of 23 children treated surgically for cerebellar pilocytic astrocytoma without additional radio- and chemotherapy are determined in a study at Sophia Children’s Hospital, Rotterdam, The Netherlands, and other medical centers.

  16. [Autosomal dominant cerebellar ataxias in the Netherlands: a national inventory

    NARCIS (Netherlands)

    Warrenburg, B.P.C. van de

    2001-01-01

    OBJECTIVE: To provide a comprehensive estimate of the number of Dutch autosomal dominant cerebellar ataxias (ADCA) families and patients and thus estimate the minimal prevalence of ADCA in the Netherlands. Furthermore, to observe the relative frequency of SCA mutations and to study genotype-phenotyp

  17. Mapping the development of cerebellar Purkinje cells in zebrafish.

    Science.gov (United States)

    Hamling, Kyla R; Tobias, Zachary J C; Weissman, Tamily A

    2015-11-01

    The cells that comprise the cerebellum perform a complex integration of neural inputs to influence motor control and coordination. The functioning of this circuit depends upon Purkinje cells and other cerebellar neurons forming in the precise place and time during development. Zebrafish provide a useful platform for modeling disease and studying gene function, thus a quantitative metric of normal zebrafish cerebellar development is key for understanding how gene mutations affect the cerebellum. To begin to quantitatively measure cerebellar development in zebrafish, we have characterized the spatial and temporal patterning of Purkinje cells during the first 2 weeks of development. Differentiated Purkinje cells first emerged by 2.8 days post fertilization and were spatially patterned into separate dorsomedial and ventrolateral clusters that merged at around 4 days. Quantification of the Purkinje cell layer revealed that there was a logarithmic increase in both Purkinje cell number as well as overall volume during the first 2 weeks, while the entire region curved forward in an anterior, then ventral direction. Purkinje cell dendrites were positioned next to parallel fibers as early as 3.3 days, and Purkinje cell diameter decreased significantly from 3.3 to 14 days, possibly due to cytoplasmic reappropriation into maturing dendritic arbors. A nearest neighbor analysis showed that Purkinje cells moved slightly apart from each other from 3 to 14 days, perhaps spreading as the organized monolayer forms. This study establishes a quantitative spatiotemporal map of Purkinje cell development in zebrafish that provides an important metric for studies of cerebellar development and disease.

  18. Cerebellar Damage Produces Selective Deficits in Verbal Working Memory

    Science.gov (United States)

    Ravizza, Susan M.; Mccormick, Cristin A.; Schlerf, John E.; Justus, Timothy; Ivry, Richard B.; Fiez, Julie A.

    2006-01-01

    The cerebellum is often active in imaging studies of verbal working memory, consistent with a putative role in articulatory rehearsal. While patients with cerebellar damage occasionally exhibit a mild impairment on standard neuropsychological tests of working memory, these tests are not diagnostic for exploring these processes in detail. The…

  19. Cerebellar rTMS disrupts predictive language processing

    Science.gov (United States)

    Lesage, Elise; Morgan, Blaire E.; Olson, Andrew C.; Meyer, Antje S.; Miall, R. Chris

    2012-01-01

    Summary The human cerebellum plays an important role in language, amongst other cognitive and motor functions [1], but a unifying theoretical framework about cerebellar language function is lacking. In an established model of motor control, the cerebellum is seen as a predictive machine, making short-term estimations about the outcome of motor commands. This allows for flexible control, on-line correction, and coordination of movements [2]. The homogeneous cytoarchitecture of the cerebellar cortex suggests that similar computations occur throughout the structure, operating on different input signals and with different output targets [3]. Several authors have therefore argued that this ‘motor’ model may extend to cerebellar nonmotor functions [3–5], and that the cerebellum may support prediction in language processing [6]. However, this hypothesis has never been directly tested. Here, we used the ‘Visual World’ paradigm [7], where on-line processing of spoken sentence content can be assessed by recording the latencies of listeners' eye movements towards objects mentioned. Repetitive transcranial magnetic stimulation (rTMS) was used to disrupt function in the right cerebellum, a region implicated in language [8]. After cerebellar rTMS, listeners showed delayed eye fixations to target objects predicted by sentence content, while there was no effect on eye fixations in sentences without predictable content. The prediction deficit was absent in two control groups. Our findings support the hypothesis that computational operations performed by the cerebellum may support prediction during both motor control and language processing. PMID:23017990

  20. Neurophysiological evidence for cerebellar dysfunction in primary focal dystonia.

    NARCIS (Netherlands)

    Teo, J.T.; Warrenburg, B.P.C. van de; Schneider, S.A.; Rothwell, J.C.; Bhatia, K.P.

    2009-01-01

    Recent studies have suggested that there may be functional and structural changes in the cerebellum of patients with adult onset primary focal dystonia. The aim of this study was to establish whether there is any neurophysiological indicator of abnormal cerebellar function, using the classic eyeblin

  1. Cerebro-cerebellar interactions underlying temporal information processing.

    Science.gov (United States)

    Aso, Kenji; Hanakawa, Takashi; Aso, Toshihiko; Fukuyama, Hidenao

    2010-12-01

    The neural basis of temporal information processing remains unclear, but it is proposed that the cerebellum plays an important role through its internal clock or feed-forward computation functions. In this study, fMRI was used to investigate the brain networks engaged in perceptual and motor aspects of subsecond temporal processing without accompanying coprocessing of spatial information. Direct comparison between perceptual and motor aspects of time processing was made with a categorical-design analysis. The right lateral cerebellum (lobule VI) was active during a time discrimination task, whereas the left cerebellar lobule VI was activated during a timed movement generation task. These findings were consistent with the idea that the cerebellum contributed to subsecond time processing in both perceptual and motor aspects. The feed-forward computational theory of the cerebellum predicted increased cerebro-cerebellar interactions during time information processing. In fact, a psychophysiological interaction analysis identified the supplementary motor and dorsal premotor areas, which had a significant functional connectivity with the right cerebellar region during a time discrimination task and with the left lateral cerebellum during a timed movement generation task. The involvement of cerebro-cerebellar interactions may provide supportive evidence that temporal information processing relies on the simulation of timing information through feed-forward computation in the cerebellum.

  2. ERK1/2 activation is involved in the neuroprotective action of P2Y13 and P2X7 receptors against glutamate excitotoxicity in cerebellar granule neurons.

    Science.gov (United States)

    Ortega, Felipe; Pérez-Sen, Raquel; Delicado, Esmerilda G; Teresa Miras-Portugal, M

    2011-12-01

    Cerebellar granule neurons express several types of nucleotide receptors, with the metabotropic P2Y(13) and the ionotropic P2X7 being the most relevant in this model. In the present study we investigated the role of P2Y(13) and P2X7 nucleotide receptors in ERK1/2 signalling. The nucleotidic agonists 2MeSADP (2-methylthioadenosine-5'-diphosphate) for P2Y(13) and BzATP (2'(3')-O-(4-benzoylbenzoyl)adenosine-5'-triphosphate) for P2X7 receptors were coupled to ERK1/2 activation in granule neurons, being able to increase around two-fold the levels of ERK1/2 phosphorylation. These effects were sensitive to the inhibitory action of the antagonists MRS-2211 and A-438079, specific for P2Y(13) and P2X7 receptors, respectively. Although both receptor subtypes shared the same pattern of transient ERK1/2 phosphorylation, they differed in the intracellular cascades they triggered, being PI3K-dependent for P2Y(13) and calcium/calmodulin kinase II (CaMKII)-dependent for P2X7. These two different ERK-mediated pathways were involved in the neuroprotective effects displayed by both P2Y(13) and P2X7 receptors against apoptosis induced by an excitotoxic concentration of glutamate, in a similar manner to the neurotrophin, BDNF. In addition, P2Y(13) and P2X7 receptor agonists were also able to phosphorylate and activate the ERK-dependent target CREB, which could be involved in their neuroprotective effect. These results indicate that nucleotide receptors share with trophic factors the same survival routes in neurons, such as the ERK signalling route, and therefore, can contribute to the maintenance of granule neurons in conditions in which survival is being compromised.

  3. Anterior and posterior inferior cerebellar artery infarction with sudden deafness and vertigo.

    Science.gov (United States)

    Murakami, Takenobu; Nakayasu, Hiroyuki; Doi, Mitsuru; Fukada, Yasuyo; Hayashi, Miwa; Suzuki, Takeo; Takeuchi, Yuichi; Nakashima, Kenji

    2006-12-01

    We report a patient with anterior and posterior inferior cerebellar artery infarction, which manifested as profound deafness, transient vertigo, and minimal cerebellar signs. We suspect that ischaemia of the left internal auditory artery, which originates from the anterior inferior cerebellar artery, caused the deafness and transient vertigo. A small lesion in the middle cerebellar peduncle in the anterior inferior cerebellar artery territory and no lesion in the dentate nucleus in the posterior inferior cerebellar artery territory are thought to explain the minimal cerebellar signs despite the relatively large size of the infarction. Thus a relatively large infarction of the vertebral-basilar territory can manifest as sudden deafness with vertigo. Neuroimaging, including magnetic resonance imaging, is strongly recommended for patients with sudden deafness and vertigo to exclude infarction of the vertebral-basilar artery territory.

  4. Post-Plasmodium vivax malaria cerebellar ataxia and optic neuritis: A new form of delayed cerebellar ataxia or cerebellar variant of acute disseminated encephalomyelitis?

    Directory of Open Access Journals (Sweden)

    Gaurav M Kasundra

    2015-01-01

    Full Text Available Acute disseminated encephalomyelitis (ADEM is commonly seen after viral and bacterial infections, immunization, and Plasmodium falciparum (PF malaria. Plasmodium vivax (PV rarely causes ADEM. We report a 14-year-old female patient who presented with acute onset bilateral cerebellar ataxia and optic neuritis, 2 weeks after recovery from PV. Magnetic resonance imaging showed bilateral cerebellar hyperintensities suggestive of ADEM. No specific viral etiology was found on cerebrospinal fluid examination. Patient responded well to treatment without any sequelae. Thus, PV too is an important cause of ADEM along with PF. Two of the previously reported cases had co-infection with falciparum malaria. The only other two reported cases, as also this patient, are from Asia. A geographical or racial predisposition needs to be evaluated. Also, a possibility of post-PV delayed cerebellar ataxia, which is classically described post-PF infection, may be considered as it may be clinically, radiologically, and prognostically indistinguishable from a milder presentation of ADEM.

  5. DNA binding properties of the small cascade subunit Csa5.

    Directory of Open Access Journals (Sweden)

    Michael Daume

    Full Text Available CRISPR-Cas systems provide immunity against viral attacks in archaeal and bacterial cells. Type I systems employ a Cas protein complex termed Cascade, which utilizes small CRISPR RNAs to detect and degrade the exogenic DNA. A small sequence motif, the PAM, marks the foreign substrates. Previously, a recombinant type I-A Cascade complex from the archaeon Thermoproteus tenax was shown to target and degrade DNA in vitro, dependent on a native PAM sequence. Here, we present the biochemical analysis of the small subunit, Csa5, of this Cascade complex. T. tenax Csa5 preferentially bound ssDNA and mutants that showed decreased ssDNA-binding and reduced Cascade-mediated DNA cleavage were identified. Csa5 oligomerization prevented DNA binding. Specific recognition of the PAM sequence was not observed. Phylogenetic analyses identified Csa5 as a universal member of type I-A systems and revealed three distinct groups. A potential role of Csa5 in R-loop stabilization is discussed.

  6. Cascaded Bragg scattering in fiber optics.

    Science.gov (United States)

    Xu, Y Q; Erkintalo, M; Genty, G; Murdoch, S G

    2013-01-15

    We report on a theoretical and experimental study of cascaded Bragg scattering in fiber optics. We show that the usual energy-momentum conservation of Bragg scattering can be considerably relaxed via cascade-induced phase-matching. Experimentally we demonstrate frequency translation over six- and 11-fold cascades, in excellent agreement with derived phase-matching conditions.

  7. Diffusion Tensor Imaging of Human Cerebellar Pathways and their Interplay with Cerebral Macrostructure

    Directory of Open Access Journals (Sweden)

    Zafer eKeser

    2015-04-01

    Full Text Available Cerebellar white matter connections to the central nervous system are classified functionally into the spinocerebellar, vestibulocerebellar, and cerebrocerebellar subdivisions. The Spinocerebellar (SC pathways project from spinal cord to cerebellum, whereas the vestibulocerebellar (VC pathways project from vestibular organs of the inner ear. Cerebrocerebellar connections are composed of feed forward and feedback connections between cerebrum and cerebellum including the cortico-ponto-cerebellar (CPC pathways being of cortical origin and the dentate-rubro-thalamo-cortical (DRTC pathway being of cerebellar origin. In this study we systematically quantified the whole cerebellar system connections using diffusion tensor magnetic resonance imaging (DT-MRI. Ten right-handed healthy subjects (7 males and 3 females, age range 20-51 years were studied. DT-MRI data were acquired with a voxel size = 2mm x 2mm x 2 mm at a 3.0 Tesla clinical MRI scanner. The DT-MRI data were prepared and analyzed using anatomically-guided deterministic tractography methods to reconstruct the SC, DRTC, fronto-ponto-cerebellar (FPC, parieto-ponto-cerebellar (PPC, temporo-ponto-cerebellar (TPC and occipito-ponto-cerebellar (OPC. The DTI-attributes or the cerebellar tracts along with their cortical representation (Brodmann areas were presented in standard Montréal Neurological Institute space. All cerebellar tract volumes were quantified and correlated with volumes of cerebral cortical, subcortical gray matter (GM, cerebral white matter (WM and cerebellar GM, and cerebellar WM. On our healthy cohort, the ratio of total cerebellar GM-to-WM was ~ 3.29 ± 0.24, whereas the ratio of cerebral GM-to-WM was approximately 1.10 ± 0.11. The sum of all cerebellar tract volumes is ~ 25.8 ± 7.3 mL, or a percentage of 1.52 ± 0.43 of the total intracranial volume.

  8. Cerebellar motor learning: when is cortical plasticity not enough?

    Directory of Open Access Journals (Sweden)

    John Porrill

    2007-10-01

    Full Text Available Classical Marr-Albus theories of cerebellar learning employ only cortical sites of plasticity. However, tests of these theories using adaptive calibration of the vestibulo-ocular reflex (VOR have indicated plasticity in both cerebellar cortex and the brainstem. To resolve this long-standing conflict, we attempted to identify the computational role of the brainstem site, by using an adaptive filter version of the cerebellar microcircuit to model VOR calibration for changes in the oculomotor plant. With only cortical plasticity, introducing a realistic delay in the retinal-slip error signal of 100 ms prevented learning at frequencies higher than 2.5 Hz, although the VOR itself is accurate up to at least 25 Hz. However, the introduction of an additional brainstem site of plasticity, driven by the correlation between cerebellar and vestibular inputs, overcame the 2.5 Hz limitation and allowed learning of accurate high-frequency gains. This "cortex-first" learning mechanism is consistent with a wide variety of evidence concerning the role of the flocculus in VOR calibration, and complements rather than replaces the previously proposed "brainstem-first" mechanism that operates when ocular tracking mechanisms are effective. These results (i describe a process whereby information originally learnt in one area of the brain (cerebellar cortex can be transferred and expressed in another (brainstem, and (ii indicate for the first time why a brainstem site of plasticity is actually required by Marr-Albus type models when high-frequency gains must be learned in the presence of error delay.

  9. Cerebellar and pontine tegmental hypermetabolism in miller-fisher syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yu Kyrong; Kim, Ji Soo; Lee, Won Woo; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    Miller Fisher syndrome (MFS) has been considered as a variant of Guillain-Barre syndrome (GBS), a type of acute immune neuropathies involving peripheral nerve system. Unlike GBS, presence of cerebellar type ataxia and supranuclear ophthalmioplesia in MFS suggests additional involvement of the central nervous system. To determine involvement of the central nervous system in MFS, we investigated the cerebral metabolic abnormalities in patients with MFS using FDG PET. Nine patients who were diagnosed as MFS based on acute ophthalmoplegia, ataxia, and areflexia without other identifiable causes participated in this study. In six patients, serum antibodies possibly related with symptom of MFS (anti- GQ1b or anti-GM1) were detected at the time of the study. With the interval of 25 26 days (range: 3-83 days) from the symptom on set, brain FDG PET were underwent in patients and compared with those from healthy controls. In group analysis comparing with healthy controls, FDG PET of patients revealed increased metabolism in the bilateral cerebellar hemispheres and vermis, and the thalamus. In contrast, the occipital cortex showed decreased metabolism. Individual analyses disclosed hypermetabolism in the cerebellar vermis or hemispheres in 5, and in the pontine tegmentum in 2 of the 9 patients. We also found that the cerebellar vermian hypermetabolism was inversely correlated with the interval between from the symptom on set to PET study. Moreover, follow-up PET of a patient demonstrated that cerebellar hypermetabolism decreased markedly with an improvement of the ophthalmoplegia and ataxia. These findings indicate an involvement of the central nervous system in MFS and suggest an antibody-associated acute inflammatory process as a mechanism of this disorder.

  10. GDNF-induced cerebellar toxicity: A brief review.

    Science.gov (United States)

    Luz, Matthias; Mohr, Erich; Fibiger, H Christian

    2016-01-01

    Recombinant-methionyl human glial cell line-derived neurotrophic factor (GDNF) is known for its neurorestorative and neuroprotective effects in rodent and primate models of Parkinson's disease (PD). When administered locally into the putamen of Parkinsonian subjects, early clinical studies showed its potential promise as a disease-modifying agent. However, the development of GDNF for the treatment of PD has been significantly clouded by findings of cerebellar toxicity after continuous intraputamenal high-dose administration in a 6-month treatment/3-month recovery toxicology study in rhesus monkeys. Specifically, multifocal cerebellar Purkinje cell loss affecting 1-21% of the cerebellar cortex was observed in 4 of 15 (26.7%; 95% confidence interval [CI]: 10.5-52.4%) animals treated at the highest dose level tested (3000μg/month). No cerebellar toxicity was observed at lower doses (450 and 900μg/month) in the same study, or at similar or higher doses (up to 10,000μg/month) in subchronic or chronic toxicology studies testing intermittent intracerebroventricular administration. While seemingly associated with the use of GDNF, the pathogenesis of the cerebellar lesions has not been fully understood to date. This review integrates available information to evaluate potential pathogenic mechanisms and provide a consolidated assessment of the findings. While other explanations are considered, the existing evidence is most consistent with the hypothesis that leakage of GDNF into cerebrospinal fluid during chronic infusions into the putamen down-regulates GDNF receptors on Purkinje cells, and that subsequent acute withdrawal of GDNF generates the observed lesions. The implications of these findings for clinical studies with GDNF are discussed.

  11. Long lasting cerebellar alterations after perinatal asphyxia in rats.

    Science.gov (United States)

    Campanille, Verónica; Saraceno, G Ezequiel; Rivière, Stéphanie; Logica, Tamara; Kölliker, Rodolfo; Capani, Francisco; Castilla, Rocío

    2015-07-01

    The developing brain may be particularly vulnerable to injury before, at and after birth. Among possible insults, hypoxia suffered as a consequence of perinatal asphyxia (PA) exhibits the highest incidence levels and the cerebellar circuitry appears to be particularly susceptible, as the cellular makeup and the quantity of inputs change quickly during days and weeks following birth. In this work, we have used a murine model to induce severe global PA in rats at the time of birth. Short-term cerebellar alterations within this PA model have been previously reported but whether such alterations remain in adulthood has not been conclusively determined yet. For this reason, and given the crucial cerebellar role in determining connectivity patterns in the brain, the aim of our work is to unveil long-term cerebellum histomorphology following a PA insult. Morphological and cytological neuronal changes and glial reaction in the cerebellar cortex were analyzed at postnatal 120 (P120) following injury performed at birth. As compared to control, PA animals exhibited: (1) an increase in molecular and granular thickness, both presenting lower cellular density; (2) a disarrayed Purkinje cell layer presenting a higher number of anomalous calbindin-stained cells. (3) focal swelling and marked fragmentation of microtubule-associated protein 2 (MAP-2) in Purkinje cell dendrites and, (4) an increase in glial fibrillary acidic protein (GFAP) expression in Bergmann cells and the granular layer. In conclusion, we demonstrate that PA produces long-term damage in cellular histomorphology in rat cerebellar cortex which could be involved in the pathogenesis of cognitive deficits observed in both animals and humans.

  12. Differential GABAergic and glycinergic inputs of inhibitory interneurons and Purkinje cells to principal cells of the cerebellar nuclei.

    Science.gov (United States)

    Husson, Zoé; Rousseau, Charly V; Broll, Ilja; Zeilhofer, Hanns Ulrich; Dieudonné, Stéphane

    2014-07-09

    The principal neurons of the cerebellar nuclei (CN), the sole output of the olivo-cerebellar system, receive a massive inhibitory input from Purkinje cells (PCs) of the cerebellar cortex. Morphological evidence suggests that CN principal cells are also contacted by inhibitory interneurons, but the properties of this connection are unknown. Using transgenic, tracing, and immunohistochemical approaches in mice, we show that CN interneurons form a large heterogeneous population with GABA/glycinergic phenotypes, distinct from GABAergic olive-projecting neurons. CN interneurons are found to contact principal output neurons, via glycine receptor (GlyR)-enriched synapses, virtually devoid of the main GABA receptor (GABAR) subunits α1 and γ2. Those clusters account for 5% of the total number of inhibitory receptor clusters on principal neurons. Brief optogenetic stimulations of CN interneurons, through selective expression of channelrhodopsin 2 after viral-mediated transfection of the flexed gene in GlyT2-Cre transgenic mice, evoked fast IPSCs in principal cells. GlyR activation accounted for 15% of interneuron IPSC amplitude, while the remaining current was mediated by activation of GABAR. Surprisingly, small GlyR clusters were also found at PC synapses onto principal CN neurons in addition to α1 and γ2 GABAR subunits. However, GlyR activation was found to account for <3% of the PC inhibitory synaptic currents evoked by electrical stimulation. This work establishes CN glycinergic neurons as a significant source of inhibition to CN principal cells, forming contacts molecularly distinct from, but functionally similar to, Purkinje cell synapses. Their impact on CN output, motor learning, and motor execution deserves further investigation.

  13. Cerebellar Transcranial Direct Current Stimulation (ctDCS): A Novel Approach to Understanding Cerebellar Function in Health and Disease.

    Science.gov (United States)

    Grimaldi, Giuliana; Argyropoulos, Georgios P; Bastian, Amy; Cortes, Mar; Davis, Nicholas J; Edwards, Dylan J; Ferrucci, Roberta; Fregni, Felipe; Galea, Joseph M; Hamada, Masahi; Manto, Mario; Miall, R Chris; Morales-Quezada, Leon; Pope, Paul A; Priori, Alberto; Rothwell, John; Tomlinson, S Paul; Celnik, Pablo

    2016-02-01

    The cerebellum is critical for both motor and cognitive control. Dysfunction of the cerebellum is a component of multiple neurological disorders. In recent years, interventions have been developed that aim to excite or inhibit the activity and function of the human cerebellum. Transcranial direct current stimulation of the cerebellum (ctDCS) promises to be a powerful tool for the modulation of cerebellar excitability. This technique has gained popularity in recent years as it can be used to investigate human cerebellar function, is easily delivered, is well tolerated, and has not shown serious adverse effects. Importantly, the ability of ctDCS to modify behavior makes it an interesting approach with a potential therapeutic role for neurological patients. Through both electrical and non-electrical effects (vascular, metabolic) ctDCS is thought to modify the activity of the cerebellum and alter the output from cerebellar nuclei. Physiological studies have shown a polarity-specific effect on the modulation of cerebellar-motor cortex connectivity, likely via cerebellar-thalamocortical pathways. Modeling studies that have assessed commonly used electrode montages have shown that the ctDCS-generated electric field reaches the human cerebellum with little diffusion to neighboring structures. The posterior and inferior parts of the cerebellum (i.e., lobules VI-VIII) seem particularly susceptible to modulation by ctDCS. Numerous studies have shown to date that ctDCS can modulate motor learning, and affect cognitive and emotional processes. Importantly, this intervention has a good safety profile; similar to when applied over cerebral areas. Thus, investigations have begun exploring ctDCS as a viable intervention for patients with neurological conditions.

  14. Bankruptcy Cascades in Interbank Markets

    Science.gov (United States)

    Tedeschi, Gabriele; Mazloumian, Amin; Gallegati, Mauro; Helbing, Dirk

    2012-01-01

    We study a credit network and, in particular, an interbank system with an agent-based model. To understand the relationship between business cycles and cascades of bankruptcies, we model a three-sector economy with goods, credit and interbank market. In the interbank market, the participating banks share the risk of bad debits, which may potentially spread a bank’s liquidity problems through the network of banks. Our agent-based model sheds light on the correlation between bankruptcy cascades and the endogenous economic cycle of booms and recessions. It also demonstrates the serious trade-off between, on the one hand, reducing risks of individual banks by sharing them and, on the other hand, creating systemic risks through credit-related interlinkages of banks. As a result of our study, the dynamics underlying the meltdown of financial markets in 2008 becomes much better understandable. PMID:23300760

  15. Thermal cascaded lattice Boltzmann method

    CERN Document Server

    Fei, Linlin

    2016-01-01

    In this paper, a thermal cascaded lattice Boltzmann method (TCLBM) is developed in combination with the double-distribution-function (DDF) approach. A density distribution function relaxed by the cascaded scheme is employed to solve the flow field, and a total energy distribution function relaxed by the BGK scheme is used to solve temperature field, where two distribution functions are coupled naturally. The forcing terms are incorporated by means of central moments, which is consistent with the previous force scheme [Premnath \\emph{et al.}, Phys. Rev. E \\textbf{80}, 036702 (2009)] but the derivation is more intelligible and the evolution process is simpler. In the method, the viscous heat dissipation and compression work are taken into account, the Prandtl number and specific-heat ratio are adjustable, the external force is considered directly without the Boussinesq assumption, and the low-Mach number compressible flows can also be simulated. The forcing scheme is tested by simulating a steady Taylor-Green f...

  16. Cascade Chaotic System With Applications.

    Science.gov (United States)

    Zhou, Yicong; Hua, Zhongyun; Pun, Chi-Man; Chen, C L Philip

    2015-09-01

    Chaotic maps are widely used in different applications. Motivated by the cascade structure in electronic circuits, this paper introduces a general chaotic framework called the cascade chaotic system (CCS). Using two 1-D chaotic maps as seed maps, CCS is able to generate a huge number of new chaotic maps. Examples and evaluations show the CCS's robustness. Compared with corresponding seed maps, newly generated chaotic maps are more unpredictable and have better chaotic performance, more parameters, and complex chaotic properties. To investigate applications of CCS, we introduce a pseudo-random number generator (PRNG) and a data encryption system using a chaotic map generated by CCS. Simulation and analysis demonstrate that the proposed PRNG has high quality of randomness and that the data encryption system is able to protect different types of data with a high-security level.

  17. Optimally Training a Cascade Classifier

    CERN Document Server

    Shen, Chunhua; Hengel, Anton van den

    2010-01-01

    Cascade classifiers are widely used in real-time object detection. Different from conventional classifiers that are designed for a low overall classification error rate, a classifier in each node of the cascade is required to achieve an extremely high detection rate and moderate false positive rate. Although there are a few reported methods addressing this requirement in the context of object detection, there is no a principled feature selection method that explicitly takes into account this asymmetric node learning objective. We provide such an algorithm here. We show a special case of the biased minimax probability machine has the same formulation as the linear asymmetric classifier (LAC) of \\cite{wu2005linear}. We then design a new boosting algorithm that directly optimizes the cost function of LAC. The resulting totally-corrective boosting algorithm is implemented by the column generation technique in convex optimization. Experimental results on object detection verify the effectiveness of the proposed bo...

  18. Bankruptcy cascades in interbank markets.

    Directory of Open Access Journals (Sweden)

    Gabriele Tedeschi

    Full Text Available We study a credit network and, in particular, an interbank system with an agent-based model. To understand the relationship between business cycles and cascades of bankruptcies, we model a three-sector economy with goods, credit and interbank market. In the interbank market, the participating banks share the risk of bad debits, which may potentially spread a bank's liquidity problems through the network of banks. Our agent-based model sheds light on the correlation between bankruptcy cascades and the endogenous economic cycle of booms and recessions. It also demonstrates the serious trade-off between, on the one hand, reducing risks of individual banks by sharing them and, on the other hand, creating systemic risks through credit-related interlinkages of banks. As a result of our study, the dynamics underlying the meltdown of financial markets in 2008 becomes much better understandable.

  19. Lens Coupled Quantum Cascade Laser

    Science.gov (United States)

    Hu, Qing (Inventor); Lee, Alan Wei Min (Inventor)

    2013-01-01

    Terahertz quantum cascade (QC) devices are disclosed that can operate, e.g., in a range of about 1 THz to about 10 THz. In some embodiments, QC lasers are disclosed in which an optical element (e.g., a lens) is coupled to an output facet of the laser's active region to enhance coupling of the lasing radiation from the active region to an external environment. In other embodiments, terahertz amplifier and tunable terahertz QC lasers are disclosed.

  20. Control of Cascaded Multilevel Inverters

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    Abstract-A new type of multilevel inverter is introduced which is created by cascading two three-phase three-level inverters using the load connection, but requires only one DC voltage source. This new inverter can operateas a seven-level inverter and naturally splits the power conversion into a higher-voltage lower-frequency inverter and a lower-voltage higher-fre-quency inverter. This type of system presents particular advantages to Naval ship propulsion systems which rely on high power quality, survivable drives. New control methods are described involving both joint and separate control of the individual three-level inverters. Simulation resuits demonstrate the effectiveness of both controls. A laboratory set-up at the Naval Surface Warfare Center power electronics laboratory was used to validate the proposed joint-inverter control. Due to the effect of compounding levels in the cascaded inverter, a high number of levels are available resulting in a voltage THD of 9% (without filtering). Index Terms-Cascaded inverter, multilevel inverter, three-level inverter.

  1. Turbulence: does energy cascade exist?

    CERN Document Server

    Josserand, Christophe; Lehner, Thierry; Pomeau, Yves

    2016-01-01

    To answer the question whether a cascade of energy exists or not in turbulence, we propose a set of correlation functions able to test if there is an irreversible transfert of energy, step by step, from large to small structures. These tests are applied to real Eulerian data of a turbulent velocity flow, taken in the wind grid tunnel of Modane, and also to a prototype model equation for wave turbulence. First we demonstrate the irreversible character of the flow by using multi-time correlation function at a given point of space. Moreover the unexpected behavior of the test function leads us to connect irreversibility and finite time singularities (intermittency). Secondly we show that turbulent cascade exists, and is a dynamical process, by using a test function depending on time and frequency. The cascade shows up only in the inertial domain where the kinetic energy is transferred more rapidly (on average) from the wavenumber $k_{1}$ to $k_{2}$ than from $k_{1}$ to $k'_{2}$ larger than $k_{2}$.

  2. Abnormality in cerebellar blood flow in solo vertigo patients

    Energy Technology Data Exchange (ETDEWEB)

    Nagahori, Takeshi [Shakaihoken Takaoka Hospital, Toyama (Japan); Nishijima, Michiharu; Endo, Shunro; Takaku, Akira

    1997-03-01

    Little is known about the blood flow of the vertebrobasilar system as a cause of vertigo and dizziness. We used Xe-CT to study cerebellar blood flow in 53 patients who ranged in age from 35 to 85 years. The patients were divided into two groups. One of them was the vertigo group that comprised 28 patients with rotatory sensation, and the other, the non-vertigo group of 25 patients with a sensation other than rotation. At the stage of severe symptoms, there was decreased cerebellar blood flow in all patients of both, the vertigo and the non-vertigo groups, and a decrease in the bilateral cerebellar hemisphere was observed in five patients and in a unilateral hemisphere in three patients of the vertigo group. By comparison, in the non-vertigo group, unilateral decrease of cerebellar blood flow was observed in only one patient, and a bilateral decrease in five. At the stage of severe symptoms, the mean regional cerebellar blood flow was 40.5{+-}8.0 ml/100 g/min (n=16 sides) in the vertigo group and 45.3{+-}9.5 ml/100 g/min (n=12 sides) in the non-vertigo group. At the stage of moderate symptoms, blood flow image was normal in four of 14 vertigo patients and in seven of 12 non-vertigo patients. The mean regional blood flow was 47.8{+-}8.6 ml/100 g/min (n=28 sides) in the vertigo group and 47.1{+-}5.1 ml/100 g/min (n=24 sides) in the non-vertigo group. At the asymptomatic stage, a high proportion of normal blood flow images (nine of 16 vertigo patients and 10 of 10 non-vertigo patients) was observed. The mean regional cerebellar blood flow was 51.6{+-}10.7 ml/100 g/min (n=32 sides) in the vertigo group and 52.8{+-}8.5 ml/100 g/min (n=20 sides) in the non-vertigo group. This study demonstrates that a unilateral or bilateral decrease in blood flow of the vertebrobasilar system may cause vertigo and dizziness. It also shows that Xe-CT of the cerebellum may be a valuable examination modality for the diagnosis and treatment of vertigo and dizziness. (author)

  3. Structure of the archaeal Cascade subunit Csa5

    Science.gov (United States)

    Reeks, Judith; Graham, Shirley; Anderson, Linzi; Liu, Huanting; White, Malcolm F.; Naismith, James H.

    2013-01-01

    The Cascade complex for CRISPR-mediated antiviral immunity uses CRISPR RNA (crRNA) to target invading DNA species from mobile elements such as viruses, leading to their destruction. The core of the Cascade effector complex consists of the Cas5 and Cas7 subunits, which are widely conserved in prokaryotes. Cas7 binds crRNA and forms the helical backbone of Cascade. Many archaea encode a version of the Cascade complex (denoted Type I-A) that includes a Csa5 (or small) subunit, which interacts weakly with the core proteins. Here, we report the crystal structure of the Csa5 protein from Sulfolobus solfataricus. Csa5 comprises a conserved α-helical domain with a small insertion consisting of a weakly conserved β-strand domain. In the crystal, the Csa5 monomers have multimerized into infinite helical threads. At each interface is a strictly conserved intersubunit salt bridge, deletion of which disrupts multimerization. Structural analysis indicates a shared evolutionary history among the small subunits of the CRISPR effector complexes. The same α-helical domain is found in the C-terminal domain of Cse2 (from Type I-E Cascade), while the N-terminal domain of Cse2 is found in Cmr5 of the CMR (Type III-B) effector complex. As Cmr5 shares no match with Csa5, two possibilities present themselves: selective domain loss from an ancestral Cse2 to create two new subfamilies or domain fusion of two separate families to create a new Cse2 family. A definitive answer awaits structural studies of further small subunits from other CRISPR effector complexes. PMID:23846216

  4. Climbing fiber synapse elimination in cerebellar Purkinje cells.

    Science.gov (United States)

    Watanabe, Masahiko; Kano, Masanobu

    2011-11-01

    Innervation of Purkinje cells (PCs) by multiple climbing fibers (CFs) is refined into mono-innervation during the first three postnatal weeks of rodents' lives. In this review article, we will integrate the current knowledge on developmental process and mechanisms of CF synapse elimination. In the 'creeper' stage of CF innervation (postnatal day 0 (P0)∼), CFs creep among PC somata to form transient synapses on immature dendrites. In the 'pericellular nest' stage (P5∼), CFs densely surround and innervate PC somata. CF innervation is then displaced to the apical portion of PC somata in the 'capuchon' stage (P9∼), and translocate to dendrites in the 'dendritic' (P12∼) stage. Along with the developmental changes in CF wiring, functional and morphological distinctions become larger among CF inputs. PCs are initially innervated by more than five CFs with similar strengths (∼P3). During P3-7 only a single CF is selectively strengthened (functional differentiation), and it undergoes dendritic translocation from P9 on (dendritic translocation). Following the functional differentiation, perisomatic CF synapses are eliminated nonselectively; this proceeds in two distinct phases. The early phase (P7-11) is conducted independently of parallel fiber (PF)-PC synapse formation, while the late phase (P12-17) critically depends on it. The P/Q-type voltage-dependent Ca(2+) channel in PCs triggers selective strengthening of single CF inputs, promotes dendritic translocation of the strengthened CFs, and drives the early phase of CF synapse elimination. In contrast, the late phase is mediated by the mGluR1-Gαq-PLCβ4-PKCγ signaling cascade in PCs driven at PF-PC synapses, whose structural connectivity is stabilized and maintained by the GluRδ2-Cbln1-neurexin system.

  5. A Study Of Sporadic Adult Onset Degenerative Cerebellar Ataxias

    Directory of Open Access Journals (Sweden)

    Sinha K K

    1999-01-01

    Full Text Available Twenty-four cases of sporadic olivo-ponto-cerebellar atrophy (OPCA of adult onset were studied over a period of two years. Results suggest that this disorder has its usual onset in the 5th and 6th decade of life with a male: female ratio of 2:1. It manifests clinically with gait ataxia in all, dysarthria, other cerebellar signs and autonomic involvement in vast majority. There were features of basal ganglia involvement in some. No known identifiable environmental cause was found and genetically they are quite distinct from the known autosomal dominant spinocerebellar ataxias though sporadic occurrence in recessive inheritance or a de novo mutation could not be ruled out completely, but it is unlikely.

  6. Palatoglossal fusion with cleft palate and hypoplasia of cerebellar vermis

    Directory of Open Access Journals (Sweden)

    Shailesh Solanki

    2016-01-01

    Full Text Available A new-born male presented within 12 h of birth with respiratory distress. On examination and workup, he had palatoglossal fusion, cleft palate and hypoplasia of the cerebellar vermis. A 2.5 Fr endotracheal tube was inserted into the pharynx through nostril as a nasopharyngeal stent, following which his respiratory distress improved. Once child was optimised, then feeding was started by nasogastric tube and feeds were tolerated well. Elective tracheostomy and gastrostomy were done, followed by release of adhesions between the tongue and palate at a later stage. Review of literature suggests that palatoglossal fusion is uncommon and presents as an emergency. Mostly, these oral synechiae are associated with digital and/or cardiac anomaly. Other disorders associated with intra-oral synechiae include congenital alveolar synechiae, van der Woude syndrome, popliteal pterygium syndrome and oromandibular limb hypogenesis syndrome. The authors report a hitherto undescribed association of palatoglossal fusion with cleft palate and hypoplasia of the cerebellar vermis.

  7. Crossed cerebellar diaschisis demonstrated by SPECT in hemiplegic children

    Energy Technology Data Exchange (ETDEWEB)

    Hamano, Shin-ichiro; Nara, Takahiro; Nozaki, Hidetsugu; Fukushima, Kiyomi (Saitama Children' s Medical Center, Iwatsuki (Japan)); Imai, Masayuki; Kumagai, Koumei; Maekawa, Kihei

    1991-01-01

    Crossed cerebellar diaschisis (CCD) in twenty five children with hemiplegia were studied using single photon emission computed tomography (SPECT) with N-isopropyl-p-I-123-iodoamphetamine. Seven of twenty-five patients had cerebral palsy, and the others were impaired by acquired brain injury between ten months and fourteen years of age. CCD was demonstrated in five patients (20%), who were impaired by acquired brain injury after seven years of age. CCD could never be detected in patients with cerebral palsy. Ipsilateral cerebellar diaschisis was also demonstrated in two patients with cerebral palsy and three with early acquired brain injury before three years of age. It is suggested that diaschisis presents itself as a different form in a contralateral and ipsilateral cerebellum before three years of age from a form which presents after seven years of age. (author).

  8. Abnormal ocular motility with brainstem and cerebellar disorders.

    Science.gov (United States)

    Carlow, T J; Bicknell, J M

    1978-01-01

    The disorders of ocular motility seen in association with brainstem or cerebellar disorders may point to rather specific anatomical or pathological correlations. Pontine gaze palsy reflects involvement of the pontine paramedian reticular formation. Internuclear ophthalmoplegia signifies a lesion in the medial longitudinal fasciculus. Skew deviation may result from a lesion anywhere in the posterior fossa. Ocular bobbing typically results from a pontine lesion. The Sylvian aqueduct syndrome is characteristic of involvement in the upper midbrain-pretectal region, usually a pinealoma. Cerebellar lesions may be manifested by gaze paresis, skew deviation, disturbances of saccadic or smooth pursuit movements, ocular myoclonus, or several characteristic forms of nystagmus. Familiarity with these disorders may be of great help to the physician dealing with a patient with a possible posterior fossa lesion.

  9. Correlation between vestibular habituation and postural recovery in cerebellar patients.

    Science.gov (United States)

    Suarez, H; Caffa, C; Macadar, O

    1992-01-01

    Vestibular habituation was studied in normal subjects and in patients with cerebellar disease using a stimulation paradigm proposed in this paper. Six caloric stimuli were repeated daily in the same ear during six days and electronystagmographic responses at the beginning and the end of that period were compared. The normal behaviour was a clear reduction of the response across time. Two groups of cerebellar patients were identified by their ability to recover from positional imbalance after treatment. Compensated patients responded to repeated caloric stimulation in the same way as normal subjects. Conversely, uncompensated patients increased their response after the stimulation paradigm. The role played by the cerebellum in vestibular plasticity is discussed together with the observed correlation between vestibular habituation and the ability for postural recovery to occur.

  10. Energy cascades in the upper ocean

    Institute of Scientific and Technical Information of China (English)

    Ray Q.Lin; Scott Chubb

    2006-01-01

    Wave-wave interactions cause energy cascades. These are the most important processes in the upper ocean because they govern wave-growth and dissipation. Through indirect cascades, wave energy is transferred from higher frequencies to lower frequencies, leading to wave growth. In direct cascades, energy is transferred from lower frequencies to the higher frequencies, which causes waves to break, and dissipation of wave energy. However, the evolution and origin of energy cascade processes are still not fully understood. In particular, for example, results from a recent theory (Kalmykov, 1998) suggest that the class I wave-wave interactions (defined by situations involving 4-, 6-, 8-, etc, even numbers of resonantly interacting waves) cause indirect cascades, and Class II wave-wave interactions (involving, 5-, 7-, 9-, etc, .., odd numbers of waves) cause direct cascades. In contrast to this theory, our model results indicate the 4-wave interactions can cause significant transfer of wave energy through both direct and indirect cascades. In most situations, 4-wave interactions provide the major source of energy transfer for both direct cascades and indirect cascades, except when the wave steepness is larger than 0.28. Our model results agree well with wave measurements, obtained using field buoy data (for example, Lin and Lin, 2002). In particular, in these observations, asymmetrical wave-wave interactions were studied. They found that direct and indirect cascades both are mainly due to the 4-wave interactions when wave steepness is less than 0.3.

  11. Cbln1 downregulates the formation and function of inhibitory synapses in mouse cerebellar Purkinje cells.

    Science.gov (United States)

    Ito-Ishida, Aya; Kakegawa, Wataru; Kohda, Kazuhisa; Miura, Eriko; Okabe, Shigeo; Yuzaki, Michisuke

    2014-04-01

    The formation of excitatory and inhibitory synapses must be tightly coordinated to establish functional neuronal circuitry during development. In the cerebellum, the formation of excitatory synapses between parallel fibers and Purkinje cells is strongly induced by Cbln1, which is released from parallel fibers and binds to the postsynaptic δ2 glutamate receptor (GluD2). However, Cbln1's role, if any, in inhibitory synapse formation has been unknown. Here, we show that Cbln1 downregulates the formation and function of inhibitory synapses between Purkinje cells and interneurons. Immunohistochemical analyses with an anti-vesicular GABA transporter antibody revealed an increased density of interneuron-Purkinje cell synapses in the cbln1-null cerebellum. Whole-cell patch-clamp recordings from Purkinje cells showed that both the amplitude and frequency of miniature inhibitory postsynaptic currents were increased in cbln1-null cerebellar slices. A 3-h incubation with recombinant Cbln1 reversed the increased amplitude of inhibitory currents in Purkinje cells in acutely prepared cbln1-null slices. Furthermore, an 8-day incubation with recombinant Cbln1 reversed the increased interneuron-Purkinje cell synapse density in cultured cbln1-null slices. In contrast, recombinant Cbln1 did not affect cerebellar slices from mice lacking both Cbln1 and GluD2. Finally, we found that tyrosine phosphorylation was upregulated in the cbln1-null cerebellum, and acute inhibition of Src-family kinases suppressed the increased inhibitory postsynaptic currents in cbln1-null Purkinje cells. These findings indicate that Cbln1-GluD2 signaling inhibits the number and function of inhibitory synapses, and shifts the excitatory-inhibitory balance towards excitation in Purkinje cells. Cbln1's effect on inhibitory synaptic transmission is probably mediated by a tyrosine kinase pathway.

  12. Studying cerebellar circuits by remote control of selected neuronal types with GABA-A receptors

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    William Wisden

    2009-12-01

    Full Text Available Although GABA-A receptor-mediated inhibition of cerebellar Purkinje cells by molecular layer interneurons (MLIs has been studied intensely on the cellular level, it has remained unclear how this inhibition regulates cerebellum-dependent behaviour. We have implemented two complementary approaches to investigate the function of the MLI-Purkinje cell synapse on the behavioral level. In the first approach we permanently disrupted inhibitory fast synaptic transmission at the synapse by genetically removing the postsynaptic GABA-A receptors from Purkinje cells (PC-Δγ2 mice. We found that chronic disruption of the MLI-Purkinje cell synapse strongly impaired cerebellar learning of the vestibular occular reflex (VOR, presumably by disrupting the temporal patterns of Purkinje cell activity. However, in PC-Δγ2 mice the baseline VOR reflex was only mildly affected; indeed PC-Δγ2 mice showed no ataxia or gait abnormalities suggesting that MLI control of Purkinje cell activity is either not involved in ongoing motor tasks or that the system has found a way to compensate for its loss. To investigate the latter possibility we have developed an alternative genetic technique; we made the MLI-Purkinje cell synapse selectively sensitive to rapid manipulation with the GABAA receptor modulator zolpidem (PC-γ2-swap mice. Minutes after intraperitoneal zolpidem injection, these PC-γ2-swap mice developed severe motor abnormalities, revealing a substantial contribution of the MLI-Purkinje cell synapse to real time motor control. The cell-type selective permanent knockout of synaptic GABAergic input, and the fast reversible modulation of GABAergic input at the same synapse illustrate how pursuing both strategies gives a fuller view.

  13. Cerebellar damage impairs internal predictions for sensory and motor function

    OpenAIRE

    Therrien, Amanda S.; Bastian, Amy J.

    2015-01-01

    The cerebellum is connected to cerebral areas that subserve a range of sensory and motor functions. In this review, we summarize new literature demonstrating deficits in visual perception, proprioception, motor control, and motor learning performance following cerebellar damage. In particular, we highlight novel results that together suggest a general role of the cerebellum in estimating and predicting movement dynamics of the body and environmental stimuli. These findings agree with the hypo...

  14. Hereditary lissencephaly and cerebellar hypoplasia in Churra lambs

    OpenAIRE

    Pérez Pérez, Valentín; Suárez-Vega, Aroa; Fuertes, M.; Benavides, Julio; Delgado, L.; Ferreras, Mª del Carmen; Arranz, Juan José

    2013-01-01

    Abstract Background Lissencephaly is a rare developmental brain disorder in veterinary and human medicine associated with defects in neuronal migration leading to a characteristic marked reduction or absence of the convolutional pattern of the cerebral hemispheres. In many human cases the disease has a genetic basis. In sheep, brain malformations, mainly cerebellar hypoplasia and forms of hydrocephalus, are frequently due to in utero viral infections. Although breed-related malformations of t...

  15. Degenerative cerebellar diseases and differential diagnoses; Degenerative Kleinhirnerkrankungen und Differenzialdiagnosen

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    Reith, W.; Roumia, S.; Dietrich, P. [Universitaetsklinikum des Saarlandes, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Homburg/Saar (Germany)

    2016-11-15

    Cerebellar syndromes result in distinct clinical symptoms, such as ataxia, dysarthria, dysmetria, intention tremor and eye movement disorders. In addition to the medical history and clinical examination, imaging is particularly important to differentiate other diseases, such as hydrocephalus and multi-infarct dementia from degenerative cerebellar diseases. Degenerative diseases with cerebellar involvement include Parkinson's disease, multiple system atrophy as well as other diseases including spinocerebellar ataxia. In addition to magnetic resonance imaging (MRI), nuclear medicine imaging investigations are also helpful for the differentiation. Axial fluid-attenuated inversion recovery (FLAIR) and T2-weighted sequences can sometimes show a signal increase in the pons as a sign of degeneration of pontine neurons and transverse fibers in the basilar part of the pons. The imaging is particularly necessary to exclude other diseases, such as normal pressure hydrocephalus (NPH), multi-infarct dementia and cerebellar lesions. (orig.) [German] Klinisch imponieren Kleinhirnsyndrome durch Ataxie, Dysarthrie, Dysmetrie, Intentionstremor und Augenbewegungsstoerungen. Neben der Anamnese und klinischen Untersuchung ist die Bildgebung v. a. wichtig um andere Erkrankungen wie Hydrozephalus und Multiinfarktdemenz von degenerativen Kleinhirnerkrankungen zu differenzieren. Zu den degenerativen Erkrankungen mit Kleinhirnbeteiligung gehoeren der Morbus Parkinson, die Multisystematrophie sowie weitere Erkrankungen einschliesslich der spinozerebellaeren Ataxien. Neben der MRT sind auch nuklearmedizinische Untersuchungen zur Differenzierung hilfreich. Axiale Fluid-attenuated-inversion-recovery(FLAIR)- und T2-gewichtete Sequenzen koennen mitunter eine Signalsteigerung im Pons als Ausdruck einer Degeneration der pontinen Neuronen und transversalen Bahnen im Brueckenfuss zeigen. Die Bildgebung ist aber v. a. notwendig, um andere Erkrankungen wie Normaldruckhydrozephalus

  16. Acute cerebellar ataxia: A neurological manifestation in malaria

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    Peddametla Shravan Kumar

    2014-01-01

    Full Text Available Malaria is a vector-borne disease transmitted by the bite of an infected female anopheles mosquito presents with varied clinical manifestations. Neurological manifestations include headaches, confusion, convulsions, hemiplegia, ataxia, cerebral palsy, cortical blindness, and Guillain-Barre syndrome (GBS. We are presenting a case report of acute cerebellar ataxia in a 20-year-old male patient who presented with fever and positive for Plasmodium vivax and Plasmodium falciparum malaria antibodies.

  17. Phenytoin-induced cerebellar atrophy in an epileptic boy

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    Nithin Kumar

    2013-01-01

    Full Text Available Epilepsy is an important health problem due to its high prevalence and potential for causing long-term morbidity. It is commonly treated in children with phenytoin sodium. It has wide pharmacokinetic variability and a narrow therapeutic range that leads to toxicity. Here, we report a case of phenytoin-induced cerebellar atrophy in a 16-year-old epileptic boy who presented to the hospital with a viral infection.

  18. Successful treatment of isolated cerebellar cysticercosis with albendazole

    Institute of Scientific and Technical Information of China (English)

    朱利平; 石尧忠; 潘孝彰; 莫凌; 翁心华

    2003-01-01

    Neurocysticercosis (NCC) is a parasitic disease of the central nervous system (CNS) found world-wide.1 NCC is the most common cause of parasitic infection of CNS in China. Patients with NCC are treated successfully with chemotherapy. However, isolated cystic lesions sited in the cerebellum are usually treated by direct surgical excision as a primary therapeutic modality.2 We present here a case of isolated cerebellar vermis cysticercosis successfully treated with albendazole.

  19. Patterns of regional cerebellar atrophy in genetic frontotemporal dementia

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    Martina Bocchetta

    2016-01-01

    Conclusion: There appears to be a differential pattern of cerebellar atrophy in the major genetic forms of FTD, being relatively spared in GRN, localized to the lobule VIIa-Crus I in the superior-posterior region of the cerebellum in C9orf72, the area connected via the thalamus to the prefrontal cortex and involved in cognitive function, and localized to the vermis in MAPT, the ‘limbic cerebellum’ involved in emotional processing.

  20. Cerebellar Herniation after Lumbar Puncture in Galactosemic Newborn

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    Salih Kalay

    2011-09-01

    Full Text Available Cerebral edema resulting in elevated intracranial pressure is a well-known complication of galactosemia. Lumbar puncture was performed for the diagnosis of clinically suspected bacterial meningitis. Herniation of cerebral tissue through the foramen magnum is not a common problem in neonatal intensive care units because of the open fontanelle in infants. We present the case of a 3-week-old infant with galactosemia who presented with signs of cerebellar herniation after lumbar puncture.

  1. [Aneurysm of the anterior inferior cerebellar artery: case report].

    Science.gov (United States)

    Adorno, Juan Oscar Alarcón; de Andrade, Guilherme Cabral

    2002-12-01

    The intracranial aneurysms of the posterior circulation have been reported between 5 and 10% of all cerebral aneurysms and the aneurysms of the anterior inferior cerebellar artery (AICA) are considered rare, can cause cerebello pontine angle (CPA) syndrome with or without subarachnoid hemorrhage. Since 1948 few cases were described in the literature. We report on a 33 year-old female patient with subarachnoid hemorrhage due to sacular aneurysm of the left AICA. She was submitted to clipage of the aneurysm without complications.

  2. Distal posterior inferior cerebellar artery aneurysm in a child

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    J. Francisco Salomão

    1992-06-01

    Full Text Available The case of a 7-year-old boy presenting with recurrent episodes of subarachnoid hemorrhage due to a distal posterior inferior cerebellar artery aneurysm (PICA, successfully operated, is reported.' The low incidence of intracranial aneurysms in the first decade of life and the rare occurrence of distal PICA aneurysms are unusual features of this case. The theories regarding the origin of intracranial berry aneurysms are discussed.

  3. Patient adaptable cerebellar retractor system: Use in posterior fossa surgery

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    Hamid Borghei-Razavi

    2015-06-01

    Full Text Available A new patient adaptable dual use soft tissue spreader and cerebellar retractor system designed for use during surgery of the posterior fossa is described. We found that this new retractor design allowed for excellent exposure, plus greater freedom and dexterity during the posterior fossa surgery. This novel instrument is an improvement over the existing instrument, because it provided more force/power transmission from pins/connectors to the brain spatula via the shorter flexible arm.

  4. Successfull management of a life threatening cerebellar haemorrhage following spine surgery - a case report -.

    Science.gov (United States)

    Pallud, Johan; Belaïd, Hayat; Aldea, Sorin

    2009-06-01

    Cerebellar haemorrhages are rare life-threatening complications following spine surgery that present challenges for their diagnostic and their therapeutic management. Their patho-physiology remains unclear.We report a case of a life-threatening cerebellar haemorrhage secondary to an occult dural tear following a planned L5-S1 laminectomy. The patient was treated with emergent external ventriculostomy following by a posterior fossa decompressive craniectomy. Cerebellar haemorrhages have to be suspected systematically when unexpected neurological signs occur after spine surgery since their rapid management lead to favourable outcomes. The present imaging findings allow us proposing that cerebellar haemorrhages result primarily from superior cerebellar venous stretching and tearing, and that cerebellar infarction and swelling occur secondarily.

  5. Magnetic resonance imaging in the diagnosis of cerebellar ataxias

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    Kato, Hiroyuki; Takase, Sadao; Mochizuki, Hiroshi; Kogure, Kyuya; Yamada, Kenji; Hishinuma, Takashi; Matsuzawa, Taiju.

    1987-11-01

    Radiological evaluation in order to quantitatively analyse the size of structures in the posterior fossa using magnetic resonance imaging (MRI) was performed in the patients with spinocerebellar degeneration (SCD). The subjects consisted of 17 patients including 11 OPCA (olivopontocerebellar atrophy)-type and 6 LCCA (late cortical cerebellar atrophy)-type SCD patients, and their disease was in the initial phase. Using a mid-line sagittal view, quantitative measurements of the cerebellum, pons and the medulla oblongata were performed. In the OPCA-type SCD patients, the area, and the longitudinal and anteroposterior diameters of the cerebellar vermis, the area and the anteroposterior diameter of the pons, the height of the fourth ventricle, and the anteroposterior diameter of the medulla oblongata were significantly smaller than those of normal subjects. In the LCCA-type SCD patients, only the area and the anteroposterior diameter of the cerebellar vermis were smaller than those of the normal. As a result, MRI is useful in the diagnosis of SCD, and in the differential diagnosis between the OPCA-type and the LCCA-type SCDs.

  6. Behavior modification after inactivation of cerebellar dentate nuclei.

    Science.gov (United States)

    Peterson, Todd C; Villatoro, Lee; Arneson, Tom; Ahuja, Brittany; Voss, Stephanie; Swain, Rodney A

    2012-08-01

    Effort-based decision making occurs when subjects are given a choice between a reward available at a high response cost and a reward available at a low response cost and is altered in individuals with disorders such as autism or particular patterns of brain injury. The current study explored the relationship between effort-based decision making and reinforcement characteristics in the T maze. This was done using both normal animals and animals with bilateral inactivation of the cerebellar dentate nuclei. Rats chose between alternatives in which one arm contained high-density reinforcement (HR) and the other arm contained low-density reinforcement (LR). During training, the HR arm was obstructed and the point at which the animal no longer worked for reinforcement (breaking point) was determined. The cerebellar dentate nuclei were then transiently inactivated and once again breaking points were assessed. The results indicated that inactivation of the dentate nucleus disrupted effort-based decision making. Additionally, altering both the palatability and the magnitude of the reinforcement were assessed in an attempt to reestablish the original preinactivation breaking point. It was hypothesized that an increase in the strength or magnitude of the reinforcement would promote an increase in the breaking point of the animal even when the cerebellum was inactivated. The results indicated that with both strategies animals effectively reestablished original breaking points. The results of this study will inform the current literature regarding the modification of behavior after brain injury and further the understanding of the behavioral deficits associated with cerebellar dysfunction.

  7. β-Catenin is critical for cerebellar foliation and lamination.

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    Jing Wen

    Full Text Available The cerebellum has a conserved foliation pattern and a well-organized layered structure. The process of foliation and lamination begins around birth. β-catenin is a downstream molecule of Wnt signaling pathway, which plays a critical role in tissue organization. Lack of β-catenin at early embryonic stages leads to either prenatal or neonatal death, therefore it has been difficult to resolve its role in cerebellar foliation and lamination. Here we used GFAP-Cre to ablate β-catenin in neuronal cells of the cerebellum after embryonic day 12.5, and found an unexpected role of β-catenin in determination of the foliation pattern. In the mutant mice, the positions of fissure formation were changed, and the meninges were improperly incorporated into fissures. At later stages, some lobules were formed by Purkinje cells remaining in deep regions of the cerebellum and the laminar structure was dramatically altered. Our results suggest that β-catenin is critical for cerebellar foliation and lamination. We also found a non cell-autonomous role of β-catenin in some developmental properties of major cerebellar cell types during specific stages.

  8. Sustained Reduction of Cerebellar Activity in Experimental Epilepsy

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    Kim Rijkers

    2015-01-01

    Full Text Available Clinical and experimental evidence suggests a role for the cerebellum in seizure control, while no data are available on cerebellar activity between seizures. We hypothesized that interictal regional activity of the deep cerebellar nuclei is reduced in epilepsy and tested this in an animal model by using ΔFosB and cytochrome oxidase (COX (immunohistochemistry. The expression of these two markers of neuronal activity was analysed in the dentate nucleus (DN, interpositus nucleus (IN, and fastigial nucleus (FN of the cerebellum of fully amygdala kindled rats that were sacrificed 48 hours after their last seizure. The DN and FN of kindled rats exhibited 25 to 29% less ΔFosB immunopositive cells than their respective counterpart in sham controls (P<0.05. COX expression in the DN and FN of kindled animals was reduced by 32 to 33% compared to respective control values (P<0.05. These results indicate that an epileptogenic state is characterized by decreased activity of deep cerebellar nuclei, especially the DN and FN. Possible consequences may include a decreased activation of the thalamus, contributing to further seizure spread. Restoration of FN activity by low frequency electrical stimulation is suggested as a possible treatment option in chronic epilepsy.

  9. Paraneoplastic cerebellar degeneration with anti-Yo antibodies - a review.

    Science.gov (United States)

    Venkatraman, Anand; Opal, Puneet

    2016-08-01

    The ataxic syndrome associated with Anti-Yo antibody, or Purkinje cell cytoplasmic antibody type 1 (PCA1), is the most common variant of paraneoplastic cerebellar degeneration (PCD). The typical presentation involves the subacute development of pancerebellar deficits with a clinical plateau within 6 months. The vast majority of cases have been reported in women with pelvic or breast tumors. Magnetic resonance imaging of the brain is often normal in the early stages, with cerebellar atrophy seen later. The underlying mechanism is believed to be an immunological reaction to cerebellar degeneration-related protein 2 (CDR2), a protein usually found in the cerebellum that is ectopically produced by tumor cells. Although both B- and T-cell abnormalities are seen, there is debate about the relative importance of the autoantibodies and cytotoxic T lymphocytes in the neuronal loss. Cerebrospinal fluid abnormalities, primarily elevated protein, lymphocytic pleocytosis, and oligoclonal bands, are common in the early stages. The low prevalence of this condition has not allowed for large-scale randomized controlled trials. Immunotherapies, such as steroids, intravenous immune globulins, and plasma exchange, have been extensively used in managing this condition, with limited success. Although some reports indicate benefit from antitumor therapies like surgery and chemotherapy, this has not been consistently observed. The prognosis for anti-Yo PCD is almost uniformly poor, with most patients left bedridden. Further studies are required to clarify the pathophysiology and provide evidence-based treatment options.

  10. The Changeable Nervous System: Studies On Neuroplasticity In Cerebellar Cultures

    Science.gov (United States)

    Seil, Fredrick J.

    2014-01-01

    Circuit reorganization after injury was studied in a cerebellar culture model. When cerebellar cultures derived from newborn mice were exposed at explantation to a preparation of cytosine arabinoside that destroyed granule cells and oligodendrocytes and compromised astrocytes, Purkinje cells surviving in greater than usual numbers were unensheathed by astrocytic processes and received twice the control number of inhibitory axosomatic synapses. Purkinje cell axon collaterals sprouted and many of their terminals formed heterotypical synapses with other Purkinje cell dendritic spines. The resulting circuit reorganization preserved inhibition in the cerebellar cortex. Following this reorganization, replacement of the missing granule cells and glia was followed by a restitution of the normal circuitry. Most of these developmental and reconstructive changes were not dependent on neuronal activity, the major exception being inhibitory synaptogenesis. The full complement of inhibitory synapses did not develop in the absence of neuronal activity, which could be mitigated by application of exogenous TrkB receptor ligands. Inhibitory synaptogenesis could also be promoted by activity-induced release of endogenous TrkB receptor ligands or by antibody activation of the TrkB receptor. PMID:24933693

  11. Inpatient Rehabilitation Performance of Patients with Paraneoplastic Cerebellar Degeneration

    Science.gov (United States)

    Fu, Jack B.; Raj, Vishwa S.; Asher, Arash; Lee, Jay; Guo, Ying; Konzen, Benedict S.; Bruera, Eduardo

    2014-01-01

    Objective To evaluate the functional improvement of rehabilitation inpatients with paraneoplastic cerebellar degeneration. Design Retrospective Review Setting Three tertiary referral based hospitals. Interventions Medical records were retrospectively analyzed for demographic, laboratory, medical and functional data. Main Outcome Measure Functional Independence Measure (FIM) Participants Cancer rehabilitation inpatients admitted to three different cancer centers with a diagnosis of paraneoplastic cerebellar degeneration (n=7). Results All 7 patients were white females. Median age was 62. Primary cancers included ovarian carcinoma (2), small cell lung cancer (2), uterine carcinoma (2), and invasive ductal breast carcinoma. Mean admission total FIM score was 61.0 (SD=23.97). Mean discharge total FIM score was 73.6 (SD=29.35). The mean change in total FIM score was 12.6 (p=.0018). The mean length of rehabilitation stay was 17.1 days. The mean total FIM efficiency was 0.73. 5/7 (71%) patients were discharged home. 1/7 (14%) was discharged to a nursing home. 1/7 (14%) transferred to the primary acute care service. Conclusions This is the first study to demonstrate the functional performance of a group of rehabilitation inpatients with paraneoplastic cerebellar degeneration. Despite the poor neurologic prognosis associated with this syndrome, these patients made significant functional improvements on inpatient rehabilitation. When appropriate, inpatient rehabilitation should be considered. Further studies with larger sample sizes are needed. PMID:25051460

  12. Morphology and biomechanical properties of cerebellar arteries in adults

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    Olga A. Fomkina

    2016-06-01

    Full Text Available The goal was to analyze the variability of a number of morphometric and biomechanical parameters of cerebellar arteries in adults aged 20-74 years. Material and Methods ― 179 samples of cerebellar arteries, obtained by autopsy of adults without acute cerebrovascular pathology have been studied; 24 preparations of arterial complexes «arterial circle – cerebral arteries» from scientific collection of Human Anatomy Department of Saratov State Medical University (Saratov, Russia have been also investigated. Research methods were: preparation, microscopy, experiments on uniaxial longitudinal stretching at a tensile testing machine Tira Test 28005 (TIRA GmbH, Germany. We studied outer diameter, angle of divergence, overall strength and maximal relative deformation of superior (SCA, anterior inferior (AICA and posterior inferior cerebellar arteries (PICA. Results and Conclusion ― It was revealed that SCA was characterized by the largest diameter and angle of divergence, the most strength and extensibility. AICA and PICA had no significant differences of the studied parameters. It was noted that AICA originated in the lower third part of basilar artery 1.5 times more likely than in the middle third part of this artery.

  13. A Comparison of Methods for Cascade Prediction

    CERN Document Server

    Guo, Ruocheng

    2016-01-01

    Information cascades exist in a wide variety of platforms on Internet. A very important real-world problem is to identify which information cascades can go viral. A system addressing this problem can be used in a variety of applications including public health, marketing and counter-terrorism. As a cascade can be considered as compound of the social network and the time series. However, in related literature where methods for solving the cascade prediction problem were proposed, the experimental settings were often limited to only a single metric for a specific problem formulation. Moreover, little attention was paid to the run time of those methods. In this paper, we first formulate the cascade prediction problem as both classification and regression. Then we compare three categories of cascade prediction methods: centrality based, feature based and point process based. We carry out the comparison through evaluation of the methods by both accuracy metrics and run time. The results show that feature based met...

  14. Congenital Cerebellar Mixed Germ Cell Tumor Presenting with Hemorrhage in a Newborn

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Mok; Kim, Ji Hye; Yoo, So Young; Park, Won Soon; Jang, Yun Sil; Shin, Hyung Jin; Suh, Yeon Lim [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2008-07-15

    We report here on a neonate with congenital cerebellar mixed germ cell tumor, and this initially presented as cerebellar hemorrhage. Postnatal cranial ultrasonography revealed an echogenic cerebellar mass that exhibited the signal characteristics of hemorrhage rather than tumor on MR images. The short-term follow-up images also suggested a resolving cerebellar hemorrhage. One month later, the neonate developed vomiting. A second set of MR images demonstrated an enlarged mass that exhibited changed signal intensity at the same site, which suggested a neoplasm. Histological examination after the surgical resection revealed a mixed germ cell tumor.

  15. Metalinguistic deficits in patients with cerebellar dysfunction: empirical support for the dysmetria of thought theory.

    Science.gov (United States)

    Guell, Xavier; Hoche, Franziska; Schmahmann, Jeremy D

    2015-02-01

    The cerebellar cognitive affective syndrome (CCAS) includes disruption of linguistic processing such as verbal fluency, verbal working memory, grammar, and speech perception. We set out to examine linguistic capabilities in patients with cerebellar lesions to determine which domains are spared and which impaired and to evaluate the underlying cognitive structure of these deficits. Forty-four patients with cerebellar disease were compared to 40 healthy controls on the Oral Sentence Production Test (OSPT) which assesses production of sentences with correct syntactic structure and semantic quality. Twenty-five of these cerebellar patients and 25 controls received the Test of Language Competence-Expanded (TLC-E) that assesses metalinguistic ability. The OSPT failed to reveal differences between patients and controls. In contrast, all cerebellar patients were impaired on each of the four TLC-E subtests. Differences between isolated cerebellar and complex cerebrocerebellar patients were nonsignificant. These results confirm and extend prior observations of the TLC-E in patients with cerebellar lesions and suggest three separate but related language impairments following cerebellar dysfunction: (1) disruption in automatic adjustment of intact grammatical and semantic abilities to a linguistic context in sentence production, (2) disruption in automatic adjustment to a linguistic context in sentence interpretation, and (3) disruption of cognitive processes essential for linguistic skills, such as analysis and sequential logical reasoning. These findings are consistent with the unifying framework of the universal cerebellar transform and the dysmetria of thought theory and provide new insights into the nature of the cognitive impairments in patients with the CCAS.

  16. Medical management of cerebellar abscess: a case report and review of the literature.

    Science.gov (United States)

    Turner, Ryan C; Dodson, Sean C; Rosen, Charles L

    2011-01-01

    A large abscess of the posterior fossa often warrants surgical intervention. We report a case of a 50-year-old male presenting with a cerebellar abscess measuring 2.8 cm x 1.6 cm located in the left cerebellar hemisphere at the level of the middle cerebellar peduncle that was treated conservatively and successfully with antibiotics. Therapeutic management options are discussed in regards to this case specifically as well as a review of the literature. This case illustrates the successful medical management of a cerebellar abscess of otogenic origin in an adult, a unique result in terms of abscess size and age of the patient.

  17. Spray formation: an inverse cascade

    CERN Document Server

    Ling, Yue; Tryggvason, Gretar; zaleski, Stephane

    2015-01-01

    We present a study of droplet formation in a gas-liquid mixing layer using direct numerical simulation. It is seen that two mechanisms compete to generate the droplets: fingering at the tip of the waves and hole formation in the thin liquid sheet. The three dimensional liquid structures are much shorter than the longitudinal wavelength of the instability at the first instant of their formation. As time evolves, the structures evolves to larger and larger scales, in a way similar to the inverse cascade of length scales in droplet impact and impact crown formation.

  18. Disaster Mythology and Availability Cascades

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    Lisa Grow Sun

    2013-04-01

    Full Text Available Sociological research conducted in the aftermath of natural disasters has uncovered a number of “disaster myths” – widely shared misconceptions about typical post-disaster human behavior. This paper discusses the possibility that perpetuation of disaster mythology reflects an “availability cascade,” defined in prior scholarship as a “self-reinforcing process of collective belief formation by which an expressed perception triggers a chain reaction that gives the perception increasing plausibility through its rising availability in public discourse.” (Kuran and Sunstein 1999. Framing the spread of disaster mythology as an availability cascade suggests that certain tools may be useful in halting the myths’ continued perpetuation. These tools include changing the legal and social incentives of so-called “availability entrepreneurs” – those principally responsible for beginning and perpetuating the cascade, as well as insulating decision-makers from political pressures generated by the availability cascade. This paper evaluates the potential effectiveness of these and other solutions for countering disaster mythology. Las investigaciones sociológicas realizadas tras los desastres naturales han hecho evidentes una serie de “mitos del desastre”, conceptos erróneos ampliamente compartidos sobre el comportamiento humano típico tras un desastre. Este artículo analiza la posibilidad de que la perpetuación de los mitos del desastre refleje una “cascada de disponibilidad”, definida en estudios anteriores como un “proceso de auto-refuerzo de la formación de una creencia colectiva, a través del que una percepción expresada produce una reacción en cadena que hace que la percepción sea cada vez más verosímil, a través de una mayor presencia en el discurso público” (Kuran y Sunstein 1999. Enmarcar la propagación de los mitos del desastre como una cascada de disponibilidad sugiere que ciertas herramientas pueden ser

  19. Cascades on clique-based graphs

    CERN Document Server

    Hackett, Adam

    2013-01-01

    We present an analytical approach to determining the expected cascade size in a broad range of dynamical models on the class of highly-clustered random graphs introduced in [J. P. Gleeson, Phys. Rev. E 80, 036107 (2009)]. A condition for the existence of global cascades is also derived. Applications of this approach include analyses of percolation, and Watts's model. We show how our techniques can be used to study the effects of in-group bias in cascades on social networks.

  20. Lateral Modes in Quantum Cascade Lasers

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    Gregory C. Dente

    2016-03-01

    Full Text Available We will examine the waveguide mode losses in ridge-guided quantum cascade lasers. Our analysis illustrates how the low-loss mode for broad-ridge quantum cascade lasers (QCLs can be a higher-order lateral waveguide mode that maximizes the feedback from the sloped ridge-wall regions. The results are in excellent agreement with the near- and far-field data taken on broad-ridge-guided quantum cascade lasers processed with sloped ridge walls.

  1. Synaptic responses evoked by tactile stimuli in Purkinje cells in mouse cerebellar cortex Crus II in vivo.

    Directory of Open Access Journals (Sweden)

    Chun-Ping Chu

    Full Text Available BACKGROUND: Sensory stimuli evoke responses in cerebellar Purkinje cells (PCs via the mossy fiber-granule cell pathway. However, the properties of synaptic responses evoked by tactile stimulation in cerebellar PCs are unknown. The present study investigated the synaptic responses of PCs in response to an air-puff stimulation on the ipsilateral whisker pad in urethane-anesthetized mice. METHODS AND MAIN RESULTS: Thirty-three PCs were recorded from 48 urethane-anesthetized adult (6-8-week-old HA/ICR mice by somatic or dendritic patch-clamp recording and pharmacological methods. Tactile stimulation to the ipsilateral whisker pad was delivered by an air-puff through a 12-gauge stainless steel tube connected with a pressurized injection system. Under current-clamp conditions (I = 0, the air-puff stimulation evoked strong inhibitory postsynaptic potentials (IPSPs in the somata of PCs. Application of SR95531, a specific GABA(A receptor antagonist, blocked IPSPs and revealed stimulation-evoked simple spike firing. Under voltage-clamp conditions, tactile stimulation evoked a sequence of transient inward currents followed by strong outward currents in the somata and dendrites in PCs. Application of SR95531 blocked outward currents and revealed excitatory postsynaptic currents (EPSCs in somata and a temporal summation of parallel fiber EPSCs in PC dendrites. We also demonstrated that PCs respond to both the onset and offset of the air-puff stimulation. CONCLUSIONS: These findings indicated that tactile stimulation induced asynchronous parallel fiber excitatory inputs onto the dendrites of PCs, and failed to evoke strong EPSCs and spike firing in PCs, but induced the rapid activation of strong GABA(A receptor-mediated inhibitory postsynaptic currents in the somata and dendrites of PCs in the cerebellar cortex Crus II in urethane-anesthetized mice.

  2. WHISTLER TURBULENCE FORWARD CASCADE VERSUS INVERSE CASCADE: THREE-DIMENSIONAL PARTICLE-IN-CELL SIMULATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Ouliang [Oracle Corporation, Redwood Shores, CA (United States); Gary, S. Peter [Space Science Institute, Boulder, CO (United States); Wang, Joseph, E-mail: ouliang@usc.edu, E-mail: pgary@lanl.gov, E-mail: josephjw@usc.edu [University of Southern California, Los Angeles, CA (United States)

    2015-02-20

    We present the results of the first fully three-dimensional particle-in-cell simulations of decaying whistler turbulence in a magnetized, homogeneous, collisionless plasma in which both forward cascades to shorter wavelengths, and inverse cascades to longer wavelengths are allowed to proceed. For the electron beta β {sub e} = 0.10 initial value considered here, the early-time rate of inverse cascade is very much smaller than the rate of forward cascade, so that at late times the fluctuation energy in the regime of the inverse cascade is much weaker than that in the forward cascade regime. Similarly, the wavevector anisotropy in the inverse cascade regime is much weaker than that in the forward cascade regime.

  3. Unsteady transonic flow over cascade blades

    Science.gov (United States)

    Surampudi, S. P.; Adamczyk, J. J.

    1986-01-01

    An attempt is made to develop an efficient staggered cascade blade unsteady aerodynamics model for the neighborhood of March 1, representing the blade row by a rectilinear two-dimensional cascade of thin, flat plate airfoils. The equations of motion are derived on the basis of linearized transonic small perturbation theory, and an analytical solution is obtained by means of the Wiener-Hopf procedure. Making use of the transonic similarity law, the results obtained are compared with those of other linearized cascade analyses. A parametric study is conducted to find the effects of reduced frequency, stagger angle, solidity, and the location of the pitching axis on cascade stability.

  4. Contingency Analysis of Cascading Line Outage Events

    Energy Technology Data Exchange (ETDEWEB)

    Thomas L Baldwin; Magdy S Tawfik; Miles McQueen

    2011-03-01

    As the US power systems continue to increase in size and complexity, including the growth of smart grids, larger blackouts due to cascading outages become more likely. Grid congestion is often associated with a cascading collapse leading to a major blackout. Such a collapse is characterized by a self-sustaining sequence of line outages followed by a topology breakup of the network. This paper addresses the implementation and testing of a process for N-k contingency analysis and sequential cascading outage simulation in order to identify potential cascading modes. A modeling approach described in this paper offers a unique capability to identify initiating events that may lead to cascading outages. It predicts the development of cascading events by identifying and visualizing potential cascading tiers. The proposed approach was implemented using a 328-bus simplified SERC power system network. The results of the study indicate that initiating events and possible cascading chains may be identified, ranked and visualized. This approach may be used to improve the reliability of a transmission grid and reduce its vulnerability to cascading outages.

  5. Single-Seed Cascades on Clustered Networks

    CERN Document Server

    McSweeney, John K

    2015-01-01

    We consider a dynamic network cascade process developed by Watts applied to a random networks with a specified amount of clustering, belonging to a class of random networks developed by Newman. We adapt existing tree-based methods to formulate an appropriate two-type branching process to describe the spread of a cascade started with a single active node, and obtain a fixed-point equation to implicitly express the extinction probability of such a cascade. In so doing, we also recover a special case of a formula of Hackett et al. giving conditions for certain extinction of the cascade.

  6. Multifunctional Cascaded Metamaterials: Integrated Transmitarrays

    Science.gov (United States)

    Elsakka, Amr A.; Asadchy, Viktar S.; Faniayeu, Ihar A.; Tcvetkova, Svetlana N.; Tretyakov, Sergei A.

    2016-10-01

    Control of electromagnetic waves using engineered materials is very important in a wide range of applications, therefore there is always a continuous need for new and more efficient solutions. Known natural and artificial materials and surfaces provide a particular functionality in the frequency range they operate but cast a "shadow" and produce reflections at other frequencies. Here, we introduce a concept of multifunctional engineered materials that possess different predetermined functionalities at different frequencies. Such response can be accomplished by cascading metasurfaces (thin composite layers) that are designed to perform a single operation at the desired frequency and are transparent elsewhere. Previously, out-of-band transparent metasurfaces for control over reflection and absorption were proposed. In this paper, to complete the full set of functionalities for wave control, we synthesize transmitarrays that tailor transmission in a desired way, being "invisible" beyond the operational band. The designed transmitarrays for wavefront shaping and anomalous refraction are tested numerically and experimentally. To demonstrate our concept of multifunctional engineered materials, we have designed a cascade of three metasurfaces that performs three different functions for waves at different frequencies. Remarkably, applied to volumetric metamaterials, our concept can enable a single composite possessing desired multifunctional response.

  7. Time evolution of cascade decay

    CERN Document Server

    Boyanovsky, Daniel

    2014-01-01

    We study non-perturbatively the time evolution of cascade decay for generic fields $\\pi \\rightarrow \\phi_1\\phi_2\\rightarrow \\phi_2\\chi_1\\chi_2$ and obtain the time dependence of amplitudes and populations for the resonant and final states. We analyze in detail the different time scales and the manifestation of unitary time evolution in the dynamics of production and decay of resonant intermediate and final states. The probability of occupation (population) ``flows'' as a function of time from the initial to the final states. When the decay width of the parent particle $\\Gamma_\\pi$ is much larger than that of the intermediate resonant state $\\Gamma_{\\phi_1}$ there is a ``bottleneck'' in the flow, the population of resonant states builds up to a maximum at $t^* = \\ln[\\Gamma_\\pi/\\Gamma_{\\phi_1}]/(\\Gamma_\\pi-\\Gamma_{\\phi_1})$ nearly saturating unitarity and decays to the final state on the longer time scale $1/\\Gamma_{\\phi_1}$. As a consequence of the wide separation of time scales in this case the cascade decay ...

  8. Clinical and genetic analysis of a four-generation family with a distinct autosomal dominant cerebellar ataxia

    NARCIS (Netherlands)

    Schelhaas, H J; Ippel, P F; Hageman, G; Sinke, R J; van der Laan, E N; Beemer, F A

    2001-01-01

    The autosomal dominant cerebellar ataxias (ADCAs) are a heterogeneous group of neurodegenerative disorders characterised by progressive cerebellar dysfunction in combination with a variety of other associative features. Since 1993 ADCAs have been increasingly characterised in terms of their genetic

  9. A SEL1L mutation links a canine progressive early-onset cerebellar ataxia to the endoplasmic reticulum-associated protein degradation (ERAD machinery.

    Directory of Open Access Journals (Sweden)

    Kaisa Kyöstilä

    Full Text Available Inherited ataxias are characterized by degeneration of the cerebellar structures, which results in progressive motor incoordination. Hereditary ataxias occur in many species, including humans and dogs. Several mutations have been found in humans, but the genetic background has remained elusive in dogs. The Finnish Hound suffers from an early-onset progressive cerebellar ataxia. We have performed clinical, pathological, and genetic studies to describe the disease phenotype and to identify its genetic cause. Neurological examinations on ten affected dogs revealed rapidly progressing generalized cerebellar ataxia, tremors, and failure to thrive. Clinical signs were present by the age of 3 months, and cerebellar shrinkage was detectable through MRI. Pathological and histological examinations indicated cerebellum-restricted neurodegeneration. Marked loss of Purkinje cells was detected in the cerebellar cortex with secondary changes in other cortical layers. A genome-wide association study in a cohort of 31 dogs mapped the ataxia gene to a 1.5 Mb locus on canine chromosome 8 (p(raw = 1.1x10(-7, p(genome = 7.5x10(-4. Sequencing of a functional candidate gene, sel-1 suppressor of lin-12-like (SEL1L, revealed a homozygous missense mutation, c.1972T>C; p.Ser658Pro, in a highly conserved protein domain. The mutation segregated fully in the recessive pedigree, and a 10% carrier frequency was indicated in a population cohort. SEL1L is a component of the endoplasmic reticulum (ER-associated protein degradation (ERAD machinery and has not been previously associated to inherited ataxias. Dysfunctional protein degradation is known to cause ER stress, and we found a significant increase in expression of nine ER stress responsive genes in the cerebellar cortex of affected dogs, supporting the pathogenicity of the mutation. Our study describes the first early-onset neurodegenerative ataxia mutation in dogs, establishes an ERAD-mediated neurodegenerative

  10. Modeling elephant-mediated cascading effects of water point closure

    NARCIS (Netherlands)

    Hilbers, J.P.; Langevelde, van F.; Prins, H.H.T.; Grant, C.C.; Peel, M.; Coughenour, M.B.; Knegt, de H.J.; Slotow, R.; Smit, I.; Kiker, G.A.; Boer, de W.F.

    2015-01-01

    Wildlife management to reduce the impact of wildlife on their habitat can be done in several ways, among which removing animals (by either culling or translocation) is most often used. There are however alternative ways to control wildlife densities, such as opening or closing water points. The effe

  11. Modeling elephant-mediated cascading effects of water point closure

    NARCIS (Netherlands)

    Hilbers, J.P.; Langevelde, van F.; Prins, H.H.T.; Grant, C.C.; Peel, M.; Coughenour, M.B.; Knegt, de H.J.; Slotow, R.; Smit, I.; Kiker, G.A.; Boer, de W.F.

    2014-01-01

    Wildlife management to reduce the impact of wildlife on their habitat can be done in several ways, among which removing animals (by either culling or translocation) is most often used. There are however alternative ways to control wildlife densities, such as opening or closing water points. The effe

  12. Modeling elephant-mediated cascading effects of water point closure.

    Science.gov (United States)

    Hilbers, Jelle P; Van Langevelde, Frank; Prins, Herbert H T; Grant, C C; Peel, Mike J S; Coughenour, Michael B; De Knegt, Henrik J; Slotow, Rob; Smit, Izak P J; Kiker, Greg A; De Boer, Willem F

    2015-03-01

    Wildlife management to reduce the impact of wildlife on their habitat can be done in several ways, among which removing animals (by either culling or translocation) is most often used. There are, however, alternative ways to control wildlife densities, such as opening or closing water points. The effects of these alternatives are poorly studied. In this paper, we focus on manipulating large herbivores through the closure of water points (WPs). Removal of artificial WPs has been suggested in order to change the distribution of African elephants, which occur in high densities in national parks in Southern Africa and are thought to have a destructive effect on the vegetation. Here, we modeled the long-term effects of different scenarios of WP closure on the spatial distribution of elephants, and consequential effects on the vegetation and other herbivores in Kruger National Park, South Africa. Using a dynamic ecosystem model, SAVANNA, scenarios were evaluated that varied in availability of artificial WPs; levels of natural water; and elephant densities. Our modeling results showed that elephants can indirectly negatively affect the distributions of meso-mixed feeders, meso-browsers, and some meso-grazers under wet conditions. The closure of artificial WPs hardly had any effect during these natural wet conditions. Under dry conditions, the spatial distribution of both elephant bulls and cows changed when the availability of artificial water was severely reduced in the model. These changes in spatial distribution triggered changes in the spatial availability of woody biomass over the simulation period of 80 years, and this led to changes in the rest of the herbivore community, resulting in increased densities of all herbivores, except for giraffe and steenbok, in areas close to rivers. The spatial distributions of elephant bulls and cows showed to be less affected by the closure of WPs than most of the other herbivore species. Our study contributes to ecologically informed decisions in wildlife management. The results from this modeling exercise imply that long-term effects of this intervention strategy should always be investigated at an ecosystem scale.

  13. LADA type diabetes, celiac diasease, cerebellar ataxia and stiff person syndrome. A rare association of autoimmune disorders.

    Science.gov (United States)

    Soós, Zsuzsanna; Salamon, Mónika; Erdei, Katalin; Kaszás, Nóra; Folyovich, András; Szücs, Anna; Barcs, Gábor; Arányi, Zsuzsanna; Skaliczkis, József; Vadasdi, Károly; Winkler, Gábor

    2014-05-30

    Celiac disease--in its typical form--is a chronic immune-mediated enteropathy with typical clinical symptoms that develops against gliadin content of cereal grains, and is often associated with other autoimmune diseases. In cases of atypical manifestation classic symptoms may be absent or mild, and extra-intestinal symptoms or associated syndromes dominate clinical picture. The authors present a longitudinal follow-up of such a case. A 63-years old woman was diagnosed with epilepsy at the age of 19, and with progressive limb ataxia at the age of 36, which was initially thought to be caused by cerebellar atrophy, later probably by stiff person syndrome. At the age 59, her diabetes mellitus manifested with type 2 diabetic phenotype, but based on GAD positivity later was reclassified as type 1 diabetes. Only the last check-up discovered the celiac disease, retrospectively explaining the entire disease course and neurological symptoms. By presenting this case, the authors would like to draw attention to the fact that one should think of the possibility of celiac disease when cerebellar ataxia, progressive neurological symptoms and diabetes are present at the same time. An early diagnosis may help to delay the progression of disease and help better treatment.

  14. Monoallelic and Biallelic Variants in EMC1 Identified in Individuals with Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy.

    Science.gov (United States)

    Harel, Tamar; Yesil, Gozde; Bayram, Yavuz; Coban-Akdemir, Zeynep; Charng, Wu-Lin; Karaca, Ender; Al Asmari, Ali; Eldomery, Mohammad K; Hunter, Jill V; Jhangiani, Shalini N; Rosenfeld, Jill A; Pehlivan, Davut; El-Hattab, Ayman W; Saleh, Mohammed A; LeDuc, Charles A; Muzny, Donna; Boerwinkle, Eric; Gibbs, Richard A; Chung, Wendy K; Yang, Yaping; Belmont, John W; Lupski, James R

    2016-03-03

    The paradigm of a single gene associated with one specific phenotype and mode of inheritance has been repeatedly challenged. Genotype-phenotype correlations can often be traced to different mutation types, localization of the variants in distinct protein domains, or the trigger of or escape from nonsense-mediated decay. Using whole-exome sequencing, we identified homozygous variants in EMC1 that segregated with a phenotype of developmental delay, hypotonia, scoliosis, and cerebellar atrophy in three families. In addition, a de novo heterozygous EMC1 variant was seen in an individual with a similar clinical and MRI imaging phenotype. EMC1 encodes a member of the endoplasmic reticulum (ER)-membrane protein complex (EMC), an evolutionarily conserved complex that has been proposed to have multiple roles in ER-associated degradation, ER-mitochondria tethering, and proper assembly of multi-pass transmembrane proteins. Perturbations of protein folding and organelle crosstalk have been implicated in neurodegenerative processes including cerebellar atrophy. We propose EMC1 as a gene in which either biallelic or monoallelic variants might lead to a syndrome including intellectual disability and preferential degeneration of the cerebellum.

  15. Reactive oxygen species are related to ionic fluxes and volume decrease in apoptotic cerebellar granule neurons: role of NOX enzymes.

    Science.gov (United States)

    Hernández-Enríquez, Berenice; Guemez-Gamboa, Alicia; Morán, Julio

    2011-05-01

    Reactive oxygen species (ROS) are produced early during apoptosis of cerebellar granule neurons induced by low potassium (K5) and staurosporine (Sts). In addition, K5 and Sts activate NADPH oxidases (NOX). Recently, we described that K5 and Sts induce apoptotic volume decrease (AVD) at a time when ROS generation and NOX activity occur. In the present study, we evaluated the relationship between ROS generation and ionic fluxes during AVD. Here, we showed that K5- and Sts-induced AVD was inhibited by antioxidants and that direct ROS production induced AVD. Moreover, NOX inhibitors eliminated AVD induced by both K5 and Sts. Sts, but not K5, failed to induce AVD in cerebellar granule neurons from NOX2 knockout mice. These findings suggest that K5- and Sts-induced AVD is largely mediated by ROS produced by NOX. On the other hand, we also found that the blockage of ionic fluxes involved in AVD inhibited both ROS generation and NOX activity. These findings suggest that ROS generation and NOX activity are involved in ionic fluxes activation, which in turn could maintain ROS generation by activating NOX, leading to a self-amplifying cycle.

  16. Monoallelic and Biallelic Variants in EMC1 Identified in Individuals with Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy

    Science.gov (United States)

    Harel, Tamar; Yesil, Gozde; Bayram, Yavuz; Coban-Akdemir, Zeynep; Charng, Wu-Lin; Karaca, Ender; Al Asmari, Ali; Eldomery, Mohammad K.; Hunter, Jill V.; Jhangiani, Shalini N.; Rosenfeld, Jill A.; Pehlivan, Davut; El-Hattab, Ayman W.; Saleh, Mohammed A.; LeDuc, Charles A.; Muzny, Donna; Boerwinkle, Eric; Gibbs, Richard A.; Chung, Wendy K.; Yang, Yaping; Belmont, John W.; Lupski, James R.

    2016-01-01

    The paradigm of a single gene associated with one specific phenotype and mode of inheritance has been repeatedly challenged. Genotype-phenotype correlations can often be traced to different mutation types, localization of the variants in distinct protein domains, or the trigger of or escape from nonsense-mediated decay. Using whole-exome sequencing, we identified homozygous variants in EMC1 that segregated with a phenotype of developmental delay, hypotonia, scoliosis, and cerebellar atrophy in three families. In addition, a de novo heterozygous EMC1 variant was seen in an individual with a similar clinical and MRI imaging phenotype. EMC1 encodes a member of the endoplasmic reticulum (ER)-membrane protein complex (EMC), an evolutionarily conserved complex that has been proposed to have multiple roles in ER-associated degradation, ER-mitochondria tethering, and proper assembly of multi-pass transmembrane proteins. Perturbations of protein folding and organelle crosstalk have been implicated in neurodegenerative processes including cerebellar atrophy. We propose EMC1 as a gene in which either biallelic or monoallelic variants might lead to a syndrome including intellectual disability and preferential degeneration of the cerebellum. PMID:26942288

  17. DISTURBANCE ATTENUATION FOR UNCERTAIN NONLINEAR CASCADED SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    BI Weiping; MU Xiaowu; SUN Yuqiang

    2004-01-01

    In present paper, the disturbance attenuation problem of uncertain nonlinear cascaded systems is studied. Based on the adding one power integrator technique and recursive design, a feedback controller that solves the disturbance attenuation problem is constructed for uncertain nonlinear cascaded systems with internal stability.

  18. Cascade Harvest’ red raspberry

    Science.gov (United States)

    Cascade Harvest’ is a new floricane fruiting raspberry cultivar (Rubus idaeus L.) jointly released by Washington State University (WSU), Oregon State University (OSU) and the U.S. Department of Agriculture (USDA). ‘Cascade Harvest’ produces a high yield of large, firm fruit suited to machine harves...

  19. A NOTE ON VECTOR CASCADE ALGORITHM

    Institute of Scientific and Technical Information of China (English)

    Qiu-hui Chen; Jin-zhao Liu; Wen-sheng Zhang

    2002-01-01

    The focus of this paper is on the relationship between accuracy of multivariate refinable vector and vector cascade algorithm. We show that, if the vector cascade algorithm (1.5) with isotropic dilation converges to a vector-valued function with regularity, then the initial function must satisfy the Strang-Fix conditions.

  20. Cascading costs: An economic nitrogen cycle

    Institute of Scientific and Technical Information of China (English)

    William R. Moomaw; Melissa B. L. Birch

    2005-01-01

    The chemical nitrogen cycle is becoming better characterized in terms of fluxes and reservoirs on a variety of scales. Galloway has demonstrated that reactive nitrogen can cascade through multiple ecosystems causing environmental damage at each stage before being denitrifled to N2. We propose to construct a parallel economic nitrogen cascade (ENC) in which economic impacts of nitrogen fluxes can be estimated by the costs associated with each stage of the chemical cascade. Using economic data for the benefits of damage avoided and costs of mitigation in the Chesapeake Bay basin, we have constructed an economic nitrogen cascade for the region. Since a single tonne of nitrogen can cascade through the system, the costs also cascade.Therefore evaluating the benefits of mitigating a tonne of reactive nitrogen released needs to consider the damage avoided in all of the ecosystems through which that tonne would cascade.The analysis reveals that it is most cost effective to remove a tonne of nitrogen coming from combustion since it has the greatest impact on human health and creates cascading damage through the atmospheric, terrestrial, aquatic and coastal ecosystems. We will discuss the implications of this analysis for determining the most cost effective policy option for achieving environmental quality goals.

  1. Tumour type and size are high risk factors for the syndrome of "cerebellar" mutism and subsequent dysarthria

    OpenAIRE

    1999-01-01

    textabstractOBJECTIVE: "Cerebellar mutis" and subsequent dysarthria (MSD) is a documented complication of posterior fossa surgery in children. In this prospective study the following risk factors for MSD were assessed: type, size and site of the tumour; hydrocephalus at presentation and after surgery, cerebellar incision site, postoperative infection, and cerebellar swelling. METHODS: In a consecutive series of 42 children with a cerebellar tumour, speech and neuroradiological studies (CT and...

  2. Multifunctional Cascaded Metamaterials: Integrated Transmitarrays

    CERN Document Server

    Elsakka, Amr A; Faniayeu, Ihar A; Tcvetkova, Svetlana N; Tretyakov, Sergei A

    2016-01-01

    Control of electromagnetic waves using engineered materials is very important in a wide range of applications, therefore there is always a continuous need for new and more efficient solutions. Known natural and artificial materials and surfaces provide a particular functionality in the frequency range they operate but cast a "shadow" and produce reflections at other frequencies. Here, we introduce a concept of multifunctional engineered materials that possess different predetermined functionalities at different frequencies. Such response can be accomplished by cascading metasurfaces (thin composite layers) that are designed to perform a single operation at the desired frequency and are transparent elsewhere. Previously, out-of-band transparent metasurfaces for control over reflection and absorption were proposed. In this paper, to complete the full set of functionalities for wave control, we synthesize transmitarrays that tailor transmission in a desired way, being "invisible" beyond the operational band. The...

  3. Network reconstruction from infection cascades

    CERN Document Server

    Braunstein, Alfredo

    2016-01-01

    Reconstructing propagation networks from observations is a fundamental inverse problem, and it's crucial to understand and control dynamics in complex systems. Here we show that it is possible to reconstruct the whole structure of an interaction network and to simultaneously infer the complete time course of activation spreading, relying just on single snapshots of a small number of activity cascades. The method, that we called Inverse Dynamics Network Reconstruction (IDNR), is shown to work successfully on several synthetic and real networks, inferring the networks and the sources of infection based on sparse observations, including single snapshots. IDNR is built on a Belief Propagation approximation, that has an impressive performance in a wide variety of topological structures. The method can be applied in absence of complete time-series data by providing a detailed modeling of the posterior distribution of trajectories conditioned to the observations. Furthermore, we show by experiments that the informat...

  4. Availability Cascades & the Sharing Economy

    DEFF Research Database (Denmark)

    Netter, Sarah

    2015-01-01

    In search of a new concept that will provide answers to as to how modern societies should not only make sense but also resolve the social and environmental problems linked with our modes of production and consumption, collaborative consumption and the sharing economy are increasingly attracting...... attention. This conceptual paper attempts to explain the emergent focus on the sharing economy and associated business and consumption models by applying cascade theory. Risks associated with this behavior will be especially examined with regard to the sustainability claim of collaborative consumption....... With academics, practitioners, and civil society alike having a shared history in being rather fast in accepting new concepts that will not only provide business opportunities but also a good conscience, this study proposes a critical study of the implications of collaborative consumption, before engaging...

  5. Availability Cascades & the Sharing Economy

    DEFF Research Database (Denmark)

    Netter, Sarah

    2014-01-01

    In search of a new concept that will provide answers to as to how modern societies should not only make sense but also resolve the social and environmental problems linked with our modes of production and consumption, collaborative consumption and the sharing economy are increasingly attracting...... attention. This conceptual paper attempts to explain the emergent focus on the sharing economy and associated business and consumption models by applying cascade theory. Risks associated with this behavior will be especially examined with regard to the sustainability claim of collaborative consumption....... With academics, practitioners, and civil society alike having a shared history in being rather fast in accepting new concepts that will not only provide business opportunities but also a good conscience, this study proposes a critical study of the implications of collaborative consumption, before engaging...

  6. Cascades in interdependent flow networks

    CERN Document Server

    Scala, Antonio; Caldarelli, Guido; D'Agostino, Gregorio

    2015-01-01

    We investigate the abrupt breakdown behavior of coupled distribution grids under load growth. This scenario mimics the ever-increasing customer demand and the foreseen introduction of energy hubs interconnecting the different energy vectors. We extend an analytical model of cascading behavior due to line overloads to the case of interdependent networks and find evidence of first order transitions due to the long-range nature of the flows. Our results indicate that the foreseen increase in the couplings between the grids has two competing effects: on the one hand, it increases the safety region where grids can operate without withstanding systemic failures; on the other hand, it increases the possibility of a joint systems' failure.

  7. Properties of bilateral spinocerebellar activation of cerebellar cortical neurons

    Directory of Open Access Journals (Sweden)

    Pontus eGeborek

    2014-10-01

    Full Text Available We aimed to explore the cerebellar cortical inputs from two spinocerebellar pathways, the spinal border cell-component of the ventral spinocerebellar tract (SBC-VSCT and the dorsal spinocerebellar tract (DSCT, respectively, in the sublobule C1 of the cerebellar posterior lobe. The two pathways were activated by electrical stimulation of the contralateral lateral funiculus (coLF and the ipsilateral LF (iLF at lower thoracic levels. Most granule cells in sublobule C1 did not respond at all but part of the granule cell population displayed high-intensity responses to either coLF or iLF stimulation. As a rule, Golgi cells and Purkinje cell simple spikes responded to input from both LFs, although Golgi cells could be more selective. In addition, a small population of granule cells responded to input from both the coLF and the iLF. However, in these cases, similarities in the temporal topography and magnitude of the responses suggested that the same axons were stimulated from the two LFs, i.e. that the axons of individual spinocerebellar neurons could be present in both funiculi. This was also confirmed for a population of spinal neurons located within known locations of SBC-VSCT neurons and dorsal horn DSCT neurons. We conclude that bilateral spinocerebellar responses can occur in cerebellar granule cells, but the VSCT and DSCT systems that provide the input can also be organized bilaterally. The implications for the traditional functional separation of VSCT and DSCT systems and the issue whether granule cells primarily integrate functionally similar information or not are discussed.

  8. Probabilistic identification of cerebellar cortical neurones across species.

    Directory of Open Access Journals (Sweden)

    Gert Van Dijck

    Full Text Available Despite our fine-grain anatomical knowledge of the cerebellar cortex, electrophysiological studies of circuit information processing over the last fifty years have been hampered by the difficulty of reliably assigning signals to identified cell types. We approached this problem by assessing the spontaneous activity signatures of identified cerebellar cortical neurones. A range of statistics describing firing frequency and irregularity were then used, individually and in combination, to build Gaussian Process Classifiers (GPC leading to a probabilistic classification of each neurone type and the computation of equi-probable decision boundaries between cell classes. Firing frequency statistics were useful for separating Purkinje cells from granular layer units, whilst firing irregularity measures proved most useful for distinguishing cells within granular layer cell classes. Considered as single statistics, we achieved classification accuracies of 72.5% and 92.7% for granular layer and molecular layer units respectively. Combining statistics to form twin-variate GPC models substantially improved classification accuracies with the combination of mean spike frequency and log-interval entropy offering classification accuracies of 92.7% and 99.2% for our molecular and granular layer models, respectively. A cross-species comparison was performed, using data drawn from anaesthetised mice and decerebrate cats, where our models offered 80% and 100% classification accuracy. We then used our models to assess non-identified data from awake monkeys and rabbits in order to highlight subsets of neurones with the greatest degree of similarity to identified cell classes. In this way, our GPC-based approach for tentatively identifying neurones from their spontaneous activity signatures, in the absence of an established ground-truth, nonetheless affords the experimenter a statistically robust means of grouping cells with properties matching known cell classes. Our

  9. Aberrant cerebellar connectivity in motor and association networks in schizophrenia

    Directory of Open Access Journals (Sweden)

    Ann K. Shinn

    2015-03-01

    Full Text Available Schizophrenia is a devastating illness characterized by disturbances in multiple domains. The cerebellum is involved in both motor and non-motor functions, and the cognitive dysmetria and dysmetria of thought models propose that abnormalities of the cerebellum may contribute to schizophrenia signs and symptoms. The cerebellum and cerebral cortex are reciprocally connected via a modular, closed-loop network architecture, but few schizophrenia neuroimaging studies have taken into account the topographical and functional heterogeneity of the cerebellum. In this study, using a previously defined 17-network cerebral cortical parcellation system as the basis for our functional connectivity seeds, we systematically investigated connectivity abnormalities within the cerebellum of 44 schizophrenia patients and 28 healthy control participants. We found selective alterations in cerebro-cerebellar functional connectivity. Specifically, schizophrenia patients showed decreased cerebro-cerebellar functional connectivity in higher level association networks (ventral attention, salience, control, and default mode networks relative to healthy control participants. Schizophrenia patients also showed increased cerebro-cerebellar connectivity in somatomotor and default mode networks, with the latter showing no overlap with the regions found to be hypoconnected within the same default mode network. Finally, we found evidence to suggest that somatomotor and default mode networks may be inappropriately linked in schizophrenia. The relationship of these dysconnectivities to schizophrenia symptoms, such as neurological soft signs and altered sense of agency, is discussed. We conclude that the cerebellum ought to be considered for analysis in all future studies of network abnormalities in SZ, and further suggest the cerebellum as a potential target for further elucidation, and possibly treatment, of the underlying mechanisms and network abnormalities producing symptoms of

  10. A distinctive pattern of cortical excitability in patients with the syndrome of dystonia and cerebellar ataxia

    NARCIS (Netherlands)

    Talelli, P.; Hoffland, B.S.; Schneider, S.A.; Edwards, M.; Bhatia, K.P.; Warrenburg, B.P.C. van de; Rothwell, J.C.

    2011-01-01

    OBJECTIVE: The syndrome of dystonia and cerebellar ataxia (DYTCA) is a recently described condition where cervical dystonia and mild cerebellar ataxia are the major clinical features. Here we attempted to explore the pathophysiology of this condition by comparing measurements of cortical excitabilit

  11. Early onset cerebellar ataxia with retained tendon reflexes : foot deformity in a first grade family member

    NARCIS (Netherlands)

    Schelhaas, HJ; Van der Hulst, M; Ippel, E; Prevo, RL; Hageman, G

    1999-01-01

    Early onset cerebellar ataxia with retained tendon reflexes (EOCA) is a clinical syndrome characterised by progressive cerebellar ataxia with an onset before the age of 25 years and a wide spectrum of associated features. It is distinguished from Friedreich's ataxia (FA) mainly by the preservation o

  12. Parvovirus associated cerebellar hypoplasia and hydrocephalus in day-old broiler chickens

    Science.gov (United States)

    Cerebellar hypoplasia and hydrocephalus were detected in day-old broiler chickens. Brains of chickens evaluated at necropsy appeared to be abnormal; some were disfigured and cerebellae appeared to be smaller than normal. Histopathologic examination of brains revealed cerebellar folia that were sho...

  13. Autosomal recessive cerebellar ataxia caused by mutations in the PEX2 gene

    NARCIS (Netherlands)

    C. Sevin; S. Ferdinandusse; H.R. Waterham; R.J. Wanders; P. Aubourg

    2011-01-01

    ABSTRACT: OBJECTIVE: To expand the spectrum of genetic causes of autosomal recessive cerebellar ataxia (ARCA). Case report: Two brothers are described who developed progressive cerebellar ataxia at 3 1/2 and 18 years, respectively. After ruling out known common genetic causes of ARCA, analysis of bl

  14. Incidence of Dysarthria in Children with Cerebellar Tumors: A Prospective Study

    Science.gov (United States)

    Richter, S.; Schoch, B.; Ozimek, A.; Gorissen, B.; Hein-Kropp, C.; Kaiser, O.; Hovel, M.; Wieland, R.; Gizewski, E.; Timmann, D.

    2005-01-01

    The present study investigated dysarthric symptoms in children with cerebellar tumors. Ten children with cerebellar tumors and 10 orthopedic control children were tested prior and one week after surgery. Clinical dysarthric symptoms were quantified in spontaneous speech. Syllable durations were analyzed in syllable repetition and sentence…

  15. Cerebellar motor learning deficits in medicated and medication-free men with recent-onset schizophrenia

    NARCIS (Netherlands)

    M.P.H. Coesmans (Michiel); C. Röder (Constantin); A.E. Smit (Albertine Eline); S.K.E. Koekkoek (Bas); C.I. de Zeeuw (Chris); M.A. Frens (Maarten); J.N. van der Geest (Jos)

    2014-01-01

    textabstractBackground: The notion that cerebellar deficits may underlie clinical symptoms in people with schizophrenia is tested by evaluating 2 forms of cerebellar learning in patients with recent-onset schizophrenia. A potential medication effect is evaluated by including patients with or without

  16. Cerebellar motor learning deficits in medicated and medication-free men with recent-onset schizophrenia

    NARCIS (Netherlands)

    Coesmans, Michael; Röder, Christian H; Smit, Albertine E; Koekkoek, Sebastiaan K E; De Zeeuw, Chris I; Frens, Maarten A; van der Geest, Josef N

    2014-01-01

    BACKGROUND: The notion that cerebellar deficits may underlie clinical symptoms in people with schizophrenia is tested by evaluating 2 forms of cerebellar learning in patients with recent-onset schizophrenia. A potential medication effect is evaluated by including patients with or without antipsychot

  17. Optogenetics in the cerebellum: Purkinje cell-specific approaches for understanding local cerebellar functions.

    Science.gov (United States)

    Tsubota, Tadashi; Ohashi, Yohei; Tamura, Keita

    2013-10-15

    The cerebellum consists of the cerebellar cortex and the cerebellar nuclei. Although the basic neuronal circuitry of the cerebellar cortex is uniform everywhere, anatomical data demonstrate that the input and output relationships of the cortex are spatially segregated between different cortical areas, which suggests that there are functional distinctions between these different areas. Perturbation of cerebellar cortical functions in a spatially restricted fashion is thus essential for investigating the distinctions among different cortical areas. In the cerebellar cortex, Purkinje cells are the sole output neurons that send information to downstream cerebellar and vestibular nuclei. Therefore, selective manipulation of Purkinje cell activities, without disturbing other neuronal types and passing fibers within the cortex, is a direct approach to spatially restrict the effects of perturbations. Although this type of approach has for many years been technically difficult, recent advances in optogenetics now enable selective activation or inhibition of Purkinje cell activities, with high temporal resolution. Here we discuss the effectiveness of using Purkinje cell-specific optogenetic approaches to elucidate the functions of local cerebellar cortex regions. We also discuss what improvements to current methods are necessary for future investigations of cerebellar functions to provide further advances.

  18. Cerebellar arteries originating from the internal carotid artery: angiographic evaluation and embryologic explanations

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Young; Han, Moon Hee; Yu, In Gyu; Chang, Ki Hyun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of); Kim, Eui Jong [Kyunghee Univ. College of Medicine, Seoul (Korea, Republic of); Kim, Dae Ho [Soonchunhyang Univ. College of Medicine, Asan(Korea, Republic of)

    1997-06-01

    To find and describe the cerebellar arteries arising from the internal carotid artery, explain them embryologically, and evaluate their clinical implication. To determine the point in the internal carotid artery from which the cereballar artery arose anomalously, consecutive angiographic studies performed in the last three years were reviewed. The distribution of such anomalous cerebellar arteries, the point in the internal carotid artery from which the anomalous vessels originated, and associated findings were analyzed. Five anomalous origins of cerebellar arteries arising arising directly from the internal carotid artery were found in five patients. Three anterior inferior cerebellar arteries (AICA) and one common trunk of an AICA and a posterior inferior cerebellar artery (PICA) were found to originate from the internal carotid artery at a point close to the origin of the primitive trigeminal artery. A PICA arose from an artery presenting a course similar to the proatlantal intersegmental artery. Intracranial aneurysms in two patients, Moyamoya disease in one, and facial arteriovenous malformation in one. In our series, AICAs supplied from the arteries considered to be persistent trigeminal artery variants were the most common type. A correlation between type of anomalous cerebellar artery and type of carotid-vertebrobasilar anastomosis may exist. Cerebellar arteries originating anomalously from the internal carotid artery seem to occur as a result of the persistence of carotid-vertebrobasilar anastomoses associated with incomplete fusion of the longitudinal neural arteries. An understanding of these anomalous cerebellar arteries may help prevent accidents during therapeutic embolization and surgical treatment, as well as misinterpretation.

  19. Cerebellar clear cell ependymoma in a 10 year old girl

    Energy Technology Data Exchange (ETDEWEB)

    Thinzar Aye Nyein; Moon, Ah Rim; Hwang, Sun Chul; Hong, Hyun Sook; Lee, A Leum; Chang, Kee Hyun; Kim, Hee Kyung; Chin, Su Sie [Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of); Park, Ji Sang [Soonchunhyang University Gumi Hospital, Gumi (Korea, Republic of)

    2016-01-15

    Clear cell ependymoma (CCE) is a histological rare variant (1–5%) of ependymoma, which is distinguished from other histological subtypes by the presence of fusiform cells arrayed radially around small blood vessels. These alleged perivascular pseudorosettes are significant characteristic features of ependymomas. About 95% of infratentorial ependymomas are found in the fourth ventricle and the remainder occurs as cerebellopontine angle lesions. In previous reports, the cerebellum is found to be a rare location for ependymoma. In this study we report one case of CCE originating from the cerebellar hemisphere, showing unusual morphology on 3T MRI.

  20. Infantile intracranial aneurysm of the superior cerebellar artery.

    Science.gov (United States)

    Del Santo, Molly Ann; Cordina, Steve Mario

    2016-02-29

    Intracranial aneurysms in the pediatric population are rare. We report a case of a 3-month-old infant who presented with inconsolable crying, vomiting, and sunset eye sign. CT revealed a subarachnoid hemorrhage, with CT angiogram revealing a superior cerebellar artery aneurysm. An external ventricular drain was placed for acute management of hydrocephalus, with definitive treatment by endovascular technique with a total of six microcoils to embolize the aneurysm. Serial transcranial Dopplers revealed no subsequent vasospasm. Although aneurysms in the pediatric population are rare, once the diagnosis is established, early treatment results in better outcomes.

  1. Endoscopic evacuation of cerebellar hematoma in a term newborn.

    Science.gov (United States)

    Tanriverdi, Sema Rala; Turhan, Tuncer; Uygur, Ozgun; Koroglu, Ozge Altun; Yalaz, Mehmet; Kultursay, Nilgun

    2013-10-01

    Intracerebellar hemorrhage is very rare in term infants and only severe cases with massive intracranial hemorrhage, posthemorrhagic hydrocephalus and clinical deterioration due to increased intracranial pressure require neurosurgical evacuation. In recent adult studies endoscopic hematoma evacuation has been shown as a rapid, effective, and safe technique. A term newborn hospitalized for meconium aspiration syndrome showed hypertonia, jitteriness and abnormal amplitude integrated electroencephalogram findings. He was diagnosed with cerebellar hematoma which caused hydrocephalus by cranial magnetic resonance imaging (MRI). The hematoma was successfully evacuated neuroendoscopically as the first case in literature to our knowledge. Neurologic, a-EEG and MRI findings resolved.

  2. Dysarthria in children with cerebellar or brainstem tumors.

    Science.gov (United States)

    van Mourik, M; Catsman-Berrevoets, C E; Yousef-Bak, E; Paquier, P F; van Dongen, H R

    1998-05-01

    Speech features were perceptually analyzed in two groups of children. The first group (n = 6) had undergone cerebellar tumor resection, and the second group (n = 6) included children with brainstem tumors. Children belonging to the first group became dysarthric after a postoperative mute phase. Slow speech rate was a specific feature, but scanning speech and irregular articulatory breakdown (i.e., prominent characteristics in adult ataxic dysarthria) were not observed. In the second group, hypernasality was a prominent characteristic and resembled flaccid dysarthria in adults. These findings suggest that acquired childhood dysarthria needs a proper classification.

  3. File list: InP.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  6. File list: InP.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Neu.50.AllAg.Cerebellar_granule_neurons mm9 Input control Neural Cerebellar granule neuron...s http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Neu.50.AllAg.Cerebellar_granule_neurons.bed ...

  7. Changes in a cerebellar peduncle lesion in a patient with Dandy-Walker malformation A diffusion tensor imaging study

    Institute of Scientific and Technical Information of China (English)

    Ah Young Lee; Sung Ho Jang; Sang Seok Yeo; Ensil Lee; Yun Woo Cho; Su Min Son

    2013-01-01

    We report a patient with severe ataxia due to Dandy-Walker malformation, who showed functional recovery over 10 months corresponding to a change in a cerebellar peduncle lesion. A 20-month-old female patient who was diagnosed with Dandy-Walker syndrome and six age- and sex-matched healthy control subjects were enrolled. The superior cerebellar peduncle, the middle cerebellar peduncle, and the inferior cerebellar peduncle were evaluated using fractional anisotropy and the apparent diffusion coefficient. The patients' functional ambulation category was 0 at the initial visit, but improved to 2 at the follow-up evaluation, and Berg's balance scale score also improved from 0 to 7. Initial diffusion tensor tractography revealed that the inferior cerebellar peduncle was not detected, that the fractional anisotropy of the superior cerebellar peduncle and middle cerebellar peduncle decreased by two standard deviations below, and that the apparent diffusion coefficient increased by two standard deviations over normal control values. However, on follow-up diffusion tensor tractography, both inferior cerebellar peduncles could be detected, and the fractional anisotropy of superior cerebellar peduncle increased to within two standard deviations of normal controls. The functional improvement in this patient appeared to correspond to changes in these cerebellar peduncles. We believe that evaluating cerebellar peduncles using diffusion tensor imaging is useful in cases when a cerebellar peduncle lesion is suspected.

  8. File list: InP.Neu.05.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  11. Babinski's contributions to cerebellar symptomatology: building the basis of the neurological examination

    Directory of Open Access Journals (Sweden)

    Jose Luiz Pedroso

    2013-12-01

    Full Text Available Several assumptions about the function of the cerebellum and semiotic signs have been described over the centuries. Among the long list of famous researchers who have provided a strong contribution and who have left their names on the highway of cerebellar research, Joseph Babinski appears as a prominent name. The description of various forms of cerebellar symptomatology was a major part of Babinski's work, and clinical terms that he introduced, namely hypermetry , diadochokinesia , and asynergy , remain part of contemporary clinical vocabulary. Babinski studied cerebellar signs in many patients and was able to conduct longitudinal studies that permitted him to understand the evolution of cerebellar dysfunction. Babinski contributions to cerebellar symptomatology continue to influence the most modern theories, including functional and neuropathological studies.

  12. Location of lesion determines motor vs. cognitive consequences in patients with cerebellar stroke

    Directory of Open Access Journals (Sweden)

    Catherine J. Stoodley

    2016-01-01

    Full Text Available Cerebellar lesions can cause motor deficits and/or the cerebellar cognitive affective syndrome (CCAS; Schmahmann's syndrome. We used voxel-based lesion-symptom mapping to test the hypothesis that the cerebellar motor syndrome results from anterior lobe damage whereas lesions in the posterolateral cerebellum produce the CCAS. Eighteen patients with isolated cerebellar stroke (13 males, 5 females; 20–66 years old were evaluated using measures of ataxia and neurocognitive ability. Patients showed a wide range of motor and cognitive performance, from normal to severely impaired; individual deficits varied according to lesion location within the cerebellum. Patients with damage to cerebellar lobules III–VI had worse ataxia scores: as predicted, the cerebellar motor syndrome resulted from lesions involving the anterior cerebellum. Poorer performance on fine motor tasks was associated primarily with strokes affecting the anterior lobe extending into lobule VI, with right-handed finger tapping and peg-placement associated with damage to the right cerebellum, and left-handed finger tapping associated with left cerebellar damage. Patients with the CCAS in the absence of cerebellar motor syndrome had damage to posterior lobe regions, with lesions leading to significantly poorer scores on language (e.g. right Crus I and II extending through IX, spatial (bilateral Crus I, Crus II, and right lobule VIII, and executive function measures (lobules VII–VIII. These data reveal clinically significant functional regions underpinning movement and cognition in the cerebellum, with a broad anterior-posterior distinction. Motor and cognitive outcomes following cerebellar damage appear to reflect the disruption of different cerebro-cerebellar motor and cognitive loops.

  13. Cerebellar gray matter and lobular volumes correlate with core autism symptoms

    Directory of Open Access Journals (Sweden)

    Anila M. D'Mello

    2015-01-01

    Full Text Available Neuroanatomical differences in the cerebellum are among the most consistent findings in autism spectrum disorder (ASD, but little is known about the relationship between cerebellar dysfunction and core ASD symptoms. The newly-emerging existence of cerebellar sensorimotor and cognitive subregions provides a new framework for interpreting the functional significance of cerebellar findings in ASD. Here we use two complementary analyses — whole-brain voxel-based morphometry (VBM and the SUIT cerebellar atlas — to investigate cerebellar regional gray matter (GM and volumetric lobular measurements in 35 children with ASD and 35 typically-developing (TD children (mean age 10.4 ± 1.6 years; range 8–13 years. To examine the relationships between cerebellar structure and core ASD symptoms, correlations were calculated between scores on the Autism Diagnostic Observation Schedule (ADOS and Autism Diagnostic Interview (ADI and the VBM and volumetric data. Both VBM and the SUIT analyses revealed reduced GM in ASD children in cerebellar lobule VII (Crus I/II. The degree of regional and lobular gray matter reductions in different cerebellar subregions correlated with the severity of symptoms in social interaction, communication, and repetitive behaviors. Structural differences and behavioral correlations converged on right cerebellar Crus I/II, a region which shows structural and functional connectivity with fronto-parietal and default mode networks. These results emphasize the importance of the location within the cerebellum to the potential functional impact of structural differences in ASD, and suggest that GM differences in cerebellar right Crus I/II are associated with the core ASD profile.

  14. Spinal level of myelomeningocele lesion as a contributing factor in posterior fossa volume, intracranial cerebellar volume, and cerebellar ectopia.

    LENUS (Irish Health Repository)

    Sweeney, Kieron J

    2013-02-01

    McLone and Knepper\\'s unified theory of Chiari malformation Type II (CM-II) describes how the loss of CSF via the open posterior neuropore fails to create adequate distending pressure for the developing rhomboencephalic vesicle. The authors of the present article describe the relationship between the posterior fossa volume and intracranial cerebellar volume as being related to the distance from the obex of the fourth ventricle to the myelomeningocele lesion using a common mathematical model, the Hagen-Poiseuille law.

  15. Diffusion spectrum imaging shows the structural basis of functional cerebellar circuits in the human cerebellum in vivo.

    Directory of Open Access Journals (Sweden)

    Cristina Granziera

    Full Text Available BACKGROUND: The cerebellum is a complex structure that can be affected by several congenital and acquired diseases leading to alteration of its function and neuronal circuits. Identifying the structural bases of cerebellar neuronal networks in humans in vivo may provide biomarkers for diagnosis and management of cerebellar diseases. OBJECTIVES: To define the anatomy of intrinsic and extrinsic cerebellar circuits using high-angular resolution diffusion spectrum imaging (DSI. METHODS: We acquired high-resolution structural MRI and DSI of the cerebellum in four healthy female subjects at 3T. DSI tractography based on a streamline algorithm was performed to identify the circuits connecting the cerebellar cortex with the deep cerebellar nuclei, selected brainstem nuclei, and the thalamus. RESULTS: Using in-vivo DSI in humans we were able to demonstrate the structure of the following cerebellar neuronal circuits: (1 connections of the inferior olivary nucleus with the cerebellar cortex, and with the deep cerebellar nuclei (2 connections between the cerebellar cortex and the deep cerebellar nuclei, (3 connections of the deep cerebellar nuclei conveyed in the superior (SCP, middle (MCP and inferior (ICP cerebellar peduncles, (4 complex intersections of fibers in the SCP, MCP and ICP, and (5 connections between the deep cerebellar nuclei and the red nucleus and the thalamus. CONCLUSION: For the first time, we show that DSI tractography in humans in vivo is capable of revealing the structural bases of complex cerebellar networks. DSI thus appears to be a promising imaging method for characterizing anatomical disruptions that occur in cerebellar diseases, and for monitoring response to therapeutic interventions.

  16. Progressive cerebellar atrophy: hereditary ataxias and disorders with spinocerebellar degeneration.

    Science.gov (United States)

    Wolf, Nicole I; Koenig, Michel

    2013-01-01

    The hereditary ataxias with onset in childhood are a group of heterogeneous disorders, usually with autosomal recessive inheritance. In many of them, magnetic resonance imaging (MRI) shows cerebellar atrophy. The most prominent exception to this is Friedreich's ataxia, where MRI shows normal cerebellar volume, but sometimes spinal cord atrophy. In several of the hereditary ataxias, the causative gene plays an important role in DNA repair: ataxia telangiectasia and ataxia telangiectasia-like disorder, and ataxia with oculomotor apraxia type I and II. Mitochondrial metabolism is impaired in another group of inherited ataxias including the emergent group of defects in coenzyme Q10 synthesis. Few of these disorders are amenable to effective treatment, the most important of these being vitamin E-responsive ataxia. The autosomal dominant spinocerebellar ataxias are rare in childhood. Some of them, especially SCA7 and SCA2, may begin in childhood or even infancy, family history being positive in these cases. Additional clinical clues such as presence or absence of neuropathy or oculomotor apraxia still help in making a definitive diagnosis albeit there are still many unsolved cases. In pontocerebellar hypoplasia, a neurodegenerative disease with prenatal onset, the genetic basis of the different subtypes has recently been elucidated and involves genes with different functions.

  17. Remodeling of monoplanar Purkinje cell dendrites during cerebellar circuit formation.

    Directory of Open Access Journals (Sweden)

    Megumi Kaneko

    Full Text Available Dendrite arborization patterns are critical determinants of neuronal connectivity and integration. Planar and highly branched dendrites of the cerebellar Purkinje cell receive specific topographical projections from two major afferent pathways; a single climbing fiber axon from the inferior olive that extend along Purkinje dendrites, and parallel fiber axons of granule cells that contact vertically to the plane of dendrites. It has been believed that murine Purkinje cell dendrites extend in a single parasagittal plane in the molecular layer after the cell polarity is determined during the early postnatal development. By three-dimensional confocal analysis of growing Purkinje cells, we observed that mouse Purkinje cells underwent dynamic dendritic remodeling during circuit maturation in the third postnatal week. After dendrites were polarized and flattened in the early second postnatal week, dendritic arbors gradually expanded in multiple sagittal planes in the molecular layer by intensive growth and branching by the third postnatal week. Dendrites then became confined to a single plane in the fourth postnatal week. Multiplanar Purkinje cells in the third week were often associated by ectopic climbing fibers innervating nearby Purkinje cells in distinct sagittal planes. The mature monoplanar arborization was disrupted in mutant mice with abnormal Purkinje cell connectivity and motor discoordination. The dendrite remodeling was also impaired by pharmacological disruption of normal afferent activity during the second or third postnatal week. Our results suggest that the monoplanar arborization of Purkinje cells is coupled with functional development of the cerebellar circuitry.

  18. Congenital disorders of glycosylation with emphasis on cerebellar involvement.

    Science.gov (United States)

    Barone, Rita; Fiumara, Agata; Jaeken, Jaak

    2014-07-01

    Congenital disorders of glycosylation (CDG) are genetic diseases due to defective glycosylation of proteins and lipids. The authors present an update on these disorders affecting the central nervous system with a focus on cerebellar involvement. The rate of identification of novel CDG shows an exponential increase. Some 76 CDG are actually known, not taking into account the defects in glycan-modifying proteins. Neurologic involvement is present in the large majority of CDG. Screening methods are limited to serum transferrin isoelectrofocusing (for N-glycosylation disorders with sialic acid deficiency), and serum apolipoprotein C-III isoelectrofocusing (for core 1 mucin-type O-glycosylation disorders). Whole exome/genome sequencing is increasingly used in the diagnostic workup of patients with CDG-X. Treatment is greatly lagging behind because only one CDG is efficiently treatable (MPI-CDG). Cerebellar involvement is an important feature of PMM2-CDG, the congenital muscular dystrophies due to dystroglycanopathy, and SRD5A3-CDG. It has also been reported in some patients with ALG1-CDG, ALG3-CDG, ALG9-CDG, ALG6-CDG, ALG8-CDG, PIGA-CDG, DPM1-CDG, DPM2-CDG, B4GALT1-CDG, SLC35A2-CDG, COG1-CDG, COG5-CDG, COG7-CDG, and COG8-CDG.

  19. Pilomyxoid astrocytoma of the cerebellar vermis in an elderly patient

    Directory of Open Access Journals (Sweden)

    Branko Skovrlj

    2014-01-01

    Full Text Available Background: Pilomyxoid astrocytoma (PMA has recently been accepted as an aggressive variant of pilocytic astrocytoma with distinct histopathological features. PMAs have been frequently described in the pediatric population with a predilection for the hypothalamic/chiasmatic region. Case Description: A 72-year-old African American male presented with 6 months of memory loss, difficulty expressing himself, and a progressively worsening gait. Magnetic resonance imaging of the brain demonstrated a heterogeneously enhancing cystic mass centered within the cerebellar vermis with mass effect on the fourth ventricle and ventriculomegaly. The patient underwent placement of a ventriculoperitoneal shunt followed by a surgical resection of the lesion, which after immunohistopathologic evaluation, was diagnosed as a World Health Organization grade II PMA. The patient refused further treatment of the lesion and expired 11 months after initial symptom presentation and 4 months after surgery. Conclusion: To our knowledge, this is the first report of PMA of the cerebellar vermis in a previously unreported age group. This case report describes the natural history of this type of tumor in a patient who refused adjuvant therapy following surgical resection.

  20. Mechanisms of ethanol-induced death of cerebellar granule cells.

    Science.gov (United States)

    Luo, Jia

    2012-03-01

    Maternal ethanol exposure during pregnancy may cause fetal alcohol spectrum disorders (FASD). FASD is the leading cause of mental retardation. The most deleterious effect of fetal alcohol exposure is inducing neuroapoptosis in the developing brain. Ethanol-induced loss of neurons in the central nervous system underlies many of the behavioral deficits observed in FASD. The cerebellum is one of the brain areas that are most susceptible to ethanol during development. Ethanol exposure causes a loss of both cerebellar Purkinje cells and granule cells. This review focuses on the toxic effect of ethanol on cerebellar granule cells (CGC) and the underlying mechanisms. Both in vitro and in vivo studies indicate that ethanol induces apoptotic death of CGC. The vulnerability of CGC to ethanol-induced death diminishes over time as neurons mature. Several mechanisms for ethanol-induced apoptosis of CGC have been suggested. These include inhibition of N-methyl-D-aspartate receptors, interference with signaling by neurotrophic factors, induction of oxidative stress, modulation of retinoid acid signaling, disturbance of potassium channel currents, thiamine deficiency, and disruption of translational regulation. Cultures of CGC provide an excellent system to investigate cellular/molecular mechanisms of ethanol-induced neurodegeneration and to evaluate interventional strategies. This review will also discuss the approaches leading to neuroprotection against ethanol-induced neuroapoptosis.

  1. Primary cerebellar extramedullary myeloid cell tumor mimicking oligodendroglioma.

    Science.gov (United States)

    Ho, D M; Wong, T T; Guo, W Y; Chang, K P; Yen, S H

    1997-10-01

    Extramedullary myeloid cell tumors (EMCTs) are tumors consisting of immature cells of the myeloid series that occur outside the bone marrow. Most of them are associated with acute myelogenous leukemia or other myeloproliferative disorders, and a small number occur as primary lesions, i.e., are not associated with hematological disorders. Occurrence inside the cranium is rare, and there has been only one case of primary EMCT involving the cerebellum reported in the literature. The case we report here is a blastic EMCT occurring in the cerebellum of a 3-year-old boy who had no signs of leukemia or any hematological disorder throughout the entire course. The cerebellar tumor was at first misdiagnosed as an "oligodendroglioma" because of the uniformity and "fried egg" artifact of the tumor cells. The tumor disappeared during chemotherapy consisting of 12 treatments. However, it recurred and metastasized to the cerebrospinal fluid (CSF) shortly after the therapy was completed. A diagnosis of EMCT was suspected because of the presence of immature myeloid cells in the CSF, and was confirmed by anti-myeloperoxidase and anti-lysozyme immunoreactivity of the cerebellar tumor. The patient succumbed 1 year and 3 months after the first presentation of the disease.

  2. Coordinated scaling of cortical and cerebellar numbers of neurons

    Directory of Open Access Journals (Sweden)

    Suzana Herculano-Houzel

    2010-03-01

    Full Text Available While larger brains possess concertedly larger cerebral cortices and cerebella, the relative size of the cerebral cortex increases with brain size, but relative cerebellar size does not. In the absence of data on numbers of neurons in these structures, this discrepancy has been used to dispute the hypothesis that the cerebral cortex and cerebellum function and have evolved in concert and to support a trend towards neocorticalization in evolution. However, the rationale for interpreting changes in absolute and relative size of the cerebral cortex and cerebellum relies on the assumption that they reflect absolute and relative numbers of neurons in these structures across all species – an assumption that our recent studies have shown to be flawed. Here I show for the first time that the numbers of neurons in the cerebral cortex and cerebellum are directly correlated across 19 mammalian species of 4 different orders, including humans, and increase concertedly in a similar fashion both within and across the orders Eulipotyphla (Insectivora, Rodentia, Scandentia and Primata, such that on average a ratio of 3.6 neurons in the cerebellum to every neuron in the cerebral cortex is maintained across species. This coordinated scaling of cortical and cerebellar numbers of neurons provides direct evidence in favor of concerted function, scaling and evolution of these brain structures, and suggests that the common notion that equates cognitive advancement with neocortical expansion should be revisited to consider in its stead the coordinated scaling of neocortex and cerebellum as a functional ensemble.

  3. Cascade Hierarchy in SUSY SU(5) GUT

    CERN Document Server

    Kojima, Kentaro; Takahashi, Ryo

    2010-01-01

    We study cascade hierarchy in supersymmetric SU(5) grand unified theory. The neutrino Dirac mass matrix of the cascade form can lead to the tri-bimaximal generation mixing at the leading order in the seesaw mechanism while the down quark mass matrix of a hybrid cascade form naturally gives the CKM structure. We embed such experimentally favored mass textures into supersymmetric SU(5) GUT, which gives a relation between the down quark and charged lepton mass matrices. Related phenomenologies, such as lepton flavor violating processes and leptogenesis, are also investigated in addition to lepton mixing angles.

  4. Cascades on clique-based graphs

    Science.gov (United States)

    Hackett, Adam; Gleeson, James P.

    2013-06-01

    We present an analytical approach to determining the expected cascade size in a broad range of dynamical models on the class of highly clustered random graphs introduced by Gleeson [J. P. Gleeson, Phys. Rev. EPLEEE81539-375510.1103/PhysRevE.80.036107 80, 036107 (2009)]. A condition for the existence of global cascades is also derived. Applications of this approach include analyses of percolation, and Watts's model. We show how our techniques can be used to study the effects of in-group bias in cascades on social networks.

  5. Cesium chloride protects cerebellar granule neurons from apoptosis induced by low potassium.

    Science.gov (United States)

    Zhong, Jin; Yao, Weiguo; Lee, Weihua

    2007-10-01

    Neuronal apoptosis plays a critical role in the pathogenesis of neurodegenerative disorders, and neuroprotective agents targeting apoptotic signaling could have therapeutic use. Here we report that cesium chloride, an alternative medicine in treating radiological poison and cancer, has neuroprotective actions. Serum and potassium deprivation induced cerebellar granule neurons to undergo apoptosis, which correlated with the activation of caspase-3. Cesium prevented both the activation of caspase-3 and neuronal apoptosis in a dose-dependent manner. Cesium at 8 mM increased the survival of neurons from 45 +/- 3% to 91 +/- 5% of control. Cesium's neuroprotection was not mediated by PI3/Akt or MAPK signaling pathways, since it was unable to activate either Akt or MAPK by phosphorylation. In addition, specific inhibitors of PI3 kinase and MAP kinase did not block cesium's neuroprotective effects. On the other hand, cesium inactivated GSK3beta by phosphorylation of serine-9 and GSK3beta-specific inhibitor SB415286 prevented neuronal apoptosis. These data indicate that cesium's neuroprotection is likely via inactivating GSK3beta. Furthermore, cesium also prevented H(2)O(2)-induced neuronal death (increased the survival of neurons from 72 +/- 4% to 89 +/- 3% of control). Given its relative safety and good penetration of the brain blood barrier, our findings support the potential therapeutic use of cesium in neurodegenerative diseases.

  6. Silencing the Majority of Cerebellar Granule Cells Uncovers Their Essential Role in Motor Learning and Consolidation

    Directory of Open Access Journals (Sweden)

    Elisa Galliano

    2013-04-01

    Full Text Available Cerebellar granule cells (GCs account for more than half of all neurons in the CNS of vertebrates. Theoretical work has suggested that the abundance of GCs is advantageous for sparse coding during memory formation. Here, we minimized the output of the majority of GCs by selectively eliminating their CaV2.1 (P/Q-type Ca2+ channels, which mediate the bulk of their neurotransmitter release. This resulted in reduced GC output to Purkinje cells (PCs and stellate cells (SCs as well as in impaired long-term plasticity at GC-PC synapses. As a consequence modulation amplitude and regularity of simple spike (SS output were affected. Surprisingly, the overall motor performance was intact, whereas demanding motor learning and memory consolidation tasks were compromised. Our findings indicate that a minority of functionally intact GCs is sufficient for the maintenance of basic motor performance, whereas acquisition and stabilization of sophisticated memories require higher numbers of normal GCs controlling PC firing.

  7. Cerebellar peduncle abscess secondary to disseminated strangles in a six-week-old miniature foal

    Directory of Open Access Journals (Sweden)

    Brianne Henderson

    2011-11-01

    Full Text Available During a strangles outbreak within a herd of minature horses, a six week old foal developed acute onset clinical signs of sepsis and neurological deficits. The foal was euthanized and submitted for post-mortem at the Animal Health Laboratories, Guelph Ontario. Gross post-mortem examination noted severe bronchopneumonia, hypopyon of the right eye and a singular cerebellar peduncle abscess. Culture of the lungs and cerebellum produced a pure growth of Streptococcus equi ssp. equi. Streptococcus equi ssp. equi, the causative agent of equine strangles, produces an acute pyrexia, purulent lymphadenopathy of submandibular and retropharyngeal lymph nodes. Commonly, lymph node abscesses rupture and resolve without complication. Rarely, complications may include: dissemination of the bacteria with diffuse abscess formation, immune mediated disease (purpura haemorrhagica, rarely abscess formation within the central nervous system (CNS can occur. These can be managed medically with appropriate antibiotics and drugs to reduce intra-cranial pressure, however surgical drainage and debulking of the abscess has been attempted successfully in a few cases.

  8. Persistent posttetanic depression at cerebellar parallel fiber to Purkinje cell synapses.

    Directory of Open Access Journals (Sweden)

    Astrid Bergerot

    Full Text Available Plasticity at the cerebellar parallel fiber to Purkinje cell synapse may underlie information processing and motor learning. In vivo, parallel fibers appear to fire in short high frequency bursts likely to activate sparsely distributed synapses over the Purkinje cell dendritic tree. Here, we report that short parallel fiber tetanic stimulation evokes a ∼7-15% depression which develops over 2 min and lasts for at least 20 min. In contrast to the concomitantly evoked short-term endocannabinoid-mediated depression, this persistent posttetanic depression (PTD does not exhibit a dependency on the spatial pattern of synapse activation and is not caused by any detectable change in presynaptic calcium signaling. This persistent PTD is however associated with increased paired-pulse facilitation and coefficient of variation of synaptic responses, suggesting that its expression is presynaptic. The chelation of postsynaptic calcium prevents its induction, suggesting that post- to presynaptic (retrograde signaling is required. We rule out endocannabinoid signaling since the inhibition of type 1 cannabinoid receptors, monoacylglycerol lipase or vanilloid receptor 1, or incubation with anandamide had no detectable effect. The persistent PTD is maximal in pre-adolescent mice, abolished by adrenergic and dopaminergic receptors block, but unaffected by adrenergic and dopaminergic agonists. Our data unveils a novel form of plasticity at parallel fiber synapses: a persistent PTD induced by physiologically relevant input patterns, age-dependent, and strongly modulated by the monoaminergic system. We further provide evidence supporting that the plasticity mechanism involves retrograde signaling and presynaptic diacylglycerol.

  9. SK2 channel modulation contributes to compartment-specific dendritic plasticity in cerebellar Purkinje cells.

    Science.gov (United States)

    Ohtsuki, Gen; Piochon, Claire; Adelman, John P; Hansel, Christian

    2012-07-12

    Small-conductance Ca(2+)-activated K(+) channels (SK channels) modulate excitability and curtail excitatory postsynaptic potentials (EPSPs) in neuronal dendrites. Here, we demonstrate long-lasting plasticity of intrinsic excitability (IE) in dendrites that results from changes in the gain of this regulatory mechanism. Using dendritic patch-clamp recordings from rat cerebellar Purkinje cells, we find that somatic depolarization or parallel fiber (PF) burst stimulation induce long-term amplification of synaptic responses to climbing fiber (CF) or PF stimulation and enhance the amplitude of passively propagated sodium spikes. Dendritic plasticity is mimicked and occluded by the SK channel blocker apamin and is absent in Purkinje cells from SK2 null mice. Triple-patch recordings from two dendritic sites and the soma and confocal calcium imaging studies show that local stimulation limits dendritic plasticity to the activated compartment of the dendrite. This plasticity mechanism allows Purkinje cells to adjust the SK2-mediated control of dendritic excitability in an activity-dependent manner.

  10. Quantum Cascade Laser Frequency Combs

    CERN Document Server

    Faist, Jérôme; Scalari, Giacomo; Rösch, Markus; Bonzon, Christopher; Hugi, Andreas; Beck, Mattias

    2015-01-01

    It was recently demonstrated that broadband quantum cascade lasers can operate as frequency combs. As such, they operate under direct electrical pumping at both mid-infrared and THz frequencies, making them very attractive for dual-comb spectroscopy. Performance levels are continuously improving, with average powers over 100 mW and frequency coverage of 100 cm$^{-1}$ in the mid-infrared. In the THz range, 10 mW of average power and 600 GHz of frequency coverage are reported. As a result of the very short upper state lifetime of the gain medium, the mode proliferation in these sources arises from four wave mixing rather than saturable absorption. As a result, their optical output is characterized by the tendency of small intensity modulation of the output power, and the relative phases of the modes to be similar to the ones of a frequency modulated laser. Recent results include the proof of comb operation down to a metrological level, the observation of a Schawlow-Townes broadened linewidth, as well as the fir...

  11. Regional cerebellar volume and cognitive function from adolescence to late middle age.

    Science.gov (United States)

    Bernard, Jessica A; Leopold, Daniel R; Calhoun, Vince D; Mittal, Vijay A

    2015-03-01

    Cerebellar morphology and function have been implicated in a variety of developmental disorders, and in healthy aging. Although recent work has sought to characterize the relationships between volume and age in this structure during adolescence, young, and older adulthood, there have been no investigations of regional cerebellar volume from adolescence through late middle age. Middle age in particular has been largely understudied, and investigating this period of the lifespan may be especially important for our understanding of senescence. Understanding regional patterns of cerebellar volume with respect to age during this portion of the lifespan may provide important insight into healthy aging and cognitive function as well as pathology from adolescence into later life. We investigated regional cerebellar volume using a highly novel lobular segmentation approach in conjunction with a battery of cognitive tasks in a cross-sectional sample of 123 individuals from 12 to 65 years old. Our results indicated that regional cerebellar volumes show different patterns with respect to age. In particular, the more posterior aspect of the neocerebellum follows a quadratic "inverse-U" pattern while the vermis and anterior cerebellum follow logarithmic patterns. In addition, we quantified the relationships between age and a variety of cognitive assessments and found relationships between regional cerebellar volumes and performance. Finally, exploratory analyses of sex differences in the relationships between regional cerebellar volume, age, and cognition were investigated. Taken together, these results provide key insights into the development and aging of the human cerebellum, and its role in cognitive function across the lifespan.

  12. Self-Organization of Polarized Cerebellar Tissue in 3D Culture of Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Keiko Muguruma

    2015-02-01

    Full Text Available During cerebellar development, the main portion of the cerebellar plate neuroepithelium gives birth to Purkinje cells and interneurons, whereas the rhombic lip, the germinal zone at its dorsal edge, generates granule cells and cerebellar nuclei neurons. However, it remains elusive how these components cooperate to form the intricate cerebellar structure. Here, we found that a polarized cerebellar structure self-organizes in 3D human embryonic stem cell (ESC culture. The self-organized neuroepithelium differentiates into electrophysiologically functional Purkinje cells. The addition of fibroblast growth factor 19 (FGF19 promotes spontaneous generation of dorsoventrally polarized neural-tube-like structures at the level of the cerebellum. Furthermore, addition of SDF1 and FGF19 promotes the generation of a continuous cerebellar plate neuroepithelium with rhombic-lip-like structure at one end and a three-layer cytoarchitecture similar to the embryonic cerebellum. Thus, human-ESC-derived cerebellar progenitors exhibit substantial self-organizing potential for generating a polarized structure reminiscent of the early human cerebellum at the first trimester.

  13. Direct and indirect spino-cerebellar pathways: shared ideas but different functions in motor control

    Directory of Open Access Journals (Sweden)

    Juan eJiang

    2015-07-01

    Full Text Available The impressive precision of mammalian limb movements relies on internal feedback pathways that convey information about ongoing motor output to cerebellar circuits. The spino-cerebellar tracts (SCT in the cervical, thoracic and lumbar spinal cord have long been considered canonical neural substrates for the conveyance of internal feedback signals. Here we consider the distinct features of an indirect spino-cerebellar route, via the brainstem lateral reticular nucleus (LRN, and the implications of this pre-cerebellar ‘detour’ for the execution and evolution of limb motor control. Both direct and indirect spino-cerebellar pathways signal spinal interneuronal activity to the cerebellum during movements, but evidence suggests that direct SCT neurons are mainly modulated by rhythmic activity, whereas the LRN also receives information from systems active during postural adjustment, reaching and grasping. Thus, while direct and indirect spino-cerebellar circuits can both be regarded as internal copy pathways, it seems likely that the direct system is principally dedicated to rhythmic motor acts like locomotion, while the indirect system also provides a means of pre-cerebellar integration relevant to the execution and coordination of de

  14. Modality specificity in the cerebro-cerebellar neurocircuitry during working memory.

    Science.gov (United States)

    Ng, H B Tommy; Kao, K-L Cathy; Chan, Y C; Chew, Effie; Chuang, K H; Chen, S H Annabel

    2016-05-15

    Previous studies have suggested cerebro-cerebellar circuitry in working memory. The present fMRI study aims to distinguish differential cerebro-cerebellar activation patterns in verbal and visual working memory, and employs a quantitative analysis to deterimine lateralization of the activation patterns observed. Consistent with Chen and Desmond (2005a,b) predictions, verbal working memory activated a cerebro-cerebellar circuitry that comprised left-lateralized language-related brain regions including the inferior frontal and posterior parietal areas, and subcortically, right-lateralized superior (lobule VI) and inferior cerebellar (lobule VIIIA/VIIB) areas. In contrast, a distributed network of bilateral inferior frontal and inferior temporal areas, and bilateral superior (lobule VI) and inferior (lobule VIIB) cerebellar areas, was recruited during visual working memory. Results of the study verified that a distinct cross cerebro-cerebellar circuitry underlies verbal working memory. However, a neural circuitry involving specialized brain areas in bilateral neocortical and bilateral cerebellar hemispheres subserving visual working memory is observed. Findings are discussed in the light of current models of working memory and data from related neuroimaging studies.

  15. Role of the complement cascade in cerebral aneurysm formation, growth, and rupture

    Directory of Open Access Journals (Sweden)

    Blake E. S. Taylor

    2015-06-01

    Full Text Available Rupture of intracranial aneurysms is the most common cause of nontraumatic subarachnoid hemorrhage, but the intricate neuroinflammatory processes which contribute to aneurysm pathophysiology are not well-understood. Mounting evidence has implicated the complement cascade in the progression of aneurysms from their formation to rupture. In this article, we identify and review studies that have sought to determine the role of the complement system in the aneurysm pathogenesis. The studies were generally conducted by immunhistological analyses on aneurysm tissue collected intraoperatively, and multiple components of the complement cascade and its modulators were identified in specific regions of the aneurysm wall. The results of the studies suggest that the complement cascade is locally upregulated and disinhibited in the perianeurysmal environment, and that it contributes to chronic as well as acute immunological damage to the aneurysm wall. In the future, understanding the mechanisms at work in complement-mediated damage is necessary to leading the development of novel therapies.

  16. Fear conditioning-related changes in cerebellar Purkinje cell activities in goldfish

    Directory of Open Access Journals (Sweden)

    Yoshida Masayuki

    2012-10-01

    Full Text Available Abstract Background Fear conditioning-induced changes in cerebellar Purkinje cell responses to a conditioned stimulus have been reported in rabbits. It has been suggested that synaptic long-term potentiation and the resulting increases in firing rates of Purkinje cells are related to the acquisition of conditioned fear in mammals. However, Purkinje cell activities during acquisition of conditioned fear have not been analysed, and changes in Purkinje cell activities throughout the development of conditioned fear have not yet been investigated. In the present study, we tracked Purkinje cell activities throughout a fear conditioning procedure and aimed to elucidate further how cerebellar circuits function during the acquisition and expression of conditioned fear. Methods Activities of single Purkinje cells in the corpus cerebelli were tracked throughout a classical fear conditioning procedure in goldfish. A delayed conditioning paradigm was used with cardiac deceleration as the conditioned response. Conditioning-related changes of Purkinje cell responses to a conditioned stimulus and unconditioned stimulus were examined. Results The majority of Purkinje cells sampled responded to the conditioned stimulus by either increasing or decreasing their firing rates before training. Although there were various types of conditioning-related changes in Purkinje cells, more than half of the cells showed suppressed activities in response to the conditioned stimulus after acquisition of conditioned fear. Purkinje cells that showed unconditioned stimulus-coupled complex-spike firings also exhibited conditioning-related suppression of simple-spike responses to the conditioned stimulus. A small number of Purkinje cells showed increased excitatory responses in the acquisition sessions. We found that the magnitudes of changes in the firing frequencies of some Purkinje cells in response to the conditioned stimulus correlated with the magnitudes of the conditioned

  17. North Cascades Grizzly Bear Ecosystem Evaluation

    Data.gov (United States)

    Oak Ridge National Laboratory — We conducted a 6-year evaluation of the North Cascades Grizzly Bear Ecosystem (NCGBE) in north-central Washington to determine the suitability of the area to support...

  18. Multilevel Inverter by Cascading Industrial VSI

    DEFF Research Database (Denmark)

    Teodorescu, Remus; Blaabjerg, Frede; Pedersen, John Kim

    2002-01-01

    In this paper the modularity concept applied to medium-voltage adjustable speed drives is addressed. First, the single-phase cascaded voltage-source inverter that uses series connection of IGBT H-bridge modules with isolated dc-buses is presented. Next, a novel three-phase cascaded voltage...... of the motor rated kVA. The concept of using cascaded inverters is further extended to a new modular motor-modular inverter system where the motor winding connections are reconnected into several three-phase groups, either six-lead or 12-lead connection according to the voltage level, each powered...... by a standard triphase IGBT inverter module. Thus, a high fault tolerance is being achieved and the output transformer requirement is eliminated. A staggered space-vector modulation technique applicable to three-phase cascaded voltage-source inverter topologies is also demonstrated. Both computer simulations...

  19. Cascade of period doublings of tori

    Science.gov (United States)

    Arneodo, A.; Coullet, P. H.; Spiegel, E. A.

    1983-02-01

    A three-dimensional map is proposed to model the effects of periodic forcing on a system displaying a transition to chaos through a cascade of period-doubling bifurcations. The study outlined here raises the problem of the existence and bifurcation of invariant tori. A principal feature of the simulations of both the differential equations and the discrete dynamical systems is that it is possible to disrupt period-doubling sequences (and inverse sequences as well) by periodic external forcing. Even though the way in which this abortion works is not understood, the mechanism is thought to be associated with the destruction of tori (Aronson et al., 1982) when the system is on the verge of bifurcation. The simulations therefore suggest that in moving farther along the cascade, the tori become more fragile. It is suspected that for arbitrarily weak driving, the cascade will eventually be disrupted after the cascade has proceeded through a sufficient number of steps.

  20. Bursting behaviours in cascaded stimulated Brillouin scattering

    Institute of Scientific and Technical Information of China (English)

    Liu Zhan-Jun; He Xian-Tu; Zheng Chun-Yang; Wang Yu-Gang

    2012-01-01

    Stimulated Brillouin scattering is studied by numerically solving the Vlasov-Maxwell system.A cascade of stimulated Brillouin scattering can occur when a linearly polarized laser pulse propagates in a plasma.It is found that a stimulated Brillouin scattering cascade can reduce the scattering and increase the transmission of light,as well as introduce a bursting behaviour in the evolution of the laser-plasma interaction.The bursting time in the reflectivity is found to be less than half the ion acoustic period.The ion temperature can affect the stimulated Brillouin scattering cascade,which can repeat several times at low ion temperatures and can be completely eliminated at high ion temperatures.For stimulated Brillouin scattering saturation,higher-harmonic generation and wave-wave interaction of the excited ion acoustic waves can restrict the amplitude of the latter.In addition,stimulated Brillouin scattering cascade can restrict the amplitude of the scattered light.

  1. Picturing perturbative parton cascades in QCD matter

    Directory of Open Access Journals (Sweden)

    Aleksi Kurkela

    2015-01-01

    Full Text Available Based on parametric reasoning, we provide a simple dynamical picture of how a perturbative parton cascade, in interaction with a QCD medium, fills phase space as a function of time.

  2. MAP kinase cascades in Arabidopsis innate immunity

    DEFF Research Database (Denmark)

    Rasmussen, Magnus Wohlfahrt; Roux, Milena Edna; Petersen, Morten

    2012-01-01

    Plant mitogen-activated protein kinase (MAPK) cascades generally transduce extracellular stimuli into cellular responses. These stimuli include the perception of pathogen-associated molecular patterns (PAMPs) by host transmembrane pattern recognition receptors which trigger MAPK-dependent innate ...

  3. Chemoenzymatic cascade processes for sustainable organic synthesis

    NARCIS (Netherlands)

    Simons, C.

    2007-01-01

    Chemical production processes often require wasteful and expensive isolation as well as purification of intermediates. Catalytic cascades offer a unique opportunity to eliminate these inefficient and polluting steps, in particular when carefully orchestrated, involving enzymes and chemocatalysts. Th

  4. Model for cascading failures in congested Internet

    Institute of Scientific and Technical Information of China (English)

    Jian WANG; Yan-heng LIU; Jian-qi ZHU; Yu JIAO

    2008-01-01

    Cascading failures often occur in congested networks such as the Internet. A cascading failure can be described as a three-phase process: generation, diffusion, and dissipation of the congestion. In this account, we present a function that represents the extent of congestion on a given node. This approach is different from existing functions based on betweenness centrality. By introducing the concept of 'delay time', we designate an intergradation between permanent removal and nouremoval. We also construct an evaluation function of network efficiency, based on congestion, which measures the damage caused by cascading failures. Finally, we investigate the effects of network structure and size, delay time, processing ability and packet generation speed on congestion propagation. Also, we uncover the relationship between the cascade dynamics and some properties of the network such as structure and size.

  5. Transport properties of cascading gauge theories

    CERN Document Server

    Buchel, A

    2005-01-01

    Cascading gauge theories of Klebanov et.al. provide a model within a framework of gauge theory/string theory duality for a four dimensional non-conformal gauge theory with a spontaneously generated mass scale. Using the dual supergravity description we study sound wave propagation in strongly coupled cascading gauge theory plasma. We analytically compute the speed of sound and the bulk viscosity of cascading gauge theory plasma at a temperature much larger than the strong coupling scale of the theory. The sound wave dispersion relation is obtained from the hydrodynamic pole in the stress-energy tensor two-point correlation function. The speed of sound extracted from the pole of the correlation function agrees with its value computed in [hep-th/0506002] using the equation of state. We find that the bulk viscosity of the hot cascading gauge theory plasma is non-zero at the leading order in the deviation from conformality.

  6. A quantum cascade phonon-polariton laser

    CERN Document Server

    Ohtani, Keita; Bosco, Lorenzo; Beck, Mattias; Faist, Jérôme

    2016-01-01

    We report a laser that coherently emits phonon-polaritons, quasi-particles arising from the coupling between photons and transverse optical phonons. The gain is provided by an intersubband transition in a quantum cascade structure. The polaritons at h$\

  7. Restoring cognitive functions using non-invasive brain stimulation techniques in patients with cerebellar disorders

    Directory of Open Access Journals (Sweden)

    Paul A Pope

    2014-04-01

    Full Text Available Numerous studies have highlighted the possibility of modulating the excitability of cerebro-cerebellar circuits bi-directionally using transcranial electrical brain stimulation, in a manner akin to that observed using magnetic stimulation protocols. It has been proposed that cerebellar stimulation activates Purkinje cells in the cerebellar cortex, leading to inhibition of the dentate nucleus, which exerts a tonic facilitatory drive onto motor and cognitive regions of cortex through a synaptic relay in the ventral-lateral thalamus. Some cerebellar deficits present with cognitive impairments if damage to non-motor regions of the cerebellum disrupts the coupling with cerebral cortical areas for thinking and reasoning. Indeed, white matter changes in the dentato-rubral tract correlate with cognitive assessments in patients with Friedreich ataxia, suggesting that this pathway is one component of the anatomical substrate supporting a cerebellar contribution to cognition. An understanding of the physiology of the cerebro-cerebellar pathway previously helped us to constrain our interpretation of results from two recent studies in which we showed cognitive enhancements in healthy participants during tests of arithmetic after electrical stimulation of the cerebellum, but only when task demands were high. Others studies have also shown how excitation of the prefrontal cortex can enhance performance in a variety of working memory tasks. Thus, future efforts might be guided towards neuro-enhancement in certain patient populations, using what is commonly termed 'non-invasive brain stimulation' as a cognitive rehabilitation tool to modulate cerebro-cerebellar circuits, or for stimulation over the cerebral cortex to compensate for decreased cerebellar drive to this region. This article will address these possibilities with a review of the relevant literature covering ataxias and cerebellar cognitive affective disorders, which are characterized by thalamo

  8. Qualitative and quantitative aspects of the microanatomy of the African elephant cerebellar cortex.

    Science.gov (United States)

    Maseko, Busisiwe C; Jacobs, Bob; Spocter, Muhammad A; Sherwood, Chet C; Hof, Patrick R; Manger, Paul R

    2013-01-01

    The current study provides a number of novel observations on the organization and structure of the cerebellar cortex of the African elephant by using a combination of basic neuroanatomical and immunohistochemical stains with Golgi and stereologic analysis. While the majority of our observations indicate that the cerebellar cortex of the African elephant is comparable to other mammalian species, several features were unique to the elephant. The three-layered organization of the cerebellar cortex, the neuronal types and some aspects of the expression of calcium-binding proteins were common to a broad range of mammalian species. The Lugaro neurons observed in the elephant were greatly enlarged in comparison to those of other large-brained mammals, suggesting a possible alteration in the processing of neural information in the elephant cerebellar cortex. Analysis of Golgi impregnations indicated that the dendritic complexity of the different interneuron types was higher in elephants than other mammals. Expression of parvalbumin in the parallel fibers and calbindin expressed in the stellate and basket cells also suggested changes in the elephant cerebellar neuronal circuitry. The stereologic analysis confirmed and extended previous observations by demonstrating that neuronal density is low in the elephant cerebellar cortex, providing for a larger volume fraction of the neuropil. With previous results indicating that the elephants have the largest relative cerebellar size amongst mammals, and one of the absolutely largest mammalian cerebella, the current observations suggest that the elephants have a greater volume of a potentially more complexly organized cerebellar cortex compared to other mammals. This quantitatively larger and more complex cerebellar cortex likely represents part of the neural machinery required to control the complex motor patterns involved in movement of the trunk and the production of infrasonic vocalizations.

  9. Restoring cognitive functions using non-invasive brain stimulation techniques in patients with cerebellar disorders.

    Science.gov (United States)

    Pope, Paul A; Miall, R Chris

    2014-01-01

    Numerous studies have highlighted the possibility of modulating the excitability of cerebro-cerebellar circuits bi-directionally using transcranial electrical brain stimulation, in a manner akin to that observed using magnetic stimulation protocols. It has been proposed that cerebellar stimulation activates Purkinje cells in the cerebellar cortex, leading to inhibition of the dentate nucleus, which exerts a tonic facilitatory drive onto motor and cognitive regions of cortex through a synaptic relay in the ventral-lateral thalamus. Some cerebellar deficits present with cognitive impairments if damage to non-motor regions of the cerebellum disrupts the coupling with cerebral cortical areas for thinking and reasoning. Indeed, white matter changes in the dentato-rubral tract correlate with cognitive assessments in patients with Friedreich ataxia, suggesting that this pathway is one component of the anatomical substrate supporting a cerebellar contribution to cognition. An understanding of the physiology of the cerebro-cerebellar pathway previously helped us to constrain our interpretation of results from two recent studies in which we showed cognitive enhancements in healthy participants during tests of arithmetic after electrical stimulation of the cerebellum, but only when task demands were high. Others studies have also shown how excitation of the prefrontal cortex can enhance performance in a variety of working memory tasks. Thus, future efforts might be guided toward neuro-enhancement in certain patient populations, using what is commonly termed "non-invasive brain stimulation" as a cognitive rehabilitation tool to modulate cerebro-cerebellar circuits, or for stimulation over the cerebral cortex to compensate for decreased cerebellar drive to this region. This article will address these possibilities with a review of the relevant literature covering ataxias and cerebellar cognitive affective disorders, which are characterized by thalamo-cortical disturbances.

  10. Tract Profiles of the Cerebellar White Matter Pathways in Children and Adolescents.

    Science.gov (United States)

    Leitner, Yael; Travis, Katherine E; Ben-Shachar, Michal; Yeom, Kristen W; Feldman, Heidi M

    2015-12-01

    Intact development of cerebellar connectivity is essential for healthy neuromotor and neurocognitive development. To date, limited knowledge about the microstructural properties of the cerebellar peduncles, the major white matter tracts of the cerebellum, is available for children and adolescents. Such information would be useful as a comparison for studies of normal development, clinical conditions, or associations of cerebellar structures with cognitive and motor functions. The goal of the present study was to evaluate the variability in diffusion measures of the cerebellar peduncles within individuals and within a normative sample of healthy children. Participants were 19 healthy children and adolescents, aged 9-17 years, mean age 13.0 ± 2.3. We analyzed diffusion magnetic resonance imaging (dMRI) data with deterministic tractography. We generated tract profiles for each of the cerebellar peduncles by extracting four diffusion properties (fractional anisotropy (FA) and mean, radial, and axial diffusivity) at 30 equidistant points along each tract. We were able to identify the middle cerebellar peduncle and the bilateral inferior and superior cerebellar peduncles in all participants. The results showed that within each of the peduncles, the diffusion properties varied along the trajectory of the tracts. However, the tracts showed consistent patterns of variation across individuals; the coefficient of variation for FA across individual profiles was low (≤20%) for each tract. We observed no systematic variation of the diffusion properties with age. These cerebellar tract profiles of the cerebellar peduncles can serve as a reference for future studies of children across the age range and for children and adolescents with clinical conditions that affect the cerebellum.

  11. Innovation cascades: artefacts, organization and attributions.

    Science.gov (United States)

    Lane, David A

    2016-03-19

    Innovation cascades inextricably link the introduction of new artefacts, transformations in social organization, and the emergence of new functionalities and new needs. This paper describes a positive feedback dynamic, exaptive bootstrapping, through which these cascades proceed, and the characteristics of the relationships in which the new attributions that drive this dynamic are generated. It concludes by arguing that the exaptive bootstrapping dynamic is the principal driver of our current Innovation Society.

  12. Cascade Textures and SUSY SO(10) GUT

    CERN Document Server

    Adulpravitchai, Adisorn; Takahashi, Ryo

    2010-01-01

    We give texture analyses of cascade hierarchical mass matrices in supersymmetric SO(10) grand unified theory. We embed cascade mass textures of the standard model fermion with right-handed neutrinos into the theory, which gives relations among the mass matrices of the fermions. The related phenomenologies, such as the lepton flavor violating processes and leptogenesis, are also investigated in addition to the PMNS mixing angles.

  13. Supersonic Chordwise Bending Flutter in Cascades

    Science.gov (United States)

    1975-05-31

    such a flutter boundary can be made by utilizing the trend lines predicted from a supersonic analysis based on supersonic cascade theory (Appendix I...bonding agent was injected via hypodermic needles after the blade tabs were properly inserted, The integrity and repeatability of the mounting of the indi...in conjunction with NASTRAN predictions and supersonic cascade aerodynamic computa- tions. Comparisons between theory and experiment are discussed. DD

  14. Compression limits in cascaded quadratic soliton compression

    DEFF Research Database (Denmark)

    Bache, Morten; Bang, Ole; Krolikowski, Wieslaw;

    2008-01-01

    Cascaded quadratic soliton compressors generate under optimal conditions few-cycle pulses. Using theory and numerical simulations in a nonlinear crystal suitable for high-energy pulse compression, we address the limits to the compression quality and efficiency.......Cascaded quadratic soliton compressors generate under optimal conditions few-cycle pulses. Using theory and numerical simulations in a nonlinear crystal suitable for high-energy pulse compression, we address the limits to the compression quality and efficiency....

  15. Emergence of event cascades in inhomogeneous networks

    Science.gov (United States)

    Onaga, Tomokatsu; Shinomoto, Shigeru

    2016-09-01

    There is a commonality among contagious diseases, tweets, and neuronal firings that past events facilitate the future occurrence of events. The spread of events has been extensively studied such that the systems exhibit catastrophic chain reactions if the interaction represented by the ratio of reproduction exceeds unity; however, their subthreshold states are not fully understood. Here, we report that these systems are possessed by nonstationary cascades of event-occurrences already in the subthreshold regime. Event cascades can be harmful in some contexts, when the peak-demand causes vaccine shortages, heavy traffic on communication lines, but may be beneficial in other contexts, such that spontaneous activity in neural networks may be used to generate motion or store memory. Thus it is important to comprehend the mechanism by which such cascades appear, and consider controlling a system to tame or facilitate fluctuations in the event-occurrences. The critical interaction for the emergence of cascades depends greatly on the network structure in which individuals are connected. We demonstrate that we can predict whether cascades may emerge, given information about the interactions between individuals. Furthermore, we develop a method of reallocating connections among individuals so that event cascades may be either impeded or impelled in a network.

  16. Differences in saccade dynamics between spinocerebellar ataxia 2 and late-onset cerebellar ataxias.

    Science.gov (United States)

    Federighi, Pamela; Cevenini, Gabriele; Dotti, Maria T; Rosini, Francesca; Pretegiani, Elena; Federico, Antonio; Rufa, Alessandra

    2011-03-01

    The cerebellum is implicated in maintaining the saccadic subsystem efficient for vision by minimizing movement inaccuracy and by learning from endpoint errors. This ability is often disrupted in degenerative cerebellar diseases, as demonstrated by saccade kinetic abnormalities. The study of saccades in these patients may therefore provide insights into the neural substrate underlying saccadic motor control. We investigated the different extent of saccade dynamic abnormalities in spinocerebellar ataxia type 2 and late-onset cerebellar ataxias, genetically undefined and with prevalent cerebellar atrophy. Reflexive and voluntary saccades of different amplitude (10°-18°) were studied in seven patients with spinocerebellar ataxia 2, eight patients with late-onset cerebellar ataxia and 25 healthy controls. Quantitative analysis of saccade parameters and measures of saccade accuracy were performed. Detailed neurological, neurophysiological and magnetic resonance imaging assessment was obtained for each patient. Genetic and laboratory screening for spinocerebellar ataxias and other forms of late-onset cerebellar ataxias were also performed. A lower peak saccade velocity and longer duration was observed in patients with spinocerebellar ataxia 2 with respect to those with late-onset cerebellar ataxia and controls. Unlike subjects with spinocerebellar ataxia 2, patients with late-onset cerebellar ataxia showed main sequence relationships to similar saccades made by normal subjects. Saccades were significantly more inaccurate, namely hypometric, in late-onset cerebellar ataxia than in spinocerebellar ataxia 2 and inaccuracy increased with saccade amplitude. The percentage of hypometric primary saccades and of larger secondary corrective saccades were consistently higher in late-onset cerebellar ataxia than in spinocerebellar ataxia 2 and controls. No other significant differences were found between groups. Two different mechanisms were adopted to redirect the fovea as fast

  17. Pediatric cerebellar stroke associated with elevated titer of antibodies to β2-glycoprotein.

    Science.gov (United States)

    Spalice, Alberto; Del Balzo, Francesca; Perla, Francesco Massimo; Papetti, Laura; Nicita, Francesco; Ursitti, Fabiana; Properzi, Enrico

    2011-06-01

    Antibodies to 2-glycoprotein I (anti-2GPI) have been associated with recurrent thrombosis and pregnancy morbidity. However, the prevalence of anti-2GPI in children suffering from cerebral and cerebellar infarction is unknown. We report on a 10-month-old boy who had an ischemic cerebellar stroke, secondary to antiphospholipid syndrome with high titers of immunoglobulin G anti-2GPI (first titer: 132U) anticardiolipin antibodies and lupus anticoagulant tests were negative. All other causes of infarction were excluded. To our knowledge, this is the first reported case of childhood cerebellar ischemic stroke with only anti-2GPI but no antibodies detectable in standard antiphospholipid assays.

  18. A Case of Multiple System Atrophy-Cerebellar Type Preceded by Dementia

    Directory of Open Access Journals (Sweden)

    Eun Hye Jang

    2012-10-01

    Full Text Available Multiple system atrophy (MSA is a sporadic, adult-onset disease characterized by progressive degeneration of nervous systems including cerebellar, pyramidal, extrapyramidal, and autonomic system. Although a few recent studies reported that cognitive impairments could occur in patients with MSA, prominent dementia with progressive decline is not a typical clinical manifestation of MSA. In particular, dementia with MSA-cerebellar type is very rare. We have experienced a patient with 2-year history of severe cognitive impairment, who was finally diagnosed as MSA-cerebellar type.

  19. Cerebellar abnormalities typical of methylmercury poisoning in a fledged saltmarsh sparrow, Ammodramus caudacutus.

    Science.gov (United States)

    Scoville, Sheila A; Lane, Oksana P

    2013-05-01

    A fledged, 12-15 day-old saltmarsh sparrow, Ammodramus caudacutus, was collected from an accidental kill on Cinder Island, Long Island, NY, USA. The sparrow was assessed for feather mercury levels and the brain analyzed for cerebellar abnormalities by microscopic examination. In humans, fetal Minamata disease is caused by maternal ingestion of mercury. It is characterized by disrupted and disordered cerebellar neuronal migration in the fetus or infant. Results from this sparrow show cerebellar abnormalities typical of Minamata disease. It is the first known avian or mammalian specimen taken from the wild to show the abnormalities typical of the human fetal syndrome.

  20. Quantum Cascade Photonic Crystal lasers

    Science.gov (United States)

    Capasso, Federico

    2004-03-01

    QC lasers have emerged in recent years as the dominant laser technology for the mid-to far infrared spectrum in light of their room temperature operation, their tunability, ultrahigh speed operation and broad range of applications to chemical sensing, spectroscopy etc. (Ref. 1-3). After briefly reviewing the latter, I will describe a new class of mid-infrared QC lasers, Quantum Cascade Photonic Crystal Surface Emitting Lasers (QCPCSELS), that combine electronic and photonic band structure engineering to achieve vertical emission from the surface (Ref. 4). Devices operating on bandedge mode and on defect modes will be discussed. Exciting potential uses of these new devices exist in nonlinear optics, microfluidics as well as novel sensors. Finally a bird's eye view of other exciting areas of QC laser research will be given including broadband QCLs and new nonlinear optical sources based on multiwavelength QCLs. 1. F. Capasso, C. Gmachl, D. L. Sivco, and A. Y. Cho, Physics Today 55, 34 (May 2002) 2. F. Capasso, C. Gmachl, R. Paiella, A. Tredicucci, A. L. Hutchinson, D. L. Sivco, J. N. Baillargeon, A. Y. Cho and H. C. Liu, IEEE Journal of Selected Topics in Quantum Electronics, 6, 931 (2000). 3. F. Capasso, R. Paiella, R. Martini, R. Colombelli, C. Gmachl, T. L. Myers, M. S. Taubman, R. M. Williams, C. G. Bethea, K. Unterrainer, H. Y. Hwang, D. L. Sivco, A. Y. Cho, A. M. Sergent, H. C. Liu, E. A. Whittaker, IEEE J. Quantum Electron. 38, 511 (2002) 4. R. Colombelli, K. Srivasan, M. Troccoli, O. Painter, C. Gmachl, D. M. Tennant, A. M. Sergent, D. L. Sivco, A. Y. Cho and F. Capasso, Science 302, 1374 (2003)

  1. Trophic cascades in rocky shore tide pools: distinguishing lethal and nonlethal effects.

    Science.gov (United States)

    Trussell, Geoffrey C; Ewanchuk, Patrick J; Bertness, Mark D; Silliman, Brian R

    2004-05-01

    The effects of predators on the density of their prey can have positive indirect effects on the abundance of the prey's resource via a trophic cascade. This concept has strongly influenced contemporary views of how communities are structured. However, predators also can transmit indirect effects by inducing changes in prey traits. We show that the mere presence of predator risk cues can initiate a trophic cascade in rocky shore tide pools. In large (mean surface area =9 m2), natural tide pools, we manipulated crab density and their foraging ability to examine the relative importance of lethal (density-mediated) and non-lethal (trait-mediated) predator effects to algal community development. We found that perceived predation risk reduced snail density as much as the direct predation treatment, showing that green crab predation was not an important factor regulating local snail density. Instead, snail emigration away from resident crabs appears to be the most important factor regulating local snail density. As a result, the abundance of ephemeral green algae was similar in the predation risk and direct predation treatments, suggesting that the consumption of snails by crabs plays a minimal role in mediating the trophic cascade. Increased attention to trait-mediated effects that are transmitted by predator-induced changes in prey behavior may change our view of how predators exert their strong influence on community structure.

  2. Cerebellar and basal ganglion involvement in Langerhans cell histiocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Saatci, I.; Baskan, O.; Haliloglu, M.; Aydingoz, U. [Department of Radiology, Hacettepe University Hospital, Sihhiye 06100, Ankara (Turkey)

    1999-06-01

    Langerhans cell histiocytosis (LCH) is a disease of unknown cause characterised by proliferation of histiocytic granulomas in tissues; the primary cerebral manifestation is diabetes insipidus caused by hypothalamic infiltration. We present a patient in whom, except for the absence of high signal on T 1 weighting in the posterior pituitary, consistent with central diabetes insipidus, MRI showed no evidence of hypothalamic involvement by histiocytosis, despite the long duration of the disease. However, there was bilateral, symmetrical involvement of the cerebellum and globus pallidus in addition to a calvarial lesion. High signal in the cerebellar white matter on T 2-weighted images may represent demyelination, gliosis and cell loss, as previously reported on pathologic examination. (orig.) With 5 figs., 22 refs.

  3. [Cerebellar abscesses secondary to infection of an occipital dermal sinus].

    Science.gov (United States)

    García Galera, A; Martínez León, M I; Pérez da Rosa, S; Ros López, B

    2013-09-01

    A dermal sinus is a congenital defect arising from a closure failure of the neural tube that results in different degrees of communication between the skin and the central nervous system. A dermal sinus can occur anywhere from the root of the nose to the conus medullaris, and the occipital location is the second most common. Dermal sinuses are often found in association with dermoid or epidermoid cysts and less frequently with teratomas. Patients with an occipital dermoid cyst associated with a dermal sinus can develop meningitis and/or abscesses as the first clinical manifestation of the disease due to the dermoid cyst itself becoming abscessed or to the formation of secondary abscesses; few cases of the formation of secondary abscesses have been reported. We present a case of a dermoid cyst associated with an infected dermal sinus and posterior development of cerebellar abscesses and hydrocephalus.

  4. Middle cerebellar peduncles:Magnetic resonance imaging and pathophysiologic correlate

    Institute of Scientific and Technical Information of China (English)

    Humberto Morales; Thomas Tomsick

    2015-01-01

    We describe common and less common diseases that can cause magnetic resonance signal abnormalities of middle cerebellar peduncles(MCP), offering a systematicapproach correlating imaging findings with clinical clues and pathologic mechanisms. Myelin abnormalities, different types of edema or neurodegenerative processes, can cause areas of abnormal T2 signal, variable enhancement, and patterns of diffusivity of MCP. Pathologies such as demyelinating disorders or certain neurodegenerative entities(e.g., multiple system atrophy or fragile X-associated tremor-ataxia syndrome) appear to have predilection for MCP. Careful evaluation of concomitant imaging findings in the brain or brainstem; and focused correlation with key clinical findings such as immunosuppression for progressive multifocal leukoencephalopahty; hypertension, post-transplant status or high dose chemotherapy for posterior reversible encephalopathy; electrolyte disorders for myelinolysis or suspected toxic-drug related encephalopathy; would yield an appropriate and accurate differential diagnosis in the majority of cases.

  5. Adult cerebellar medulloblastoma: CT and MRI findings in eight cases

    Energy Technology Data Exchange (ETDEWEB)

    Carvalho Neto, Arnolfo de; Bertoldi, Guilherme A. [Parana Univ., Curitiba, PR (Brazil). Radiologia Diagnostica]. E-mail: arnolfo.carvalho@avalon.sul.com.br; Gasparetto, Emerson L. [Parana Univ., Curitiba, PR (Brazil). Hospital das Clinicas. Secao de Radiologia Diagnostica; Ono, Sergio E. [Parana Univ., Curitiba, PR (Brazil). Faculdade de Medicina; Gomes, Andre F. [Diagnostico Avancado Por Imagem (DAPI), Curitiba, PR (Brazil)

    2003-06-01

    Medulloblastoma is a brain tumor of neuro epithelial origin, which represents 15 to 30% of all pediatric brain tumors, and less than 1% of CNS adult neoplasms. We report the imaging findings of 8 adult patients with medulloblastoma. The mean age was 35 years, ranging from 20 to 65 years, and the male:female rate was 3:5. The tumors were predominantly lateral (63%), hyperdense on CT scans (83%), and on the MRI, hypointense on T1 (100%) and hyperintense on T2 (80%) weighted images. It was seen intratumoral necrosis and cysts in six cases and calcifications in three. Hydrocephalus was observed in 5 cases and brain stem invasion in four. The imaging findings of medulloblastomas in adults are different of those in child, and also nonspecific. Although these tumors are uncommon in adults, they must be considered in the differential diagnosis of cerebellar masses in the posterior fossa of this age group. (author)

  6. Consensus paper on post-operative pediatric cerebellar mutism syndrome

    DEFF Research Database (Denmark)

    Gudrunardottir, Thora; Morgan, Angela T; Lux, Andrew L

    2016-01-01

    INTRODUCTION: Confusion has surrounded the description of post-operative mutism and associated morbidity in pediatric patients with cerebellar tumors for years. The heterogeneity of definitions and diagnostic features has hampered research progress within the field, and to date, no international...... guidelines exist on diagnosis, prevention, treatment, or follow-up of this debilitating condition. An international group of clinicians and researchers from multiple relevant disciplines recently formed a cohesive panel to formulate a new working definition and agree upon standardized methods for diagnosis...... and follow-up. METHODS: Consensus was obtained using the modified nominal group technique, involving four rounds of online Delphi questionnaires interspersed with a structured consensus conference with lectures, group work, and open discussion sessions. RESULTS: A new, proposed definition of "post-operative...

  7. Cerebellar infarct with neurogenic pulmonary edema following viper bite

    Directory of Open Access Journals (Sweden)

    Salil Gupta

    2012-01-01

    Full Text Available Russell′s viper (Daboia russelli bites are well known to cause bleeding complications. However, thrombotic complications are rare. We present the case details of a female who was bitten by a Russell′s viper (Daboia russelli in her village. She then developed features of envenomation in the form of hemorrhagic episodes. She received 27 vials of polyvalent anti-snake venom to which the hemorrhagic complications responded. After about 48 h of the bite she developed features of cerebellar infarct along with pulmonary edema which was in all probability neurogenic in origin. She was managed with mechanical ventilation and extra ventricular drainage with good recovery. We discuss the likely pathogenesis of the infarct and pulmonary edema occurring in a patient with viper bite and other features of envenomation.

  8. Nerve growth factor enhances DNA synthesis in cultured cerebellar neuroblasts.

    Science.gov (United States)

    Confort, C; Charrasse, S; Clos, J

    1991-10-01

    The cerebellar neuroblasts in primary cultures from five-day-old rats bore NGF receptor immunoreactivity, suggesting a potential responsive to NGF. At low plating density, NGF was found to enhance DNA synthesis in these cells in a dose-dependent manner. As these cells synthesize NGF, one possibility to account for the lack of response of neuroblasts plated at high density is that the amount of endogenous trophic agent produced in this culture condition is sufficient to ensure an optimal effect. The results demonstrate that premitotic neuroblasts in the CNS, as well postmitotic neurons, are responsive to NGF. At the early stage of its development, the cerebellum therefore appears to be a very good autocrine model of NGF action.

  9. Cerebellar stimulation for cerebral palsy--double blind study.

    Science.gov (United States)

    Davis, R; Schulman, J; Delehanty, A

    1987-01-01

    Twenty spastic cerebral palsy (CP) patients undergoing chronic cerebellar stimulation (CCS) for reduction of spasticity and improvement in function have participated in a double-blind study. Seven US centers involving 9 neurosurgeons (1984-6) have replaced the depleted Neurolith 601 fully implantable pulse generator (Pacesetter Systems Incorp.-Neurodyne Corp., Sylmar, CA) with new units in 19 CP patients, 1 patient entered the study following his initial implant. A magnetically controllable switch was placed in line between the Neurolith stimulator and the cerebellar lead, so allowing switching sequences for the study. Physical therapists, living in the vicinity of the patient's home, carried out two quantitative evaluations: 1. Joint angle motion measurements (passive and active). 2. Motor performance testing was done when possible and included: reaction time, hand dynamonetry, grooved peg board placement, hand/foot tapping, and rotary pursuit testing. Testing was done presurgery, at 2 weeks postimplant, then the switch was activated either "on" or "off" to a schedule, with testing and reswitching at 1, 2 and 4 months, then the switch was left turned "on". Of the 20 patients, 16 finished the tests, 2 patients failed to finish and 2 had switch problems and were deleted from the study. Two of the 16 patients were "off" through the entire testing. Of the 14 that had periods of the stimulator being "on", 10 patients (72%) had quantitative improvements of over 20%, (1 pt: 50+% improvements; 4 pts: 30-50%, 5 pts: 20-30%); while 1 patient (7%) had improvements in the 10-20% level, whereas 3 patients (21%) showed no improvement.

  10. Period-doubling cascades for large perturbations of Henon families

    OpenAIRE

    Sander, Evelyn; Yorke, James A.

    2009-01-01

    The Henon family has been shown to have period-doubling cascades. We show here that the same occurs for a much larger class: Large perturbations do not destroy cascades. Furthermore, we can classify the period of a cascade in terms of the set of orbits it contains, and count the number of cascades of each period. This class of families extends a general theory explaining why cascades occur.

  11. Cerebellar Development and Plasticity: Perspectives for Motor Coordination Strategies, for Motor Skills, and for Therapy

    Directory of Open Access Journals (Sweden)

    J. D. Swinny

    2005-01-01

    Full Text Available The role of the mammalian cerebellum ranges from motor coordination, sensory-motor integration, motor learning, and timing to nonmotor functions such as cognition. In terms of motor function, the development of the cerebellum is of particular interest because animal studies show that the development of the cerebellar cortical circuitry closely parallels motor coordination. Ultrastructural analysis of the morphological development of the cerebellar circuitry, coupled with the temporal and spatial identification of the neurochemical substrates expressed during development, will help to elucidate their roles in the establishment of the cerebellar circuitry and hence motor activity. Furthermore, the convenience of a number of naturally occurring mouse mutations has allowed a functional dissection of the various cellular elements that make up the cerebellar circuitry. This understanding will also help in the approach to possible therapies of pathologies arising during development because tile cerebellum is especially prone to such perturbation because of its late development.

  12. Effects of drotaverine hydrochloride on viability of rat cultured cerebellar granulocytes.

    Science.gov (United States)

    Demushkin, V P; Zhavoronkova, E V; Khaspekov, L G

    2012-02-01

    The neurocytotoxic effect of drotaverine hydrochloride was studied in culture of rat cerebellar granulocytes. Incubation of cells with 100 and 250 μM drotaverine reduced neuronal survival to 60 and 4%, respectively.

  13. Uneven distribution of NG2 cells in the rat cerebellar vermis and changes in aging

    Directory of Open Access Journals (Sweden)

    S. Lomoio

    2012-06-01

    Full Text Available We describe by NG2 (neuron-glia chondroitin sulphate proteoglycan 2 immunocytochemistry an uneven distribution of NG2 glial cells in the rat cerebellum, being them more represented in the central lobules of the cerebellar vermis, belonging to the cerebrocerebellum. The cerebellar distribution of NG2 cells changes in aging rats, in which the area where the cells appear to be densely scattered throughout all cerebellar layers involves also more rostral and caudal lobules. In addition, in aging rats, in the most rostral and caudal lobules belonging to the spinocerebellum, punctate reaction product is present at the apical pole of Purkinje cells, i.e. in the area where the majority of synapses between olivary climbing fibers and Purkinje cells occur. Data suggest that the different distribution of NG2 cells is correlated to differences in physiology among cerebellar areas and reflects changes during aging.

  14. Post-traumatic cerebellar infarction due to vertebral artery foramina fracture: case report

    Directory of Open Access Journals (Sweden)

    Moscote-Salazar Luis Rafael

    2016-03-01

    Full Text Available Posttraumatic cerebral infarction is an uncommon cause of morbidity and mortality and many studies have highlighted that trauma needs to considered as causative factor for cerebellar infarction. We present a case of cerebellar infarction in a 35 year old young patient secondary to vertebral fracture involving the vertebral foramen and vertebral artery injury. CT scan cervical spine showed C2-3 fracture on left side with fracture extending into the left vertebral foramen. A CT scan angiogram could not be performed because of poor neurological status. Possibly the infarction was due to left vertebral artery injury. Without surgical intervention prognosis of these patients remain poor. Prognosis of patients with traumatic cerebellar infarction depends on the neurological status of the patient, intrinsic parenchymal damage and more importantly extrinsic compression of the brainstem by the edematous cerebellar hemispheres.

  15. Evolving Models of Pavlovian Conditioning : Cerebellar Cortical Dynamics in Awake Behaving Mice

    NARCIS (Netherlands)

    Ten Brinke, Michiel M; Boele, Henk-Jan; Spanke, Jochen K; Potters, Jan-Willem; Kornysheva, Katja; Wulff, Peer; IJpelaar, Anna C H G; Koekkoek, Sebastiaan K E; De Zeeuw, Chris I

    2015-01-01

    Three decades of electrophysiological research on cerebellar cortical activity underlying Pavlovian conditioning have expanded our understanding of motor learning in the brain. Purkinje cell simple spike suppression is considered to be crucial in the expression of conditional blink responses (CRs).

  16. A case of cerebellar dysarthria as the presenting symptom of HIV infection.

    Science.gov (United States)

    Siddiqi, Zeba; Karoli, Ritu; Fatima, Jalees; Dey, Rahul; Kazmi, Khursheed

    2014-08-01

    A 37 year old man presented with progressive dysarthria for 2 weeks. A week later he developed ataxia and bilateral cerebellar signs including intention tremors, dysmetria and dysdiadokokinesia. During evaluation for aetiology of cerebellar dysarthria, MRI brain revealed asymmetric altered signal intensities in bilateral cerebellar hemispheres and right side of pons suggesting demyelinating lesions. ELISA for Human Immune Deficiency virus-1 was positive. We kept a presumptive diagnosis of Progressive Multifocal Leukoencephalopathy (PML) on the basis of clinico-radiological picture. PML is an under investigated and under diagnosed CNS infection seen in HIV patients with advanced disease. We present an unusual case report where isolated cerebellar involvement occurred as the first AIDS defining event in the absence of appreciable immunodeficiency in a patient with previously undiagnosed HIV infection.

  17. Uneven distribution of NG2 cells in the rat cerebellar vermis and changes in aging

    Science.gov (United States)

    Lomoio, S.; Necchi, D.; Scherini, E.

    2012-01-01

    We describe by NG2 (neuron-glia chondroitin sulphate proteoglycan 2) immunocytochemistry an uneven distribution of NG2 glial cells in the rat cerebellum, being them more represented in the central lobules of the cerebellar vermis, belonging to the cerebrocerebellum. The cerebellar distribution of NG2 cells changes in aging rats, in which the area where the cells appear to be densely scattered throughout all cerebellar layers involves also more rostral and caudal lobules. In addition, in aging rats, in the most rostral and caudal lobules belonging to the spinocerebellum, punctate reaction product is present at the apical pole of Purkinje cells, i.e. in the area where the majority of synapses between olivary climbing fibers and Purkinje cells occur. Data suggest that the different distribution of NG2 cells is correlated to differences in physiology among cerebellar areas and reflects changes during aging. PMID:23027343

  18. A PET study of cerebellar metabolism in normal and abnormal states

    Energy Technology Data Exchange (ETDEWEB)

    Kushner, M.; Alavi, A.; Chawluk, J.; Silver, F.; Dann, R.; Rosen, M.; Reivich, M.

    1985-05-01

    The authors studied cerebellar metabolism under varying conditions of sensory stimulation. Cerebellar glucose consumption was measured by positron emission scanning and 18F-fluorodeoxyglucose in 64 subjects. Cerebellar metabolism relative to the whole brain (CM), and the asymmetry of metabolism between the cerebellar hemispheres (CA) was determined. The lowest CM occurred with maximal sensory deprivation, eyes and ears closed, (CM=96%, n=6). CM increased nonsignificantly with visual stimulation (CM=99%,n=17) and was highest for auditory stimulation (CM=104%,n=10,p<.05). CA was unaffected by sensory input. Under ambient conditions the CM values were 101%, 113% and 135% respectively for young controls (n=9, age=22), old controls (n=8, age=61) and Alzheimer patients (SDAT, n=14, age=69). This difference was significant for SDAT vs young and old controls and was nearly significant for young vs old controls.

  19. Changes in cerebro-cerebellar interaction during response inhibition after performance improvement.

    Science.gov (United States)

    Hirose, Satoshi; Jimura, Koji; Kunimatsu, Akira; Abe, Osamu; Ohtomo, Kuni; Miyashita, Yasushi; Konishi, Seiki

    2014-10-01

    It has been demonstrated that motor learning is supported by the cerebellum and the cerebro-cerebellar interaction. Response inhibition involves motor responses and the higher-order inhibition that controls the motor responses. In this functional MRI study, we measured the cerebro-cerebellar interaction during response inhibition in two separate days of task performance, and detected the changes in the interaction following performance improvement. Behaviorally, performance improved in the second day, compared to the first day. The psycho-physiological interaction (PPI) analysis revealed the interaction decrease from the right inferior frontal cortex (rIFC) to the cerebellum (lobule VII or VI). It was also revealed that the interaction increased from the same cerebellar region to the primary motor area. These results suggest the involvement of the cerebellum in response inhibition, and raise the possibility that the performance improvement was supported by the changes in the cerebro-cerebellar interaction.

  20. Intracellular correlates of acquisition and long-term memory of classical conditioning in Purkinje cell dendrites in slices of rabbit cerebellar lobule HVI.

    Science.gov (United States)

    Schreurs, B G; Gusev, P A; Tomsic, D; Alkon, D L; Shi, T

    1998-07-15

    Intradendritic recordings in Purkinje cells from a defined area in parasaggital slices of cerebellar lobule HVI, obtained after rabbits were given either paired (classical conditioning) or explicitly unpaired (control) presentations of tone and periorbital electrical stimulation, were used to assess the nature and duration of conditioning-specific changes in Purkinje cell dendritic membrane excitability. We found a strong relationship between the level of conditioning and Purkinje cell dendritic membrane excitability after initial acquisition of the conditioned response. Moreover, conditioning-specific increases in Purkinje cell excitability were still present 1 month after classical conditioning. Although dendritically recorded membrane potential, input resistance, and amplitude of somatic and dendritic spikes were not different in cells from paired or control animals, the size of a potassium channel-mediated transient hyperpolarization was significantly smaller in cells from animals that received classical conditioning. In slices of lobule HVI obtained from naive rabbits, the conditioning-related increases in membrane excitability could be mimicked by application of potassium channel antagonist tetraethylammonium chloride, iberiotoxin, or 4-aminopyridine. However, only 4-aminopyridine was able to reduce the transient hyperpolarization. The pharmacological data suggest a role for potassium channels and, possibly, channels mediating an IA-like current, in learning-specific changes in membrane excitability. The conditioning-specific increase in Purkinje cell dendritic excitability produces an afterhyperpolarization, which is hypothesized to release the cerebellar deep nuclei from inhibition, allowing conditioned responses to be elicited via the red nucleus and accessory abducens motorneurons.

  1. A case report of patient with cerebellar variant of stiff person syndrome.

    Science.gov (United States)

    Maludzińska, Ewa; Rudzińska, Monika; Stępień, Artur; Szczudlik, Andrzej

    2016-01-01

    Stiff person syndrome (SPS) is a rare autoimmune neurological disorder with antibodies against antigens involved in neurotransmission of gamma-aminobutyric acid (GABA). About 10% of patients with SPS may develop ataxia. This cerebellar variant is a distinct subset of SPS with more severe and complex clinical phenotype. We report the clinical, neuropsychological and neuroradiological findings in a 39-year-old female with cerebellar variant of SPS.

  2. Cerebellar Lesions of Uremic Encephalopathy on MRI in Hemodialyzed Diabetic Patient: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kil, Min Chul; Lee, Seung Young; Cha, Sang Hoon; Cho, Bum Sang; Kang, Min Ho [Dept. of Radiology, Chungbuk National Universty Hospital, Cheongju (Korea, Republic of)

    2012-01-15

    Uremic encephalopathy (UE) is a well-known complication of uremia, but its pathophysiology remains unknown. It is widely reported that in UE, the bilateral basal ganglia (BG) shows hyperintensities on T2/fluid attenuated inversion recovery magnetic resonance imaging (MRI), but cerebellar lesions are extremely rare, with to the best of our knowledge, only one case reported to date. We describe the findings from computed tomography and MRI for typical BG and cerebellar vermis lesions.

  3. Encephalitis due to antibodies to voltage gated potassium channel (VGKC with cerebellar involvement in a teenager

    Directory of Open Access Journals (Sweden)

    Megan M Langille

    2015-01-01

    Full Text Available Encephalitis due to antibodies to voltage gated potassium channel (VGKC typically presents with limbic encephalitis and medial temporal lobe involvement on neuroimaging. We describe a case of 13 year girl female with encephalitis due to antibodies to VGKC with signal changes in the cerebellar dentate nuclei bilaterally and clinical features that suggested predominant cerebellar involvement. These have never been reported previously in the literature. Our case expands the phenotypic spectrum of this rare condition.

  4. Encephalitis due to antibodies to voltage gated potassium channel (VGKC) with cerebellar involvement in a teenager.

    Science.gov (United States)

    Langille, Megan M; Desai, Jay

    2015-01-01

    Encephalitis due to antibodies to voltage gated potassium channel (VGKC) typically presents with limbic encephalitis and medial temporal lobe involvement on neuroimaging. We describe a case of 13 year girl female with encephalitis due to antibodies to VGKC with signal changes in the cerebellar dentate nuclei bilaterally and clinical features that suggested predominant cerebellar involvement. These have never been reported previously in the literature. Our case expands the phenotypic spectrum of this rare condition.

  5. A Turkish newborn infant with cerebellar agenesis/neonatal diabetes mellitus and PTF1A mutation.

    Science.gov (United States)

    Tutak, E; Satar, M; Yapicioğlu, H; Altintaş, A; Narli, N; Hergüner, O; Bayram, Y

    2009-01-01

    Classical neonatal diabetes mellitus is defined as hyperglycemia that occurs within the first month of life in term infants. It can be either permanent or transient. Cerebellar agenesis and permanent neonatal diabetes has been previously reported as a new autosomal recessive disorder. Pancreas Transcription Factor 1 Alpha (PTF1A) mutations have been related with this constellation of abnormalities. Here we report a new case of cerebellar agenesis and neonatal diabetes mellitus whose parents are PTF1A mutation carriers.

  6. Cerebellar involvement that occurred during treatment of Legionella pneumonia: A case report

    Directory of Open Access Journals (Sweden)

    Ozlem Alici

    2013-06-01

    Full Text Available Legionnaires’ disease can appear with different levels of severity. A case of a previously healthy lady with communityacquiredpneumonia who progressed to severe acute respiratory distress syndrome and developed cerebellar dysfunctionis reported. In patients presenting with neurological symptoms after an episode of pneumonia, Legionella infectionshould be considered. J Microbiol Infect Dis 2013; 3(2: 83-85Key words: Legionella, cerebellar dysfunction, dysarthria, ataxia

  7. Post-traumatic cerebellar infarction due to vertebral artery foramina fracture: case report

    OpenAIRE

    Moscote-Salazar Luis Rafael; Rubiano Andres M.; Calderon-Miranda Willem Guillermo; Agrawal Amit

    2016-01-01

    Posttraumatic cerebral infarction is an uncommon cause of morbidity and mortality and many studies have highlighted that trauma needs to considered as causative factor for cerebellar infarction. We present a case of cerebellar infarction in a 35 year old young patient secondary to vertebral fracture involving the vertebral foramen and vertebral artery injury. CT scan cervical spine showed C2-3 fracture on left side with fracture extending into the left vertebral foramen. A CT scan angiogram c...

  8. Cerebellar Development and Plasticity: Perspectives for Motor Coordination Strategies, for Motor Skills, and for Therapy

    OpenAIRE

    Swinny, J. D; van der Want, J.J.L.; Gramsbergen, A.

    2005-01-01

    The role of the mammalian cerebellum ranges from motor coordination, sensory-motor integration, motor learning, and timing to nonmotor functions such as cognition. In terms of motor function, the development of the cerebellum is of particular interest because animal studies show that the development of the cerebellar cortical circuitry closely parallels motor coordination. Ultrastructural analysis of the morphological development of the cerebellar circuitry, coupled with the temporal and spat...

  9. The complement cascade in kidney disease: from sideline to center stage.

    Science.gov (United States)

    McCaughan, Jennifer A; O'Rourke, Declan M; Courtney, Aisling E

    2013-09-01

    Activation of the complement pathway is implicated in the pathogenesis of many kidney diseases. The pathologic and clinical features of these diseases are determined in part by the mechanism and location of complement activation within the kidney parenchyma. This review describes the physiology, action, and control of the complement cascade and explains the role of complement overactivation and dysregulation in kidney disease. There have been recent advances in the understanding of the effects of upregulation of the complement cascade after kidney transplantation. Complement plays an important role in initiating and propagating damage to transplanted kidneys in ischemia-reperfusion injury, antibody-mediated rejection, and cell-mediated rejection. Complement-targeting therapies presently are in development, and the first direct complement medication for kidney disease was licensed in 2011. The potential therapeutic targets for anticomplement drugs in kidney disease are described. Clinical and experimental studies are ongoing to identify further roles for complement-targeting therapy.

  10. Cascade reactions catalyzed by metal organic frameworks.

    Science.gov (United States)

    Dhakshinamoorthy, Amarajothi; Garcia, Hermenegildo

    2014-09-01

    Cascade or tandem reactions where two or more individual reactions are carried out in one pot constitute a clear example of process intensification, targeting the maximization of spatial and temporal productivity with mobilization of minimum resources. In the case of catalytic reactions, cascade processes require bi-/multifunctional catalysts that contain different classes of active sites. Herein, we show that the features and properties of metal-organic frameworks (MOFs) make these solids very appropriate materials for the development of catalysts for cascade reactions. Due to composition and structure, MOFs can incorporate different types of sites at the metal nodes, organic linkers, or at the empty internal pores, allowing the flexible design and synthesis of multifunctional catalysts. After some introductory sections on the relevance of cascade reactions from the point of view of competitiveness, sustainability, and environmental friendliness, the main part of the text provides a comprehensive review of the literature reporting the use of MOFs as heterogeneous catalysts for cascade reactions including those that combine in different ways acid/base, oxidation/reduction, and metal-organic centers. The final section summarizes the current state of the art, indicating that the development of a first commercial synthesis of a high-added-value fine chemical will be a crucial milestone in this area.

  11. Intra-cerebellar infusion of the protein kinase Mzeta (PKMζ) inhibitor ZIP disrupts eyeblink classical conditioning

    Science.gov (United States)

    Chihabi, Kutibh; Morielli, Anthony D.; Green, John T.

    2016-01-01

    PKM-ζ, a constitutively active N-terminal truncated form of PKC-ζ, has long been implicated in a cellular correlate of learning, long-term potentiation (LTP). Inhibition of PKM-ζ with Zeta-inhibitory peptide (ZIP) has been shown in many brain structures to disrupt maintenance of AMPA receptors, irreversibly disrupting numerous forms of learning and memory that have been maintained for weeks. Delay eyeblink conditioning (EBC) is an established model for the assessment of cerebellar learning; here, we show that PKC-ζ and PKM-ζ are highly expressed in the cerebellar cortex, with highest expression found in Purkinje cell (PC) nuclei. Despite being highly expressed in the cerebellar cortex, no studies have examined how regulation of cerebellar PKM-ζ may affect cerebellar-dependent learning and memory. Given its disruption of learning in other brain structures, we hypothesized that ZIP would also disrupt delay EBC. We have shown that infusion of ZIP into the lobulus simplex of the rat cerebellar cortex can indeed significantly disrupt delay EBC. PMID:26949968

  12. Adaptive control of 2-wheeled balancing robot by cerebellar neuronal network model.

    Science.gov (United States)

    Tanaka, Yoshiyuki; Ohata, Yohei; Kawamoto, Tomohiro; Hirata, Yutaka

    2010-01-01

    A new adaptive motor controller was constructed, and tested on the control of a 2-wheeled balancing robot in simulation and real world. The controller consists of a feedback (PD) controller and a cerebellar neuronal network model. The structure of the cerebellar model was configured based upon known anatomical neuronal connection in the cerebellar cortex. Namely it consists of 120 granular (Gr) cells, 1 Golgi cell, 6 basket/stellate cells, and 1 Purkinje (Pk) cell. Each cell is described by a typical artificial neuron model that outputs a weighted sum of inputs after a sigmoidal nonlinear transformation. The 2 components of the proposed controller work in parallel, in a way that the cerebellar model adaptively modifies the synaptic weights between Gr and Pk as in the real cerebellum to minimize the output of the PD controller. We demonstrate that the proposed controller successfully controls a 2-wheeled balancing robot, and the cerebellar model rapidly takes over the PD controller in simulation. We also show that an abrupt load change on the robot, which the PD controller alone cannot compensate for, can be adaptively compensated by the cerebellar model. We further confirmed that the proposed controller can be applied to the control of the robot in real world.

  13. TERRA INCOGNITA - CEREBELLAR CONTRIBUTIONS TO NEUROPSYCHIATRIC AND COGNITIVE DYSFUNCTION IN BEHAVIOURAL VARIANT FRONTOTEMPORAL DEMENTIA

    Directory of Open Access Journals (Sweden)

    Rachel H Tan

    2015-07-01

    Full Text Available Although converging evidence has positioned the human cerebellum as an important relay for intact cognitive and neuropsychiatric processing, changes in this large structure remain mostly overlooked in behavioural variant frontotemporal dementia (bvFTD, a disease which is characterized by cognitive and neuropsychiatric deficits. The present study assessed whether degeneration in specific cerebellar subregions associate with indices of cognition and neuropsychiatric performance in bvFTD. Our results demonstrate a relationship between cognitive and neuropsychiatric decline across various domains of memory, language, emotion, executive, visuospatial function and motivation and the degree of grey matter degeneration in cerebellar lobules V-VII. Most notably, bilateral cerebellar lobule VII and the posterior vermis emerged as distinct for memory processes, the right cerebellar hemisphere underpinned emotion, and the posterior vermis was highlighted in language dysfunction in bvFTD. Based on cortico-cerebellar connectivity maps, these findings in the cerebellum are consistent with the neural connections with the cortices involved in these domains in patients with bvFTD. Overall, the present study underscores the significance of cortical-cerebellar networks associated with cognition and neuropsychiatric dysfunction in bvFTD.

  14. Integrated plasticity at inhibitory and excitatory synapses in the cerebellar circuit

    Directory of Open Access Journals (Sweden)

    Lisa eMapelli

    2015-05-01

    Full Text Available The way long-term potentiation (LTP and depression (LTD are integrated within the different synapses of brain neuronal circuits is poorly understood. In order to progress beyond the identification of specific molecular mechanisms, a system in which multiple forms of plasticity can be correlated with large-scale neural processing is required. In this paper we take as an example the cerebellar network , in which extensive investigations have revealed LTP and LTD at several excitatory and inhibitory synapses. Cerebellar LTP and LTD occur in all three main cerebellar subcircuits (granular layer, molecular layer, deep cerebellar nuclei and correspondingly regulate the function of their three main neurons: granule cells (GrCs, Purkinje cells (PCs and deep cerebellar nuclear (DCN cells. All these neurons, in addition to be excited, are reached by feed-forward and feed-back inhibitory connections, in which LTP and LTD may either operate synergistically or homeostatically in order to control information flow through the circuit. Although the investigation of individual synaptic plasticities in vitro is essential to prove their existence and mechanisms, it is insufficient to generate a coherent view of their impact on network functioning in vivo. Recent computational models and cell-specific genetic mutations in mice are shedding light on how plasticity at multiple excitatory and inhibitory synapses might regulate neuronal activities in the cerebellar circuit and contribute to learning and memory and behavioral control.

  15. Electron tomographic structure and protein composition of isolated rat cerebellar, hippocampal and cortical postsynaptic densities.

    Science.gov (United States)

    Farley, M M; Swulius, M T; Waxham, M N

    2015-09-24

    Electron tomography and immunogold labeling were used to analyze similarities and differences in the morphology and protein composition of postsynaptic densities (PSDs) isolated from adult rat cerebella, hippocampi, and cortices. There were similarities in physical dimensions and gross morphology between cortical, hippocampal and most cerebellar PSDs, although the morphology among cerebellar PSDs could be categorized into three distinct groups. The majority of cerebellar PSDs were composed of dense regions of protein, similar to cortical and hippocampal PSDs, while others were either composed of granular or lattice-like protein regions. Significant differences were found in protein composition and organization across PSDs from the different brain regions. The signaling protein, βCaMKII, was found to be a major component of each PSD type and was more abundant than αCaMKII in both hippocampal and cerebellar PSDs. The scaffold molecule PSD-95, a major component of cortical PSDs, was found absent in a fraction of cerebellar PSDs and when present was clustered in its distribution. In contrast, immunogold labeling for the proteasome was significantly more abundant in cerebellar and hippocampal PSDs than cortical PSDs. Together, these results indicate that PSDs exhibit remarkable diversity in their composition and morphology, presumably as a reflection of the unique functional demands placed on different synapses.

  16. Integrated plasticity at inhibitory and excitatory synapses in the cerebellar circuit.

    Science.gov (United States)

    Mapelli, Lisa; Pagani, Martina; Garrido, Jesus A; D'Angelo, Egidio

    2015-01-01

    The way long-term potentiation (LTP) and depression (LTD) are integrated within the different synapses of brain neuronal circuits is poorly understood. In order to progress beyond the identification of specific molecular mechanisms, a system in which multiple forms of plasticity can be correlated with large-scale neural processing is required. In this paper we take as an example the cerebellar network, in which extensive investigations have revealed LTP and LTD at several excitatory and inhibitory synapses. Cerebellar LTP and LTD occur in all three main cerebellar subcircuits (granular layer, molecular layer, deep cerebellar nuclei) and correspondingly regulate the function of their three main neurons: granule cells (GrCs), Purkinje cells (PCs) and deep cerebellar nuclear (DCN) cells. All these neurons, in addition to be excited, are reached by feed-forward and feed-back inhibitory connections, in which LTP and LTD may either operate synergistically or homeostatically in order to control information flow through the circuit. Although the investigation of individual synaptic plasticities in vitro is essential to prove their existence and mechanisms, it is insufficient to generate a coherent view of their impact on network functioning in vivo. Recent computational models and cell-specific genetic mutations in mice are shedding light on how plasticity at multiple excitatory and inhibitory synapses might regulate neuronal activities in the cerebellar circuit and contribute to learning and memory and behavioral control.

  17. VAMP-2, SNAP-25A/B and syntaxin-1 in glutamatergic and GABAergic synapses of the rat cerebellar cortex

    Directory of Open Access Journals (Sweden)

    Benagiano Vincenzo

    2011-11-01

    Full Text Available Abstract Background The aim of this study was to assess the distribution of key SNARE proteins in glutamatergic and GABAergic synapses of the adult rat cerebellar cortex using light microscopy immunohistochemical techniques. Analysis was made of co-localizations of vGluT-1 and vGluT-2, vesicular transporters of glutamate and markers of glutamatergic synapses, or GAD, the GABA synthetic enzyme and marker of GABAergic synapses, with VAMP-2, SNAP-25A/B and syntaxin-1. Results The examined SNARE proteins were found to be diffusely expressed in glutamatergic synapses, whereas they were rarely observed in GABAergic synapses. However, among glutamatergic synapses, subpopulations which did not contain VAMP-2, SNAP-25A/B and syntaxin-1 were detected. They included virtually all the synapses established by terminals of climbing fibres (immunoreactive for vGluT-2 and some synapses established by terminals of parallel and mossy fibres (immunoreactive for vGluT-1, and for vGluT-1 and 2, respectively. The only GABA synapses expressing the SNARE proteins studied were the synapses established by axon terminals of basket neurons. Conclusion The present study supplies a detailed morphological description of VAMP-2, SNAP-25A/B and syntaxin-1 in the different types of glutamatergic and GABAergic synapses of the rat cerebellar cortex. The examined SNARE proteins characterize most of glutamatergic synapses and only one type of GABAergic synapses. In the subpopulations of glutamatergic and GABAergic synapses lacking the SNARE protein isoforms examined, alternative mechanisms for regulating trafficking of synaptic vesicles may be hypothesized, possibly mediated by different isoforms or homologous proteins.

  18. Always around, never the same: Pathways of amyloid beta induced neurodegeneration throughout the pathogenic cascade of Alzheimer's disease

    NARCIS (Netherlands)

    J.J.M. Hoozemans; S.M. Chafekar; F. Baas; P. Eikelenboom; W. Scheper

    2006-01-01

    There is an increasing amount of evidence showing the importance of intermediate aggregation species of amyloid beta (A beta) in the pathogenic cascade of Alzheimer's disease (AD). Different A beta assembly forms may mediate diverse toxic effects at different stages of the disease. Mouse models for

  19. Emergence of event cascades in inhomogeneous networks

    CERN Document Server

    Onaga, Tomokatsu

    2016-01-01

    There is a commonality among contagious diseases, tweets, urban crimes, nuclear reactions, and neuronal firings that past events facilitate the future occurrence of events. The spread of events has been extensively studied such that the systems exhibit catastrophic chain reactions if the interaction represented by the ratio of reproduction exceeds unity; however, their subthreshold states for the case of the weaker interaction are not fully understood. Here, we report that these systems are possessed by nonstationary cascades of event-occurrences already in the subthreshold regime. Event cascades can be harmful in some contexts, when the peak-demand causes vaccine shortages, heavy traffic on communication lines, frequent crimes, or large fluctuations in nuclear reactions, but may be beneficial in other contexts, such that spontaneous activity in neural networks may be used to generate motion or store memory. Thus it is important to comprehend the mechanism by which such cascades appear, and consider controlli...

  20. Epidemic and Cascading Survivability of Complex Networks

    CERN Document Server

    Manzano, Marc; Ripoll, Jordi; Fagertun, Anna Manolova; Torres-Padrosa, Victor; Pahwa, Sakshi; Scoglio, Caterina

    2014-01-01

    Our society nowadays is governed by complex networks, examples being the power grids, telecommunication networks, biological networks, and social networks. It has become of paramount importance to understand and characterize the dynamic events (e.g. failures) that might happen in these complex networks. For this reason, in this paper, we propose two measures to evaluate the vulnerability of complex networks in two different dynamic multiple failure scenarios: epidemic-like and cascading failures. Firstly, we present \\emph{epidemic survivability} ($ES$), a new network measure that describes the vulnerability of each node of a network under a specific epidemic intensity. Secondly, we propose \\emph{cascading survivability} ($CS$), which characterizes how potentially injurious a node is according to a cascading failure scenario. Then, we show that by using the distribution of values obtained from $ES$ and $CS$ it is possible to describe the vulnerability of a given network. We consider a set of 17 different compl...