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Sample records for acute cerebellar slices

  1. Acute cerebellar ataxia

    MedlinePlus

    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. Fingolimod Attenuates Splenocyte-Induced Demyelination in Cerebellar Slice Cultures

    PubMed Central

    Pritchard, Adam J.; Mir, Anis K.; Dev, Kumlesh K.

    2014-01-01

    The family of sphingosine-1-phosphate receptors (S1PRs) is G-protein-coupled, comprised of subtypes S1PR1-S1PR5 and activated by the endogenous ligand S1P. The phosphorylated version of Fingolimod (pFTY720), an oral therapy for multiple sclerosis (MS), induces S1PR1 internalisation in T cells, subsequent insensitivity to S1P gradients and sequestering of these cells within lymphoid organs, thus limiting immune response. S1PRs are also expressed in neuronal and glial cells where pFTY720 is suggested to directly protect against lysolecithin-induced deficits in myelination state in organotypic cerebellar slices. Of note, the effect of pFTY720 on immune cells already migrated into the CNS, prior to treatment, has not been well established. We have previously found that organotypic slice cultures do contain immune cells, which, in principle, could also be regulated by pFTY720 to maintain levels of myelin. Here, a mouse organotypic cerebellar slice and splenocyte co-culture model was thus used to investigate the effects of pFTY720 on splenocyte-induced demyelination. Spleen cells isolated from myelin oligodendrocyte glycoprotein immunised mice (MOG-splenocytes) or from 2D2 transgenic mice (2D2-splenocytes) both induced demyelination when co-cultured with mouse organotypic cerebellar slices, to a similar extent as lysolecithin. As expected, in vivo treatment of MOG-immunised mice with FTY720 inhibited demyelination induced by MOG-splenocytes. Importantly, in vitro treatment of MOG- and 2D2-splenocytes with pFTY720 also attenuated demyelination caused by these cells. In addition, while in vitro treatment of 2D2-splenocytes with pFTY720 did not alter cell phenotype, pFTY720 inhibited the release of the pro-inflammatory cytokines such as interferon gamma (IFNγ) and interleukin 6 (IL6) from these cells. This work suggests that treatment of splenocytes by pFTY720 attenuates demyelination and reduces pro-inflammatory cytokine release, which likely contributes to enhanced

  3. Asymptomatic cerebellar atrophy after acute enteroviral encephalitis.

    PubMed

    Vitaszil, Edina; Kamondi, Anita; Csillik, Anita; Velkey, Imre; Szirmai, Imre

    2005-07-01

    We report on a 13-year-old male who had acute enteroviral encephalitis causing cerebellar symptoms at the age of 10 years. Magnetic resonance imaging (MRI) showed no abnormalities. Clinically he appeared to be recovered completely after 6 months. Twenty-three months after the recovery, MRI was performed because he presented with slight lower-limb and truncal ataxia experienced as lack of foot coordination while playing football or riding a bicycle. MRI demonstrated severe cerebellar atrophy. Clinically he recovered completely in 10 days. Only sophisticated electrophysiological methods revealed cerebellar dysfunction. The case provides evidence for the plasticity of cerebellar regulatory structures involved in the coordination of fine movements. It seems that in childhood the slow, isolated disintegration of cerebellar systems can be compensated for by upper thalamic or telencephalic connections, in a similar way to a congenital deficit of the cerebellum. PMID:15991870

  4. Orthostatic hypotension in acute cerebellar infarction.

    PubMed

    Kim, Hyun-Ah; Lee, Hyung

    2016-01-01

    To investigate the frequency and pattern of orthostatic hypotension (OH) associated with acute isolated cerebellar infarction, and to identify the cerebellar structure(s) potentially responsible for OH, 29 patients (mean age 60.0) with acute isolated cerebellar infarction performed a standard battery of autonomic function tests including the head up tilt test using Finapres for recording of the beat-to-beat BP response during the acute period. Cerebellar infarction related OH was defined as fall in BP (>20 mmHg systolic BP) on tilting in patients without any disease(s) that could potentially cause autonomic dysfunction, or in patients who had a potential cause of autonomic dysfunction, but showed the absence of OH during a follow-up test. The severity and distribution of autonomic dysfunction were measured by the composite autonomic severity score (CASS). Nine patients (31 %) had OH (range 24-53 mmHg) on tilting during the acute period. Most patients (7/9) had a remarkable decrement in systolic BP immediately upon tilting, but OH rapidly normalized. Mean of maximal decrease in systolic BP during head up tilt test was 37.0 mmHg. The OH group showed mild autonomic dysfunctions (CASS, 3.7) with adrenergic sympathetic dysfunction appearing as the most common abnormality. Lesion subtraction analyses revealed that damage to the medial part of the superior semilunar lobule (Crus I) and tonsil was more frequent in OH group compared to non-OH group. Cerebellar infarction may cause a brief episode of OH. The medial part of the superior semilunar lobule and tonsil may participate in regulating the early BP response during orthostasis. PMID:26530504

  5. Extending the viability of acute brain slices.

    PubMed

    Buskila, Yossi; Breen, Paul P; Tapson, Jonathan; van Schaik, André; Barton, Matthew; Morley, John W

    2014-01-01

    The lifespan of an acute brain slice is approximately 6-12 hours, limiting potential experimentation time. We have designed a new recovery incubation system capable of extending their lifespan to more than 36 hours. This system controls the temperature of the incubated artificial cerebral spinal fluid (aCSF) while continuously passing the fluid through a UVC filtration system and simultaneously monitoring temperature and pH. The combination of controlled temperature and UVC filtering maintains bacteria levels in the lag phase and leads to the dramatic extension of the brain slice lifespan. Brain slice viability was validated through electrophysiological recordings as well as live/dead cell assays. This system benefits researchers by monitoring incubation conditions and standardizing this artificial environment. It further provides viable tissue for two experimental days, reducing the time spent preparing brain slices and the number of animals required for research. PMID:24930889

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

    PubMed

    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 (p<0.05 cluster-corrected). Remitted patients exhibited bilaterally increased area IX volume. 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. PMID:27321187

  7. [Residual cerebellar ataxia following acute phenytoin intoxication].

    PubMed

    Awada, A; Amene, P; al Jumah, M; al Beladi, K

    1999-04-01

    A 30-year-old man was given high doses of phenytoin together with 4 antituberculous drugs for a seizure associated with a probable brain tuberculoma. He developed hepatic toxicity and his serum phenytoin reached the high level of 298 mumol/l (therapeutic range 40-79 mumol/l). All drugs were stopped and the biological parameters returned progressively to normal over the next 15 days. However, he remained with a cerebellar axial syndrome and was still severely ataxic 2 months later. Brain CT and MRI showed mild cerebellar atrophy. This case and the few other published ones, together with some recent experimental data, show that high doses of phenytoin can be toxic to the cerebellar cortical cells. The rarity of similar cases, while millions of epileptics are under phenytoin treatment, would however suggest that individual susceptibility may play a role in this toxicity. PMID:10367328

  8. Verb Generation in Children and Adolescents with Acute Cerebellar Lesions

    ERIC Educational Resources Information Center

    Frank, B.; Schoch, B.; Hein-Kropp, C.; Dimitrova, A.; Hovel, M.; Ziegler, W.; Gizewski, E. R.; Timmann, D.

    2007-01-01

    The aim of the present study was to examine verb generation in a larger group of children and adolescents with acute focal lesions of the cerebellum. Nine children and adolescents with cerebellar tumours participated. Subjects were tested a few days after tumour surgery. For comparison, a subgroup was tested also 1 or 2 days before surgery. None…

  9. Rapid manifestation of reactive astrogliosis in acute hippocampal brain slices

    PubMed Central

    Takano, Takahiro; He, Wei; Han, Xiaoning; Wang, Fushun; Xu, Qiwu; Wang, Xiaohai; Oberheim Bush, Nancy Ann; Cruz, Nancy; Dienel, Gerald A.; Nedergaard, Maiken

    2014-01-01

    A flurry of studies over the past decade has shown that astrocytes play a more active role in neural function than previously recognized. Hippocampal slices prepared from young rodent pups have served as a popular model for studying the pathways by which astrocytes participate in synaptic transmission. It is, however, not known how well astrocytes tolerate traumatic injury and hypoxia, which are unavoidable when preparing acute slices. We here show that astrocytes exhibit striking changes in expression of several receptors and structural proteins, including re-expression of the developmental marker nestin within 90 min following preparation of live vibratome slices. Moreover, immunoelectron microscopy showed a 2.7-fold loss of astrocytic processes in acute hippocampal slices prepared from GFAP-GFP reporter mice. A sharp decrease in the number of mitochondria was also noted in acute slices, concurrently with an increase in mitochondrial size. Glycogen content decreased 3-fold upon slice preparation and did not recover despite stable recordings of field EPSC. Analysis of Ca2+ signaling showed that astrocytic responses to purine receptor and mGluR5 agonists differed in slice vs. in vivo. These observations suggest that the functional properties and the fine structure of astrocytes in slices may be reflective of early stages of reactive gliosis and should be confirmed in vivo when possible. PMID:24272704

  10. Rapid manifestation of reactive astrogliosis in acute hippocampal brain slices.

    PubMed

    Takano, Takahiro; He, Wei; Han, Xiaoning; Wang, Fushun; Xu, Qiwu; Wang, Xiaohai; Oberheim Bush, Nancy Ann; Cruz, Nancy; Dienel, Gerald A; Nedergaard, Maiken

    2014-01-01

    A flurry of studies over the past decade has shown that astrocytes play a more active role in neural function than previously recognized. Hippocampal slices prepared from young rodent pups have served as a popular model for studying the pathways by which astrocytes participate in synaptic transmission. It is, however, not known how well astrocytes tolerate traumatic injury and hypoxia, which are unavoidable when preparing acute slices. We here showed that astrocytes exhibit striking changes in expression of several receptors and structural proteins, including re-expression of the developmental marker nestin within 90 min following preparation of live vibratome slices. Moreover, immunoelectron microscopy showed a 2.7-fold loss of astrocytic processes in acute hippocampal slices prepared from glial fibrillary acidic protein-green fluorescent protein reporter mice. A sharp decrease in the number of mitochondria was also noted in acute slices, concurrently with an increase in mitochondrial size. Glycogen content decreased 3-fold upon slice preparation and did not recover despite stable recordings of field excitatory postsynaptic current. Analysis of Ca(2+) signaling showed that astrocytic responses to purine receptor and mGluR5 agonists differed in slice versus in vivo. These observations suggest that the functional properties and the fine structure of astrocytes in slices may be reflective of early stages of reactive gliosis and should be confirmed in vivo when possible. PMID:24272704

  11. Walking unsteadily: a case of acute cerebellar ataxia.

    PubMed

    Simonetta, Federico; Christou, Fotini; Vandoni, Riccardo E; Nierle, Thomas

    2013-01-01

    Acute cerebellar ataxia is an infrequent neurological syndrome in adults especially if complicated by additional neurological deficits. We report the case of a 69-year-old woman who presented with sudden onset of left facial droop, dizziness, slurred speech and impaired balance. Her medical history included paroxysmal atrial fibrillation and a sigmoid diverticular abscess treated with ciprofloxacin and metronidazole. Cranial computed tomographic angiography and MRI showed no signs of acute ischaemia or haemorrhage but demonstrated symmetrically distributed lesions in the cerebellar dentate nuclei. A diagnosis of metronidazole-induced encephalopathy was suspected. Metronidazole was stopped and the patient completely recovered. Metronidazole is a commonly prescribed medication. Clinicians should be aware of the clinical and radiological presentation of metronidazole-induced encephalopathy so that this serious but completely reversible condition can be promptly diagnosed. PMID:23283615

  12. Fingolimod (FTY720) Enhances Remyelination Following Demyelination of Organotypic Cerebellar Slices

    PubMed Central

    Miron, Veronique E.; Ludwin, Samuel K.; Darlington, Peter J.; Jarjour, Andrew A.; Soliven, Betty; Kennedy, Timothy E.; Antel, Jack P.

    2010-01-01

    Remyelination, which occurs subsequent to demyelination, contributes to functional recovery and is mediated by oligodendrocyte progenitor cells (OPCs) that have differentiated into myelinating cells. Therapeutics that impact remyelination in the CNS could be critical determinants of long-term functional outcome in multiple sclerosis (MS). Fingolimod is a S1P receptor modulator in MS clinical trials due to systemic anti-inflammatory properties, yet may impact cells within the CNS by crossing the blood-brain barrier. Previous studies using isolated dissociated cultures indicate that neural cells express S1P receptors and respond to receptor engagement. Our objective was to assess the effects of fingolimod on myelin-related processes within a multicellular environment that maintains physiological cell-cell interactions, using organotypic cerebellar slice cultures. Fingolimod treatment had no impact on myelin under basal conditions. Fingolimod treatment subsequent to lysolecithin-induced demyelination enhanced remyelination and process extension by OPCs and mature oligodendrocytes, while increasing microglia numbers and immunoreactivity for the astrocytic marker glial fibrillary acidic protein. The number of phagocytosing microglia was not increased by fingolimod. Using S1P receptor specific agonists and antagonists, we determined that fingolimod-induced effects on remyelination and astrogliosis were mediated primarily through S1P3 and S1P5, whereas enhanced microgliosis was mediated through S1P1 and S1P5. Taken together, these data demonstrate that fingolimod modulates multiple neuroglial cell responses, resulting in enhanced remyelination in organotypic slice cultures that maintain the complex cellular interactions of the mammalian brain. PMID:20413685

  13. In Vitro Assessment Reveals Parameters-Dependent Modulation on Excitability and Functional Connectivity of Cerebellar Slice by Repetitive Transcranial Magnetic Stimulation

    PubMed Central

    Tang, Rongyu; Zhang, Guanghao; Weng, Xiechuan; Han, Yao; Lang, Yiran; Zhao, Yuwei; Zhao, Xiaobo; Wang, Kun; Lin, Qiuxia; Wang, Changyong

    2016-01-01

    Repetitive transcranial magnetic stimulation (rTMS) is an increasingly common technique used to selectively modify neural excitability and plasticity. There is still controversy concerning the cortical response to rTMS of different frequencies. In this study, a novel in vitro paradigm utilizing the Multi-Electrodes Array (MEA) system and acute cerebellar slicing is described. In a controllable environment that comprises perfusion, incubation, recording and stimulation modules, the spontaneous single-unit spiking activity in response to rTMS of different frequencies and powers was directly measured and analyzed. Investigation using this in vitro paradigm revealed frequency-dependent modulation upon the excitability and functional connectivity of cerebellar slices. The 1-Hz rTMS sessions induced short-term inhibition or lagged inhibition, whereas 20-Hz sessions induced excitation. The level of modulation is influenced by the value of power. However the long-term response fluctuated without persistent direction. The choice of evaluation method may also interfere with the interpretation of modulation direction. Furthermore, both short-term and long-term functional connectivity was strengthened by 1-Hz rTMS and weakened by 20-Hz rTMS. PMID:27000527

  14. Simvastatin induces cell death in a mouse cerebellar slice culture (CSC) model of developmental myelination

    PubMed Central

    Xiang, Zhongmin; Reeves, Steven A.

    2009-01-01

    Statins (inhibitors of HMG-CoA reductase) have shown promise in treating multiple sclerosis (MS). However, their effect on oligodendrocyte remyelination of demyelinated axons has not been clarified. Since developmental myelination shares many features with the remyelination process, we investigated the effect of lipophilic simvastatin on developmental myelination in organotypic cerebellar slice cultures (CSC). In this study, we first characterized developmental myelination in CSC from postnatal day (P)5 and P10 mice that express enhanced green fluorescence protein (eGFP) in oligodendrocyte-lineage cells. We then examined the effect of simvastain on three developmental myelination stages: early myelination (P5 CSC, 2DIV), late myelination (P10 CSC, 2DIV) and full myelination (P10 CSC, 10DIV). We found that treatment with simvastatin (0.1 μM) for 6 days decreased the survival of Purkinje cells and oligodendrocytes drastically during the early myelination stage, while moderately during the late and full myelination stages. Oligodendrocytes are more resistant than Purkinje cells. The toxic effect of simvastatin could be rescued by the product of HMG-CoA reductase mevalonate but not low-density lipoprotein (LDL). Additionally, this toxic effect is independent of isoprenylation since farnesyl pyrophosphate (Fpp) but not geranylgeranyl pyrophosphate (GGpp) provided partial rescue. Our findings therefore suggest that inhibition of cholesterol synthesis is detrimental to neuronal tissue. PMID:18929563

  15. Methylmercury-Dependent Increases in Fluo4 Fluorescence in Neonatal Rat Cerebellar Slices Depend on Granule Cell Migrational Stage and GABAA Receptor Modulation.

    PubMed

    Bradford, Aaron B; Mancini, Jayme D; Atchison, William D

    2016-01-01

    Methylmercury (MeHg) disrupts cerebellar function, especially during development. Cerebellar granule cells (CGC), which are particularly susceptible to MeHg by unknown mechanisms, migrate during this process. Transient changes in intracellular Ca(2+) (Ca(2+) i) are crucial to proper migration, and MeHg is well known to disrupt CGC Ca(2+) i regulation. Acutely prepared slices of neonatal rat cerebellum in conjunction with confocal microscopy and fluo4 epifluorescence were used to track changes induced by MeHg in CGC Ca(2+) i regulation in the external (EGL) and internal granule cell layers (IGL) as well as the molecular layer (ML). MeHg caused no cytotoxicity but did cause a time-dependent increase in fluo4 fluorescence that depended on the stage of CGC development. CGCs in the EGL were most susceptible to MeHg-induced increases in fluo4 fluorescence. MeHg increased fluorescence in CGC processes but only diffusely; Purkinje cells rarely fluoresced in these slices. Neither muscimol nor bicuculline alone altered baseline fluo4 fluorescence in any CGC layer, but each delayed the onset and reduced the magnitude of effect of MeHg on fluo4 fluorescence in the EGL and ML. In the IGL, both muscimol and bicuculline delayed the onset of MeHg-induced increases in fluo4 fluorescence but did not affect fluorescence magnitude. Thus, acute exposure to MeHg causes developmental stage-dependent increases in Ca(2+) i in CGCs. Effects are most prominent in CGCs during development or early stages of migration. GABAA receptors participate in an as yet unclear manner to MeHg-induced Ca(2+) i dysregulation of CGCs. PMID:26514794

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

    PubMed Central

    Kasundra, Gaurav M.; Bhargava, Amita Narendra; Bhushan, Bharat; Shubhakaran, Khichar; Sood, Isha

    2015-01-01

    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. PMID:25878748

  17. Persistent cerebellar dysfunction following acute lithium toxicity: A report of two cases

    PubMed Central

    Banwari, Girish; Chaudhary, Pradhyuman; Panchmatia, Ankit; Patel, Nisheet

    2016-01-01

    Neurological disturbances caused by lithium range from simple side effects such as benign tremor to acute reversible neurotoxicity. Rarely, lithium is reported to cause irreversible, permanent neurological sequelae most commonly manifested as cerebellar dysfunction, although other presentations have also been described. We report two cases of persistent cerebellar syndrome following acute lithium toxicity and discuss them in the light of existing literature on the subject. PMID:27298510

  18. A case of midbrain infarction with acute bilateral cerebellar ataxia visualized by diffusion tensor imaging.

    PubMed

    Maya, Yuka; Kawabori, Masahito; Oura, Daisuke; Niiya, Yoshimasa; Iwasaki, Motoyuki; Mabuchi, Shoji

    2016-08-31

    An 85-year-old woman with hypertension was admitted with a sudden onset of gait disturbance and dysarthria. On admission, the patient showed severe bilateral cerebellar ataxia with moderate right medial longitudinal fasciculus (MLF) syndrome. Magnetic resonance (MR) imaging showed an acute infarction in the lower and medial part of midbrain. Diffusion tensor imaging (DTI) started from both cerebellar peduncles revealed that the lesion of the acute infarction matched the decussation of superior cerebellar peduncle where crossing of tract was seen and a part of its tract was interrupted at the site. Interruption of the cerebellum red nuclear path at the medial part of midbrain was considered to be the reason for bilateral cerebellar ataxia and visualization of cerebellum red nuclear path by DTI can give better understanding of the neurological symptom. PMID:27477572

  19. Humor, laughter, and the cerebellum: insights from patients with acute cerebellar stroke.

    PubMed

    Frank, B; Andrzejewski, K; Göricke, S; Wondzinski, E; Siebler, M; Wild, B; Timmann, D

    2013-12-01

    Extent of cerebellar involvement in cognition and emotion is still a topic of ongoing research. In particular, the cerebellar role in humor processing and control of laughter is not well known. A hypermetric dysregulation of affective behavior has been assumed in cerebellar damage. Thus, we aimed at investigating humor comprehension and appreciation as well as the expression of laughter in 21 patients in the acute or subacute state after stroke restricted to the cerebellum, and in the same number of matched healthy control subjects. Patients with acute and subacute cerebellar damage showed preserved comprehension and appreciation of humor using a validated humor test evaluating comprehension, funniness and aversiveness of cartoons ("3WD Humor Test"). Additionally, there was no difference when compared to healthy controls in the number and intensity of facial reactions and laughter while observing jokes, humorous cartoons, or video sketches measured by the Facial Action Coding System. However, as depression scores were significantly increased in patients with cerebellar stroke, a concealing effect of accompanying depression cannot be excluded. Current findings add to descriptions in the literature that cognitive or affective disorders in patients with lesions restricted to the cerebellum, even in the acute state after damage, are frequently mild and might only be present in more sensitive or specific tests. PMID:23661243

  20. Methylmercury differentially affects GABAA receptor-mediated spontaneous IPSCs in Purkinje and granule cells of rat cerebellar slices

    PubMed Central

    Yuan, Yukun; Atchison, William D

    2003-01-01

    Using whole-cell recording techniques we compared effects of the environmental cerebellar neurotoxicant methylmercury (MeHg) on spontaneous IPSCs (sIPSCs) of both Purkinje and granule cells in cerebellar slices of the rat. In Purkinje cells, bath application of 10, 20 or 100 μM MeHg initially increased then suppressed the frequency of sIPSCs to zero. In granule cells, the initial increase in frequency was not observed in ≈50 % of cells examined, but suppression of sIPSCs by MeHg occurred in every cell tested. For both cells, time to onset of effects of MeHg was inversely related to the concentration; moreover, the pattern of changes in mIPSCs induced by MeHg in the presence of tetrodotoxin was similar to that in sIPSCs. For each concentration of MeHg, it took 2–3 times longer to block sIPSCs in Purkinje cells than it did in granule cells. MeHg also initially increased then decreased amplitudes of sIPSCs to block in both cells; again the response was more variable in granule cells. In most Purkinje and some granule cells, MeHg induced a giant, slow inward current during the late stages of exposure. Appearance of this current appeared to be MeHg concentration dependent, and the direction of current flow was reversed by changing the holding potentials. Reduction of the [Cl−] in the internal solution caused inwardly directed, but not outwardly directed giant currents to disappear, suggesting that this current is a Cl−-mediated response. However, bicuculline and picrotoxin failed to block it. MeHg apparently acts at both presynaptic and postsynaptic sites to alter GABAA receptor-mediated inhibitory synaptic transmission. GABAA receptors in granule cells appear to be more sensitive to block by MeHg than are those in Purkinje cells, although the general patterns of effects on the two cells are similar. PMID:12879869

  1. Altered Cerebellar White Matter Integrity in Patients with Mild Traumatic Brain Injury in the Acute Stage

    PubMed Central

    Wang, Zhongqiu; Wu, Wenzhong; Liu, Yongkang; Wang, Tianyao; Chen, Xiao; Zhang, Jianhua; Zhou, Guoxing; Chen, Rong

    2016-01-01

    Background and Purpose Imaging studies of traumatic brain injury demonstrate that the cerebellum is often affected. We aim to examine fractional anisotropy alteration in acute-phase mild traumatic brain injury patients in cerebellum-related white matter tracts. Materials and Methods This prospective study included 47 mild traumatic brain injury patients in the acute stage and 37 controls. MR imaging and neurocognitive tests were performed in patients within 7 days of injury. White matter integrity was examined by using diffusion tensor imaging. We used three approaches, tract-based spatial statistics, graphical-model-based multivariate analysis, and region-of-interest analysis, to detect altered cerebellar white matter integrity in mild traumatic brain injury patients. Results Results from three analysis methods were in accordance with each other, and suggested fractional anisotropy in the middle cerebellar peduncle and the pontine crossing tract was changed in the acute-phase mild traumatic brain injury patients, relative to controls (adjusted p-value < 0.05). Higher fractional anisotropy in the middle cerebellar peduncle was associated with worse performance in the fluid cognition composite (r = -0.289, p-value = 0.037). Conclusion Altered cerebellar fractional anisotropy in acute-phase mild traumatic brain injury patients is localized in specific regions and statistically associated with cognitive deficits detectable on neurocognitive testing. PMID:26967320

  2. Promoting Motor Cortical Plasticity with Acute Aerobic Exercise: A Role for Cerebellar Circuits

    PubMed Central

    Mang, Cameron S.; Brown, Katlyn E.; Neva, Jason L.; Snow, Nicholas J.; Campbell, Kristin L.; Boyd, Lara A.

    2016-01-01

    Acute aerobic exercise facilitated long-term potentiation-like plasticity in the human primary motor cortex (M1). Here, we investigated the effect of acute aerobic exercise on cerebellar circuits, and their potential contribution to altered M1 plasticity in healthy individuals (age: 24.8 ± 4.1 years). In Experiment   1, acute aerobic exercise reduced cerebellar inhibition (CBI) (n = 10, p = 0.01), elicited by dual-coil paired-pulse transcranial magnetic stimulation. In Experiment   2, we evaluated the facilitatory effects of aerobic exercise on responses to paired associative stimulation, delivered with a 25 ms (PAS25) or 21 ms (PAS21) interstimulus interval (n = 16 per group). Increased M1 excitability evoked by PAS25, but not PAS21, relies on trans-cerebellar sensory pathways. The magnitude of the aerobic exercise effect on PAS response was not significantly different between PAS protocols (interaction effect: p = 0.30); however, planned comparisons indicated that, relative to a period of rest, acute aerobic exercise enhanced the excitatory response to PAS25 (p = 0.02), but not PAS21 (p = 0.30). Thus, the results of these planned comparisons indirectly provide modest evidence that modulation of cerebellar circuits may contribute to exercise-induced increases in M1 plasticity. The findings have implications for developing aerobic exercise strategies to “prime” M1 plasticity for enhanced motor skill learning in applied settings. PMID:27127659

  3. Rare case of phenytoin induced acute generalized exanthematous pustulosis with cerebellar syndrome

    PubMed Central

    Shingade, Pravin U; Wankhede, Vaishali; Kataria, Pritam S; Sonone, Nitin

    2014-01-01

    Acute generalized exanthematous pustulosis (AGEP) is a rare drug induced cutaneous hypersensitivity reaction characterized by sudden onset of fever with sterile pustules overlying an erythematous skin occurring all over the body. The offending drugs are usually B-lactams and macrolides. Among anticonvulsants carbamazepine and Phenobarbital are commonly associated with AGEP. Only one case of phenytoin induced AGEP has been reported in literature. We present a rare case of AGEP with cerebellar syndrome occurring after receiving loading dose of phenytoin. PMID:24700960

  4. Acute brain slice methods for adult and aging animals: application of targeted patch clampanalysis and optogenetics

    PubMed Central

    Daigle, Tanya L.; Chen, Qian; Feng, Guoping

    2014-01-01

    Summary The development of the living acute brain slice preparation for analyzing synaptic function roughly a half century ago was a pivotal achievement that greatly influenced the landscape of modern neuroscience. Indeed, many neuroscientists regard brain slices as the gold-standard model system for detailed cellular, molecular, and circuitry level analysis and perturbation of neuronal function. A critical limitation of this model system is the difficulty in preparing slices from adult and aging animals, and over the past several decades few substantial methodological improvements have emerged to facilitate patch clamp analysis in the mature adult stage. In this chapter we describe a robust and practical protocol for preparing brain slices from mature adult mice that are suitable for patch clamp analysis. This method reduces swelling and damage in superficial layers of the slices and improves the success rate for targeted patch clamp recordings, including recordings from fluorescently labeled populations in slices derived from transgenic mice. This adult brain slice method is suitable for diverse experimental applications, including both monitoring and manipulating neuronal activity with genetically encoded calcium indicators and optogenetic actuators, respectively. We describe the application of this adult brain slice platform and associated methods for screening kinetic properties of Channelrhodopsin (ChR) variants expressed in genetically-defined neuronal subtypes. PMID:25023312

  5. Clinical and radiologic features and their relationships with neurofunctional scores in patients with acute cerebellar infarct

    PubMed Central

    Kozak, Hasan Hüseyin; Uca, Ali Ulvi; Poyraz, Necdet; Anliaçık, Süleyman Ömer; Tokgöz, Osman Serhat

    2016-01-01

    Background: Cerebellar infarct is a rare condition with very nonspecific clinical features. The aim of this study was to assess the full spectrum of the clinical characteristics, neuroimaging findings and neurofunctional analyses of cerebellar infarction, and the relationship between them. Materials and Methods: Data were collected from 59 patients admitted to our department during an 8-year period. We retrospectively analyzed the relationship between demographic characteristics, clinical symptomatology, etiological factors, functional condition, vascular distribution, frequency of subcortical white matter lesions (WMLs), and concomitant lesion outside the cerebellum in patients with acute cerebellar infarct (ACI) at time of admission. Results: The mean age in our series was 65.2 years, with most being male (57.6%). The posterior inferior cerebellar (PICA) artery was the most commonly affected territory at 62.7%. There was concomitant lesion outside the cerebellum in 45.7%. The main etiology in PICA was cardioembolism. While mean National Institutes of Health Stroke Scale on admission was 2.08 ± 1.67 in study group, modified Rankin Scale (mRS) on admission was detected to be mRS1 (n: 44, 74.5%) and mRS2 (n: 12, 20.3%) most frequently. Fourteen (35%) patients were detected to be in Fazekas stage 0; 11 (27.5%) patients in Fazekas stage 1; 6 (15%) patients in Fazekas stage 2; and 9 (22.5%) patients in Fazekas stage 3. Conclusion: Cerebellar infarct is very heterogeneous. The other cerebral area infarcts which accompany ACI negatively affect neurologic functional scores. Although it is difficult to detect the relationship between WMLs and neurologic functional severity, timely detection of risk factors and their modulation may be associated with prevention and treatability of WMLs, and this may be one of the important points for prevention of stroke-related disability. PMID:27293332

  6. The Usefulness of the TOAST Classification and Prognostic Significance of Pyramidal Symptoms During the Acute Phase of Cerebellar Ischemic Stroke.

    PubMed

    Dziadkowiak, Edyta; Chojdak-Łukasiewicz, Justyna; Guziński, Maciej; Noga, Leszek; Paradowski, Bogusław

    2016-04-01

    Cerebellar stroke is a rare condition with very nonspecific clinical features. The symptoms in the acute phase could imitate acute peripheral vestibular disorders or a brainstem lesion. The aim of this study was to assess the usefulness of the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification in cerebellar stroke and the impact of clinical features on the prognosis. We retrospectively analyzed 107 patients with diagnosed ischemic cerebellar infarction. We studied the clinical features and compared them based on the location of the ischemic lesion and its distribution in the posterior interior cerebellar artery (PICA), superior cerebellar artery (SCA), and anterior inferior cerebellar artery (AICA) territories. According to the TOAST classification, stroke was more prevalent in atrial fibrillation (26/107) and when the lesion was in the PICA territory (39/107). Pyramidal signs occurred in 29/107 of patients and were more prevalent when the lesion was distributed in more than two vascular regions (p = 0.00640). Mortality was higher among patients with ischemic lesion caused by cardiac sources (p = 0.00094) and with pyramidal signs (p = 0.00640). The TOAST classification is less useful in assessing supratentorial ischemic infarcts. Cardioembolic etiology, location of the ischemic lesion, and pyramidal signs support a negative prognosis. PMID:26041073

  7. Modulation of potassium evoked secretory function in rat cerebellar slices measured by real time monitoring: evidence of a possible role for methylfolate in cerebral tissue.

    PubMed

    Lucock, M D; Levene, M I; Hartley, R

    1993-05-01

    The real time dynamics of K+ evoked neurosecretion in cerebellar slices has been monitored electrochemically. In the presence of 5-methyltetrahydrofolate a statistically significant diminution in secretory response occurs. Agonists to probe the pharmacological basis for this indicate it is not due to voltage sensitive Ca2+ channel blockade, nor does it show any similarity of effect with kainate, whose receptor is a putative binding site for 5-methyltetrahydrofolate. The method is fully validated, although no account is taken of individual molecular species. High performance liquid chromatography combined with off line microbiological assay could only detect 5-methyltetrahydrofolate in cerebrospinal fluid. We therefore discuss our findings in relation to possible cerebral roles for cerebrospinal fluid 5-methyltetrahydrofolate in the context of both membrane and transmitter related interactions. PMID:8474580

  8. Electrophysiology of Hypothalamic Magnocellular Neurons In vitro: A Rhythmic Drive in Organotypic Cultures and Acute Slices

    PubMed Central

    Israel, Jean-Marc; Oliet, Stéphane H.; Ciofi, Philippe

    2016-01-01

    Hypothalamic neurohormones are released in a pulsatile manner. The mechanisms of this pulsatility remain poorly understood and several hypotheses are available, depending upon the neuroendocrine system considered. Among these systems, hypothalamo-neurohypophyseal magnocellular neurons have been early-considered models, as they typically display an electrical activity consisting of bursts of action potentials that is optimal for the release of boluses of the neurohormones oxytocin and vasopressin. The cellular mechanisms underlying this bursting behavior have been studied in vitro, using either acute slices of the adult hypothalamus, or organotypic cultures of neonatal hypothalamic tissue. We have recently proposed, from experiments in organotypic cultures, that specific central pattern generator networks, upstream of magnocellular neurons, determine their bursting activity. Here, we have tested whether a similar hypothesis can be derived from in vitro experiments in acute slices of the adult hypothalamus. To this aim we have screened our electrophysiological recordings of the magnocellular neurons, previously obtained from acute slices, with an analysis of autocorrelation of action potentials to detect a rhythmic drive as we recently did for organotypic cultures. This confirmed that the bursting behavior of magnocellular neurons is governed by central pattern generator networks whose rhythmic drive, and thus probably integrity, is however less satisfactorily preserved in the acute slices from adult brains. PMID:27065780

  9. Anti-Yo Antibody Uptake and Interaction with Its Intracellular Target Antigen Causes Purkinje Cell Death in Rat Cerebellar Slice Cultures: A Possible Mechanism for Paraneoplastic Cerebellar Degeneration in Humans with Gynecological or Breast Cancers

    PubMed Central

    Greenlee, John E.; Clawson, Susan A.; Hill, Kenneth E.; Wood, Blair; Clardy, Stacey L.; Tsunoda, Ikuo; Carlson, Noel G.

    2015-01-01

    Anti-Yo antibodies are immunoglobulin G (IgG) autoantibodies reactive with a 62 kDa Purkinje cell cytoplasmic protein. These antibodies are closely associated with paraneoplastic cerebellar degeneration in the setting of gynecological and breast malignancies. We have previously demonstrated that incubation of rat cerebellar slice cultures with patient sera and cerebrospinal fluid containing anti-Yo antibodies resulted in Purkinje cell death. The present study addressed three fundamental questions regarding the role of anti-Yo antibodies in disease pathogenesis: 1) Whether the Purkinje cell cytotoxicity required binding of anti-Yo antibody to its intraneuronal 62 kDa target antigen; 2) whether Purkinje cell death might be initiated by antibody-dependent cellular cytotoxicity rather than intracellular antibody binding; and 3) whether Purkinje cell death might simply be a more general result of intracellular antibody accumulation, rather than of specific antibody-antigen interaction. In our study, incubation of rat cerebellar slice cultures with anti-Yo IgG resulted in intracellular antibody binding, and cell death. Infiltration of the Purkinje cell layer by cells of macrophage/microglia lineage was not observed until extensive cell death was already present. Adsorption of anti-Yo IgG with its 62 kDa target antigen abolished both antibody accumulation and cytotoxicity. Antibodies to other intracellular Purkinje cell proteins were also taken up by Purkinje cells and accumulated intracellularly; these included calbindin, calmodulin, PCP-2, and patient anti-Purkinje cell antibodies not reactive with the 62 kDa Yo antigen. However, intracellular accumulation of these antibodies did not affect Purkinje cell viability. The present study is the first to demonstrate that anti-Yo antibodies cause Purkinje cell death by binding to the intracellular 62 kDa Yo antigen. Anti-Yo antibody cytotoxicity did not involve other antibodies or factors present in patient serum and was not

  10. Barr humbug: acute cerebellar ataxia due to Epstein-Barr virus.

    PubMed

    Davies, Benjamin; Machin, Nicholas; Lavin, Timothy; Ul Haq, Mian Ayaz

    2016-01-01

    Epstein-Barr virus (EBV) infection is associated with neurological sequellae, but rarely there is acute cerebellar ataxia (ACA) in an adult. We present a novel case of a 26-year-old man, who presented with ACA. He had normal MRI and CSF analysis. Serum testing confirmed active EBV. A course of oral prednisolone 1 mg/kg for 4 weeks, with a subsequent taper was started. He made a full recovery within 3 weeks of presentation. PMID:27558189

  11. Two-Photon Excitation STED Microscopy in Two Colors in Acute Brain Slices

    PubMed Central

    Bethge, Philipp; Chéreau, Ronan; Avignone, Elena; Marsicano, Giovanni; Nägerl, U. Valentin

    2013-01-01

    Many cellular structures and organelles are too small to be properly resolved by conventional light microscopy. This is particularly true for dendritic spines and glial processes, which are very small, dynamic, and embedded in dense tissue, making it difficult to image them under realistic experimental conditions. Two-photon microscopy is currently the method of choice for imaging in thick living tissue preparations, both in acute brain slices and in vivo. However, the spatial resolution of a two-photon microscope, which is limited to ∼350 nm by the diffraction of light, is not sufficient for resolving many important details of neural morphology, such as the width of spine necks or thin glial processes. Recently developed superresolution approaches, such as stimulated emission depletion microscopy, have set new standards of optical resolution in imaging living tissue. However, the important goal of superresolution imaging with significant subdiffraction resolution has not yet been accomplished in acute brain slices. To overcome this limitation, we have developed a new microscope based on two-photon excitation and pulsed stimulated emission depletion microscopy, which provides unprecedented spatial resolution and excellent experimental access in acute brain slices using a long-working distance objective. The new microscope improves on the spatial resolution of a regular two-photon microscope by a factor of four to six, and it is compatible with time-lapse and simultaneous two-color superresolution imaging in living cells. We demonstrate the potential of this nanoscopy approach for brain slice physiology by imaging the morphology of dendritic spines and microglial cells well below the surface of acute brain slices. PMID:23442956

  12. Synaptic action of ethanol on cerebellar auditory granule cells reveals acute tolerance

    SciTech Connect

    Huang, C.M.; Liu, G.; Huang, R.H. )

    1991-03-11

    The cerebellum is very sensitive to acute intoxication by ethanol. The authors have recorded electrophysiological responses of granule cells to auditory stimulation from the posterior cerebellar vermis of cats before and after a relatively low dose of ethanol. Auditory responses of granule cells were severely inhibited by ethanol at a transient, peak ethanol concentration of 15-18 mM in the cerebrospinal fluid (CSF). Thereafter, the clearance of ethanol from CSF followed an exponential time course, with 50% of the CSF ethanol being cleared with every passing hour. Auditory responses of granule cells returned to control levels within 60-90 minutes, despite the presence of a DSF ethanol concentration at 8-10mM, indicating acute tolerance. Moreover, a second, identical dose of ethanol, delivered two hours after the first dose produced an attenuated inhibition in the auditory response of cerebellar granule cells. The inhibition took a longer time to be evident but a shorter time to recover than that followed by the first dose of ethanol.

  13. Solitary C1 spinal osteochondroma causing vertebral artery compression and acute cerebellar infarct.

    PubMed

    Zhang, Yaxia; Ilaslan, Hakan; Hussain, Muhammad S; Bain, Mark; Bauer, Thomas W

    2015-02-01

    Osteochondroma is a common benign bone lesion, usually involving the long bones. Spinal involvement is rare. The clinical presentation of spinal osteochondroma varies according to the site of the lesion. The most common reported clinical presentation is secondary to encroachment of the lesion on the spinal canal or nerve roots. Less common presentations such as a palpable neck mass, dysphagia, sleep apnea, paralysis of left vocal cord or acute respiratory distress have been reported when the lesions compress the anatomic structures anteriorly. We describe a rare case of a young patient who presented with an emergent critical condition of acute cerebellar infarct as a result of vertebral artery compression caused by a solitary C1 spinal osteochondroma. PMID:25109381

  14. Uptake and metabolism of L-(/sup 3/H)glutamate and L-(/sup 3/H)glutamine in adult rat cerebellar slices

    SciTech Connect

    de Barry, J.; Vincendon, G.; Gombos, G.

    1983-10-01

    Using very low concentrations (1 mumol range) of L-2-3-(/sup 3/H)glutamate, (/sup 3/H-Glu) or L-2-3-(/sup 3/H)glutamine (/sup 3/H-Gln), the authors have previously shown by autoradiography that these amino acids were preferentially taken up in the molecular layer of the cerebellar cortex. Furthermore, the accumulation of /sup 3/H-Glu was essentially glial in these conditions. Uptake and metabolism of either (/sup 3/H-Glu) or (/sup 3/H-Gln) were studied in adult rat cerebellar slices. Both amino acids were rapidly converted into other metabolic compounds: after seven minutes of incubation in the presence of exogenous /sup 3/H-Glu, 70% of the tissue accumulated radioactivity was found to be in compounds other than glutamate. The main metabolites were Gln (42%), alpha-ketoglutarate (25%) and GABA (1,4%). In the presence of exogenous /sup 3/H-Gln the rate of metabolism was slightly slower (50% after seven minutes of incubation) and the metabolites were also Glu (29%), alpha-ketoglutarate (15%) and GABA (5%). Using depolarizing conditions (56 mM KCl) with either exogenous /sup 3/H-Glu or /sup 3/H-Gln, the radioactivity was preferentially accumulated in glutamate compared to control. From these results we conclude: i) there are two cellular compartments for the neurotransmission-glutamate-glutamine cycle; one is glial, the other neuronal; ii) these two cellular compartments contain both Gln and Glu; iii) transmitter glutamate is always in equilibrium with the so-called ''metabolic'' pool of glutamate; iv) the regulation of the glutamate-glutamine cycle occurs at least at two different levels: the uptake of glutamate and the enzymatic activity of the neuronal glutaminase.

  15. Targeting neurotransmitter receptors with nanoparticles in vivo allows single-molecule tracking in acute brain slices

    PubMed Central

    Varela, Juan A.; Dupuis, Julien P.; Etchepare, Laetitia; Espana, Agnès; Cognet, Laurent; Groc, Laurent

    2016-01-01

    Single-molecule imaging has changed the way we understand many biological mechanisms, particularly in neurobiology, by shedding light on intricate molecular events down to the nanoscale. However, current single-molecule studies in neuroscience have been limited to cultured neurons or organotypic slices, leaving as an open question the existence of fast receptor diffusion in intact brain tissue. Here, for the first time, we targeted dopamine receptors in vivo with functionalized quantum dots and were able to perform single-molecule tracking in acute rat brain slices. We propose a novel delocalized and non-inflammatory way of delivering nanoparticles (NPs) in vivo to the brain, which allowed us to label and track genetically engineered surface dopamine receptors in neocortical neurons, revealing inherent behaviour and receptor activity regulations. We thus propose a NP-based platform for single-molecule studies in the living brain, opening new avenues of research in physiological and pathological animal models. PMID:26971573

  16. Targeting neurotransmitter receptors with nanoparticles in vivo allows single-molecule tracking in acute brain slices

    NASA Astrophysics Data System (ADS)

    Varela, Juan A.; Dupuis, Julien P.; Etchepare, Laetitia; Espana, Agnès; Cognet, Laurent; Groc, Laurent

    2016-03-01

    Single-molecule imaging has changed the way we understand many biological mechanisms, particularly in neurobiology, by shedding light on intricate molecular events down to the nanoscale. However, current single-molecule studies in neuroscience have been limited to cultured neurons or organotypic slices, leaving as an open question the existence of fast receptor diffusion in intact brain tissue. Here, for the first time, we targeted dopamine receptors in vivo with functionalized quantum dots and were able to perform single-molecule tracking in acute rat brain slices. We propose a novel delocalized and non-inflammatory way of delivering nanoparticles (NPs) in vivo to the brain, which allowed us to label and track genetically engineered surface dopamine receptors in neocortical neurons, revealing inherent behaviour and receptor activity regulations. We thus propose a NP-based platform for single-molecule studies in the living brain, opening new avenues of research in physiological and pathological animal models.

  17. Optical recording of electrical activity from parallel fibres and other cell types in skate cerebellar slices in vitro.

    PubMed Central

    Konnerth, A; Obaid, A L; Salzberg, B M

    1987-01-01

    1. A reliable and simple fish brain slice preparation was obtained from the cerebellum of the skate, and its properties were described. 2. A potentiometric oxonol dye, RH-482, and multiple site optical recording of transmembrane voltage (MSORTV) were used to reveal the electrophysiological properties of the parallel fibre action potential and to measure its conduction (0.13 m/s). The parallel fibre action potential was blocked in the presence of tetrodotoxin (TTX) and prolonged by tetraethylammonium (TEA), suggesting that the upstroke depends upon sodium entry and the repolarization upon potassium efflux. An after-hyperpolarization results from a calcium-dependent potassium conductance. 3. A second potentiometric dye, RH-155, differing only slightly from RH-482, exhibited a high affinity for glial cell membrane, and could be used to monitor changes in extracellular potassium concentration by detecting changes in glial membrane potential. 4. Calcium channel blockers such as cadmium ions blocked the optical signal that reflected the extracellular accumulation of potassium. 5. Interventions that modified the extracellular volume, and thereby affected the accumulation of potassium, produced large changes in the optical signal that monitored glial depolarization. Hypertonic and hypotonic bathing solutions resulted in decreases and increases, respectively, in the magnitude of the extrinsic absorption change that tracked potassium accumulation. 6. Blocking sodium-potassium pump activity by means of ouabain prolonged the time course of the optical signal that was related to potassium accumulation in the extracellular space. 7. Extracellular potassium accumulation was revealed to be critically dependent upon intracellular calcium ions. Images Fig. 2 PMID:3446807

  18. Time-lapse imaging of neuroblast migration in acute slices of the adult mouse forebrain.

    PubMed

    Khlghatyan, Jivan; Saghatelyan, Armen

    2012-01-01

    There is a substantial body of evidence indicating that new functional neurons are constitutively generated from an endogenous pool of neural stem cells in restricted areas of the adult mammalian brain. Newborn neuroblasts from the subventricular zone (SVZ) migrate along the rostral migratory stream (RMS) to their final destination in the olfactory bulb (OB). In the RMS, neuroblasts migrate tangentially in chains ensheathed by astrocytic processes using blood vessels as a structural support and a source of molecular factors required for migration. In the OB, neuroblasts detach from the chains and migrate radially into the different bulbar layers where they differentiate into interneurons and integrate into the existing network. In this manuscript we describe the procedure for monitoring cell migration in acute slices of the rodent brain. The use of acute slices allows the assessment of cell migration in the microenvironment that closely resembling to in vivo conditions and in brain regions that are difficult to access for in vivo imaging. In addition, it avoids long culturing condition as in the case of organotypic and cell cultures that may eventually alter the migration properties of the cells. Neuronal precursors in acute slices can be visualized using DIC optics or fluorescent proteins. Viral labeling of neuronal precursors in the SVZ, grafting neuroblasts from reporter mice into the SVZ of wild-type mice, and using transgenic mice that express fluorescent protein in neuroblasts are all suitable methods for visualizing neuroblasts and following their migration. The later method, however, does not allow individual cells to be tracked for long periods of time because of the high density of labeled cells. We used a wide-field fluorescent upright microscope equipped with a CCD camera to achieve a relatively rapid acquisition interval (one image every 15 or 30 sec) to reliably identify the stationary and migratory phases. A precise identification of the duration of

  19. Investigation of Synaptic Tagging/Capture and Cross-capture using Acute Hippocampal Slices from Rodents

    PubMed Central

    Shetty, Mahesh Shivarama; Sharma, Mahima; Hui, Neo Sin; Dasgupta, Ananya; Gopinadhan, Suma; Sajikumar, Sreedharan

    2015-01-01

    Synaptic tagging and capture (STC) and cross-tagging are two important mechanisms at cellular level that explain how synapse-specificity and associativity is achieved in neurons within a specific time frame. These long-term plasticity-related processes are the leading candidate models to study the basis of memory formation and persistence at the cellular level. Both STC and cross-tagging involve two serial processes: (1) setting of the synaptic tag as triggered by a specific pattern of stimulation, and (2) synaptic capture, whereby the synaptic tag interacts with newly synthesized plasticity-related proteins (PRPs). Much of the understanding about the concepts of STC and cross-tagging arises from the studies done in CA1 region of the hippocampus and because of the technical complexity many of the laboratories are still unable to study these processes. Experimental conditions for the preparation of hippocampal slices and the recording of stable late-LTP/LTD are extremely important to study synaptic tagging/cross-tagging. This video article describes the experimental procedures to study long-term plasticity processes such as STC and cross-tagging in the CA1 pyramidal neurons using stable, long-term field-potential recordings from acute hippocampal slices of rats. PMID:26381286

  20. Investigation of Synaptic Tagging/Capture and Cross-capture using Acute Hippocampal Slices from Rodents.

    PubMed

    Shetty, Mahesh Shivarama; Sharma, Mahima; Hui, Neo Sin; Dasgupta, Ananya; Gopinadhan, Suma; Sajikumar, Sreedharan

    2015-01-01

    Synaptic tagging and capture (STC) and cross-tagging are two important mechanisms at cellular level that explain how synapse-specificity and associativity is achieved in neurons within a specific time frame. These long-term plasticity-related processes are the leading candidate models to study the basis of memory formation and persistence at the cellular level. Both STC and cross-tagging involve two serial processes: (1) setting of the synaptic tag as triggered by a specific pattern of stimulation, and (2) synaptic capture, whereby the synaptic tag interacts with newly synthesized plasticity-related proteins (PRPs). Much of the understanding about the concepts of STC and cross-tagging arises from the studies done in CA1 region of the hippocampus and because of the technical complexity many of the laboratories are still unable to study these processes. Experimental conditions for the preparation of hippocampal slices and the recording of stable late-LTP/LTD are extremely important to study synaptic tagging/cross-tagging. This video article describes the experimental procedures to study long-term plasticity processes such as STC and cross-tagging in the CA1 pyramidal neurons using stable, long-term field-potential recordings from acute hippocampal slices of rats. PMID:26381286

  1. Long-Term Potentiation by Theta-Burst Stimulation Using Extracellular Field Potential Recordings in Acute Hippocampal Slices.

    PubMed

    Abrahamsson, Therese; Lalanne, Txomin; Watt, Alanna J; Sjöström, P Jesper

    2016-01-01

    This protocol describes how to carry out theta-burst long-term potentiation (LTP) with extracellular field recordings in acute rodent hippocampal slices. This method is relatively simple and noninvasive and provides a way to sample many neurons simultaneously, making it suitable for applications requiring higher throughput than whole-cell recording. PMID:27250947

  2. [An acute severe heat stroke patient showing abnormal diffuse high intensity of the cerebellar cortex in diffusion weighted image: a case report].

    PubMed

    Fujioka, Yusuke; Yasui, Keizo; Hasegawa, Yasuhiro; Takahashi, Akira; Sobue, Gen

    2009-10-01

    A 47-year-old man was admitted to the hospital because of general convulsion, loss of consciousness and hyperthermia. A diagnosis of acute heat stroke was made clinically and neuroradiologically. As the consciousness level ameliorated, he developed severe abulia and mutism, then cerebellar ataxic syndrome (viz. truncal ataxia, hypermetria, ataxic speech and nystagmus). An MRI (diffusion weighted image; DWI) disclosed abnormal diffuse high signal intensity of the cerebellar cortex with reduced apparent diffusion coefficient (ADC). Two months later after the onset, truncal ataxia and dysarthria significantly improved, while dysmetria of the extremities rather worsened. At that time, the abnormal signal intensity of the cerebellar cortex disappeared, and the cerebellum became atrophic. The cerebellar blood flow was significantly decreased on brain SPECT (99mTc-ECD). The abnormal DWI signal intensity of the cerebellar cortex in the present patient may represent the cytotoxic edema of Purkinje cells resulting from heat stroke-related hyperthermia It is essential to repeat MRI examination for cerebellar pathology and to obtain better insight into sequelae in patients with acute heat stroke. Protirelin tartrate seemed to be valid for improvement of abulia in the present patient. Further study is indicated. PMID:19999144

  3. Acute cerebellar dysfunction with neuromuscular manifestations after scorpionism presumably caused by Tityus obscurus in Santarém, Pará / Brazil.

    PubMed

    Torrez, Pasesa P Q; Quiroga, Mariana M M; Abati, Paulo A M; Mascheretti, Melissa; Costa, Walter Silva; Campos, Luciana P; França, Francisco O S

    2015-03-01

    Scorpionism is a public health problem in many tropical countries, especially in North Africa, South India, Latin America and the Middle East. In Brazil, patients with severe scorpion envenoming have mainly cardiovascular events, including acute heart failure, acute respiratory distress syndrome and shock, death is rare. We described 58 accidents presumably caused by Tityus obscurus in Brazilian Amazonia. Patients reported a sensation of "electric shocks" which could last hours. The vast majority of patients presented a clinical picture compatible with acute cerebellar dysfunction, beginning minutes and lasting up to 2 days after the accident. They presented cerebellar ataxia, dysdiadochokinesia, dysmetry, dysarthria, dyslalia, nausea and vomiting. Besides, some patients presented myoclonus and fasciculation which can also be attributed to cerebellar dysfunction or maybe the result of direct action on skeletal muscle. Two patients had evidence of intense rhabdomyolysis and acute kidney injury. The clinical picture in this scorpion envenoming is mainly characterized by an acute dysfunction of cerebellar activities and abnormal neuromuscular manifestations and in some cases muscle injury which are not described in any other region of the world. This work presents clinical, epidemiologic, laboratory and treatment aspects of this unmatched scorpion envenoming in the state of Pará, northern Brazil. PMID:25549940

  4. The relationship between decorrelation time and sample thickness in acute rat brain tissue slices (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Brake, Joshua; Jang, Mooseok; Yang, Changhuei

    2016-03-01

    The optical opacity of biological tissue has long been a challenge in biomedical optics due to the strong scattering nature of tissue in the optical regime. While most conventional optical techniques attempt to gate out multiply scattered light and use only unscattered light, new approaches in the field of wavefront shaping exploit the time reversible symmetry of optical scattering in order to focus light inside or through scattering media. While these approaches have been demonstrated effectively on static samples, it has proven difficult to apply them to dynamic biological samples since even small changes in the relative positions of the scatterers within will cause the time symmetry that wavefront shaping relies upon to decorrelate. In this paper we investigate the decorrelation curves of acute rat brain slices for thicknesses in the range 1-3 mm (1/e decorrelation time on the order of seconds) using multi-speckle diffusing wave spectroscopy (MSDWS) and compare the results with theoretical predictions. The results of this study demonstrate that the 1/L^2 relationship between decorrelation time and thickness predicted by diffusing wave spectroscopy provides a good rule of thumb for estimating how the decorrelation of a sample will change with increasing thickness. Understanding this relationship will provide insight to guide the future development of biophotonic wavefront shaping tools by giving an estimate of how fast wavefront shaping systems need to operate to overcome the dynamic nature of biological samples.

  5. S100B secretion in acute brain slices: modulation by extracellular levels of Ca(2+) and K (+).

    PubMed

    Nardin, Patrícia; Tortorelli, Lucas; Quincozes-Santos, André; de Almeida, Lúcia Maria V; Leite, Marina C; Thomazi, Ana Paula; Gottfried, Carmem; Wofchuk, Susana T; Donato, Rosario; Gonçalves, Carlos-Alberto

    2009-09-01

    Hippocampal slices have been widely used to investigate electrophysiological and metabolic neuronal parameters, as well as parameters of astroglial activity including protein phosphorylation and glutamate uptake. S100B is an astroglial-derived protein, which extracellularly plays a neurotrophic activity during development and excitotoxic insult. Herein, we characterized S100B secretion in acute hippocampal slices exposed to different concentrations of K(+) and Ca(2+) in the extracellular medium. Absence of Ca(2+) and/or low K(+) (0.2 mM KCl) caused an increase in S100B secretion, possibly by mobilization of internal stores of Ca(2+). In contrast, high K(+) (30 mM KCl) or calcium channel blockers caused a decrease in S100B secretion. This study suggests that exposure of acute hippocampal slices to low- and high-K(+) could be used as an assay to evaluate astrocyte activity by S100B secretion: positively regulated by low K(+) (possibly involving mobilization of internal stores of Ca(2+)) and negatively regulated by high-K(+) (likely secondary to influx of K(+)). PMID:19288274

  6. Optical recording of fast neuronal membrane potential transients in acute mammalian brain slices by second-harmonic generation microscopy.

    PubMed

    Dombeck, Daniel A; Sacconi, Leonardo; Blanchard-Desce, Mireille; Webb, Watt W

    2005-11-01

    Although nonlinear microscopy and fast (approximately 1 ms) membrane potential (Vm) recording have proven valuable for neuroscience applications, their potentially powerful combination has not yet been shown for studies of Vm activity deep in intact tissue. We show that laser illumination of neurons in acute rat brain slices intracellularly filled with FM4-64 dye generates an intense second-harmonic generation (SHG) signal from somatic and dendritic plasma membranes with high contrast >125 microm below the slice surface. The SHG signal provides a linear response to DeltaVm of approximately 7.5%/100 mV. By averaging repeated line scans (approximately 50), we show the ability to record action potentials (APs) optically with a signal-to-noise ratio (S/N) of approximately 7-8. We also show recording of fast Vm steps from the dendritic arbor at depths inaccessible with previous methods. The high membrane contrast and linear response of SHG to DeltaVm provides the advantage that signal changes are not degraded by background and can be directly quantified in terms of DeltaVm. Experimental comparison of SHG and two-photon fluorescence Vm recording with the best known probes for each showed that the SHG technique is superior for Vm recording in brain slice applications, with FM4-64 as the best tested SHG Vm probe. PMID:16093337

  7. Dopamine Modulates Spike Timing-Dependent Plasticity and Action Potential Properties in CA1 Pyramidal Neurons of Acute Rat Hippocampal Slices

    PubMed Central

    Edelmann, Elke; Lessmann, Volkmar

    2011-01-01

    Spike timing-dependent plasticity (STDP) is a cellular model of Hebbian synaptic plasticity which is believed to underlie memory formation. In an attempt to establish a STDP paradigm in CA1 of acute hippocampal slices from juvenile rats (P15–20), we found that changes in excitability resulting from different slice preparation protocols correlate with the success of STDP induction. Slice preparation with sucrose containing ACSF prolonged rise time, reduced frequency adaptation, and decreased latency of action potentials in CA1 pyramidal neurons compared to preparation in conventional ASCF, while other basal electrophysiological parameters remained unaffected. Whereas we observed prominent timing-dependent long-term potentiation (t-LTP) to 171 ± 10% of controls in conventional ACSF, STDP was absent in sucrose prepared slices. This sucrose-induced STDP deficit could not be rescued by stronger STDP paradigms, applying either more pre- and/or postsynaptic stimuli, or by a higher stimulation frequency. Importantly, slice preparation with sucrose containing ACSF did not eliminate theta-burst stimulation induced LTP in CA1 in field potential recordings in our rat hippocampal slices. Application of dopamine (for 10–20 min) to sucrose prepared slices completely rescued t-LTP and recovered action potential properties back to levels observed in ACSF prepared slices. Conversely, acute inhibition of D1 receptor signaling impaired t-LTP in ACSF prepared slices. No similar restoring effect for STDP as seen with dopamine was observed in response to the β-adrenergic agonist isoproterenol. ELISA measurements demonstrated a significant reduction of endogenous dopamine levels (to 61.9 ± 6.9% of ACSF values) in sucrose prepared slices. These results suggest that dopamine signaling is involved in regulating the efficiency to elicit STDP in CA1 pyramidal neurons. PMID:22065958

  8. High-strain-rate brain injury model using submerged acute rat brain tissue slices.

    PubMed

    Sarntinoranont, Malisa; Lee, Sung J; Hong, Yu; King, Michael A; Subhash, Ghatu; Kwon, Jiwoon; Moore, David F

    2012-01-20

    Blast-induced traumatic brain injury (bTBI) has received increasing attention in recent years due to ongoing military operations in Iraq and Afghanistan. Sudden impacts or explosive blasts generate stress and pressure waves that propagate at high velocities and affect sensitive neurological tissues. The immediate soft tissue response to these stress waves is difficult to assess using current in vivo imaging technologies. However, these stress waves and resultant stretching and shearing of tissue within the nano- to microsecond time scale of blast and impact are likely to cause initial injury. To visualize the effects of stress wave loading, we have developed a new ex vivo model in which living tissue slices from rat brain, attached to a ballistic gelatin substrate, were subjected to high-strain-rate loads using a polymer split Hopkinson pressure bar (PSHPB) with real-time high-speed imaging. In this study, average peak fluid pressure within the test chamber reached a value of 1584±63.3 psi. Cavitation due to a trailing underpressure wave was also observed. Time-resolved images of tissue deformation were collected and large maximum eigenstrains (0.03-0.42), minimum eigenstrains (-0.33 to -0.03), maximum shear strains (0.09-0.45), and strain rates (8.4×10³/sec) were estimated using digital image correlation (DIC). Injury at 4 and 6 h was quantified using Fluoro-Jade C. Neuronal injury due to PSHPB testing was found to be significantly greater than injury associated with the tissue slice paradigm alone. While large pressures and strains were encountered for these tests, this system provides a controllable test environment to study injury to submerged brain slices over a range of strain rate, pressure, and strain loads. PMID:21970544

  9. Myocarditis along with acute ischaemic cerebellar, pontine and lacunar infarction following viper bite.

    PubMed

    Bhatt, Alok; Menon, Aravind Ajakumar; Bhat, Rama; Ramamoorthi, Kusugodlu

    2013-01-01

    Cerebrovascular complications are rare following viper bites. A 65-year-old man presented with loss of consciousness and developed haemiparesis following a viper bite. Coagulation parameters were severely deranged. MRI showed acute ischaemic infarction on the left side in the precentral and postcentral gyrus, hemipons and cerebellum. Troponin T was elevated and transient left bundle branch block was seen. The patient had a good outcome following treatment with Anti Snake Venom and supportive therapy. Possible mechanisms of infarction are discussed. PMID:24014571

  10. Myocarditis along with acute ischaemic cerebellar, pontine and lacunar infarction following viper bite

    PubMed Central

    Bhatt, Alok; Menon, Aravind Ajakumar; Bhat, Rama; Ramamoorthi, Kusugodlu

    2013-01-01

    Cerebrovascular complications are rare following viper bites. A 65-year-old man presented with loss of consciousness and developed haemiparesis following a viper bite. Coagulation parameters were severely deranged. MRI showed acute ischaemic infarction on the left side in the precentral and postcentral gyrus, hemipons and cerebellum. Troponin T was elevated and transient left bundle branch block was seen. The patient had a good outcome following treatment with Anti Snake Venom and supportive therapy. Possible mechanisms of infarction are discussed. PMID:24014571

  11. Analyzing the relationship between decorrelation time and tissue thickness in acute rat brain slices using multispeckle diffusing wave spectroscopy.

    PubMed

    Brake, Joshua; Jang, Mooseok; Yang, Changhuei

    2016-02-01

    Novel techniques in the field of wavefront shaping have enabled light to be focused deep inside or through scattering media such as biological tissue. However, most of these demonstrations have been limited to thin, static samples since these techniques are very sensitive to changes in the arrangement of the scatterers within. As the samples of interest get thicker, the influence of the dynamic nature of the sample becomes even more pronounced and the window of time in which the wavefront solutions remain valid shrinks further. In this paper, we examine the time scales upon which this decorrelation happens in acute rat brain slices via multispeckle diffusing wave spectroscopy and investigate the relationship between this decorrelation time and the thickness of the sample using diffusing wave spectroscopy theory and Monte Carlo photon transport simulation. PMID:26831778

  12. Analyzing the relationship between decorrelation time and tissue thickness in acute rat brain slices using multispeckle diffusing wave spectroscopy

    PubMed Central

    Brake, Joshua; Jang, Mooseok; Yang, Changhuei

    2016-01-01

    Novel techniques in the field of wavefront shaping have enabled light to be focused deep inside or through scattering media such as biological tissue. However, most of these demonstrations have been limited to thin, static samples since these techniques are very sensitive to changes in the arrangement of the scatterers within. As the samples of interest get thicker, the influence of the dynamic nature of the sample becomes even more pronounced and the window of time in which the wavefront solutions remain valid shrinks further. In this paper, we examine the time scales upon which this decorrelation happens in acute rat brain slices via multispeckle diffusing wave spectroscopy and investigate the relationship between this decorrelation time and the thickness of the sample using diffusing wave spectroscopy theory and Monte Carlo photon transport simulation. PMID:26831778

  13. Acute Slices of Mice Testis Seminiferous Tubules Unveil Spontaneous and Synchronous Ca2+ Oscillations in Germ Cell Clusters1

    PubMed Central

    Sánchez-Cárdenas, Claudia; Guerrero, Adán; Treviño, Claudia Lydia; Hernández-Cruz, Arturo; Darszon, Alberto

    2012-01-01

    ABSTRACT Spermatogenic cell differentiation involves changes in the concentration of cytoplasmic Ca2+ ([Ca2+]i); however, very few studies exist on [Ca2+]i dynamics in these cells. Other tissues display Ca2+ oscillations involving multicellular functional arrangements. These phenomena have been studied in acute slice preparations that preserve tissue architecture and intercellular communications. Here we report the implementation of intracellular Ca2+ imaging in a sliced seminiferous tubule (SST) preparation to visualize [Ca2+]i changes of living germ cells in situ within the SST preparation. Ca2+ imaging revealed that a subpopulation of male germ cells display spontaneous [Ca2+]i fluctuations resulting from Ca2+ entry possibly throughout CaV3 channels. These [Ca2+]i fluctuation patterns are also present in single acutely dissociated germ cells, but they differ from those recorded from germ cells in the SST preparation. Often, spontaneous Ca2+ fluctuations of spermatogenic cells in the SST occur synchronously, so that clusters of cells can display Ca2+ oscillations for at least 10 min. Synchronous Ca2+ oscillations could be mediated by intercellular communication via gap junctions, although intercellular bridges could also be involved. We also observed an increase in [Ca2+]i after testosterone application, suggesting the presence of functional Sertoli cells in the SST. In summary, we believe that the SST preparation is suitable to explore the physiology of spermatogenic cells in their natural environment, within the seminiferous tubules, in particular Ca2+ signaling phenomena, functional cell-cell communication, and multicellular functional arrangements. PMID:22914313

  14. In vivo Postnatal Electroporation and Time-lapse Imaging of Neuroblast Migration in Mouse Acute Brain Slices

    PubMed Central

    Oudin, Madeleine Julie; Doherty, Patrick; Lalli, Giovanna

    2013-01-01

    The subventricular zone (SVZ) is one of the main neurogenic niches in the postnatal brain. Here, neural progenitors proliferate and give rise to neuroblasts able to move along the rostral migratory stream (RMS) towards the olfactory bulb (OB). This long-distance migration is required for the subsequent maturation of newborn neurons in the OB, but the molecular mechanisms regulating this process are still unclear. Investigating the signaling pathways controlling neuroblast motility may not only help understand a fundamental step in neurogenesis, but also have therapeutic regenerative potential, given the ability of these neuroblasts to target brain sites affected by injury, stroke, or degeneration. In this manuscript we describe a detailed protocol for in vivo postnatal electroporation and subsequent time-lapse imaging of neuroblast migration in the mouse RMS. Postnatal electroporation can efficiently transfect SVZ progenitor cells, which in turn generate neuroblasts migrating along the RMS. Using confocal spinning disk time-lapse microscopy on acute brain slice cultures, neuroblast migration can be monitored in an environment closely resembling the in vivo condition. Moreover, neuroblast motility can be tracked and quantitatively analyzed. As an example, we describe how to use in vivo postnatal electroporation of a GFP-expressing plasmid to label and visualize neuroblasts migrating along the RMS. Electroporation of shRNA or CRE recombinase-expressing plasmids in conditional knockout mice employing the LoxP system can also be used to target genes of interest. Pharmacological manipulation of acute brain slice cultures can be performed to investigate the role of different signaling molecules in neuroblast migration. By coupling in vivo electroporation with time-lapse imaging, we hope to understand the molecular mechanisms controlling neuroblast motility and contribute to the development of novel approaches to promote brain repair. PMID:24326479

  15. Dual Electrophysiological Recordings of Synaptically-evoked Astroglial and Neuronal Responses in Acute Hippocampal Slices

    PubMed Central

    Rouach, Nathalie

    2012-01-01

    Astrocytes form together with neurons tripartite synapses, where they integrate and modulate neuronal activity. Indeed, astrocytes sense neuronal inputs through activation of their ion channels and neurotransmitter receptors, and process information in part through activity-dependent release of gliotransmitters. Furthermore, astrocytes constitute the main uptake system for glutamate, contribute to potassium spatial buffering, as well as to GABA clearance. These cells therefore constantly monitor synaptic activity, and are thereby sensitive indicators for alterations in synaptically-released glutamate, GABA and extracellular potassium levels. Additionally, alterations in astroglial uptake activity or buffering capacity can have severe effects on neuronal functions, and might be overlooked when characterizing physiopathological situations or knockout mice. Dual recording of neuronal and astroglial activities is therefore an important method to study alterations in synaptic strength associated to concomitant changes in astroglial uptake and buffering capacities. Here we describe how to prepare hippocampal slices, how to identify stratum radiatum astrocytes, and how to record simultaneously neuronal and astroglial electrophysiological responses. Furthermore, we describe how to isolate pharmacologically the synaptically-evoked astroglial currents. PMID:23222635

  16. Cerebellar Hypoplasia

    MedlinePlus

    ... disorders that begin in early childhood, such as ataxia telangiectasia. In an infant or young child, symptoms of a disorder that features cerebellar hypoplasia might include floppy muscle tone, developmental or ...

  17. Cerebellar Degeneration

    MedlinePlus

    ... Degeneration? Cerebellar degeneration is a process in which neurons in the cerebellum - the area of the brain ... proteins that are necessary for the survival of neurons. Associated diseases: Diseases that are specific to the ...

  18. Cerebellar liponeurocytoma.

    PubMed

    Owler, Brian K; Makeham, John M; Shingde, Meena; Besser, Michael

    2005-04-01

    A case of cerebellar liponeurocytoma in a 34-year-old man is reported. There are only 19 other cases reporting this entity in the medical literature. The diagnostic, radiological and clinical features associated with this tumour are reviewed and discussed in relation to our case. The differences in behaviour and prognosis between medulloblastoma and cerebellar liponeurocytoma are presented with the corresponding implications for management. PMID:15851097

  19. Resveratrol protects against oxidative injury induced by H2O2 in acute hippocampal slice preparations from Wistar rats.

    PubMed

    de Almeida, Lúcia Maria Vieira; Leite, Marina Concli; Thomazi, Ana Paula; Battu, Cíntia; Nardin, Patrícia; Tortorelli, Lucas Silva; Zanotto, Caroline; Posser, Thaís; Wofchuk, Susana Tchernin; Leal, Rodrigo Bainy; Gonçalves, Carlos-Alberto; Gottfried, Carmem

    2008-12-01

    There is a current interest in dietary compounds (such as trans-resveratrol) that can inhibit or reverse oxidative stress, the common pathway for a variety of brain disorders, including Alzheimer's disease and stroke. The objective of the present study was to investigate the effects of resveratrol, under conditions of oxidative stress induced by H(2)O(2), on acute hippocampal slices from Wistar rats. Here, we evaluated cell viability, extracellular lactate, glutathione content, ERK(MAPK) activity, glutamate uptake and S100B secretion. Resveratrol did not change the decrease in lactate levels and in cell viability (by MTT assay) induced by 1mM H(2)O(2), but prevented the increase in cell permeability to Trypan blue induced by H(2)O(2). Moreover, resveratrol per se increased total glutathione levels and prevented the decrease in glutathione induced by 1mM H(2)O(2). The reduction of S100B secretion induced by H(2)O(2) was not changed by resveratrol. Glutamate uptake was decreased in the presence of 1mM H(2)O(2) and this effect was not prevented by resveratrol. There was also a significant activation of ERK1/2 by 1mM H(2)O(2) and resveratrol was able to completely prevent this activation, leading to activity values lower than control levels. The impairments in astrocyte activities, induced by H(2)O(2), confirmed the importance of these cells as targets for therapeutic strategy in brain disorders involving oxidative stress. This study reinforces the protective role of resveratrol and indicates some possible molecular sites of activity of this compound on glial cells, in the acute damage of brain tissue during oxidative stress. PMID:18835240

  20. NAAG reduces NMDA receptor current in CA1 hippocampal pyramidal neurons of acute slices and dissociated neurons.

    PubMed

    Bergeron, Richard; Coyle, Joseph T; Tsai, Guochan; Greene, Robert W

    2005-01-01

    N-acetylaspartylglutamate (NAAG) is an abundant neuropeptide in the nervous system, yet its functions are not well understood. Pyramidal neurons of the CA1 sector of acutely prepared hippocampal slices were recorded using the whole-cell patch-clamp technique. At low concentrations (20 microM), NAAG reduced isolated N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic currents or NMDA-induced currents. The NAAG-induced change in the NMDA concentration/response curve suggested that the antagonism was not competitive. However, the NAAG-induced change in the concentration/response curve for the NMDAR co-agonist, glycine, indicated that glycine can overcome the NAAG antagonism. The antagonism of the NMDAR induced by NAAG was still observed in the presence of LY-341495, a potent and selective mGluR3 antagonist. Moreover, in dissociated pyramidal neurons of the CA1 region, NAAG also reduced the NMDA current and this effect was reversed by glycine. These results suggest that NAAG reduces the NMDA currents in hippocampal CA1 pyramidal neurons. PMID:15354184

  1. Alcohol enhances GABAergic transmission to cerebellar granule cells via an increase in Golgi cell excitability.

    PubMed

    Carta, Mario; Mameli, Manuel; Valenzuela, C Fernando

    2004-04-14

    Alcohol intoxication alters coordination and motor skills, and this is responsible for a significant number of traffic accident-related deaths around the world. Although the precise mechanism of action of ethanol (EtOH) is presently unknown, studies suggest that it acts, in part, by interfering with normal cerebellar functioning. An important component of cerebellar circuits is the granule cell. The excitability of these abundantly expressed neurons is controlled by the Golgi cell, a subtype of GABAergic interneuron. Granule cells receive GABAergic input in the form of phasic and tonic currents that are mediated by synaptic and extrasynaptic receptors, respectively. Using the acute cerebellar slice preparation and patch-clamp electrophysiological techniques, we found that ethanol induces a parallel increase in both the frequency of spontaneous IPSCs and the magnitude of the tonic current. EtOH (50 mm) did not produce this effect when spontaneous action potentials were blocked with tetrodotoxin. Recordings in the loose-patch cell-attached configuration demonstrated that ethanol increases the frequency of spontaneous action potentials in Golgi cells. Taken together, these findings indicate that ethanol enhances GABAergic inhibition of granule cells via a presynaptic mechanism that involves an increase in action potential-dependent GABA release from Golgi cells. This effect is likely to have an impact on the flow of information through the cerebellar cortex and may contribute to the mechanism by which acute ingestion of alcoholic beverages induces motor impairment. PMID:15084654

  2. Organotypic slice cultures containing the preBötzinger complex generate respiratory-like rhythms.

    PubMed

    Phillips, Wiktor S; Herly, Mikkel; Del Negro, Christopher A; Rekling, Jens C

    2016-02-01

    Study of acute brain stem slice preparations in vitro has advanced our understanding of the cellular and synaptic mechanisms of respiratory rhythm generation, but their inherent limitations preclude long-term manipulation and recording experiments. In the current study, we have developed an organotypic slice culture preparation containing the preBötzinger complex (preBötC), the core inspiratory rhythm generator of the ventrolateral brain stem. We measured bilateral synchronous network oscillations, using calcium-sensitive fluorescent dyes, in both ventrolateral (presumably the preBötC) and dorsomedial regions of slice cultures at 7-43 days in vitro. These calcium oscillations appear to be driven by periodic bursts of inspiratory neuronal activity, because whole cell recordings from ventrolateral neurons in culture revealed inspiratory-like drive potentials, and no oscillatory activity was detected from glial fibrillary associated protein-expressing astrocytes in cultures. Acute slices showed a burst frequency of 10.9 ± 4.2 bursts/min, which was not different from that of brain stem slice cultures (13.7 ± 10.6 bursts/min). However, slice cocultures that include two cerebellar explants placed along the dorsolateral border of the brainstem displayed up to 193% faster burst frequency (22.4 ± 8.3 bursts/min) and higher signal amplitude (340%) compared with acute slices. We conclude that preBötC-containing slice cultures retain inspiratory-like rhythmic function and therefore may facilitate lines of experimentation that involve extended incubation (e.g., genetic transfection or chronic drug exposure) while simultaneously being amenable to imaging and electrophysiology at cellular, synaptic, and network levels. PMID:26655824

  3. [Cerebellar stroke].

    PubMed

    Paradowski, Michał; Zimny, Anna; Paradowski, Bogusław

    2015-01-01

    Cerebellar stroke belongs to a group of rare diseases of vascular origin. Cerebellum, supplied by three pairs of arteries (AICA, PICA, SCA) with many anastomoses between them is less susceptible for a stroke, especially ischemic one. Diagnosis of the stroke in this region is harder due to lower sensibility of commonly used CT of the head in case of stroke suspicion. The authors highlight clinical symptoms distinguishing between vascular territories or topographical locations of the stroke, diagnostic procedures, classical and surgical treatment, the most common misdiagnoses are also mentioned. The authors suggest a diagnostic and therapeutic algorithm development, including rtPA treatment criteria for ischemic cerebellar stroke. PMID:26181157

  4. Cerebellar abiotrophy.

    PubMed

    DeBowes, R M; Leipold, H W; Turner-Beatty, M

    1987-08-01

    Cerebellar abiotrophy is a degenerative condition of Arabian horses that produces signs of head tremors and ataxia. Affected foals demonstrate clinical signs between the time of birth and 6 months of age. The condition is untreatable, although some animals have reportedly improved to varying degrees. The disease is believed to be inherited; however, definitive evidence is lacking at this time. PMID:3497695

  5. Alcohol Excites Cerebellar Golgi Cells by Inhibiting the Na+/K+ ATPase

    PubMed Central

    Botta, Paolo; de Souza, Fabio M Simões; Sangrey, Thomas; De Schutter, Erik; Valenzuela, C Fernando

    2010-01-01

    Alcohol-induced alterations of cerebellar function cause motor coordination impairments that are responsible for millions of injuries and deaths worldwide. Cognitive deficits associated with alcoholism are also a consequence of cerebellar dysfunction. The mechanisms responsible for these effects of ethanol are poorly understood. Recent studies have identified neurons in the input layer of the cerebellar cortex as important ethanol targets. In this layer, granule cells (GrCs) receive the majority of sensory inputs to the cerebellum through the mossy fibers. Information flow at these neurons is gated by a specialized pacemaker interneuron known as the Golgi cell, which provides divergent GABAergic input to thousands of GrCs. In vivo electrophysiological experiments have previously shown that acute ethanol exposure abolishes GrC responsiveness to sensory inputs carried by mossy fibers. Slice electrophysiological studies suggest that ethanol causes this effect by potentiating GABAergic transmission at Golgi cell-to-GrC synapses through an increase in Golgi cell excitability. Using patch-clamp electrophysiological techniques in cerebellar slices and computer modeling, we show here that ethanol excites Golgi cells by inhibiting the Na+/K+ ATPase. Voltage-clamp recordings of Na+/K+ ATPase currents indicated that ethanol partially inhibits this pump and this effect could be mimicked by low concentrations of ouabain. Partial inhibition of Na+/K+ ATPase function in a computer model of the Golgi cell reproduced these experimental findings. These results establish a novel mechanism of action of ethanol on neuronal excitability, which likely has a role in ethanol-induced cerebellar dysfunction and may also contribute to neuronal functional alterations in other brain regions. PMID:20520600

  6. Analysis of acute brain slices by electron microscopy: a correlative light-electron microscopy workflow based on Tokuyasu cryo-sectioning.

    PubMed

    Loussert Fonta, Celine; Leis, Andrew; Mathisen, Cliff; Bouvier, David S; Blanchard, Willy; Volterra, Andrea; Lich, Ben; Humbel, Bruno M

    2015-01-01

    Acute brain slices are slices of brain tissue that are kept vital in vitro for further recordings and analyses. This tool is of major importance in neurobiology and allows the study of brain cells such as microglia, astrocytes, neurons and their inter/intracellular communications via ion channels or transporters. In combination with light/fluorescence microscopies, acute brain slices enable the ex vivo analysis of specific cells or groups of cells inside the slice, e.g. astrocytes. To bridge ex vivo knowledge of a cell with its ultrastructure, we developed a correlative microscopy approach for acute brain slices. The workflow begins with sampling of the tissue and precise trimming of a region of interest, which contains GFP-tagged astrocytes that can be visualised by fluorescence microscopy of ultrathin sections. The astrocytes and their surroundings are then analysed by high resolution scanning transmission electron microscopy (STEM). An important aspect of this workflow is the modification of a commercial cryo-ultramicrotome to observe the fluorescent GFP signal during the trimming process. It ensured that sections contained at least one GFP astrocyte. After cryo-sectioning, a map of the GFP-expressing astrocytes is established and transferred to correlation software installed on a focused ion beam scanning electron microscope equipped with a STEM detector. Next, the areas displaying fluorescence are selected for high resolution STEM imaging. An overview area (e.g. a whole mesh of the grid) is imaged with an automated tiling and stitching process. In the final stitched image, the local organisation of the brain tissue can be surveyed or areas of interest can be magnified to observe fine details, e.g. vesicles or gold labels on specific proteins. The robustness of this workflow is contingent on the quality of sample preparation, based on Tokuyasu's protocol. This method results in a reasonable compromise between preservation of morphology and maintenance of

  7. [Case of cerebellar and spinal cord infarction presenting with acute brachial diplegia due to right vertebral artery occlusion].

    PubMed

    Fujii, Takayuki; Santa, Yo; Akutagawa, Noriko; Nagano, Sukehisa; Yoshimura, Takeo

    2012-01-01

    A 73-year-old man was admitted for evaluation of sudden onset of dizziness, bilateral shoulder pain, and brachial diplegia. Neurological examination revealed severe bilateral weakness of the triceps brachii, wrist flexor, and wrist extensor muscles. There was no paresis of the lower limbs. His gait was ataxic. Pinprick and temperature sensations were diminished at the bilateral C6-C8 dermatomes. Vibration and position senses were intact. An MRI of the head revealed a right cerebellar infarction and occlusion of the right vertebral artery. An MRI of the cervical spine on T₂ weighted imaging (T₂WI) showed cord compression at the C3/4-C5/6 level secondary to spondylotic degeneration without any intramedullary signal changes of the cord. On the following day, however, high-signal lesions on T₂WI appeared in the C5-C6 spinal cord, suggesting cord infarction. Unilateral vertebral artery occlusion does not usually result in cervical cord infarction because of anastomosis of arteries. Because of the long-term mechanical compression in our case, it was likely that cervical cord ischemia was present before the onset of symptoms. On the basis of chronic cord compression, our case suggests that occlusion of a unilateral vertebral artery could cause cervical cord infarction. PMID:22790805

  8. Voltage-gated calcium channel autoimmune cerebellar degeneration

    PubMed Central

    McKasson, Marilyn; Clawson, Susan A.; Hill, Kenneth E.; Wood, Blair; Carlson, Noel; Bromberg, Mark; Greenlee, John E.

    2016-01-01

    Objectives: To describe response to treatment in a patient with autoantibodies against voltage-gated calcium channels (VGCCs) who presented with autoimmune cerebellar degeneration and subsequently developed Lambert-Eaton myasthenic syndrome (LEMS), and to study the effect of the patient's autoantibodies on Purkinje cells in rat cerebellar slice cultures. Methods: Case report and study of rat cerebellar slice cultures incubated with patient VGCC autoantibodies. Results: A 53-year-old man developed progressive incoordination with ataxic speech. Laboratory evaluation revealed VGCC autoantibodies without other antineuronal autoantibodies. Whole-body PET scans 6 and 12 months after presentation detected no malignancy. The patient improved significantly with IV immunoglobulin G (IgG), prednisone, and mycophenolate mofetil, but worsened after IV IgG was halted secondary to aseptic meningitis. He subsequently developed weakness with electrodiagnostic evidence of LEMS. The patient's IgG bound to Purkinje cells in rat cerebellar slice cultures, followed by neuronal death. Reactivity of the patient's autoantibodies with VGCCs was confirmed by blocking studies with defined VGCC antibodies. Conclusions: Autoimmune cerebellar degeneration associated with VGCC autoantibodies may precede onset of LEMS and may improve with immunosuppressive treatment. Binding of anti-VGCC antibodies to Purkinje cells in cerebellar slice cultures may be followed by cell death. Patients with anti-VGCC autoantibodies may be at risk of irreversible neurologic injury over time, and treatment should be initiated early. PMID:27088118

  9. 4-aminopyridine reverses ataxia and cerebellar firing deficiency in a mouse model of spinocerebellar ataxia type 6

    PubMed Central

    Jayabal, Sriram; Chang, Hui Ho Vanessa; Cullen, Kathleen E.; Watt, Alanna J.

    2016-01-01

    Spinocerebellar ataxia type 6 (SCA6) is a devastating midlife-onset autosomal dominant motor control disease with no known treatment. Using a hyper-expanded polyglutamine (84Q) knock-in mouse, we found that cerebellar Purkinje cell firing precision was degraded in heterozygous (SCA684Q/+) mice at 19 months when motor deficits are observed. Similar alterations in firing precision and motor control were observed at disease onset at 7 months in homozygous (SCA684Q/84Q) mice, as well as a reduction in firing rate. We further found that chronic administration of the FDA-approved drug 4-aminopyridine (4-AP), which targets potassium channels, alleviated motor coordination deficits and restored cerebellar Purkinje cell firing precision to wildtype (WT) levels in SCA684Q/84Q mice both in acute slices and in vivo. These results provide a novel therapeutic approach for treating ataxic symptoms associated with SCA6. PMID:27381005

  10. 4-aminopyridine reverses ataxia and cerebellar firing deficiency in a mouse model of spinocerebellar ataxia type 6.

    PubMed

    Jayabal, Sriram; Chang, Hui Ho Vanessa; Cullen, Kathleen E; Watt, Alanna J

    2016-01-01

    Spinocerebellar ataxia type 6 (SCA6) is a devastating midlife-onset autosomal dominant motor control disease with no known treatment. Using a hyper-expanded polyglutamine (84Q) knock-in mouse, we found that cerebellar Purkinje cell firing precision was degraded in heterozygous (SCA6(84Q/+)) mice at 19 months when motor deficits are observed. Similar alterations in firing precision and motor control were observed at disease onset at 7 months in homozygous (SCA6(84Q/84Q)) mice, as well as a reduction in firing rate. We further found that chronic administration of the FDA-approved drug 4-aminopyridine (4-AP), which targets potassium channels, alleviated motor coordination deficits and restored cerebellar Purkinje cell firing precision to wildtype (WT) levels in SCA6(84Q/84Q) mice both in acute slices and in vivo. These results provide a novel therapeutic approach for treating ataxic symptoms associated with SCA6. PMID:27381005

  11. Murine precision-cut lung slices exhibit acute responses following exposure to gasoline direct injection engine emissions.

    PubMed

    Maikawa, Caitlin L; Zimmerman, Naomi; Rais, Khaled; Shah, Mittal; Hawley, Brie; Pant, Pallavi; Jeong, Cheol-Heon; Delgado-Saborit, Juana Maria; Volckens, John; Evans, Greg; Wallace, James S; Godri Pollitt, Krystal J

    2016-10-15

    Gasoline direct injection (GDI) engines are increasingly prevalent in the global vehicle fleet. Particulate matter emissions from GDI engines are elevated compared to conventional gasoline engines. The pulmonary effects of these higher particulate emissions are unclear. This study investigated the pulmonary responses induced by GDI engine exhaust using an ex vivo model. The physiochemical properties of GDI engine exhaust were assessed. Precision cut lung slices were prepared using Balb/c mice to evaluate the pulmonary response induced by one-hour exposure to engine-out exhaust from a laboratory GDI engine operated at conditions equivalent to vehicle highway cruise conditions. Lung slices were exposed at an air-liquid interface using an electrostatic aerosol in vitro exposure system. Particulate and gaseous exhaust was fractionated to contrast mRNA production related to polycyclic aromatic hydrocarbon (PAH) metabolism and oxidative stress. Exposure to GDI engine exhaust upregulated genes involved in PAH metabolism, including Cyp1a1 (2.71, SE=0.22), and Cyp1b1 (3.24, SE=0.12) compared to HEPA filtered air (p<0.05). GDI engine exhaust further increased Cyp1b1 expression compared to filtered GDI engine exhaust (i.e., gas fraction only), suggesting this response was associated with the particulate fraction. Exhaust particulate was dominated by high molecular weight PAHs. Hmox1, an oxidative stress marker, exhibited increased expression after exposure to GDI (1.63, SE=0.03) and filtered GDI (1.55, SE=0.04) engine exhaust compared to HEPA filtered air (p<0.05), likely attributable to a combination of the gas and particulate fractions. Exposure to GDI engine exhaust contributes to upregulation of genes related to the metabolism of PAHs and oxidative stress. PMID:27369091

  12. Massive splenic infarction and splenic venous thrombosis observed in a patient with acute splenic syndrome of sickle cell traits on contrast-enhanced thin-slice computed tomography.

    PubMed

    Hayashi, Takana Yamakawa; Matsuda, Izuru; Hagiwara, Kazuchika; Takayanagi, Tomoko; Hagiwara, Akifumi

    2016-09-01

    We report a case of splenic infarction in a patient with sickle cell traits (SCT), focusing on the computed tomography (CT) findings. The patient was an African-American man in his twenties with no past medical history who experienced sudden left upper quadrant pain while climbing a mountain (over 3000 m above sea level). Dynamic contrast-enhanced CT revealed massive non-segmental splenic infarction accompanied with nodule-like preserved splenic tissue. The region of splenic infarction did not coincide with the arterial vascular territory and differed from the features of infarction caused by large arterial embolism. In addition, thrombotic occlusion of the distal splenic vein was depicted on plain and contrast-enhanced thin-slice CT images. Early-phase contrast-enhanced images also showed inhomogeneous enhancement of the hepatic parenchyma. The patient's symptoms improved with conservative therapy. A hemoglobin electrophoresis test confirmed the diagnosis of SCT. SCT is usually asymptomatic, but hypoxic environments may induce acute splenic syndrome, which is commonly manifested as splenic infarction. We observed splenic venous thrombosis and inhomogeneous hepatic parenchymal enhancement in addition to a huge splenic infarction in our patient. To the best of our knowledge, this is the first report describing the specific imaging findings, particularly splenic venous thrombosis and inhomogeneous hepatic parenchymal enhancement, of acute splenic syndrome in a patient with previously undiagnosed SCT. These findings demonstrate the pathophysiology of SCT, and may help with the diagnosis of this disease. PMID:27251735

  13. Ex vivo imaging of postnatal cerebellar granule cell migration using confocal macroscopy.

    PubMed

    Bénard, Magalie; Lebon, Alexis; Komuro, Hitoshi; Vaudry, David; Galas, Ludovic

    2015-01-01

    During postnatal development, immature granule cells (excitatory interneurons) exhibit tangential migration in the external granular layer, and then radial migration in the molecular layer and the Purkinje cell layer to reach the internal granular layer of the cerebellar cortex. Default in migratory processes induces either cell death or misplacement of the neurons, leading to deficits in diverse cerebellar functions. Centripetal granule cell migration involves several mechanisms, such as chemotaxis and extracellular matrix degradation, to guide the cells towards their final position, but the factors that regulate cell migration in each cortical layer are only partially known. In our method, acute cerebellar slices are prepared from P10 rats, granule cells are labeled with a fluorescent cytoplasmic marker and tissues are cultured on membrane inserts from 4 to 10 hr before starting real-time monitoring of cell migration by confocal macroscopy at 37 °C in the presence of CO2. During their migration in the different cortical layers of the cerebellum, granule cells can be exposed to neuropeptide agonists or antagonists, protease inhibitors, blockers of intracellular effectors or even toxic substances such as alcohol or methylmercury to investigate their possible role in the regulation of neuronal migration. PMID:25992599

  14. Ex Vivo Imaging of Postnatal Cerebellar Granule Cell Migration Using Confocal Macroscopy

    PubMed Central

    Bénard, Magalie; Lebon, Alexis; Komuro, Hitoshi; Vaudry, David; Galas, Ludovic

    2015-01-01

    During postnatal development, immature granule cells (excitatory interneurons) exhibit tangential migration in the external granular layer, and then radial migration in the molecular layer and the Purkinje cell layer to reach the internal granular layer of the cerebellar cortex. Default in migratory processes induces either cell death or misplacement of the neurons, leading to deficits in diverse cerebellar functions. Centripetal granule cell migration involves several mechanisms, such as chemotaxis and extracellular matrix degradation, to guide the cells towards their final position, but the factors that regulate cell migration in each cortical layer are only partially known. In our method, acute cerebellar slices are prepared from P10 rats, granule cells are labeled with a fluorescent cytoplasmic marker and tissues are cultured on membrane inserts from 4 to 10 hr before starting real-time monitoring of cell migration by confocal macroscopy at 37 °C in the presence of CO2. During their migration in the different cortical layers of the cerebellum, granule cells can be exposed to neuropeptide agonists or antagonists, protease inhibitors, blockers of intracellular effectors or even toxic substances such as alcohol or methylmercury to investigate their possible role in the regulation of neuronal migration. PMID:25992599

  15. Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation

    PubMed Central

    Pashut, Tamar; Magidov, Dafna; Ben-Porat, Hana; Wolfus, Shuki; Friedman, Alex; Perel, Eli; Lavidor, Michal; Bar-Gad, Izhar; Yeshurun, Yosef; Korngreen, Alon

    2014-01-01

    Although transcranial magnetic stimulation (TMS) is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood. We have previously predicted, using compartmental modeling, that magnetic stimulation of central nervous system neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. The simulations also predict that neurons with low current threshold are more susceptible to magnetic stimulation. Here we tested these theoretical predictions by combining in vitro patch-clamp recordings from rat brain slices with magnetic stimulation and compartmental modeling. In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field. Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies. PMID:24917788

  16. The tricyclic antidepressant desipramine inhibited the neurotoxic, kainate-induced [Ca(2+)]i increases in CA1 pyramidal cells in acute hippocampal slices.

    PubMed

    Koncz, István; Szász, Bernadett K; Szabó, Szilárd I; Kiss, János P; Mike, Arpád; Lendvai, Balázs; Sylvester Vizi, E; Zelles, Tibor

    2014-05-01

    Kainate (KA), used for modelling neurodegenerative diseases, evokes excitotoxicity. However, the precise mechanism of KA-evoked [Ca(2+)]i increase is unexplored, especially in acute brain slice preparations. We used [Ca(2+)]i imaging and patch clamp electrophysiology to decipher the mechanism of KA-evoked [Ca(2+)]i rise and its inhibition by the tricyclic antidepressant desipramine (DMI) in CA1 pyramidal cells in rat hippocampal slices and in cultured hippocampal cells. The effect of KA was dose-dependent and relied totally on extracellular Ca(2+). The lack of effect of dl-2-amino-5-phosphonopentanoic acid (AP-5) and abolishment of the response by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) suggested the involvement of non-N-methyl-d-aspartate receptors (non-NMDARs). The predominant role of the Ca(2+)-impermeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) in the initiation of the Ca(2+) response was supported by the inhibitory effect of the selective AMPAR antagonist GYKI 53655 and the ineffectiveness of 1-naphthyl acetylspermine (NASPM), an inhibitor of the Ca(2+)-permeable AMPARs. The voltage-gated Ca(2+) channels (VGCC), blocked by ω-Conotoxin MVIIC+nifedipine+NiCl2, contributed to the [Ca(2+)]i rise. VGCCs were also involved, similarly to AMPAR current, in the KA-evoked depolarisation. Inhibition of voltage-gated Na(+) channels (VGSCs; tetrodotoxin, TTX) did not affect the depolarisation of pyramidal cells but blocked the depolarisation-evoked action potential bursts and reduced the Ca(2+) response. The tricyclic antidepressant DMI inhibited the KA-evoked [Ca(2+)]i rise in a dose-dependent manner. It directly attenuated the AMPA-/KAR current, but its more potent inhibition on the Ca(2+) response supports additional effect on VGCCs, VGSCs and Na(+)/Ca(2+) exchangers. The multitarget action on decisive players of excitotoxicity holds out more promise in clinical therapy of neurodegenerative diseases. PMID:24742525

  17. Non-specific inhibitors of aquaporin-4 stimulate S100B secretion in acute hippocampal slices of rats.

    PubMed

    Zanotto, Caroline; Abib, Renata Torres; Batassini, Cristiane; Tortorelli, Lucas Silva; Biasibetti, Regina; Rodrigues, Letícia; Nardin, Patrícia; Hansen, Fernanda; Gottfried, Carmem; Leite, Marina Concli; Gonçalves, Carlos-Alberto

    2013-01-23

    Aquaporin-4 (AQP-4) is the principal brain water channel and is predominantly expressed in astrocytes suggesting its dynamic involvement in water homeostasis in brain tissue. Due to the co-localization of AQP-4 and inward rectifier K(+) channels Kir 4.1, a functional coupling between these proteins has been proposed. AQP-4 has a putative role in the physiopathology of brain disorders including epilepsy and trauma. S100B is a calcium-binding protein expressed and secreted by astrocytes, and commonly used as a parameter of astroglial activation. Here, we investigate a possible link between AQP-4 activity (and Kir 4.1) and S100B secretion in hippocampal slices of rats of different ages using non-specific inhibitors of AQP-4 (AZA, acetazolamide and TEA, tetraethylammonium) and Kir 4.1 (barium chloride). We found that blockade of AQP-4 with TEA and AZA produced an increase in S100B secretion in young rats, compatible with an astroglial activation observed in many conditions of brain injury. On the other hand, BaCl(2) induced Kir 4.1 inhibition caused a decrease in S100B secretion. Both channels, AQP-4 and Kir 4.1, exhibited a similar ontogenetic profile, in spite of the functional uncoupling, in relation to S100B secretion. Moreover, we found a significant increase in the S100B secretion basal levels with the increasing of animal age and the incubation with high levels of potassium resulted in a decrease of S100B secretion in 30 and 90-day old rats. These data, together with previous observations from gap junctions and glutamate transport of astrocytes, contribute to characterize the operational system involving astroglial activation, particularly on S100B secretion, in brain disorders. PMID:23142267

  18. Evaluation of Mitochondrial Function in the CNS of Rodent Models of Alzheimer's Disease - High Resolution Respirometry Applied to Acute Hippocampal Slices.

    PubMed

    Dias, Candida; Barbosa, Rui M; Laranjinha, Joao; Ledo, Ana

    2014-10-01

    Alzheimer's disease (AD) is a multifactorial disease characterized by extracellular deposits of amyloid plaques and intracellular neurofibrillary tangles. These hallmark alterations are preceded by synaptic deterioration, changes in neuromolecular plasticity phenomena, mitochondrial dysfunction, increase in oxidative damage to cellular constituents and decreased energy metabolism. The hippocampus is a structure of the temporal medial lobe implicated in specific forms of memory processes. It is also one of the first and most affected regions of the CNS in AD. Here we present a novel approach to the study if mitochondrial function/disfunction in 2 rodent models of AD: an acute rat model obtained by intracerebroventricular injection of the toxin streptozotocin (STZ) and a progressive triple transgenic mouse model (3TgAD) harboring PS1M146V, APPSwe, and tauP301L transgenes. Mitochondrial dysfunction has classically been assessed in such models by isolating mitochondria, synaptossoms or working with cell cultures. Anyone of these approaches destroys the intricate intercellular connectivity and cytoarchitecture of neuronal tissue. We used acute hippocampal slices obtained from the 2 models of AD and evaluated changes in mitochondrial function as a function of disease and/or age. Mitochondrial stress test were performed on the high resolution respirometry (Oroboros 2K Oxymeter). Upon analysis of oxygen consumption rates (OCR) we observed significant decreases in basal OCR, maximal respiratory capacity, ATP turnover and a tendency for decrease in sparing capacity in the STZ rat model compared to shame injected animals. Regarding the 3TgAD model we observed an age-dependent decrease in all parameters evaluated in the mitochondrial stress test, in both 3TgAD and NTg animals. However, although a tendency towards decreased OCR was observed when comparing 3TgAD and age-matched NTg animals, no statistically significant difference was observed. PMID:26461355

  19. Lumican as a novel potential clinical indicator for acute aortic dissection: A comparative study, based on multi-slice computed tomography angiography

    PubMed Central

    GU, GUORONG; WAN, FANG; XUE, YUAN; CHENG, WEIZHONG; ZHENG, HAIYIN; ZHAO, YUN; FAN, FAN; HAN, YI; TONG, CHAOYANG; YAO, CHENLING

    2016-01-01

    The aim of the present study was to investigate the association between serum lumican levels and acute aortic dissection (AAD) severity. A total of 82 patients with chest or back pain and 30 healthy volunteers were recruited. Among the patients, there were 70 cases of AAD and 12 cases of intramural hematoma (IMH). AAD severity was determined using multi-slice computed tomography angiography (MSCTA). Serum was collected from the patients upon admission, and lumican levels were detected using an enzyme-linked immunosorbent assay. In addition, correlation analyses were conducted between lumican levels and AAD severity by designing a ‘SCORE X, RANGE Y’ system to measure the number of affected vital arteries and vertical range of false lumen, based on the MSCTA. Lumican levels differed significantly among the AAD patients (2.32±4.29 ng/ml), IMH patients (0.72±0.32 ng/ml) and healthy volunteers (0.85±0.53 ng/ml; P=0.003). In the AAD patients presenting within 12–72 h of symptom onset, the Spearman's rho correlation coefficient between lumican and SCORE or RANGE was 0.373 (P=0.046) and 0.468 (P=0.010), respectively. The present results suggest that lumican may be a potential marker for aiding the diagnosis and screening for AAD, and may be used to predict the severity of AAD. PMID:26998013

  20. Mice deficient in carbonic anhydrase type 8 exhibit motor dysfunctions and abnormal calcium dynamics in the somatic region of cerebellar granule cells.

    PubMed

    Lamont, Matthew G; Weber, John T

    2015-06-01

    The waddles (wdl) mouse is characterized by a namesake "side-to-side" waddling gait due to a homozygous mutation of the Car8 gene. This mutation results in non-functional copies of the protein carbonic anhydrase type 8. Rota-rod testing was conducted to characterize the wdl mutations' effect on motor output. Results indicated that younger homozygotes outperformed their older cohorts, an effect not seen in previous studies. Heterozygotes, which were thought to be free of motor impairment, displayed motor learning deficiencies when compared with wild type performance. Acute cerebellar slices were then utilized for fluorescent calcium imaging experiments, which revealed significant alterations in cerebellar granule cell somatic calcium signaling when exposed to glutamate. The contribution of GABAergic signaling to these alterations was also verified using bath application of bicuculline. Changes in somatic calcium signals were found to be applicable to an in vivo scenario by comparing group responses to electrical stimulation of afferent mossy fiber projections. Finally, intracellular calcium store function was also found to be altered by the wdl mutation when slices were treated with thapsigargin. These findings, taken together with previous work on the wdl mouse, indicate a widespread disruption in cerebellar circuitry hampering proper neuronal communication. PMID:25721739

  1. Development and characterization of an ex-vivo brain slice culture model of chronic wasting disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prion diseases have long incubation times in vivo, therefore, modeling the diseases ex-vivo will advance the development of rationale-based therapeutic strategies. An organotypic slice culture assay (POSCA) was recently developed for scrapie prions by inoculating mouse cerebellar brain slices with R...

  2. The spatiotemporal organization of cerebellar network activity resolved by two-photon imaging of multiple single neurons

    PubMed Central

    Gandolfi, Daniela; Pozzi, Paolo; Tognolina, Marialuisa; Chirico, Giuseppe; Mapelli, Jonathan; D'Angelo, Egidio

    2014-01-01

    In order to investigate the spatiotemporal organization of neuronal activity in local microcircuits, techniques allowing the simultaneous recording from multiple single neurons are required. To this end, we implemented an advanced spatial-light modulator two-photon microscope (SLM-2PM). A critical issue for cerebellar theory is the organization of granular layer activity in the cerebellum, which has been predicted by single-cell recordings and computational models. With SLM-2PM, calcium signals could be recorded from different network elements in acute cerebellar slices including granule cells (GrCs), Purkinje cells (PCs) and molecular layer interneurons. By combining WCRs with SLM-2PM, the spike/calcium relationship in GrCs and PCs could be extrapolated toward the detection of single spikes. The SLM-2PM technique made it possible to monitor activity of over tens to hundreds neurons simultaneously. GrC activity depended on the number of spikes in the input mossy fiber bursts. PC and molecular layer interneuron activity paralleled that in the underlying GrC population revealing the spread of activity through the cerebellar cortical network. Moreover, circuit activity was increased by the GABA-A receptor blocker, gabazine, and reduced by the AMPA and NMDA receptor blockers, NBQX and APV. The SLM-2PM analysis of spatiotemporal patterns lent experimental support to the time-window and center-surround organizing principles of the granular layer. PMID:24782707

  3. Cerebellar ataxia as a possible complication of babesiosis in two dogs.

    PubMed

    Jacobson, L S

    1994-09-01

    A 6-month-old Miniature Doberman Pinscher was presented with inappetance and cerebellar signs. Babesia canis organisms were found on a capillary bloodsmear. The cerebellar signs resolved rapidly following treatment with diminazene aceturate. A 7-month-old Siberian Husky developed cerebellar signs, blindness and quadriparesis 9 d after presentation with clinical signs typical of uncomplicated canine babesiosis. The dog responded favourably to treatment with prednisolone. Both acute and delayed cerebellar ataxia have been associated with malaria in humans. The clinical signs shown by these dogs were similar to those reported for malaria in humans. Cerebellar ataxia should be considered a possible complication of canine babesiosis. PMID:7595921

  4. Cerebellar and Brainstem Malformations.

    PubMed

    Poretti, Andrea; Boltshauser, Eugen; Huisman, Thierry A G M

    2016-08-01

    The frequency and importance of the evaluation of the posterior fossa have increased significantly over the past 20 years owing to advances in neuroimaging. Conventional and advanced neuroimaging techniques allow detailed evaluation of the complex anatomic structures within the posterior fossa. A wide spectrum of cerebellar and brainstem malformations has been shown. Familiarity with the spectrum of cerebellar and brainstem malformations and their well-defined diagnostic criteria is crucial for optimal therapy, an accurate prognosis, and correct genetic counseling. This article discusses cerebellar and brainstem malformations, with emphasis on neuroimaging findings (including diagnostic criteria), neurologic presentation, systemic involvement, prognosis, and recurrence. PMID:27423798

  5. Humor and laughter in patients with cerebellar degeneration.

    PubMed

    Frank, B; Propson, B; Göricke, S; Jacobi, H; Wild, B; Timmann, D

    2012-06-01

    Humor is a complex behavior which includes cognitive, affective and motor responses. Based on observations of affective changes in patients with cerebellar lesions, the cerebellum may support cerebral and brainstem areas involved in understanding and appreciation of humorous stimuli and expression of laughter. The aim of the present study was to examine if humor appreciation, perception of humorous stimuli, and the succeeding facial reaction differ between patients with cerebellar degeneration and healthy controls. Twenty-three adults with pure cerebellar degeneration were compared with 23 age-, gender-, and education-matched healthy control subjects. No significant difference in humor appreciation and perception of humorous stimuli could be found between groups using the 3 Witz-Dimensionen Test, a validated test asking for funniness and aversiveness of jokes and cartoons. Furthermore, while observing jokes, humorous cartoons, and video sketches, facial expressions of subjects were videotaped and afterwards analysed using the Facial Action Coding System. Using depression as a covariate, the number, and to a lesser degree, the duration of facial expressions during laughter were reduced in cerebellar patients compared to healthy controls. In sum, appreciation of humor appears to be largely preserved in patients with chronic cerebellar degeneration. Cerebellar circuits may contribute to the expression of laughter. Findings add to the literature that non-motor disorders in patients with chronic cerebellar disease are generally mild, but do not exclude that more marked disorders may show up in acute cerebellar disease and/or in more specific tests of humor appreciation. PMID:22012411

  6. Dendritic patch-clamp recordings from cerebellar granule cells demonstrate electrotonic compactness

    PubMed Central

    Delvendahl, Igor; Straub, Isabelle; Hallermann, Stefan

    2015-01-01

    Cerebellar granule cells (GCs), the smallest neurons in the brain, have on average four short dendrites that receive high-frequency mossy fiber inputs conveying sensory information. The short length of the dendrites suggests that GCs are electrotonically compact allowing unfiltered integration of dendritic inputs. The small average diameter of the dendrites (~0.7 µm), however, argues for dendritic filtering. Previous studies based on somatic recordings and modeling indicated that GCs are electrotonically extremely compact. Here, we performed patch-clamp recordings from GC dendrites in acute brain slices of mice to directly analyze the electrotonic properties of GCs. Strikingly, the input resistance did not differ significantly between dendrites and somata of GCs. Furthermore, spontaneous excitatory postsynaptic potentials (EPSP) were similar in amplitude at dendritic and somatic recording sites. From the dendritic and somatic input resistances we determined parameters characterizing the electrotonic compactness of GCs. These data directly demonstrate that cerebellar GCs are electrotonically compact and thus ideally suited for efficient high-frequency information transfer. PMID:25852483

  7. Thick Slice and Thin Slice Teaching Evaluations

    ERIC Educational Resources Information Center

    Tom, Gail; Tong, Stephanie Tom; Hesse, Charles

    2010-01-01

    Student-based teaching evaluations are an integral component to institutions of higher education. Previous work on student-based teaching evaluations suggest that evaluations of instructors based upon "thin slice" 30-s video clips of them in the classroom correlate strongly with their end of the term "thick slice" student evaluations. This study's…

  8. Preserving GABAergic interneurons in acute brain slices of mice using the N-methyl-D-glucamine-based artificial cerebrospinal fluid method.

    PubMed

    Pan, Geng; Li, Yue; Geng, Hong-Yan; Yang, Jian-Ming; Li, Ke-Xin; Li, Xiao-Ming

    2015-04-01

    Defects in the function and development of GABAergic interneurons have been linked to psychiatric disorders, so preservation of these interneurons in brain slices is important for successful electrophysiological recording in various ex vivo methods. However, it is difficult to maintain the activity and morphology of neurons in slices from mice of >30 days old. Here we evaluated the N-methyl-D-glucamine (NMDG)-based artificial cerebrospinal fluid (aCSF) method for the preservation of interneurons in slices from mice of up to ∼6 months old and discussed the steps that may affect their quality during slicing. We found that the NMDG-aCSF method rescued more cells than sucrose-aCSF and successfully preserved different types of interneurons including parvalbumin- and somatostatin-positive interneurons. In addition, both the chemical and electrical synaptic signaling of interneurons were maintained. These results demonstrate that the NMDG-aCSF method is suitable for the preservation of interneurons, especially in studies of gap junctions. PMID:25648546

  9. The inhibitory input to mouse cerebellar Purkinje cells is reciprocally modulated by Bergmann glial P2Y1 and AMPA receptor signaling.

    PubMed

    Rudolph, Ramona; Jahn, Hannah M; Courjaret, Raphael; Messemer, Nanette; Kirchhoff, Frank; Deitmer, Joachim W

    2016-07-01

    Synaptic transmission has been shown to be modulated by glial functions, but the modes of specific glial action may vary in different neural circuits. We have tested the hypothesis, if Bergmann GLIA (BG) are involved in shaping neuronal communication in the mouse cerebellar cortex, using acutely isolated cerebellar slices of wild-type (WT) and of glia-specific receptor knockout mice. Activation of P2Y1 receptors by ADP (100 µM) or glutamatergic receptors by AMPA (0.3 µM) resulted in a robust, reversible and repeatable rise of evoked inhibitory input in Purkinje cells by 80% and 150%, respectively. The ADP-induced response was suppressed by prior application of AMPA, and the AMPA-induced response was suppressed by prior application of ADP. Genetic deletion or pharmacological blockade of either receptor restored the response to the other receptor agonist. Both ADP and AMPA responses were sensitive to Rose Bengal, which blocks vesicular glutamate uptake, and to the NMDA receptor antagonist D-AP5. Our results provide strong evidence that activation of both ADP and AMPA receptors, located on BGs, results in the release of glutamate, which in turn activates inhibitory interneurons via NMDA-type glutamate receptors. This infers that BG cells, by means of metabotropic signaling via their AMPA and P2Y1 receptors, which mutually suppress each other, would interdependently contribute to the fine-tuning of Purkinje cell activity in the cerebellar cortex. GLIA 2016. GLIA 2016;64:1265-1280. PMID:27144942

  10. Unilateral cerebellar aplasia.

    PubMed

    Boltshauser, E; Steinlin, M; Martin, E; Deonna, T

    1996-02-01

    We describe three children with unilateral cerebellar aplasia (UCA). Deliveries at term and neonatal periods were uneventful. Pregnancy was normal in one and complicated by mild bleeding (in second and fourth month respectively) in two instances. Presenting signs were delayed motor development with marked contralateral torticollis (n = 1), hemiplegia (n = 1) and unusual head nodding (n = 1). Neuroradiological investigations revealed complete aplasia (n = 1) and subtotal aplasia (n = 2) of one cerebellar hemisphere with only a residual wing-like structure below the tentorium. There was contralateral underdevelopment of the brainstem. The infant with hemiplegic cerebral palsy had an additional supratentorial periventricular parenchymal defect, contralateral to the cerebellar hypoplasia. In view of literature reports, describing similar neuroradiological or neuropathological findings in asymptomatic individuals, it is doubtful whether UCA is responsible for our patient's problems. In our cases UCA has presumably resulted from a prenatal destructive lesion, possibly an infarct, but the timing and exact nature are unknown. PMID:8677027

  11. Cerebellar ataxia as presenting feature of hypothyroidism.

    PubMed

    Kotwal, Suman Kumar; Kotwal, Shalija; Gupta, Rohan; Singh, Jang Bhadur; Mahajan, Annil

    2016-04-01

    Symptoms and signs of the hypothyroidism vary in relation to the magnitude and acuteness of the thyroid hormone deficiency. The usual clinical features are constipation, fatigue, cold intolerance and weight gain. Rarely it can present with neurologic problems like reversible cerebellar ataxia, dementia, peripheral neuropathy, psychosis and coma. Hypothyroidism should be suspected in all cases of ataxia, as it is easily treatable. A 40 year-old male presented with the history facial puffiness, hoarseness of voice and gait-ataxia. Investigations revealed frank primary hypothyroidism. Anti-TPO antibody was positive. Thyroxine was started and patient improved completely within eight weeks. Hypothyroidism can present with ataxia as presenting feature. Hypothyroidism should be considered in all cases of cerebellar ataxia as it is a reversible cause of ataxia. PMID:26886095

  12. Parametric Trace Slicing

    NASA Technical Reports Server (NTRS)

    Rosu, Grigore (Inventor); Chen, Feng (Inventor); Chen, Guo-fang; Wu, Yamei; Meredith, Patrick O. (Inventor)

    2014-01-01

    A program trace is obtained and events of the program trace are traversed. For each event identified in traversing the program trace, a trace slice of which the identified event is a part is identified based on the parameter instance of the identified event. For each trace slice of which the identified event is a part, the identified event is added to an end of a record of the trace slice. These parametric trace slices can be used in a variety of different manners, such as for monitoring, mining, and predicting.

  13. Consensus Paper: Neuroimmune Mechanisms of Cerebellar Ataxias.

    PubMed

    Mitoma, Hiroshi; Adhikari, Keya; Aeschlimann, Daniel; Chattopadhyay, Partha; Hadjivassiliou, Marios; Hampe, Christiane S; Honnorat, Jérôme; Joubert, Bastien; Kakei, Shinji; Lee, Jongho; Manto, Mario; Matsunaga, Akiko; Mizusawa, Hidehiro; Nanri, Kazunori; Shanmugarajah, Priya; Yoneda, Makoto; Yuki, Nobuhiro

    2016-04-01

    In the last few years, a lot of publications suggested that disabling cerebellar ataxias may develop through immune-mediated mechanisms. In this consensus paper, we discuss the clinical features of the main described immune-mediated cerebellar ataxias and address their presumed pathogenesis. Immune-mediated cerebellar ataxias include cerebellar ataxia associated with anti-GAD antibodies, the cerebellar type of Hashimoto's encephalopathy, primary autoimmune cerebellar ataxia, gluten ataxia, Miller Fisher syndrome, ataxia associated with systemic lupus erythematosus, and paraneoplastic cerebellar degeneration. Humoral mechanisms, cell-mediated immunity, inflammation, and vascular injuries contribute to the cerebellar deficits in immune-mediated cerebellar ataxias. PMID:25823827

  14. Estrogen Receptor Beta and 2-arachidonoylglycerol Mediate the Suppressive Effects of Estradiol on Frequency of Postsynaptic Currents in Gonadotropin-Releasing Hormone Neurons of Metestrous Mice: An Acute Slice Electrophysiological Study

    PubMed Central

    Bálint, Flóra; Liposits, Zsolt; Farkas, Imre

    2016-01-01

    Gonadotropin-releasing hormone (GnRH) neurons are controlled by 17β-estradiol (E2) contributing to the steroid feedback regulation of the reproductive axis. In rodents, E2 exerts a negative feedback effect upon GnRH neurons throughout the estrus-diestrus phase of the ovarian cycle. The present study was undertaken to reveal the role of estrogen receptor subtypes in the mediation of the E2 signal and elucidate the downstream molecular machinery of suppression. The effect of E2 administration at low physiological concentration (10 pM) on GnRH neurons in acute brain slices obtained from metestrous GnRH-green fluorescent protein (GFP) mice was studied under paradigms of blocking or activating estrogen receptor subtypes and interfering with retrograde 2-arachidonoylglycerol (2-AG) signaling. Whole-cell patch clamp recordings revealed that E2 significantly diminished the frequency of spontaneous postsynaptic currents (sPSCs) in GnRH neurons (49.62 ± 7.6%) which effect was abolished by application of the estrogen receptor (ER) α/β blocker Faslodex (1 μM). Pretreatment of the brain slices with cannabinoid receptor type 1 (CB1) inverse agonist AM251 (1 μM) and intracellularly applied endocannabinoid synthesis blocker THL (10 μM) significantly attenuated the effect of E2 on the sPSCs. E2 remained effective in the presence of tetrodotoxin (TTX) indicating a direct action of E2 on GnRH cells. The ERβ specific agonist DPN (10 pM) also significantly decreased the frequency of miniature postsynaptic currents (mPSCs) in GnRH neurons. In addition, the suppressive effect of E2 was completely blocked by the selective ERβ antagonist PHTPP (1 μM) indicating that ERβ is required for the observed rapid effect of the E2. In contrast, the ERα agonist PPT (10 pM) or the membrane-associated G protein-coupled estrogen receptor (GPR30) agonist G1 (10 pM) had no significant effect on the frequency of mPSCs in these neurons. AM251 and tetrahydrolipstatin (THL) significantly abolished

  15. Clinically relevant concentration of pregabalin has no acute inhibitory effect on excitation of dorsal horn neurons under normal or neuropathic pain conditions: An intracellular calcium-imaging study in spinal cord slices from adult rats.

    PubMed

    Baba, Hiroshi; Petrenko, Andrey B; Fujiwara, Naoshi

    2016-10-01

    Pregabalin is thought to exert its therapeutic effect in neuropathic pain via binding to α2δ-1 subunits of voltage-gated calcium (Ca(2+)) channels. However, the exact analgesic mechanism after its binding to α2δ-1 subunits remains largely unknown. Whether a clinical concentration of pregabalin (≈10μM) can cause acute inhibition of dorsal horn neurons in the spinal cord is controversial. To address this issue, we undertook intracellular Ca(2+)-imaging studies using spinal cord slices with an intact attached L5 dorsal root, and examined if pregabalin acutely inhibits the primary afferent stimulation-evoked excitation of dorsal horn neurons in normal rats and in rats with streptozotocin-induced painful diabetic neuropathy. Under normal conditions, stimulation of a dorsal root evoked Ca(2+) signals predominantly in the superficial dorsal horn. Clinically relevant (10μM) and a very high concentration of pregabalin (100μM) did not affect the intensity or spread of dorsal root stimulation-evoked Ca(2+) signals, whereas an extremely high dose of pregabalin (300μM) slightly but significantly attenuated Ca(2+) signals in normal rats and in diabetic neuropathic (DN) rats. There was no difference between normal rats and DN rats with regard to the extent of signal attenuation at all concentrations tested. These results suggest that the activity of dorsal horn neurons in the spinal cord is not inhibited acutely by clinical doses of pregabalin under normal or DN conditions. It is very unlikely that an acute inhibitory action in the dorsal horn is the main analgesic mechanism of pregabalin in neuropathic pain states. PMID:27543338

  16. Developmental change in the contribution of voltage-gated Ca(2+) channels to the pacemaking of deep cerebellar nuclei neurons.

    PubMed

    Alviña, K; Tara, E; Khodakhah, K

    2016-05-13

    The activity of the deep cerebellar nuclei (DCN) neurons conveys the bulk of the output of the cerebellum. To generate these motor signals, DCN neurons integrate synaptic inputs with their own spontaneous activity. We have previously reported that N-type voltage-gated Ca(2+) channels modulate the spontaneous activity of the majority of juvenile DCN neurons in vitro. Specifically, pharmacologically blocking N-type Ca(2+) channels increases their firing rate causing DCN cells to burst. Adult DCN neurons however, behaved differently. To further investigate this change, we have studied here the effect of cadmium on the firing rate of DCN neurons in acute cerebellar slices obtained from adult (>2 months old) or juvenile (12-21 days old) rats and mice. Strikingly, and in contrast to juvenile DCN cells, cadmium did not affect the pacemaking of adult DCN cells. The activity of Purkinje cells (PCs) however was transformed into high-frequency bursting, regardless the age. Further, we questioned whether these findings could be due to an artifact associated with the added difficulty of preparing adult DCN slices. Hence we proceeded to examine the spontaneous activity of DCN neurons in anesthetized juvenile and adult rats and mice in vivo. When cadmium was injected into the DCN in vivo no significant change in firing rate was observed, conversely to most juvenile DCN neurons which showed high-frequency bursts after cadmium injection. In these same animals, PCs pacemaking showed no developmental difference. Thus our results demonstrate a remarkable age-dependent functional modification in the regulation of DCN neurons pacemaking. PMID:26902515

  17. DEVELOPMENTAL CHANGE IN THE CONTRIBUTION OF VOLTAGE-GATED Ca2+ CHANNELS TO THE PACEMAKING OF DEEP CEREBELLAR NUCLEI NEURONS

    PubMed Central

    ALVIÑA, K.; TARA, E.; KHODAKHAH, K.

    2016-01-01

    The activity of the deep cerebellar nuclei (DCN) neurons conveys the bulk of the output of the cerebellum. To generate these motor signals, DCN neurons integrate synaptic inputs with their own spontaneous activity. We have previously reported that N-type voltage-gated Ca2+ channels modulate the spontaneous activity of the majority of juvenile DCN neurons in vitro. Specifically, pharmacologically blocking N-type Ca2+ channels increases their firing rate causing DCN cells to burst. Adult DCN neurons however, behaved differently. To further investigate this change, we have studied here the effect of cadmium on the firing rate of DCN neurons in acute cerebellar slices obtained from adult ( > 2 months old) or juvenile (12–21 days old) rats and mice. Strikingly, and in contrast to juvenile DCN cells, cadmium did not affect the pacemaking of adult DCN cells. The activity of Purkinje cells (PCs) however was transformed into high-frequency bursting, regardless the age. Further, we questioned whether these findings could be due to an artifact associated with the added difficulty of preparing adult DCN slices. Hence we proceeded to examine the spontaneous activity of DCN neurons in anesthetized juvenile and adult rats and mice in vivo. When cadmium was injected into the DCN in vivo no significant change in firing rate was observed, conversely to most juvenile DCN neurons which showed high-frequency bursts after cadmium injection. In these same animals, PCs pacemaking showed no developmental difference. Thus our results demonstrate a remarkable age-dependent functional modification in the regulation of DCN neurons pacemaking. PMID:26902515

  18. Metronidazole induced cerebellar ataxia

    PubMed Central

    Hari, Aditya; Srikanth, B. Akshaya; Lakshmi, G. Sriranga

    2013-01-01

    Metronidazole is a widely used antimicrobial usually prescribed by many specialist doctors for a short duration of 10-15 days. Prolonged use of metronidazole is rare. The present case is of a patient who used the drug for 4 months and developed peripheral neuropathy, convulsions, and cerebellar ataxia. He was treated with diazepam and levetiracetam. The patient recovered completely following discontinuation of metronidazole. PMID:23833378

  19. Automated Factor Slice Sampling.

    PubMed

    Tibbits, Matthew M; Groendyke, Chris; Haran, Murali; Liechty, John C

    2014-01-01

    Markov chain Monte Carlo (MCMC) algorithms offer a very general approach for sampling from arbitrary distributions. However, designing and tuning MCMC algorithms for each new distribution, can be challenging and time consuming. It is particularly difficult to create an efficient sampler when there is strong dependence among the variables in a multivariate distribution. We describe a two-pronged approach for constructing efficient, automated MCMC algorithms: (1) we propose the "factor slice sampler", a generalization of the univariate slice sampler where we treat the selection of a coordinate basis (factors) as an additional tuning parameter, and (2) we develop an approach for automatically selecting tuning parameters in order to construct an efficient factor slice sampler. In addition to automating the factor slice sampler, our tuning approach also applies to the standard univariate slice samplers. We demonstrate the efficiency and general applicability of our automated MCMC algorithm with a number of illustrative examples. PMID:24955002

  20. Automated Factor Slice Sampling

    PubMed Central

    Tibbits, Matthew M.; Groendyke, Chris; Haran, Murali; Liechty, John C.

    2013-01-01

    Markov chain Monte Carlo (MCMC) algorithms offer a very general approach for sampling from arbitrary distributions. However, designing and tuning MCMC algorithms for each new distribution, can be challenging and time consuming. It is particularly difficult to create an efficient sampler when there is strong dependence among the variables in a multivariate distribution. We describe a two-pronged approach for constructing efficient, automated MCMC algorithms: (1) we propose the “factor slice sampler”, a generalization of the univariate slice sampler where we treat the selection of a coordinate basis (factors) as an additional tuning parameter, and (2) we develop an approach for automatically selecting tuning parameters in order to construct an efficient factor slice sampler. In addition to automating the factor slice sampler, our tuning approach also applies to the standard univariate slice samplers. We demonstrate the efficiency and general applicability of our automated MCMC algorithm with a number of illustrative examples. PMID:24955002

  1. Role of Tet1/3 Genes and Chromatin Remodeling Genes in Cerebellar Circuit Formation.

    PubMed

    Zhu, Xiaodong; Girardo, David; Govek, Eve-Ellen; John, Keisha; Mellén, Marian; Tamayo, Pablo; Mesirov, Jill P; Hatten, Mary E

    2016-01-01

    Although mechanisms underlying early steps in cerebellar development are known, evidence is lacking on genetic and epigenetic changes during the establishment of the synaptic circuitry. Using metagene analysis, we report pivotal changes in multiple reactomes of epigenetic pathway genes in cerebellar granule cells (GCs) during circuit formation. During this stage, Tet genes are upregulated and vitamin C activation of Tet enzymes increases the levels of 5-hydroxymethylcytosine (5hmC) at exon start sites of upregulated genes, notably axon guidance genes and ion channel genes. Knockdown of Tet1 and Tet3 by RNAi in ex vivo cerebellar slice cultures inhibits dendritic arborization of developing GCs, a critical step in circuit formation. These findings demonstrate a role for Tet genes and chromatin remodeling genes in the formation of cerebellar circuitry. PMID:26711116

  2. A Reinforcing Circuit Action of Extrasynaptic GABAA Receptor Modulators on Cerebellar Granule Cell Inhibition

    PubMed Central

    Santhakumar, Vijayalakshmi; Otis, Thomas S.

    2013-01-01

    GABAA receptors (GABARs) are the targets of a wide variety of modulatory drugs which enhance chloride flux through GABAR ion channels. Certain GABAR modulators appear to acutely enhance the function of δ subunit-containing GABAR subtypes responsible for tonic forms of inhibition. Here we identify a reinforcing circuit mechanism by which these drugs, in addition to directly enhancing GABAR function, also increase GABA release. Electrophysiological recordings in cerebellar slices from rats homozygous for the ethanol-hypersensitive (α6100Q) allele show that modulators and agonists selective for δ-containing GABARs such as THDOC, ethanol and THIP (gaboxadol) increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in granule cells. Ethanol fails to augment granule cell sIPSC frequency in the presence of glutamate receptor antagonists, indicating that circuit mechanisms involving granule cell output contribute to ethanol-enhancement of synaptic inhibition. Additionally, GABAR antagonists decrease ethanol-induced enhancement of Golgi cell firing. Consistent with a role for glutamatergic inputs, THIP-induced increases in Golgi cell firing are abolished by glutamate receptor antagonists. Moreover, THIP enhances the frequency of spontaneous excitatory postsynaptic currents in Golgi cells. Analyses of knockout mice indicate that δ subunit-containing GABARs are required for enhancing GABA release in the presence of ethanol and THIP. The limited expression of the GABAR δ subunit protein within the cerebellar cortex suggests that an indirect, circuit mechanism is responsible for stimulating Golgi cell GABA release by drugs selective for extrasynaptic isoforms of GABARs. Such circuit effects reinforce direct actions of these positive modulators on tonic GABAergic inhibition and are likely to contribute to the potent effect of these compounds as nervous system depressants. PMID:23977374

  3. A reinforcing circuit action of extrasynaptic GABAA receptor modulators on cerebellar granule cell inhibition.

    PubMed

    Santhakumar, Vijayalakshmi; Meera, Pratap; Karakossian, Movses H; Otis, Thomas S

    2013-01-01

    GABAA receptors (GABARs) are the targets of a wide variety of modulatory drugs which enhance chloride flux through GABAR ion channels. Certain GABAR modulators appear to acutely enhance the function of δ subunit-containing GABAR subtypes responsible for tonic forms of inhibition. Here we identify a reinforcing circuit mechanism by which these drugs, in addition to directly enhancing GABAR function, also increase GABA release. Electrophysiological recordings in cerebellar slices from rats homozygous for the ethanol-hypersensitive (α6100Q) allele show that modulators and agonists selective for δ-containing GABARs such as THDOC, ethanol and THIP (gaboxadol) increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in granule cells. Ethanol fails to augment granule cell sIPSC frequency in the presence of glutamate receptor antagonists, indicating that circuit mechanisms involving granule cell output contribute to ethanol-enhancement of synaptic inhibition. Additionally, GABAR antagonists decrease ethanol-induced enhancement of Golgi cell firing. Consistent with a role for glutamatergic inputs, THIP-induced increases in Golgi cell firing are abolished by glutamate receptor antagonists. Moreover, THIP enhances the frequency of spontaneous excitatory postsynaptic currents in Golgi cells. Analyses of knockout mice indicate that δ subunit-containing GABARs are required for enhancing GABA release in the presence of ethanol and THIP. The limited expression of the GABAR δ subunit protein within the cerebellar cortex suggests that an indirect, circuit mechanism is responsible for stimulating Golgi cell GABA release by drugs selective for extrasynaptic isoforms of GABARs. Such circuit effects reinforce direct actions of these positive modulators on tonic GABAergic inhibition and are likely to contribute to the potent effect of these compounds as nervous system depressants. PMID:23977374

  4. [Cerebellar cognitive affective syndrome secondary to a cerebellar tumour].

    PubMed

    Domínguez-Carral, J; Carreras-Sáez, I; García-Peñas, J J; Fournier-Del Castillo, C; Villalobos-Reales, J

    2015-01-01

    Cerebellar cognitive affective syndrome is characterized by disturbances of executive function, impaired spatial cognition, linguistic difficulties, and personality change. The case of an 11 year old boy is presented, with behavior problems, learning difficulties and social interaction problems. In the physical examination he had poor visual contact, immature behavior, reduced expressive language and global motor disability with gait dyspraxia, with no defined cerebellar motor signs. In the neuropsychological evaluation he has a full scale overall intellectual quotient of 84, with signs of cerebellar cognitive affective syndrome. A tumour affecting inferior cerebellar vermis was observed in the magnetic resonance imaging, which had not significantly grown during 5 years of follow up. The cerebellum participates in controlling cognitive and affective functions. Cerebellar pathology must be considered in the differential diagnosis of children with cognitive or learning disorder with associated behavioral and emotional components. PMID:24954915

  5. Clinical manifestations of cerebellar disease.

    PubMed

    Javalkar, Vijayakumar; Khan, Misbba; Davis, Debra E

    2014-11-01

    Clinical manifestations of cerebellar disease include ataxia and tremor, as well as nystagmus, dysarthria, and cognitive dysfunction. Recognition of the cerebellar pattern of disease can aid in the prompt and correct diagnosis and lead to appropriate treatment and rehabilitation to minimize disability. PMID:25439285

  6. Slicing black hole spacetimes

    NASA Astrophysics Data System (ADS)

    Bini, Donato; Bittencourt, Eduardo; Geralico, Andrea; Jantzen, Robert T.

    2015-04-01

    A general framework is developed to investigate the properties of useful choices of stationary spacelike slicings of stationary spacetimes whose congruences of timelike orthogonal trajectories are interpreted as the world lines of an associated family of observers, the kinematical properties of which in turn may be used to geometrically characterize the original slicings. On the other hand, properties of the slicings themselves can directly characterize their utility motivated instead by other considerations like the initial value and evolution problems in the 3-plus-1 approach to general relativity. An attempt is made to categorize the various slicing conditions or "time gauges" used in the literature for the most familiar stationary spacetimes: black holes and their flat spacetime limit.

  7. Propofol effects on cerebellar long-term depression.

    PubMed

    Lee, Kwan Young; Kim, Young Im; Kim, Se Hoon; Park, Hyung Seo; Park, Youn Joon; Ha, Myung Sook; Jin, Yunju; Kim, Dong Kwan

    2015-11-16

    Propofol is an intravenously administered anesthetic that induces γ-aminobutyric acid-mediated inhibition in the central nervous system. It has been implicated in prolonged movement disorders. Since the cerebellum is important for motor coordination and learning, we investigated the potential effects of propofol on cerebellar circuitry. Using the whole-cell patch-clamp technique in Wister rat cerebellar slices, we demonstrated that propofol administration impaired long-term depression from the parallel fiber (PF) to Purkinje cell (PC) synapses (PF-LTD). Also, propofol reduced metabotropic glutamate receptor 1 (mGluR1)-mediated and group I mGluR agonist-induced slow currents in PCs. These results suggest that the propofol-induced PF-LTD impairment may be related to an alteration in mGluR1 signaling, which is essential to motor learning. PMID:26455962

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

    PubMed

    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. PMID:25578036

  9. The Virtual Slice Setup

    PubMed Central

    Lytton, William W; Neymotin, Samuel A; Hines, Michael L

    2008-01-01

    In an effort to design a simulation environment that is more similar to that of neurophysiology, we introduce a virtual slice setup in the NEURON simulator. The virtual slice setup runs continuously and permits parameter changes including changes to synaptic weights and time course and to intrinsic cell properties. The virtual slice setup permits shocks to be applied at chosen locations and activity to be sampled intra- or extracellularly from chosen locations. By default, a summed population display is shown during a run to indicate the level of activity and no states are saved. Simulations can run for hours of model time, therefore it is not practical to save all of the state variables which in any case are primarily of interest at discrete times when experiments are being run: the simulation can be stopped momentarily at such times to save activity patterns. The virtual slice setup maintains an automated notebook showing shocks and parameter changes as well as user comments. We demonstrate how interaction with a continuously running simulation encourages experimental prototyping and can suggest additional dynamical features such as ligand wash-in and wash-out – alternatives to typical instantaneous parameter change. The virtual slice setup currently uses event-driven cells and runs at approximately 2 minutes/hour on a laptop. PMID:18452996

  10. Expression of GFP-tagged neuronal glutamate transporters in cerebellar Purkinje neurons.

    PubMed

    Meera, Pratap; Dodson, Paul D; Karakossian, Movses H; Otis, Thomas S

    2005-11-01

    Of the five excitatory amino acid transporters (EAATs) identified, two genes are expressed by neurons (EAAT3 and EAAT4) and give rise to transporters confined to neuronal cell bodies and dendrites. At an ultrastructural level, EAAT3 and EAAT4 proteins are clustered at the edges of postsynaptic densities of excitatory synapses. This pattern of localization suggests that postsynaptic EAATs may help to limit spillover of glutamate from excitatory synapses. In an effort to study transporter localization in living neurons and ultimately to manipulate uptake at intact synapses, we have developed viral reagents encoding neuronal EAATs tagged with GFP. We demonstrate that these fusion proteins are capable of Na(+)-dependent glutamate uptake, that they generate ionic conductances indistinguishable from their wild-type counterparts, and that GFP does not alter their glutamate dose-dependence. Two-photon microscopy was used to examine fusion protein expression in Purkinje neurons in acute cerebellar slices. Both EAAT3-GFP and EAAT4-GFP were observed at high levels in the dendritic spines of transfected Purkinje neurons. These findings indicate that functional EAAT fusion proteins can be synthesized and appropriately trafficked to postsynaptic compartments. Furthermore, they validate a powerful system for looking at EAAT function in situ. PMID:16212990

  11. Automated cerebellar lobule segmentation with application to cerebellar structural analysis in cerebellar disease.

    PubMed

    Yang, Zhen; Ye, Chuyang; Bogovic, John A; Carass, Aaron; Jedynak, Bruno M; Ying, Sarah H; Prince, Jerry L

    2016-02-15

    The cerebellum plays an important role in both motor control and cognitive function. Cerebellar function is topographically organized and diseases that affect specific parts of the cerebellum are associated with specific patterns of symptoms. Accordingly, delineation and quantification of cerebellar sub-regions from magnetic resonance images are important in the study of cerebellar atrophy and associated functional losses. This paper describes an automated cerebellar lobule segmentation method based on a graph cut segmentation framework. Results from multi-atlas labeling and tissue classification contribute to the region terms in the graph cut energy function and boundary classification contributes to the boundary term in the energy function. A cerebellar parcellation is achieved by minimizing the energy function using the α-expansion technique. The proposed method was evaluated using a leave-one-out cross-validation on 15 subjects including both healthy controls and patients with cerebellar diseases. Based on reported Dice coefficients, the proposed method outperforms two state-of-the-art methods. The proposed method was then applied to 77 subjects to study the region-specific cerebellar structural differences in three spinocerebellar ataxia (SCA) genetic subtypes. Quantitative analysis of the lobule volumes shows distinct patterns of volume changes associated with different SCA subtypes consistent with known patterns of atrophy in these genetic subtypes. PMID:26408861

  12. Autosomal recessive cerebellar ataxias

    PubMed Central

    Palau, Francesc; Espinós, Carmen

    2006-01-01

    Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both central and peripheral nervous system, and in some case other systems and organs, and characterized by degeneration or abnormal development of cerebellum and spinal cord, autosomal recessive inheritance and, in most cases, early onset occurring before the age of 20 years. This group encompasses a large number of rare diseases, the most frequent in Caucasian population being Friedreich ataxia (estimated prevalence 2–4/100,000), ataxia-telangiectasia (1–2.5/100,000) and early onset cerebellar ataxia with retained tendon reflexes (1/100,000). Other forms ARCA are much less common. Based on clinicogenetic criteria, five main types ARCA can be distinguished: congenital ataxias (developmental disorder), ataxias associated with metabolic disorders, ataxias with a DNA repair defect, degenerative ataxias, and ataxia associated with other features. These diseases are due to mutations in specific genes, some of which have been identified, such as frataxin in Friedreich ataxia, α-tocopherol transfer protein in ataxia with vitamin E deficiency (AVED), aprataxin in ataxia with oculomotor apraxia (AOA1), and senataxin in ataxia with oculomotor apraxia (AOA2). Clinical diagnosis is confirmed by ancillary tests such as neuroimaging (magnetic resonance imaging, scanning), electrophysiological examination, and mutation analysis when the causative gene is identified. Correct clinical and genetic diagnosis is important for appropriate genetic counseling and prognosis and, in some instances, pharmacological treatment. Due to autosomal recessive inheritance, previous familial history of affected individuals is unlikely. For most ARCA there is no specific drug treatment except for coenzyme Q10 deficiency and abetalipoproteinemia. PMID:17112370

  13. Speech prosody in cerebellar ataxia

    NASA Astrophysics Data System (ADS)

    Casper, Maureen

    The present study sought an acoustic signature for the speech disturbance recognized in cerebellar degeneration. Magnetic resonance imaging was used for a radiological rating of cerebellar involvement in six cerebellar ataxic dysarthric speakers. Acoustic measures of the [pap] syllables in contrastive prosodic conditions and of normal vs. brain-damaged patients were used to further our understanding both of the speech degeneration that accompanies cerebellar pathology and of speech motor control and movement in general. Pair-wise comparisons of the prosodic conditions within the normal group showed statistically significant differences for four prosodic contrasts. For three of the four contrasts analyzed, the normal speakers showed both longer durations and higher formant and fundamental frequency values in the more prominent first condition of the contrast. The acoustic measures of the normal prosodic contrast values were then used as a model to measure the degree of speech deterioration for individual cerebellar subjects. This estimate of speech deterioration as determined by individual differences between cerebellar and normal subjects' acoustic values of the four prosodic contrasts was used in correlation analyses with MRI ratings. Moderate correlations between speech deterioration and cerebellar atrophy were found in the measures of syllable duration and f0. A strong negative correlation was found for F1. Moreover, the normal model presented by these acoustic data allows for a description of the flexibility of task- oriented behavior in normal speech motor control. These data challenge spatio-temporal theory which explains movement as an artifact of time wherein longer durations predict more extreme movements and give further evidence for gestural internal dynamics of movement in which time emerges from articulatory events rather than dictating those events. This model provides a sensitive index of cerebellar pathology with quantitative acoustic

  14. Organotypic slice culture of the hypothalamic paraventricular nucleus of rat

    PubMed Central

    Cho, Eun Seong; Lee, So Yeong; Park, Jae-Yong; Hong, Seong-Geun

    2007-01-01

    Organotypic slice cultures have been developed as an alternative to acute brain slices because the neuronal viability and synaptic connectivity in these cultures can be preserved well for a prolonged period of time. This study evaluated a stationary organotypic slice culture developed for the hypothalamic paraventricular nucleus (PVN) of rat. The results showed that the slice cultures maintain the typical shape of the nucleus, the immunocytochemical signals for oxytocin, vasopressin, and corticotropin-releasing hormone, and the electrophysiological properties of PVN neurons for up to 3 weeks in vitro. The PVN neurons in the culture expressed the green fluorescent protein gene that had been delivered by the adenoviral vectors. The results indicate that the cultured slices preserve the properties of the PVN neurons, and can be used in longterm studies on these neurons in vitro. PMID:17322769

  15. Slice of Comet Dust

    NASA Technical Reports Server (NTRS)

    2006-01-01

    This image illustrates one of several ways scientists have begun extracting comet particles from the Stardust spacecraft's collector. First, a particle and its track are cut out of the collector material, called aerogel, in a wedge-shaped slice called a keystone. A specialized silicon pickle fork is then used to remove the keystone from the remaining aerogel for further analysis.

  16. Bestrophin1 Channels are Insensitive to Ethanol and Do not Mediate Tonic GABAergic Currents in Cerebellar Granule Cells

    PubMed Central

    Diaz, Marvin R.; Wadleigh, Aya; Hughes, Benjamin A.; Woodward, John J.; Valenzuela, C. Fernando

    2012-01-01

    The granule cell layer of the cerebellum functions in spatio-temporal encoding of information. Granule cells (GCs) are tonically inhibited by spillover of GABA released from Golgi cells and this tonic inhibition is facilitated by acute ethanol. Recently, it was demonstrated that a specialized Ca2+-activated anion-channel, bestrophin1 (Best1), found on glial cells, can release GABA that contributes up to 50–75% of the tonic GABAergic current. However, it is unknown if ethanol has any actions on Best1 function. Using whole-cell electrophysiology, we found that recombinant Best1 channels expressed in HEK-293 cells were insensitive to 40 and 80 mM ethanol. We attempted to measure the Best1-mediated component of the tonic current in slices using 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB). We confirmed that this agent blocks recombinant Best1 channels. Unexpectedly, we found that NPPB significantly potentiated the tonic current and the area and decay of GABAA-mediated spontaneous inhibitory post-synaptic currents (IPSCs) in GCs in rodent slices under two different recording conditions. To better isolate the Best1-dependent tonic current component, we blocked the Golgi cell component of the tonic current with tetrodotoxin and found that NPPB similarly and significantly potentiated the tonic current amplitude and decay time of miniature IPSCs. Two other Cl−-channel blockers were also tested: 4′-diisothiocyanatostilbene-2,2′-disulfonic acid disodium salt hydrate (DIDS) showed no effect on GABAergic transmission, while niflumic acid (NFA) significantly suppressed the tonic current noise, as well as the mIPSC frequency, amplitude, and area. These data suggest that acute ethanol exposure does not modulate Best1 channels and these findings serve to challenge recent data indicating that these channels participate in the generation of tonic GABAergic currents in cerebellar GCs. PMID:22275879

  17. Regulation of store-operated calcium entry by calcium-independent phospholipase A2 in rat cerebellar astrocytes.

    PubMed

    Singaravelu, Karthika; Lohr, Christian; Deitmer, Joachim W

    2006-09-13

    We have studied store-operated Ca2+ entry (SOCE) in Bergmann glia and granule cell layer astrocytes in acute brain slices of the rat cerebellum, using the Ca2+-sensitive fluorescent dye Fluo-4 and confocal laser scanning microscopy. Astrocytes were identified by their morphology, location, and their Ca2+ response in K+-free solution. Depletion of Ca2+ stores by cyclopiazonic acid (CPA) (20 microM) induced SOCE in both types of astrocyte. A similar Ca2+ influx was elicited by the calmodulin antagonist calmidazolium (CMZ) (1 microM). The SOCE channel blocker 2-aminoethoxy-diphenylborate (2-APB) (100 microM) and the Ca2+ release-activated channel blocker 3,5-bistrifluoromethyl pyrazole derivative (BTP2) (20 microM) suppressed the CPA- and the CMZ-induced Ca2+ influx. Pretreatment of acute slices with the specific Ca2+-independent phospholipase A2 (iPLA2) inhibitor bromoenol lactone (BEL) (25 microM) blocked the CPA- and the CMZ-induced Ca2+ influx. The lysophospholipid products of iPLA2, lysophosphatidylcholine (250 nM) and lysophosphatidylinositol (250 nM), but not lysophosphatidic acid (250 nM), induced a BTP2- and 2-APB-sensitive, but BEL-insensitive, Ca2+ influx. CPA or CMZ enhanced the BEL-sensitive enzymatic activity of iPLA2 in cerebellar astrocyte culture. Inhibition of iPLA2 expression by specific antisense oligodeoxynucleotide of iPLA2 reduced the SOCE and the Ca2+ store refilling in cultured astrocytes. Spontaneous Ca2+ oscillations in astrocytes in situ were reduced after inhibiting SOCE channels or iPLA2 activity. The results suggest that the depletion of Ca2+ stores activates iPLA2 to open Ca2+ channels in the plasma membrane by the formation of lysophospholipids in astrocytes, presumably to refill the stores and allow normal Ca2+ signaling. PMID:16971542

  18. Portable Device Slices Thermoplastic Prepregs

    NASA Technical Reports Server (NTRS)

    Taylor, Beverly A.; Boston, Morton W.; Wilson, Maywood L.

    1993-01-01

    Prepreg slitter designed to slit various widths rapidly by use of slicing bar holding several blades, each capable of slicing strip of preset width in single pass. Produces material evenly sliced and does not contain jagged edges. Used for various applications in such batch processes involving composite materials as press molding and autoclaving, and in such continuous processes as pultrusion. Useful to all manufacturers of thermoplastic composites, and in slicing B-staged thermoset composites.

  19. [Pharmacotherapy of Vestibular Disorders, Nystagmus and Cerebellar Disorders].

    PubMed

    Feil, K; Böttcher, N; Kremmyda, O; Muth, C; Teufel, J; Zwergal, A; Brandt, T; Strupp, M

    2015-09-01

    There are currently different groups of drugs for the pharmacotherapy of vertigo, nystagmus and cerebellar disorders: antiemetics; anti-inflammatories, antimenieres, and antimigraineous medications and antidepressants, anticonvulsants, aminopyridines as well as acetyl-DL-leucine. In acute unilateral vestibulopathy, corticosteroids improve the recovery of peripheral vestibular function, but currently there is not sufficient evidence for a general recommendation. There is insufficient evidence to support the view that 16 mg t. i. d. or 48 mg t. i. d. betahistine has an effect in Menière's disease. Therefore, higher dosages are recommended. In animal studies, it was shown that betahistine increases cochlear blood flow. In vestibular paroxysmia, oxcarbazepine was effective (one randomized controlled trial (RCT)). Aminopyridines are recommended for the treatment of downbeat nystagmus (two RCTs) and episodic ataxia type 2 (EA2, one RCT). There has been no RCT on the efficacy of beta-blockers or topiramate but one RCT on flunarizine in vestibular migraine. Based on clinical experience, a treatment analogous to that for migraine without aura can be recommended. Acetyl-DL-leucine improved cerebellar ataxia (two observational studies); it also accelerated central compensation in an animal model of acute unilateral lesion, but RCTs were negative. There are ongoing RCTs on treatment of vestibular paroxysmia with carbamazepine (VESPA), acute unilateral vestibulopathy with betahistine (BETAVEST), vestibular migraine with metoprolol (PROVEMIG), benign paroxysmal positional vertigo with vitamin D (VitD@BPPV), EA2 with 4-aminopyridine versus acetazolamide (EAT-2-TREAT), and cerebellar ataxias with acetyl-DL-leucine (ALCAT). PMID:26421856

  20. Slice profile distortions in single slice continuously moving table MRI

    NASA Astrophysics Data System (ADS)

    Sengupta, Saikat; Smith, David S.; Welch, E. B.

    2015-03-01

    Continuously Moving Table (CMT) MRI is a rapid imaging technique that allows scanning of extended fields of view (FOVs) such as the whole-body in a single continuous scan.1 A highly efficient approach to CMT MRI is single slice imaging, where data are continuously acquired from a single axial slice at isocenter with concurrent movement of the patient table.2 However, the continuous motion of the scanner table and supply of fresh magnetization into the excited slice can introduce deviations in the slice magnetization profile. The goal of this work is to investigate and quantify the distortion in the slice profile in CMT MRI. CMT MRI with a table speed of 20 mm/s was implemented on a 3 Tesla whole-body MRI scanner, with continuous radial data acquisition. Simulations were performed to characterize the transient and steady state slice profiles and magnetization effects. Simulated slice profiles were compared to actual slice profile measurements performed in the scanner. Both simulations and experiments revealed an asymmetric slice profile characterized by a skew towards the lagging edge of the moving table, in contrast to the nominal profiles associated with scanning a stationary object. The true excited slice width (FWHM) and pitch of the acquisition was observed to be dependent on table velocity, with larger table speeds resulting in larger slice profile deviations from the nominal shape.

  1. Flash lamp light slicing

    NASA Astrophysics Data System (ADS)

    Saber, A. J.; Abdel-Wahab, T.; Georgallis, M.

    A light slicing system using a short-arc-length high-power flashlamp as the source is discussed, with application to the observation of fluid phenomena such as gas discharge and fuel injection into engines. The geometrical optics of the method, in addition to the attenuation of luminous intensity in the system, is considered, and varying the relative radius of curvature of the cylindrical lens with respect to the width of the laser beam is shown to change the extension of the light sheet lamina. Light slice system generation using CAD is discussed, and experimental results of the observation of pulsed gas discharges in a small scale valve system designed to simulate large-scale dispersion and mixing of gases in air are reported.

  2. Persistent Nav1.6 current at axon initial segments tunes spike timing of cerebellar granule cells

    PubMed Central

    Osorio, Nancy; Cathala, Laurence; Meisler, Miriam H; Crest, Marcel; Magistretti, Jacopo; Delmas, Patrick

    2010-01-01

    Cerebellar granule (CG) cells generate high-frequency action potentials that have been proposed to depend on the unique properties of their voltage-gated ion channels. To address the in vivo function of Nav1.6 channels in developing and mature CG cells, we combined the study of the developmental expression of Nav subunits with recording of acute cerebellar slices from young and adult granule-specific Scn8a KO mice. Nav1.2 accumulated rapidly at early-formed axon initial segments (AISs). In contrast, Nav1.6 was absent at early postnatal stages but accumulated at AISs of CG cells from P21 to P40. By P40–P65, both Nav1.6 and Nav1.2 co-localized at CG cell AISs. By comparing Na+ currents in mature CG cells (P66–P74) from wild-type and CG-specific Scn8a KO mice, we found that transient and resurgent Na+ currents were not modified in the absence of Nav1.6 whereas persistent Na+ current was strongly reduced. Action potentials in conditional Scn8a KO CG cells showed no alteration in threshold and overshoot, but had a faster repolarization phase and larger post-spike hyperpolarization. In addition, although Scn8a KO CG cells kept their ability to fire action potentials at very high frequency, they displayed increased interspike-interval variability and firing irregularity in response to sustained depolarization. We conclude that Nav1.6 channels at axon initial segments contribute to persistent Na+ current and ensure a high degree of temporal precision in repetitive firing of CG cells. PMID:20173079

  3. Speech prosody in cerebellar ataxia.

    PubMed

    Casper, Maureen A; Raphael, Lawrence J; Harris, Katherine S; Geibel, Jennifer M

    2007-01-01

    Persons with cerebellar ataxia exhibit changes in physical coordination and speech and voice production. Previously, these alterations of speech and voice production were described primarily via perceptual coordinates. In this study, the spatial-temporal properties of syllable production were examined in 12 speakers, six of whom were healthy speakers and six with ataxia. The speaking task was designed to elicit six different prosodic conditions and four contrastive prosodic events. Distinct prosodic patterns were elicited by the examiner for cerebellar patients and healthy speakers. These utterances were digitally recorded and analysed acoustically and statistically. The healthy speakers showed statistically significant differences among all four prosodic contrasts. The normal model described by the prosodic contrasts provided a sensitive index of cerebellar pathology with quantitative acoustic analyses. A significant interaction between subject groups and prosodic conditions revealed a compromised prosody in cerebellar patients. Significant differences were found for durational parameters, F0 and formant frequencies. The cerebellar speakers demonstrated different patterns of syllable lengthening and syllable reduction from that of the healthy speakers. PMID:17613097

  4. Ataxias and Cerebellar or Spinocerebellar Degeneration

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Ataxias and Cerebellar or Spinocerebellar Degeneration Information Page Synonym(s): ... Publications and Information Publicaciones en Español What are Ataxias and Cerebellar or Spinocerebellar Degeneration? Ataxia often occurs ...

  5. Primary cerebellar endodermal sinus tumor: A case report.

    PubMed

    Kuang, Hongmei; Zhang, Chun; Gong, Honghan; Guo, Linghong; Yu, Chen; Zeng, Xianjun

    2014-10-01

    Endodermal sinus tumors are rare malignant germ cell tumors that usually originate from the gonads and are rarely observed extragonadally. Pure primary endodermal sinus tumors of the cerebellar hemisphere are extremely rare and patients diagnosed with the disease often have a poor prognosis. The symptoms of YSTs are unspecific and associated with the location of tumors. Intracranial YSTs (such as cerebellar hemispheres) always present with symptoms including headache and poor vision. The present study reports the case of a three-year-old male who presented to The First Affiliated Hospital of Nanchang University (Nanchang, China) with a headache that had persisted for one month, and then worsened for the last 10 days. This was accompanied by vomiting and gait disturbance. An abnormal signal mass was identified in the left cerebellar hemisphere on brain magnetic resonance imaging. The case initially presented as a medulloblastoma and the patient was followed up for six months. The final pathology report revealed an endodermal sinus tumor, also known as a yolk sac tumor. Six months following resection of the left cerebellar tumor, the patient succumbed to recurrence of the disease, due to acute vomiting and severe headache. PMID:25202397

  6. Alcohol Withdrawal and Cerebellar Mitochondria.

    PubMed

    Jung, Marianna E

    2015-08-01

    Cerebellar disorders trigger the symptoms of movement problems, imbalance, incoordination, and frequent fall. Cerebellar disorders are shown in various CNS illnesses including a drinking disorder called alcoholism. Alcoholism is manifested as an inability to control drinking in spite of adverse consequences. Human and animal studies have shown that cerebellar symptoms persist even after complete abstinence from drinking. In particular, the abrupt termination (ethanol withdrawal) of long-term excessive ethanol consumption has shown to provoke a variety of neuronal and mitochondrial damage to the cerebellum. Upon ethanol withdrawal, excitatory neurotransmitter molecules such as glutamate are overly released in brain areas including cerebellum. This is particularly relevant to the cerebellar neuronal network as glutamate signals are projected to Purkinje neurons through granular cells that are the most populated neuronal type in CNS. This excitatory neuronal signal may be elevated by ethanol withdrawal stress, which promotes an increase in intracellular Ca(2+) level and a decrease in a Ca(2+)-binding protein, both of which result in the excessive entry of Ca(2+) to the mitochondria. Subsequently, mitochondria undergo a prolonged opening of mitochondrial permeability transition pore and the overproduction of harmful free radicals, impeding adenosine triphosphate (ATP)-generating function. This in turn provokes the leakage of mitochondrial molecule cytochrome c to the cytosol, which triggers a cascade of adverse cytosol reactions. Upstream to this pathway, cerebellum under the condition of ethanol withdrawal has shown aberrant gene modifications through altered DNA methylation, histone acetylation, or microRNA expression. Interplay between these events and molecules may result in functional damage to cerebellar mitochondria and consequent neuronal degeneration, thereby contributing to motoric deficit. Mitochondria-targeting research may help develop a powerful new

  7. Failure of Fixation Suppression of Spontaneous Nystagmus in Cerebellar Infarction: Frequency, Pattern, and a Possible Structure.

    PubMed

    Kim, Hyun-Ah; Yi, Hyon-Ah; Lee, Hyung

    2016-04-01

    To investigate the frequency and pattern of failure of the fixation suppression (FFS) of spontaneous nystagmus (SN) in unilateral cerebellar infarction, and to identify the structure responsible for FFS, 29 patients with acute, mainly unilateral, isolated cerebellar infarction who had SN with a predominantly horizontal component were enrolled in this study. The ocular fixation index (OFI) was defined as the mean slow phase velocity (SPV) of the horizontal component of SN with fixation divided by the mean SPV of the horizontal component of SN without fixation. The OFI from age- and sex-matched patients with vestibular neuritis was calculated and used as the control data. The FFS of SN was only found in less than half (41 %, 12/29) of the patients. Approximately 65 % (n = 7) of the patients with isolated anterior inferior cerebellar artery territory cerebellar infarction showed FFS, whereas only a quarter (n = 3) of the patients with isolated posterior inferior cerebellar artery (PICA) territory cerebellar infarction showed FFS. The proportion of gaze-evoked nystagmus (6/12 [50 %] vs. 2/17 [12 %], p = 0.04) and deficient gain of ipsilesional pursuit (10/12 [83 %] vs. 6/17 [35 %], p = 0.05) was more frequent in the FFS group than in the group without FFS. Lesion subtraction analysis in isolated PICA territory cerebellar infarction revealed that the nodulus was commonly damaged in patients with FFS, compared to that of patients without FFS. Our study shows that FFS of SN due to acute cerebellar infarction is less common than previously thought and the nodulus may be an important structure for the suppression of SN in humans. PMID:26082303

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

    PubMed

    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. PMID:26535469

  9. [Clinical manifestations of cerebellar ataxias].

    PubMed

    Abdulkerimov, Kh T

    2003-01-01

    The analysis of clinical manifestations and focal symptoms in 18 patients with cerebellar ataxia (CA) has shown that these markers are not sufficient for making an accurate diagnosis in all CA cases. It is recommended to verify an ataxia form with objective methods, computed stabilography, in particular. PMID:12958853

  10. Orthostatic tremor: a cerebellar pathology?

    PubMed Central

    Popa, Traian; García-Lorenzo, Daniel; Valabregue, Romain; Legrand, André-Pierre; Apartis, Emmanuelle; Marais, Lea; Degos, Bertrand; Hubsch, Cecile; Fernández-Vidal, Sara; Bardinet, Eric; Roze, Emmanuel; Lehéricy, Stéphane; Meunier, Sabine; Vidailhet, Marie

    2016-01-01

    See Muthuraman et al. (doi:10.1093/aww164) for a scientific commentary on this article. Primary orthostatic tremor is characterized by high frequency tremor affecting the legs and trunk during the standing position. Cerebellar defects were suggested in orthostatic tremor without direct evidence. We aimed to characterize the anatomo-functional defects of the cerebellar motor pathways in orthostatic tremor. We used multimodal neuroimaging to compare 17 patients with orthostatic tremor and 17 age- and gender-matched healthy volunteers. Nine of the patients with orthostatic tremor underwent repetitive transcranial stimulation applied over the cerebellum during five consecutive days. We quantified the duration of standing position and tremor severity through electromyographic recordings. Compared to healthy volunteers, grey matter volume in patients with orthostatic tremor was (i) increased in the cerebellar vermis and correlated positively with the duration of the standing position; and (ii) increased in the supplementary motor area and decreased in the lateral cerebellum, which both correlated with the disease duration. Functional connectivity between the lateral cerebellum and the supplementary motor area was abnormally increased in patients with orthostatic tremor, and correlated positively with tremor severity. After repetitive transcranial stimulation, tremor severity and functional connectivity between the lateral cerebellum and the supplementary motor area were reduced. We provide an explanation for orthostatic tremor pathophysiology, and demonstrate the functional relevance of cerebello-thalamo-cortical connections in tremor related to cerebellar defects. PMID:27329770

  11. Speech Prosody in Cerebellar Ataxia

    ERIC Educational Resources Information Center

    Casper, Maureen A.; Raphael, Lawrence J.; Harris, Katherine S.; Geibel, Jennifer M.

    2007-01-01

    Persons with cerebellar ataxia exhibit changes in physical coordination and speech and voice production. Previously, these alterations of speech and voice production were described primarily via perceptual coordinates. In this study, the spatial-temporal properties of syllable production were examined in 12 speakers, six of whom were healthy…

  12. The compartmental restriction of cerebellar interneurons

    PubMed Central

    Consalez, G. Giacomo; Hawkes, Richard

    2013-01-01

    The Purkinje cells (PC's) of the cerebellar cortex are subdivided into multiple different molecular phenotypes that form an elaborate array of parasagittal stripes. This array serves as a scaffold around which afferent topography is organized. The ways in which cerebellar interneurons may be restricted by this scaffolding are less well-understood. This review begins with a brief survey of cerebellar topography. Next, it reviews the development of stripes in the cerebellum with a particular emphasis on the embryological origins of cerebellar interneurons. These data serve as a foundation to discuss the hypothesis that cerebellar compartment boundaries also restrict cerebellar interneurons, both excitatory [granule cells, unipolar brush cells (UBCs)] and inhibitory (e.g., Golgi cells, basket cells). Finally, it is proposed that the same PC scaffold that restricts afferent terminal fields to stripes may also act to organize cerebellar interneurons. PMID:23346049

  13. The theory of interface slicing

    NASA Technical Reports Server (NTRS)

    Beck, Jon

    1993-01-01

    Interface slicing is a new tool which was developed to facilitate reuse-based software engineering, by addressing the following problems, needs, and issues: (1) size of systems incorporating reused modules; (2) knowledge requirements for program modification; (3) program understanding for reverse engineering; (4) module granularity and domain management; and (5) time and space complexity of conventional slicing. The definition of a form of static program analysis called interface slicing is addressed.

  14. Long-Term Spatiotemporal Reconfiguration of Neuronal Activity Revealed by Voltage-Sensitive Dye Imaging in the Cerebellar Granular Layer.

    PubMed

    Gandolfi, Daniela; Mapelli, Jonathan; D'Angelo, Egidio

    2015-01-01

    Understanding the spatiotemporal organization of long-term synaptic plasticity in neuronal networks demands techniques capable of monitoring changes in synaptic responsiveness over extended multineuronal structures. Among these techniques, voltage-sensitive dye imaging (VSD imaging) is of particular interest due to its good spatial resolution. However, improvements of the technique are needed in order to overcome limits imposed by its low signal-to-noise ratio. Here, we show that VSD imaging can detect long-term potentiation (LTP) and long-term depression (LTD) in acute cerebellar slices. Combined VSD imaging and patch-clamp recordings revealed that the most excited regions were predominantly associated with granule cells (GrCs) generating EPSP-spike complexes, while poorly responding regions were associated with GrCs generating EPSPs only. The correspondence with cellular changes occurring during LTP and LTD was highlighted by a vector representation obtained by combining amplitude with time-to-peak of VSD signals. This showed that LTP occurred in the most excited regions lying in the core of activated areas and increased the number of EPSP-spike complexes, while LTD occurred in the less excited regions lying in the surround. VSD imaging appears to be an efficient tool for investigating how synaptic plasticity contributes to the reorganization of multineuronal activity in neuronal circuits. PMID:26294979

  15. Differences in in vitro cerebellar neuronal responses to hypoxia in eider ducks, chicken and rats.

    PubMed

    Ludvigsen, Stian; Folkow, Lars P

    2009-11-01

    Ducks are well-known to be more tolerant to asphyxia than non-diving birds, but it is not known if their defences include enhanced neuronal hypoxia tolerance. To test this, we compared extracellular recordings of spontaneous activity in the Purkinje cell layer of 400 mum thick isolated cerebellar slices from eider ducks, chickens and rats, before, during and after 60 min hypoxia (95%N(2)-5%CO(2)) or chemical anoxia (hypoxia + 2 mM NaCN). Most slices rapidly lost activity in hypoxia, with or without recovery after rinse and return to normoxia (95%O(2)-5%CO(2)), but some maintained spontaneous activity throughout the insult. Proportions of 'surviving' (i.e. recovering or active) duck slices were significantly higher than for chickens in anoxia, and relative activity levels were higher for ducks than for chickens during hypoxia, anoxia and recovery. Survival of rat slices was significantly poorer than for birds under all conditions. Results suggest that (1) duck cerebellar neurons are intrinsically more hypoxia-tolerant than chicken neurons; (2) avian neurons are more hypoxia-tolerant than rat neurons, and (3) the enhanced hypoxic tolerance of duck neurons largely depended on efficient anaerobiosis since it mainly manifested itself in chemical anoxia. Mechanisms underlying the observed differences in neuronal hypoxic responses remain to be elucidated. PMID:19779726

  16. Kinetic and functional analysis of transient, persistent and resurgent sodium currents in rat cerebellar granule cells in situ: an electrophysiological and modelling study

    PubMed Central

    Magistretti, Jacopo; Castelli, Loretta; Forti, Lia; D'Angelo, Egidio

    2006-01-01

    Cerebellar neurones show complex and differentiated mechanisms of action potential generation that have been proposed to depend on peculiar properties of their voltage-dependent Na+ currents. In this study we analysed voltage-dependent Na+ currents of rat cerebellar granule cells (GCs) by performing whole-cell, patch-clamp experiments in acute rat cerebellar slices. A transient Na+ current (INaT) was always present and had the properties of a typical fast-activating/inactivating Na+ current. In addition to INaT, robust persistent (INaP) and resurgent (INaR) Na+ currents were observed. INaP peaked at ∼−40 mV, showed half-maximal activation at ∼−55 mV, and its maximal amplitude was about 1.5% of that of INaT. INaR was elicited by repolarizing pulses applied following step depolarizations able to activate/inactivate INaT, and showed voltage- and time-dependent activation and voltage-dependent decay kinetics. The conductance underlying INaR showed a bell-shaped voltage dependence, with peak at −35 mV. A significant correlation was found between GC INaR and INaT peak amplitudes; however, GCs expressing INaT of similar size showed marked variability in terms of INaR amplitude, and in a fraction of cells INaR was undetectable. INaT, INaP and INaR could be accounted for by a 13-state kinetic scheme comprising closed, open, inactivated and blocked states. Current-clamp experiments carried out to identify possible functional correlates of INaP and/or INaR revealed that in GCs single action potentials were followed by depolarizing afterpotentials (DAPs). In a majority of cells, DAPs showed properties consistent with INaR playing a role in their generation. Computer modelling showed that INaR promotes DAP generation and enhances high-frequency firing, whereas INaP boosts near-threshold firing activity. Our findings suggest that special properties of voltage-dependent Na+ currents provides GCs with mechanisms suitable for shaping activity patterns, with potentially

  17. Maternal milk as methylmercury source for suckling mice: neurotoxic effects involved with the cerebellar glutamatergic system.

    PubMed

    Manfroi, C B; Schwalm, F D; Cereser, V; Abreu, F; Oliveira, A; Bizarro, L; Rocha, J B T; Frizzo, M E S; Souza, D O; Farina, M

    2004-09-01

    Methylmercury (MeHg) is a highly neurotoxic compound and several studies have reported intoxication signs in children whose mothers were exposed to this environmental toxicant. Although it is well established that the in utero exposure to MeHg causes neurological deficits in animals and humans, there is no evidence of the exclusive contribution of lactational exposure to MeHg as a possible cause of neurotoxicity in the offspring. In this study, we investigated the exclusive contribution of MeHg exposure through maternal milk on biochemical parameters related to the glutamatergic homeostasis (glutamate uptake by slices) and to the oxidative stress (total and nonprotein sulfhydryl groups, nonprotein hydroperoxides, glutathione peroxidase and catalase activities) in the cerebellum of suckling mice (Swiss albino). The same parameters were also evaluated in the cerebellum of mothers. Our results showed, for the first time, that lactational exposure to MeHg caused a high percent of inhibition (50%) on glutamate uptake by cerebellar slices in pups. Contrarily, this effect was not observed in mothers, which were submitted to a direct oral exposure to MeHg (15 mg/l in drinking water). In addition, behavioral/functional changes were observed in the weaning mice exposed to MeHg. It was observed an increase in the levels of nonprotein hydroperoxides in cerebellum, and this increase was negatively correlated to the glutamate uptake by cerebellar slices. This study indicates that (1) the exposure of lactating mice to MeHg causes inhibition of the glutamate uptake by cerebellar slices in the offspring; (2) this inhibitory effect seems to be related to increased levels of hydroperoxide. PMID:15201443

  18. Cerebellar mature teratoma in adulthood.

    PubMed

    Zavanone, M; Alimehmeti, R; Campanella, R; Ram-Pini, P; Locatelli, M; Egidi, M; Righini, A; Bauer, D

    2002-03-01

    Mature teratoma of the posterior cranial fossa in adults is extremely rare. We report a particularly rare case of medio-lateral cerebellar mature teratoma that became symptomatic in a middle-aged man. The CT revealed the lesion of heterogeneous density with calcifications in the solid medial portion. Only the MRI could reliably define the borders of the cystic component extending into the left cerebellar lobe. Histologically the presence of fully matured representative tissues of the 3 germ layers ensured the diagnosis of mature teratoma. We suggest that the cyst formation from progressive latent hemorrhage and/or secretion from the gland cells of the tumor, may be responsible for the clinical decompensation even in adulthood. PMID:12118223

  19. Cerebellar neurocognition and Korsakoff's syndrome: an hypothesis.

    PubMed

    Wijnia, Jan W; Goossensen, Anne

    2010-08-01

    In literature, the cerebellum is given a substantial role in cognitive processes, in addition to traditional views on cerebellar function of regulating motor behaviour. The phenomenon of cerebellar damage causing impairments in memory and executive functioning was observed in various cerebellar disorders. Cerebellar cognitive dysfunction can be interpreted as a disturbance of cerebello-cerebral connections to areas of the cerebral cortex involved in cognitive processing, but the exact nature of the cognitive dysregulation is not known. Memory and executive dysfunction are important clinical features of Korsakoff's syndrome. We hypothesize that the Korsakoff syndrome might be an example of cerebellar neurocognitive dysfunctioning, caused by cerebello-cerebral pathways being disconnected in brain areas that are classically affected in Wernicke's encephalopathy. Further research is needed to support the possibility of cerebellar neurocognitive disturbances in Korsakoff's syndrome. If correct, this hypothesis may contribute to a better understanding of the clinical and neuropsychological profile of Korsakoff's syndrome. PMID:20303220

  20. Influence of thyroid hormones on maturation of rat cerebellar astrocytes.

    PubMed

    Manzano, Jimena; Bernal, Juan; Morte, Beatriz

    2007-05-01

    Thyroid hormone influences brain maturation through interaction with nuclear receptors and regulation of gene expression. Their role on astrocyte maturation remains unclear. We have analyzed the role of thyroid hormone in rat cerebellar astrocyte maturation by comparing the sequential patterns of intermediate filament expression in normal and hypothyroid animals. During normal development astroglial cells sequentially express nestin, vimentin, and glial fibrillary acidic protein. Differentiated astrocytes appeared in the superior medullary vellum by postnatal day 2 and reached the white mater and internal granular layer by postnatal day 4. Intermediate filament marker expression was transiently lost from postnatal days 6 to 8 in anterior lobes, without an increased apoptosis. Vimentin expression was replaced by glial fibrillary acidic protein between postnatal days 10 and 32. The differentiated astrocytes were evenly distributed throughout the cerebellar slices, including the internal granular layer. Differences between normal and hypothyroid rats were observed starting from postnatal day 4, with lack of differentiated astrocytes in the internal granular layer. The transient decrease of astrocyte markers immunoreactivity in the anterior lobe did not take place in hypothyroid rats. The vimentin-glial fibrillary acidic protein transition was delayed and most differentiated astrocytes remained confined to the white matter. The results indicate that thyroid hormone deficiency induces a delay and a partial arrest of astrocyte differentiation. Astrocytes express thyroid hormone receptor alpha and beta subtypes suggesting that astrocytes are direct target cells of thyroid hormones. PMID:17408906

  1. Infantile intracranial aneurysm of the superior cerebellar artery.

    PubMed

    Del Santo, Molly Ann; Cordina, Steve Mario

    2016-01-01

    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. PMID:26929222

  2. FGF-2 signal promotes proliferation of cerebellar progenitor cells and their oligodendrocytic differentiation at early postnatal stage

    SciTech Connect

    Naruse, Masae; Shibasaki, Koji; Ishizaki, Yasuki

    2015-08-07

    The origins and developmental regulation of cerebellar oligodendrocytes are largely unknown, although some hypotheses of embryonic origins have been suggested. Neural stem cells exist in the white matter of postnatal cerebellum, but it is unclear whether these neural stem cells generate oligodendrocytes at postnatal stages. We previously showed that cerebellar progenitor cells, including neural stem cells, widely express CD44 at around postnatal day 3. In the present study, we showed that CD44-positive cells prepared from the postnatal day 3 cerebellum gave rise to neurospheres, while CD44-negative cells prepared from the same cerebellum did not. These neurospheres differentiated mainly into oligodendrocytes and astrocytes, suggesting that CD44-positive neural stem/progenitor cells might generate oligodendrocytes in postnatal cerebellum. We cultured CD44-positive cells from the postnatal day 3 cerebellum in the presence of signaling molecules known as mitogens or inductive differentiation factors for oligodendrocyte progenitor cells. Of these, only FGF-2 promoted survival and proliferation of CD44-positive cells, and these cells differentiated into O4+ oligodendrocytes. Furthermore, we examined the effect of FGF-2 on cerebellar oligodendrocyte development ex vivo. FGF-2 enhanced proliferation of oligodendrocyte progenitor cells and increased the number of O4+ and CC1+ oligodendrocytes in slice cultures. These results suggest that CD44-positive cells might be a source of cerebellar oligodendrocytes and that FGF-2 plays important roles in their development at an early postnatal stage. - Highlights: • CD44 is expressed in cerebellar neural stem/progenitor cells at postnatal day 3 (P3). • FGF-2 promoted proliferation of CD44-positive progenitor cells from P3 cerebellum. • FGF-2 promoted oligodendrocytic differentiation of CD44-positive progenitor cells. • FGF-2 increased the number of oligodendrocytes in P3 cerebellar slice culture.

  3. Learning of Sensory Sequences in Cerebellar Patients

    ERIC Educational Resources Information Center

    Frings, Markus; Boenisch, Raoul; Gerwig, Marcus; Diener, Hans-Christoph; Timmann, Dagmar

    2004-01-01

    A possible role of the cerebellum in detecting and recognizing event sequences has been proposed. The present study sought to determine whether patients with cerebellar lesions are impaired in the acquisition and discrimination of sequences of sensory stimuli of different modalities. A group of 26 cerebellar patients and 26 controls matched for…

  4. Consensus Paper: Management of Degenerative Cerebellar Disorders

    PubMed Central

    Ilg, W.; Bastian, A. J.; Boesch, S.; Burciu, R. G.; Celnik, P.; Claaßen, J.; Feil, K.; Kalla, R.; Miyai, I.; Nachbauer, W.; Schöls, L.; Strupp, M.; Synofzik, M.; Teufel, J.

    2015-01-01

    Treatment of motor symptoms of degenerative cerebellar ataxia remains difficult. Yet there are recent developments that are likely to lead to significant improvements in the future. Most desirable would be a causative treatment of the underlying cerebellar disease. This is currently available only for a very small subset of cerebellar ataxias with known metabolic dysfunction. However, increasing knowledge of the pathophysiology of hereditary ataxia should lead to an increasing number of medically sensible drug trials. In this paper, data from recent drug trials in patients with recessive and dominant cerebellar ataxias will be summarized. There is consensus that up to date, no medication has been proven effective. Aminopyridines and acetazolamide are the only exception, which are beneficial in patients with episodic ataxia type 2. Aminopyridines are also effective in a subset of patients presenting with downbeat nystagmus. As such, all authors agreed that the mainstays of treatment of degenerative cerebellar ataxia are currently physiotherapy, occupational therapy, and speech therapy. For many years, well-controlled rehabilitation studies in patients with cerebellar ataxia were lacking. Data of recently published studies show that coordinative training improves motor function in both adult and juvenile patients with cerebellar degeneration. Given the well-known contribution of the cerebellum to motor learning, possible mechanisms underlying improvement will be outlined. There is consensus that evidence-based guidelines for the physiotherapy of degenerative cerebellar ataxia need to be developed. Future developments in physiotherapeutical interventions will be discussed including application of non-invasive brain stimulation. PMID:24222635

  5. Roles for nitric oxide and arachidonic acid in the induction of heterosynaptic cerebellar LTD.

    PubMed

    Reynolds, T; Hartell, N A

    2001-01-22

    In cerebellar slices conjunctive pairing of parallel fibre (PF) stimulation with depolarization of Purkinje cells (PCs) induces a long-term depression (LTD) of PF synaptic transmission that spreads to unpaired PF inputs to the same cell. Inhibitors of NO synthase (7-nitro-indazole), soluble guanylate cyclase (ODQ) and PKG (KT5823) all prevented depression at each of two independent PF pathways to a single PC. Inhibition of NOS also unmasked a platelet activating factor (PAF)-mediated synaptic potentiation of possible presynaptic origin. LTD was also prevented by the phospholipase A2 inhibitor OBAA but was rescued by co-perfusion with arachidonic acid. We conclude that NO and diffusible products of phospholipase A2 metabolism are potential mediators of the spread of cerebellar plasticity at the single cell level. PMID:11201073

  6. Metronidazole-Induced Cerebellar Toxicity

    PubMed Central

    Agarwal, Amit; Kanekar, Sangam; Sabat, Shyam; Thamburaj, Krishnamurthy

    2016-01-01

    Metronidazole is a very common antibacterial and antiprotozoal with wide usage across the globe, including the least developed countries. It is generally well-tolerated with a low incidence of serious side-effects. Neurological toxicity is fairly common with this drug, however majority of these are peripheral neuropathy with very few cases of central nervous toxicity reported. We report the imaging findings in two patients with cerebellar dysfunction after Metronidazole usage. Signal changes in the dentate and red nucleus were seen on magnetic resonance imaging in these patients. Most of the cases reported in literature reported similar findings, suggesting high predilection for the dentate nucleus in metronidazole induced encephalopathy. PMID:27127600

  7. Cerebellar Stroke-manifesting as Mania.

    PubMed

    Jagadesan, Venkatesan; Thiruvengadam, Kannapiran R; Muralidharan, Rengarajalu

    2014-07-01

    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. PMID:25035567

  8. Cerebellar Stroke-manifesting as Mania

    PubMed Central

    Jagadesan, Venkatesan; Thiruvengadam, Kannapiran R.; Muralidharan, Rengarajalu

    2014-01-01

    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. PMID:25035567

  9. Cellular and molecular basis of cerebellar development

    PubMed Central

    Martinez, Salvador; Andreu, Abraham; Mecklenburg, Nora; Echevarria, Diego

    2013-01-01

    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. PMID:23805080

  10. Isolated Hemiataxia and Cerebellar Diaschisis after a Small Dorsolateral Medullary Infarct

    PubMed Central

    Kishi, Masahiko; Sakakibara, Ryuji; Nagao, Takeki; Terada, Hitoshi; Ogawa, Emina

    2009-01-01

    Isolated hemiataxia after a medullary infarct is rare. We describe a case of isolated hemiataxia after a small infarct localized at the ipsilateral dorsolateral medulla. An 83-year-old man developed acute onset of ataxia in the left arm and in both legs. Speech and extraocular movement were normal, and he did not have any other neurological manifestations. Brain MRI showed a small infarct localized at the left dorsolateral medulla, which involved the inferior cerebellar peduncle. 123ECD-SPECT showed hypoperfusion in the left cerebellar hemisphere without clear vascular territory. Neuroimaging findings for our patient suggested the involvement of the inferior cerebellar peduncle that projects to the cerebellum in our patient. PMID:20847835

  11. Developmental Cerebellar Cognitive Affective Syndrome in Ex-preterm Survivors Following Cerebellar Injury

    PubMed Central

    Brossard-Racine, Marie; du Plessis, Adre J.; Limperopoulos, Catherine

    2015-01-01

    Cerebellar injury is increasingly recognized as an important complication of very preterm birth. However, the neurodevelopmental consequences of early life cerebellar injury in prematurely born infants have not been well elucidated. We performed a literature search of studies published between 1997 and 2014 describing neurodevelopmental outcomes of preterm infants following direct cerebellar injury or indirect cerebellar injury/underdevelopment. Available data suggests that both direct and indirect mechanisms of cerebellar injury appear to stunt cerebellar growth and adversely affect neurodevelopment. This review also provides important insights into the highly integrated cerebral-cerebellar structural and functional correlates. Finally, this review highlights that early life impairment of cerebellar growth extends far beyond motor impairments and plays a critical, previously underrecognized role in the long-term cognitive, behavioral, and social deficits associated with brain injury among premature infants. These data point to a developmental form of the cerebellar cognitive affective syndrome previously described in adults. Longitudinal prospective studies using serial advanced magnetic resonance imaging techniques are needed to better delineate the full extent of the role of prematurity-related cerebellar injury and topography in the genesis of cognitive, social-behavioral dysfunction. PMID:25241880

  12. LXR agonist rescued the deficit in the proliferation of the cerebellar granule cells induced by dexamethasone.

    PubMed

    Bian, Xuting; Zhong, Hongyu; Li, Fen; Cai, Yulong; Li, Xin; Wang, Lian; Fan, Xiaotang

    2016-09-01

    Dexamethasone (DEX) exposure during early postnatal life produces permanent neuromotor and intellectual deficits and stunts cerebellar growth. The liver X receptor (LXR) plays important roles in CNS development. However, the effects of LXR on the DEX-mediated impairment of cerebellar development remain undetermined. Thus, mice were pretreated with LXR agonist TO901317 (TO) and were later exposed to DEX to evaluate its protective effects on DEX-mediated deficit during cerebellar development. The results showed that an acute exposure of DEX on postnatal day 7 resulted in a significant impairment in cerebellar development and decreased the proliferation of granule neuron precursors in the external granule layer of cerebellum. This effect was attenuated by pretreatment with TO. We further found that the decrease in the proliferation caused by DEX occurred via up-regulation of glucocorticoid receptor and p27kip1, which could be partially prevented by LXR agonist pretreatment. Overall, our results suggest that LXR agonist pretreatment could protect against DEX-induced deficits in cerebellar development in postnatal mice and may thus be perspective recruited to counteract such GC side effects. PMID:27369072

  13. Cerebellar Motor Function in Spina Bifida Meningomyelocele

    PubMed Central

    Dennis, Maureen; Salman, Michael S.; Juranek, Jenifer; Fletcher, Jack M.

    2010-01-01

    Spina bifida meningomyelocele (SBM), a congenital neurodevelopmental disorder, involves dysmorphology of the cerebellum, and its most obvious manifestations are motor deficits. This paper reviews cerebellar neuropathology and motor function across several motor systems well studied in SBM in relation to current models of cerebellar motor and timing function. Children and adults with SBM have widespread motor deficits in trunk, upper limbs, eyes, and speech articulators that are broadly congruent with those observed in adults with cerebellar lesions. The structure and function of the cerebellum are correlated with a range of motor functions. While motor learning is generally preserved in SBM, those motor functions requiring predictive signals and precise calibration of the temporal features of movement are impaired, resulting in deficits in smooth movement coordination as well as in the classical cerebellar triad of dysmetria, ataxia, and dysarthria. That motor function in individuals with SBM is disordered in a manner phenotypically similar to that in adult cerebellar lesions, and appears to involve similar deficits in predictive cerebellar motor control, suggests that age-based cerebellar motor plasticity is limited in individuals with this neurodevelopmental disorder. PMID:20652468

  14. X-linked disorders with cerebellar dysgenesis

    PubMed Central

    2011-01-01

    X-linked disorders with cerebellar dysgenesis (XLCD) are a genetically heterogeneous and clinically variable group of disorders in which the hallmark is a cerebellar defect (hypoplasia, atrophy or dysplasia) visible on brain imaging, caused by gene mutations or genomic imbalances on the X-chromosome. The neurological features of XLCD include hypotonia, developmental delay, intellectual disability, ataxia and/or other cerebellar signs. Normal cognitive development has also been reported. Cerebellar dysgenesis may be isolated or associated with other brain malformations or multiorgan involvement. There are at least 15 genes on the X-chromosome that have been constantly or occasionally associated with a pathological cerebellar phenotype. 8 XLCD loci have been mapped and several families with X-linked inheritance have been reported. Recently, two recurrent duplication syndromes in Xq28 have been associated with cerebellar hypoplasia. Given the report of several forms of XLCD and the excess of males with ataxia, this group of conditions is probably underestimated and families of patients with neuroradiological and clinical evidence of a cerebellar disorder should be counseled for high risk of X-linked inheritance. PMID:21569638

  15. Pediatric Neurocutaneous Syndromes with Cerebellar Involvement.

    PubMed

    Bosemani, Thangamadhan; Huisman, Thierry A G M; Poretti, Andrea

    2016-08-01

    Neurocutaneous syndromes encompasses a broad group of genetic disorders with different clinical, genetic, and pathologic features that share developmental lesions of the skin as well as central and peripheral nervous system. Cerebellar involvement has been shown in numerous types of neurocutaneous syndrome. It may help or be needed for the diagnosis and to explain the cognitive and behavioral phenotype of affected children. This article describes various types of neurocutaneous syndrome with cerebellar involvement. For each neurocutaneous disease or syndrome, clinical features, genetic, neuroimaging findings, and the potential role of the cerebellar involvement is discussed. PMID:27423801

  16. Sonic hedgehog patterning during cerebellar development.

    PubMed

    De Luca, Annarita; Cerrato, Valentina; Fucà, Elisa; Parmigiani, Elena; Buffo, Annalisa; Leto, Ketty

    2016-01-01

    The morphogenic factor sonic hedgehog (Shh) actively orchestrates many aspects of cerebellar development and maturation. During embryogenesis, Shh signaling is active in the ventricular germinal zone (VZ) and represents an essential signal for proliferation of VZ-derived progenitors. Later, Shh secreted by Purkinje cells sustains the amplification of postnatal neurogenic niches: the external granular layer and the prospective white matter, where excitatory granule cells and inhibitory interneurons are produced, respectively. Moreover, Shh signaling affects Bergmann glial differentiation and promotes cerebellar foliation during development. Here we review the most relevant functions of Shh during cerebellar ontogenesis, underlying its role in physiological and pathological conditions. PMID:26499980

  17. Trumpet slices in Kerr spacetimes.

    PubMed

    Dennison, Kenneth A; Baumgarte, Thomas W; Montero, Pedro J

    2014-12-31

    We introduce a new time-independent family of analytical coordinate systems for the Kerr spacetime representing rotating black holes. We also propose a (2+1)+1 formalism for the characterization of trumpet geometries. Applying this formalism to our new family of coordinate systems we identify, for the first time, analytical and stationary trumpet slices for general rotating black holes, even for charged black holes in the presence of a cosmological constant. We present results for metric functions in this slicing and analyze the geometry of the rotating trumpet surface. PMID:25615297

  18. Optogenetic mapping of cerebellar inhibitory circuitry reveals spatially biased coordination of interneurons via electrical synapses.

    PubMed

    Kim, Jinsook; Lee, Soojung; Tsuda, Sachiko; Zhang, Xuying; Asrican, Brent; Gloss, Bernd; Feng, Guoping; Augustine, George J

    2014-06-12

    We used high-speed optogenetic mapping technology to examine the spatial organization of local inhibitory circuits formed by cerebellar interneurons. Transgenic mice expressing channelrhodopsin-2 exclusively in molecular layer interneurons allowed us to focally photostimulate these neurons, while measuring resulting responses in postsynaptic Purkinje cells. This approach revealed that interneurons converge upon Purkinje cells over a broad area and that at least seven interneurons form functional synapses with a single Purkinje cell. The number of converging interneurons was reduced by treatment with gap junction blockers, revealing that electrical synapses between interneurons contribute substantially to the spatial convergence. Remarkably, gap junction blockers affected convergence in sagittal slices, but not in coronal slices, indicating a sagittal bias in electrical coupling between interneurons. We conclude that electrical synapse networks spatially coordinate interneurons in the cerebellum and may also serve this function in other brain regions. PMID:24857665

  19. Urea Biosynthesis Using Liver Slices

    ERIC Educational Resources Information Center

    Teal, A. R.

    1976-01-01

    Presented is a practical scheme to enable introductory biology students to investigate the mechanism by which urea is synthesized in the liver. The tissue-slice technique is discussed, and methods for the quantitative analysis of metabolites are presented. (Author/SL)

  20. Consensus Paper: Radiological Biomarkers of Cerebellar Diseases

    PubMed Central

    Baldarçara, Leonardo; Currie, Stuart; Hadjivassiliou, M.; Hoggard, Nigel; Jack, Allison; Jackowski, Andrea P.; Mascalchi, Mario; Parazzini, Cecilia; Reetz, Kathrin; Righini, Andrea; Schulz, Jörg B.; Vella, Alessandra; Webb, Sara Jane; Habas, Christophe

    2016-01-01

    Hereditary and sporadic cerebellar ataxias represent a vast and still growing group of diseases whose diagnosis and differentiation cannot only rely on clinical evaluation. Brain imaging including magnetic resonance (MR) and nuclear medicine techniques allows for characterization of structural and functional abnormalities underlying symptomatic ataxias. These methods thus constitute a potential source of radiological biomarkers, which could be used to identify these diseases and differentiate subgroups of them, and to assess their severity and their evolution. Such biomarkers mainly comprise qualitative and quantitative data obtained from MR including proton spectroscopy, diffusion imaging, tractography, voxel-based morphometry, functional imaging during task execution or in a resting state, and from SPETC and PET with several radiotracers. In the current article, we aim to illustrate briefly some applications of these neuroimaging tools to evaluation of cerebellar disorders such as inherited cerebellar ataxia, fetal developmental malformations, and immune-mediated cerebellar diseases and of neurodegenerative or early-developing diseases, such as dementia and autism in which cerebellar involvement is an emerging feature. Although these radiological biomarkers appear promising and helpful to better understand ataxia-related anatomical and physiological impairments, to date, very few of them have turned out to be specific for a given ataxia with atrophy of the cerebellar system being the main and the most usual alteration being observed. Consequently, much remains to be done to establish sensitivity, specificity, and reproducibility of available MR and nuclear medicine features as diagnostic, progression and surrogate biomarkers in clinical routine. PMID:25382714

  1. Wire blade development for Fixed Abrasive Slicing Technique (FAST) slicing

    NASA Technical Reports Server (NTRS)

    Khattak, C. P.; Schmid, F.; Smith, M. B.

    1982-01-01

    A low cost, effective slicing method is essential to make ingot technology viable for photovoltaics in terrestrial applications. The fixed abrasive slicing technique (FAST) combines the advantages of the three commercially developed techniques. In its development stage FAST demonstrated cutting effectiveness of 10 cm and 15 cm diameter workpieces. Wire blade development is still the critical element for commercialization of FAST technology. Both impregnated and electroplated wire blades have been developed; techniques have been developed to fix diamonds only in the cutting edge of the wire. Electroplated wires show the most near term promise and this approach is emphasized. With plated wires it has been possible to control the size and shape of the electroplating, it is expected that this feature reduces kerf and prolongs the life of the wirepack.

  2. KATP-channels play a minor role in the protective hypoxic shut-down of cerebellar activity in eider ducks (Somateria mollissima).

    PubMed

    Geiseler, S J; Ludvigsen, S; Folkow, L P

    2015-01-22

    Eider duck (Somateria mollissima) cerebellar neurons are highly tolerant toward hypoxia in vitro, which in part is due to a hypoxia-induced depression of their spontaneous activity. We have studied whether this response involves ATP-sensitive potassium (KATP) channels, which are known to be involved in the hypoxic/ischemic defense of mammalian neural and muscular tissues, by causing hyperpolarization and reduced ATP demand. Extracellular recordings in the Purkinje layer of isolated normoxic eider duck cerebellar slices showed that their spontaneous neuronal activity decreased significantly compared to in control slices when the KATP channel opener diazoxide (600 μM) was added (F1,70=92.781, p<0.001). Adding the KATP channel blocker tolbutamide (400 μM) 5 min prior to diazoxide completely abolished its effect (F1,55=39.639, p<0.001), strongly suggesting that these drugs have a similar mode of action in this avian species as in mammals. The spontaneous activity of slices treated with tolbutamide in combined hypoxia/chemical anoxia (95% N2-5% CO2 and 2 mM NaCN) was not significantly different from that of control slices (F1,203=0.071, p=0.791). Recovery from hypoxia/anoxia was, however, slightly but significantly weaker in tolbutamide-treated slices than in control slices (F1,137=15.539, p<0.001). We conclude that KATP channels are present in eider duck cerebellar neurons and are activated in hypoxia/anoxia, but that they do not play a key role in the protective shut-down response to hypoxia/anoxia. PMID:25451290

  3. Cerebellar Globular Cells Receive Monoaminergic Excitation and Monosynaptic Inhibition from Purkinje Cells

    PubMed Central

    Hirono, Moritoshi; Saitow, Fumihito; Kudo, Moeko; Suzuki, Hidenori; Yanagawa, Yuchio; Yamada, Masahisa; Nagao, Soichi; Konishi, Shiro; Obata, Kunihiko

    2012-01-01

    Inhibitory interneurons in the cerebellar granular layer are more heterogeneous than traditionally depicted. In contrast to Golgi cells, which are ubiquitously distributed in the granular layer, small fusiform Lugaro cells and globular cells are located underneath the Purkinje cell layer and small in number. Globular cells have not been characterized physiologically. Here, using cerebellar slices obtained from a strain of gene-manipulated mice expressing GFP specifically in GABAergic neurons, we morphologically identified globular cells, and compared their synaptic activity and monoaminergic influence of their electrical activity with those of small Golgi cells and small fusiform Lugaro cells. Globular cells were characterized by prominent IPSCs together with monosynaptic inputs from the axon collaterals of Purkinje cells, whereas small Golgi cells or small fusiform Lugaro cells displayed fewer and smaller spontaneous IPSCs. Globular cells were silent at rest and fired spike discharges in response to application of either serotonin (5-HT) or noradrenaline. The two monoamines also facilitated small Golgi cell firing, but only 5-HT elicited firing in small fusiform Lugaro cells. Furthermore, globular cells likely received excitatory monosynaptic inputs through mossy fibers. Because globular cells project their axons long in the transversal direction, the neuronal circuit that includes interplay between Purkinje cells and globular cells could regulate Purkinje cell activity in different microzones under the influence of monoamines and mossy fiber inputs, suggesting that globular cells likely play a unique modulatory role in cerebellar motor control. PMID:22235322

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

    PubMed

    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. PMID:26482421

  5. Exogenous Sonic hedgehog modulates the pool of GABAergic interneurons during cerebellar development.

    PubMed

    De Luca, A; Parmigiani, E; Tosatto, G; Martire, S; Hoshino, M; Buffo, A; Leto, K; Rossi, F

    2015-04-01

    All cerebellar GABAergic interneurons were derived from a common pool of precursor cells residing in the embryonic ventricular zone (VZ) and migrating in the prospective white matter (PWM) after birth, where both intrinsic and extrinsic factors contribute to regulate their amplification. Among the environmental factors, we focused on Sonic hedgehog (Shh), a morphogen well known to regulate neural progenitor cell proliferation. We asked if and how exogenous Shh treatment affects the lineage of cerebellar GABAergic interneurons. To address these issues, exogenous Shh was administered to embryonic and postnatal organotypic slices. We found that Shh is able to expand the pool of interneuron progenitors residing in the embryonic epithelium and in the postnatal PWM. In particular, Shh signalling pathway was highly mitogenic at early developmental stages of interneuron production, whereas its effect decreased after the first postnatal week. Gene expression analysis of sorted cells and in situ hybridization further showed that immature interneurons express both the Shh receptor patched and the Shh target gene Gli1. Thus, within the interneuron lineage, Shh might exert regulatory functions also in postmitotic cells. On the whole, our data enlighten the role of Shh during cerebellar maturation and further broaden our knowledge on the amplification mechanisms of the interneuron progenitor pool. PMID:25245619

  6. Evaluating cerebellar functions using optogenetic transgenic mice

    NASA Astrophysics Data System (ADS)

    Welsh, John P.; Turecek, Josef; Turner, Eric E.

    2013-03-01

    We employed a transgenic mouse having conditional expression of ChR2(H134R) in neurons of the inferior olive to facilitate understanding of the role of electrical coupling and oscillation in central nervous system function. Two-photon excitation of ChR2-expressing neurons using 64 laser beams restricted to single inferior olive cell bodies depolarized neurons and evoked voltage deflections in neighboring neurons demonstrating electrical coupling. Broader illumination of neuronal ensembles using blue light induced an optical clamp of endogenous electrical rhythms in the inferior olive of acutely-prepared brain slices, which when applied in vivo directly modulated the local field potential activity and induced tremor. The experiments demonstrate novel methods to optically manipulate electrically coupled potentials and rhythmogenesis within a neuronal ensemble. From a functional perspective, the experiments shed light on the cellular and circuitry mechanisms of essential tremor, a prevalent neurological condition, by indicating time- and frequencydependence of tremor upon varying rhythms of inferior olive stimulation. The experiments indicate analog control of a brain rhythm that may be used to enhance our understanding of the functional consequences of central rhythmogenesis.

  7. Primary cerebellar extramedullary myeloid cell tumor mimicking oligodendroglioma.

    PubMed

    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. PMID:9341943

  8. Ischemia deteriorates the spike encoding of rat cerebellar Purkinje cells by raising intracellular Ca{sup 2+}

    SciTech Connect

    Zhao Shidi; Chen Na; Yang Zhilai; Huang Li; Zhu Yan; Guan Sudong; Chen Qianfen; Wang Jinhui

    2008-02-08

    Ischemia-induced excitotoxicity at cerebellar Purkinje cells is presumably due to a persistent glutamate action. To the fact that they are more vulnerable to ischemia than other glutamate-innervated neurons, we studied whether additional mechanisms are present and whether cytoplasm Ca{sup 2+} plays a key role in their ischemic excitotoxicity. Ischemic changes in the excitability of Purkinje cells were measured by whole-cell recording in cerebellar slices of rats with less glutamate action. The role of cytoplasm Ca{sup 2+} was examined by two-photon cellular imaging and BAPTA infusion in Purkinje cells. Lowering perfusion rate to cerebellar slices deteriorated spike timing and raised spike capacity of Purkinje cells. These changes were associated with the reduction of spike refractory periods and threshold potentials, as well as the loss of their control to spike encoding. Ischemia-induced functional deterioration at Purkinje neurons was accompanied by cytoplasm Ca{sup 2+} rise and prevented by BAPTA infusion. Therefore, the ischemia destabilizes the spike encoding of Purkinje cells via raising cytoplasm Ca{sup 2+} without a need for glutamate, which subsequently causes their excitotoxic death.

  9. Acute Ataxia in Childhood: 11-Year Experience at a Major Pediatric Neurology Referral Center.

    PubMed

    Thakkar, Kavita; Maricich, Stephen M; Alper, Gulay

    2016-08-01

    We categorized the causes of acute ataxia in the pediatric population-referred to the Division of Neurology-at a large, urban pediatric medical center. Of the 120 cases identified over the past 11 years, post-infectious cerebellar ataxia was the most commonly diagnosed (59%), followed by drug intoxication, opsoclonus-myoclonus ataxia syndrome, episodic ataxia, acute cerebellitis, cerebellar stroke, ADEM, meningitis, cerebral vein thrombosis, Leigh's disease, Miller-Fisher syndrome, and concussion. Among the patients with post-infectious cerebellar ataxia, 85% were 1-6 years old and all had a history of antecedent viral illness. CSF pleocytosis was present in 40% of patients; all had normal brain MRIs. The majority (91%) recovered within 30 days. We conclude that post-infectious cerebellar ataxia remains the most common cause of acute ataxia in childhood and that it carries a good prognosis. We also differentiate acute post-infectious cerebellar ataxia from other causes with similar presentations. PMID:27071467

  10. Implications on cerebellar function from information coding.

    PubMed

    Huang, Chiming

    2008-01-01

    One function of the cerebellar cortex is to process information. There are at least two types of information. Temporal information is encoded in the timing pattern of action and synaptic potentials, whereas structural information is encoded in the spatial pattern of the cerebellar synaptic circuitry. Intuitively, analysis of highly complex information in the time domain would require a cerebellar cortex with structural complexity to match. Information theory offers a way to estimate quantitatively both types of information and thereby helps to test hypotheses or advance theories of cerebellar neurobiology. These estimates suggest: (i) That the mossy-fiber-granule-cell system carries far more (temporal) information than the climbing fiber system, (ii) that Purkinje cells extract only a fraction of the (temporal) information from their afferents, and (iii) that the cerebellar cortex has a large (spatial) information coding capacity. Concerning information, one can argue that the cerebellar cortex analyzes temporal information in its afferents as a search engine, in search of coincidental mossy fiber events based on timing cues provided by climbing fiber events. Results of successive searches are continuously being converted into structural information encoded in the spatial distribution pattern of granule-cell-Purkinje-cell synapses along granule cell axons, thereby providing an adaptive and indeed self-correcting dimension to the structural information code. The search engine operation involves cellular mechanisms acting on temporal events and is part of an associative learning process. The conversion and generation of structural information involves neuroplasticity mechanisms acting at the synaptic level, with electrophysiological as well as structural consequences, and may be part of the short- and long-term memory process. These and other attributes qualify the cerebellar cortex as a dynamic information processing center, contributing to memory and learning while

  11. Pharmacotherapy of vestibular and cerebellar disorders and downbeat nystagmus: translational and back-translational research.

    PubMed

    Strupp, Michael; Zwergal, Andreas; Feil, Katharina; Bremova, Tatiana; Brandt, Thomas

    2015-04-01

    There are currently eight groups of drugs for the pharmacotherapy of vertigo, nystagmus, and cerebellar disorders: antiemetics; anti-inflammatories, antimenieres, and antimigraineous medications; antidepressants, anticonvulsants, aminopyridines, and acetyl-DL-leucine ("the eight A's"). In acute unilateral vestibulopathy, corticosteroids improve the recovery of peripheral vestibular function, but there is not sufficient current evidence for a general recommendation. There is also insufficient evidence that 48 or 144 mg/day betahistine has an effect in Ménière's disease. Therefore, higher dosages are currently recommended; in animal studies, it was shown that betahistine increases cochlear blood flow. In vestibular paroxysmia, oxcarbazepine was effective (one yet not randomized controlled trial (RCT)). Aminopyridines are recommended for the treatment of downbeat nystagmus (two RCTs) and episodic ataxia type 2 (EA2, one RCT). There are so far no RCTs on vestibular migraine, so currently no treatment can be recommended. Acetyl-dl-leucine improves cerebellar ataxia (three observational studies); it also accelerates central compensation in an animal model of acute unilateral lesion, but RCTs were negative. There are ongoing RCTs on vestibular paroxysmia with carbamazepine (VESPA), acute unilateral vestibulopathy with betahistine (BETAVEST), vestibular migraine with metoprolol (PROVEMIG), benign paroxysmal positional vertigo with vitamin D (VitD@BPPV), EA2 with 4-aminopyridine versus acetazolamide (EAT-2-TREAT), and cerebellar ataxias with acetyl-DL-leucine (ALCAT). PMID:25903394

  12. Ingot slicing machine and method

    NASA Technical Reports Server (NTRS)

    Kuo, Y. S. (Inventor)

    1984-01-01

    An improved method for simultaneously slicing one or a multiplicity of boules of silicon into silicon wafers is described. A plurality of vertical stacks of horizontal saw blades of circular configuration are arranged in juxtaposed coaxial alignment. Each blade is characterized by having a cutting diameter slightly greater than the cutting diameter of the blade arranged immediately above, imparting a simultaneous rotation to the blades.

  13. Studying T Cell Development in Thymic Slices.

    PubMed

    Ross, Jenny O; Melichar, Heather J; Halkias, Joanna; Robey, Ellen A

    2016-01-01

    Recently, tissue slices have been adapted to study both mouse and human T cell development. Thymic slices combine and complement the strengths of existing organotypic culture systems to study thymocyte differentiation. Specifically, the thymic slice system allows for high throughput experiments and the ability to introduce homogenous developmental intermediate populations into an environment with a well-established cortex and medulla. These qualities make thymic slices a highly versatile and technically accessible model to study thymocyte development. Here we describe methods to prepare, embed, and slice thymic lobes to study T cell development in situ. PMID:26294404

  14. Oculomotor studies of cerebellar function in autism.

    PubMed

    Nowinski, Caralynn V; Minshew, Nancy J; Luna, Beatriz; Takarae, Yukari; Sweeney, John A

    2005-11-15

    Histopathological, neuroimaging and genetic findings indicate cerebellar abnormalities in autism, but the extent of neurophysiological dysfunction associated with those findings has not been systematically examined. Suppression of intrusive saccades (square wave jerks) and the ability to sustain eccentric gaze, two phenomena requiring intact cerebellar function, were examined in 52 high-functioning individuals with autism and 52 age- and IQ-matched healthy subjects during visual fixation of static central and peripheral targets. Rates of intrusive saccades were not increased in autism during visual fixation, and foveopetal ocular drift was also not increased when subjects held an eccentric gaze. The absence of gross disturbances of visual fixation associated with cerebellar disease in individuals with autism, such as increased square wave jerk rates and foveopetal drift when holding eccentric gaze, indicates that the functional integrity of cerebellar--brainstem networks devoted to oculomotor control is preserved in autism despite reported anatomic variations. However, increased amplitude of intrusive saccades and reduced latency of target refixation after intrusive saccades were observed in individuals with autism, especially when subjects maintained fixation of remembered target locations without sensory guidance. The atypical metrics of intrusive saccades that were observed may be attributable to faulty functional connectivity in cortico-cerebellar networks. PMID:16214219

  15. Cerebellar modules operate at different frequencies

    PubMed Central

    Zhou, Haibo; Lin, Zhanmin; Voges, Kai; Ju, Chiheng; Gao, Zhenyu; Bosman, Laurens WJ; Ruigrok, Tom JH; Hoebeek, Freek E

    2014-01-01

    Due to the uniform cyto-architecture of the cerebellar cortex, its overall physiological characteristics have traditionally been considered to be homogeneous. In this study, we show in awake mice at rest that spiking activity of Purkinje cells, the sole output cells of the cerebellar cortex, differs between cerebellar modules and correlates with their expression of the glycolytic enzyme aldolase C or zebrin. Simple spike and complex spike frequencies were significantly higher in Purkinje cells located in zebrin-negative than zebrin-positive modules. The difference in simple spike frequency persisted when the synaptic input to, but not intrinsic activity of, Purkinje cells was manipulated. Blocking TRPC3, the effector channel of a cascade of proteins that have zebrin-like distribution patterns, attenuated the simple spike frequency difference. Our results indicate that zebrin-discriminated cerebellar modules operate at different frequencies, which depend on activation of TRPC3, and that this property is relevant for all cerebellar functions. DOI: http://dx.doi.org/10.7554/eLife.02536.001 PMID:24843004

  16. Metabolic anatomy of paraneoplastic cerebellar degeneration

    SciTech Connect

    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.

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

    MedlinePlus

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

  18. Neurodevelopmental malformations of the cerebellar vermis in genetically engineered rats

    EPA Science Inventory

    The cerebellar vermis is particularly vulnerable to neurodevelopmental malformations in humans and rodents. Sprague-Dawley, and Long-Evans rats exhibit spontaneous cerebellar malformations consisting of heterotopic neurons and glia in the molecular layer of the vermis. Malformati...

  19. Restricted diffusion in Wallerian degeneration of the middle cerebellar peduncles following pontine infarction

    PubMed Central

    Musson, Rachel; Romanowski, Charles

    2010-01-01

    Summary Background: Acute Wallerian degeneration following infarction has been show to result in areas of restricted diffusion within the brain. Very few reports describe this appearance in middle cerebellar peduncles. Case Report: A 37 year old woman was admitted to hospital following sudden collapse and was subsequently found to have a pontine infarct. The complex clinical course resulted in MR imaging including DWI at day 4, 9 and 23 after the initial presentation. The cerebellar peduncles were normal when imaged on day 4 and 9. At day 23, symmetrical high T2 signal was seen in both cerebellar peduncles. The DWI illustrated high signal with corresponding low signal on the ADC map consistent with restricted diffusion. We discuss why this appearance is in keeping with Wallerian degeneration and also describe the fibre pathways involved. Conclusions: Symmetrical high signal with restricted diffusion in the middle cerebellar peduncles following a pontine lesion is almost certainly attributable to Wallerian degeneration and should not be mistaken for a new ischaemia. PMID:22802803

  20. Ethanol modulates facial stimulation-evoked outward currents in cerebellar Purkinje cells in vivo in mice.

    PubMed

    Wu, Mao-Cheng; Bing, Yan-Hua; Chu, Chun-Ping; Qiu, De-Lai

    2016-01-01

    Acute ethanol overdose can induce dysfunction of cerebellar motor regulation and cerebellar ataxia. In this study, we investigated the effect of ethanol on facial stimulation-evoked inhibitory synaptic responses in cerebellar Purkinje cells (PCs) in urethane-anesthetized mice, using in vivo patch-clamp recordings. Under voltage-clamp conditions, ethanol (300 mM) decreased the amplitude, half-width, rise time and decay time of facial stimulation-evoked outward currents in PCs. The ethanol-induced inhibition of facial stimulation-evoked outward currents was dose-dependent, with an IC50 of 148.5 mM. Notably, the ethanol-induced inhibition of facial stimulation-evoked outward currents were significantly abrogated by cannabinoid receptor 1 (CB1) antagonists, AM251 and O-2050, as well as by the CB1 agonist WIN55212-2. Moreover, the ethanol-induced inhibition of facial stimulation-evoked outward currents was prevented by cerebellar surface perfusion of the PKA inhibitors H-89 and Rp-cAMP, but not by intracellular administration of the PKA inhibitor PKI. Our present results indicate that ethanol inhibits the facial stimulation-evoked outward currents by activating presynaptic CB1 receptors via the PKA signaling pathway. These findings suggest that ethanol overdose impairs sensory information processing, at least in part, by inhibiting GABA release from molecular layer interneurons onto PCs. PMID:27489024

  1. Ethanol modulates facial stimulation-evoked outward currents in cerebellar Purkinje cells in vivo in mice

    PubMed Central

    Wu, Mao-Cheng; Bing, Yan-Hua; Chu, Chun-Ping; Qiu, De-Lai

    2016-01-01

    Acute ethanol overdose can induce dysfunction of cerebellar motor regulation and cerebellar ataxia. In this study, we investigated the effect of ethanol on facial stimulation-evoked inhibitory synaptic responses in cerebellar Purkinje cells (PCs) in urethane-anesthetized mice, using in vivo patch-clamp recordings. Under voltage-clamp conditions, ethanol (300 mM) decreased the amplitude, half-width, rise time and decay time of facial stimulation-evoked outward currents in PCs. The ethanol-induced inhibition of facial stimulation-evoked outward currents was dose-dependent, with an IC50 of 148.5 mM. Notably, the ethanol-induced inhibition of facial stimulation-evoked outward currents were significantly abrogated by cannabinoid receptor 1 (CB1) antagonists, AM251 and O-2050, as well as by the CB1 agonist WIN55212-2. Moreover, the ethanol-induced inhibition of facial stimulation-evoked outward currents was prevented by cerebellar surface perfusion of the PKA inhibitors H-89 and Rp-cAMP, but not by intracellular administration of the PKA inhibitor PKI. Our present results indicate that ethanol inhibits the facial stimulation-evoked outward currents by activating presynaptic CB1 receptors via the PKA signaling pathway. These findings suggest that ethanol overdose impairs sensory information processing, at least in part, by inhibiting GABA release from molecular layer interneurons onto PCs. PMID:27489024

  2. Continuous network of endoplasmic reticulum in cerebellar Purkinje neurons.

    PubMed Central

    Terasaki, M; Slater, N T; Fein, A; Schmidek, A; Reese, T S

    1994-01-01

    Purkinje neurons in rat cerebellar slices injected with an oil drop saturated with 1,1'-dihexadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate [DiIC16(3) or DiI] to label the endoplasmic reticulum were observed by confocal microscopy. DiI spread throughout the cell body and dendrites and into the axon. DiI spreading is due to diffusion in a continuous bilayer and is not due to membrane trafficking because it also spreads in fixed neurons. DiI stained such features of the endoplasmic reticulum as densities at branch points, reticular networks in the cell body and dendrites, nuclear envelope, spines, and aggregates formed during anoxia nuclear envelope, spines, and aggregates formed during anoxia in low extracellular Ca2+. In cultured rat hippocampal neurons, where optical conditions provide more detail, DiI labeled a clearly delineated network of endoplasmic reticulum in the cell body. We conclude that there is a continuous compartment of endoplasmic reticulum extending from the cell body throughout the dendrites. This compartment may coordinate and integrate neuronal functions. Images PMID:7519781

  3. Automatic basal slice detection for cardiac analysis

    NASA Astrophysics Data System (ADS)

    Paknezhad, Mahsa; Marchesseau, Stephanie; Brown, Michael S.

    2016-03-01

    Identification of the basal slice in cardiac imaging is a key step to measuring the ejection fraction (EF) of the left ventricle (LV). Despite research on cardiac segmentation, basal slice identification is routinely performed manually. Manual identification, however, has been shown to have high inter-observer variability, with a variation of the EF by up to 8%. Therefore, an automatic way of identifying the basal slice is still required. Prior published methods operate by automatically tracking the mitral valve points from the long-axis view of the LV. These approaches assumed that the basal slice is the first short-axis slice below the mitral valve. However, guidelines published in 2013 by the society for cardiovascular magnetic resonance indicate that the basal slice is the uppermost short-axis slice with more than 50% myocardium surrounding the blood cavity. Consequently, these existing methods are at times identifying the incorrect short-axis slice. Correct identification of the basal slice under these guidelines is challenging due to the poor image quality and blood movement during image acquisition. This paper proposes an automatic tool that focuses on the two-chamber slice to find the basal slice. To this end, an active shape model is trained to automatically segment the two-chamber view for 51 samples using the leave-one-out strategy. The basal slice was detected using temporal binary profiles created for each short-axis slice from the segmented two-chamber slice. From the 51 successfully tested samples, 92% and 84% of detection results were accurate at the end-systolic and the end-diastolic phases of the cardiac cycle, respectively.

  4. Landmark Based Shape Analysis for Cerebellar Ataxia Classification and Cerebellar Atrophy Pattern Visualization

    PubMed Central

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

    2016-01-01

    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. PMID:27303111

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

    NASA Astrophysics Data System (ADS)

    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.

  6. Subarachnoid hemorrhage then thrombosis of posterior inferior cerebellar artery dissection: is early surgical exploration warranted?

    PubMed

    Alexiades, Nikita G; Ellis, Jason A; Meyers, Philip M; Connolly, E Sander

    2016-06-01

    The natural history of spontaneous cerebral artery dissection and thrombosis remains uncertain. Concurrent subarachnoid hemorrhage further complicates the therapeutic approach. Thus the best strategy for managing patients with acute vessel thrombosis in the setting of subarachnoid hemorrhage is unclear. Here we present a case of spontaneous posterior inferior cerebellar artery dissection presenting with subarachnoid hemorrhage and acute thrombosis. Although the patient was initially managed conservatively, angiographic follow-up demonstrated recanalization of the diseased vessel, necessitating definitive treatment. Thus we propose that angiographic follow-up is necessary in the management of patients with subarachnoid hemorrhage in association with apparent vessel thrombosis. PMID:25987592

  7. Simultaneous occurrence of internal capsule infarct and cerebellar haemorrhage in a patient with hemiplegia.

    PubMed

    Pande, Nikhil; Vivek, Ganapathiraman; Hande, Manjunath; Acharya, Vasudeva

    2014-01-01

    A 68-year-old woman with hypertension with no history of cerebrovascular events presented with a left-sided hemiplegia which had developed acutely 2 days ago. She was not on maintenance therapy with antiplatelets or anticoagulants. A CT scan showed acute ischaemic infarction of the right internal capsule and cerebellar haemorrhage. Cardiac evaluation was normal. Doppler ultrasonography of the extracranial carotid and vertebral arteries showed diffuse arteriosclerotic changes, but did not reveal any haemodynamic occlusion. The simultaneous development of dual strokes was considered to be an extension of the same arteriosclerotic process to the intracranial carotid and basilar arteries. PMID:24408941

  8. Cerebellar contribution to feedforward control of locomotion

    PubMed Central

    Pisotta, Iolanda; Molinari, Marco

    2014-01-01

    The cerebellum is an important contributor to feedforward control mechanisms of the central nervous system, and sequencing—the process that allows spatial and temporal relationships between events to be recognized—has been implicated as the fundamental cerebellar mode of operation. By adopting such a mode and because cerebellar activity patterns are sensitive to a variety of sensorimotor-related tasks, the cerebellum is believed to support motor and cognitive functions that are encoded in the frontal and parietal lobes of the cerebral cortex. In this model, the cerebellum is hypothesized to make predictions about the consequences of a motor or cognitive command that originates from the cortex to prepare the entire system to cope with ongoing changes. In this framework, cerebellar predictive mechanisms for locomotion are addressed, focusing on sensorial and motoric sequencing. The hypothesis that sequence recognition is the mechanism by which the cerebellum functions in gait control is presented and discussed. PMID:25009490

  9. Cerebellar Glioblastoma Multiforme in an Adult

    PubMed Central

    Hur, Hyuk; Jung, Tae-Young; Kim, In-Young

    2008-01-01

    Primary cerebellar glioblastoma multiforme (GBM) is a rare tumor in adults that accounts for just 1% of all cases of GBM. Due to their rarity, cerebellar GBMs are not yet completely understood about the pathogenesis and the prognosis. Here, we present a case of GBM in a 69-year-old man. Neurologic examination revealed the presence of cerebellar signs. Magnetic resonance imaging (MRI) showed a 4.5 × 3.6 cm-sized, ill-defined, heterogeneously enhancing mass in the left cerebellum and two patchy hyperintense lesions in the right cerebellum with minimal enhancement. After operation, glioblastoma was histologically confirmed. Postoperative radiotherapy with concomitant and adjuvant temozolomide chemotherapy was subsequently followed. Here, a case of unusual GBM in the cerebellum is reported with review of literature regarding the pathogenesis, the differential diagnosis and prognosis. There was no evidence of recurrence during postoperative one year. This patient showed a good prognosis in spite of the multiple lesions. PMID:19096643

  10. Cerebellar contribution to feedforward control of locomotion.

    PubMed

    Pisotta, Iolanda; Molinari, Marco

    2014-01-01

    The cerebellum is an important contributor to feedforward control mechanisms of the central nervous system, and sequencing-the process that allows spatial and temporal relationships between events to be recognized-has been implicated as the fundamental cerebellar mode of operation. By adopting such a mode and because cerebellar activity patterns are sensitive to a variety of sensorimotor-related tasks, the cerebellum is believed to support motor and cognitive functions that are encoded in the frontal and parietal lobes of the cerebral cortex. In this model, the cerebellum is hypothesized to make predictions about the consequences of a motor or cognitive command that originates from the cortex to prepare the entire system to cope with ongoing changes. In this framework, cerebellar predictive mechanisms for locomotion are addressed, focusing on sensorial and motoric sequencing. The hypothesis that sequence recognition is the mechanism by which the cerebellum functions in gait control is presented and discussed. PMID:25009490

  11. 21 CFR 882.5820 - Implanted cerebellar stimulator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 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...

  12. 21 CFR 882.5820 - Implanted cerebellar stimulator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 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...

  13. 21 CFR 882.5820 - Implanted cerebellar stimulator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 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...

  14. Postirradiation cerebellar glioma. Case report

    SciTech Connect

    Raffel, C.; Edwards, M.S.; Davis, R.L.; Ablin, A.R.

    1985-02-01

    A 13-year-old girl developed an anaplastic astrocytoma of the cerebellum 7 years after irradiation of the central nervous system and prophylactic chemotherapy for acute lymphocytic leukemia. The fact that the astrocytoma was anaplastic and infiltrative was unusual for astroglial tumors at this site. It is proposed that this is a radiation-induced glioma.

  15. Robust reflective pupil slicing technology

    NASA Astrophysics Data System (ADS)

    Meade, Jeffrey T.; Behr, Bradford B.; Cenko, Andrew T.; Hajian, Arsen R.

    2014-07-01

    Tornado Spectral Systems (TSS) has developed the High Throughput Virtual Slit (HTVSTM), robust all-reflective pupil slicing technology capable of replacing the slit in research-, commercial- and MIL-SPEC-grade spectrometer systems. In the simplest configuration, the HTVS allows optical designers to remove the lossy slit from pointsource spectrometers and widen the input slit of long-slit spectrometers, greatly increasing throughput without loss of spectral resolution or cross-dispersion information. The HTVS works by transferring etendue between image plane axes but operating in the pupil domain rather than at a focal plane. While useful for other technologies, this is especially relevant for spectroscopic applications by performing the same spectral narrowing as a slit without throwing away light on the slit aperture. HTVS can be implemented in all-reflective designs and only requires a small number of reflections for significant spectral resolution enhancement-HTVS systems can be efficiently implemented in most wavelength regions. The etendueshifting operation also provides smooth scaling with input spot/image size without requiring reconfiguration for different targets (such as different seeing disk diameters or different fiber core sizes). Like most slicing technologies, HTVS provides throughput increases of several times without resolution loss over equivalent slitbased designs. HTVS technology enables robust slit replacement in point-source spectrometer systems. By virtue of pupilspace operation this technology has several advantages over comparable image-space slicer technology, including the ability to adapt gracefully and linearly to changing source size and better vertical packing of the flux distribution. Additionally, this technology can be implemented with large slicing factors in both fast and slow beams and can easily scale from large, room-sized spectrometers through to small, telescope-mounted devices. Finally, this same technology is directly

  16. Antiphospholipid antibodies bind to rat cerebellar granule cells: the role of N-methyl-D-aspartate receptors.

    PubMed

    Riccio, A; Andreassi, C; Eboli, M L

    1998-11-27

    IgGs from sera containing antiphospholipid antibodies (aPL), detected as antibodies to cardiolipin, or control sera were incubated with rat cerebellar granule cells in primary culture. Using a mitochondrial dehydrogenase activity assay (MTT test), aPL IgGs were shown to decrease MTT metabolism after 24 h incubation with the cells, and to cause non-toxic amounts of glutamate to become neurotoxic when added to the cells for 45 min. Acute and chronic aPL toxicity were prevented by MK-801. Sera containing aPL bound to intact cerebellar neurons, as revealed by an immunofluorescent technique. These results suggest that antiphospholipid antibodies interfere with excitatory pathways in glutamatergic cerebellar granule cells by a mechanism involving overactivation of the NMDA glutamate receptor. PMID:9865941

  17. The Cerebellar Mutism Syndrome and Its Relation to Cerebellar Cognitive Function and the Cerebellar Cognitive Affective Disorder

    ERIC Educational Resources Information Center

    Wells, Elizabeth M.; Walsh, Karin S.; Khademian, Zarir P.; Keating, Robert F.; Packer, Roger J.

    2008-01-01

    The postoperative cerebellar mutism syndrome (CMS), consisting of diminished speech output, hypotonia, ataxia, and emotional lability, occurs after surgery in up to 25% of patients with medulloblastoma and occasionally after removal of other posterior fossa tumors. Although the mutism is transient, speech rarely normalizes and the syndrome is…

  18. Lgr4 protein deficiency induces ataxia-like phenotype in mice and impairs long term depression at cerebellar parallel fiber-Purkinje cell synapses.

    PubMed

    Guan, Xin; Duan, Yanhong; Zeng, Qingwen; Pan, Hongjie; Qian, Yu; Li, Dali; Cao, Xiaohua; Liu, Mingyao

    2014-09-19

    Cerebellar dysfunction causes ataxia characterized by loss of balance and coordination. Until now, the molecular and neuronal mechanisms of several types of inherited cerebellar ataxia have not been completely clarified. Here, we report that leucine-rich G protein-coupled receptor 4 (Lgr4/Gpr48) is highly expressed in Purkinje cells (PCs) in the cerebellum. Deficiency of Lgr4 leads to an ataxia-like phenotype in mice. Histologically, no obvious morphological changes were observed in the cerebellum of Lgr4 mutant mice. However, the number of PCs was slightly but significantly reduced in Lgr4(-/-) mice. In addition, in vitro electrophysiological analysis showed an impaired long term depression (LTD) at parallel fiber-PC (PF-PC) synapses in Lgr4(-/-) mice. Consistently, immunostaining experiments showed that the level of phosphorylated cAMP-responsive element-binding protein (Creb) was significantly decreased in Lgr4(-/-) PCs. Furthermore, treatment with forskolin, an adenylyl cyclase agonist, rescued phospho-Creb in PCs and reversed the impairment in PF-PC LTD in Lgr4(-/-) cerebellar slices, indicating that Lgr4 is an upstream regulator of Creb signaling, which is underlying PF-PC LTD. Together, our findings demonstrate for first time an important role for Lgr4 in motor coordination and cerebellar synaptic plasticity and provide a potential therapeutic target for certain types of inherited cerebellar ataxia. PMID:25063812

  19. Radiation-induced cerebellar chondrosarcoma. Case report

    SciTech Connect

    Bernstein, M.; Perrin, R.G.; Platts, M.E.; Simpson, W.J.

    1984-07-01

    The authors report a case of chondrosarcoma arising in the cerebellum 16 years after treatment of a cerebellar malignant astrocytoma by subtotal resection and irradiation. It is thought that the chondrosarcoma arising within the intracranial cavity was a probable consequence of previous ionizing radiation.

  20. Improving cerebellar segmentation with statistical fusion

    NASA Astrophysics Data System (ADS)

    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.

  1. Improving Cerebellar Segmentation with Statistical Fusion

    PubMed Central

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

    2016-01-01

    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 multi-atlas 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. PMID:27127334

  2. Vergence Deficits in Patients with Cerebellar Lesions

    ERIC Educational Resources Information Center

    Sander, T.; Sprenger, A.; Neumann, G.; Machner, B.; Gottschalk, S.; Rambold, H.; Helmchen, C.

    2009-01-01

    The cerebellum is part of the cortico-ponto-cerebellar circuit for conjugate eye movements. Recent animal data suggest an additional role of the cerebellum for the control of binocular alignment and disconjugate, i.e. vergence eye movements. The latter is separated into two different components: fast vergence (to step targets) and slow vergence…

  3. Inverse Stochastic Resonance in Cerebellar Purkinje Cells

    PubMed Central

    Häusser, Michael; Gutkin, Boris S.; Roth, Arnd

    2016-01-01

    Purkinje neurons play an important role in cerebellar computation since their axons are the only projection from the cerebellar cortex to deeper cerebellar structures. They have complex internal dynamics, which allow them to fire spontaneously, display bistability, and also to be involved in network phenomena such as high frequency oscillations and travelling waves. Purkinje cells exhibit type II excitability, which can be revealed by a discontinuity in their f-I curves. We show that this excitability mechanism allows Purkinje cells to be efficiently inhibited by noise of a particular variance, a phenomenon known as inverse stochastic resonance (ISR). While ISR has been described in theoretical models of single neurons, here we provide the first experimental evidence for this effect. We find that an adaptive exponential integrate-and-fire model fitted to the basic Purkinje cell characteristics using a modified dynamic IV method displays ISR and bistability between the resting state and a repetitive activity limit cycle. ISR allows the Purkinje cell to operate in different functional regimes: the all-or-none toggle or the linear filter mode, depending on the variance of the synaptic input. We propose that synaptic noise allows Purkinje cells to quickly switch between these functional regimes. Using mutual information analysis, we demonstrate that ISR can lead to a locally optimal information transfer between the input and output spike train of the Purkinje cell. These results provide the first experimental evidence for ISR and suggest a functional role for ISR in cerebellar information processing. PMID:27541958

  4. Cerebellar Disease in an Adult Cow

    PubMed Central

    Oz, H. H.; Nicholson, S. S.; Al-Bagdadi, F. K.; Zeman, D. H.

    1986-01-01

    This is the report of clinical signs and lesions of a cerebellar disorder in an adult four year old Limousin cow grazing perennial ryegrass (Lolium perenne). The most striking histopathological lesion was a marked paucity of Purkinje cells throughout the cerebellum. ImagesFigure 1.Figure 2. PMID:17422607

  5. Inverse Stochastic Resonance in Cerebellar Purkinje Cells.

    PubMed

    Buchin, Anatoly; Rieubland, Sarah; Häusser, Michael; Gutkin, Boris S; Roth, Arnd

    2016-08-01

    Purkinje neurons play an important role in cerebellar computation since their axons are the only projection from the cerebellar cortex to deeper cerebellar structures. They have complex internal dynamics, which allow them to fire spontaneously, display bistability, and also to be involved in network phenomena such as high frequency oscillations and travelling waves. Purkinje cells exhibit type II excitability, which can be revealed by a discontinuity in their f-I curves. We show that this excitability mechanism allows Purkinje cells to be efficiently inhibited by noise of a particular variance, a phenomenon known as inverse stochastic resonance (ISR). While ISR has been described in theoretical models of single neurons, here we provide the first experimental evidence for this effect. We find that an adaptive exponential integrate-and-fire model fitted to the basic Purkinje cell characteristics using a modified dynamic IV method displays ISR and bistability between the resting state and a repetitive activity limit cycle. ISR allows the Purkinje cell to operate in different functional regimes: the all-or-none toggle or the linear filter mode, depending on the variance of the synaptic input. We propose that synaptic noise allows Purkinje cells to quickly switch between these functional regimes. Using mutual information analysis, we demonstrate that ISR can lead to a locally optimal information transfer between the input and output spike train of the Purkinje cell. These results provide the first experimental evidence for ISR and suggest a functional role for ISR in cerebellar information processing. PMID:27541958

  6. Synchronized slice viewing of similar image series

    NASA Astrophysics Data System (ADS)

    Ali, Sharib; Foncubierta, Antonio; Depeursinge, Adrien; Meriaudeau, Fabrice; Ratib, Osman; Müller, Henning

    2012-02-01

    Comparing several series of images is not always easy as the corresponding slices often need to be selected manually. In times where series contain an ever-increasing number of slices this can mean manual work when moving several series to the corresponding slice. Particularly two situations were identified in this context: (1) patients with a large number of image series over time (such as patients with cancers that are monitored) frequently need to compare the series, for example to compare tumor growth over time. Manually adapting two series is possible but with four or more series this can mean loosing time. Having automatically the closest slice by comparing visual similarity also in older series with differing slice thickness and inter slice distance can save time and synchronize the viewing instantly. (2) analyzing visually similar image series of several patients can profit from being viewed in a synchronized way to compare the cases, so when sliding through the slices in one volume, the corresponding slices in the other volumes are shown. This application could be employed after content-based 3D image retrieval has found similar series, for example. Synchronized viewing can help finding or confirming the most relevant cases quickly. To allow for synchronized viewing of several image volumes, the test image series are first registered applying affine transformation for the global registration of images followed by diffeomorphic image registration. Then corresponding slices in the two volumes are estimated based on a visual similarity. Once the registration is finished, the user can subsequently move inside the slices of one volume (reference volume) and can view the corresponding slices in the other volumes. These corresponding slices are obtained after a correspondence match in the registration procedure. These volumes are synchronized in that the slice closest to the original reference volume is shown even when the slice thicknesses or inter slice

  7. Neurogenic stunned myocardium as a manifestation of encephalitis involving cerebellar tonsils.

    PubMed

    Lin, Wen-Sou; Sung, Yueh-Feng

    2012-11-01

    Neurogenic stunned myocardium is defined as a myocardial injury or dysfunction after neurological insults. It is most commonly reported in patients with subarachnoid hemorrhage, and the presenting symptoms may mimic an acute myocardial infarction or myocarditis. In severe cases, cardiogenic shock and acute pulmonary edema may occur and lead to a devastating event. Therefore, it requires prompt recognition and proper intervention. We herein report the case of a 25-year-old woman who presented to our hospital with the symptoms of acute pulmonary edema, shock, and consciousness disturbance. The diagnosis of encephalitis of cerebellar tonsils complicated with acute hydrocephalus and neurogenic stunned myocardium was made. Detailed neurologic examinations, neuroimaging studies, and characteristic echocardiographic changes expedite the correct diagnosis and treatment. PMID:22205010

  8. Improved segmentation of cerebellar structures in children

    PubMed Central

    Narayanan, Priya Lakshmi; Boonazier, Natalie; Warton, Christopher; Molteno, Christopher D; Joseph, Jesuchristopher; Jacobson, Joseph L; Jacobson, Sandra W; Zöllei, Lilla; Meintjes, Ernesta M

    2016-01-01

    Background Consistent localization of cerebellar cortex in a standard coordinate system is important for functional studies and detection of anatomical alterations in studies of morphometry. To date, no pediatric cerebellar atlas is available. New method The probabilistic Cape Town Pediatric Cerebellar Atlas (CAPCA18) was constructed in the age-appropriate National Institute of Health Pediatric Database asymmetric template space using manual tracings of 16 cerebellar compartments in 18 healthy children (9–13 years) from Cape Town, South Africa. The individual atlases of the training subjects were also used to implement multi atlas label fusion using multi atlas majority voting (MAMV) and multi atlas generative model (MAGM) approaches. Segmentation accuracy in 14 test subjects was compared for each method to ‘gold standard’ manual tracings. Results Spatial overlap between manual tracings and CAPCA18 automated segmentation was 73% or higher for all lobules in both hemispheres, except VIIb and X. Automated segmentation using MAGM yielded the best segmentation accuracy over all lobules (mean Dice Similarity Coefficient 0.76; range 0.55–0.91). Comparison with existing methods In all lobules, spatial overlap of CAPCA18 segmentations with manual tracings was similar or higher than those obtained with SUIT (spatially unbiased infra-tentorial template), providing additional evidence of the benefits of an age appropriate atlas. MAGM segmentation accuracy was comparable to values reported recently by Park et al. (2014) in adults (across all lobules mean DSC = 0.73, range 0.40–0.89). Conclusions CAPCA18 and the associated multi atlases of the training subjects yield improved segmentation of cerebellar structures in children. PMID:26743973

  9. Modification of hippocampal excitability in brain slices pretreated with a low nanomolar concentration of Zn2+.

    PubMed

    Takeda, Atsushi; Shakushi, Yukina; Tamano, Haruna

    2015-11-01

    Synaptic Zn2+ homeostasis may be changed during brain slice preparation. However, much less attention has been paid to Zn2+ in artificial cerebrospinal fluid (ACSF) used for slice experiments than has been paid to Ca2+ . The present study assesses addition of Zn2+ to ACSF, focused on hippocampal excitability after acute brain slice preparation. When the static levels of intracellular Zn2+ and Ca2+ were compared between brain slices prepared with conventional ACSF without Zn2+ and those pretreated with ACSF containing 20 nM ZnCl2 for 1 hr, both levels were almost the same. On the other hand, intracellular Ca2+ levels were significantly increased in the stratum lucidum of the control brain slices after stimulation with high K+, although the increase was significantly suppressed by the pretreatment with ACSF containing Zn2+, suggesting that neuronal excitation is enhanced in brain slices prepared with ACSF without Zn2+. The increase in extracellular Zn2+ level, an index of glutamate release, after stimulation with high K+ was also significantly suppressed by pretreatment with ACSF containing Zn2+. When mossy fiber excitation was assessed in brain slices with FM4-64, an indicator of presynaptic activity, attenuation of FM 4-64 fluorescence based on presynaptic activity was suppressed in the stratum lucidum of brain slices pretreated with ACSF containing Zn2+. The present study indicates that hippocampal excitability is enhanced in brain slices prepared with ACSF without Zn2+. It is likely that a low nanomolar concentration of Zn2+ is necessary for ACSF. PMID:26268632

  10. A slice of the universe

    NASA Technical Reports Server (NTRS)

    De Lapparent, V.; Geller, M. J.; Huchra, J. P.

    1986-01-01

    A preliminary discussion is presented of recent results obtained as part of the extension of the Center of Astrophysics redshift survey. Several features of the results are striking. The distribution of galaxies in the sample, which contains 1100 galaxies in a 6 deg x 117 deg strip going through the Coma cluster, looks like a slice through the suds in the kitchen sink. It appears that the galaxies are on the surfaces of bubble-like structures with diameters of 25-50/h-Mpc. The largest bubble in the survey has a diameter comparable with the most recent estimates of the diameter of the void in Bootes. This topology poses serious challenges for current models for the formation of large-scale structure. The best available model for generating these structures is the explosive galaxy formation theory of Ostriker and Cowie (1981).

  11. Ruminant organotypic brain-slice cultures as a model for the investigation of CNS listeriosis

    PubMed Central

    Guldimann, Claudia; Lejeune, Beatrice; Hofer, Sandra; Leib, Stephen L; Frey, Joachim; Zurbriggen, Andreas; Seuberlich, Torsten; Oevermann, Anna

    2012-01-01

    Central nervous system (CNS) infections in ruminant livestock, such as listeriosis, are of major concern for veterinary and public health. To date, no host-specific in vitro models for ruminant CNS infections are available. Here, we established and evaluated the suitability of organotypic brain-slices of ruminant origin as in vitro model to study mechanisms of Listeria monocytogenes CNS infection. Ruminants are frequently affected by fatal listeric rhombencephalitis that closely resembles the same condition occurring in humans. Better insight into host–pathogen interactions in ruminants is therefore of interest, not only from a veterinary but also from a public health perspective. Brains were obtained at the slaughterhouse, and hippocampal and cerebellar brain-slices were cultured up to 49 days. Viability as well as the composition of cell populations was assessed weekly. Viable neurons, astrocytes, microglia and oligodendrocytes were observed up to 49 days in vitro. Slice cultures were infected with L. monocytogenes, and infection kinetics were monitored. Infected brain cells were identified by double immunofluorescence, and results were compared to natural cases of listeric rhombencephalitis. Similar to the natural infection, infected brain-slices showed focal replication of L. monocytogenes and bacteria were predominantly observed in microglia, but also in astrocytes, and associated with axons. These results demonstrate that organotypic brain-slice cultures of bovine origin survive for extended periods and can be infected easily with L. monocytogenes. Therefore, they are a suitable model to study aspects of host–pathogen interaction in listeric encephalitis and potentially in other neuroinfectious diseases. PMID:22804762

  12. Ruminant organotypic brain-slice cultures as a model for the investigation of CNS listeriosis.

    PubMed

    Guldimann, Claudia; Lejeune, Beatrice; Hofer, Sandra; Leib, Stephen L; Frey, Joachim; Zurbriggen, Andreas; Seuberlich, Torsten; Oevermann, Anna

    2012-08-01

    Central nervous system (CNS) infections in ruminant livestock, such as listeriosis, are of major concern for veterinary and public health. To date, no host-specific in vitro models for ruminant CNS infections are available. Here, we established and evaluated the suitability of organotypic brain-slices of ruminant origin as in vitro model to study mechanisms of Listeria monocytogenes CNS infection. Ruminants are frequently affected by fatal listeric rhombencephalitis that closely resembles the same condition occurring in humans. Better insight into host-pathogen interactions in ruminants is therefore of interest, not only from a veterinary but also from a public health perspective. Brains were obtained at the slaughterhouse, and hippocampal and cerebellar brain-slices were cultured up to 49 days. Viability as well as the composition of cell populations was assessed weekly. Viable neurons, astrocytes, microglia and oligodendrocytes were observed up to 49 days in vitro. Slice cultures were infected with L. monocytogenes, and infection kinetics were monitored. Infected brain cells were identified by double immunofluorescence, and results were compared to natural cases of listeric rhombencephalitis. Similar to the natural infection, infected brain-slices showed focal replication of L. monocytogenes and bacteria were predominantly observed in microglia, but also in astrocytes, and associated with axons. These results demonstrate that organotypic brain-slice cultures of bovine origin survive for extended periods and can be infected easily with L. monocytogenes. Therefore, they are a suitable model to study aspects of host-pathogen interaction in listeric encephalitis and potentially in other neuroinfectious diseases. PMID:22804762

  13. Electrohydrodynamic drying of carrot slices.

    PubMed

    Ding, Changjiang; Lu, Jun; Song, Zhiqing

    2015-01-01

    Carrots have one of the highest levels of carotene, and they are rich in vitamins, fiber and minerals. However, since fresh carrots wilt rapidly after harvest under inappropriate storage conditions, drying has been used to improve their shelf life and retain nutritional quality. Therefore, to further investigate the potential of this method, carrot slices were dried in an EHD system in order to study the effect of different voltages on drying rate. As measures of quality, carotene content and rehydration ratio were, respectively, compared against the conventional oven drying regime. Carotene, the main component of the dried carrot, and rehydration characteristics of the dried product can both indicate quality by physical and chemical changes during the drying process. Mathematical modeling and simulation of drying curves were also performed, using root mean square error, reduced mean square of the deviation and modeling efficiency as the primary criteria to select the equation that best accounts for the variation in the drying curves of the dried samples. Theoretically, the Page model was best suited for describing the drying rate curve of carrot slices at 10kV to 30kV. Experimentally, the drying rate of carrots was notably greater in the EHD system when compared to control, and quality, as determined by carotene content and rehydration ratio, was also improved when compared to oven drying. Therefore, this work presents a facile and effective strategy for experimentally and theoretically determining the drying properties of carrots, and, as a result, it provides deeper insight into the industrial potential of the EHD drying technique. PMID:25874695

  14. Electrohydrodynamic Drying of Carrot Slices

    PubMed Central

    Ding, Changjiang; Lu, Jun; Song, Zhiqing

    2015-01-01

    Carrots have one of the highest levels of carotene, and they are rich in vitamins, fiber and minerals. However, since fresh carrots wilt rapidly after harvest under inappropriate storage conditions, drying has been used to improve their shelf life and retain nutritional quality. Therefore, to further investigate the potential of this method, carrot slices were dried in an EHD system in order to study the effect of different voltages on drying rate. As measures of quality, carotene content and rehydration ratio were, respectively, compared against the conventional oven drying regime. Carotene, the main component of the dried carrot, and rehydration characteristics of the dried product can both indicate quality by physical and chemical changes during the drying process. Mathematical modeling and simulation of drying curves were also performed, using root mean square error, reduced mean square of the deviation and modeling efficiency as the primary criteria to select the equation that best accounts for the variation in the drying curves of the dried samples. Theoretically, the Page model was best suited for describing the drying rate curve of carrot slices at 10kV to 30kV. Experimentally, the drying rate of carrots was notably greater in the EHD system when compared to control, and quality, as determined by carotene content and rehydration ratio, was also improved when compared to oven drying. Therefore, this work presents a facile and effective strategy for experimentally and theoretically determining the drying properties of carrots, and, as a result, it provides deeper insight into the industrial potential of the EHD drying technique. PMID:25874695

  15. MODELLING TRANSFER OF LISTERIA MONOCYTOGENES DURING SLICING OF "GRAVAD" SALMON

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Transfer of a rifampicin-resistant mutant of Listeria monocytogenes strain F2365 from an inoculated slicing blade to slices of gravad salmon (Salmo salar), and from inoculated salmon fillet to the slicing machine and subsequently to slices of uninoculated fillet was studied. The effect of slicing te...

  16. Anatomy and approaches along the cerebellar-brainstem fissures.

    PubMed

    Matsushima, Ken; Yagmurlu, Kaan; Kohno, Michihiro; Rhoton, Albert L

    2016-01-01

    OBJECT Fissure dissection is routinely used in the supratentorial region to access deeply situated pathology while minimizing division of neural tissue. Use of fissure dissection is also practical in the posterior fossa. In this study, the microsurgical anatomy of the 3 cerebellar-brainstem fissures (cerebellomesencephalic, cerebellopontine, and cerebellomedullary) and the various procedures exposing these fissures in brainstem surgery were examined. METHODS Seven cadaveric heads were examined with a microsurgical technique and 3 with fiber dissection to clarify the anatomy of the cerebellar-brainstem and adjacent cerebellar fissures, in which the major vessels and neural structures are located. Several approaches directed along the cerebellar surfaces and fissures, including the supracerebellar infratentorial, occipital transtentorial, retrosigmoid, and midline suboccipital approaches, were examined. The 3 heads examined using fiber dissection defined the anatomy of the cerebellar peduncles coursing in the depths of these fissures. RESULTS Dissections directed along the cerebellar-brainstem and cerebellar fissures provided access to the posterior and posterolateral midbrain and upper pons, lateral pons, floor and lateral wall of the fourth ventricle, and dorsal and lateral medulla. CONCLUSIONS Opening the cerebellar-brainstem and adjacent cerebellar fissures provided access to the brainstem surface hidden by the cerebellum, while minimizing division of neural tissue. Most of the major cerebellar arteries, veins, and vital neural structures are located in or near these fissures and can be accessed through them. PMID:26274986

  17. Integrating interface slicing into software engineering processes

    NASA Technical Reports Server (NTRS)

    Beck, Jon

    1993-01-01

    Interface slicing is a tool which was developed to facilitate software engineering. As previously presented, it was described in terms of its techniques and mechanisms. The integration of interface slicing into specific software engineering activities is considered by discussing a number of potential applications of interface slicing. The applications discussed specifically address the problems, issues, or concerns raised in a previous project. Because a complete interface slicer is still under development, these applications must be phrased in future tenses. Nonetheless, the interface slicing techniques which were presented can be implemented using current compiler and static analysis technology. Whether implemented as a standalone tool or as a module in an integrated development or reverse engineering environment, they require analysis no more complex than that required for current system development environments. By contrast, conventional slicing is a methodology which, while showing much promise and intuitive appeal, has yet to be fully implemented in a production language environment despite 12 years of development.

  18. Developmental Decrease of Neuronal Chloride Concentration Is Independent of Trauma in Thalamocortical Brain Slices

    PubMed Central

    Glykys, Joseph; Staley, Kevin J.

    2016-01-01

    The intraneuronal chloride concentration ([Cl-]i) is paramount for determining the polarity of signaling at GABAA synapses in the central nervous system. Sectioning hippocampal brain slices increases [Cl-]i in the superficial layers. It is not known whether cutting trauma also increases [Cl-]i in the neocortex and thalamus, and whether the effects of trauma change during development. We used Cl- imaging to study the [Cl-]i vs. the distance from the cut surface in acute thalamocortical slices from mice at developmental ages ranging from post-natal day 5 (P5) to P20. We demonstrate: 1) [Cl-]i is higher in the most superficial areas in both neocortical and thalamic brain slices at all ages tested and, 2) there is a developmental decrease in [Cl-]i that is independent of acute trauma caused by brain slicing. We conclude that [Cl-]i has a developmental progression during P5-20 in both the neocortex and thalamus. However, in both brain regions and during development the neurons closest to the slicing trauma have an elevated [Cl-]i. PMID:27337272

  19. An update on Spino-cerebellar ataxias

    PubMed Central

    Mondal, Banashree; Paul, Pritikanta; Paul, Madhuparna; Kumar, Hrishikesh

    2013-01-01

    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. PMID:24101804

  20. Changes in Spontaneous Firing Patterns of Cerebellar Purkinje Cells in p75 Knockout Mice

    PubMed Central

    Tian, Jinbin; Tep, Chhavy; Zhu, Michael X.; Yoon, Sung Ok

    2013-01-01

    The p75 neurotrophin receptor is highly expressed in the developing nervous system and is required for neuronal survival, growth and synaptic transmission. In young mice, p75 is present in both granular cells and Purkinje cells of the cerebellum. Although p75 has been implicated in modulation of neuronal excitability in several neuronal types, whether and how it affects the excitability of cerebellar Purkinje neurons remained unclear. Using extracellular recordings of spontaneous firing of Purkinje neurons in cerebellar slices prepared from wild type and p75 knockout mice, we measured intrinsic firing properties in the presence of fast synaptic blockers of more than 200 Purkinje cells, each for a period of 5 min, for each genotype. We detected a significant increase in the mean firing frequency in p75−/− neurons comparing to the wild type littermates. Upon separating tonically firing from phasically firing cells, i.e. cells with firing pauses of longer than 300 msec, we observed that the change mainly arose from phasic firing cells and can be explained by an increase in the firing/silence ratio and a decrease in the number of long pauses during the 5-min recording period. We conclude that p75 plays an important role in regulating the firing-to-silence transition during the phasic firing period of the spontaneous firing of Purkinje cells. Thus, p75 exerts a modulatory function on Purkinje cell firing patterns, through which it may act as a key player in motor coordination and other cerebellum-regulated activities since Purkinje cells represent the sole neuronal output of the cerebellar cortex. PMID:23307658

  1. Functional circuitry of a unique cerebellar specialization: the valvula cerebelli of a mormyrid fish.

    PubMed

    Zhang, Y; Shi, Z; Magnus, G; Meek, J; Han, V Z; Qiao, J T

    2011-05-19

    The valvula cerebelli of the mormyrid electric fish is a useful site for the study of cerebellar function. The valvula forms a part of the electrosensory-electromotor system of this fish, a system that offers many possibilities for the study of sensory-motor integration. The valvula also has a number of histological features not present in mammals which facilitate investigation of cerebellar circuitry and its plasticity. This initial study characterizes the basic physiology and pharmacology of cells in the valvula using an in vitro slice preparation. Intrinsic properties and synaptic responses of Purkinje cells and other cell types were examined. We found that Purkinje cells fire a small narrow Na(+) spike and a large broad Ca(2+) spike, generated in the axon initial segment and dendritic-soma region, respectively. Purkinje cells respond to parallel fiber inputs with graded excitatory postsynaptic potentials (EPSPs) and to climbing fiber inputs with all-or-none EPSPs. Efferent cells, Golgi cells, and deep stellate cells all fire a single type of large narrow spike and respond only to parallel fiber inputs. Both parallel fiber and climbing fiber responses in Purkinje cells appear to be entirely mediated by AMPA-type glutamate receptors, whereas parallel fiber responses in efferent cells and stellate cells include AMPA and NMDA components. In addition, a strong synaptic inhibition was uncovered in both Purkinje cells and efferent cells in response to the focal stimulation of parallel fibers. Dual cell recordings indicate that deep stellate cells contribute at least partially to this inhibition. We conclude that despite its unique histology, the local functional circuitry of the mormyrid valvula cerebelli is largely similar to that of the mammalian cerebellum. Thus, what is learned concerning the functioning of the mormyrid valvula cerebelli may be expected to be informative about cerebellar function in general. PMID:21414387

  2. [Diagnostic and treatment of hypertensive cerebellar hematomas].

    PubMed

    Krylov, V V; Dash'ian, V G; Murashko, A A; Burov, S A

    2009-01-01

    Authors analyzed the results of treatment of 56 patients with hypertensive cerebellar hemorrhages (volume 0,5-41 cm3). Brain stem symptoms were found in 45 (80%) of patients. The dislocation of brain stem was observed in 38 (68%) cases, occlusive hydrocephaly - in 22 (39%), intraventricular hemorrhage - in 26 (46%). Severity of state depended on character of disease course, presence of stem symptoms, awakening level, volume and localization of cerebellar hematoma, development of intraventricular hemorrhage, occlusive hydrocephaly and dislocation of brain stem. Thirty-six patients were operated. After the neurosurgical intervention, 22 (61%) patients were discharged without or with the minimal neurological deficit, 1 (3%) with marked disability and 13 (36%) patients died. In conclusion, the removal of hematoma is recommended in dislocation of brain stem and disturbance of consiousnes: the ventricular drainage - in occlusive hydrocephaly developed as a consequence of hemotamponade of IV ventricular. The surgical treatment is not recommended to patients with cerebellar hematomas with the volume less than 7 cm3. PMID:19491806

  3. Learning of Sensory Sequences in Cerebellar Patients

    PubMed Central

    Frings, Markus; Boenisch, Raoul; Gerwig, Marcus; Diener, Hans-Christoph; Timmann, Dagmar

    2004-01-01

    A possible role of the cerebellum in detecting and recognizing event sequences has been proposed. The present study sought to determine whether patients with cerebellar lesions are impaired in the acquisition and discrimination of sequences of sensory stimuli of different modalities. A group of 26 cerebellar patients and 26 controls matched for age, sex, handedness, musicality, and level of education were tested. Auditory and visual sensory sequences were presented out of different sensory pattern categories (tones with different acoustic frequencies and durations, visual stimuli with different spatial locations and colors, sequential vision of irregular shapes) and different ranges of inter-cue time intervals (fast and slow). Motor requirements were small, with vocal responses and no time restrictions. Perception of visual and acoustic stimuli was generally preserved in patients and controls. The number of errors was significantly higher in the faster tempo of sequence presentation in learning of sequences of tones of different frequencies and in learning of sequences of visual stimuli of different spatial locations and different colors. No difference in tempo between the groups was shown. The total number of errors between the two groups was identical in the sequence conditions. No major disturbances in acquisition or discrimination of various sensory sequences were observed in the group of cerebellar patients. Sequence learning may be impaired only in tasks with significant motor demands. PMID:15169865

  4. From cerebellar texture to movement optimization.

    PubMed

    Sultan, Fahad

    2014-10-01

    The cerebellum is a major site for supervised procedural learning and appears to be crucial for optimizing sensorimotor performance. However, the site and origin of the supervising signal are still elusive. Furthermore, its relationship with the prominent neuronal circuitry remains puzzling. In this paper, I will review the relevant information and seek to synthesize a working hypothesis that explains the unique cerebellar structure. The aim of this review was to link the distinctive functions of the cerebellum, as derived from cerebellar lesion studies, with potential elementary computations, as observed by a bottom-up approach from the cerebellar microcircuitry. The parallel fiber geometry is ideal for performing millisecond computations that extract instructive signals. In this scenario, the higher time derivatives of kinematics such as acceleration and/or jerk that occur during motor performance are detected via a tidal wave mechanism and are used (with appropriate gating) as the instructive signal to guide motor smoothing. The advantage of such a mechanism is that movements are optimized by reducing "jerkiness" which, in turn, lowers their energy requirements. PMID:25037239

  5. Visible human slice sequence animation Web server

    NASA Astrophysics Data System (ADS)

    Bessaud, Jean-Christophe; Hersch, Roger D.

    2000-12-01

    Since June 1998, EPFL's Visible Human Slice Server (http://visiblehuman.epfl.ch) allows to extract arbitrarily oriented and positioned slices. More than 300,000 slices are extracted each year. In order to give a 3D view of anatomic structures, a new service has been added for extracting slice animations along a user-defined trajectory. This service is useful both for research and teaching purposes (http:visiblehuman.epfl.ch/animation/). Extracting slices of animations at any desired position and orientation from the Visible Human volume (Visible Man or Woman) requires both high throughput and much processing power. The I/O disk bandwidth can be increased by accessing more than one disk at the same time, i.e. by stripping data across several disks and by carrying out parallel asynchronous disk accesses. Since processing operations such as slice and animation extraction are compute- intensive, they require the program execution to be carried out in parallel on several computers. In the present contribution, we describe the new slice sequence animation service as well as the approach taken for parallelizing this service on a multi-PC multi-disk Web server.

  6. Cavernous angioma with olivary hypertrophy and contralateral cerebellar diaschisis.

    PubMed

    Komaba, Y; Nomoto, T; Kitamura, S; Terashi, A

    1997-07-01

    We describe a 66-year-old man with a 20-year history of ataxic gait who suddenly developed diplopia on rightward gaze. Neurologic examination revealed right hemi-ataxia and hemi-hypesthesia, and left internuclear ophthalmoplegia. MRI showed a cavernous angioma in the left tectum, mild right cerebellar atrophy, and left interior olivary hypertrophy. Single photon emission computed tomography (SPECT) imaging demonstrated contralateral cerebellar diaschisis. We discuss the findings and review the literature concerning contralateral cerebellar diaschisis. PMID:9240502

  7. Cerebro-cerebellar circuits in autism spectrum disorder

    PubMed Central

    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. PMID:26594140

  8. Cerebellar liponeurocytoma in two siblings suggests a possible familial predisposition.

    PubMed

    Pikis, Stylianos; Fellig, Yakov; Margolin, Emil

    2016-10-01

    There is limited data on the genetic origin and natural history of cerebellar liponeurocytoma. To the best of our knowledge there has been only one report of a familial presentation of this rare entity. We report a 72-year-old female with a posterior fossa tumor presenting with progressive cerebellar signs and symptoms. The patient underwent total tumor resection via an uncomplicated sub-occipital craniotomy. Histopathologic examination was diagnostic for cerebellar liponeurocytoma. Her sister was previously treated for a similar tumor. Our report provides further evidence for the possible existence of a hereditary abnormality predisposing afflicted families to cerebellar liponeurocytoma development. PMID:27349466

  9. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds.

    PubMed

    Chang, Yung-Yee; Liu, Jia-Shou; Lai, Shung-Lon; Wu, Hsiu-Shan; Lan, Min-Yu

    2008-01-01

    Nattokinase is used as a health-promoting medicine for preventing thrombosis due to its fibrinolytic activity. Cerebral microbleed is remnant of blood extravasations from the damaged vessels related to cerebral microangiopathies. We report a patient, having used aspirin for secondary stroke prevention, who had an acute cerebellar hemorrhage after taking nattokinase 400 mg daily for 7 consecutive days. In addition to the hemorrhagic lesion, multiple microbleeds were demonstrated on brain MR images. We suggest that nattokinase may increase risk of intracerebral hemorrhage in patients who have bleeding-prone cerebral microangiopathy and are receiving other antithrombotic agent at the same time. PMID:18310985

  10. Reconstructive endovascular treatment of ruptured vertebral artery dissection involving the posterior inferior cerebellar artery.

    PubMed

    Ota, Takahiro; Sato, Masayuki; Amano, Tatsuo; Saito, Akira; Matsumaru, Yuji

    2016-06-01

    Two cases with ruptured vertebral artery (VA) dissection involving the origin of the posterior inferior cerebellar artery (PICA) are presented. Endovascular proximal occlusion of the dissected segment proximal to the PICA origin was performed, leaving the PICA patent in the acute stage. Stent placement from the PICA to the VA through the contralateral VA and coil embolization were added to the residual dissection in the chronic stage. Rebleedings were not observed. This is the first report of a staged, combined strategy for the treatment of a ruptured PICA involving VA dissection, which enabled preservation of the PICA without bypass surgery. PMID:27038168

  11. Coordinate singularities in harmonically sliced cosmologies

    NASA Astrophysics Data System (ADS)

    Hern, Simon D.

    2000-08-01

    Harmonic slicing has in recent years become a standard way of prescribing the lapse function in numerical simulations of general relativity. However, as was first noticed by Alcubierre [Phys. Rev. D 55, 5981 (1997)], numerical solutions generated using this slicing condition can show pathological behavior. In this paper, analytic and numerical methods are used to examine harmonic slicings of Kasner and Gowdy cosmological spacetimes. It is shown that in general the slicings are prevented from covering the whole of the spacetimes by the appearance of coordinate singularities. As well as limiting the maximum running times of numerical simulations, the coordinate singularities can lead to features being produced in numerically evolved solutions which must be distinguished from genuine physical effects.

  12. Photosynthesis and Respiration in Leaf Slices.

    ERIC Educational Resources Information Center

    Brown, Simon

    1998-01-01

    Demonstrates how leaf slices provide an inexpensive material for illustrating several fundamental points about the biochemistry of photosynthesis and respiration. Presents experiments that illustrate the effects of photon flux density and herbicides and carbon dioxide concentration. (DDR)

  13. [Cerebellar Control of Ocular Movements: Application to the Topographical Diagnosis of Cerebellar Lesions].

    PubMed

    Hirose, Genjiro

    2016-03-01

    Over the last decade, substantial information on cerebellar oculomotor control has been provided by the use of sophisticated neuroanatomical, neurophysiological, and imaging techniques. We now know that an intact cerebellum is a prerequisite for normal oculomotor performance. This review clarifies the current knowledge on structure-function correlations of the cerebellum in relation to ocular movements and allows them to be applied to topographical diagnosis of cerebellar lesions. The cerebellar regions most closely related to oculomotor function are: (1) the flocculus/paraflocculus for VOR suppression, cancellation, smooth pursuit eye movement and gaze-holding, (2) the nodulus/ventral uvula for velocity storage and low frequency prolonged vestibular response, and (3) the dorsal oculomotor vermis (declive VI, folium VII) and the posterior portion of the fastigial nucleus (fastigial oculomotor region) for saccades and smooth pursuit initiation. Symptomatically, defects in the flocculus/parflocculus cause saccadic pursuit, downbeat nystagmus, and impairments to visual suppression of the VOR. Lesions of the nodulus/uvula reveal as periodic alternating nystagmus. Lesions of the oculomotor vermis and the fastigial nucleus can induce saccadic dysmetria, while fastigial nucleus lesions may also cause ocular flutter/opsoclonus. A detailed knowledge of cerebellar anatomy and the physiology of eye movements enables localization of lesions to specific areas of the cerebellum. PMID:27001776

  14. Foxc1 dependent mesenchymal signalling drives embryonic cerebellar growth

    PubMed Central

    Haldipur, Parthiv; Gillies, Gwendolyn S; Janson, Olivia K; Chizhikov, Victor V; Mithal, Divakar S; Miller, Richard J; Millen, Kathleen J

    2014-01-01

    Loss of Foxc1 is associated with Dandy-Walker malformation, the most common human cerebellar malformation characterized by cerebellar hypoplasia and an enlarged posterior fossa and fourth ventricle. Although expressed in the mouse posterior fossa mesenchyme, loss of Foxc1 non-autonomously induces a rapid and devastating decrease in embryonic cerebellar ventricular zone radial glial proliferation and concurrent increase in cerebellar neuronal differentiation. Subsequent migration of cerebellar neurons is disrupted, associated with disordered radial glial morphology. In vitro, SDF1α, a direct Foxc1 target also expressed in the head mesenchyme, acts as a cerebellar radial glial mitogen and a chemoattractant for nascent Purkinje cells. Its receptor, Cxcr4, is expressed in cerebellar radial glial cells and conditional Cxcr4 ablation with Nes-Cre mimics the Foxc1−/− cerebellar phenotype. SDF1α also rescues the Foxc1−/− phenotype. Our data emphasizes that the head mesenchyme exerts a considerable influence on early embryonic brain development and its disruption contributes to neurodevelopmental disorders in humans. DOI: http://dx.doi.org/10.7554/eLife.03962.001 PMID:25513817

  15. Cerebellar atrophy and prognosis after temporal lobe resection.

    PubMed Central

    Specht, U; May, T; Schulz, R; Rohde, M; Ebner, A; Schmidt, R C; Schütz, M; Wolf, P

    1997-01-01

    OBJECTIVE: Experimental data indicate inhibitory effects of the cerebellum on seizure activity. Structural damage such as cerebellar atrophy, which is a common finding in patients with chronic epilepsy, may reduce these effects. METHODS: Outcome after temporal lobectomy was studied in 78 consecutive patients, with or without cerebellar atrophy diagnosed by MRI. RESULTS: Thirty five patients (45%) showed cerebellar atrophy. At a mean follow up of 14.6 (range, 6-40) months, 50 patients (64%) had no postoperative seizures. In these patients, the frequency of cerebellar atrophy was significantly lower (34%) than in patients who relapsed (64%, p < 0.01). Occurrence of generalised tonic-clonic seizures (GTCS) within two years before surgery, occurrence of GTCS at any time preoperatively, long duration of epilepsy, and older age at surgery were also associated with recurrence of seizures. Multiple logistic regression analysis suggested occurrence of GTCS within two years before surgery and cerebellar atrophy as the main predictive indicators. When both factors were present, the percentage of patients remaining seizure free since surgery fell to 30%, compared with 60% when only GTCS were present, 78.6% when only cerebellar atrophy was present, and 87.5% when both factors were absent. CONCLUSIONS: Cerebellar atrophy shown by MRI was a frequent finding in surgically treated patients with temporal lobe epilepsy. The presence of cerebellar atrophy seems to worsen the prognosis after temporal lobe resection. Images PMID:9153610

  16. Pre- and Postnatal Neuroimaging of Congenital Cerebellar Abnormalities.

    PubMed

    Poretti, Andrea; Boltshauser, Eugen; Huisman, Thierry A G M

    2016-02-01

    The human cerebellum has a protracted development that makes it vulnerable to a broad spectrum of developmental disorders including malformations and disruptions. Starting from 19 to 20 weeks of gestation, prenatal magnetic resonance imaging (MRI) can reliably study the developing cerebellum. Pre- and postnatal neuroimaging plays a key role in the diagnostic work-up of congenital cerebellar abnormalities. Diagnostic criteria for cerebellar malformations and disruptions are based mostly on neuroimaging findings. The diagnosis of a Dandy-Walker malformation is based on the presence of hypoplasia, elevation, and counterclockwise upward rotation of the cerebellar vermis and cystic dilatation of the fourth ventricle, which extends posteriorly filling out the posterior fossa. For the diagnosis of Joubert syndrome, the presence of the molar tooth sign (thickened, elongated, and horizontally orientated superior cerebellar peduncles and an abnormally deep interpeduncular fossa) is needed. The diagnostic criteria of rhombencephalosynapsis include a complete or partial absence of the cerebellar vermis and continuity of the cerebellar hemispheres across the midline. Unilateral cerebellar hypoplasia is defined by the complete aplasia or hypoplasia of one cerebellar hemisphere. Familiarity with these diagnostic criteria as well as the broad spectrum of additional neuroimaging findings is important for a correct pre- and postnatal diagnosis. A correct diagnosis is essential for management, prognosis, and counseling of the affected children and their family. PMID:26166429

  17. De novo cerebellar malignant glioma: A case report

    PubMed Central

    Matsumoto, Hiroaki; Yoshida, Yasuhisa

    2016-01-01

    Introduction Gliomas of the cerebellum are rare in adults, and their natural history and clinical behavior are not well known. Because cerebellar glioma is not usually diagnosed until clinical symptoms have appeared, no reports have described the developmental process of new cerebellar gliomas. We describe a case of de novo cerebellar anaplastic astrocytoma in which the developmental process was detected on magnetic resonance imaging (MRI). Presentation of case A 78-year-old man with a history of cerebral infarction was undergoing follow-up MRI every 6 months. This follow-up revealed a small abnormality in the left cerebellar hemisphere without clinical symptoms. Subsequent MRI showed lesion growth accompanying clinical symptoms. As cerebellar tumor was suspected, the lesion was extirpated. The histological diagnosis was anaplastic astrocytoma. Local recurrence developed and the patient died 20 months postoperatively. Discussion Cerebellar gliomas sometimes do not exhibit the common MRI findings of supratentorial gliomas, leading to difficulty with preoperative diagnosis. In this case, we initially diagnosed asymptomatic cerebellar infarction because the lesion was small and asymptomatic. The abnormal lesion gradually grew and clinical symptoms appeared. Cerebellar glioma may show few signs characteristic of tumor on MRI in the initial stages. Conclusion When MRI detects a new, faint abnormality in the cerebellum, close follow-up of clinical symptoms and MRI on suspicion of glioma is warranted PMID:27017277

  18. Increased cerebellar volume and BDNF level following quadrato motor training.

    PubMed

    Ben-Soussan, Tal Dotan; Piervincenzi, Claudia; Venditti, Sabrina; Verdone, Loredana; Caserta, Micaela; Carducci, Filippo

    2015-01-01

    Using whole-brain structural measures coupled to analysis of salivary brain-derived neurotrophic factor (BDNF), we demonstrate sensory motor training-induced plasticity, including cerebellar gray matter volume increment and increased BDNF level. The increase of cerebellar volume was positively correlated with the increase of BDNF level. PMID:25311848

  19. Dystonia and Cerebellar Degeneration in the Leaner Mouse Mutant

    PubMed Central

    Raike, Robert S.; Hess, Ellen J.; Jinnah, H.A.

    2015-01-01

    Cerebellar degeneration is traditionally associated with ataxia. Yet, there are examples of both ataxia and dystonia occurring in individuals with cerebellar degeneration. There is also substantial evidence suggesting that cerebellar dysfunction alone may cause dystonia. The types of cerebellar defects that may cause ataxia, dystonia, or both have not been delineated. In the current study, we explored the relationship between cerebellar degeneration and dystonia using the leaner mouse mutant. Leaner mice have severe dystonia that is associated with dysfunctional and degenerating cerebellar Purkinje cells. Whereas the density of Purkinje cells was not significantly reduced in 4 week-old leaner mice, approximately 50% of the neurons were lost by 34 weeks of age. On the other hand, the dystonia and associated functional disability became significantly less severe during this same interval. In other words, dystonia improved as Purkinje cells were lost, suggesting that dysfunctional Purkinje cells, rather than Purkinje cell loss, contribute to the dystonia. These results provide evidence that distorted cerebellar function may cause dystonia and support the concept that different types of cerebellar defects can have different functional consequences. PMID:25791619

  20. Distinct Critical Cerebellar Subregions for Components of Verbal Working Memory

    ERIC Educational Resources Information Center

    Cooper, Freya E.; Grube, Manon; Von Kriegstein, Katharina; Kumar, Sukhbinder; English, Philip; Kelly, Thomas P.; Chinnery, Patrick F.; Griffiths, Timothy D.

    2012-01-01

    A role for the cerebellum in cognition has been proposed based on studies suggesting a profile of cognitive deficits due to cerebellar stroke. Such studies are limited in the determination of the detailed organisation of cerebellar subregions that are critical for different aspects of cognition. In this study we examined the correlation between…

  1. Cerebellar control of gait and interlimb coordination.

    PubMed

    Vinueza Veloz, María Fernanda; Zhou, Kuikui; Bosman, Laurens W J; Potters, Jan-Willem; Negrello, Mario; Seepers, Robert M; Strydis, Christos; Koekkoek, Sebastiaan K E; De Zeeuw, Chris I

    2015-11-01

    Synaptic and intrinsic processing in Purkinje cells, interneurons and granule cells of the cerebellar cortex have been shown to underlie various relatively simple, single-joint, reflex types of motor learning, including eyeblink conditioning and adaptation of the vestibulo-ocular reflex. However, to what extent these processes contribute to more complex, multi-joint motor behaviors, such as locomotion performance and adaptation during obstacle crossing, is not well understood. Here, we investigated these functions using the Erasmus Ladder in cell-specific mouse mutant lines that suffer from impaired Purkinje cell output (Pcd), Purkinje cell potentiation (L7-Pp2b), molecular layer interneuron output (L7-Δγ2), and granule cell output (α6-Cacna1a). We found that locomotion performance was severely impaired with small steps and long step times in Pcd and L7-Pp2b mice, whereas it was mildly altered in L7-Δγ2 and not significantly affected in α6-Cacna1a mice. Locomotion adaptation triggered by pairing obstacle appearances with preceding tones at fixed time intervals was impaired in all four mouse lines, in that they all showed inaccurate and inconsistent adaptive walking patterns. Furthermore, all mutants exhibited altered front-hind and left-right interlimb coordination during both performance and adaptation, and inconsistent walking stepping patterns while crossing obstacles. Instead, motivation and avoidance behavior were not compromised in any of the mutants during the Erasmus Ladder task. Our findings indicate that cell type-specific abnormalities in cerebellar microcircuitry can translate into pronounced impairments in locomotion performance and adaptation as well as interlimb coordination, highlighting the general role of the cerebellar cortex in spatiotemporal control of complex multi-joint movements. PMID:25139623

  2. Culturing thick brain slices: An interstitial 3D microperfusion system for enhanced viability

    PubMed Central

    Rambani, Komal; Vukasinovic, Jelena; Glezer, Ari; Potter, Steve M.

    2009-01-01

    Brain slice preparations are well-established models for a wide spectrum of in vitro investigations in the neuroscience discipline. However, these investigations are limited to acute preparations or thin organotypic culture preparations due to the lack of a successful method that allows culturing of thick organotypic brain slices. Thick brain slice cultures suffer necrosis due to ischemia deep in the tissue resulting from a destroyed circulatory system and subsequent diffusion-limited supply of nutrients and oxygen. Although thin organotypic brain slice cultures can be successfully cultured using a well established roller tube method (a monolayer organotypic culture) (Gahwiler B H, 1981) or a membrane insert method (up to 1–4 cell layers, <150μm)(Stoppini L et al., 1991), these methods fail to support thick tissue preparations. A few perfusion methods (using submerged or interface/microfluidic chambers) have been reported to enhance the longevity (up to few hours) of acute slice preparations (up to 600μm thick) (Hass H L et al., 1979; Nicoll R A and Alger B E, 1981; Passeraub P A et al., 2003). Here, we report a unique interstitial microfluidic perfusion technique to culture thick (700μm) organotypic brain slices. The design of the custom-made micro-perfusion chamber facilitates laminar, interstitial perfusion of oxygenated nutrient medium throughout the tissue thickness with concomitant removal of depleted medium and catabolites. We examined the utility of this perfusion method to enhance the viability of the thick organotypic brain slice cultures after 2 days and 5 days in vitro (DIV). We investigated the range of amenable flow rates that enhance the viability of 700μm thick organotypic brain slices compared to the unperfused control cultures. Our perfusion method allows up to 84.6% viability (P<0.01) and up to 700μm thickness, even after 5 DIV. Our results also confirm that these cultures are functionally active and have their in vivo cytoarchitecture

  3. Otogenic cerebellar abscess: a case report.

    PubMed

    Richter, Gresham T; Smith, Jason A; Dornhoffer, John L

    2009-04-01

    This case report describes the gradual deterioration of a healthy, highly functioning man who initially presented with a draining right ear. The patient's indolent neurologic decline and referral to an otologist ultimately led to the diagnosis and treatment of an otogenic cerebellar abscess, an increasingly rare intracranial complication of otitis media. We report this case to illustrate that severe complications of chronic otitis media still occur in the United States, to stress the importance of clinical suspicion in the postantibiotic era, and to review the literature regarding the most appropriate time to perform the otologic portion of the surgery. PMID:19358116

  4. Adaptation of Microplate-based Respirometry for Hippocampal Slices and Analysis of Respiratory Capacity

    PubMed Central

    Schuh, Rosemary A.; Clerc, Pascaline; Hwang, Hyehyun; Mehrabian, Zara; Bittman, Kevin; Chen, Hegang; Polster, Brian M.

    2011-01-01

    Multiple neurodegenerative disorders are associated with altered mitochondrial bioenergetics. Although mitochondrial O2 consumption is frequently measured in isolated mitochondria, isolated synaptic nerve terminals (synaptosomes), or cultured cells, the absence of mature brain circuitry is a remaining limitation. Here we describe the development of a method that adapts the Seahorse Extracellular Flux Analyzer (XF24) for the microplate-based measurement of hippocampal slice O2 consumption. As a first evaluation of the technique, we compared whole slice bioenergetics to previous measurements made with synaptosomes or cultured neurons. We found that mitochondrial respiratory capacity and O2 consumption coupled to ATP synthesis could be estimated in cultured or acute hippocampal slices with preserved neural architecture. Mouse organotypic hippocampal slices oxidizing glucose displayed mitochondrial O2 consumption that was well-coupled, as determined by the sensitivity to the ATP synthase inhibitor oligomycin. However stimulation of respiration by uncoupler was modest (<120% of basal respiration) compared to previous measurements in cells or synaptosomes, although enhanced slightly (to ~150% of basal respiration) by the acute addition of the mitochondrial complex I-linked substrate pyruvate. These findings suggest a high basal utilization of respiratory capacity in slices and a limitation of glucose-derived substrate for maximal respiration. The improved throughput of microplate-based hippocampal respirometry over traditional O2 electrode-based methods is conducive to neuroprotective drug screening. When coupled with cell type-specific pharmacology or genetic manipulations, the ability to efficiently measure O2 consumption from whole slices should advance our understanding of mitochondrial roles in physiology and neuropathology. PMID:21520220

  5. The physiological basis of therapies for cerebellar ataxias.

    PubMed

    Mitoma, Hiroshi; Manto, Mario

    2016-09-01

    Cerebellar ataxias represent a group of heterogeneous disorders impacting on activities of daily living and quality of life. Various therapies have been proposed to improve symptoms in cerebellar ataxias. This review examines the physiological background of the various treatments currently administered worldwide. We analyze the mechanisms of action of drugs with a focus on aminopyridines and other antiataxic medications, of noninvasive cerebellar stimulation, and of motor rehabilitation. Considering the cerebellum as a controller, we propose the novel concept of 'restorable stage'. Because of its unique anatomical architecture and its diffuse connectivity in particular with the cerebral cortex, keeping in mind the anatomophysiology of the cerebellar circuitry is a necessary step to understand the rationale of therapies of cerebellar ataxias and develop novel therapeutic tools. PMID:27582895

  6. New evidence for the cerebellar involvement in personality traits

    PubMed Central

    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. PMID:24106465

  7. The physiological basis of therapies for cerebellar ataxias

    PubMed Central

    Mitoma, Hiroshi; Manto, Mario

    2016-01-01

    Cerebellar ataxias represent a group of heterogeneous disorders impacting on activities of daily living and quality of life. Various therapies have been proposed to improve symptoms in cerebellar ataxias. This review examines the physiological background of the various treatments currently administered worldwide. We analyze the mechanisms of action of drugs with a focus on aminopyridines and other antiataxic medications, of noninvasive cerebellar stimulation, and of motor rehabilitation. Considering the cerebellum as a controller, we propose the novel concept of ‘restorable stage’. Because of its unique anatomical architecture and its diffuse connectivity in particular with the cerebral cortex, keeping in mind the anatomophysiology of the cerebellar circuitry is a necessary step to understand the rationale of therapies of cerebellar ataxias and develop novel therapeutic tools. PMID:27582895

  8. [Familial cerebellar ataxia: clinical, radiological and electrophysiological findings].

    PubMed

    Gajkowski, K; Rysz, A; Walecki, J; Bojakowski, J

    1988-01-01

    A family with cerebellar ataxia of late onset occurring in four generations was observed. Neurological abnormalities included signs of cerebellar ataxia, pyramidal tract damage and damage to the peripheral motor neuron. Computerized tomography demonstrated in five out of six studied patients an image suggesting olivo-ponto-cerebellar atrophy. In the cerebellar structures, brainstem and cerebral hemispheres evidence of atrophy was detected. No correlation was demonstrated between the intensity of the clinical signs and the progression of changes in CT image. Electrophysiological investigations demonstrated changes compatible with damage to the motor and sensory fibres in the peripheral nerves and signs suggesting damage to the spinal motor neurons and pyramidal tract. These observations confirm the multilevel development of the process. The use of similar diagnostic methods will permit a more accurate classification of cerebellar ataxia and obtaining of better information for prognostication of individual cases. PMID:3164096

  9. Thin layer drying of tomato slices.

    PubMed

    Das Purkayastha, Manashi; Nath, Amit; Deka, Bidyut Chandra; Mahanta, Charu Lata

    2013-08-01

    The hot air convective drying characteristics of blanched tomato (Lycopersicon esculantum L.) slices have been investigated. Drying experiments were carried out at four different temperatures (50, 60, 65 and 70 °C). The effect of drying temperatures on the drying behavior of the tomato slices was evaluated. All drying experiments had only falling rate period. The average effective diffusivity values varied from 0.5453 × 10(-9) to 2.3871 × 10(-9) m(2)/s over the temperature range studied and the activation energy was estimated to be 61.004 kJ/mol. In order to select a suitable form of the drying curve, six different thin layer drying models (Henderson-Pabis, Page, Diamante et al., Wang and Singh, Logarithmic and Newton models) were fitted to the experimental data. The goodness of fit tests indicated that the Logarithmic model gave the best fit to experimental results, which was closely followed by the Henderson-Pabis model. The influence of varied drying temperatures on quality attributes of the tomato slices viz. Hunter color parameters, ascorbic acid, lycopene, titratable acidity, total sugars, reducing sugars and sugar/acid ratio of dried slices was also studied. Slices dried at 50 and 60 °C had high amount of total sugars, lycopene, sugar/acid ratio, Hunter L- and a-values. Drying of slices at 50 °C revealed optimum retention of ascorbic acid, sugar/acid ratio and red hue, whereas, drying at higher temperature (65 and 70 °C) resulted in a considerable decrease in nutrients and colour quality of the slices. PMID:24425966

  10. Human Organotypic Cultured Cardiac Slices: New Platform For High Throughput Preclinical Human Trials

    PubMed Central

    Kang, C.; Qiao, Y.; Li, G.; Baechle, K.; Camelliti, P.; Rentschler, S.; Efimov, I. R.

    2016-01-01

    Translation of novel therapies from bench to bedside is hampered by profound disparities between animal and human genetics and physiology. The ability to test for efficacy and cardiotoxicity in a clinically relevant human model system would enable more rapid therapy development. We have developed a preclinical platform for validation of new therapies in human heart tissue using organotypic slices isolated from donor and end-stage failing hearts. A major advantage of the slices when compared with human iPS-derived cardiomyocytes is that native tissue architecture and extracellular matrix are preserved, thereby allowing investigation of multi-cellular physiology in normal or diseased myocardium. To validate this model, we used optical mapping of transmembrane potential and calcium transients. We found that normal human electrophysiology is preserved in slice preparations when compared with intact hearts, including slices obtained from the region of the sinus node. Physiology is maintained in slices during culture, enabling testing the acute and chronic effects of pharmacological, gene, cell, optogenetic, device, and other therapies. This methodology offers a powerful high-throughput platform for assessing the physiological response of the human heart to disease and novel putative therapies. PMID:27356882

  11. Human Organotypic Cultured Cardiac Slices: New Platform For High Throughput Preclinical Human Trials.

    PubMed

    Kang, C; Qiao, Y; Li, G; Baechle, K; Camelliti, P; Rentschler, S; Efimov, I R

    2016-01-01

    Translation of novel therapies from bench to bedside is hampered by profound disparities between animal and human genetics and physiology. The ability to test for efficacy and cardiotoxicity in a clinically relevant human model system would enable more rapid therapy development. We have developed a preclinical platform for validation of new therapies in human heart tissue using organotypic slices isolated from donor and end-stage failing hearts. A major advantage of the slices when compared with human iPS-derived cardiomyocytes is that native tissue architecture and extracellular matrix are preserved, thereby allowing investigation of multi-cellular physiology in normal or diseased myocardium. To validate this model, we used optical mapping of transmembrane potential and calcium transients. We found that normal human electrophysiology is preserved in slice preparations when compared with intact hearts, including slices obtained from the region of the sinus node. Physiology is maintained in slices during culture, enabling testing the acute and chronic effects of pharmacological, gene, cell, optogenetic, device, and other therapies. This methodology offers a powerful high-throughput platform for assessing the physiological response of the human heart to disease and novel putative therapies. PMID:27356882

  12. Ultrafast multi-slice spatiotemporally encoded MRI with slice-selective dimension segmented.

    PubMed

    Zhang, Ting; Chen, Lin; Huang, Jianpan; Li, Jing; Cai, Shuhui; Cai, Congbo; Chen, Zhong

    2016-08-01

    As a recently emerging method, spatiotemporally encoded (SPEN) magnetic resonance imaging (MRI) has a high robustness to field inhomogeneity and chemical shift effect. It has been broadened from single-slice scanning to multi-slice scanning. In this paper, a novel multi-slice SPEN MRI method was proposed. In this method, the slice-selective dimension was segmented to lower the specific absorption rate (SAR) and improve the image quality. This segmented method, dubbed SeSPEN method, was theoretically analyzed and demonstrated with phantom, lemon and in vivo rat brain experiments. The experimental results were compared with the results obtained from the spin-echo EPI, spin-echo SPEN method and multi-slice global SPEN method proposed by Frydman and coauthors (abbr. GlSPEN method). All the SPEN images were super-resolved reconstructed using deconvolution method. The results indicate that the SeSPEN method retains the advantage of SPEN MRI with respect to resistance to field inhomogeneity and can provide better signal-to-noise ratio than multi-slice GlSPEN MRI technique. The SeSPEN method has comparable SAR to the GlSPEN method while the T1 signal attenuation effect is alleviated. The proposed method will facilitate the multi-slice SPEN MRI to scan more slices within one scan with better image quality. PMID:27301072

  13. Ultrafast multi-slice spatiotemporally encoded MRI with slice-selective dimension segmented

    NASA Astrophysics Data System (ADS)

    Zhang, Ting; Chen, Lin; Huang, Jianpan; Li, Jing; Cai, Shuhui; Cai, Congbo; Chen, Zhong

    2016-08-01

    As a recently emerging method, spatiotemporally encoded (SPEN) magnetic resonance imaging (MRI) has a high robustness to field inhomogeneity and chemical shift effect. It has been broadened from single-slice scanning to multi-slice scanning. In this paper, a novel multi-slice SPEN MRI method was proposed. In this method, the slice-selective dimension was segmented to lower the specific absorption rate (SAR) and improve the image quality. This segmented method, dubbed SeSPEN method, was theoretically analyzed and demonstrated with phantom, lemon and in vivo rat brain experiments. The experimental results were compared with the results obtained from the spin-echo EPI, spin-echo SPEN method and multi-slice global SPEN method proposed by Frydman and coauthors (abbr. GlSPEN method). All the SPEN images were super-resolved reconstructed using deconvolution method. The results indicate that the SeSPEN method retains the advantage of SPEN MRI with respect to resistance to field inhomogeneity and can provide better signal-to-noise ratio than multi-slice GlSPEN MRI technique. The SeSPEN method has comparable SAR to the GlSPEN method while the T1 signal attenuation effect is alleviated. The proposed method will facilitate the multi-slice SPEN MRI to scan more slices within one scan with better image quality.

  14. Insights into cerebellar development and medulloblastoma.

    PubMed

    Bihannic, Laure; Ayrault, Olivier

    2016-01-01

    Cerebellar development is an extensive process that begins during early embryonic stages and persists more than one year after birth in human. Therefore, the cerebellum is susceptible to acquire various developmental abnormalities leading to numerous diseases such as medulloblastoma, the most common pediatric malignant brain tumor. One third of the patients with medulloblastoma are incurable and survivors have a poor quality of life due to the aggressiveness of the broad-spectrum treatments. Within the past few years, it has been highlighted that medulloblastoma is a heterogeneous disease that is divided in four molecular subgroups. This recent advance in the field, combined with the development of associated preclinical models for each subgroup, should enable, in the future, the discovery and use of targeted therapy in clinical treatments for each subtype of medulloblastoma. In this review, we first aim to show how deregulation of cerebellar development can lead to medulloblastoma formation and then to present the advances in the molecular subgrouping of medulloblastoma and the associated preclinical models. PMID:26688373

  15. Glycine metabolism in rat kidney cortex slices.

    PubMed

    Rowsell, E V; Al-Naama, M M; Rowsell, K V

    1982-04-15

    When rat kidney cortex slices were incubated with glycine or [1-14C]glycine, after correcting for metabolite changes with control slices, product formation and glycine utilization fitted the requirements of the equation: 2 Glycine leads to ammonia + CO2 + serine. Evidence is presented that degradation via glyoxylate, by oxidation or transamination, is unlikely to have any significant role in kidney glycine catabolism. It is concluded that glycine metabolism in rat kidney is largely via glycine cleavage closely coupled with serine formation. 1-C decarboxylation and urea formation with glycine in rat hepatocyte suspensions were somewhat greater than decarboxylation or ammonia formation in kidney slices, showing that in the rat, potentially, the liver is quantitatively the more important organ in glycine catabolism. There was no evidence of ammonia formation from glycine with rat brain cortex, heart, spleen or diaphragm and 1-C decarboxylation was very weak. PMID:6810880

  16. Prenatal Cerebellar Disruptions: Neuroimaging Spectrum of Findings in Correlation with Likely Mechanisms and Etiologies of Injury.

    PubMed

    Poretti, Andrea; Boltshauser, Eugen; Huisman, Thierry A G M

    2016-08-01

    There is increasing evidence that the cerebellum is susceptible to prenatal infections and hemorrhages and that congenital morphologic anomalies of the cerebellum may be caused by disruptive (acquired) causes. Starting from the neuroimaging pattern, this report describes a spectrum of prenatal cerebellar disruptions including cerebellar agenesis, unilateral cerebellar hypoplasia, cerebellar cleft, global cerebellar hypoplasia, and vanishing cerebellum in Chiari type II malformation. The neuroimaging findings, possible causative disruptive events, and clinical features of each disruption are discussed. Recognition of cerebellar disruptions and their differentiation from cerebellar malformations is important in terms of diagnosis, prognosis, and genetic counselling. PMID:27423799

  17. Contribution of Cerebellar Sensorimotor Adaptation to Hippocampal Spatial Memory

    PubMed Central

    Passot, Jean-Baptiste; Sheynikhovich, Denis; Duvelle, Éléonore; Arleo, Angelo

    2012-01-01

    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. PMID:22485133

  18. Neural correlates of impaired emotional face recognition in cerebellar lesions.

    PubMed

    Adamaszek, Michael; Kirkby, Kenneth C; D'Agata, Fedrico; Olbrich, Sebastian; Langner, Sönke; Steele, Christopher; Sehm, Bernhard; Busse, Stefan; Kessler, Christof; Hamm, Alfons

    2015-07-10

    Clinical and neuroimaging data indicate a cerebellar contribution to emotional processing, which may account for affective-behavioral disturbances in patients with cerebellar lesions. We studied the neurophysiology of cerebellar involvement in recognition of emotional facial expression. Participants comprised eight patients with discrete ischemic cerebellar lesions and eight control patients without any cerebrovascular stroke. Event-related potentials (ERP) were used to measure responses to faces from the Karolinska Directed Emotional Faces Database (KDEF), interspersed in a stream of images with salient contents. Images of faces augmented N170 in both groups, but increased late positive potential (LPP) only in control patients without brain lesions. Dipole analysis revealed altered activation patterns for negative emotions in patients with cerebellar lesions, including activation of the left inferior prefrontal area to images of faces showing fear, contralateral to controls. Correlation analysis indicated that lesions of cerebellar area Crus I contribute to ERP deviations. Overall, our results implicate the cerebellum in integrating emotional information at different higher order stages, suggesting distinct cerebellar contributions to the proposed large-scale cerebral network of emotional face recognition. PMID:25912431

  19. Cerebellar Processing of Sensory Inputs Primes Motor Cortex Plasticity

    PubMed Central

    Velayudhan, B.; Hubsch, C.; Pradeep, S.; Roze, E.; Vidailhet, M.; Meunier, S.; Kishore, A.

    2013-01-01

    Plasticity of the human primary motor cortex (M1) has a critical role in motor control and learning. The cerebellum facilitates these functions using sensory feedback. We investigated whether cerebellar processing of sensory afferent information influences the plasticity of the primary motor cortex (M1). Theta-burst stimulation protocols (TBS), both excitatory and inhibitory, were used to modulate the excitability of the posterior cerebellar cortex and to condition an ongoing M1 plasticity. M1 plasticity was subsequently induced in 2 different ways: by paired associative stimulation (PAS) involving sensory processing and TBS that exclusively involves intracortical circuits of M1. Cerebellar excitation attenuated the PAS-induced M1 plasticity, whereas cerebellar inhibition enhanced and prolonged it. Furthermore, cerebellar inhibition abolished the topography-specific response of PAS-induced M1 plasticity, with the effects spreading to adjacent motor maps. Conversely, cerebellar excitation had no effect on the TBS-induced M1 plasticity. This demonstrates the key role of the cerebellum in priming M1 plasticity, and we propose that it is likely to occur at the thalamic or olivo-dentate nuclear level by influencing the sensory processing. We suggest that such a cerebellar priming of M1 plasticity could shape the impending motor command by favoring or inhibiting the recruitment of several muscle representations. PMID:22351647

  20. Developmental dyslexia and widespread activation across the cerebellar hemispheres.

    PubMed

    Baillieux, Hanne; Vandervliet, Everhard J M; Manto, Mario; Parizel, Paul M; De Deyn, Peter P; Mariën, Peter

    2009-02-01

    Developmental dyslexia is the most common learning disability in school-aged children with an estimated incidence of five to ten percent. The cause and pathophysiological substrate of this developmental disorder is unclear. Recently, a possible involvement of the cerebellum in the pathogenesis of dyslexia has been postulated. In this study, 15 dyslexic children and 7 age-matched control subjects were investigated by means of functional neuroimaging (fMRI) using a noun-verb association paradigm. Comparison of activation patterns between dyslexic and control subjects revealed distinct and significant differences in cerebral and cerebellar activation. Control subjects showed bilaterally well-defined and focal activation patterns in the frontal and parietal lobes and the posterior regions of the cerebellar hemispheres. The dyslexic children, however, presented widespread and diffuse activations on the cerebral and cerebellar level. Cerebral activations were found in frontal, parietal, temporal and occipital regions. Activations in the cerebellum were found predominantly in the cerebellar cortex, including Crus I, Crus II, hemispheric lobule VI, VII and vermal lobules I, II, III, IV and VII. This preliminary study is the first to reveal a significant difference in cerebellar functioning between dyslexic children and controls during a semantic association task. As a result, we propose a new hypothesis regarding the pathophysiological mechanisms of developmental dyslexia. Given the sites of activation in the cerebellum in the dyslexic group, a defect of the intra-cerebellar distribution of activity is suspected, suggesting a disorder of the processing or transfer of information within the cerebellar cortex. PMID:18986695

  1. Update on the pharmacotherapy of cerebellar and central vestibular disorders.

    PubMed

    Kalla, Roger; Teufel, Julian; Feil, Katharina; Muth, Caroline; Strupp, Michael

    2016-04-01

    An overview of the current pharmacotherapy of central vestibular syndromes and the most common forms of central nystagmus as well as cerebellar disorders is given. 4-aminopyridine (4-AP) is recommended for the treatment of downbeat nystagmus, a frequent form of acquired persisting fixation nystagmus, and upbeat nystagmus. Animal studies showed that this non-selective blocker of voltage-gated potassium channels increases Purkinje cell excitability and normalizes the irregular firing rate, so that the inhibitory influence of the cerebellar cortex on vestibular and deep cerebellar nuclei is restored. The efficacy of 4-AP in episodic ataxia type 2, which is most often caused by mutations of the PQ-calcium channel, was demonstrated in a randomized controlled trial. It was also shown in an animal model (the tottering mouse) of episodic ataxia type 2. In a case series, chlorzoxazone, a non-selective activator of small-conductance calcium-activated potassium channels, was shown to reduce the DBN. The efficacy of acetyl-DL-leucine as a potential new symptomatic treatment for cerebellar diseases has been demonstrated in three case series. The ongoing randomized controlled trials on episodic ataxia type 2 (sustained-release form of 4-aminopyridine vs. acetazolamide vs. placebo; EAT2TREAT), vestibular migraine with metoprolol (PROVEMIG-trial), cerebellar gait disorders (sustained-release form of 4-aminopyridine vs. placebo; FACEG) and cerebellar ataxia (acetyl-DL-leucine vs. placebo; ALCAT) will provide new insights into the pharmacotherapy of cerebellar and central vestibular disorders. PMID:27083881

  2. ID slicing and the automated factory

    NASA Technical Reports Server (NTRS)

    Lewandowski, T.

    1982-01-01

    The automation of the slicing system utilizing internal-diameter saws for the production of the silicon wafers used in solar arrays is discussed. It is argued that saw productivity can be increased by reducing silicon waste, decreasing usage of consumables, keeping the saw slicing, and increasing the cutting speed. Several machine enhancements utilizing automatic control are discussed. The need for record keeping to anticipate maintenance operations is noted, and a digital serial communication interface with the microprocessor-based saws is recommended. Distributed control of the manufacturing process is discussed in detail, and is recommended as a method for increasing productivity.

  3. Consensus Paper: Revisiting the Symptoms and Signs of Cerebellar Syndrome.

    PubMed

    Bodranghien, Florian; Bastian, Amy; Casali, Carlo; Hallett, Mark; Louis, Elan D; Manto, Mario; Mariën, Peter; Nowak, Dennis A; Schmahmann, Jeremy D; Serrao, Mariano; Steiner, Katharina Marie; Strupp, Michael; Tilikete, Caroline; Timmann, Dagmar; van Dun, Kim

    2016-06-01

    The cerebellum is involved in sensorimotor operations, cognitive tasks and affective processes. Here, we revisit the concept of the cerebellar syndrome in the light of recent advances in our understanding of cerebellar operations. The key symptoms and signs of cerebellar dysfunction, often grouped under the generic term of ataxia, are discussed. Vertigo, dizziness, and imbalance are associated with lesions of the vestibulo-cerebellar, vestibulo-spinal, or cerebellar ocular motor systems. The cerebellum plays a major role in the online to long-term control of eye movements (control of calibration, reduction of eye instability, maintenance of ocular alignment). Ocular instability, nystagmus, saccadic intrusions, impaired smooth pursuit, impaired vestibulo-ocular reflex (VOR), and ocular misalignment are at the core of oculomotor cerebellar deficits. As a motor speech disorder, ataxic dysarthria is highly suggestive of cerebellar pathology. Regarding motor control of limbs, hypotonia, a- or dysdiadochokinesia, dysmetria, grasping deficits and various tremor phenomenologies are observed in cerebellar disorders to varying degrees. There is clear evidence that the cerebellum participates in force perception and proprioceptive sense during active movements. Gait is staggering with a wide base, and tandem gait is very often impaired in cerebellar disorders. In terms of cognitive and affective operations, impairments are found in executive functions, visual-spatial processing, linguistic function, and affective regulation (Schmahmann's syndrome). Nonmotor linguistic deficits including disruption of articulatory and graphomotor planning, language dynamics, verbal fluency, phonological, and semantic word retrieval, expressive and receptive syntax, and various aspects of reading and writing may be impaired after cerebellar damage. The cerebellum is organized into (a) a primary sensorimotor region in the anterior lobe and adjacent part of lobule VI, (b) a second sensorimotor

  4. Variant PTA Terminating in Cerebellar Artery, Associated with Multiple Aneurysms

    PubMed Central

    Hwang, Yeong Uk

    2016-01-01

    Persistent trigeminal artery (PTA) is one of the remnant fetal anastomoses between the carotid artery and basilar artery. PTAs are classified according to angiographic appearance and various connection. Among them, those directly terminating in the cerebellar arteries are rare subtype. In addition, aneurysms of the PTA are unusual in the literature and have not previously accompanied this subtype of PTA connecting cerebellar artery. We present the first case of an aneurysm of the PTA which is directly terminating in the cerebellar arteries and combined with multiple aneurysms. PMID:27446623

  5. Variant PTA Terminating in Cerebellar Artery, Associated with Multiple Aneurysms.

    PubMed

    Hwang, Yeong Uk; Kim, Jin Woo

    2016-01-01

    Persistent trigeminal artery (PTA) is one of the remnant fetal anastomoses between the carotid artery and basilar artery. PTAs are classified according to angiographic appearance and various connection. Among them, those directly terminating in the cerebellar arteries are rare subtype. In addition, aneurysms of the PTA are unusual in the literature and have not previously accompanied this subtype of PTA connecting cerebellar artery. We present the first case of an aneurysm of the PTA which is directly terminating in the cerebellar arteries and combined with multiple aneurysms. PMID:27446623

  6. Silicon ingot casting: Heat exchanger method. Multi-wire slicing: Fixed abrasive slicing technique, phase 3

    NASA Technical Reports Server (NTRS)

    Schmid, F.; Khattak, C. P.

    1979-01-01

    In the area of ingot casting the proof of concept of heat exchanger method (HEM) was established. It was also established that HEM cast silicon yielded solar cell performance comparable to Czochralski grown material. Solar cells with conversion efficiencies of up to 15% were fabricated. It was shown that square cross-section ingots can be cast. In the area of crystal slicing, it was established that silicon can be sliced efficiently with the fixed abrasive slicing technique approach. This concept was carried forward to 10 cm diameter workpiece.

  7. Hereditary Cerebellar Ataxias: A Korean Perspective

    PubMed Central

    Kim, Ji Sun; Cho, Jin Whan

    2015-01-01

    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. PMID:26090078

  8. nem_slice ver. 3.34

    2009-06-08

    Nem_slice reads in a finite element model description of the geometry of a problem from an ExodusII file and generates either a nodal or elemental graph of the problem. It then calls Chaco to load balance the graph and then outputs a NemesisI load-balance file.

  9. [A simple vibratome for brain slice].

    PubMed

    Xia, J H; Xing, B R; Gu, Q; Hua, S Y

    1989-12-01

    A simple vibratome was fabricated using double-function electric shaver and microscopic platform. Spontaneous discharge of neurons in hippocampal and hypothalamic brain slices (in 300-400 microns thick) prepared by the vibratome could kept above 12 hours in artificial cerebro-spinal fluid. PMID:2697084

  10. Detecting Psychopathy from Thin Slices of Behavior

    ERIC Educational Resources Information Center

    Fowler, Katherine A.; Lilienfeld, Scott O.; Patrick, Christopher J.

    2009-01-01

    This study is the first to demonstrate that features of psychopathy can be reliably and validly detected by lay raters from "thin slices" (i.e., small samples) of behavior. Brief excerpts (5 s, 10 s, and 20 s) from interviews with 96 maximum-security inmates were presented in video or audio form or in both modalities combined. Forty raters used…

  11. Thin-Slice Perception Develops Slowly

    ERIC Educational Resources Information Center

    Balas, Benjamin; Kanwisher, Nancy; Saxe, Rebecca

    2012-01-01

    Body language and facial gesture provide sufficient visual information to support high-level social inferences from "thin slices" of behavior. Given short movies of nonverbal behavior, adults make reliable judgments in a large number of tasks. Here we find that the high precision of adults' nonverbal social perception depends on the slow…

  12. Anomalous Cerebellar Anatomy in Chinese Children with Dyslexia

    PubMed Central

    Yang, Yang; Chen, Bao-Guo; Zhang, Yi-Wei; Bi, Hong-Yan

    2016-01-01

    The cerebellar deficit hypothesis for developmental dyslexia 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. PMID:27047403

  13. Cerebellar transcranial direct current stimulation in neurological disease.

    PubMed

    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 a number of interesting studies on the application of cerebellar tDCS for various neurological conditions (ataxia, Parkinson's disease, dystonia, essential tremor) and the possible mechanism by which the stimulation acts on the cerebellum. Study findings indicate that cerebellar tDCS is a promising therapeutic tool in treating several neurological disorders; however, this method's efficacy appears to be limited, given the current data. PMID:27595007

  14. Anomalous Cerebellar Anatomy in Chinese Children with Dyslexia.

    PubMed

    Yang, Ying-Hui; Yang, Yang; Chen, Bao-Guo; Zhang, Yi-Wei; Bi, Hong-Yan

    2016-01-01

    The cerebellar deficit hypothesis for developmental dyslexia 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. PMID:27047403

  15. Novel Approaches to Studying the Genetic Basis of Cerebellar Development

    PubMed Central

    Sajan, Samin A.; Waimey, Kathryn E.

    2010-01-01

    The list of genes that when mutated cause disruptions in cerebellar development is rapidly increasing. The study of both spontaneous and engineered mouse mutants has been essential to this progress, as it has revealed much of our current understanding of the developmental processes required to construct the mature cerebellum. Improvements in brain imaging, such as magnetic resonance imaging (MRI) and the emergence of better classification schemes for human cerebellar malformations, have recently led to the identification of a number of genes which cause human cerebellar disorders. In this review we argue that synergistic approaches combining classical molecular techniques, genomics, and mouse models of human malformations will be essential to fuel additional discoveries of cerebellar developmental genes and mechanisms. PMID:20387026

  16. Malignant cerebellar peduncle lesions - rapid progression and poor outcome

    PubMed Central

    Singla, Navneet; Kapoor, Ankur; Savardekar, Amey; Radotra, B. D.; Chatterjee, Debjyoti; Gupta, Sunil K.

    2016-01-01

    Background: Tumors arising from cerebellar peduncle are extremely rare and behave aggressively. The inclusion of these into either cerebellar or brainstem gliomas is contentious. Case Description: We performed clinicopathological review of three patients treated at our institute and surveyed the literature for previous such reported cases. Mean duration of symptoms in our patients was 2 weeks. Subtotal tumor resection was performed in two patients while the third underwent stereotactic biopsy followed by chemoradiotherapy. Histopathology revealed glioblastoma in initial two patients and medulloblastoma Grade IV in the third. The two patients who underwent surgical excision succumbed to the illness within 2 days and a month, respectively. Conclusion: Malignant cerebellar peduncular lesions have poor overall survival despite surgical debulking. It is not confirmed whether these tumors should be considered as cerebellar lesions or brainstem gliomas due to aggressive clinical behavior, and so the ideal line of management is not yet known. PMID:27057396

  17. Esophoria or esotropia in adulthood: a sign of cerebellar dysfunction?

    PubMed

    Hüfner, Katharina; Frenzel, Claudia; Kremmyda, Olympia; Adrion, Christine; Bardins, Stanislavs; Glasauer, Stefan; Brandt, Thomas; Strupp, Michael

    2015-03-01

    Convergent strabismus is a common diagnosis in early childhood, when it is mostly considered benign. If it develops later in life, strabismus can, however, be a sign of neurological disease. In these cases the underlying pathophysiological mechanisms are largely unknown. In this retrospective case-control study we analyzed the neuro-ophthalmological examination reports of 400 adult patients who presented at the German Center for Vertigo and Balance Disorders to determine an association between ocular misalignment and cerebellar dysfunction. Patients with cerebellar signs (i.e., cerebellar ataxia and/or cerebellar ocular motor signs) had a 4.49 (95 % CI [1.60; 13.78]) times higher frequency of ocular misalignment and specifically a 13.3 (95 % CI [3.80; 55.73]) times increased frequency of esophoria/esotropia (ESO) during distant gaze than patients without cerebellar dysfunction. ESO when looking into the distance was associated with saccadic smooth pursuit, dysmetria of saccades, and downbeat nystagmus (DBN) (χ (2) test, p < 0.0001 for all associations). Patients with cerebellar dysfunction also showed mildly impaired eye abduction (χ (2) test, left eye and right eye: p < 0.0001), associated with horizontal gaze-evoked nystagmus (χ (2) test, p < 0.0001). The association of ESO and DBN implicates a pathophysiological involvement of the cerebellar flocculus, while the association with dysmetric saccades suggests involvement of the oculomotor vermis. This is compatible with animal studies showing that the pathways of the flocculus/posterior interposed nucleus and vermis/nucleus fastigii are both involved in vergence movements and static binocular alignment. From a clinical point of view, a newly diagnosed esophoria/esotropia only during distant gaze may be a sign of a cerebellar disease. PMID:25522697

  18. Cerebellar contributions to neurological soft signs in healthy young adults.

    PubMed

    Hirjak, Dusan; Thomann, Philipp A; Kubera, Katharina M; Stieltjes, Bram; Wolf, Robert C

    2016-02-01

    Neurological soft signs (NSS) are frequently found in psychiatric disorders of significant neurodevelopmental origin, e.g., in patients with schizophrenia and autism. Yet NSS are also present in healthy individuals suggesting a neurodevelopmental signature of motor function, probably as a continuum between health and disease. So far, little is known about the neural mechanisms underlying these motor phenomena in healthy persons, and it is even less known whether the cerebellum contributes to NSS expression. Thirty-seven healthy young adults (mean age = 23 years) were studied using high-resolution structural magnetic resonance imaging (MRI) and "resting-state" functional MRI at three Tesla. NSS levels were measured using the "Heidelberg Scale." Cerebellar gray matter volume was investigated using cerebellum-optimized voxel-based analysis methods. Cerebellar function was assessed using regional homogeneity (ReHo), a measure of local network strength. The relationship between cerebellar structure and function and NSS was analyzed using regression models. There was no significant relationship between cerebellar volume and NSS (p < 0.005, uncorrected for height, p < 0.05 corrected for spatial extent). Positive associations with cerebellar lobule VI activity were found for the "motor coordination" and "hard signs" NSS domains. A negative relationship was found between lobule VI activity and "complex motor task" domain (p < 0.005, uncorrected for height, p < 0.05 corrected for spatial extent). The data indicate that in healthy young adults, distinct NSS domains are related to cerebellar activity, specifically with activity of cerebellar subregions with known cortical somatomotor projections. In contrast, cerebellar volume is not predictive of NSS in healthy persons. PMID:25708455

  19. Primary cerebellar agenesis presenting as isolated cognitive impairment

    PubMed Central

    Ashraf, Obaid; Jabeen, Shumyla; Khan, Azhar; Shaheen, Feroze

    2016-01-01

    Primary cerebellar agenesis is a rare entity. To the best of our knowledge, eleven living cases have been reported till date. Most of these were associated with some degree of motor impairment. We present a case of cerebellar agenesis in a child who presented with cognitive abnormalities leading to poor performance at school. No motor impairment was seen. Among the eleven cases reported earlier, only one case showed lack of motor impairment.

  20. The Characteristics of LTP Induced in Hippocampal Slices Are Dependent on Slice-Recovery Conditions

    ERIC Educational Resources Information Center

    Godaux, Emile; Ris, Laurence; Capron, Brigitte; Sindic, Christian

    2006-01-01

    In area CA1 of hippocampal slices which are allowed to recover from slicing "in interface" and where recordings are carried out in interface, a single 1-sec train of 100-Hz stimulation triggers a short-lasting long-term potentiation (S-LTP), which lasts 1-2 h, whereas multiple 1-sec trains induce a long-lasting LTP (L-LTP), which lasts several…

  1. Hemorrhagic presentations of cerebellar pilocytic astrocytomas in children resulting in death: report of 2 cases.

    PubMed

    Wilson, Mitchell P; Johnson, Edward S; Hawkins, Cynthia; Atkins, Kerry; Alshaya, Wael; Pugh, Jeffrey A

    2016-04-01

    Acute hemorrhagic presentation in pilocytic astrocytomas (PAs) has become increasingly recognized. This type of presentation poses a clinically emergent situation in those hemorrhages arising in PAs of the cerebellum, the most frequent site, because of the limited capacity of the posterior fossa to compensate for mass effect, predisposing to rapid neurological deterioration. As examples, we describe two cases of fatal hemorrhagic cerebellar PAs: one of a child with a slowly growing stereotypical WHO Grade I PA with a 1-year period of symptomatology that preceded a rapid clinical deterioration, and another of an asymptomatic child having a PA variant, presenting with progressive obtundation following a presumed Valsalva event. These two scenarios parallel previous reports in the literature of either a setting of progressive expression of cerebellar dysfunction and transient episodes of raised intracranial pressure (ICP), or abrupt onset of features of increased ICP in a previously well child. The literature is further reviewed for a current understanding of the factors that predispose, initiate and propagate bleeding, with specific reference to the role of vascular endothelial growth factor and other angiogenic agents in the genesis and stability of the vasculature in PAs. In this context, we propose that obliterative vascular mural hyalinization with associated altered flow dynamics and microaneurysm formation was the pathogenesis of the hemorrhage in our first case. In the second case, large tumor size, increased growth rate, looseness of the background myxoid matrix, and thinness of the tumor blood vessels with calcospherite deposition predisposed to vascular leakage and bleeding concurrent with sudden increases in intravascular hydrostatic pressure. In that cerebellar PAs are common, this report underscores the importance of considering in the differential diagnosis the possibility of a spontaneous hemorrhage in a posterior fossa PA in a child presenting with a

  2. Transplantation and Stem Cell Therapy for Cerebellar Degenerations.

    PubMed

    Cendelin, Jan

    2016-02-01

    Stem cell-based and regenerative therapy may become a hopeful treatment for neurodegenerative diseases including hereditary cerebellar degenerations. Neurotransplantation therapy mainly aims to substitute lost cells, but potential effects might include various mechanisms including nonspecific trophic effects and stimulation of endogenous regenerative processes and neural plasticity. Nevertheless, currently, there remain serious limitations. There is a wide spectrum of human hereditary cerebellar degenerations as well as numerous cerebellar mutant mouse strains that serve as models for the development of effective therapy. By now, transplantation has been shown to ameliorate cerebellar function, e.g. in Purkinje cell degeneration mice, Lurcher mutant mice and mouse models of spinocerebellar ataxia type 1 and type 2 and Niemann-Pick disease type C. Despite the lack of direct comparative studies, it appears that there might be differences in graft development and functioning between various types of cerebellar degeneration. Investigation of the relation of graft development to specific morphological, microvascular or biochemical features of the diseased host tissue in various cerebellar degenerations may help to identify factors determining the fate of grafted cells and potential of their functional integration. PMID:26155762

  3. Emotions and their cognitive control in children with cerebellar tumors.

    PubMed

    Hopyan, Talar; Laughlin, Suzanne; Dennis, Maureen

    2010-11-01

    A constellation of deficits, termed the cerebellar cognitive affective syndrome (CCAS), has been reported following acquired cerebellar lesions. We studied emotion identification and the cognitive control of emotion in children treated for acquired tumors of the cerebellum. Participants were 37 children (7-16 years) treated for cerebellar tumors (19 benign astrocytomas (AST), 18 malignant medulloblastomas (MB), and 37 matched controls (CON). The Emotion Identification Task investigated recognition of happy and sad emotions in music. In two cognitive control tasks, we investigated whether children could identify emotion in situations in which the emotion in the music and the emotion in the lyrics was either congruent or incongruent. Children with cerebellar tumors identified emotion as accurately and quickly as controls (p > .05), although there was a significant interaction of emotions and group (p < .01), with the MB group performing less accurately identifying sad emotions, and both cerebellar tumor groups were impaired in the cognitive control of emotions (p < .01). The fact that childhood acquired cerebellar tumors disrupt cognitive control of emotion rather than emotion identification provides some support for a model of the CCAS as a disorder, not so much of emotion as of the regulation of emotion by cognition. PMID:20887648

  4. Disrupted cortico-cerebellar connectivity in older adults

    PubMed Central

    Bernard, Jessica A.; Peltier, Scott J.; Wiggins, Jillian Lee; Jaeggi, Susanne M.; Buschkuehl, Martin; Fling, Brett W.; Kwak, Youngbin; Jonides, John; Monk, Christopher S.; Seidler, Rachael D.

    2013-01-01

    Healthy aging is marked by declines in a variety of cognitive and motor abilities. A better understanding of the aging brain may aid in elucidating the neural substrates of these behavioral effects. Investigations of resting state functional brain connectivity have provided insights into pathology, and to some degree, healthy aging. Given the role of the cerebellum in both motor and cognitive behaviors, as well as its known volumetric declines with age, investigating cerebellar networks may shed light on the neural bases of age-related functional declines. We mapped the resting state networks of the lobules of the right hemisphere and the vermis of the cerebellum in a group of healthy older adults and compared them to those of young adults. We report disrupted cortico-cerebellar resting state network connectivity in older adults. These results remain even when controlling for cerebellar volume, signal-to-noise ratio, and signal-to-fluctuation noise ratio. Specifically, there was consistent disruption of cerebellar connectivity with both the striatum and the medial temporal lobe. Associations between connectivity strength and both sensorimotor and cognitive task performance indicate that cerebellar engagement with the default mode network and striatal pathways is associated with better performance for older adults. These results extend our understanding of the resting state networks of the aging brain to include cortico-cerebellar networks, and indicate that age differences in network connectivity strength are important for behavior. PMID:23792980

  5. Verbal memory impairments in children after cerebellar tumor resection

    PubMed Central

    Kirschen, Matthew P.; Davis-Ratner, Mathew S.; Milner, Marnee W.; Annabel Chen, S.H.; Schraedley-Desmond, Pam; Fisher, Paul G.; Desmond, John E.

    2009-01-01

    This study was designed to investigate cerebellar lobular contributions to specific cognitive deficits observed after cerebellar tumor resection. Verbal working memory (VWM) tasks were administered to children following surgical resection of cerebellar pilocytic astrocytomas and age-matched controls. Anatomical MRI scans were used to quantify the extent of cerebellar lobular damage from each patient’s resection. Patients exhibited significantly reduced digit span for auditory but not visual stimuli, relative to controls, and damage to left hemispheral lobule VIII was significantly correlated with this deficit. Patients also showed reduced effects of articulatory suppression and this was correlated with damage to the vermis and hemispheral lobule IV/V bilaterally. Phonological similarity and recency effects did not differ overall between patients and controls, but outlier patients with abnormal phonological similarity effects to either auditory or visual stimuli were found to have damage to hemispheral lobule VIII/VIIB on the left and right, respectively. We postulate that damage to left hemispheral lobule VIII may interfere with encoding of auditory stimuli into the phonological store. These data corroborate neuroimaging studies showing focal cerebellar activation during VWM paradigms, and thereby allow us to predict with greater accuracy which specific neurocognitive processes will be affected by a cerebellar tumor resection. PMID:19491473

  6. Oxidative injury in multiple sclerosis cerebellar grey matter.

    PubMed

    Kemp, Kevin; Redondo, Juliana; Hares, Kelly; Rice, Claire; Scolding, Neil; Wilkins, Alastair

    2016-07-01

    Cerebellar dysfunction is a significant contributor to disability in multiple sclerosis (MS). Both white matter (WM) and grey matter (GM) injury occurs within MS cerebellum and, within GM, demyelination, inflammatory cell infiltration and neuronal injury contribute to on-going pathology. The precise nature of cerebellar GM injury is, however, unknown. Oxidative stress pathways with ultimate lipid peroxidation and cell membrane injury occur extensively in MS and the purpose of this study was to investigate these processes in MS cerebellar GM. Post-mortem human cerebellar GM from MS and control subjects was analysed immunohistochemically, followed by semi-quantitative analysis of markers of cellular injury, lipid peroxidation and anti-oxidant enzyme expression. We have shown evidence for reduction in myelin and neuronal markers in MS GM, coupled to an increase in expression of a microglial marker. We also show that the lipid peroxidation product 4-hydroxynonenal co-localises with myelin and its levels negatively correlate to myelin basic protein levels. Furthermore, superoxide dismutase (SOD1 and 2) enzymes, localised within cerebellar neurons, are up-regulated, yet the activation of subsequent enzymes responsible for the detoxification of hydrogen peroxide, catalase and glutathione peroxidase are relatively deficient. These studies provide evidence for oxidative injury in MS cerebellar GM and further help define disease mechanisms within the MS brain. PMID:27086975

  7. Altered cerebellar connectivity in Parkinson's patients ON and OFF L-DOPA medication

    PubMed Central

    Festini, Sara B.; Bernard, Jessica A.; Kwak, Youngbin; Peltier, Scott; Bohnen, Nicolaas I.; Müller, Martijn L. T. M.; Dayalu, Praveen; Seidler, Rachael D.

    2015-01-01

    Although nigrostriatal changes are most commonly affiliated with Parkinson's disease, the role of the cerebellum in Parkinson's has become increasingly apparent. The present study used lobule-based cerebellar resting state functional connectivity to (1) compare cerebellar-whole brain and cerebellar-cerebellar connectivity in Parkinson's patients both ON and OFF L-DOPA medication and controls, and to (2) relate variations in cerebellar connectivity to behavioral performance. Results indicated that, when contrasted to the control group, Parkinson's patients OFF medication had increased levels of cerebellar-whole brain and cerebellar-cerebellar connectivity, whereas Parkinson's patients ON medication had decreased levels of cerebellar-whole brain and cerebellar-cerebellar connectivity. Moreover, analyses relating levels of cerebellar connectivity to behavioral measures demonstrated that, within each group, increased levels of connectivity were most often associated with improved cognitive and motor performance, but there were several instances where increased connectivity was related to poorer performance. Overall, the present study found medication-variant cerebellar connectivity in Parkinson's patients, further demonstrating cerebellar changes associated with Parkinson's disease and the moderating effects of medication. PMID:25954184

  8. Cerebellar-Motor Dysfunction in Schizophrenia and Psychosis-Risk: The Importance of Regional Cerebellar Analysis Approaches

    PubMed Central

    Bernard, Jessica A.; Mittal, Vijay A.

    2014-01-01

    Motor abnormalities in individuals with schizophrenia and those at-risk for psychosis are well documented. An accumulating body of work has also highlighted motor abnormalities related to cerebellar dysfunction in schizophrenia including eye-blink conditioning, timing, postural control, and motor learning. We have also recently found evidence for motor dysfunction in individuals at ultra high-risk for psychosis (1–3). This is particularly relevant as the cerebellum is thought to be central to the cognitive dysmetria model of schizophrenia, and these overt motor signs may point to more general cerebellar dysfunction in the etiology of psychotic disorders. While studies have provided evidence indicative of motor cerebellar dysfunction in at-risk populations and in schizophrenia, findings with respect to the cerebellum have been mixed. One factor potentially contributing to these mixed results is the whole-structure approach taken when investigating the cerebellum. In non-human primates, there are distinct closed-loop circuits between the cerebellum, thalamus, and brain with motor and non-motor cortical regions. Recent human neuroimaging has supported this finding and indicates that there is a cerebellar functional topography (4), and this information is being missed with whole-structure approaches. Here, we review cerebellar-motor dysfunction in individuals with schizophrenia and those at-risk for psychosis. We also discuss cerebellar abnormalities in psychosis, and the cerebellar functional topography. Because of the segregated functional regions of the cerebellum, we propose that it is important to look at the structure regionally in order to better understand its role in motor dysfunction in these populations. This is analogous to approaches taken with the basal ganglia, where each region is considered separately. Such an approach is necessary to better understand cerebellar pathophysiology on a macro-structural level with respect to the pathogenesis of

  9. Modulatory effects of serotonin on glutamatergic synaptic transmission and long-term depression in the deep cerebellar nuclei.

    PubMed

    Murano, M; Saitow, F; Suzuki, H

    2011-01-13

    The deep cerebellar nuclei (DCN) are the terminal components of the cerebellar circuitry and constitute its primary output structure. Their activity is important for certain forms of motor learning as well as generation and control of movement. DCN neurons receive glutamatergic excitatory inputs from the pontine nuclei via mossy fibres (MFs) and concomitantly receive inputs from 5-HT-containing neurons of the raphe nuclei. We aimed to explore the roles of 5-HT at MF-DCN synapses by using cerebellar slices from 11 to 15-day-old rats. Bath application of 5-HT reversibly decreased the amplitude of stimulation-evoked excitatory postsynaptic currents (eEPSCs) via the activation of 5-HT1B receptors at the presynaptic terminals of the MFs. Burst stimulation of the MFs elicited long-term depression (LTD) at the MF-DCN synapses that require activation of the group I metabotropic glutamate receptor (mGluR). In the presence of 5-HT, the extent of burst-induced LTD of MF EPSCs was significantly reduced. Application of 5-HT also decreased the amplitude of mGluR-dependent slow EPSCs evoked by similar burst stimulation. Furthermore, (S)-3,5-dihydroxyphenylglycine (DHPG), a group I mGluR agonist, induced chemical LTD of MF EPSCs, and 5-HT had no significant effect on this LTD. Taken together, the results suggest that 5-HT not only has transitory inhibitory effects on MF EPSCs but also plays a role in regulating the long-term synaptic efficacy. PMID:20969929

  10. TISSUE SLICES IN THE STUDY OF LUNG METABOLISM AND TOXICOLOGY

    EPA Science Inventory

    Lung tissue slices are model systems for the study of pulmonary metabolism. Because of the speed and simplicity of slice preparation, lung slices have been used in studies of oxygen, amino acid, carbohydrate and lipid utilization and adenine nucleotide metabolism. Dose-response c...

  11. Visible Human Slice Web Server: a first assessment

    NASA Astrophysics Data System (ADS)

    Hersch, Roger D.; Gennart, Benoit A.; Figueiredo, Oscar; Mazzariol, Marc; Tarraga, Joaquin; Vetsch, S.; Messerli, Vincent; Welz, R.; Bidaut, Luc M.

    1999-12-01

    The Visible Human Slice Server started offering its slicing services at the end of June 1998. From that date until the end of May, more than 280,000 slices were extracted from the Visible Man, by layman interested in anatomy, by students and by specialists. The Slice Server is based one Bi-Pentium PC and 16 disks. It is a scaled down version of a powerful parallel server comprising 5 Bi-Pentium Pro PCs and 60 disks. The parallel server program was created thanks to a computer-aided parallelization framework, which takes over the task of creating a multi-threaded pipelined parallel program from a high-level parallel program description. On the full blown architecture, the parallel program enables the extraction and resampling of up to 5 color slices per second. Extracting 5 slice/s requires to access the disks and extract subvolumes of the Visible Human at an aggregate throughput of 105 MB/s. The publicly accessible server enables to extract slices having any orientation. The slice position and orientation can either be specified for each slice separately or as a position and orientation offered by a Java applet and possible future improvements. In the very near future, the Web Slice Server will offer additional services, such as the possibility to extract ruled surfaces and to extract animations incorporating slices perpendicular to a user defined trajectory.

  12. Role of cerebellar adrenomedullin in blood pressure regulation.

    PubMed

    Figueira, Leticia; Israel, Anita

    2015-12-01

    Adrenomedullin (AM) and their receptor components, calcitonin-receptor-like receptor (CRLR) and receptor activity-modifying protein (RAMP1, RMP2 and RAMP3) are widely expressed in the central nervous system, including cerebellum. We have shown that AM binding sites are altered in cerebellum during hypertension, suggesting a role for cerebellar adrenomedullinergic system in blood pressure regulation. To further evaluate the role of AM in cerebellum, we assessed the expression of AM, RAMP1, RAMP2, RAMP3 and CRLR in the cerebellar vermis of 8 and 16week old spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. In addition, the effect of microinjection of AM into rat cerebellar vermis on arterial blood pressure (BP) was determined. Animals were sacrificed by decapitation and cerebellar vermis was dissected for quantification of AM, CRLR, RAMP1, RAMP2 and RAMP3 expression using western blot analysis. Another group of male, 16week old SHR and WKY rats was anesthetized, and a cannula was implanted in the cerebellar vermis. Following recovery AM (0.02 to 200pmol/5μL) or vehicle was injected into cerebellar vermis. BP was determined, before and after treatments, by non-invasive plethysmography. In addition, to establish the receptor subtype involved in AM action in vivo, animals received microinjections of AM22-52 (200pmol/5μL), an AM1 receptor antagonist, or the CGRP1 receptor antagonist, CGRP8-37 (200pmol/5μL) into the cerebellar vermis, administered simultaneously with AM or vehicle microinjection. Cannulation was verified post mortem with the in situ injection of a dye solution. Our findings demonstrated that the expression of CRLR, RAMP1 and RAMP3 was higher in cerebellum of SHR rats, while AM and RAMP2 expression was lower than those of WKY rats, both in 8 and 16week old rats. In vivo microinjection of AM into the cerebellar vermis caused a profound, dose dependent, hypotensive effect in SHR but not in normotensive WKY rats. Coinjections of a

  13. Cerebellar control of postural scaling and central set in stance.

    PubMed

    Horak, F B; Diener, H C

    1994-08-01

    1. The effects of cerebellar deficits in humans on scaling the magnitude of automatic postural responses based on sensory feedback and on predictive central set was investigated. Electromyographic (EMG) and surface reactive torques were compared in patients with anterior lobe cerebellar disorders and in normal healthy adults exposed to blocks of four velocities and five amplitudes of surface translations during stance. Correlations between the earliest postural responses (integrated EMG and initial rate of change of torque) and translation velocity provided a measure of postural magnitude scaling using sensory information from the current displacement. Correlations of responses with translation amplitude provided a measure of scaling dependent on predictive central set based on sequential experience with previous like displacements because the earliest postural responses occurred before completion of the displacements and because scaling to displacement amplitude disappeared when amplitudes were randomized in normal subjects. 2. Responses of cerebellar patients to forward body sway induced by backward surface displacements were hypermetric, that is, surface-reactive torque responses were two to three times larger than normal with longer muscle bursts resulting in overshooting of initial posture. Despite this postural hypermetria, the absolute and relative latencies of agonist muscle bursts at the ankle, knee, and hip were normal in cerebellar patients. 3. Although they were hypermetric, the earliest postural responses of cerebellar patients were scaled normally to platform displacement velocities using somatosensory feedback. Cerebellar patients, however, were unable to scale initial postural response magnitude to expected displacement amplitudes based on prior experience using central set. Randomization of displacement amplitudes eliminated the set effect of amplitude on initial responses in normal subjects, but responses to randomized and blocked trials were not

  14. Disruptive SCYL1 Mutations Underlie a Syndrome Characterized by Recurrent Episodes of Liver Failure, Peripheral Neuropathy, Cerebellar Atrophy, and Ataxia

    PubMed Central

    Schmidt, Wolfgang M.; Rutledge, S. Lane; Schüle, Rebecca; Mayerhofer, Benjamin; Züchner, Stephan; Boltshauser, Eugen; Bittner, Reginald E.

    2015-01-01

    Hereditary ataxias comprise a group of genetically heterogeneous disorders characterized by clinically variable cerebellar dysfunction and accompanied by involvement of other organ systems. The molecular underpinnings for many of these diseases are widely unknown. Previously, we discovered the disruption of Scyl1 as the molecular basis of the mouse mutant mdf, which is affected by neurogenic muscular atrophy, progressive gait ataxia with tremor, cerebellar vermis atrophy, and optic-nerve thinning. Here, we report on three human individuals, from two unrelated families, who presented with recurrent episodes of acute liver failure in early infancy and are affected by cerebellar vermis atrophy, ataxia, and peripheral neuropathy. By whole-exome sequencing, compound-heterozygous mutations within SCYL1 were identified in all affected individuals. We further show that in SCYL1-deficient human fibroblasts, the Golgi apparatus is massively enlarged, which is in line with the concept that SCYL1 regulates Golgi integrity. Thus, our findings define SCYL1 mutations as the genetic cause of a human hepatocerebellar neuropathy syndrome. PMID:26581903

  15. Disruptive SCYL1 Mutations Underlie a Syndrome Characterized by Recurrent Episodes of Liver Failure, Peripheral Neuropathy, Cerebellar Atrophy, and Ataxia.

    PubMed

    Schmidt, Wolfgang M; Rutledge, S Lane; Schüle, Rebecca; Mayerhofer, Benjamin; Züchner, Stephan; Boltshauser, Eugen; Bittner, Reginald E

    2015-12-01

    Hereditary ataxias comprise a group of genetically heterogeneous disorders characterized by clinically variable cerebellar dysfunction and accompanied by involvement of other organ systems. The molecular underpinnings for many of these diseases are widely unknown. Previously, we discovered the disruption of Scyl1 as the molecular basis of the mouse mutant mdf, which is affected by neurogenic muscular atrophy, progressive gait ataxia with tremor, cerebellar vermis atrophy, and optic-nerve thinning. Here, we report on three human individuals, from two unrelated families, who presented with recurrent episodes of acute liver failure in early infancy and are affected by cerebellar vermis atrophy, ataxia, and peripheral neuropathy. By whole-exome sequencing, compound-heterozygous mutations within SCYL1 were identified in all affected individuals. We further show that in SCYL1-deficient human fibroblasts, the Golgi apparatus is massively enlarged, which is in line with the concept that SCYL1 regulates Golgi integrity. Thus, our findings define SCYL1 mutations as the genetic cause of a human hepatocerebellar neuropathy syndrome. PMID:26581903

  16. Trafficking of astrocytic vesicles in hippocampal slices

    SciTech Connect

    Potokar, Maja; Kreft, Marko; Celica Biomedical Center, Technology Park 24, 1000 Ljubljana ; Lee, So-Young; Takano, Hajime; Haydon, Philip G.; Zorec, Robert; Celica Biomedical Center, Technology Park 24, 1000 Ljubljana

    2009-12-25

    The increasingly appreciated role of astrocytes in neurophysiology dictates a thorough understanding of the mechanisms underlying the communication between astrocytes and neurons. In particular, the uptake and release of signaling substances into/from astrocytes is considered as crucial. The release of different gliotransmitters involves regulated exocytosis, consisting of the fusion between the vesicle and the plasma membranes. After fusion with the plasma membrane vesicles may be retrieved into the cytoplasm and may continue to recycle. To study the mobility implicated in the retrieval of secretory vesicles, these structures have been previously efficiently and specifically labeled in cultured astrocytes, by exposing live cells to primary and secondary antibodies. Since the vesicle labeling and the vesicle mobility properties may be an artifact of cell culture conditions, we here asked whether the retrieving exocytotic vesicles can be labeled in brain tissue slices and whether their mobility differs to that observed in cell cultures. We labeled astrocytic vesicles and recorded their mobility with two-photon microscopy in hippocampal slices from transgenic mice with fluorescently tagged astrocytes (GFP mice) and in wild-type mice with astrocytes labeled by Fluo4 fluorescence indicator. Glutamatergic vesicles and peptidergic granules were labeled by the anti-vesicular glutamate transporter 1 (vGlut1) and anti-atrial natriuretic peptide (ANP) antibodies, respectively. We report that the vesicle mobility parameters (velocity, maximal displacement and track length) recorded in astrocytes from tissue slices are similar to those reported previously in cultured astrocytes.

  17. [Steroid therapy for hydrocephalus due to acute cerebellitis in a child].

    PubMed

    Tabarki, B; Thabet, F

    2007-08-01

    Severe acute inflammatory cerebellitis is a rare but life threatening disease. We report the case of a 8-year-old boy presenting with cerebellitis and acute cerebellar swelling complicated by brain stem compression and hydrocephalus. Outcome was good on steroid therapy. PMID:17498931

  18. Brain Slices as Models for Neurodegenerative Disease and Screening Platforms to Identify Novel Therapeutics

    PubMed Central

    Cho, Seongeun; Wood, Andrew; Bowlby, Mark R

    2007-01-01

    Recent improvements in brain slice technology have made this biological preparation increasingly useful for examining pathophysiology of brain diseases in a tissue context. Brain slices maintain many aspects of in vivo biology, including functional local synaptic circuitry with preserved brain architecture, while allowing good experimental access and precise control of the extracellular environment, making them ideal platforms for dissection of molecular pathways underlying neuronal dysfunction. Importantly, these ex vivo systems permit direct treatment with pharmacological agents modulating these responses and thus provide surrogate therapeutic screening systems without recourse to whole animal studies. Virus or particle mediated transgenic expression can also be accomplished relatively easily to study the function of novel genes in a normal or injured brain tissue context. In this review we will discuss acute brain injury models in organotypic hippocampal and co-culture systems and the effects of pharmacological modulation on neurodegeneration. The review will also cover the evidence of developmental plasticity in these ex vivo models, demonstrating emergence of injury-stimulated neuronal progenitor cells, and neurite sprouting and axonal regeneration following pathway lesioning. Neuro-and axo-genesis are emerging as significant factors contributing to brain repair following many acute and chronic neurodegenerative disorders. Therefore brain slice models may provide a critical contextual experimental system to explore regenerative mechanisms in vitro. PMID:18615151

  19. A Cerebellar Neuroprosthetic System: Computational Architecture and in vivo Test.

    PubMed

    Herreros, Ivan; Giovannucci, Andrea; Taub, Aryeh H; Hogri, Roni; Magal, Ari; Bamford, Sim; Prueckl, Robert; Verschure, Paul F M J

    2014-01-01

    Emulating the input-output functions performed by a brain structure opens the possibility for developing neuroprosthetic 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 neuroprosthetic 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 toward replacing lost functions of the central nervous system via neuroprosthetics, 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 neuroprosthetic system directly validates a theory of cerebellar learning that informed the design of the system, and on the other one it takes a step toward the development of neuro-prostheses that could recover lost learning functions in animals and, in the longer term, humans. PMID:25152887

  20. A Cerebellar Neuroprosthetic System: Computational Architecture and in vivo Test

    PubMed Central

    Herreros, Ivan; Giovannucci, Andrea; Taub, Aryeh H.; Hogri, Roni; Magal, Ari; Bamford, Sim; Prueckl, Robert; Verschure, Paul F. M. J.

    2014-01-01

    Emulating the input–output functions performed by a brain structure opens the possibility for developing neuroprosthetic 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 neuroprosthetic 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 toward replacing lost functions of the central nervous system via neuroprosthetics, 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 neuroprosthetic system directly validates a theory of cerebellar learning that informed the design of the system, and on the other one it takes a step toward the development of neuro-prostheses that could recover lost learning functions in animals and, in the longer term, humans. PMID:25152887

  1. Cerebellar hypoplasia of genetic origin in calves.

    PubMed

    O'Sullivan, B M; McPhee, C P

    1975-10-01

    Within 2 years, following the introduction of 2 Shorthorn bulls from the same stud into an Australian Illawarra Shorthorn (AIS) herd, 16 calves were born with cerebellar hypoplasia. All affected calves were the progeny of one bull mated to the daughters of the other. All other progeny of these bulls, most of which were from AIS dams, were normal. Affected calves exhibited severe ataxia, consistent head movement and abduction of the forelimbs. Microscopic changes in the cerebellum included sparsity of cells of the granular layer, loss of Purkinje cells and narrowing of the molecular layer. Observations on the frequencies of normal and abnormal calves are consistent with the hypothesis that the condition is caused by an autosomal recessive gene for which affected calves were homozygous and which was introduced into the herd in heterozygous condition by both of the Shorthorn bulls. Evidence is given for an unusually high frequency of the gene in the stud of origin of the Shorthorn bulls and a procedure for reducing its frequency is outlined. The possibility of a viral or toxic aetiology is discussed but is considered to be an unlikely explanation for the condition in this herd. PMID:1200928

  2. Multiplexed coding by cerebellar Purkinje neurons

    PubMed Central

    Hong, Sungho; Negrello, Mario; Junker, Marc; Smilgin, Aleksandra; Thier, Peter; De Schutter, Erik

    2016-01-01

    Purkinje cells (PC), the sole output neurons of the cerebellar cortex, encode sensorimotor information, but how they do it remains a matter of debate. Here we show that PCs use a multiplexed spike code. Synchrony/spike time and firing rate encode different information in behaving monkeys during saccadic eye motion tasks. Using the local field potential (LFP) as a probe of local network activity, we found that infrequent pause spikes, which initiated or terminated intermittent pauses in simple spike trains, provide a temporally reliable signal for eye motion onset, with strong phase-coupling to the β/γ band LFP. Concurrently, regularly firing, non-pause spikes were weakly correlated with the LFP, but were crucial to linear encoding of eye movement kinematics by firing rate. Therefore, PC spike trains can simultaneously convey information necessary to achieve precision in both timing and continuous control of motion. DOI: http://dx.doi.org/10.7554/eLife.13810.001 PMID:27458803

  3. Morphological characteristics of the superior cerebellar artery.

    PubMed

    Dodevski, A; Tosovska Lazarova, D; Zhivadinovik, J; Lazareska, M; Stojovska-Jovanovska, E

    2015-01-01

    With the introduction of new techniques in diagnostic and interventional radiology and progress in micro neurosurgery, accurate knowledge of the brain blood vessels is essential for daily clinical work. The aim of this study was to describe the morphological characteristics of the superior cerebellar artery and to emphasize their clinical significance. In this study we examined radiographs of 109 patients who had CT angiography at the University Clinic for Radiology in Skopje, R. Macedonia. This study included 49 females and 60 males, ranging in age from 27 to 83 years; mean age 57.4 ± 11.8 years. In 105 patients SCA arose from the basilar artery on both sides as a single vessel. In two patients SCA arose as a duplicate trunk from the basilar artery. We found unilateral duplication on the right SCA in one patient, and bilateral duplication in one patient. In two patients was noticed origin of the SCA from PCA as a single trunk from adult type of the PCA. Through knowledge of the anatomy and variations of SCA is important for clinicians as well as basic scientists who deal with problems related to intracranial vasculature in daily basis for save performance of diagnostic and interventional procedures. PMID:26076777

  4. Acute hemicerebellitis in a young adult: a case report and literature review.

    PubMed

    Suzuki, Keisuke; Nakamura, Toshiki; Numao, Ayaka; Fujita, Hiroaki; Komagamine, Tomoko; Nagashima, Takahide; Asakawa, Yohei; Watanabe, Yuji; Takekawa, Hidehiro; Hirata, Koichi

    2014-12-15

    Acute hemicerebellitis, marked by headache with or without cerebellar signs, is a rare clinical entity involving a unilateral cerebellar hemisphere. The pathogenesis of acute hemicerebellitis remains unclear, and the disease rarely occurs in adults. Here, we report an 18-year-old woman who presented with a lack of coordination of the right hand and leg lasting longer than one week, following a pulsatile headache. A neurological examination disclosed ocular dysmetria, right-sided limb ataxia and slight truncal ataxia. Cerebrospinal fluid analysis showed mononuclear pleocytosis. The serology and autoimmune studies were unremarkable. Brain magnetic resonance imaging (MRI) revealed a focal signal change in the right cerebellar hemisphere and vermis. Acute hemicerebellitis was diagnosed, and the patient was treated with intravenous methylprednisolone sodium succinate and acyclovir. Subsequently, the headache resolved, and the cerebellar signs were markedly improved. Twenty days after admission, she became asymptomatic and brain MRI showed resolution of cerebellar hyperintensity on the right side. In conclusion, we identified only 6 additional patients with adult-onset acute hemicerebellitis from previous reports, highlighting the importance of recognizing this rare clinical entity. Its clinical outcome is usually favorable, but in the acute phase, attention should be directed toward clinical symptoms that are suggestive of increased intracranial pressure. PMID:25454647

  5. Distributed Cerebellar Motor Learning: A Spike-Timing-Dependent Plasticity Model

    PubMed Central

    Luque, Niceto R.; Garrido, Jesús A.; Naveros, Francisco; Carrillo, Richard R.; D'Angelo, Egidio; Ros, Eduardo

    2016-01-01

    Deep cerebellar nuclei neurons receive both inhibitory (GABAergic) synaptic currents from Purkinje cells (within the cerebellar cortex) and excitatory (glutamatergic) synaptic currents from mossy fibers. Those two deep cerebellar nucleus inputs are thought to be also adaptive, embedding interesting properties in the framework of accurate movements. We show that distributed spike-timing-dependent plasticity mechanisms (STDP) located at different cerebellar sites (parallel fibers to Purkinje cells, mossy fibers to deep cerebellar nucleus cells, and Purkinje cells to deep cerebellar nucleus cells) in close-loop simulations provide an explanation for the complex learning properties of the cerebellum in motor learning. Concretely, we propose a new mechanistic cerebellar spiking model. In this new model, deep cerebellar nuclei embed a dual functionality: deep cerebellar nuclei acting as a gain adaptation mechanism and as a facilitator for the slow memory consolidation at mossy fibers to deep cerebellar nucleus synapses. Equipping the cerebellum with excitatory (e-STDP) and inhibitory (i-STDP) mechanisms at deep cerebellar nuclei afferents allows the accommodation of synaptic memories that were formed at parallel fibers to Purkinje cells synapses and then transferred to mossy fibers to deep cerebellar nucleus synapses. These adaptive mechanisms also contribute to modulate the deep-cerebellar-nucleus-output firing rate (output gain modulation toward optimizing its working range). PMID:26973504

  6. Modulation of methylmercury uptake by methionine: Prevention of mitochondrial dysfunction in rat liver slices by a mimicry mechanism

    SciTech Connect

    Roos, Daniel Henrique; Puntel, Robson Luiz; Farina, Marcelo; Aschner, Michael; Bohrer, Denise; Rocha, Joao Batista T.; Vargas Barbosa, Nilda B. de

    2011-04-01

    Methylmercury (MeHg) is an ubiquitous environmental pollutant which is transported into the mammalian cells when present as the methylmercury-cysteine conjugate (MeHg-Cys). With special emphasis on hepatic cells, due to their particular propensity to accumulate an appreciable amount of Hg after exposure to MeHg, this study was performed to evaluate the effects of methionine (Met) on Hg uptake, reactive species (RS) formation, oxygen consumption and mitochondrial function/cellular viability in both liver slices and mitochondria isolated from these slices, after exposure to MeHg or the MeHg-Cys complex. The liver slices were pre-treated with Met (250 {mu}M) 15 min before being exposed to MeHg (25 {mu}M) or MeHg-Cys (25 {mu}M each) for 30 min at 37 {sup o}C. The treatment with MeHg caused a significant increase in the Hg concentration in both liver slices and mitochondria isolated from liver slices. Moreover, the Hg uptake was higher in the group exposed to the MeHg-Cys complex. In the DCF (dichlorofluorescein) assay, the exposure to MeHg and MeHg-Cys produced a significant increase in DFC reactive species (DFC-RS) formation only in the mitochondria isolated from liver slices. As observed with Hg uptake, DFC-RS levels were significantly higher in the mitochondria treated with the MeHg-Cys complex compared to MeHg alone. MeHg exposure also caused a marked decrease in the oxygen consumption of liver slices when compared to the control group, and this effect was more pronounced in the liver slices treated with the MeHg-Cys complex. Similarly, the loss of mitochondrial activity/cell viability was greater in liver slices exposed to the MeHg-Cys complex when compared to slices treated only with MeHg. In all studied parameters, Met pre-treatment was effective in preventing the MeHg- and/or MeHg-Cys-induced toxicity in both liver slices and mitochondria. Part of the protection afforded by Met against MeHg may be related to a direct interaction with MeHg or to the competition

  7. Modulation of methylmercury uptake by methionine: Prevention of mitochondrial dysfunction in rat liver slices by a mimicry mechanism

    PubMed Central

    Roos, Daniel Henrique; Puntel, Robson Luiz; Farina, Marcelo; Aschner, Michael; Bohrer, Denise; Rocha, João Batista T.; de Vargas Barbosa, Nilda B.

    2016-01-01

    Methylmercury (MeHg) is an ubiquitous environmental pollutant which is transported into the mammalian cells when present as the methylmercury-cysteine conjugate (MeHg–Cys). With special emphasis on hepatic cells, due to their particular propensity to accumulate an appreciable amount of Hg after exposure to MeHg, this study was performed to evaluate the effects of methionine (Met) on Hg uptake, reactive species (RS) formation, oxygen consumption and mitochondrial function/cellular viability in both liver slices and mitochondria isolated from these slices, after exposure to MeHg or the MeHg–Cys complex. The liver slices were pre-treated with Met (250 μM) 15 min before being exposed to MeHg (25 μM) or MeHg–Cys (25 μM each) for 30 min at 37 °C. The treatment with MeHg caused a significant increase in the Hg concentration in both liver slices and mitochondria isolated from liver slices. Moreover, the Hg uptake was higher in the group exposed to the MeHg–Cys complex. In the DCF (dichlorofluorescein) assay, the exposure to MeHg and MeHg–Cys produced a significant increase in DFC reactive species (DFC-RS) formation only in the mitochondria isolated from liver slices. As observed with Hg uptake, DFC-RS levels were significantly higher in the mitochondria treated with the MeHg–Cys complex compared to MeHg alone. MeHg exposure also caused a marked decrease in the oxygen consumption of liver slices when compared to the control group, and this effect was more pronounced in the liver slices treated with the MeHg–Cys complex. Similarly, the loss of mitochondrial activity/cell viability was greater in liver slices exposed to the MeHg–Cys complex when compared to slices treated only with MeHg. In all studied parameters, Met pre-treatment was effective in preventing the MeHg-and/or MeHg–Cys-induced toxicity in both liver slices and mitochondria. Part of the protection afforded by Met against MeHg may be related to a direct interaction with MeHg or to the

  8. A Review of Variable Slicing in Fused Deposition Modeling

    NASA Astrophysics Data System (ADS)

    Nadiyapara, Hitesh Hirjibhai; Pande, Sarang

    2016-06-01

    The paper presents a literature survey in the field of fused deposition of plastic wires especially in the field of slicing and deposition using extrusion of thermoplastic wires. Various researchers working in the field of computation of deposition path have used their algorithms for variable slicing. In the study, a flowchart has also been proposed for the slicing and deposition process. The algorithm already been developed by previous researcher will be used to be implemented on the fused deposition modelling machine. To demonstrate the capabilities of the fused deposition modeling machine a case study has been taken. It uses a manipulated G-code to be fed to the fused deposition modeling machine. Two types of slicing strategies, namely uniform slicing and variable slicing have been evaluated. In the uniform slicing, the slice thickness has been used for deposition is varying from 0.1 to 0.4 mm. In the variable slicing, thickness has been varied from 0.1 in the polar region to 0.4 in the equatorial region Time required and the number of slices required to deposit a hemisphere of 20 mm diameter have been compared with that using the variable slicing.

  9. Cerebellar cortex and cerebellar nuclei are concomitantly activated during eyeblink conditioning: a 7T fMRI study in humans.

    PubMed

    Thürling, Markus; Kahl, Fabian; Maderwald, Stefan; Stefanescu, Roxana M; Schlamann, Marc; Boele, Henk-Jan; De Zeeuw, Chris I; Diedrichsen, Jörn; Ladd, Mark E; Koekkoek, Sebastiaan K E; Timmann, Dagmar

    2015-01-21

    There are controversies whether learning of conditioned eyeblink responses primarily takes place within the cerebellar cortex, the interposed nuclei, or both. It has also been suggested that the cerebellar cortex may be important during early stages of learning, and that there is a shift to the cerebellar nuclei during later stages. As yet, human studies have provided little to resolve this question. In the present study, we established a setup that allows ultra-high-field 7T functional magnetic resonance imaging (fMRI) of the cerebellar cortex and interposed cerebellar nuclei simultaneously during delay eyeblink conditioning in humans. Event-related fMRI signals increased concomitantly in the cerebellar cortex and nuclei during early acquisition of conditioned eyeblink responses in 20 healthy human subjects. ANOVAs with repeated-measures showed significant effects of time across five blocks of 20 conditioning trials in the cortex and nuclei (p < 0.05, permutation corrected). Activations were most pronounced in, but not limited to, lobules VI and interposed nuclei. Increased activations were most prominent at the first time the maximum number of conditioned responses was achieved. Our data are consistent with a simultaneous and synergistic two-site model of learning during acquisition of classically conditioned eyeblinks. Because increased MRI signal reflects synaptic activity, concomitantly increased signals in the cerebellar nuclei and cortex are consistent with findings of learning related potentiation at the mossy fiber to nuclear cell synapse and mossy fiber to granule cell synapse. Activity related to the expression of conditioned responses, however, cannot be excluded. PMID:25609637

  10. Protective Effect of Edaravone in Primary Cerebellar Granule Neurons against Iodoacetic Acid-Induced Cell Injury

    PubMed Central

    Zhou, Xinhua; Zhu, Longjun; Wang, Liang; Guo, Baojian; Zhang, Gaoxiao; Sun, Yewei; Zhang, Zaijun; Lee, Simon Ming-Yuen; Yu, Pei; Wang, Yuqiang

    2015-01-01

    Edaravone (EDA) is clinically used for treatment of acute ischemic stroke in Japan and China due to its potent free radical-scavenging effect. However, it has yet to be determined whether EDA can attenuate iodoacetic acid- (IAA-) induced neuronal death in vitro. In the present study, we investigated the effect of EDA on damage of IAA-induced primary cerebellar granule neurons (CGNs) and its possible underlying mechanisms. We found that EDA attenuated IAA-induced cell injury in CGNs. Moreover, EDA significantly reduced intracellular reactive oxidative stress production, loss of mitochondrial membrane potential, and caspase 3 activity induced by IAA. Taken together, EDA protected CGNs against IAA-induced neuronal damage, which may be attributed to its antiapoptotic and antioxidative activities. PMID:26557222

  11. Proteomic analysis of native cerebellar iFGF14 complexes.

    PubMed

    Bosch, Marie K; Nerbonne, Jeanne M; Townsend, R Reid; Miyazaki, Haruko; Nukina, Nobuyuki; Ornitz, David M; Marionneau, Céline

    2016-07-01

    Intracellular Fibroblast Growth Factor 14 (iFGF14) and the other intracellular FGFs (iFGF11-13) regulate the properties and densities of voltage-gated neuronal and cardiac Na(+) (Nav) channels. Recent studies have demonstrated that the iFGFs can also regulate native voltage-gated Ca(2+) (Cav) channels. In the present study, a mass spectrometry (MS)-based proteomic approach was used to identify the components of native cerebellar iFGF14 complexes. Using an anti-iFGF14 antibody, native iFGF14 complexes were immunoprecipitated from wild type adult mouse cerebellum. Parallel control experiments were performed on cerebellar proteins isolated from mice (Fgf14(-/-)) harboring a targeted disruption of the Fgf14 locus. MS analyses of immunoprecipitated proteins demonstrated that the vast majority of proteins identified in native cerebellar iFGF14 complexes are Nav channel pore-forming (α) subunits or proteins previously reported to interact with Nav α subunits. In contrast, no Cav channel α or accessory subunits were revealed in cerebellar iFGF14 immunoprecipitates. Additional experiments were completed using an anti-PanNav antibody to immunoprecipitate Nav channel complexes from wild type and Fgf14(-/-) mouse cerebellum. Western blot and MS analyses revealed that the loss of iFGF14 does not measurably affect the protein composition or the relative abundance of Nav channel interacting proteins in native adult mouse cerebellar Nav channel complexes. PMID:26889602

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

    SciTech Connect

    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.

  13. Motor learning of mice lacking cerebellar Purkinje cells.

    PubMed

    Porras-García, M Elena; Ruiz, Rocío; Pérez-Villegas, Eva M; Armengol, José Á

    2013-01-01

    The cerebellum plays a key role in the acquisition and execution of motor tasks whose physiological foundations were postulated on Purkinje cells' long-term depression (LTD). Numerous research efforts have been focused on understanding the cerebellum as a site of learning and/or memory storage. However, the controversy on which part of the cerebellum participates in motor learning, and how the process takes place, remains unsolved. In fact, it has been suggested that cerebellar cortex, deep cerebellar nuclei, and/or their combination with some brain structures other than the cerebellum are responsible for motor learning. Different experimental approaches have been used to tackle this question (cerebellar lesions, pharmacological agonist and/or antagonist of cerebellar neurotransmitters, virus tract tracings, etc.). One of these approaches is the study of spontaneous mutations affecting the cerebellar cortex and depriving it of its main input-output organizer (i.e., the Purkinje cell). In this review, we discuss the results obtained in our laboratory in motor learning of both Lurcher (Lc/+) and tambaleante (tbl/tbl) mice as models of Purkinje-cell-devoid cerebellum. PMID:23630472

  14. Motor learning of mice lacking cerebellar Purkinje cells

    PubMed Central

    Porras-García, M. Elena; Ruiz, Rocío; Pérez-Villegas, Eva M.; Armengol, José Á.

    2013-01-01

    The cerebellum plays a key role in the acquisition and execution of motor tasks whose physiological foundations were postulated on Purkinje cells' long-term depression (LTD). Numerous research efforts have been focused on understanding the cerebellum as a site of learning and/or memory storage. However, the controversy on which part of the cerebellum participates in motor learning, and how the process takes place, remains unsolved. In fact, it has been suggested that cerebellar cortex, deep cerebellar nuclei, and/or their combination with some brain structures other than the cerebellum are responsible for motor learning. Different experimental approaches have been used to tackle this question (cerebellar lesions, pharmacological agonist and/or antagonist of cerebellar neurotransmitters, virus tract tracings, etc.). One of these approaches is the study of spontaneous mutations affecting the cerebellar cortex and depriving it of its main input–output organizer (i.e., the Purkinje cell). In this review, we discuss the results obtained in our laboratory in motor learning of both Lurcher (Lc/+) and tambaleante (tbl/tbl) mice as models of Purkinje-cell-devoid cerebellum. PMID:23630472

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

    PubMed Central

    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

  16. Presynaptic Calcium Signalling in Cerebellar Mossy Fibres

    PubMed Central

    Thomsen, Louiza B.; Jörntell, Henrik; Midtgaard, Jens

    2009-01-01

    Whole-cell recordings were obtained from mossy fibre terminals in adult turtles in order to characterize the basic membrane properties. Calcium imaging of presynaptic calcium signals was carried out in order to analyse calcium dynamics and presynaptic GABA B inhibition. A tetrodotoxin (TTX)-sensitive fast Na+ spike faithfully followed repetitive depolarizing pulses with little change in spike duration or amplitude, while a strong outward rectification dominated responses to long-lasting depolarizations. High-threshold calcium spikes were uncovered following addition of potassium channel blockers. Calcium imaging using Calcium-Green dextran revealed a stimulus-evoked all-or-none TTX-sensitive calcium signal in simple and complex rosettes. All compartments of a complex rosette were activated during electrical activation of the mossy fibre, while individual simple and complex rosettes along an axon appeared to be isolated from one another in terms of calcium signalling. CGP55845 application showed that GABA B receptors mediated presynaptic inhibition of the calcium signal over the entire firing frequency range of mossy fibres. A paired-pulse depression of the calcium signal lasting more than 1 s affected burst firing in mossy fibres; this paired-pulse depression was reduced by GABA B antagonists. While our results indicated that a presynaptic rosette electrophysiologically functioned as a unit, topical GABA application showed that calcium signals in the branches of complex rosettes could be modulated locally, suggesting that cerebellar glomeruli may be dynamically sub-compartmentalized due to ongoing inhibition mediated by Golgi cells. This could provide a fine-grained control of mossy fibre-granule cell information transfer and synaptic plasticity within a mossy fibre rosette. PMID:20162034

  17. Modelling transfer of Listeria monocytogenes during slicing of 'gravad' salmon.

    PubMed

    Aarnisalo, Kaarina; Sheen, Shiowshuh; Raaska, Laura; Tamplin, Mark

    2007-08-15

    Transfer of a rifampicin-resistant mutant of Listeria monocytogenes from an inoculated slicing blade to slices of 'gravad' salmon (Salmo salar), and from inoculated salmon fillet to the slicing machine and subsequently to slices of uninoculated fillet was studied. The effect of slicing temperature (0 degrees C, 10 degrees C and room temperature), inoculum level (approx. 3, 5 and 8 log CFU/blade), and attachment time of inoculum to blade (10 min and 2.5 h) were investigated and predictive models of the transfer were produced. In the tests of transfer from inoculated blade (5.9-9.0 log CFU/blade) initially 2.5-5.3 log CFU/g was present on the slices, slowly decreasing to an overall average decrease of 1.6+/-0.2 log CFU/g during slicing of 39 slices; the lowest reduction being 1.3 log CFU/g at 0 degrees C. In tests of transfer from contaminated salmon (7.6+/-0.1 log CFU/fillet) to uninoculated blade and further to uninoculated salmon, the reduction in number of L. monocytogenes in slices was 1.5 log CFU/g during slicing of 39 slices. For example 5.3+/-0.3 log CFU/g was transferred to second slice when the inoculum level was 8.4+/-0.4 log CFU/blade, but clearly (p<0.05) lower total number of L. monocytogenes were transferred to slices when the inoculum level was lower, the temperature was colder or the attachment time was longer. There was a progressive exponential reduction in the quantity of L. monocytogenes transferred and, based on statistical parameters, an exponential model (y=ae((-x/b))) fit the data from different test conditions and was suitable for predicting an expected number of L. monocytogenes on the salmon slices. Based on the predicted values, the logarithmic reduction in number of L. monocytogenes in slices was highest at room temperature with an inoculum level of 8.4+/-0.4 log CFU/blade (attachment time 10 min); the other test conditions differed significantly from this (p<0.05). Despite statistically significant differences, in all test conditions

  18. Early Childhood Obesity is Associated with Compromised Cerebellar Development

    PubMed Central

    Miller, Jennifer L; Couch, Jessica; Schwenk, Krista; Long, Michelle; Towler, Stephen; Theriaque, Douglas W; He, Guojun; Liu, Yijun; Driscoll, Daniel J; Leonard, Christiana M

    2009-01-01

    As part of a study investigating commonalities between Prader-Willi syndrome (PWS — a genetic imprinting disorder) and early-onset obesity of unknown etiology (EMO) we measured total cerebral and cerebellar volume on volumetric MRI images. Individuals with PWS (n=16) and EMO (n=12) had smaller cerebellar volumes than a control group of 15 siblings (p=0.02 control vs. EMO; p=0.0005 control vs. PWS), although there was no difference among the groups in cerebral volume. Individuals with PWS and EMO also had impaired cognitive function: general intellectual ability (GIA): PWS 65 ± 25; EMO 81 ± 19; and Controls 112 ± 13 (p<0.0001 controls vs. PWS and controls vs. EMO). As both conditions are characterized by early-onset obesity and slowed cognitive development, these results raise the possibility that early childhood obesity retards both cerebellar and cognitive development. PMID:19437203

  19. Behavioral effects of neonatal lesions on the cerebellar system.

    PubMed

    Lalonde, Robert; Strazielle, Catherine

    2015-06-01

    Several rodent models with spontaneous mutations causing cerebellar pathology are impaired in motor functions during the neonatal period, including Grid2(Lc), Rora(sg), Dab1(scm), Girk2(Wv), Lmx1a(dr-sst), Myo5a(dn), Inpp4a(wbl), and Cacna1a(rol) mice as well as shaker and dystonic rats. Deficits are also evident in murine null mutants such as Zic1, Fgfr1/FgFr2, and Xpa/Ercc8. Behavioral deficits are time-dependent following X-irradiated- or aspiration-induced lesions of the cerebellum in rats. In addition, motor functions are deficient after lesions in cerebellar-related pathways. As in animal subjects, sensorimotor disturbances have been described in children with cerebellar lesions. These results underline the importance of the cerebellum and its connections in the development of motor functions. PMID:25907855

  20. Cerebellar networks with the cerebral cortex and basal ganglia.

    PubMed

    Bostan, Andreea C; Dum, Richard P; Strick, Peter L

    2013-05-01

    The dominant view of cerebellar function has been that it is exclusively concerned with motor control and coordination. Recent findings from neuroanatomical, behavioral, and imaging studies have profoundly changed this view. Neuroanatomical studies using virus transneuronal tracers have demonstrated that cerebellar output reaches vast areas of the neocortex, including regions of prefrontal and posterior parietal cortex. Furthermore, it has recently become clear that the cerebellum is reciprocally connected with the basal ganglia, which suggests that the two subcortical structures are part of a densely interconnected network. Taken together, these findings elucidate the neuroanatomical substrate for cerebellar involvement in non-motor functions mediated by the prefrontal and posterior parietal cortex, as well as in processes traditionally associated with the basal ganglia. PMID:23579055

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

    PubMed Central

    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

    Summary 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 eyeblink conditioning. We find that excitatory output neurons in the interposed nucleus provide efference-copy signals via mossy fibers to the cerebellar cortical zones that belong to the same module, triggering monosynaptic responses in granule and Golgi cells and indirectly inhibiting Purkinje cells. Upon conditioning, the local density of nucleocortical mossy fiber terminals significantly increases. Optogenetic activation and inhibition of nucleocortical fibers in conditioned animals increases and decreases the amplitude of learned eyeblink responses, respectively. Our data show that the excitatory nucleocortical closed-loop circuitry of the cerebellum relays a corollary discharge of premotor signals and suggests an amplifying role of this circuitry in controlling associative motor learning. PMID:26844836

  2. Influence of Thin Slice Reconstruction on CT Brain Perfusion Analysis

    PubMed Central

    Bennink, Edwin; Oosterbroek, Jaap; Horsch, Alexander D.; Dankbaar, Jan Willem; Velthuis, Birgitta K.; Viergever, Max A.; de Jong, Hugo W. A. M.

    2015-01-01

    Objectives Although CT scanners generally allow dynamic acquisition of thin slices (1 mm), thick slice (≥5 mm) reconstruction is commonly used for stroke imaging to reduce data, processing time, and noise level. Thin slice CT perfusion (CTP) reconstruction may suffer less from partial volume effects, and thus yield more accurate quantitative results with increased resolution. Before thin slice protocols are to be introduced clinically, it needs to be ensured that this does not affect overall CTP constancy. We studied the influence of thin slice reconstruction on average perfusion values by comparing it with standard thick slice reconstruction. Materials and Methods From 50 patient studies, absolute and relative hemisphere averaged estimates of cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and permeability-surface area product (PS) were analyzed using 0.8, 2.4, 4.8, and 9.6 mm slice reconstructions. Specifically, the influence of Gaussian and bilateral filtering, the arterial input function (AIF), and motion correction on the perfusion values was investigated. Results Bilateral filtering gave noise levels comparable to isotropic Gaussian filtering, with less partial volume effects. Absolute CBF, CBV and PS were 22%, 14% and 46% lower with 0.8 mm than with 4.8 mm slices. If the AIF and motion correction were based on thin slices prior to reconstruction of thicker slices, these differences reduced to 3%, 4% and 3%. The effect of slice thickness on relative values was very small. Conclusions This study shows that thin slice reconstruction for CTP with unaltered acquisition protocol gives relative perfusion values without clinically relevant bias. It does however affect absolute perfusion values, of which CBF and CBV are most sensitive. Partial volume effects in large arteries and veins lead to overestimation of these values. The effects of reconstruction slice thickness should be taken into account when absolute perfusion values are

  3. Multi-slice imAGe generation using intra-slice paraLLel imaging and Inter-slice shifting (MAGGULLI)

    NASA Astrophysics Data System (ADS)

    Kim, Dongchan; Seo, Hyunseok; Oh, Changheun; Han, Yeji; Park, HyunWook

    2016-02-01

    For acceleration of imaging time, multi-band imaging techniques (e.g. CAIPIRINHA) use the sensitivity differences of the multi-channel RF coils in the slice selection direction. To more effectively utilize the RF coil characteristics than the conventional multi-band imaging techniques, we propose a new imaging technique, called multi-slice image generation using intra-slice parallel imaging and inter-slice shifting (MAGGULLI). The proposed technique used an inter-slice shifting gradient in slice selection direction to make multi-slice images shift in the frequency encoding direction. Thus, aliasing caused by sub-sampling in the phase encoding direction is orthogonal to that by multi-band imaging with the inter-slice shifting, both of which are resolved by using the sensitivity information of the RF coil. Phantom and in vivo imaging experiments for the acceleration factors up to 10 demonstrate that the quality of the images reconstructed by MAGGULLI are better than that of CAIPIRINHA for high acceleration factors in the qualitative and quantitative analysis.

  4. Spontaneous, synchronized, and corrective timing behavior in cerebellar lesion patients.

    PubMed

    Schwartze, Michael; Keller, Peter E; Kotz, Sonja A

    2016-10-01

    To successfully navigate through and interact with a dynamic environment it is necessary to acquire and use adequate temporal information to guide behavior. Apart from several areas in the cerebral cortex and cortico-striatal networks, the cerebellum has been proposed to engage in the processing of temporal information. Damage to the cerebellum can impair precise event-based temporal processing in motor and non-motor behavior. To further substantiate cerebellar contributions to temporal processing and to explore its specific role in adapting to a dynamic environment, we investigated sensorimotor temporal processing in ten patients with cerebellar lesions and a corresponding number of healthy matched controls. Experimental tasks included simple self-paced repetitive finger-tapping (spontaneous motor tempo), temporally non-adaptive (isochronous pacing) and adaptive (tempo-changing pacing) sensorimotor synchronization with auditory sequences (synchronization-continuation tapping), and a perceptual tempo judgment. The results indicate that patients' performance diverges systematically from controls on several measures. Cerebellar patients demonstrate more variable self-paced tapping, larger negative asynchronies when synchronizing with isochronous pacing sequences, altered automatic error correction responses to tempo changes (phase correction), and decreased perceptual sensitivity to these perturbations, especially for small accelerations. These findings confirm imprecise temporal processing in cerebellar patients, and hint at a specific impairment in the tens-of-milliseconds range preceding critical events, in line with a temporally predictive account of cerebellar function. Moreover, this cerebellar profile complements previous findings concerning dysfunctional temporal processing in basal ganglia patients assessed with the same experimental setup, suggesting structural and functional differentiation within an integrative temporal processing network. PMID:27345424

  5. Modulatory Effects of Theta Burst Stimulation on Cerebellar Nonsomatic Functions

    PubMed Central

    Demirtas-Tatlidede, Asli; Freitas, Catarina; Pascual-Leone, Alvaro; Schmahmann, Jeremy D.

    2011-01-01

    Clinical and functional imaging studies suggest that the cerebellar vermis is involved in the regulation of a range of nonsomatic functions including cardiovascular control, thirst, feeding behavior, and primal emotions. Cerebello-hypothalamic circuits have been postulated to be a potential neuroanatomical substrate underlying this modulation. We tested this putative relationship between the cerebellar vermis and nonsomatic functions by stimulating the cerebellum noninvasively via neuronavigated transcranial magnetic stimulation. In this randomized, counter-balanced, within-subject study, intermittent theta burst stimulation (TBS) was applied on three different days to the vermis and the right and left cerebellar hemispheres of 12 right-handed normal subjects with the aim of modulating activity in the targeted cerebellar structure. TBS-associated changes were investigated via cardiovascular monitoring, a series of emotionally arousing picture stimuli, subjective analog scales for primal emotions, and the Profile of Mood States test. All 36 sessions of cerebellar stimulation were tolerated well without serious adverse events. Cardiovascular monitoring pointed to a mild but significant decrease in heart rate subsequent to vermal stimulation; no changes were detected in systolic or diastolic blood pressure measurements. Subjective ratings detected a significant increase in Thirst and a trend toward increased Appetite following vermal stimulation. These observations are consistent with existing neurophysiological and neuroimaging data indicating a role for the cerebellum in the regulation of visceral responses. In conjunction with the modulatory function of the cerebellum, our results suggest a role for the vermis in somatovisceral integration likely through cerebello-hypothalamic pathways. Further research is warranted to elucidate the potential mechanisms underlying the cerebellar modulation of nonsomatic functions. PMID:21132574

  6. Cerebellar substrates for error correction in motor conditioning.

    PubMed

    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. PMID:11726240

  7. Microglial polarization and plasticity: evidence from organotypic hippocampal slice cultures.

    PubMed

    Ajmone-Cat, Maria Antonietta; Mancini, Melissa; De Simone, Roberta; Cilli, Piera; Minghetti, Luisa

    2013-10-01

    Increasing evidence indicates that "functional plasticity" is not solely a neuronal attribute but a hallmark of microglial cells, the main brain resident macrophage population. Far from being a univocal phenomenon, microglial activation can originate a plethora of functional phenotypes, encompassing the classic M1 proinflammatory and the alternative M2 anti-inflammatory phenotypes. This concept overturns the popular view of microglial activation as a synonym of neurotoxicity and neurogenesis failure in brain disorders. The characterization of the alternative programs is a matter of intense investigation, but still scarce information is available on the course of microglial activation, on the reversibility of the different commitments and on the capability of preserving molecular memory of previous priming stimuli. By using organotypic hippocampal slice cultures as a model, we developed paradigms of stimulation aimed at shedding light on some of these aspects. We show that persistent stimulation of TLR4 signaling promotes an anti-inflammatory response and microglial polarization toward M2-like phenotype. Moreover, acute and chronic preconditioning regimens permanently affect the capability to respond to a later challenge, suggesting the onset of mechanisms of molecular memory. Similar phenomena could occur in the intact brain and differently affect the vulnerability of mature and newborn neurons to noxious signals. PMID:23918452

  8. Cerebellar atrophy in a patient with velocardiofacial syndrome.

    PubMed Central

    Lynch, D R; McDonald-McGinn, D M; Zackai, E H; Emanuel, B S; Driscoll, D A; Whitaker, L A; Fischbeck, K H

    1995-01-01

    Velocardiofacial syndrome and DiGeorge syndrome have not previously been associated with central nervous system degeneration. We report a 34 year old man who presented for neurological evaluation with cerebellar atrophy of unknown aetiology. On historical review, he had neonatal hypocalcaemia, an atrial septal defect, and a corrected cleft palate. His physical examination showed the characteristic facies of velocardiofacial syndrome as well as dysmetria and dysdiadocho-kinesia consistent with cerebellar degeneration. Molecular cytogenetic studies showed a deletion of 22q11.2. This man is the first reported patient with the association of a neurodegenerative disorder and 22q11.2 deletion syndrome. Images PMID:7562973

  9. Bilateral cerebellar dysfunctions in a unilateral meso-diencephalic lesion.

    PubMed Central

    von Cramon, D

    1981-01-01

    The clinical syndrome of a 65-year-old patient with a slit-shaped right-sided meso-diencephalic lesion was analysed. A cerebellar syndrome with limb-kinetic ataxia, intention tremor and hypotonicity in all extremities as well as ataxic dysarthria was found. The disruption of the two cerebello-(rubro)-thalamic pathways probably explained the signs of bilateral cerebellar dysfunction. The uncrossed ascending limb of the right, and the crossed one of the left brachium conjunctivum may have been damaged by the unilateral lesion extending between caudal midbrain and dorsal thalamus. Images PMID:7241166

  10. Movement Disorders Following Cerebrovascular Lesions in Cerebellar Circuits

    PubMed Central

    Choi, Seong-Min

    2016-01-01

    Cerebellar circuitry is important to controlling and modifying motor activity. It conducts the coordination and correction of errors in muscle contractions during active movements. Therefore, cerebrovascular lesions of the cerebellum or its pathways can cause diverse movement disorders, such as action tremor, Holmes’ tremor, palatal tremor, asterixis, and dystonia. The pathophysiology of abnormal movements after stroke remains poorly understood. However, due to the current advances in functional neuroimaging, it has recently been described as changes in functional brain networks. This review describes the clinical features and pathophysiological mechanisms in different types of movement disorders following cerebrovascular lesions in the cerebellar circuits. PMID:27240809

  11. Movement Disorders Following Cerebrovascular Lesions in Cerebellar Circuits.

    PubMed

    Choi, Seong-Min

    2016-05-01

    Cerebellar circuitry is important to controlling and modifying motor activity. It conducts the coordination and correction of errors in muscle contractions during active movements. Therefore, cerebrovascular lesions of the cerebellum or its pathways can cause diverse movement disorders, such as action tremor, Holmes' tremor, palatal tremor, asterixis, and dystonia. The pathophysiology of abnormal movements after stroke remains poorly understood. However, due to the current advances in functional neuroimaging, it has recently been described as changes in functional brain networks. This review describes the clinical features and pathophysiological mechanisms in different types of movement disorders following cerebrovascular lesions in the cerebellar circuits. PMID:27240809

  12. Lactic acidosis associated with cerebellar vermal atrophy and cardiomyopathy.

    PubMed

    Challa, V R; Markesbery, W R; Baumann, R J; Noonan, J A

    1978-08-01

    The association of fluctuating neurological signs and congestive cardiomyopathy with chronic lactic acidosis is described in a 5 1/2 year-old-boy who ultimately succumbed to congestive heart failure. The autopsy findings included severe atrophy of the anterior cerebellar vermis and a hypertrophied heart with left sided endocardial fibroelastosis. Skeletal and cardial muscle calcification was prominent and probably due to the effect of intracellular metabolic alterations associated with lactic acidosis. A review of the literature shows that the combination of cardiomyopathy, isolated atrophy of cerebellar vermis and muscle fiber calcification have not been reported in association with idiopathic lactic acidosis previously. PMID:152418

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

    PubMed

    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. PMID:21073973

  14. ORGANOTYPIC BRAIN SLICE CULTURES: A REVIEW

    PubMed Central

    HUMPEL, C.

    2015-01-01

    In vitro cell cultures are an important tool for obtaining insights into cellular processes in an isolated system and a supplement to in vivo animal experiments. While primary dissociated cultures permit a single homogeneous cell population to be studied, there is a clear need to explore the function of brain cells in a three-dimensional system where the main architecture of the cells is preserved. Thus, organotypic brain slice cultures have proven to be very useful in investigating cellular and molecular processes of the brain in vitro. This review summarizes (1) the historical development of organotypic brain slices focusing on the membrane technology, (2) methodological aspects regarding culturing procedures, age of donors or media, (3) whether the cholinergic neurons serve as a model of neurodegeneration in Alzheimer’s disease, (4) or the nigrostriatal dopaminergic neurons as a model of Parkinson’s disease and (5) how the vascular network can be studied, especially with regard to a synthetic blood–brain barrier. This review will also highlight some limits of the model and give an outlook on future applications. PMID:26254240

  15. Copper sensitivity in dorsal hippocampus slices.

    PubMed

    Leiva, J; Palestini, M; Tetas, M; López, J

    2000-04-01

    The action of copper on the pyramidal neurons in CA1 of the hippocampus is little understood. Our main aim was to study the possible interaction of copper on the synaptic network in CA1 pyramidal neurons. We used Wistar rats hippocampus slices in a recording chamber. The population response ("population of spikes") collected by an extracellular micropipette under baseline conditions served as control. Copper, GABA, bicuculline and picrotoxin were delivered in different experimental conditions to the slice. One, 10 and 100 microM of copper concentration decreased significantly the amplitude and duration of the population spikes in relation to the control response. This effect did not show concentration dependency. Copper in bicuculline medium decreased significantly the duration response in relation to the control response and in relation to copper effect in a free bicuculline medium. This phenomenon emphasizes the copper action on the GABA (B) and (C) receptors. Copper in a picrotoxin medium increased significantly the excitability of the response. This new effect suggests that copper acts on non-GABA receptors, an effect that could be detected when the GABA receptors were inactivated. As a result of these findings it appears that, under our experimental conditions, copper generated transient sensitivity changes in pyramidal neurons of CA1 dorsal hippocampus. PMID:10782257

  16. AMBER: a PIC slice code for DARHT

    NASA Astrophysics Data System (ADS)

    Vay, Jean-Luc; Fawley, William

    1999-11-01

    The accelerator for the second axis of the Dual Axis Radiographic Hydrodynamic Test (DARHT) facility will produce a 4-kA, 20-MeV, 2-μ s output electron beam with a design goal of less than 1000 π mm-mrad normalized transverse emittance and less than 0.5-mm beam centroid motion. In order to study the beam dynamics throughout the accelerator, we have developed a slice Particle-In-Cell code named AMBER, in which the beam is modeled as a time-steady flow, subject to self, as well as external, electrostatic and magnetostatic fields. The code follows the evolution of a slice of the beam as it propagates through the DARHT accelerator lattice, modeled as an assembly of pipes, solenoids and gaps. In particular, we have paid careful attention to non-paraxial phenomena that can contribute to nonlinear forces and possible emittance growth. We will present the model and the numerical techniques implemented, as well as some test cases and some preliminary results obtained when studying emittance growth during the beam propagation.

  17. Early Increase and Late Decrease of Purkinje Cell Dendritic Spine Density in Prion-Infected Organotypic Mouse Cerebellar Cultures

    PubMed Central

    Campeau, Jody L.; Wu, Gengshu; Bell, John R.; Rasmussen, Jay; Sim, Valerie L.

    2013-01-01

    Prion diseases are infectious neurodegenerative diseases associated with the accumulation of protease-resistant prion protein, neuronal loss, spongiform change and astrogliosis. In the mouse model, the loss of dendritic spines is one of the earliest pathological changes observed in vivo, occurring 4–5 weeks after the first detection of protease-resistant prion protein in the brain. While there are cell culture models of prion infection, most do not recapitulate the neuropathology seen in vivo. Only the recently developed prion organotypic slice culture assay has been reported to undergo neuronal loss and the development of some aspects of prion pathology, namely small vacuolar degeneration and tubulovesicular bodies. Given the rapid replication of prions in this system, with protease-resistant prion protein detectable by 21 days, we investigated whether the dendritic spine loss and altered dendritic morphology seen in prion disease might also develop within the lifetime of this culture system. Indeed, six weeks after first detection of protease-resistant prion protein in tga20 mouse cerebellar slice cultures infected with RML prion strain, we found a statistically significant loss of Purkinje cell dendritic spines and altered dendritic morphology in infected cultures, analogous to that seen in vivo. In addition, we found a transient but statistically significant increase in Purkinje cell dendritic spine density during infection, at the time when protease-resistant prion protein was first detectable in culture. Our findings support the use of this slice culture system as one which recapitulates prion disease pathology and one which may facilitate study of the earliest stages of prion disease pathogenesis. PMID:24312586

  18. Metabolism of Red Beet Slices I. Effects of Washing 1

    PubMed Central

    Reed, D. J.; Kolattukudy, P. E.

    1966-01-01

    The changes in relative participation of pathways of glucose catabolism in red beet slices during washing have been examined using specifically 14C labeled glucoses. Washing of these slices brings about an increase in participation of the pentose phosphate pathway. The composition of the washing medium influences slightly the extent of change in pathway participation. The activity level of certain enzymes participating in the initial stages of glucose catabolism has been measured in fresh and washed beet slices. Fresh slices which barely metabolized gluconate were found to have very little 6-phosphogluconate dehydrogenase activity. Washing brings about a dramatic increase in 6-phosphogluconate dehydrogenase activity and this increase was accompanied by a marked increase in the ability of the slices to metabolize gluconate. In red beet slices the TPNH generated via pentose phosphate pathway appears to be utilized for biosynthetic reductions rather than as respiratory substrate. PMID:16656302

  19. Contribution of Somatic and Dendritic SK Channels in the Firing Rate of Deep Cerebellar Nuclei: Implication in Cerebellar Ataxia

    PubMed Central

    Abbasi, Samira; Abbasi, Ataollah; Sarbaz, Yashar; Shahabi, Parviz

    2016-01-01

    Introduction: Loss of inhibitory output from Purkinje cells leads to hyperexcitability of the Deep Cerebellar Nuclei (DCN), which results in cerebellar ataxia. Also, inhibition of small-conductance calcium-activated potassium (SK) channel increases firing rate of DCN, which could cause cerebellar ataxia. Therefore, SK channel activators can be effective in reducing the symptoms of this disease, and used for the treatment of cerebellar ataxia. In this regard, we hypothesized that blockade of SK channels in different compartments of DCN would increase firing rate with different value. The location of these channels has different effects on increasing firing rate. Methods: In this study, multi-compartment computational model of DCN was used. This computational stimulation allowed us to study the changes in the firing activity of DCN neuron without concerns about interfering parameters in the experiment. Results: The simulation results demonstrated that blockade of somatic and dendritic SK channel increased the firing rate of DCN. In addition, after hyperpolarization (AHP) amplitude increased with blocking SK channel, and its regularity and resting potential changed. However, action potentials amplitude and duration had no significant changes. The simulation results illustrated a more significant contribution of SK channels on the dendritic tree to the DCN firing rate. SK channels in the proximal dendrites have more impact on firing rate compared to distal dendrites. Discussion: Therefore, inhibition of SK channel in DCN can cause cerebellar ataxia, and SK channel openers can have a therapeutic effect on cerebellar ataxia. In addition, the location of SK channels could be important in therapeutic goals. Dendritic SK channels can be a more effective target compared to somatic SK channels. PMID:27303600

  20. Evaluation of multiple-session delay eyeblink conditioning comparing patients with focal cerebellar lesions and cerebellar degeneration.

    PubMed

    Gerwig, Marcus; Guberina, Hana; Esser, Anna Catharina; Siebler, Mario; Schoch, Beate; Frings, Markus; Kolb, Florian P; Aurich, Volker; Beck, Andreas; Forsting, Michael; Timmann, Dagmar

    2010-10-15

    The acquisition and timing of delay-conditioned eyeblink responses (CRs) have been shown to be significantly impaired in patients with disorders restricted to the cortex of the superior cerebellum. We were interested if patients improve incidences and timing of CRs across three sessions on three consecutive days. A standard delay paradigm was used in 9 patients with diffuse cerebellar degeneration, 13 patients with ischemic cortical cerebellar lesions and in 13 controls. High-resolution magnetic resonance imaging (MR imaging) was used to ensure that hemispheral lobules VI and/ or Crus I were lesioned in all stroke patients with the interposed nuclei being preserved. On day 1 patients with stroke but not with degenerative disorders showed significant CR acquisition, although total CR incidences remained significantly lower than in controls. No further improvement was visible on days 2 and 3 neither in patients with focal lesions nor in patients with cerebellar degeneration. CRs occurred earlier in cerebellar patients, most pronounced in patients with degenerative disorders. In patients with stroke but not in the degenerative group timing had improved on the third day close to values of the control subjects. Findings show that lesions of the cerebellar cortex produce permanent deficits in the acquisition of delay-conditioned eyeblink responses. Overall, mean CR incidence was higher in focal compared to degenerative disorders, most likely because the critical lobules (VI and Crus I) were lesioned only in part. Intact anterior lobe, which it thought to contribute to CR timing, may explain recovery of disordered timing in focal cerebellar patients. PMID:20385171

  1. The identification of a Pliocene time slice(s) for data/model comparison

    NASA Astrophysics Data System (ADS)

    Haywood, A. M.; Dolan, A. M.; Pickering, S.; Dowsett, H. J.; McClymont, E. L.; Prescott, C.; Salzmann, U.; Hill, D. J.; Hunter, S. J.; Lunt, D. J.; Pope, J. O.; Valdes, P. J.

    2012-12-01

    The characteristics of the mid-Pliocene Warm Period (3.264 to 3.025 Ma BP) have been examined using geological proxies and climate models. Whilst there is agreement between models and data, details of regional climate differ. Uncertainties in prescribed forcings and in proxy data, limit the utility of the interval to understand the dynamics of a warmer than present climate or evaluate models. This uncertainty comes, in part, from the reconstruction of a time slab rather than a time slice, where forcings required by climate models can be more adequately constrained. Here we describe the rationale and approach for identifying a time slice(s) for Pliocene environmental reconstruction. A time slice centred on 3.205 Ma BP (3.204 to 3.207 Ma BP) has been identified as a priority for investigation. It is a warm interval characterised by a negative benthic oxygen isotope excursion (0.21-0.23‰) centred on Marine Isotope Stage KM5c (KM5.3). It occurred during a period of orbital forcing which was very similar to present-day. Climate model simulations indicate that proxy temperature estimates are unlikely to be significantly affected by orbital forcing for at least a precession cycle centred on the time slice, with the North Atlantic being an important exception. As a result, uncertainties in the chronological control of proxy records will only be moderately detrimental to the synthesis of temperature data. Furthermore, proxy estimates are already able to restrict the carbon dioxide increase in the atmosphere to <120 ppmv above the pre-industrial concentration, and sea-level rise to ~22 m ± 10 m higher than present-day.

  2. Multilayer PDMS microfluidic chamber for controlling brain slice microenvironment

    PubMed Central

    Blake, A. J.; Pearce, T. M.; Rao, N. S.; Johnson, S. M.; Williams, J. C.

    2008-01-01

    A novel three-layer microfluidic polydimethylsiloxane (PDMS) device was constructed with two fluid chambers that holds a brain slice in place with microposts while maintaining laminar perfusate flow above and below the slice. Our fabrication technique permits rapid production of PDMS layers that can be applied to brain slices of different shapes and sizes. In this study, the device was designed to fit the shape and thickness (530-700 μm) of a medullary brain slice taken from P0-P4 neonatal rats. Medullary slices in this chamber spontaneously produced rhythmic, respiratory-related motor output for up to 3 h, thereby demonstrating that brain slice viability was maintained for prolonged periods. This design is unique in that it achieves independent control of fluids through multiple channels in two separate fluid chambers. The laminar flow exhibited by the microfluidic chamber allows controlled solutions to target specific areas of the brain slice based on the input flow rates. To demonstrate this capability, a stream of Na+-free solution was focused on one half of a medullary slice to abolish spontaneous neural activity in only that half of the brain slice, while the other half remained active. We also demonstrated that flow of different solutions can be focused over the midline of the brain slice. The multilayer brain slice chamber design can integrate several traditional types of electrophysiology tools that are commonly used to measure neurophysiological properties of brain slices. Thus, this new microfluidic chamber is advantageous for experiments that involve controlled drug or solution delivery at high spatiotemporal resolution. PMID:17594002

  3. SLICE/MARC-O: Description of Services. Second Revised Edition.

    ERIC Educational Resources Information Center

    Oklahoma State Dept. of Libraries, Oklahoma City.

    Following the discussions of: what is SLICE, what is MARC, what is MARC-O, and what is SLICE/MARC-O are descriptions of the five services offered by SLICE/MARC-O. These services are: (1) cataloging data search and print, (2) MARC record and search and copy, (3) standard S.D.I. current awareness, (4) custom S.D.I. current awareness and (5) SLICE…

  4. Slice sampling technique in Bayesian extreme of gold price modelling

    NASA Astrophysics Data System (ADS)

    Rostami, Mohammad; Adam, Mohd Bakri; Ibrahim, Noor Akma; Yahya, Mohamed Hisham

    2013-09-01

    In this paper, a simulation study of Bayesian extreme values by using Markov Chain Monte Carlo via slice sampling algorithm is implemented. We compared the accuracy of slice sampling with other methods for a Gumbel model. This study revealed that slice sampling algorithm offers more accurate and closer estimates with less RMSE than other methods . Finally we successfully employed this procedure to estimate the parameters of Malaysia extreme gold price from 2000 to 2011.

  5. Constant mean curvature slicings of Kantowski-Sachs spacetimes

    SciTech Connect

    Heinzle, J. Mark

    2011-04-15

    We investigate existence, uniqueness, and the asymptotic properties of constant mean curvature (CMC) slicings in vacuum Kantowski-Sachs spacetimes with positive cosmological constant. Since these spacetimes violate the strong energy condition, most of the general theorems on CMC slicings do not apply. Although there are in fact Kantowski-Sachs spacetimes with a unique CMC foliation or CMC time function, we prove that there also exist Kantowski-Sachs spacetimes with an arbitrary number of (families of) CMC slicings. The properties of these slicings are analyzed in some detail.

  6. Analysis of Slice Transverse Emittance Evolution ina Photocathode RF Gun

    SciTech Connect

    Huang, Z.; Ding, Y.; Qiang, J.; /LBL, Berkeley

    2007-10-17

    The slice transverse emittance of an electron beam is of critical significance for an x-ray FEL. In a photocathode RF gun, the slice transverse emittance is not only determined by the emission process, but also influenced strongly by the non-linear space charge effect. In this paper, we study the slice transverse emittance evolution in a photocathode RF gun using a simple model that includes effects of RF acceleration, focusing, and space charge force. The results are compared with IMPACT-T space charge simulations and may be used to understand the development of the slice emittance in an RF gun.

  7. Cerebellar Damage Produces Selective Deficits in Verbal Working Memory

    ERIC Educational Resources Information Center

    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…

  8. Neurodevelopmental Outcomes in Children with Cerebellar Malformations: A Systematic Review

    ERIC Educational Resources Information Center

    Bolduc, Marie-Eve; Limperopoulos, Catherine

    2009-01-01

    Cerebellar malformations are increasingly diagnosed in the fetal period. Consequently, their consideration requires stressful and often critical decisions from both clinicians and families. This has resulted in an emergent need to understand better the impact of these early life lesions on child development. We performed a comprehensive literature…

  9. Predicting and correcting ataxia using a model of cerebellar function

    PubMed Central

    Bhanpuri, Nasir H.; Okamura, Allison M.

    2014-01-01

    Cerebellar damage results in uncoordinated, variable and dysmetric movements known as ataxia. Here we show that we can reliably model single-joint reaching trajectories of patients (n = 10), reproduce patient-like deficits in the behaviour of controls (n = 11), and apply patient-specific compensations that improve reaching accuracy (P < 0.02). Our approach was motivated by the theory that the cerebellum is essential for updating and/or storing an internal dynamic model that relates motor commands to changes in body state (e.g. arm position and velocity). We hypothesized that cerebellar damage causes a mismatch between the brain’s modelled dynamics and the actual body dynamics, resulting in ataxia. We used both behavioural and computational approaches to demonstrate that specific cerebellar patient deficits result from biased internal models. Our results strongly support the idea that an intact cerebellum is critical for maintaining accurate internal models of dynamics. Importantly, we demonstrate how subject-specific compensation can improve movement in cerebellar patients, who are notoriously unresponsive to treatment. PMID:24812203

  10. Cortical networks of procedural learning: evidence from cerebellar damage.

    PubMed

    Torriero, Sara; Oliveri, Massimiliano; Koch, Giacomo; Lo Gerfo, Emanuele; Salerno, Silvia; Petrosini, Laura; Caltagirone, Carlo

    2007-03-25

    The lateral cerebellum plays a critical role in procedural learning that goes beyond the strict motor control functions attributed to it. Patients with cerebellar damage show marked impairment in the acquisition of procedures, as revealed by their performance on the serial reaction time task (SRTT). Here we present the case of a patient affected by ischemic damage involving the left cerebellum who showed a selective deficit in procedural learning while performing the SRTT with the left hand. The deficit recovered when the cortical excitability of an extensive network involving both cerebellar hemispheres and the dorsolateral prefrontal cortex (DLPFC) was decreased by low-frequency repetitive transcranial magnetic stimulation (rTMS). Although inhibition of the right DLPFC or a control fronto-parietal region did not modify the patient's performance, inhibition of the right (unaffected) cerebellum and the left DLPFC markedly improved task performance. These findings could be explained by the modulation of a set of inhibitory and excitatory connections between the lateral cerebellum and the contralateral prefrontal area induced by rTMS. The presence of left cerebellar damage is likely associated with a reduced excitatory drive from sub-cortical left cerebellar nuclei towards the right DLPFC, causing reduced excitability of the right DLPFC and, conversely, unbalanced activation of the left DLPFC. Inhibition of the left DLPFC would reduce the unbalancing of cortical activation, thus explaining the observed selective recovery of procedural memory. PMID:17166525

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

    PubMed

    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. PMID:26209844

  12. Cerebellar Zonal Patterning Relies on Purkinje Cell Neurotransmission

    PubMed Central

    White, Joshua J.; Arancillo, Marife; Stay, Trace L.; George-Jones, Nicholas A.; Levy, Sabrina L.; Heck, Detlef H.

    2014-01-01

    Cerebellar circuits are patterned into an array of topographic parasagittal domains called zones. The proper connectivity of zones is critical for motor coordination and motor learning, and in several neurological diseases cerebellar circuits degenerate in zonal patterns. Despite recent advances in understanding zone function, we still have a limited understanding of how zones are formed. Here, we focused our attention on Purkinje cells to gain a better understanding of their specific role in establishing zonal circuits. We used conditional mouse genetics to test the hypothesis that Purkinje cell neurotransmission is essential for refining prefunctional developmental zones into sharp functional zones. Our results show that inhibitory synaptic transmission in Purkinje cells is necessary for the precise patterning of Purkinje cell zones and the topographic targeting of mossy fiber afferents. As expected, blocking Purkinje cell neurotransmission caused ataxia. Using in vivo electrophysiology, we demonstrate that loss of Purkinje cell communication altered the firing rate and pattern of their target cerebellar nuclear neurons. Analysis of Purkinje cell complex spike firing revealed that feedback in the cerebellar nuclei to inferior olive to Purkinje cell loop is obstructed. Loss of Purkinje neurotransmission also caused ectopic zonal expression of tyrosine hydroxylase, which is only expressed in adult Purkinje cells when calcium is dysregulated and if excitability is altered. Our results suggest that Purkinje cell inhibitory neurotransmission establishes the functional circuitry of the cerebellum by patterning the molecular zones, fine-tuning afferent circuitry, and shaping neuronal activity. PMID:24920627

  13. Speech and oral motor learning in individuals with cerebellar atrophy.

    PubMed

    Schulz, G M; Dingwall, W O; Ludlow, C L

    1999-10-01

    The purpose of this study was to determine whether cerebellar pathology interferes with motor learning for either speech or novel tasks. Practice effects were contrasted between persons with cerebellar cortical atrophy (CCA) and control participants on previously learned real speech, nonsense speech, and novel nonspeech oral-movement tasks. Studies of limb motor learning suggested that control participants would evidence reduced variability, increased speed of movement, and reduced movement amplitude with practice as compared with the CCA group. No significant differences were found between the real- and nonsense-speech tasks. For both speech tasks, although neither group reduced their movement variability with practice, both groups significantly reduced jaw closing displacement and velocity with practice. For the novel nonspeech oral-movement task, no change with practice was observed in either group in terms of variability, amplitude, or peak velocity. No effects of cerebellar pathology were seen in either the speech- or oral-movement tasks. These results demonstrated that with practice of speech tasks, a previously learned motor skill, movement speed and displacement decreased in both groups. Therefore, the effects of practice differed between previously learned speech tasks and the novel oral-movement task regardless of cerebellar pathology. PMID:10515513

  14. Translational Approach to Behavioral Learning: Lessons from Cerebellar Plasticity

    PubMed Central

    Cheron, Guy; Dan, Bernard; Márquez-Ruiz, Javier

    2013-01-01

    The role of cerebellar plasticity has been increasingly recognized in learning. The privileged relationship between the cerebellum and the inferior olive offers an ideal circuit for attempting to integrate the numerous evidences of neuronal plasticity into a translational perspective. The high learning capacity of the Purkinje cells specifically controlled by the climbing fiber represents a major element within the feed-forward and feedback loops of the cerebellar cortex. Reciprocally connected with the basal ganglia and multimodal cerebral domains, this cerebellar network may realize fundamental functions in a wide range of behaviors. This review will outline the current understanding of three main experimental paradigms largely used for revealing cerebellar functions in behavioral learning: (1) the vestibuloocular reflex and smooth pursuit control, (2) the eyeblink conditioning, and (3) the sensory envelope plasticity. For each of these experimental conditions, we have critically revisited the chain of causalities linking together neural circuits, neural signals, and plasticity mechanisms, giving preference to behaving or alert animal physiology. Namely, recent experimental approaches mixing neural units and local field potentials recordings have demonstrated a spike timing dependent plasticity by which the cerebellum remains at a strategic crossroad for deciphering fundamental and translational mechanisms from cellular to network levels. PMID:24319600

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

    ERIC Educational Resources Information Center

    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…

  16. Grip-load force coordination in cerebellar patients.

    PubMed

    Serrien, D J; Wiesendanger, M

    1999-09-01

    The study examined the anticipatory grip force modulations to load force changes during a drawer-opening task. An impact force was induced by a mechanical stop which abruptly arrested movement of the pulling hand. In performing this task, normal subjects generated a typical grip force profile characterized by an initial force impulse related to drawer movement onset, followed by a ramp-like grip force increase prior to the impending load perturbation. Finally, a reactive response was triggered by the impact. In patients with bilateral cerebellar dysfunction, the drawer-opening task was performed with an alternative control strategy. During pulling, grip force was increased to a high (overestimated) default level. The latter suggests that cerebellar patients were unable to adjust and to scale precisely the grip force according to the load force. In addition, the latency between impact and reactive activity was prolonged in the patients, suggesting an impaired cerebellar transmission of the long-latency responses. In conclusion, these data demonstrate the involvement of cerebellar circuits in both proactive and reactive mechanisms in view of predictable load perturbations during manipulative behavior. PMID:10473743

  17. Speech and Language Findings Associated with Paraneoplastic Cerebellar Degeneration

    ERIC Educational Resources Information Center

    Paslawski, Teresa; Duffy, Joseph R.; Vernino, Steven

    2005-01-01

    Paraneoplastic cerebellar degeneration (PCD) is an autoimmune disease that can be associated with cancer of the breast, lung, and ovary. The clinical presentation of PCD commonly includes ataxia, visual disturbances, and dysarthria. The speech disturbances associated with PCD have not been well characterized, despite general acceptance that…

  18. Hippocampo-cerebellar theta band phase synchrony in rabbits.

    PubMed

    Wikgren, J; Nokia, M S; Penttonen, M

    2010-02-17

    Hippocampal functioning, in the form of theta band oscillation, has been shown to modulate and predict cerebellar learning of which rabbit eyeblink conditioning is perhaps the most well-known example. The contribution of hippocampal neural activity to cerebellar learning is only possible if there is a functional connection between the two structures. Here, in the context of trace eyeblink conditioning, we show (1) that, in addition to the hippocampus, prominent theta oscillation also occurs in the cerebellum, and (2) that cerebellar theta oscillation is synchronized with that in the hippocampus. Further, the degree of phase synchrony (PS) increased both as a response to the conditioning stimuli and as a function of the relative power of hippocampal theta oscillation. However, the degree of PS did not change as a function of either training or learning nor did it predict learning rate as the hippocampal theta ratio did. Nevertheless, theta band synchronization might reflect the formation of transient neural assemblies between the hippocampus and the cerebellum. These findings help us understand how hippocampal function can affect eyeblink conditioning, during which the critical plasticity occurs in the cerebellum. Future studies should examine cerebellar unit activity in relation to hippocampal theta oscillations in order to discover the detailed mechanisms of theta-paced neural activity. PMID:19945512

  19. Caytaxin Deficiency Disrupts Signaling Pathways in Cerebellar Cortex

    PubMed Central

    Xiao, Jianfeng; Gong, Suzhen; LeDoux, Mark S.

    2007-01-01

    The genetically dystonic (dt) rat, an autosomal recessive model of generalized dystonia, harbors an insertional mutation in Atcay. As a result, dt rats are deficient in Atcay transcript and the neuronally-restricted protein caytaxin. Previous electrophysiological and biochemical studies have defined olivocerebellar pathways, particularly the climbing fiber projection to Purkinje cells, as a site of significant functional abnormality in dt rats. In normal rats, Atcay transcript is abundantly expressed in the granular and Purkinje cell layers of cerebellar cortex. To better understand the consequences of caytaxin deficiency in cerebellar cortex, differential gene expression was examined in dt rats and their normal littermates. Data from oligonucleotide microarrays and quantitative real-time RT-PCR (QRT-PCR) identified phosphatidylinositol signaling pathways, calcium homeostasis, and extracellular matrix interactions as domains of cellular dysfunction in dt rats. In dt rats, genes encoding the corticotropin-releasing hormone receptor 1 (CRH-R1, Crhr1) and calcium-transporting plasma membrane ATPase 4 (PMCA4, Atp2b4) showed the greatest up-regulation with QRT-PCR. Immunocytochemical experiments demonstrated that CRH-R1, CRH, and PMCA4 were up-regulated in cerebellar cortex of mutant rats. Along with previous electrophysiological and pharmacological studies, our data indicate that caytaxin plays a critical role in the molecular response of Purkinje cells to climbing fiber input. Caytaxin may also contribute to maturational events in cerebellar cortex. PMID:17092653

  20. The history of the development of the cerebellar examination.

    PubMed

    Fine, Edward J; Ionita, Catalina C; Lohr, Linda

    2002-12-01

    The cerebellar examination evolved from observations of experimental lesions made by neurophysiologists and clinical descriptions of patients with trauma to the cerebellum. At the beginning of the 19th century, neurophysiologists such as Luigi Rolando, Marie-Jean-Pierre Flourens, and John Call Dalton, Jr. ablated portions of the cerebellum of a variety of animals and observed staggering gait, clumsiness, and falling from side to side without loss of strength. They concluded that the cerebellum coordinated voluntary movements. In 1899, Joseph Francois Félix Babinski observed that patients with cerebellar lesions could not execute complex movements without breaking down into their elemental movements and described the defect as dysmetria. In 1902, Babinski coined the term dysdiodochokinesis to describe the inability to perform rapid execution of movements requiring alternate contractions of agonist and antagonist muscles. Gordon Holmes in 1904 described the phenomena of rebound, noting that if a limb ipsilateral to a cerebellar lesion is suddenly released from tension, the appendage will flail. In 1917, Gordon Holmes reported hypotonia and dysmetria in men wounded by gunshot wounds to their cerebellum. These observations were rapidly included in descriptions of the cerebellar examination in popular contemporaneous textbooks of neurology. Modern observations have demonstrated that the cerebellum influences such cognitive functions such as planning, verbal fluency, abstract reasoning, prosody, and use of correct grammar. PMID:12539058

  1. Milder progressive cerebellar atrophy caused by biallelic SEPSECS mutations.

    PubMed

    Iwama, Kazuhiro; Sasaki, Masayuki; Hirabayashi, Shinichi; Ohba, Chihiro; Iwabuchi, Emi; Miyatake, Satoko; Nakashima, Mitsuko; Miyake, Noriko; Ito, Shuichi; Saitsu, Hirotomo; Matsumoto, Naomichi

    2016-06-01

    Cerebellar atrophy is recognized in various types of childhood neurological disorders with clinical and genetic heterogeneity. Genetic analyses such as whole exome sequencing are useful for elucidating the genetic basis of these conditions. Pathological recessive mutations in Sep (O-phosphoserine) tRNA:Sec (selenocysteine) tRNA synthase (SEPSECS) have been reported in a total of 11 patients with pontocerebellar hypoplasia type 2, progressive cerebellocerebral atrophy or progressive encephalopathy, yet detailed clinical features are limited to only four patients. We identified two new families with progressive cerebellar atrophy, and by whole exome sequencing detected biallelic SEPSECS mutations: c.356A>G (p.Asn119Ser) and c.77delG (p.Arg26Profs*42) in family 1, and c.356A>G (p.Asn119Ser) and c.467G>A (p.Arg156Gln) in family 2. Their development was slightly delayed regardless of normal brain magnetic resonance imaging (MRI) in infancy. The progression of clinical symptoms in these families is evidently slower than in previously reported cases, and the cerebellar atrophy milder by brain MRI, indicating that SEPSECS mutations are also involved in milder late-onset cerebellar atrophy. PMID:26888482

  2. Interhemispheric Asymmetry of Corticomotor Excitability After Chronic Cerebellar Infarcts

    PubMed Central

    Cohen, Leonardo G.; da Cunha Pinho, Marco; Yamamoto, Fábio Iuji; Marchiori, Paulo Eurípedes; Scaff, Milberto; Conforto, Adriana Bastos

    2016-01-01

    Early after stroke, there is loss of intracortical facilitation (ICF) and increase in short-interval intracortical inhibition (SICI) in the primary motor cortex (M1) contralateral to a cerebellar infarct. Our goal was to investigate intracortical M1 function in the chronic stage following cerebellar infarcts (>4 months). We measured resting motor threshold (rMT), SICI, ICF, and ratios between motor-evoked potential amplitudes (MEP) and supramaximal M response amplitudes (MEP/M; %), after transcranial magnetic stimulation was applied to the M1 contralateral (M1contralesional) and ipsilateral (M1ipsilesional) to the cerebellar infarct in patients and to both M1s of healthy age-matched volunteers. SICI was decreased in M1contralesional compared to M1ipsilesional in the patient group in the absence of side-to-side differences in controls. There were no significant interhemispheric or between-group differences in rMT, ICF, or MEP/M (%). Our results document disinhibition of M1contralesional in the chronic phase after cerebellar stroke. PMID:20461489

  3. Cerebellar glucose consumption in normal and pathologic states using fluorine-FDG and PET

    SciTech Connect

    Kushner, M.; Tobin, M.; Alavi, A.; Chawluk, J.; Rosen, M.; Fazekas, F.; Alavi, J.; Reivich, M.

    1987-11-01

    We studied cerebellar metabolism in 118 subjects including young and elderly controls and patients suffering from stroke, supratentorial brain tumor and Alzheimer's disease using fluorine-18 fluorodeoxyglucose ((/sup 18/F)FDG) and position emission tomography (PET). Alzheimer's disease and normal aging did not alter mean cerebellar metabolism. In stroke and tumor mean cerebellar metabolism was lower in the hemisphere contralateral to the supratentorial lesion. In tumor bilaterally significant reductions in absolute cerebellar metabolism also were noted, unlike stroke. Primary sensory stimulation did not alter absolute or relative cerebellar metabolism. These results show that absolute and relative values for cerebellar metabolism vary depending on the process under study. Thus, analysis schemes employing normalization of regional metabolic data to cerebellar values may be subject to error.

  4. Gaze holding deficits discriminate early from late onset cerebellar degeneration.

    PubMed

    Tarnutzer, Alexander A; Weber, K P; Schuknecht, B; Straumann, D; Marti, S; Bertolini, G

    2015-08-01

    The vestibulo-cerebellum calibrates the output of the inherently leaky brainstem neural velocity-to-position integrator to provide stable gaze holding. In healthy humans small-amplitude centrifugal nystagmus is present at extreme gaze-angles, with a non-linear relationship between eye-drift velocity and eye eccentricity. In cerebellar degeneration this calibration is impaired, resulting in pathological gaze-evoked nystagmus (GEN). For cerebellar dysfunction, increased eye drift may be present at any gaze angle (reflecting pure scaling of eye drift found in controls) or restricted to far-lateral gaze (reflecting changes in shape of the non-linear relationship) and resulting eyed-drift patterns could be related to specific disorders. We recorded horizontal eye positions in 21 patients with cerebellar neurodegeneration (gaze-angle = ±40°) and clinically confirmed GEN. Eye-drift velocity, linearity and symmetry of drift were determined. MR-images were assessed for cerebellar atrophy. In our patients, the relation between eye-drift velocity and gaze eccentricity was non-linear, yielding (compared to controls) significant GEN at gaze-eccentricities ≥20°. Pure scaling was most frequently observed (n = 10/18), followed by pure shape-changing (n = 4/18) and a mixed pattern (n = 4/18). Pure shape-changing patients were significantly (p = 0.001) younger at disease-onset compared to pure scaling patients. Atrophy centered around the superior/dorsal vermis, flocculus/paraflocculus and dentate nucleus and did not correlate with the specific drift behaviors observed. Eye drift in cerebellar degeneration varies in magnitude; however, it retains its non-linear properties. With different drift patterns being linked to age at disease-onset, we propose that the gaze-holding pattern (scaling vs. shape-changing) may discriminate early- from late-onset cerebellar degeneration. Whether this allows a distinction among specific cerebellar disorders remains to be determined

  5. Slicing the Torus: Obscuring Structures in Quasars

    NASA Astrophysics Data System (ADS)

    Elvis, Martin

    2012-07-01

    Quasars and Active Galactic Nuclei (AGNs) are often obscured by dust and gas. It is normally assumed that the obscuration occurs in an oblate "obscuring torus", that begins at the radius at which the most refractive dust can remain solid. The most famous form of this torus is a donut-shaped region of molecular gas with a large scale-height. While this model is elegant and accounts for many phenomena at once, it does not hold up to detailed tests. Instead the obscuration in AGNs must occur on a wide range of scales and be due to a minimum of three physically distinct absorbers. Slicing the "torus" into these three regions will allow interesting physics of the AGN to be extracted.

  6. Slicing AADL Specifications for Model Checking

    NASA Technical Reports Server (NTRS)

    Odenbrett, Maximilian; Nguyen, Viet Yen; Noll, Thomas

    2010-01-01

    To combat the state-space explosion problem in model checking larger systems, abstraction techniques can be employed. Here, methods that operate on the system specification before constructing its state space are preferable to those that try to minimize the resulting transition system as they generally reduce peak memory requirements. We sketch a slicing algorithm for system specifications written in (a variant of) the Architecture Analysis and Design Language (AADL). Given a specification and a property to be verified, it automatically removes those parts of the specification that are irrelevant for model checking the property, thus reducing the size of the corresponding transition system. The applicability and effectiveness of our approach is demonstrated by analyzing the state-space reduction for an example, employing a translator from AADL to Promela, the input language of the SPIN model checker.

  7. Diffusion tensor imaging of the human cerebellar pathways and their interplay with cerebral macrostructure

    PubMed Central

    Keser, Zafer; Hasan, Khader M.; Mwangi, Benson I.; Kamali, Arash; Ucisik-Keser, Fehime Eymen; Riascos, Roy F.; Yozbatiran, Nuray; Francisco, Gerard E.; Narayana, Ponnada A.

    2015-01-01

    Cerebellar white matter (WM) connections to the central nervous system are classified functionally into the Spinocerebellar (SC), vestibulocerebellar (VC), and cerebrocerebellar subdivisions. The SC pathways project from spinal cord to cerebellum, whereas the 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 = 2 mm × 2 mm × 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 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 1.6 ± 0.45 of the total intracranial volume (ICV). PMID:25904851

  8. Patterns of regional cerebellar atrophy in genetic frontotemporal dementia

    PubMed Central

    Bocchetta, Martina; Cardoso, M. Jorge; Cash, David M.; Ourselin, Sebastien; Warren, Jason D.; Rohrer, Jonathan D.

    2016-01-01

    Background Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder with a strong genetic component. The cerebellum has not traditionally been felt to be involved in FTD but recent research has suggested a potential role. Methods We investigated the volumetry of the cerebellum and its subregions in a cohort of 44 patients with genetic FTD (20 MAPT, 7 GRN, and 17 C9orf72 mutation carriers) compared with 18 cognitively normal controls. All groups were matched for age and gender. On volumetric T1-weighted magnetic resonance brain images we used an atlas propagation and label fusion strategy of the Diedrichsen cerebellar atlas to automatically extract subregions including the cerebellar lobules, the vermis and the deep nuclei. Results The global cerebellar volume was significantly smaller in C9orf72 carriers (mean (SD): 99989 (8939) mm3) compared with controls (108136 (7407) mm3). However, no significant differences were seen in the MAPT and GRN carriers compared with controls (104191 (6491) mm3 and 107883 (6205) mm3 respectively). Investigating the individual subregions, C9orf72 carriers had a significantly lower volume than controls in lobule VIIa-Crus I (15% smaller, p < 0.0005), whilst MAPT mutation carriers had a significantly lower vermal volume (10% smaller, p = 0.001) than controls. All cerebellar subregion volumes were preserved in GRN carriers compared with controls. 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. PMID:26977398

  9. Automated MRI Cerebellar Size Measurements Using Active Appearance Modeling

    PubMed Central

    Price, Mathew; Cardenas, Valerie A.; Fein, George

    2014-01-01

    Although the human cerebellum has been increasingly identified as an important hub that shows potential for helping in the diagnosis of a large spectrum of disorders, such as alcoholism, autism, and fetal alcohol spectrum disorder, the high costs associated with manual segmentation, and low availability of reliable automated cerebellar segmentation tools, has resulted in a limited focus on cerebellar measurement in human neuroimaging studies. We present here the CATK (Cerebellar Analysis Toolkit), which is based on the Bayesian framework implemented in FMRIB’s FIRST. This approach involves training Active Appearance Models (AAM) using hand-delineated examples. CATK can currently delineate the cerebellar hemispheres and three vermal groups (lobules I–V, VI–VII, and VIII–X). Linear registration with the low-resolution MNI152 template is used to provide initial alignment, and Point Distribution Models (PDM) are parameterized using stellar sampling. The Bayesian approach models the relationship between shape and texture through computation of conditionals in the training set. Our method varies from the FIRST framework in that initial fitting is driven by 1D intensity profile matching, and the conditional likelihood function is subsequently used to refine fitting. The method was developed using T1-weighted images from 63 subjects that were imaged and manually labeled: 43 subjects were scanned once and were used for training models, and 20 subjects were imaged twice (with manual labeling applied to both runs) and used to assess reliability and validity. Intraclass correlation analysis shows that CATK is highly reliable (average test-retest ICCs of 0.96), and offers excellent agreement with the gold standard (average validity ICC of 0.87 against manual labels). Comparisons against an alternative atlas-based approach, SUIT (Spatially Unbiased Infratentorial Template), that registers images with a high-resolution template of the cerebellum, show that our AAM

  10. Sun1 deficiency leads to cerebellar ataxia in mice

    PubMed Central

    Wang, Jing-Ya; Yu, I.-Shing; Huang, Chien-Chi; Chen, Chia-Yen; Wang, Wan-Ping; Lin, Shu-Wha; Jeang, Kuan-Teh; Chi, Ya-Hui

    2015-01-01

    ABSTRACT Migration and organization of the nucleus are essential for the proliferation and differentiation of cells, including neurons. However, the relationship between the positioning of the nucleus and cellular morphogenesis remains poorly understood. Inherited recessive cerebellar ataxia has been attributed to mutations in SYNE1, a component of the linker of nucleoskeleton and cytoskeleton (LINC) complex. Regardless, Syne1-mutant mice present with normal cerebellar development. The Sad1-Unc-84 homology (SUN)-domain proteins are located at the inner nuclear membrane and recruit Syne proteins through the KASH domain to the outer nuclear membrane. Here, we report an unrecognized contribution of Sun1 and Sun2 to the postnatal development of murine cerebellum. Mice depleted of Sun1 showed a marked reduction in the cerebellar volume, and this phenotype is exacerbated with additional loss of a Sun2 allele. Consistent with these histological changes, Sun1−/− and Sun1−/−Sun2+/− mice exhibited defective motor coordination. Results of immunohistochemical analyses suggested that Sun1 is highly expressed in Purkinje cells and recruits Syne2 to the periphery of the nucleus. Approximately 33% of Purkinje cells in Sun1−/− mice and 66% of Purkinje cells in Sun1−/−Sun2+/− mice were absent from the surface of the internal granule layer (IGL), whereas the proliferation and migration of granule neurons were unaffected. Furthermore, the Sun1−/−Sun2+/− Purkinje cells exhibited retarded primary dendrite specification, reduced dendritic complexity and aberrant patterning of synapses. Our findings reveal a cell-type-specific role for Sun1 and Sun2 in nucleokinesis during cerebellar development, and we propose the use of Sun-deficient mice as a model for studying cerebellar ataxia that is associated with mutation of human SYNE genes or loss of Purkinje cells. PMID:26035387

  11. Adaptive Robotic Control Driven by a Versatile Spiking Cerebellar Network

    PubMed Central

    Casellato, Claudia; Antonietti, Alberto; Garrido, Jesus A.; Carrillo, Richard R.; Luque, Niceto R.; Ros, Eduardo; Pedrocchi, Alessandra; D'Angelo, Egidio

    2014-01-01

    The cerebellum is involved in a large number of different neural processes, especially in associative learning and in fine motor control. To develop a comprehensive theory of sensorimotor learning and control, it is crucial to determine the neural basis of coding and plasticity embedded into the cerebellar neural circuit and how they are translated into behavioral outcomes in learning paradigms. Learning has to be inferred from the interaction of an embodied system with its real environment, and the same cerebellar principles derived from cell physiology have to be able to drive a variety of tasks of different nature, calling for complex timing and movement patterns. We have coupled a realistic cerebellar spiking neural network (SNN) with a real robot and challenged it in multiple diverse sensorimotor tasks. Encoding and decoding strategies based on neuronal firing rates were applied. Adaptive motor control protocols with acquisition and extinction phases have been designed and tested, including an associative Pavlovian task (Eye blinking classical conditioning), a vestibulo-ocular task and a perturbed arm reaching task operating in closed-loop. The SNN processed in real-time mossy fiber inputs as arbitrary contextual signals, irrespective of whether they conveyed a tone, a vestibular stimulus or the position of a limb. A bidirectional long-term plasticity rule implemented at parallel fibers-Purkinje cell synapses modulated the output activity in the deep cerebellar nuclei. In all tasks, the neurorobot learned to adjust timing and gain of the motor responses by tuning its output discharge. It succeeded in reproducing how human biological systems acquire, extinguish and express knowledge of a noisy and changing world. By varying stimuli and perturbations patterns, real-time control robustness and generalizability were validated. The implicit spiking dynamics of the cerebellar model fulfill timing, prediction and learning functions. PMID:25390365

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

    PubMed

    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. PMID:26116983

  13. Adaptive robotic control driven by a versatile spiking cerebellar network.

    PubMed

    Casellato, Claudia; Antonietti, Alberto; Garrido, Jesus A; Carrillo, Richard R; Luque, Niceto R; Ros, Eduardo; Pedrocchi, Alessandra; D'Angelo, Egidio

    2014-01-01

    The cerebellum is involved in a large number of different neural processes, especially in associative learning and in fine motor control. To develop a comprehensive theory of sensorimotor learning and control, it is crucial to determine the neural basis of coding and plasticity embedded into the cerebellar neural circuit and how they are translated into behavioral outcomes in learning paradigms. Learning has to be inferred from the interaction of an embodied system with its real environment, and the same cerebellar principles derived from cell physiology have to be able to drive a variety of tasks of different nature, calling for complex timing and movement patterns. We have coupled a realistic cerebellar spiking neural network (SNN) with a real robot and challenged it in multiple diverse sensorimotor tasks. Encoding and decoding strategies based on neuronal firing rates were applied. Adaptive motor control protocols with acquisition and extinction phases have been designed and tested, including an associative Pavlovian task (Eye blinking classical conditioning), a vestibulo-ocular task and a perturbed arm reaching task operating in closed-loop. The SNN processed in real-time mossy fiber inputs as arbitrary contextual signals, irrespective of whether they conveyed a tone, a vestibular stimulus or the position of a limb. A bidirectional long-term plasticity rule implemented at parallel fibers-Purkinje cell synapses modulated the output activity in the deep cerebellar nuclei. In all tasks, the neurorobot learned to adjust timing and gain of the motor responses by tuning its output discharge. It succeeded in reproducing how human biological systems acquire, extinguish and express knowledge of a noisy and changing world. By varying stimuli and perturbations patterns, real-time control robustness and generalizability were validated. The implicit spiking dynamics of the cerebellar model fulfill timing, prediction and learning functions. PMID:25390365

  14. Ultrastructural pathology of human peritumoural oedematous cerebellar cortex.

    PubMed

    Castejón, O J

    2016-01-01

    Cerebellar cortical biopsies of the peritumoural region of seven patients with cerebellar haemangioma, mesencephalic meningioma, cerebellopontine astrocytoma, cerebellopontine meningioma, and medulloblastoma of cerebellar vermis were examined by means of conventional transmission electron microscopy. Granule cells showed oedematous cytoplasm and mitochondria. Swollen Golgi cells exhibited lipofuscin granules and intranuclear inclusions. Both neuron cell types displayed swollen dendritic digits synapsing with afferent mossy fibre endings. Degenerated myelinated axons corresponding to afferent mossy and climbing fibres and efferent Purkinje cell axons were observed at the granular layer. Dense and clear ischaemic Purkinje cells established degenerated synapses with swollen parallel fibre synaptic varicosities. Degenerated Purkinje cell recurrent axonal collaterals were found at the molecular layer. Swollen and clear Bergmann glial cell cytoplasm was observed closely applied to the oedematous clear and dark Purkinje cell body, dendritic trunk, secondary and tertiary dendritic branches. Swollen climbing fibre endings featured by numerous microtubules and neurofilaments, and a decreased number of synaptic vesicles were observed making degenerated axo-spinodendritic synapses with clear and swollen dendritic spines from Purkinje, Golgi, basket and stellate cell dendrites. Swollen stellate neurons showed oedematous mitochondria. Lipofuscin-rich astrocytes and reactive phagocytic astrocytes were observed. The latter appeared engulfing haematogenous proteinaceous oedema fluid. All cerebellar neurons showed stress endoplasmic reticulum dysfunction featured by focal dilated cisterns and detachment of associated ribosomes. Myelin sheath degeneration was related with oligodendrocyte degenerating hydropic changes. The peritumoural ischaemic cerebellar nerve and glial cell abnormalities were related with neurobehavioral changes, tremor, nystagmus, dismetry and gait disturbance

  15. Functional Relations of Cerebellar Modules of the Cat

    PubMed Central

    Pong, Milton; Gibson, Alan R.

    2010-01-01

    The cerebellum consists of parasagittal zones that define fundamental modules of neural processing. Each zone receives input from a distinct subdivision of the inferior olive (IO)—activity in one olivary subdivision will affect activity in one cerebellar module. To define functions of the cerebellar modules, we inactivated specific olivary subdivisions in six male cats with a glutamate receptor blocker. Olivary inactivation eliminates Purkinje cell complex spikes, which results in a high rate of Purkinje cell simple spike discharge. The increased simple spike discharge inhibits output from connected regions of the cerebellar nuclei. After inactivation, behavior was evaluated during a reach-to-grasp task and during locomotion. Inactivation of each subdivision produced unique behavioral deficits. Performance of the reach-to-grasp task was affected by inactivation of the rostral dorsal accessory olive (rDAO) and the rostral medial accessory olive (rMAO) and, possibly, the principal olive. rDAO inactivation produced paw drag during locomotion and a deficit in grasping the handle during the reach-to-grasp task. rMAO inactivation caused the cats to reach under the handle and produced severe limb drag during locomotion. Inactivation of the dorsal medial cell column, cell group β, or caudal medial accessory olive produced little deficit in the reach-to-grasp task, but each produced a different deficit during locomotion. In all cases, the cats appeared to have intact sensation, good spatial awareness, and no change of affect. Normal cerebellar function requires low rates of IO discharge, and each cerebellar module has a specific and unique function in sensory–motor integration. PMID:20631170

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

    PubMed

    Wang, Yubin; Hersheson, Joshua; Lopez, Dulce; Hammer, Monia; Liu, Yan; Lee, Ka-Hung; Pinto, Vanessa; Seinfeld, Jeff; Wiethoff, Sarah; Sun, Jiandong; Amouri, Rim; Hentati, Faycal; Baudry, Neema; Tran, Jennifer; Singleton, Andrew B; Coutelier, Marie; Brice, Alexis; Stevanin, Giovanni; Durr, Alexandra; Bi, Xiaoning; Houlden, Henry; Baudry, Michel

    2016-06-28

    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. PMID:27320912

  17. Defects in the CAPN1 gene result in alterations in cerebellar development and in cerebellar ataxia in mice and humans

    PubMed Central

    Wang, Yubin; Hersheson, Joshua; Lopez, Dulce; Hamad, Monia Ben; Liu, Yan; Lee, Ka-Hung; Pinto, Vanessa; Seinfeld, Jeff; Wiethoff, Sarah; Sun, Jiandong; Amouri, Rim; Hentati, Faycal; Baudry, Neema; Tran, Jennifer; Singleton, Andrew B; Coutelier, Marie; Brice, Alexis; Stevanin, Giovanni; Durr, Alexandra; Bi, Xiaoning; Houlden, Henry; Baudry, Michel

    2016-01-01

    SUMMARY A CAPN1 missense mutation in Parson Russell Terrier dogs is associated with spinocerebellar ataxia. We now report that homozygous CAPN1 null mutations in humans result in cerebellar ataxia and limb spasticity in four independent pedigrees. Calpain-1 knock-out (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. PMID:27320912

  18. PHYSIOLOGICAL CHANGES IN PINEAPPLE SLICES TREATED WITH ANTIBROWNING AGENTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The physiological responses of pineapple slices to antibrowning agents have been studied. Slices were immersed for 2 minutes in solutions of Isoascorbic acid (IAA) 0.1 M, ascorbic acid (AA) 0.05 M or acetyl cysteine (AC) 0.05 M, packaged in polystyrene trays, prior to storage for up to 14 days at 1...

  19. Mathematical Modeling of Thin Layer Microwave Drying of Taro Slices

    NASA Astrophysics Data System (ADS)

    Kumar, Vivek; Sharma, H. K.; Singh, K.

    2016-03-01

    The present study investigated the drying kinetics of taro slices precooked in different medium viz water (WC), steam (SC) and Lemon Solution (LC) and dried at different microwave power 360, 540 and 720 W. Drying curves of all precooked slices at all microwave powers showed falling rate period along with a very short accelerating period at the beginning of the drying. At all microwave powers, higher drying rate was observed for LC slices as compared to WC and SC slices. To select a suitable drying curve, seven thin-layer drying models were fitted to the experimental data. The data revealed that the Page model was most adequate in describing the microwave drying behavior of taro slices precooked in different medium. The highest effective moisture diffusivity value of 2.11 × 10-8 m2/s was obtained for LC samples while the lowest 0.83 × 10-8 m2/s was obtained for WC taro slices. The activation energy (E a ) of LC taro slices was lower than the E a of WC and SC taro slices.

  20. Modeling surface transfer of L. monocytogenes on salami during slicing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Listeria monocytogenes has been implicated in several listeriosis outbreaks linked to the consumption of pre-sliced ready-to-eat (RTE) deli meats, which has drawn considerable attention in regard to possible cross-contamination during slicing operation at retail and food service environment. Salami...

  1. Target recognition for ladar range image using slice image

    NASA Astrophysics Data System (ADS)

    Xia, Wenze; Han, Shaokun; Wang, Liang

    2015-12-01

    A shape descriptor and a complete shape-based recognition system using slice images as geometric feature descriptor for ladar range images are introduced. A slice image is a two-dimensional image generated by three-dimensional Hough transform and the corresponding mathematical transformation. The system consists of two processes, the model library construction and recognition. In the model library construction process, a series of range images are obtained after the model object is sampled at preset attitude angles. Then, all the range images are converted into slice images. The number of slice images is reduced by clustering analysis and finding a representation to reduce the size of the model library. In the recognition process, the slice image of the scene is compared with the slice image in the model library. The recognition results depend on the comparison. Simulated ladar range images are used to analyze the recognition and misjudgment rates, and comparison between the slice image representation method and moment invariants representation method is performed. The experimental results show that whether in conditions without noise or with ladar noise, the system has a high recognition rate and low misjudgment rate. The comparison experiment demonstrates that the slice image has better representation ability than moment invariants.

  2. Timing Tasks Synchronize Cerebellar and Frontal Ramping Activity and Theta Oscillations: Implications for Cerebellar Stimulation in Diseases of Impaired Cognition

    PubMed Central

    Parker, Krystal L.

    2016-01-01

    Timing is a fundamental and highly conserved mammalian capability, yet the underlying neural mechanisms are widely debated. Ramping activity of single neurons that gradually increase or decrease activity to encode the passage of time has been speculated to predict a behaviorally relevant temporal event. Cue-evoked low-frequency activity has also been implicated in temporal processing. Ramping activity and low-frequency oscillations occur throughout the brain and could indicate a network-based approach to timing. Temporal processing requires cognitive mechanisms of working memory, attention, and reasoning, which are dysfunctional in neuropsychiatric disease. Therefore, timing tasks could be used to probe cognition in animals with disease phenotypes. The medial frontal cortex and cerebellum are involved in cognition. Cerebellar stimulation has been shown to influence medial frontal activity and improve cognition in schizophrenia. However, the mechanism underlying the efficacy of cerebellar stimulation is unknown. Here, we discuss how timing tasks can be used to probe cerebellar interactions with the frontal cortex and the therapeutic potential of cerebellar stimulation. The goal of this theory and hypothesis manuscript is threefold. First, we will summarize evidence indicating that in addition to motor learning, timing tasks involve cognitive processes that are present within both the cerebellum and medial frontal cortex. Second, we propose methodologies to investigate the connections between these areas in patients with Parkinson’s disease, autism, and schizophrenia. Lastly, we hypothesize that cerebellar transcranial stimulation may rescue medial frontal ramping activity, theta oscillations, and timing abnormalities, thereby restoring executive function in diseases of impaired cognition. This hypothesis could inspire the use of timing tasks as biomarkers for neuronal and cognitive abnormalities in neuropsychiatric disease and promote the therapeutic potential of

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

    PubMed

    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. PMID:25406224

  4. A survey of program slicing for software engineering

    NASA Technical Reports Server (NTRS)

    Beck, Jon

    1993-01-01

    This research concerns program slicing which is used as a tool for program maintainence of software systems. Program slicing decreases the level of effort required to understand and maintain complex software systems. It was first designed as a debugging aid, but it has since been generalized into various tools and extended to include program comprehension, module cohesion estimation, requirements verification, dead code elimination, and maintainence of several software systems, including reverse engineering, parallelization, portability, and reuse component generation. This paper seeks to address and define terminology, theoretical concepts, program representation, different program graphs, developments in static slicing, dynamic slicing, and semantics and mathematical models. Applications for conventional slicing are presented, along with a prognosis of future work in this field.

  5. Seamless Ligation Cloning Extract (SLiCE) cloning method.

    PubMed

    Zhang, Yongwei; Werling, Uwe; Edelmann, Winfried

    2014-01-01

    SLiCE (Seamless Ligation Cloning Extract) is a novel cloning method that utilizes easy to generate bacterial cell extracts to assemble multiple DNA fragments into recombinant DNA molecules in a single in vitro recombination reaction. SLiCE overcomes the sequence limitations of traditional cloning methods, facilitates seamless cloning by recombining short end homologies (15-52 bp) with or without flanking heterologous sequences and provides an effective strategy for directional subcloning of DNA fragments from bacterial artificial chromosomes or other sources. SLiCE is highly cost-effective and demonstrates the versatility as a number of standard laboratory bacterial strains can serve as sources for SLiCE extract. We established a DH10B-derived E. coli strain expressing an optimized λ prophage Red recombination system, termed PPY, which facilitates SLiCE with very high efficiencies. PMID:24395368

  6. Cerebellar contributions to self-motion perception: evidence from patients with congenital cerebellar agenesis.

    PubMed

    Dahlem, Kilian; Valko, Yulia; Schmahmann, Jeremy D; Lewis, Richard F

    2016-05-01

    The cerebellum was historically considered a brain region dedicated to motor control, but it has become clear that it also contributes to sensory processing, particularly when sensory discrimination is required. Prior work, for example, has demonstrated a cerebellar contribution to sensory discrimination in the visual and auditory systems. The cerebellum also receives extensive inputs from the motion and gravity sensors in the vestibular labyrinth, but its role in the perception of head motion and orientation has received little attention. Drawing on the lesion-deficit approach to understanding brain function, we evaluated the contributions of the cerebellum to head motion perception by measuring perceptual thresholds in two subjects with congenital agenesis of the cerebellum. We used a set of passive motion paradigms that activated the semicircular canals or otolith organs in isolation or combination, and compared results of the agenesis patients with healthy control subjects. Perceptual thresholds for head motion were elevated in the agenesis subjects for all motion protocols, most prominently for paradigms that only activated otolith inputs. These results demonstrate that the cerebellum increases the sensitivity of the brain to the motion and orientation signals provided by the labyrinth during passive head movements. PMID:26888100

  7. In and out of the loop: external and internal modulation of the olivo-cerebellar loop

    PubMed Central

    Libster, Avraham M.; Yarom, Yosef

    2013-01-01

    Cerebellar anatomy is known for its crystal like structure, where neurons and connections are precisely and repeatedly organized with minor variations across the Cerebellar Cortex. The olivo-cerebellar loop, denoting the connections between the Cerebellar cortex, Inferior Olive and Cerebellar Nuclei (CN), is also modularly organized to form what is known as the cerebellar module. In contrast to the relatively organized and static anatomy, the cerebellum is innervated by a wide variety of neuromodulator carrying axons that are heterogeneously distributed along the olivo-cerebellar loop, providing heterogeneity to the static structure. In this manuscript we review modulatory processes in the olivo-cerebellar loop. We start by discussing the relationship between neuromodulators and the animal behavioral states. This is followed with an overview of the cerebellar neuromodulatory signals and a short discussion of why and when the cerebellar activity should be modulated. We then devote a section for three types of neurons where we briefly review its properties and propose possible neuromodulation scenarios. PMID:23626524

  8. Potential sources of intrinsic optical signals imaged in live brain slices.

    PubMed

    Andrew, R D; Jarvis, C R; Obeidat, A S

    1999-06-01

    Changes in how light is absorbed or scattered in biological tissue are termed intrinsic optical signals (IOSs). Imaging IOSs in the submerged brain slice preparation provides insight into brain activity if it involves significant water movement between intracellular and extracellular compartments. This includes responses to osmotic imbalance, excitotoxic glutamate agonists, and oxygen/glucose deprivation, the latter leading to spreading depression. There are several misconceptions regarding these signals. (1) IOSs are not generated by glial swelling alone. Although neuronal and glia sources cannot yet be directly imaged, several lines of evidence indicate that neurons contribute significantly to the changes in light transmittance. (2) Excitotoxic swelling and osmotic swelling are physiologically different, as are their associated IOSs. Hyposmotic swelling involves no detectable neuronal depolarization of cortical pyramidal neurons, only the passive drawing in of water from a dilute medium across the cell membrane. In contrast excitotoxic swelling involves sustained membrane depolarization associated with inordinate amounts of Na+ and Cl- entry followed by water. IOSs demonstrate substantial damage in the latter case. (3) Osmotic perturbations do not induce volume regulatory mechanisms as measured by IOSs. The osmotic responses measured by IOSs in brain slices are passive, without the compensatory mechanisms that are assumed to be active on a scale suggested by studies of cultured brain cells under excessive osmotic stress. (4) Spreading depression (SD) can cause neuronal damage. Innocuous during migraine aura, SD induces acute neuronal damage in brain slices that are metabolically compromised by oxygen/glucose deprivation, as demonstrated by IOSs. Neighboring tissue where SD does not spread remains relatively healthy as judged by a minimal reduction in light transmittance. IOSs show that the metabolic stress of SD combined with the compromise of energy resources

  9. Model of very fast (>75 Hz) network oscillations generated by electrical coupling between the proximal axons of cerebellar Purkinje cells

    PubMed Central

    Traub, Roger D; Middleton, Steven J; Knöpfel, Thomas; Whittington, Miles A

    2009-01-01

    Very fast oscillations (VFO, >75 Hz) occur transiently in vivo, in the cerebellum of mice genetically modified to model Angelman syndrome, and in a mouse model of fetal alcohol syndrome. We recently reported VFO in slices of mouse cerebellar cortex (Crus I and II of ansiform and paramedian lobules), either in association with gamma oscillations (~40 Hz, evoked by nicotine), or in isolation (evoked by nicotine in combination with GABAA receptor blockade). The experimental data suggest a role for electrical coupling between Purkinje cells (blockade of VFO by drugs reducing gap junction conductance, and spikelets in some Purkinje cells); and the data suggest the specific involvement of Purkinje cell axons (because of field oscillation maxima in the granular layer). We show here that a detailed network model (1,000 multicompartment Purkinje cells) replicates the experimental data, when gap junctions are located on the proximal axons of Purkinje cells, provided sufficient spontaneous firing is present. Unlike other VFO models, most somatic spikelets do not correspond to axonal spikes in the parent axon, but reflect spikes in electrically coupled axons. The model predicts gating of VFO frequency by gNa inactivation, and experiments prolonging this inactivation time constant, with β-pompilidotoxin, are consistent with this prediction. The model also predicts that cerebellar VFO can be explained as an electrically coupled system of axons which are not intrinsic oscillators: the electrically uncoupled cells do not individually oscillate (in the model), and axonal firing rates are much lower in the uncoupled state than in the coupled state. PMID:18973579

  10. Caffeine Modulates Vesicle Release and Recovery at Cerebellar Parallel Fibre Terminals, Independently of Calcium and Cyclic AMP Signalling

    PubMed Central

    Dobson, Katharine L.; Jackson, Claire; Balakrishnan, Saju; Bellamy, Tomas C.

    2015-01-01

    Background Cerebellar parallel fibres release glutamate at both the synaptic active zone and at extrasynaptic sites—a process known as ectopic release. These sites exhibit different short-term and long-term plasticity, the basis of which is incompletely understood but depends on the efficiency of vesicle release and recycling. To investigate whether release of calcium from internal stores contributes to these differences in plasticity, we tested the effects of the ryanodine receptor agonist caffeine on both synaptic and ectopic transmission. Methods Whole cell patch clamp recordings from Purkinje neurons and Bergmann glia were carried out in transverse cerebellar slices from juvenile (P16-20) Wistar rats. Key Results Caffeine caused complex changes in transmission at both synaptic and ectopic sites. The amplitude of postsynaptic currents in Purkinje neurons and extrasynaptic currents in Bergmann glia were increased 2-fold and 4-fold respectively, but paired pulse ratio was substantially reduced, reversing the short-term facilitation observed under control conditions. Caffeine treatment also caused synaptic sites to depress during 1 Hz stimulation, consistent with inhibition of the usual mechanisms for replenishing vesicles at the active zone. Unexpectedly, pharmacological intervention at known targets for caffeine—intracellular calcium release, and cAMP signalling—had no impact on these effects. Conclusions We conclude that caffeine increases release probability and inhibits vesicle recovery at parallel fibre synapses, independently of known pharmacological targets. This complex effect would lead to potentiation of transmission at fibres firing at low frequencies, but depression of transmission at high frequency connections. PMID:25933382

  11. Holographic Photolysis for Multiple Cell Stimulation in Mouse Hippocampal Slices

    PubMed Central

    Papagiakoumou, Eirini; Ventalon, Cathie; Angulo, María Cecilia; Emiliani, Valentina

    2010-01-01

    Background Advanced light microscopy offers sensitive and non-invasive means to image neural activity and to control signaling with photolysable molecules and, recently, light-gated channels. These approaches require precise and yet flexible light excitation patterns. For synchronous stimulation of subsets of cells, they also require large excitation areas with millisecond and micrometric resolution. We have recently developed a new method for such optical control using a phase holographic modulation of optical wave-fronts, which minimizes power loss, enables rapid switching between excitation patterns, and allows a true 3D sculpting of the excitation volumes. In previous studies we have used holographic photololysis to control glutamate uncaging on single neuronal cells. Here, we extend the use of holographic photolysis for the excitation of multiple neurons and of glial cells. Methods/Principal Findings The system combines a liquid crystal device for holographic patterned photostimulation, high-resolution optical imaging, the HiLo microscopy, to define the stimulated regions and a conventional Ca2+ imaging system to detect neural activity. By means of electrophysiological recordings and calcium imaging in acute hippocampal slices, we show that the use of excitation patterns precisely tailored to the shape of multiple neuronal somata represents a very efficient way for the simultaneous excitation of a group of neurons. In addition, we demonstrate that fast shaped illumination patterns also induce reliable responses in single glial cells. Conclusions/Significance We show that the main advantage of holographic illumination is that it allows for an efficient excitation of multiple cells with a spatiotemporal resolution unachievable with other existing approaches. Although this paper focuses on the photoactivation of caged molecules, our approach will surely prove very efficient for other probes, such as light-gated channels, genetically encoded photoactivatable

  12. Modification of a Colliculo-thalamocortical Mouse Brain Slice, Incorporating 3-D printing of Chamber Components and Multi-scale Optical Imaging.

    PubMed

    Slater, Bernard J; Fan, Anthony Y; Stebbings, Kevin A; Saif, M Taher A; Llano, Daniel A

    2015-01-01

    The ability of the brain to process sensory information relies on both ascending and descending sets of projections. Until recently, the only way to study these two systems and how they interact has been with the use of in vivo preparations. Major advances have been made with acute brain slices containing the thalamocortical and cortico-thalamic pathways in the somatosensory, visual, and auditory systems. With key refinements to our recent modification of the auditory thalamocortical slice(1), we are able to more reliably capture the projections between most of the major auditory midbrain and forebrain structures: the inferior colliculus (IC), medial geniculate body (MGB), thalamic reticular nucleus (TRN), and the auditory cortex (AC). With portions of all these connections retained, we are able to answer detailed questions that complement the questions that can be answered with in vivo preparations. The use of flavoprotein autofluorescence imaging enables us to rapidly assess connectivity in any given slice and guide the ensuing experiment. Using this slice in conjunction with recording and imaging techniques, we are now better equipped to understand how information processing occurs at each point in the auditory forebrain as information ascends to the cortex, and the impact of descending cortical modulation. 3-D printing to build slice chamber components permits double-sided perfusion and broad access to networks within the slice and maintains the widespread connections key to fully utilizing this preparation. PMID:26437382

  13. Sliced Inverse Regression for Time Series Analysis

    NASA Astrophysics Data System (ADS)

    Chen, Li-Sue

    1995-11-01

    In this thesis, general nonlinear models for time series data are considered. A basic form is x _{t} = f(beta_sp{1} {T}X_{t-1},beta_sp {2}{T}X_{t-1},... , beta_sp{k}{T}X_ {t-1},varepsilon_{t}), where x_{t} is an observed time series data, X_{t } is the first d time lag vector, (x _{t},x_{t-1},... ,x _{t-d-1}), f is an unknown function, beta_{i}'s are unknown vectors, varepsilon_{t }'s are independent distributed. Special cases include AR and TAR models. We investigate the feasibility applying SIR/PHD (Li 1990, 1991) (the sliced inverse regression and principal Hessian methods) in estimating beta _{i}'s. PCA (Principal component analysis) is brought in to check one critical condition for SIR/PHD. Through simulation and a study on 3 well -known data sets of Canadian lynx, U.S. unemployment rate and sunspot numbers, we demonstrate how SIR/PHD can effectively retrieve the interesting low-dimension structures for time series data.

  14. Thin-slice perception develops slowly.

    PubMed

    Balas, Benjamin; Kanwisher, Nancy; Saxe, Rebecca

    2012-06-01

    Body language and facial gesture provide sufficient visual information to support high-level social inferences from "thin slices" of behavior. Given short movies of nonverbal behavior, adults make reliable judgments in a large number of tasks. Here we find that the high precision of adults' nonverbal social perception depends on the slow development, over childhood, of sensitivity to subtle visual cues. Children and adult participants watched short silent clips in which a target child played with Lego blocks either in the (off-screen) presence of an adult or alone. Participants judged whether the target was playing alone or not; that is, they detected the presence of a social interaction (from the behavior of one participant in that interaction). This task allowed us to compare performance across ages with the true answer. Children did not reach adult levels of performance on this task until 9 or 10 years of age, and we observed an interaction between age and video reversal. Adults and older children benefitted from the videos being played in temporal sequence, rather than reversed, suggesting that adults (but not young children) are sensitive to natural movement in social interactions. PMID:22417920

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

    PubMed

    Solanki, Shailesh; Babu, M Narendra; Gowrishankar; Ramesh, S

    2016-01-01

    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. PMID:27274132

  16. Short latency cerebellar modulation of the basal ganglia

    PubMed Central

    Chen, Christopher H.; Fremont, Rachel; Arteaga-Bracho, Eduardo E.; Khodakhah, Kamran

    2014-01-01

    The graceful, purposeful motion of our body is an engineering feat which remains unparalleled in robotic devices using advanced artificial intelligence. Much of the information required for complex movements is generated by the cerebellum and the basal ganglia in conjunction with the cortex. Cerebellum and basal ganglia have been thought to communicate with each other only through slow multi-synaptic cortical loops, begging the question as to how they coordinate their outputs in real time. Here we show in mice that the cerebellum rapidly modulates the activity of the striatum via a disynaptic pathway. Under physiological conditions this short latency pathway is capable of facilitating optimal motor control by allowing the basal ganglia to incorporate time-sensitive cerebellar information and by guiding the sign of cortico-striatal plasticity. Conversely, under pathological condition this pathway relays aberrant cerebellar activity to the basal ganglia to cause dystonia. PMID:25402853

  17. Cognitive planning deficit in patients with cerebellar atrophy.

    PubMed

    Grafman, J; Litvan, I; Massaquoi, S; Stewart, M; Sirigu, A; Hallett, M

    1992-08-01

    We compared the performance of 12 patients with cerebellar atrophy (CA) and 12 normal controls matched for age and education on the Tower of Hanoi, a nine-problem task that requires cognitive planning. CA patients performed significantly worse than controls on this task despite no difference in planning and between-move pause times. A reanalysis of the data using just the subgroup of patients with pure cerebellar cortical atrophy (CCA) (N = 9) replicated the above results and also showed that CCA patients had significantly increased planning times compared with controls. Neither age, sex, education level, severity of dementia, word fluency, response time, memory, nor visuomotor procedural learning predicted CA or CCA performance. This deficit in cognitive planning suggests a functional link between the cerebellum, basal ganglia, and the frontal lobe concerning specific cognitive processes. However, the exact role of the cerebellum in cognitive planning remains undetermined. PMID:1641142

  18. Ruptured Total Intrameatal Anterior Inferior Cerebellar Artery Aneurysm

    PubMed Central

    Kim, Hyung Cheol; Chang, In Bok; Lee, Ho Kook

    2015-01-01

    Among the distal anterior inferior cerebellar artery (AICA) aneurysms, a unique aneurysm at the meatal loop inside the internal auditory meatus is extremely rare. The authors report a case of surgically treated total intrameatal AICA aneurysm. A 62-year-old female patient presenting with sudden bursting headache and neck pain was transferred to our department. Computed tomography and digital subtraction angiography showed subarachnoid hemorrhage at the basal, prepontine cistern and an aneurysm of the distal anterior inferior cerebellar artery inside the internal auditory meatus. Surgery was performed by retrosigmoid craniotomy with unroofing of the internal auditory meatus. The aneurysm was identified between the seventh and eighth cranial nerve in the meatus and was removed from the canal and clipped with a small straight Sugita clip. After operation the patient experienced transient facial paresis and tinnitus but improved during follow up. PMID:26361531

  19. [Atypical cerebellar neurocytoma resembling a hemangioblastoma. A case report].

    PubMed

    Lista Martínez, Olalla; Rivas López, Luis Alfredo; Pombo Otero, Jorge Francisco; Amaro Cendón, Santiago; Bravo García, Christian; Villa Fernández, Juan Manuel

    2014-01-01

    Through August 2013, 105 cases of intracranial extraventricular neurocytoma (EVN) had been described; 6% were located in cerebellum and 22% were atypical EVN. A rare morphologic form of neurocytoma, atypical EVN has had only 24 cases reported to date. Its prognosis is poorer than the typical central neurocytoma. This case report describes an atypical cerebellar EVN, a form that has not been reported yet, hence the interest of this article. We emphasise its cystic nature and mural nodule, in an infrequent presentation. EVN are low-incidence tumours that we need to take into consideration when making the differential diagnosis of cystic cerebellar lesions with mural nodule. Given that the prognosis of atypical EVNs depends on the atypical nature and on the grade of resection, medical follow up has to be more constant, due to the greater degree of recurrence. PMID:24837842

  20. Short latency cerebellar modulation of the basal ganglia.

    PubMed

    Chen, Christopher H; Fremont, Rachel; Arteaga-Bracho, Eduardo E; Khodakhah, Kamran

    2014-12-01

    The graceful, purposeful motion of our body is an engineering feat that remains unparalleled in robotic devices using advanced artificial intelligence. Much of the information required for complex movements is generated by the cerebellum and the basal ganglia in conjunction with the cortex. Cerebellum and basal ganglia have been thought to communicate with each other only through slow, multi-synaptic cortical loops, begging the question as to how they coordinate their outputs in real time. We found that the cerebellum rapidly modulates the activity of the striatum via a disynaptic pathway in mice. Under physiological conditions, this short latency pathway was capable of facilitating optimal motor control by allowing the basal ganglia to incorporate time-sensitive cerebellar information and by guiding the sign of cortico-striatal plasticity. Conversely, under pathological condition, this pathway relayed aberrant cerebellar activity to the basal ganglia to cause dystonia. PMID:25402853

  1. Neurotrophic effects of PACAP in the cerebellar cortex.

    PubMed

    Botia, Béatrice; Basille, Magali; Allais, Aurélie; Raoult, Emilie; Falluel-Morel, Anthony; Galas, Ludovic; Jolivel, Valérie; Wurtz, Olivier; Komuro, Hitoshi; Fournier, Alain; Vaudry, Hubert; Burel, Delphine; Gonzalez, Bruno J; Vaudry, David

    2007-09-01

    In the rodent cerebellum, PACAP is expressed by Purkinje neurons and PAC1 receptors are present on granule cells during both the development period and in adulthood. Treatment of granule neurons with PACAP inhibits proliferation, slows migration, promotes survival and induces differentiation. PACAP also protects cerebellar granule cells against the deleterious effects of neurotoxic agents. Most of the neurotrophic effects of PACAP are mediated through the cAMP/PKA signaling pathway and often involve the ERK MAPkinase. Caspase-3 is one of the key enzymes implicated in the neuroprotective action of PACAP but PACAP also inhibits caspase-9 activity and increases Bcl-2 expression. PACAP and functional PAC1 receptors are expressed in the monkey and human cerebellar cortex with a pattern of expression very similar to that described in rodents, suggesting that PACAP could also exert neurodevelopmental and neuroprotective functions in the cerebellum of primates including human. PMID:17544170

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

    PubMed Central

    Solanki, Shailesh; Babu, M. Narendra; Gowrishankar; Ramesh, S.

    2016-01-01

    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. PMID:27274132

  3. Glial-Restricted Precursors Protect Neonatal Brain Slices from Hypoxic-Ischemic Cell Death Without Direct Tissue Contact.

    PubMed

    Sweda, Romy; Phillips, Andre W; Marx, Joel; Johnston, Michael V; Wilson, Mary Ann; Fatemi, Ali

    2016-07-01

    Glial-Restricted Precursors (GRPs) are tripotential progenitors that have been shown to exhibit beneficial effects in several preclinical models of neurological disorders, including neonatal brain injury. The mechanisms of action of these cells, however, require further study, as do clinically relevant questions such as timing and route of cell administration. Here, we explored the effects of GRPs on neonatal hypoxia-ischemia during acute and subacute stages, using an in vitro transwell co-culture system with organotypic brain slices exposed to oxygen-glucose deprivation (OGD). OGD-exposed slices that were then co-cultured with GRPs without direct cell contact had decreased tissue injury and cortical cell death, as evaluated by lactate dehydrogenase (LDH) release and propidium iodide (PI) staining. This effect was more pronounced when cells were added during the subacute phase of the injury. Furthermore, GRPs reduced the amount of glutamate in the slice supernatant and changed the proliferation pattern of endogenous progenitor cells in brain slices. In summary, we show that GRPs exert a neuroprotective effect on neonatal hypoxia-ischemia without the need for direct cell-cell contact, thus confirming the rising view that beneficial actions of stem cells are more likely attributable to trophic or immunomodulatory support rather than to long-term integration. PMID:27149035

  4. Presumptive caudal cerebellar artery infarct in a dog: clinical and MRI findings.

    PubMed

    Negrin, A; Gaitero, L; Añor, S

    2009-11-01

    Clinical signs and magnetic resonance imaging findings of a caudal cerebellar artery infarct are reported for the first time in a dog. Clinical signs were characterised by a peracute, non-progressive, right-sided central vestibular syndrome with paradoxical right-sided head tilt. Magnetic resonance images were consistent with a territorial, non-haemorrhagic, ischaemic lesion affecting the caudo-ventral part of the right cerebellar hemisphere, mainly involving the right paramedian lobe, the ansiform lobe and the caudal cerebellar peduncle. Bloodwork results were suggestive of an underlying hypercoagulable state, although the concomitant presence of a histologically confirmed mammary gland adenocarcinoma could have also been related to the cerebellar vascular obstruction through metastatic emboli formation. Posterior-inferior cerebellar artery infarction is the human equivalent of caudal cerebellar artery infarct in dogs. PMID:19891725

  5. The cerebellar component of Friedreich’s ataxia

    PubMed Central

    Davis, Ashley N.; Morral, Jennifer A.

    2016-01-01

    Lack of frataxin in Friedreich’s ataxia (FRDA) causes a complex neurological and pathological phenotype. Progressive atrophy of the dentate nucleus (DN) is a major intrinsic central nervous system lesion. Antibodies to neuron-specific enolase (NSE), calbindin, glutamic acid decarboxylase (GAD), and vesicular glutamate transporters 1 and 2 (VGluT1, VGluT2) allowed insight into the disturbed synaptic circuitry of the DN. The available case material included autopsy specimens of 24 patients with genetically defined FRDA and 14 normal controls. In FRDA, the cerebellar cortex revealed intact Purkinje cell somata and dendrites as assessed by calbindin immunore-activity. The DN, however, displayed severe loss of large NSE-reactive neurons. Small neurons remained intact. Labeling of Purkinje cells, basket fibers, Golgi neurons, and Golgi axonal plexuses with antibodies to GAD indicated normal intrinsic circuitry of the cerebellar cortex involving γ-aminobutyric acid (GABA). In contrast, the DN displayed severe loss of GABA-ergic terminals and formation of GAD- and calbindin-reactive grumose degeneration. The surviving small GAD-positive DN neurons provided normal GABA-ergic terminals to intact inferior olivary nuclei. The olives also received normal glutamatergic terminals as shown by VGluT2-reactivity. VGluT1-immunocytochemistry of the cerebellar cortex confirmed normal glutamatergic input to the molecular layer by parallel fibers and the granular layer by mossy fibers. VGluT2-immunoreactivity visualized normal climbing fibers and mossy fiber terminals. The DN, however, showed depletion of VGluT1- and VGluT2-reactive terminals arising from climbing and mossy fiber collaterals. The main functional deficit underlying cerebellar ataxia in FRDA is defective processing of inhibitory and excitatory impulses that converge on the large neurons of the DN. The reason for the selective vulnerability of these nerve cells remains elusive. PMID:21638087

  6. Direct transcranial puncture for Onyx embolization of a cerebellar hemangioblastoma.

    PubMed

    Ding, Dale; Starke, Robert M; Evans, Avery J; Liu, Kenneth C

    2014-06-01

    Intracranial hemangioblastomas are benign but hypervascular tumors, most commonly located in the cerebellum, which are difficult to resect without significant operative blood loss. While preoperative embolization may decrease the amount of operative bleeding, the vascular supply of cerebellar hemangioblastomas frequently precludes safe embolization by an endovascular route due to the risk of thromboembolic vertebrobasilar infarction. Direct puncture embolization overcomes many of the limitations of endovascular embolization but its safety and feasibility for intracranial tumors is unknown. We report a 48-year-old man who was diagnosed with a large cerebellar mass after presenting with headaches and gait ataxia. Based on diagnostic angiography, which demonstrated a highly vascular tumor supplied by the posterior inferior cerebellar and posterior meningeal arteries, we decided to embolize the tumor by a direct transcranial puncture approach. After trephinating the skull in a standard fashion, a catheter-needle construct, composed of an Echelon 10 microcatheter (ev3 Endovascular, Plymouth, MN, USA) placed into a 21-gauge spinal needle, was inserted into the tumor under biplanar angiographic guidance. Using continuous angiographic monitoring, 9cc of Onyx 34 (ev3 Endovascular) was injected through the catheter, resulting in 75% tumor devascularization without evidence of complications. The patient was taken directly to surgery where a gross total resection of the hemangioblastoma was achieved with an acceptable operative blood loss. At his 2 year follow-up, the patient was neurologically intact without neuroimaging evidence of residual tumor. We describe, to our knowledge, the first case of direct transcranial puncture for preoperative embolization of a cerebellar hemangioblastoma. PMID:24370504

  7. [Cerebellar hemangioblastoma and thrombocytopenia: Report of one case].

    PubMed

    Patiño G, Santiago

    2016-04-01

    The association between vascular tumors and thrombocytopenia is rare. Kasabach-Merritt Syndrome is seen in childhood and is characterized by hemangiomas and thrombocytopenia. A 42 years-old man with a cerebellar hemangioblastoma and thrombocytopenia, admitted with a subarachnoid hemorrhage is reported. The patient was operated and required a splenectomy to manage the thrombocytopenia. After the splenectomy the patient developed a subdural hematoma that was operated. Despite the surgical treatment, the patient died. PMID:27401386

  8. Imaging Spectrum of Cerebellar Pathologies: A Pictorial Essay

    PubMed Central

    Arora, Richa

    2015-01-01

    Summary The cerebellum is a crucial structure of hindbrain which helps in maintaining motor tone, posture, gait and also coordinates skilled voluntary movements including eye movements. Cerebellar abnormalities have different spectrum, presenting symptoms and prognosis as compared to supratentorial structures and brainstem. This article intends to review the various pathological processes involving the cerebellum along with their imaging features on MR, which are must to know for all radiologists, neurologists and neurosurgeons for their prompt diagnosis and management. PMID:25806100

  9. Bilateral cerebellar activation in unilaterally challenged essential tremor

    PubMed Central

    Broersma, Marja; van der Stouwe, Anna M.M.; Buijink, Arthur W.G.; de Jong, Bauke M.; Groot, Paul F.C.; Speelman, Johannes D.; Tijssen, Marina A.J.; van Rootselaar, Anne-Fleur; Maurits, Natasha M.

    2015-01-01

    Background Essential tremor (ET) is one of the most common hyperkinetic movement disorders. Previous research into the pathophysiology of ET suggested underlying cerebellar abnormalities. Objective In this study, we added electromyography as an index of tremor intensity to functional Magnetic Resonance Imaging (EMG-fMRI) to study a group of ET patients selected according to strict criteria to achieve maximal homogeneity. With this approach we expected to improve upon the localization of the bilateral cerebellar abnormalities found in earlier fMRI studies. Methods We included 21 propranolol sensitive patients, who were not using other tremor medication, with a definite diagnosis of ET defined by the Tremor Investigation Group. Simultaneous EMG-fMRI recordings were performed while patients were off tremor medication. Patients performed unilateral right hand and arm extension, inducing tremor, alternated with relaxation (rest). Twenty-one healthy, age- and sex-matched participants mimicked tremor during right arm extension. EMG power variability at the individual tremor frequency as a measure of tremor intensity variability was used as a regressor, mathematically independent of the block regressor, in the general linear model used for fMRI analysis, to find specific tremor-related activations. Results Block-related activations were found in the classical upper-limb motor network, both for ET patients and healthy participants in motor, premotor and supplementary motor areas. In ET patients, we found tremor-related activations bilaterally in the cerebellum: in left lobules V, VI, VIIb and IX and in right lobules V, VI, VIIIa and b, and in the brainstem. In healthy controls we found simulated tremor-related activations in right cerebellar lobule V. 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. PMID:26909321

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

    PubMed

    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. PMID:25655100

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

    PubMed

    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

  12. AMPA receptor-mediated alterations of intracellular calcium homeostasis in rat cerebellar Purkinje cells in vitro: correlates to dark cell degeneration.

    PubMed

    Strahlendorf, J C; Brandon, T; Miles, R; Strahlendorf, H K

    1998-11-01

    In the rat cerebellar slice preparation in vitro, excessive DL-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA)-receptor activation elicits a characteristic type of excitotoxicity of Purkinje cells (PCs) known as dark cell degeneration (DCD). DCD models neurotoxicity of PCs and hippocampal pyramidal neurons in vivo following hyperexcitable states. The intent of this study was to: a) determine whether AMPA-induced neurotoxicity of PCs is correlated with temporally and spatially restricted rises in intracellular Ca2+ and b) whether GYKI 52466 and nominal external Ca2+, conditions that reduced expression of AMPA-elicited DCD, altered the induced Ca2+ patterns. Employing the Ca2+-sensitive dye Fluo-3 and a confocal laser scanning microscope, we evaluated changes in intracellular Ca2+ within PCs in a cerebellar slice preparation. AMPA application alone (30 microM for 30 min) caused a significant initial rise in perinuclear and cytoplasmic Ca2+ that returned to control levels during the latter part of the AMPA exposure period. Following removal of AMPA (expression period), perinuclear and cytoplasmic Ca2+ displayed a significant delayed rise peaking transiently 60 min after AMPA removal. The efficacy of GYKI 52466 and nominal external Ca2+ conditions to attenuate AMPA-induced DCD was correlated to reductions in AMPA-induced transient elevations in perinuclear and cytoplasmic Ca2+ levels during the expression phase and to a lesser extent during the exposure period. The present data suggest that during the expression phase, the delayed perinuclear and cytoplasmic Ca2+ transient may be the harbinger of impending loss of Ca2+ homeostasis and cell damage. PMID:9814545

  13. [A woman with cerebellar ataxia and hypergonadotropic hypogonadism].

    PubMed

    Wada, Sayoko; Takaoka, Toshio; Kasama, Shuhei; Kimura, Takashi; Kajiyama, Koji; Takeda, Masanaka; Yoshikawa, Hiroo

    2010-01-01

    A 26-year-old woman with primary amenorrhea in association with hypergonadotropinism, and lacking a vagina and uterus, suffered from a gradually progressive gait disturbance in her adolescence. The patient has no family history of ataxia and a chromosome study showed a normal karyotype (46,XX). Using the revised Hasegawa Dementia Scale, her cognitive function was measured as that of a normal adult, however, neurological examination revealed symptoms of scanning speech, horizontal gaze-evoked nystagmus, and ataxia. Bulging eyes, high-arched palate, scoliosis and ventricular septal defect were also observed. A brain MRI showed atrophy of the cerebellum. A 123I-IMP brain SPECT study showed hypoperfusion in the cerebellum. Previous studies show that among patients with cerebellar ataxia and hypergonadotropic hypogonadism, some show an autosomal recessive inheritance, while others have no family history. As a cause, a chromosomal abnormality is unlikely because all reported karyotypes were normal. This case is different from other reported cases in that she is not mentally impaired or deaf. The present case indicates that there is a close relationship between cerebellar ataxia and hypogonadism, and that other symptoms such as deafness and mental impairment could be an additional variable in patients with cerebellar ataxia arid hypergonadotropic hypogonadism. PMID:20120350

  14. Sustained Reduction of Cerebellar Activity in Experimental Epilepsy

    PubMed Central

    Rijkers, Kim; Moers-Hornikx, Véronique M. P.; Hemmes, Roelof J.; Aalbers, Marlien W.; Temel, Yasin; Vles, Johan S. H.; Hoogland, Govert

    2015-01-01

    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) (immuno)histochemistry. 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. PMID:26417599

  15. A case of cystinuria presenting with cerebellar ataxia and dementia.

    PubMed

    Tohge, Rie; Sakamoto, Shinichi; Takahashi, Makio

    2016-08-01

    Cystinuria normally manifests as recurrent urinary stones and renal dysfunction, but can present to neurologists with ataxia, posterior column impairment, intellectual deficiency and pyramidal and extrapyramidal signs; the neuroradiological features include cerebellar, brainstem and cerebral atrophy. It is an autosomal recessive disease caused by a transport disorder of cystine and dibasic amino acids in renal proximal tubules. Most cases have an SLC3A1 and/or SLC7A9 gene mutation but some recent Japanese patients have had distinct heterozygous gene mutations. We report a patient with cystinuria with a heterozygous P482L mutation in the SLC7A9 gene, presenting with atrophy in the cerebellum, brainstem and cerebrum and with no urinary stones. Cystine, an amino acid comprising two cysteine molecules, is transported into cells via a cystine transporter. It is essential for producing hydrogen sulfate and the cellular antioxidant glutathione: these exert neuroprotection in astrocytes and cerebellar Purkinje cells. Although cystinuria is a metabolic disorder associated with renal dysfunction, we suspect that a trafficking defect of transporter rBAT-BAT1 in brain might cause neuronal degeneration, leading to cerebellar and cerebral atrophy. PMID:26929440

  16. Evidence for Cerebellar Contributions to Adaptive Plasticity in Speech Perception.

    PubMed

    Guediche, Sara; Holt, Lori L; Laurent, Patryk; Lim, Sung-Joo; Fiez, Julie A

    2015-07-01

    Human speech perception rapidly adapts to maintain comprehension under adverse listening conditions. For example, with exposure listeners can adapt to heavily accented speech produced by a non-native speaker. Outside the domain of speech perception, adaptive changes in sensory and motor processing have been attributed to cerebellar functions. The present functional magnetic resonance imaging study investigates whether adaptation in speech perception also involves the cerebellum. Acoustic stimuli were distorted using a vocoding plus spectral-shift manipulation and presented in a word recognition task. Regions in the cerebellum that showed differences before versus after adaptation were identified, and the relationship between activity during adaptation and subsequent behavioral improvements was examined. These analyses implicated the right Crus I region of the cerebellum in adaptive changes in speech perception. A functional correlation analysis with the right Crus I as a seed region probed for cerebral cortical regions with covarying hemodynamic responses during the adaptation period. The results provided evidence of a functional network between the cerebellum and language-related regions in the temporal and parietal lobes of the cerebral cortex. Consistent with known cerebellar contributions to sensorimotor adaptation, cerebro-cerebellar interactions may support supervised learning mechanisms that rely on sensory prediction error signals in speech perception. PMID:24451660

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

    PubMed Central

    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

  18. Deficits in reflexive covert attention following cerebellar injury.

    PubMed

    Striemer, Christopher L; Cantelmi, David; Cusimano, Michael D; Danckert, James A; Schweizer, Tom A

    2015-01-01

    Traditionally the cerebellum has been known for its important role in coordinating motor output. Over the past 15 years numerous studies have indicated that the cerebellum plays a role in a variety of cognitive functions including working memory, language, perceptual functions, and emotion. In addition, recent work suggests that regions of the cerebellum involved in eye movements also play a role in controlling covert visual attention. Here we investigated whether regions of the cerebellum that are not strictly tied to the control of eye movements might also contribute to covert attention. To address this question we examined the effects of circumscribed cerebellar lesions on reflexive covert attention in a group of patients (n = 11) without any gross motor or oculomotor deficits, and compared their performance to a group of age-matched controls (n = 11). Results indicated that the traditional RT advantage for validly cued targets was significantly smaller at the shortest (50 ms) SOA for cerebellar patients compared to controls. Critically, a lesion overlap analysis indicated that this deficit in the rapid deployment of attention was linked to damage in Crus I and Crus II of the lateral cerebellum. Importantly, both cerebellar regions have connections to non-motor regions of the prefrontal and posterior parietal cortices-regions important for controlling visuospatial attention. Together, these data provide converging evidence that both lateral and midline regions of the cerebellum play an important role in the control of reflexive covert visual attention. PMID:26300756

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

    PubMed

    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. PMID:25524412

  20. Visuospatial hemi-inattention following cerebellar/brain stem bleeding.

    PubMed

    Hildebrandt, H; Spang, K; Ebke, M

    2002-01-01

    Neglect is a unilateral lack of responsiveness to stimuli caused by visuospatial hemi-inattention, a unilateral representation deficit and/or a unilateral hypokinesia. It results most frequently from right-hemisphere brain damage, particularly of the parietal lobe but also of the frontal cortex, the basal ganglia, the thalamus, and recently it has also been described after a cerebellar lesion. We report a patient with right-sided bleeding of the posterior inferior cerebellar artery, who developed a left-sided visual hemi-inattention. She had no visual field defects, yet she had problems detecting left-sided targets in visual extinction. Furthermore, she was impaired in detecting complex motion on the left side and targets in a fixation offset paradigm. Reactions to left-sided targets in covert shifts of attention were slowed in the invalid condition. Her text reading was impaired as she could not always find the initial word of the next line. However, she was aware of her deficit. Her visuoconstructive ability was normal and she gave no indication of tactile or acoustic extinction. As the cerebellar lesion was located in the right hemisphere and the inattention involved the left side of space, we suggest that the damage to the right brain stem led to a transient imbalance of the noradrenergic ascending activation system which may explain her hemi-inattention. PMID:12221145

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

    PubMed

    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. PMID:27606347

  2. Cerebellar information processing in relapsing-remitting multiple sclerosis (RRMS).

    PubMed

    Lesage, E; Apps, M A J; Hayter, A L; Beckmann, C F; Barnes, D; Langdon, D W; Ramnani, N

    2010-01-01

    Recent research has characterized the anatomical connectivity of the cortico-cerebellar system - a large and important fibre system in the primate brain. Within this system, there are reciprocal projections between the prefrontal cortex and Crus II of the cerebellar cortex, which both play important roles in the acquisition and execution of cognitive skills. Here, we propose that this system also plays a particular role in sustaining skilled cognitive performance in patients with Relapsing-Remitting Multiple Sclerosis (RRMS), in whom advancing neuropathology causes increasingly inefficient information processing. We scanned RRMS patients and closely matched healthy subjects while they performed the Paced Auditory Serial Addition Test (PASAT), a demanding test of information processing speed, and a control task. This enabled us to localize differences between conditions that change as a function of group (group-by-condition interactions). Hemodynamic activity in some patient populations with CNS pathology are not well understood and may be atypical, so we avoided analysis strategies that rely exclusively on models of hemodynamic activity derived from the healthy brain, using instead an approach that combined a 'model-free' analysis technique (Tensor Independent Component Analysis, TICA) that was relatively free of such assumptions, with a post-hoc 'model-based' approach (General Linear Model, GLM). Our results showed group-by-condition interactions in cerebellar cortical Crus II. We suggest that this area may have in role maintaining performance in working memory tasks by compensating for inefficient data transfer associated with white matter lesions in MS. PMID:20714060

  3. Deficits in reflexive covert attention following cerebellar injury

    PubMed Central

    Striemer, Christopher L.; Cantelmi, David; Cusimano, Michael D.; Danckert, James A.; Schweizer, Tom A.

    2015-01-01

    Traditionally the cerebellum has been known for its important role in coordinating motor output. Over the past 15 years numerous studies have indicated that the cerebellum plays a role in a variety of cognitive functions including working memory, language, perceptual functions, and emotion. In addition, recent work suggests that regions of the cerebellum involved in eye movements also play a role in controlling covert visual attention. Here we investigated whether regions of the cerebellum that are not strictly tied to the control of eye movements might also contribute to covert attention. To address this question we examined the effects of circumscribed cerebellar lesions on reflexive covert attention in a group of patients (n = 11) without any gross motor or oculomotor deficits, and compared their performance to a group of age-matched controls (n = 11). Results indicated that the traditional RT advantage for validly cued targets was significantly smaller at the shortest (50 ms) SOA for cerebellar patients compared to controls. Critically, a lesion overlap analysis indicated that this deficit in the rapid deployment of attention was linked to damage in Crus I and Crus II of the lateral cerebellum. Importantly, both cerebellar regions have connections to non-motor regions of the prefrontal and posterior parietal cortices—regions important for controlling visuospatial attention. Together, these data provide converging evidence that both lateral and midline regions of the cerebellum play an important role in the control of reflexive covert visual attention. PMID:26300756

  4. Cerebellar Cortical Lamination and Foliation Require Cyclin A2

    PubMed Central

    Otero, José Javier; Kalaszczynska, Ilona; Michowski, Wojciech; Wong, Michael; Gygli, Patrick Edwin; Gokozan, Hamza Numan; Griveau, Amélie; Odajima, Junko; Czeisler, Catherine; Catacutan, Fay Patsy; Murnen, Alice; Schüler, Ulrich; Sicinski, Piotr; Rowitch, David

    2014-01-01

    The mammalian genome encodes two A-type cyclins, which are considered potentially redundant yet essential regulators of the cell cycle. Here, we tested requirements for cyclin A1 and cyclin A2 function in cerebellar development. Compound conditional loss of cyclin A1/A2 in neural progenitors resulted in severe cerebellar hypoplasia, decreased proliferation of cerebellar granule neuron progenitors (CGNP), and Purkinje (PC) neuron dyslamination. Deletion of cyclin A2 alone showed an identical phenotype, demonstrating that cyclin A1 does not compensate for cyclin A2 loss in neural progenitors. Cyclin A2 loss lead to increased apoptosis at early embryonic time points but not at post-natal time points. In contrast, neural progenitors of the VZ/SVZ did not undergo increased apoptosis, indicating that VZ/SVZ-derived and rhombic lip-derived progenitor cells show differential requirements to cyclin A2. Conditional knockout of cyclin A2 or the SHH proliferative target Nmyc in CGNP also resulted in PC neuron dyslamination. Although cyclin E1 has been reported to compensate for cyclin A2 function in fibroblasts and is upregulated in cyclin A2 null cerebella, cyclin E1 expression was unable to compensate for loss-of cyclin A2 function. PMID:24184637

  5. Executive Function Deficits in Patients after Cerebellar Neurosurgery.

    PubMed

    Mak, Monika; Tyburski, Ernest; Madany, Łukasz; Sokołowski, Andrzej; Samochowiec, Agnieszka

    2016-01-01

    The cerebellum has long been perceived as a structure responsible for the human motor function. According to the contemporary approach, however, it plays a significant role in complex behavior regulatory processes. The aim of this study was to describe executive functions in patients after cerebellar surgery. The study involved 30 patients with cerebellar pathology. The control group comprised 30 neurologically and mentally healthy individuals, matched for sex, age, and number of years of education. Executive functions were measured by the Wisconsin Card Sorting Test (WCST), Stroop Color Word Test (SCWT), Trail Making Test (TMT), and working memory by the Digit Span. Compared to healthy controls, patients made more Errors and Perseverative errors in the WCST, gave more Perseverative responses, and had a lower Number of categories completed. The patients exhibited higher response times in all three parts of the SCWT and TMT A and B. No significant differences between the two groups were reported in their performance of the SCWT and TMT with regard to the measures of absolute or relative interference. The patients had lower score on the backward Digit Span. Patients with cerebellar pathology may exhibit some impairment within problem solving and working memory. Their worse performance on the SCWT and TMT could, in turn, stem from their poor motor-somatosensory control, and not necessarily executive deficits. Our results thus support the hypothesis of the cerebellum's mediating role in the regulation of the activity of the superordinate cognitive control network in the brain. (JINS, 2016, 22, 47-57). PMID:26626541

  6. Adams Oliver syndrome: Description of a new phenotype with cerebellar abnormalities in a family

    PubMed Central

    D’Amico, Alessandra; Melis, Daniela; D’Arco, Felice; Di Paolo, Nilde; Carotenuto, Barbara; D’Anna, Gennaro; Russo, Carmela; Boemio, Pasquale; Brunetti, Arturo

    2013-01-01

    Summary Background To describe cerebellar abnormalities in a family composed by a father and two affected sibs with Adams Oliver syndrome (AOS) (OMIM 100300). Material/Methods Brain MRI and MR angiography were performed at 1.5T. Results The siblings presented cerebellar cortex dysplasia characterized by the presence of cysts. Conclusions Abnormalities of CNS are an unusual manifestation of AOS. To our knowledge, this is the first report of cerebellar cortical dysplasia in a family with AOS. PMID:24505229

  7. Atrophy of the Cerebellar Vermis in Essential Tremor: Segmental Volumetric MRI Analysis.

    PubMed

    Shin, Hyeeun; Lee, Dong-Kyun; Lee, Jong-Min; Huh, Young-Eun; Youn, Jinyoung; Louis, Elan D; Cho, Jin Whan

    2016-04-01

    Postmortem studies of essential tremor (ET) have demonstrated the presence of degenerative changes in the cerebellum, and imaging studies have examined related structural changes in the brain. However, their results have not been completely consistent and the number of imaging studies has been limited. We aimed to study cerebellar involvement in ET using MRI segmental volumetric analysis. In addition, a unique feature of this study was that we stratified ET patients into subtypes based on the clinical presence of cerebellar signs and compared their MRI findings. Thirty-nine ET patients and 36 normal healthy controls, matched for age and sex, were enrolled. Cerebellar signs in ET patients were assessed using the clinical tremor rating scale and International Cooperative Ataxia Rating Scale. ET patients were divided into two groups: patients with cerebellar signs (cerebellar-ET) and those without (classic-ET). MRI volumetry was performed using CIVET pipeline software. Data on whole and segmented cerebellar volumes were analyzed using SPSS. While there was a trend for whole cerebellar volume to decrease from controls to classic-ET to cerebellar-ET, this trend was not significant. The volume of several contiguous segments of the cerebellar vermis was reduced in ET patients versus controls. Furthermore, these vermis volumes were reduced in the cerebellar-ET group versus the classic-ET group. The volume of several adjacent segments of the cerebellar vermis was reduced in ET. This effect was more evident in ET patients with clinical signs of cerebellar dysfunction. The presence of tissue atrophy suggests that ET might be a neurodegenerative disease. PMID:26062905

  8. Remote Cerebellar Infarction after Supratentorial Craniotomy and Its Management: Two Case Reports

    PubMed Central

    Yoon, Seon-Jin

    2015-01-01

    The cerebellar infarction resulting from supratentorial craniotomy is uncommon event and its management has been controversial. After removal of space occupying lesion on right frontal area, two cases of remote cerebellar infarctions occurred. We reviewed each cases and the techniques to manage such complications are discussed. Early extraventricular catheter insertion and midline suboccipital craniectomy were effectively performed in obtunded patients from cerebellar infarction. PMID:26605273

  9. Administration of copper reduced the hyper-excitability of neurons in CA1 hippocampal slices from epileptic rats.

    PubMed

    Leiva, Juan; Infante, Claudio

    2016-04-01

    Copper as a trace metal is involved in several neurodegenerative illnesses, such as Menkes, Wilson's, Alzheimer's, amyotrophic lateral sclerosis (ALS), and Creutzfeldt-Jakob. Electrophysiological evidence indicates that acute perfusion of copper can inhibit long-term synaptic potentiation in hippocampal slices. The objective of this work is to determine whether Cu perfusion can perturb synaptic transmission in hippocampal slices derived from pilocarpine treated epileptic rats. Field potential (FP) recordings of the CA1 neurons of rats with chronic epilepsy showed voltage and response duration decrease following copper sulfate perfusion. However, voltage and response duration were higher after removing copper by washing. The discharge frequency of the CA1 neurons of hippocampal slices from non-epileptic control rats was increased after acute perfusion of 10 μM of pilocarpine. This increase was blocked by administering copper sulphate 10 μM. Krebs-Ringer solution washing re-established the discharges, with a higher frequency than that provoked by pilocarpine perfusion. We discuss the blocking effect of copper and the synaptic hyper-excitability generated by its removal. PMID:27548095

  10. Re-defining the cerebellar cortex as an assembly of non-uniform Purkinje cell microcircuits

    PubMed Central

    Cerminara, Nadia L; Lang, Eric J; Sillitoe, Roy V; Apps, Richard

    2015-01-01

    The adult mammalian cerebellar cortex is generally assumed to have a uniform cytoarchitecture. Differences in cerebellar function are thought to arise, in the main, through distinct patterns of input and output connectivity, rather than as a result of variations in cortical microcircuitry. However, evidence from anatomical, physiological and genetic studies is increasingly challenging this orthodoxy and there are now various lines of evidence that the cerebellar cortex is non uniform. Here we develop the hypothesis that regional differences in cerebellar cortical microcircuit properties lead to important differences in information processing. PMID:25601779

  11. Recovery of biological motion perception and network plasticity after cerebellar tumor removal.

    PubMed

    Sokolov, Arseny A; Erb, Michael; Grodd, Wolfgang; Tatagiba, Marcos S; Frackowiak, Richard S J; Pavlova, Marina A

    2014-10-01

    Visual perception of body motion is vital for everyday activities such as social interaction, motor learning or car driving. Tumors to the left lateral cerebellum impair visual perception of body motion. However, compensatory potential after cerebellar damage and underlying neural mechanisms remain unknown. In the present study, visual sensitivity to point-light body motion was psychophysically assessed in patient SL with dysplastic gangliocytoma (Lhermitte-Duclos disease) to the left cerebellum before and after neurosurgery, and in a group of healthy matched controls. Brain activity during processing of body motion was assessed by functional magnetic resonance imaging (MRI). Alterations in underlying cerebro-cerebellar circuitry were studied by psychophysiological interaction (PPI) analysis. Visual sensitivity to body motion in patient SL before neurosurgery was substantially lower than in controls, with significant improvement after neurosurgery. Functional MRI in patient SL revealed a similar pattern of cerebellar activation during biological motion processing as in healthy participants, but located more medially, in the left cerebellar lobules III and IX. As in normalcy, PPI analysis showed cerebellar communication with a region in the superior temporal sulcus, but located more anteriorly. The findings demonstrate a potential for recovery of visual body motion processing after cerebellar damage, likely mediated by topographic shifts within the corresponding cerebro-cerebellar circuitry induced by cerebellar reorganization. The outcome is of importance for further understanding of cerebellar plasticity and neural circuits underpinning visual social cognition. PMID:25017648

  12. Importance of genetics in fetal alcohol effects: null mutation of the nNOS gene worsens alcohol-induced cerebellar neuronal losses and behavioral deficits

    PubMed Central

    Bonthius, Daniel J.; Winters, Zachary; Karacay, Bahri; Bousquet, Samantha Larimer; Bonthius, Daniel J.

    2014-01-01

    The cerebellum is a major target of alcohol-induced damage in the developing brain. However, the cerebella of some children are much more seriously affected than others by prenatal alcohol exposure. As a consequence of in utero alcohol exposure, some children have substantial reductions in cerebellar volume and corresponding neurodevelopmental problems, including microencephaly, ataxia, and balance deficits, while other children who were exposed to similar alcohol quantities are spared. One factor that likely plays a key role in determining the impact of alcohol on the fetal cerebellum is genetics. However, no specific gene variant has yet been identified that worsens cerebellar function as a consequence of developmental alcohol exposure. Previous studies have revealed that mice carrying a homozygous mutation of the gene for neuronal nitric oxide synthase (nNOS−/− mice) have more severe acute alcohol-induced neuronal losses from the cerebellum than wild type mice. Therefore, the goals of this study were to determine whether alcohol induces more severe cerebellum-based behavioral deficits in nNOS−/− mice than in wild type mice and to determine whether these worsened behavior deficits are associated with worsened cerebellar neuronal losses. nNOS−/− mice and their wild type controls received alcohol (0.0, 2.2, or 4.4 mg/g) daily over postnatal days 4–9. In adulthood, the mice underwent behavioral testing, followed by neuronal quantification. Alcohol caused dose-related deficits in rotarod and balance beam performance in both nNOS−/− and wild type mice. However, the alcohol-induced behavioral deficits were substantially worse in the nNOS−/− mice than in wild type. Likewise, alcohol exposure led to losses of Purkinje cells and cerebellar granule cells in mice of both genotypes, but the cell losses were more severe in the nNOS−/− mice than in wild type. Behavioral performances were correlated with neuronal number in the nNOS−/− mice, but not

  13. Flavoprotein imaging in the cerebellar cortex in vivo: cellular and metabolic basis and insights into cerebellar function

    NASA Astrophysics Data System (ADS)

    Gao, Wangcai; Chen, Gang; Ebner, Timothy J.

    2009-02-01

    Flavoprotein autofluorescence is an activity dependent intrinsic signal. Flavoproteins are involved in the electron transport chain and change their fluorescence according to the cellular redox state. We have been using flavoprotein autofluorescence in the cerebellum to examine properties of cerebellar circuits. Studies have also focused on understanding the cellular and metabolic origins of this intrinsic optical signal. Parallel fiber stimulation evokes a beamlike response intersected by bands of decreased fluorescence. The beam response is biphasic, with an early fluorescence increase (light phase) followed by a slower decrease (dark phase). We show this signal originates from flavoproteins as determined by its wavelength selectivity and sensitivity to blockers of the electron transport chain. Selectively blocking glutamate receptors abolished the on-beam light phase with the dark phase remaining intact. This demonstrates that the light phase is due to postsynaptic neuronal activation and suggests the dark phase is primarily due to glial activation. The bands of reduced fluorescence intersecting the beam are primarily neuronal in origin, mediated by GABAergic transmission, and due to the inhibitory action of molecular layer interneurons on Purkinje cells and the interneurons themselves. This parasagittally organized molecular layer inhibition differentially modulates the spatial pattern of cerebellar cortical activity. Flavoprotein imaging also reveals the functional architectures underlying the responses to inferior olive and peripheral whisker pad stimulation. Therefore, flavoprotein autofluorescence imaging is providing new insights into cerebellar cortical function and neurometabolic coupling.

  14. Adiabatic slice-selective excitation for surface coils.

    PubMed

    Shen, J; Rothman, D L

    1997-01-01

    A novel RF pulse designed to perform a diabatic slice-selective excitation for surface coils (ASSESS) is proposed in which Bzero gradient is modulated in concert with RF frequency modulation. Within the selected slice, the principles of BIR4 pulses are employed to obtain well-defined, pure-phase and self-refocused spin rotation of arbitrary flip angles despite the presence of high B1 inhomogeneity produced by surface coils. Outside the slice, advantage is taken of the B1 field to dephase equilibrium magnetization to achieve slice selection or outer-volume suppression. This scheme should be useful for many localization techniques. Quaternion analysis of the overall propagator of the proposed pulse and numerical simulations using Bloch equations are performed. The pulse is tested experimentally on a phantom sample. PMID:9169211

  15. Communication: Time- and space-sliced velocity map electron imaging

    SciTech Connect

    Lee, Suk Kyoung; Lin, Yun Fei; Lingenfelter, Steven; Fan, Lin; Winney, Alexander H.; Li, Wen

    2014-12-14

    We develop a new method to achieve slice electron imaging using a conventional velocity map imaging apparatus with two additional components: a fast frame complementary metal-oxide semiconductor camera and a high-speed digitizer. The setup was previously shown to be capable of 3D detection and coincidence measurements of ions. Here, we show that when this method is applied to electron imaging, a time slice of 32 ps and a spatial slice of less than 1 mm thick can be achieved. Each slice directly extracts 3D velocity distributions of electrons and provides electron velocity distributions that are impossible or difficult to obtain with a standard 2D imaging electron detector.

  16. Computed tomographic coronary angiography: how many slices do you need?

    PubMed Central

    Peebles, C

    2006-01-01

    While increasing the number of slices in multislice computed tomography clearly brings benefits in terms of detecting significant coronary disease, heavy calcification remains a problem, as does the high radiation burden PMID:16614268

  17. Cardiac tissue slices: preparation, handling, and successful optical mapping.

    PubMed

    Wang, Ken; Lee, Peter; Mirams, Gary R; Sarathchandra, Padmini; Borg, Thomas K; Gavaghan, David J; Kohl, Peter; Bollensdorff, Christian

    2015-05-01

    Cardiac tissue slices are becoming increasingly popular as a model system for cardiac electrophysiology and pharmacology research and development. Here, we describe in detail the preparation, handling, and optical mapping of transmembrane potential and intracellular free calcium concentration transients (CaT) in ventricular tissue slices from guinea pigs and rabbits. Slices cut in the epicardium-tangential plane contained well-aligned in-slice myocardial cell strands ("fibers") in subepicardial and midmyocardial sections. Cut with a high-precision slow-advancing microtome at a thickness of 350 to 400 μm, tissue slices preserved essential action potential (AP) properties of the precutting Langendorff-perfused heart. We identified the need for a postcutting recovery period of 36 min (guinea pig) and 63 min (rabbit) to reach 97.5% of final steady-state values for AP duration (APD) (identified by exponential fitting). There was no significant difference between the postcutting recovery dynamics in slices obtained using 2,3-butanedione 2-monoxime or blebistatin as electromechanical uncouplers during the cutting process. A rapid increase in APD, seen after cutting, was caused by exposure to ice-cold solution during the slicing procedure, not by tissue injury, differences in uncouplers, or pH-buffers (bicarbonate; HEPES). To characterize intrinsic patterns of CaT, AP, and conduction, a combination of multipoint and field stimulation should be used to avoid misinterpretation based on source-sink effects. In summary, we describe in detail the preparation, mapping, and data analysis approaches for reproducible cardiac tissue slice-based investigations into AP and CaT dynamics. PMID:25595366

  18. Eight-Bit-Slice GaAs General Processor Circuit

    NASA Technical Reports Server (NTRS)

    Weissman, John; Gauthier, Robert V.

    1989-01-01

    Novel GaAs 8-bit slice enables quick and efficient implementation of variety of fast GaAs digital systems ranging from central processing units of computers to special-purpose processors for communications and signal-processing applications. With GaAs 8-bit slice, designers quickly configure and test hearts of many digital systems that demand fast complex arithmetic, fast and sufficient register storage, efficient multiplexing and routing of data words, and ease of control.

  19. Multiple-bipolar-tap tunable spectrum sliced microwave photonic filter.

    PubMed

    Chen, Tong; Yi, Xiaoke; Huang, Thomas; Minasian, Robert A

    2010-12-01

    A spectrum sliced microwave photonic signal processor structure, which is all-fiber based and features simplicity, together with the ability to realize tunability, reconfigurability, bipolar taps, and multiple-tap rf filtering, is presented. It is based on thermally controlled optical slicing filters induced into two linearly chirped fiber Bragg gratings. Experimental results demonstrate the realization of versatile microwave photonic filters with frequency tunable, reconfiguration, and bipolar-tap generation capabilities. PMID:21124570

  20. PRECISION-CUT SLICE CULTURE METHOD FOR RAT PLACENTA

    PubMed Central

    Gilligan, Jeffrey; Tong, Ming; Longato, Lisa; de la Monte, Suzanne M; Gundogan, Fusun

    2011-01-01

    Primary trophoblasts, placental explants, and cell line cultures are commonly used to investigate placental development, physiology, and pathology, particularly in relation to pregnancy outcomes. Organotypic slice cultures are increasingly used in other systems because they maintain the normal three-dimensional tissue architecture and have all cell types represented. Herein, we demonstrate the utility of the precision-cut placental slice culture model for studying trophoblastic diseases. PMID:22079834

  1. Cardiac tissue slices: preparation, handling, and successful optical mapping

    PubMed Central

    Wang, Ken; Lee, Peter; Mirams, Gary R.; Sarathchandra, Padmini; Borg, Thomas K.; Gavaghan, David J.; Kohl, Peter

    2015-01-01

    Cardiac tissue slices are becoming increasingly popular as a model system for cardiac electrophysiology and pharmacology research and development. Here, we describe in detail the preparation, handling, and optical mapping of transmembrane potential and intracellular free calcium concentration transients (CaT) in ventricular tissue slices from guinea pigs and rabbits. Slices cut in the epicardium-tangential plane contained well-aligned in-slice myocardial cell strands (“fibers”) in subepicardial and midmyocardial sections. Cut with a high-precision slow-advancing microtome at a thickness of 350 to 400 μm, tissue slices preserved essential action potential (AP) properties of the precutting Langendorff-perfused heart. We identified the need for a postcutting recovery period of 36 min (guinea pig) and 63 min (rabbit) to reach 97.5% of final steady-state values for AP duration (APD) (identified by exponential fitting). There was no significant difference between the postcutting recovery dynamics in slices obtained using 2,3-butanedione 2-monoxime or blebistatin as electromechanical uncouplers during the cutting process. A rapid increase in APD, seen after cutting, was caused by exposure to ice-cold solution during the slicing procedure, not by tissue injury, differences in uncouplers, or pH-buffers (bicarbonate; HEPES). To characterize intrinsic patterns of CaT, AP, and conduction, a combination of multipoint and field stimulation should be used to avoid misinterpretation based on source-sink effects. In summary, we describe in detail the preparation, mapping, and data analysis approaches for reproducible cardiac tissue slice-based investigations into AP and CaT dynamics. PMID:25595366

  2. Tryptophan availability modulates serotonin release from rat hypothalamic slices

    NASA Technical Reports Server (NTRS)

    Schaechter, Judith D.; Wurtman, Richard J.

    1989-01-01

    The relationship between the tryptophan availability and serononin release from rat hypothalamus was investigated using a new in vitro technique for estimating rates at which endogenous serotonin is released spontaneously or upon electrical depolarization from hypothalamic slices superfused with a solution containing various amounts of tryptophan. It was found that the spontaneous, as well as electrically induced, release of serotonin from the brain slices exhibited a dose-dependent relationship with the tryptophan concentration of the superfusion medium.

  3. Combined infrared-vacuum drying of pumpkin slices.

    PubMed

    Ghaboos, Seyyed Hossein Hosseini; Ardabili, Seyed Mahdi Seyedain; Kashaninejad, Mahdi; Asadi, Gholamhassan; Aalami, Mehran

    2016-05-01

    Infrared-vacuum dehydration characteristics of pumpkin (Cucurbita moschata) were evaluated in a combined dryer system. The effects of drying parameters, infrared radiation power (204-272 W), system pressure (5-15 kPa), slice thickness (5 and 7 mm) and time (0-220 min) on the drying kinetics and characteristics of pumpkin slices were investigated. The vacuum pressure, lamp power and slice had significant effect on the drying kinetics and various qualities of the dried pumpkin. Moisture ratios were fitted to 10 different mathematical equations using nonlinear regression analysis. The quadratic equation satisfactorily described the drying behavior of pumpkin slices with the highest r value and the lowest SE values. The effective moisture diffusivity increased with power and ranged between 0.71 and 2.86 × 10(-9) m(2)/s. With increasing in infrared radiation power from 204 to 272 W, β-carotene content of dried pumpkins decreased from 30.04 to 24.55 mg/100 g. The rise in infrared power has a negative effect on the color changes (ΔE). The optimum condition was determined as power, 238W, pressure, 5 kPa and slice thickness, 5mm. These conditions resulted into dried pumpkin slices with maximum B-carotene retention. PMID:27407204

  4. Preservation of low slice emittance in bunch compressors

    NASA Astrophysics Data System (ADS)

    Bettoni, S.; Aiba, M.; Beutner, B.; Pedrozzi, M.; Prat, E.; Reiche, S.; Schietinger, T.

    2016-03-01

    Minimizing the dilution of the electron beam emittance is crucial for the performance of accelerators, in particular for free electron laser facilities, where the length of the machine and the efficiency of the lasing process depend on it. Measurements performed at the SwissFEL Injector Test Facility revealed an increase in slice emittance after compressing the bunch even for moderate compression factors. The phenomenon was experimentally studied by characterizing the dependence of the effect on beam and machine parameters relevant for the bunch compression. The reproduction of these measurements in simulation required the use of a 3D beam dynamics model along the bunch compressor that includes coherent synchrotron radiation. Our investigations identified transverse effects, such as coherent synchrotron radiation and transverse space charge as the sources of the observed emittance dilution, excluding other effects, such as chromatic effects on single slices or spurious dispersion. We also present studies, both experimental and simulation based, on the effect of the optics mismatch of the slices on the variation of the slice emittance along the bunch. After a corresponding reoptimization of the beam optics in the test facility we reached slice emittances below 200 nm for the central slices along the longitudinal dimension with a moderate increase up to 300 nm in the head and tail for a compression factor of 7.5 and a bunch charge of 200 pC, equivalent to a final current of 150 A, at about 230 MeV energy.

  5. Cerebellar atrophy in Parkinson's disease and its implication for network connectivity.

    PubMed

    O'Callaghan, Claire; Hornberger, Michael; Balsters, Joshua H; Halliday, Glenda M; Lewis, Simon J G; Shine, James M

    2016-03-01

    Pathophysiological and atrophic changes in the cerebellum are documented in Parkinson's disease. Without compensatory activity, such abnormalities could potentially have more widespread effects on both motor and non-motor symptoms. We examined how atrophic change in the cerebellum impacts functional connectivity patterns within the cerebellum and between cerebellar-cortical networks in 42 patients with Parkinson's disease and 29 control subjects. Voxel-based morphometry confirmed grey matter loss across the motor and cognitive cerebellar territories in the patient cohort. The extent of cerebellar atrophy correlated with decreased resting-state connectivity between the cerebellum and large-scale cortical networks, including the sensorimotor, dorsal attention and default networks, but with increased connectivity between the cerebellum and frontoparietal networks. The severity of patients' motor impairment was predicted by a combination of cerebellar atrophy and decreased cerebellar-sensorimotor connectivity. These findings demonstrate that cerebellar atrophy is related to both increases and decreases in cerebellar-cortical connectivity in Parkinson's disease, identifying potential cerebellar driven functional changes associated with sensorimotor deficits. A post hoc analysis exploring the effect of atrophy in the subthalamic nucleus, a cerebellar input source, confirmed that a significant negative relationship between grey matter volume and intrinsic cerebellar connectivity seen in controls was absent in the patients. This suggests that the modulatory relationship of the subthalamic nucleus on intracerebellar connectivity is lost in Parkinson's disease, which may contribute to pathological activation within the cerebellum. The results confirm significant changes in cerebellar network activity in Parkinson's disease and reveal that such changes occur in association with atrophy of the cerebellum. PMID:26794597

  6. Regional variations in protein phosphorylating activity in rat brain studied in micro-slices labeled with ( sup 32 P)phosphate

    SciTech Connect

    Rodnight, R.; Leal, R. )

    1990-01-01

    Regional variations in protein phosphorylating activity in the rat brain were studied. Micro-slices (1 mm diameter) were prepared from 19 brain areas, phosphoproteins labeled by incubation with ({sup 32}P)phosphate, and the tissue analyzed by nonequilibrium two-dimensional electrophoresis and autoradiography. Attention was focused on three phosphorylating systems that showed consistent variation in activity. (1) A system that phosphorylates a substrate of 47 kDa (ppH-47) whose activity was highest in the hippocampus. The next highest activity of this system was observed in the globus pallidus, followed by the periventricular gray matter of the aqueduct, lateral septum, cerebellar cortex, entorhinal cortex, hypothalamus, mammillary nuclei, amygdala, and substantia nigra. Activity was low or undetectable in the cerebral cortex, neostriatum, and the colliculi. (2) A system that phosphorylates a substrate of 50 kDa (ppC-50) whose activity was highest in the caudate nucleus. The activity of this system was roughly inversely correlated with that of the ppH-47 system. (3) The protein kinase C system that phosphorylates an 82- to 87-kDa substrate known as MARCKS. The highest activity of this system was observed in the cerebellar cortex, followed by the hypothalamus, mammillary nuclei, periventricular gray matter of the aqueduct, and the superior colliculus. Activity of this system was relatively low in several regions of the cerebral cortex, the neostriatum, and the inferior colliculus.

  7. Paired-pulse facilitation of multivesicular release and intersynaptic spillover of glutamate at rat cerebellar granule cell–interneurone synapses

    PubMed Central

    Satake, Shin’Ichiro; Inoue, Tsuyoshi; Imoto, Keiji

    2012-01-01

    A simple form of presynaptic plasticity, paired-pulse facilitation (PPF), has been explained as a transient increase in the probability of vesicular release. Using the whole-cell patch-clamp technique to record synaptic activity in rat cerebellar slices, we found different forms of presynaptically originated short-term plasticity during glutamatergic excitatory neurotransmission from granule cells (GCs) to molecular-layer interneurones (INs). Paired-pulse activation of GC axons at short intervals (30–100 ms) elicited not only a facilitation in the peak amplitude (PPFamp), but also a prolongation in the decay-time constant (PPPdecay) of the EPSCs recorded from INs. The results of pharmacological tests and kinetics analyses suggest that the mechanisms underlying the respective types of short-term plasticity were different. PPFamp was elicited by a transient increase in the number of released vesicles. On the other hand, PPPdecay was caused not only by delayed release as has been reported but also by extrasynaptic spillover of the GC transmitter and the subsequent intersynaptic pooling. Both PPFamp and PPPdecay closely rely on repetitive-activation-induced multivesicular release. Using a dynamic clamp technique, we further examined the physiological significance of different presynaptic plasticity, and found that PPFamp and PPPdecay can differentially encode and process neuronal information by influencing the total synaptic charge transferred to postsynaptic INs to reflect activation frequency of the presynaptic GCs. PMID:22930264

  8. Local Application of Drugs to Study Nicotinic Acetylcholine Receptor Function in Mouse Brain Slices

    PubMed Central

    Engle, Staci E.; Broderick, Hilary J.; Drenan, Ryan M.

    2012-01-01

    Tobacco use leads to numerous health problems, including cancer, heart disease, emphysema, and stroke. Addiction to cigarette smoking is a prevalent neuropsychiatric disorder that stems from the biophysical and cellular actions of nicotine on nicotinic acetylcholine receptors (nAChRs) throughout the central nervous system. Understanding the various nAChR subtypes that exist in brain areas relevant to nicotine addiction is a major priority. Experiments that employ electrophysiology techniques such as whole-cell patch clamp or two-electrode voltage clamp recordings are useful for pharmacological characterization of nAChRs of interest. Cells expressing nAChRs, such as mammalian tissue culture cells or Xenopus laevis oocytes, are physically isolated and are therefore easily studied using the tools of modern pharmacology. Much progress has been made using these techniques, particularly when the target receptor was already known and ectopic expression was easily achieved. Often, however, it is necessary to study nAChRs in their native environment: in neurons within brain slices acutely harvested from laboratory mice or rats. For example, mice expressing "hypersensitive" nAChR subunits such as α4 L9′A mice 1 and α6 L9′S mice 2, allow for unambiguous identification of neurons based on their functional expression of a specific nAChR subunit. Although whole-cell patch clamp recordings from neurons in brain slices is routinely done by the skilled electrophysiologist, it is challenging to locally apply drugs such as acetylcholine or nicotine to the recorded cell within a brain slice. Dilution of drugs into the superfusate (bath application) is not rapidly reversible, and U-tube systems are not easily adapted to work with brain slices. In this paper, we describe a method for rapidly applying nAChR-activating drugs to neurons recorded in adult mouse brain slices. Standard whole-cell recordings are made from neurons in slices, and a second micropipette filled with a drug of

  9. Silicon Ingot Casting: Heat Exchanger Method. Multi-wire Slicing: Fixed Abrasine Slicing Technique, Phase 3

    NASA Technical Reports Server (NTRS)

    Schmid, F.; Khattak, C. P.

    1979-01-01

    Ingot casting was scaled up to 16 cm by 16 cm square cross section size and ingots weighing up to 8.1 kg were cast. The high degree of crystallinity was maintained in the large ingot. For large sizes, the nonuniformity of heat treatment causes chipping of the surface of the ingot. Progress was made in the development of a uniform graded structure in the silica crucibles. The high speed slicer blade-head weight was reduced to 37 pounds, allowing surface speeds of up to 500 feet per minute. Slicing of 10 cm diameter workpieces at these speeds increased the through-put of the machine to 0.145 mm/min.

  10. Preparation and Applications of Organotypic Thymic Slice Cultures.

    PubMed

    Sood, Aditi; Dong, Mengqi; Melichar, Heather J

    2016-01-01

    Thymic selection proceeds in a unique and highly organized thymic microenvironment resulting in the generation of a functional, self-tolerant T cell repertoire. In vitro models to study T lineage commitment and development have provided valuable insights into this process. However, these systems lack the complete three-dimensional thymic milieu necessary for T cell development and, therefore, are incomplete approximations of in vivo thymic selection. Some of the challenges related to modeling T cell development can be overcome by using in situ models that provide an intact thymic microenvironment that fully supports thymic selection of developing T cells. Thymic slice organotypic cultures complement existing in situ techniques. Thymic slices preserve the integrity of the thymic cortical and medullary regions and provide a platform to study development of overlaid thymocytes of a defined developmental stage or of endogenous T cells within a mature thymic microenvironment. Given the ability to generate ~20 slices per mouse, thymic slices present a unique advantage in terms of scalability for high throughput experiments. Further, the relative ease in generating thymic slices and potential to overlay different thymic subsets or other cell populations from diverse genetic backgrounds enhances the versatility of this method. Here we describe a protocol for the preparation of thymic slices, isolation and overlay of thymocytes, and dissociation of thymic slices for flow cytometric analysis. This system can also be adapted to study non-conventional T cell development as well as visualize thymocyte migration, thymocyte-stromal cell interactions, and TCR signals associated with thymic selection by two-photon microscopy. PMID:27585240

  11. Cerebellar connections to the dorsomedial and posterior nuclei of the hypothalamus in the rat

    PubMed Central

    ÇAVDAR, SAFİYE; ŞAN, TANGÜL; AKER, REZZAN; ŞEHİRLİ, ÜMİT; ONAT, FİLİZ

    2001-01-01

    The stimulation or ablation of cerebellar structures has produced a variety of visceral responses, indicating a cerebellar role in visceral functions. Studies using anterograde and retrograde tracing methods have revealed connections between the hypothalamus and cerebellar structures. The aim of this study is to investigate the cerebellar connections of the dorsomedial (DMH) and posterior hypothalamic nuclei using retrograde axonal transport of horseradish peroxidase (HRP). In the present study, micro-injection of HRP restricted within the borders of the DMH showed that the projections of this nucleus are not uniform throughout its extent. The posterior DMH receives projections from the cerebellum, whereas the anterior DMH does not. These projections were from the (greatest to least concentration) lateral (dentate), anterior interposed (emboliform), and medial (fastigial) cerebellar nuclei. In addition, both the anterior and posterior DMH receive projections from various areas of the brainstem which confirms earlier studies and provides detailed descriptions. This study also demonstrates the distribution of labelled neurons to cerebellar and brainstem nuclei following HRP injection into the posterior hypothalamic nucleus. It provides clear evidence for a direct cerebellar nuclei-posterior DMH and cerebellar nuclei-posterior hypothalamic nucleus connections. We suggest that the brainstem reticular nuclei and other connections, such as the solitary, trigeminal and vestibular nuclei, of both DMH and posterior hypothalamus may contribute to the indirect cerebellohypothalamic connections. These observations offer a new perspective on the question of how the cerebellum may influence autonomic activity. PMID:11215766

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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. The Cerebellar Deficit Hypothesis and Dyslexic Tendencies in a Non-Clinical Sample

    ERIC Educational Resources Information Center

    Brookes, Rebecca L.; Stirling, John

    2005-01-01

    In order to assess the relationship between cerebellar deficits and dyslexic tendencies in a non-clinical sample, 27 primary school children aged 8-9 completed a cerebellar soft signs battery and were additionally assessed for reading age, sequential memory, picture arrangement and knowledge of common sequences. An average measure of the soft…

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

    ERIC Educational Resources Information Center

    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. Purkinje Cell Activity in the Cerebellar Anterior Lobe after Rabbit Eyeblink Conditioning

    ERIC Educational Resources Information Center

    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.…

  16. Cerebellar Volume in Schizophrenia and Bipolar I Disorder with and without Psychotic Features

    PubMed Central

    Laidi, Charles; d’Albis, Marc-Antoine; Wessa, Michèle; Linke, Julia; Phillips, Mary; Delavest, Marine; Bellivier, Frank; Versace, Amelia; Almeida, Jorge; Sarrazin, Samuel; Poupon, Cyril; Le Dudal, Katia; Daban, Claire; Hamdani, Nora; Leboyer, Marion; Houenou, Josselin

    2014-01-01

    Objective There is growing evidence that cerebellum plays a crucial role in cognition and emotional regulation. Cerebellum is likely to be involved in the physiopathology of both bipolar disorder and schizophrenia. The objective of our study was to compare cerebellar size between patients with bipolar disorder patients with schizophrenia and healthy controls in a multicenter sample. In addition, we studied the influence of psychotic features on cerebellar size in bipolar patients. Method One hundred and fifteen bipolar I patients, thirty-two patients with schizophrenia and fifty-two healthy controls underwent 3 Tesla MRI. Automated segmentation of cerebellum was performed using FreeSurfer software. Volumes of cerebellar cortex and white matter were extracted. Analyses of covariance were conducted and age, sex and intracranial volume were considered as covariates. Results Bilateral cerebellar cortical volumes were smaller in patients with schizophrenia compared to patients with bipolar I disorder and healthy controls. We found no significant difference of cerebellar volume between bipolar patients with and without psychotic features. No change was evidenced in white matter. Conclusion Our results suggest that reduction of cerebellar cortical volume is specific to schizophrenia. Cerebellar dysfunction in bipolar disorder, if present, appears to be more subtle than a reduction in cerebellar volume. PMID:25430729

  17. Optogenetic Manipulation of Cerebellar Purkinje Cell Activity In Vivo

    PubMed Central

    Tsubota, Tadashi; Ohashi, Yohei; Tamura, Keita; Sato, Ayana; Miyashita, Yasushi

    2011-01-01

    Purkinje cells (PCs) are the sole output neurons of the cerebellar cortex. Although their anatomical connections and physiological response properties have been extensively studied, the causal role of their activity in behavioral, cognitive and autonomic functions is still unclear because PC activity cannot be selectively controlled. Here we developed a novel technique using optogenetics for selective and rapidly reversible manipulation of PC activity in vivo. We injected into rat cerebellar cortex lentiviruses expressing either the light-activated cationic channel channelrhodopsin-2 (ChR2) or light-driven chloride pump halorhodopsin (eNpHR) under the control of the PC-specific L7 promoter. Transgene expression was observed in most PCs (ChR2, 92.6%; eNpHR, 95.3%), as determined by immunohistochemical analysis. In vivo electrophysiological recordings showed that all light-responsive PCs in ChR2-transduced rats increased frequency of simple spike in response to blue laser illumination. Similarly, most light-responsive PCs (93.8%) in eNpHR-transduced rats decreased frequency of simple spike in response to orange laser illumination. We then applied these techniques to characterize the roles of rat cerebellar uvula, one of the cardiovascular regulatory regions in the cerebellum, in resting blood pressure (BP) regulation in anesthetized rats. ChR2-mediated photostimulation and eNpHR-mediated photoinhibition of the uvula had opposite effects on resting BP, inducing depressor and pressor responses, respectively. In contrast, manipulation of PC activity within the neighboring lobule VIII had no effect on BP. Blue and orange laser illumination onto PBS-injected lobule IX didn't affect BP, indicating the observed effects on BP were actually due to PC activation and inhibition. These results clearly demonstrate that the optogenetic method we developed here will provide a powerful way to elucidate a causal relationship between local PC activity and functions of the cerebellum

  18. Behavior modification after inactivation of cerebellar dentate nuclei.

    PubMed

    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. PMID:22845704

  19. Cerebellar Contribution to Context Processing in Extinction Learning and Recall.

    PubMed

    Chang, D-I; Lissek, S; Ernst, T M; Thürling, M; Uengoer, M; Tegenthoff, M; Ladd, M E; Timmann, D

    2015-12-01

    Whereas acquisition of new associations is considered largely independent of the context, context dependency is a hallmark of extinction of the learned associations. The hippocampus and the prefrontal cortex are known to be involved in context processing during extinction learning and recall. Although the cerebellum has known functional and anatomic connections to the hippocampus and the prefrontal cortex, cerebellar contributions to context processing of extinction have rarely been studied. In the present study, we reanalyzed functional brain imaging data (fMRI) of previous work investigating context effects during extinction in a cognitive associative learning paradigm in 28 young and healthy subjects (Lissek et al. Neuroimage. 81:131-3, 2013). In that study, event-related fMRI analysis did not include the cerebellum. The 3 T fMRI dataset was reanalyzed using a spatial normalization method optimized for the cerebellum. Data of seven participants had to be excluded because the cerebellum had not been scanned in full. Cerebellar activation related to context change during extinction learning was most prominent in lobule Crus II bilaterally (p < 0.01, t > 2.53; partially corrected by predetermined cluster size). No significant cerebellar activations were observed related to context change during extinction retrieval. The posterolateral cerebellum appears to contribute to context-related processes during extinction learning, but not (or less) during extinction retrieval. The cerebellum may support context learning during extinction via its connections to the hippocampus. Alternatively, the cerebellum may support the shifting of attention to the context via its known connections to the dorsolateral prefrontal cortex. Because the ventromedial prefrontal cortex (vmPFC) is critically involved in context-related processes during extinction retrieval, and there are no known connections between the cerebellum and the vmPFC, the cerebellum may be less important

  20. Cerebellar Transcranial Direct Current Stimulation (ctDCS)

    PubMed Central

    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

    2016-01-01

    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. PMID:25406224

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

    PubMed Central

    Shinn, Ann K.; Baker, Justin T.; Lewandowski, Kathryn E.; Öngür, Dost; Cohen, Bruce M.

    2015-01-01

    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

  2. Probabilistic Identification of Cerebellar Cortical Neurones across Species

    PubMed Central

    Van Dijck, Gert; Van Hulle, Marc M.; Heiney, Shane A.; Blazquez, Pablo M.; Meng, Hui; Angelaki, Dora E.; Arenz, Alexander; Margrie, Troy W.; Mostofi, Abteen; Edgley, Steve; Bengtsson, Fredrik; Ekerot, Carl-Fredrik; Jörntell, Henrik; Dalley, Jeffrey W.; Holtzman, Tahl

    2013-01-01

    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 approach therefore

  3. Acute Bronchitis

    MedlinePlus

    ... or though physical contact (for example, on unwashed hands). Being exposed to tobacco smoke, air pollution, dusts, vapors, and fumes can also cause acute bronchitis. Less often, bacteria can also cause acute bronchitis. To diagnose acute ...

  4. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... control. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  5. Application of a simple cerebellar model to geologic surface mapping

    USGS Publications Warehouse

    Hagens, A.; Doveton, J.H.

    1991-01-01

    Neurophysiological research into the structure and function of the cerebellum has inspired computational models that simulate information processing associated with coordination and motor movement. The cerebellar model arithmetic computer (CMAC) has a design structure which makes it readily applicable as an automated mapping device that "senses" a surface, based on a sample of discrete observations of surface elevation. The model operates as an iterative learning process, where cell weights are continuously modified by feedback to improve surface representation. The storage requirements are substantially less than those of a conventional memory allocation, and the model is extended easily to mapping in multidimensional space, where the memory savings are even greater. ?? 1991.

  6. Late effects of radiotherapy on patients with cerebellar medulloblastoma

    SciTech Connect

    Silverman, C.L.; Palkes, H.; Talent, B.; Kovnar, E.; Clouse, J.W.; Thomas, P.R.

    1984-09-01

    Nine long-term survivors of cerebellar medulloblastoma treated with surgery and irradiation were retrospectively examined with a complete battery of neuropsychological tests and the results compared with their nonirradiated siblings. Significant decreased scores were found in the full-scale intelligence quotients (IQ), performance IQ, and verbal IQ with all nine irradiated patients scoring below their siblings. Also, educational quotients (EQ) of the irradiated patients were 12 to 17 points below the nonirradiated siblings with arithmetic EQ significantly decreased. Most severely affected were those children younger than 8 years at time of irradiation. No correlation was found with whole-brain dose, or objective physical or neurologic findings.

  7. Clipping of ipsilateral posterior communicating and superior cerebellar artery aneurysms.

    PubMed

    Welch, Babu G

    2015-01-01

    The case is a 55-year-old female who presented with dizziness as the chief complaint. She has a family history of two relatives with subarachnoid hemorrhage. Digital subtraction angiography revealed the presence of a left-sided posterior communicating artery aneurysm and an ipsilateral superior cerebellar artery (SCA) aneurysm. Due to the smaller nature of the SCA, a decision was made to proceed with surgical clipping of both lesions through a pterional approach. A narrated video with illustrations depicts the intraoperative management of these lesions with postoperative angiography results. The video can be found here: http://youtu.be/HCHToSsXv-4 . PMID:25554845

  8. Purkinje cell apoptosis in arabian horses with cerebellar abiotrophy.

    PubMed

    Blanco, A; Moyano, R; Vivo, J; Flores-Acuña, R; Molina, A; Blanco, C; Monterde, J G

    2006-08-01

    Purkinje cerebellar cells were studied in three Arabian horses aged between 6 and 8 months with clinical disorders in their movements, tremors and ataxia; the occurrence of apoptosis in this cell population was investigated by the (terminal deoxynucleotidyl transferase biotin-dUTP nick-end labelling (TUNEL) method. Both optical and electron microscopical images showed a scant number of Purkinje cells, most of them with morphological features of apoptosis such as condensation of the nucleus and cytoplasm as well as segregation and fragmentation of the nucleus into apoptotic bodies. The TUNEL technique revealed a substantial number (65%) of positive immunoreactive Purkinje cells. PMID:16901270

  9. Hereditary lissencephaly and cerebellar hypoplasia in Churra lambs

    PubMed Central

    2013-01-01

    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 the brain have been described in sheep, breed-related lissencephaly has not been previously recorded in a peer reviewed publication. Results Here we report neuropathological findings in 42 newborn lambs from a pure Churra breed flock, with clinical signs of weakness, inability to walk, difficulty in sucking and muscular rigidity observed immediately after birth. All the lambs showed near-total agyria with only a rudimentary formation of few sulci and gyri, and a severe cerebellar hypoplasia. On coronal section, the cerebral grey matter was markedly thicker than that of age-matched unaffected lambs and the ventricular system was moderately dilated. Histologically, the normal layers of the cerebral cortex were disorganized and, using an immunohistochemical technique against neurofilaments, three layers were identified instead of the six present in normal brains. The hippocampus was also markedly disorganised and the number and size of lobules were reduced in the cerebellum. Heterotopic neurons were present in different areas of the white matter. The remainder of the brain structures appeared normal. The pathological features reported are consistent with the type LCH-b (lissencephaly with cerebellar hypoplasia group b) defined in human medicine. No involvement of pestivirus or bluetongue virus was detected by immunohistochemistry. An analysis of pedigree data was consistent with a monogenic autosomal recessive pattern inheritance. Conclusions The study describes the clinical and

  10. Cerebellar neurones: differentiation and modulation of sensitivity to excitotoxic treatment.

    PubMed

    Mercanti, D; Angelini, A; Ciotti, M T; Eboli, M L; Galli, C; Battistini, L; Merlo, D; Calissano, P

    1993-01-01

    The neurite outgrowth and adhesion complex (NOAC), isolated from rabbit sera has been dissociated in its major components by reverse-phase chromatography in HPLC by using a C18 column. SDS-PAGE analysis of the active fractions revealed the presence of three major bands of approximately 100, 70 and 50 kDa. Studies on the biological activity of NOAC were carried out on rat cerebellar granule cells. NOAC-cultured cells exhibit a marked resistance to excitotoxic stimuli carried by glutamate. PMID:7763737

  11. Cerebellar neurones: Differentiation and modulation of sensitivity to excitotoxic treatment.

    PubMed

    Mercanti, D; Angelini, A; Ciotti, M; Eboli, M; Galli, C; Battistini, L; Merlo, D; Calissano, P

    1993-01-01

    The neurite outgrowth and adhesion complex (NOAC), isolated from rabbit sera has been dissociated in its major components by reverse-phase chromatography in HPLC by using a C(18) column. SDS-PAGE analisys of the active fractions revealed the presence of three major bands of approximately 100, 70 and 50 kDa. Studies on the biological activity of NOAC were carried out on rat cerebellar granule cells. NOAC-cultured cells exhibit a marked resistance to excitotoxic stimuli carried by glutamate. PMID:22358672

  12. The Role of Intermittent Hypoxia on the Proliferative Inhibition of Rat Cerebellar Astrocytes

    PubMed Central

    Chiu, Sheng-Chun; Lin, Yu-Jou; Huang, Sung-Ying; Lien, Chih-Feng; Chen, Shee-Ping; Pang, Cheng-Yoong; Lin, Jian-Hong; Yang, Kun-Ta

    2015-01-01

    Sleep apnea syndrome, characterized by intermittent hypoxia (IH), is linked with increased oxidative stress. This study investigates the mechanisms underlying IH and the effects of IH-induced oxidative stress on cerebellar astrocytes. Rat primary cerebellar astrocytes were kept in an incubator with an oscillating O2 concentration between 20% and 5% every 30 min for 1–4 days. Although the cell loss increased with the duration, the IH incubation didn’t induce apoptosis or necrosis, but rather a G0/G1 cell cycle arrest of cerebellar astrocytes was noted. ROS accumulation was associated with cell loss during IH. PARP activation, resulting in p21 activation and cyclin D1 degradation was associated with cell cycle G0/G1 arrest of IH-treated cerebellar astrocytes. Our results suggest that IH induces cell loss by enhancing oxidative stress, PARP activation and cell cycle G0/G1 arrest in rat primary cerebellar astrocytes. PMID:26172116

  13. Magnetic resonance image-based cerebellar volumetry in healthy Korean adults.

    PubMed

    Rhyu, I J; Cho, T H; Lee, N J; Uhm, C S; Kim, H; Suh, Y S

    1999-08-01

    The effects of age and gender on cerebellar size have not been established yet. To understand these effects, the area of cerebellar vermis and the volume of cerebellum were measured using serial magnetic resonance images of 124 Korean adults free of neurologic symptoms and signs. Cerebellar volume of male was significantly larger than that of female, although the size of vermis did not show significant gender difference. Correlation analysis revealed that cerebellar volume was not affected by aging. Regressional analysis demonstrated that female vermis had a tendency to shrink after age of 50, whereas male vermis and total cerebellar volume in both sexes were not altered with aging. The different response of vermis with aging and maintenance of cerebellum volume need to be more explored. PMID:10462116

  14. Diagnostic Approach to Childhood-onset Cerebellar Atrophy: A 10-Year Retrospective Study of 300 Patients

    PubMed Central

    Al-Maawali, Almundher; Blaser, Susan; Yoon, Grace

    2013-01-01

    Hereditary ataxias associated with cerebellar atrophy are a heterogeneous group of disorders. Selection of appropriate clinical and genetic tests for patients with cerebellar atrophy poses a diagnostic challenge. Neuroimaging is a crucial initial investigation in the diagnostic evaluation of ataxia in childhood, and the presence of cerebellar atrophy helps guide further investigations. We performed a detailed review of 300 patients with confirmed cerebellar atrophy on magnetic resonance imaging over a 10-year period. A diagnosis was established in 47% of patients: Mitochondrial disorders were most common, followed by the neuronal ceroid lipofuscinoses, ataxia telangectasia, and late GM2-gangliosidosis. We review the common causes of cerebellar atrophy in childhood and propose a diagnostic approach based on correlating specific neuroimaging patterns with clinical and genetic diagnoses. PMID:22764178

  15. Case Series: Fractional Anisotropy Profiles of the Cerebellar Peduncles in Adolescents Born Preterm With Ventricular Dilation.

    PubMed

    Travis, Katherine E; Leitner, Yael; Ben-Shachar, Michal; Yeom, Kristen W; Feldman, Heidi M

    2016-03-01

    This case series assesses white matter microstructure of the cerebellar peduncles in 4 adolescents born preterm with enlarged ventricles and reduced white matter volume in the cerebrum but no apparent injury to the cerebellum. Subjects (ages 12-17 years, gestational age 26-32 weeks, birth weight 825-2211 g) were compared to a normative sample of 19 full-term controls (9-17 years, mean gestational age 39 weeks, mean birth weight 3154 g). Tract profiles for each of the cerebellar peduncles were generated by calculating fractional anisotropy at 30 points along the central portion of each tract. One or more case subjects exhibited higher fractional anisotropy beyond the 90th percentile in the inferior, middle, and superior cerebellar peduncles. Findings demonstrate that differences in cerebellar white matter microstructure can be detected in the absence of macrostructural cerebellar abnormalities. PMID:26116381

  16. Megalographia in children with cerebellar lesions and in children with attention-deficit/hyperactivity disorder.

    PubMed

    Frings, Markus; Gaertner, Kristina; Buderath, Paul; Christiansen, Hanna; Gerwig, Marcus; Hein-Kropp, Christoph; Schoch, Beate; Hebebrand, Johannes; Timmann, Dagmar

    2010-09-01

    Structural changes of the cerebellum have been reported in attention-deficit/hyperactivity disorder (ADHD) in several studies. The cerebellum is a structure essential for motor coordination and motor learning. Beside behavioral deficits, children with ADHD often show slight motor abnormalities. In the present study, handwriting was examined in both children with ADHD and children with cerebellar lesions. By writing the same sentence several times, letter height increased in the ADHD and cerebellar groups but not in controls. Comparable disorders of handwriting in cerebellar and ADHD children support previous studies, which suggest a contribution of cerebellar dysfunction to motor abnormalities in ADHD. However, an involvement of non-cerebellar dysfunctions in ADHD cannot be excluded. PMID:20480275

  17. Cerebellar cortical degeneration in three English bulldogs: clinical and neuropathological findings.

    PubMed

    Gandini, G; Botteron, C; Brini, E; Fatzer, R; Diana, A; Jaggy, A

    2005-06-01

    This case report describes the clinical and neuropathological findings in three young English bulldogs affected by cerebellar cortical degeneration. The dogs, born from the same parents, were presented with clinical signs indicating progressive cerebellar dysfunction: a wide-based stance, severe cerebellar ataxia characterised by marked hypermetria, spasticity, and intention tremors of the head and trunk with loss of balance. On histopathological examination, lesions were confined to the cerebellum and consisted of diffuse degenerative cortical lesions, and there was a loss of Purkinje and granule cells. The history, clinical signs and neuropathological findings confirmed the diagnosis of cerebellar cortical degeneration. To the authors' knowledge, this is the first report of cerebellar cortical degeneration in the English bulldog. PMID:15971900

  18. Isolation of CA1 nuclear enriched fractions from hippocampal slices to study activity-dependent nuclear import of synapto-nuclear messenger proteins.

    PubMed

    Yuanxiang, Pingan; Bera, Sujoy; Karpova, Anna; Kreutz, Michael R; Mikhaylova, Marina

    2014-01-01

    Studying activity dependent protein expression, subcellular translocation, or phosphorylation is essential to understand the underlying cellular mechanisms of synaptic plasticity. Long-term potentiation (LTP) and long-term depression (LTD) induced in acute hippocampal slices are widely accepted as cellular models of learning and memory. There are numerous studies that use live cell imaging or immunohistochemistry approaches to visualize activity dependent protein dynamics. However these methods rely on the suitability of antibodies for immunocytochemistry or overexpression of fluorescence-tagged proteins in single neurons. Immunoblotting of proteins is an alternative method providing independent confirmation of the findings. The first limiting factor in preparation of subcellular fractions from individual tetanized hippocampal slices is the low amount of material. Second, the handling procedure is crucial because even very short and minor manipulations of living slices might induce activation of certain signaling cascades. Here we describe an optimized workflow in order to obtain sufficient quantity of nuclear enriched fraction of sufficient purity from the CA1 region of acute hippocampal slices from rat brain. As a representative example we show that the ERK1/2 phosphorylated form of the synapto-nuclear protein messenger Jacob actively translocates to the nucleus upon induction of LTP and can be detected in a nuclear enriched fraction from CA1 neurons. PMID:25145907

  19. Brain tissue slice thickness monitored by ion-profile measurement.

    PubMed

    Lipinski, H G

    1992-04-01

    The thickness of a brain tissue slice preparation governs the amount of time required for substances to diffuse from the bathing solution to preparation. Slice thickness may increase during the experiment, e.g., in cases of hypoxia where osmotic pressure within the tissue changes, enabling water to enter the preparation. With increasing slice thickness diffusion paths from the bath to central layers of the preparation increase possibly resulting in an insufficient O2 supply to central layers. Therefore, the actual slice thickness should be monitored during the experiment especially in cases where osmolarity is changed or during hypoxia. This paper describes a simple method to monitor the actual slice thickness using ion profiles measured by ion selective micro-electrodes driven at a constant rate of approximately 10 microns/s (sample rate ca. 10/s). The method is based on steep changes in the concentration gradients at the upper and lower surfaces of the preparation induced by simple diffusion in the presence of concentration gradients between the non-tortuous bath and the tortuous tissue. The thickness of the preparation is derived from the location of the steep gradient changes as reflected by the registered profile. PMID:1405733

  20. Diffusion of radiotracers in normal and ischemic brain slices.

    PubMed

    Patlak, C S; Hospod, F E; Trowbridge, S D; Newman, G C

    1998-07-01

    Diffusion in the extracellular space (ECS) is important in physiologic and pathologic brain processes but remains poorly understood. To learn more about factors influencing tissue diffusion and the role of diffusion in solute-tissue interactions, particularly during cerebral ischemia, we have studied the kinetics of several radiotracers in control and hypoxic 450-microm hippocampal slices and in 1,050-microm thick slices that model the ischemic penumbra. Kinetics were analyzed by nonlinear least squares methods using models that combine extracellular diffusion with tissue compartments in series or in parallel. Studies with 14C-polyethylene glycol confirmed prior measurements of extracellular volume and that ECS shrinks during ischemia. Separating diffusion from transport also revealed large amounts of 45Ca that bind to or enter brain as well as demonstrating a small, irreversibly bound compartment during ischemia. The rapidity of 3H2O entry into cells made it impossible for us to distinguish intracellular from extracellular diffusion. The diffusion-compartment analysis of 3-O-methylglucose data appears to indicate that 5 mmol/L glucose is inadequate to support glycolysis fully in thick slices. Unexpectedly, the diffusion coefficient for all four tracers rose in thick slices compared with thin slices, suggesting that ECS becomes less tortuous in the penumbra. PMID:9663508

  1. Short pulse generation by laser slicing at NSLSII

    SciTech Connect

    Yu, L.; Blednykh, A.; Guo, W.; Krinsky, S.; Li, Y.; Shaftan, T.; Tchoubar, O.; Wang, G.; Willeke, F.; Yang, L.

    2011-03-28

    We discuss an upgrade R&D project for NSLSII to generate sub-pico-second short x-ray pulses using laser slicing. We discuss its basic parameters and present a specific example for a viable design and its performance. Since the installation of the laser slicing system into the storage ring will break the symmetry of the lattice, we demonstrate it is possible to recover the dynamical aperture to the original design goal of the ring. There is a rapid growth of ultrafast user community interested in science using sub-pico-second x-ray pulses. In BNL's Short Pulse Workshop, the discussion from users shows clearly the need for a sub-pico-second pulse source using laser slicing method. In the proposal submitted following this workshop, NSLS team proposed both hard x-ray and soft x-ray beamlines using laser slicing pulses. Hence there is clearly a need to consider the R&D efforts of laser slicing short pulse generation at NSLSII to meet these goals.

  2. Rapid and quantitative discrimination of tumour cells on tissue slices

    NASA Astrophysics Data System (ADS)

    Huang, Kai-Wen; Chieh, Jen-Jie; Liao, Shu-Hsien; Wei, Wen-Chun; Hsiao, Pei-Yi; Yang, Hong-Chang; Horng, Herng-Er

    2016-06-01

    After a needle biopsy, immunohistochemistry is generally used to stain tissue slices for clinically confirming tumours. Currently, tissue slices are immersed in a bioprobe-linked fluorescent reagent for several minutes, washed to remove the unbound reagent, and then observed using a fluorescence microscope. However, the observation must be performed by experienced pathologists, and producing a qualitative analysis is time consuming. Therefore, this study proposes a novel scanning superconducting quantum interference device biosusceptometry (SSB) method for avoiding these drawbacks. First, stain reagents were synthesised for the dual modalities of fluorescent and magnetic imaging by combining iron-oxide magnetic nanoparticles and the currently used fluorescent reagent. The reagent for the proposed approach was stained using the same procedure as that for the current fluorescent reagent, and tissue slices were rapidly imaged using the developed SSB for obtaining coregistered optical and magnetic images. Analysing the total intensity of magnetic spots in SSB images enables quantitatively determining the tumour cells of tissue slices. To confirm the magnetic imaging results, a traditional observation methodology entailing the use of a fluorescence microscope was also performed as the gold standard. This study determined high consistency between the fluorescent and magnetic spots in different regions of the tissue slices, demonstrating the feasibility of the proposed approach, which will benefit future clinical pathology.

  3. Rapid and quantitative discrimination of tumour cells on tissue slices.

    PubMed

    Huang, Kai-Wen; Chieh, Jen-Jie; Liao, Shu-Hsien; Wei, Wen-Chun; Hsiao, Pei-Yi; Yang, Hong-Chang; Horng, Herng-Er

    2016-06-10

    After a needle biopsy, immunohistochemistry is generally used to stain tissue slices for clinically confirming tumours. Currently, tissue slices are immersed in a bioprobe-linked fluorescent reagent for several minutes, washed to remove the unbound reagent, and then observed using a fluorescence microscope. However, the observation must be performed by experienced pathologists, and producing a qualitative analysis is time consuming. Therefore, this study proposes a novel scanning superconducting quantum interference device biosusceptometry (SSB) method for avoiding these drawbacks. First, stain reagents were synthesised for the dual modalities of fluorescent and magnetic imaging by combining iron-oxide magnetic nanoparticles and the currently used fluorescent reagent. The reagent for the proposed approach was stained using the same procedure as that for the current fluorescent reagent, and tissue slices were rapidly imaged using the developed SSB for obtaining coregistered optical and magnetic images. Analysing the total intensity of magnetic spots in SSB images enables quantitatively determining the tumour cells of tissue slices. To confirm the magnetic imaging results, a traditional observation methodology entailing the use of a fluorescence microscope was also performed as the gold standard. This study determined high consistency between the fluorescent and magnetic spots in different regions of the tissue slices, demonstrating the feasibility of the proposed approach, which will benefit future clinical pathology. PMID:27138705

  4. Organotypic slice cultures of human gastric and esophagogastric junction cancer.

    PubMed

    Koerfer, Justus; Kallendrusch, Sonja; Merz, Felicitas; Wittekind, Christian; Kubick, Christoph; Kassahun, Woubet T; Schumacher, Guido; Moebius, Christian; Gaßler, Nikolaus; Schopow, Nikolas; Geister, Daniela; Wiechmann, Volker; Weimann, Arved; Eckmann, Christian; Aigner, Achim; Bechmann, Ingo; Lordick, Florian

    2016-07-01

    Gastric and esophagogastric junction cancers are heterogeneous and aggressive tumors with an unpredictable response to cytotoxic treatment. New methods allowing for the analysis of drug resistance are needed. Here, we describe a novel technique by which human tumor specimens can be cultured ex vivo, preserving parts of the natural cancer microenvironment. Using a tissue chopper, fresh surgical tissue samples were cut in 400 μm slices and cultivated in 6-well plates for up to 6 days. The slices were processed for routine histopathology and immunohistochemistry. Cytokeratin stains (CK8, AE1/3) were applied for determining tumor cellularity, Ki-67 for proliferation, and cleaved caspase-3 staining for apoptosis. The slices were analyzed under naive conditions and following 2-4 days in vitro exposure to 5-FU and cisplatin. The slice culture technology allowed for a good preservation of tissue morphology and tumor cell integrity during the culture period. After chemotherapy exposure, a loss of tumor cellularity and an increase in apoptosis were observed. Drug sensitivity of the tumors could be assessed. Organotypic slice cultures of gastric and esophagogastric junction cancers were successfully established. Cytotoxic drug effects could be monitored. They may be used to examine mechanisms of drug resistance in human tissue and may provide a unique and powerful ex vivo platform for the prediction of treatment response. PMID:27073068

  5. Fractal Segmentation and Clustering Analysis for Seismic Time Slices

    NASA Astrophysics Data System (ADS)

    Ronquillo, G.; Oleschko, K.; Korvin, G.; Arizabalo, R. D.

    2002-05-01

    Fractal analysis has become part of the standard approach for quantifying texture on gray-tone or colored images. In this research we introduce a multi-stage fractal procedure to segment, classify and measure the clustering patterns on seismic time slices from a 3-D seismic survey. Five fractal classifiers (c1)-(c5) were designed to yield standardized, unbiased and precise measures of the clustering of seismic signals. The classifiers were tested on seismic time slices from the AKAL field, Cantarell Oil Complex, Mexico. The generalized lacunarity (c1), fractal signature (c2), heterogeneity (c3), rugosity of boundaries (c4) and continuity resp. tortuosity (c5) of the clusters are shown to be efficient measures of the time-space variability of seismic signals. The Local Fractal Analysis (LFA) of time slices has proved to be a powerful edge detection filter to detect and enhance linear features, like faults or buried meandering rivers. The local fractal dimensions of the time slices were also compared with the self-affinity dimensions of the corresponding parts of porosity-logs. It is speculated that the spectral dimension of the negative-amplitude parts of the time-slice yields a measure of connectivity between the formation's high-porosity zones, and correlates with overall permeability.

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

    PubMed

    D'Mello, Anila M; Crocetti, Deana; Mostofsky, Stewart H; Stoodley, Catherine J

    2015-01-01

    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. PMID:25844317

  7. Imaging neuronal responses in slice preparations of vomeronasal organ expressing a genetically encoded calcium sensor.

    PubMed

    Ma, Limei; Haga-Yamanaka, Sachiko; Yu, Qingfeng Elden; Qiu, Qiang; Kim, Sangseong; Yu, C Ron

    2011-01-01

    The vomeronasal organ (VNO) detects chemosensory signals that carry information about the social, sexual and reproductive status of the individuals within the same species. These intraspecies signals, the pheromones, as well as signals from some predators, activate the vomeronasal sensory neurons (VSNs) with high levels of specificity and sensitivity. At least three distinct families of G-protein coupled receptors, V1R, V2R and FPR, are expressed in VNO neurons to mediate the detection of the chemosensory cues. To understand how pheromone information is encoded by the VNO, it is critical to analyze the response profiles of individual VSNs to various stimuli and identify the specific receptors that mediate these responses. The neuroepithelia of VNO are enclosed in a pair of vomer bones. The semi-blind tubular structure of VNO has one open end (the vomeronasal duct) connecting to the nasal cavity. VSNs extend their dendrites to the lumen part of the VNO, where the pheromone cues are in contact with the receptors expressed at the dendritic knobs. The cell bodies of the VSNs form pseudo-stratified layers with V1R and V2R expressed in the apical and basal layers respectively. Several techniques have been utilized to monitor responses of VSNs to sensory stimuli. Among these techniques, acute slice preparation offers several advantages. First, compared to dissociated VSNs, slice preparations maintain the neurons in their native morphology and the dendrites of the cells stay relatively intact. Second, the cell bodies of the VSNs are easily accessible in coronal slice of the VNO to allow electrophysiology studies and imaging experiments as compared to whole epithelium and whole-mount preparations. Third, this method can be combined with molecular cloning techniques to allow receptor identification. Sensory stimulation elicits strong Ca2+ influx in VSNs that is indicative of receptor activation. We thus develop transgenic mice that express G-CaMP2 in the olfactory sensory

  8. Procedural learning in Parkinson's disease and cerebellar degeneration.

    PubMed

    Pascual-Leone, A; Grafman, J; Clark, K; Stewart, M; Massaquoi, S; Lou, J S; Hallett, M

    1993-10-01

    We compared procedural learning, translation of procedural knowledge into declarative knowledge, and use of declarative knowledge in age-matched normal volunteers (n = 30), patients with Parkinson's disease (n = 20), and patients with cerebellar degeneration (n = 15) by using a serial reaction time task. Patients with Parkinson's disease achieved procedural knowledge and used declarative knowledge of the task to improve performance, but they required a larger number of repetitions of the task to translate procedural knowledge into declarative knowledge. Patients with cerebellar degeneration did not show performance improvement due to procedural learning, failed to achieve declarative knowledge, and showed limited use of declarative knowledge of the task to improve their performance. Both basal ganglia and cerebellum are involved in procedural learning, but their roles are different. The normal influence of the basal ganglia on the prefrontal cortex may be required for timely access of information to and from the working memory buffer, while the cerebellum may index and order events in the time domain and be therefore essential for any cognitive functions involving sequences. PMID:8215247

  9. Diphtheria toxin mutant selectively kills cerebellar Purkinje neurons.

    PubMed Central

    Riedel, C J; Muraszko, K M; Youle, R J

    1990-01-01

    CRM107 (crossreacting material 107), a double point mutant of diphtheria toxin that lacks receptor-binding activity, specifically kills cerebellar Purkinje cells in vivo. After injection into guinea pig cerebrospinal fluid, CRM107 (0.9 micrograms) and CRM107-monoclonal antibody conjugates (10 micrograms) kill up to 90% of the total Purkinje cell population with no detectable toxicity to other neurons. Animals exhibit ataxia, tremor, and abnormalities of posture and tone. Native diphtheria toxin, ricin, and ricin A chain do not cause ataxia and do not reduce the Purkinje cell population after intrathecal injection into guinea pigs at toxic or maximally tolerated doses. However, in rats, which will tolerate higher doses of diphtheria toxin than guinea pigs, Purkinje cells can be killed by both CRM107 and diphtheria toxin. A truncated mutant of diphtheria toxin, called CRM45, can also cause Purkinje cell killing but has additional toxicity not seen with CRM107. Animals treated with intrathecal CRM107 or CRM107 linked to antibodies may serve as models for Purkinje cell loss in a broad spectrum of human diseases and may be used to further study cerebellar physiology. Understanding the basis for the Purkinje cell sensitivity to CRM107 may illuminate other causes of Purkinje cell loss. Images PMID:2367523

  10. Extracellular potassium concentration regulates proliferation of immature cerebellar granule cells.

    PubMed

    Borodinsky, L N; Fiszman, M L

    1998-04-17

    The present study examines the effect of depolarizing potassium concentrations on the proliferation of immature rat cerebellar neurons. Cells inoculated in serum free medium and 5 mM KCl (5 K) showed a high degree of 3H-thymidine incorporation that decreased 24-48 h after plating as differentiation began. During the first 24 h after inoculation, cells grown in high potassium (25 K), showed a 34 +/- 3% increase (mean +/- S.E.M., n = 12) in 3H-thymidine incorporation as compared with the values observed in 5 K. After 24 h in vitro, cells grown in 25 K showed 23 +/- 3% (mean +/- S.E.M., n = 3) less DNA synthesis than those inoculated in 5 K. The increase in DNA synthesis due to 25 K was blocked by MgCl2 and nifedipine, but not by omega-conotoxin GVIA, suggesting that it is mediated by a Ca2+ influx via voltage-gated calcium channels (VGCC) of the L-subtype. High potassium-induced cell proliferation was blocked by the mitogen-activated protein kinase kinase (MEK1) inhibitor (PD98059, 75 microM). The number of neurons counted after 48 h in vitro in 25 K was 35-100% above of the number obtained with 5 K and this increase also was blocked by MgCl2 and nifedipine. These data support the hypothesis that depolarizing activity during neurogenesis plays a role in the modulation of cerebellar granule cells proliferation. PMID:9602050

  11. HSF1-deficiency affects gait coordination and cerebellar calbindin levels.

    PubMed

    Ingenwerth, Marc; Estrada, Veronica; Stahr, Anna; Müller, Hans Werner; von Gall, Charlotte

    2016-09-01

    Heat shock proteins (HSPs) play an important role in cell homeostasis and protect against cell damage. They were previously identified as key players in different ataxia models. HSF1 is the main transcription factor for HSP activation. HSF1-deficient mice (HSF1-/-) are known to have deficiencies in motor control test. However, little is known about effects of HSF1-deficiency on locomotor, especially gait, coordination. Therefore, we compared HSF-deficient (HSF1-/-) mice and wildtype littermates using an automated gait analysis system for objective assessment of gait coordination. We found significant changes in gait parameters of HSF1-/- mice reminiscent of cerebellar ataxia. Immunohistochemical analyses of a cerebellum revealed co-localization of HSF1 and calbindin in Purkinje cells. Therefore, we tested the hypothesis of a potential interconnection between HSF1 and calbindin in Purkinje cells. Calbindin levels were analyzed qualitatively and quantitatively by immunohistochemistry and immunoblotting, respectively. While quantitative PCR revealed no differences in calbindin mRNA levels between HSF1+/+ and HSF1-/- mice, calbindin protein levels, however, were significantly decreased in a cerebellum of HSF1-/- mice. A pathway analysis supports the hypothesis of an interconnection between HSF1 and calbindin. In summary, the targeted deletion of HSF1 results in changes of locomotor function associated with changes in cerebellar calbindin protein levels. These findings suggest a role of HSF1 in regular Purkinje cell calcium homeostasis. PMID:27173427

  12. Inhibition of Cerebellar Granule Cell Turning by Alcohol

    PubMed Central

    Kumada, Tatsuro; Komuro, Yutaro; Li, Ying; Hu, Taofang; Wang, Zhe; Littner, Yoav; Komuro, Hitoshi

    2010-01-01

    Ectopic neurons are often found in the brains of fetal alcohol spectrum disorders (FASD) and fetal alcohol syndrome (FAS) patients, suggesting that alcohol exposure impairs neuronal cell migration. Although it has been reported that alcohol decreases the speed of neuronal cell migration, little is known about whether alcohol also affects the turning of neurons. Here we show that ethanol exposure inhibits the turning of cerebellar granule cells in vivo and in vitro. First, in vivo studies using P10 mice demonstrated that a single i.p. injection of ethanol not only reduces the number of turning granule cells but also alters the mode of turning at the EGL-ML border of the cerebellum. Second, in vitro analysis using microexplant cultures of P0-P3 mouse cerebella revealed that ethanol directly reduces the frequency of spontaneous granule cell turning in a dose-dependent manner. Third, the action of ethanol on the frequency of granule cell turning was significantly ameliorated by stimulating Ca2+ and cGMP signaling or by inhibiting cAMP signaling. Taken together, these results indicate that ethanol affects the frequency and mode of cerebellar granule cell turning through alteration of the Ca2+ and cyclic nucleotide signaling pathways, suggesting that the abnormal allocation of neurons found in the brains of FASD and FSA patients results, at least in part, from impaired turning of immature neurons by alcohol. PMID:20691765

  13. Deep Learning for Cerebellar Ataxia Classification and Functional Score Regression

    PubMed Central

    Yang, Zhen; Zhong, Shenghua; Carass, Aaron; Ying, Sarah H.; Prince, Jerry L.

    2014-01-01

    Cerebellar ataxia is a progressive neuro-degenerative disease that has multiple genetic versions, each with a characteristic pattern of anatomical degeneration that yields distinctive motor and cognitive problems. Studying this pattern of degeneration can help with the diagnosis of disease subtypes, evaluation of disease stage, and treatment planning. In this work, we propose a learning framework using MR image data for discriminating a set of cerebellar ataxia types and predicting a disease related functional score. We address the difficulty in analyzing high-dimensional image data with limited training subjects by: 1) training weak classifiers/regressors on a set of image subdomains separately, and combining the weak classifier/regressor outputs to make the decision; 2) perturbing the image subdomain to increase the training samples; 3) using a deep learning technique called the stacked auto-encoder to develop highly representative feature vectors of the input data. Experiments show that our approach can reliably classify between one of four categories (healthy control and three types of ataxia), and predict the functional staging score for ataxia. PMID:25553339

  14. Aspm sustains postnatal cerebellar neurogenesis and medulloblastoma growth in mice.

    PubMed

    Williams, Scott E; Garcia, Idoia; Crowther, Andrew J; Li, Shiyi; Stewart, Alyssa; Liu, Hedi; Lough, Kendall J; O'Neill, Sean; Veleta, Katherine; Oyarzabal, Esteban A; Merrill, Joseph R; Shih, Yen-Yu Ian; Gershon, Timothy R

    2015-11-15

    Alterations in genes that regulate brain size may contribute to both microcephaly and brain tumor formation. Here, we report that Aspm, a gene that is mutated in familial microcephaly, regulates postnatal neurogenesis in the cerebellum and supports the growth of medulloblastoma, the most common malignant pediatric brain tumor. Cerebellar granule neuron progenitors (CGNPs) express Aspm when maintained in a proliferative state by sonic hedgehog (Shh) signaling, and Aspm is expressed in Shh-driven medulloblastoma in mice. Genetic deletion of Aspm reduces cerebellar growth, while paradoxically increasing the mitotic rate of CGNPs. Aspm-deficient CGNPs show impaired mitotic progression, altered patterns of division orientation and differentiation, and increased DNA damage, which causes progenitor attrition through apoptosis. Deletion of Aspm in mice with Smo-induced medulloblastoma reduces tumor growth and increases DNA damage. Co-deletion of Aspm and either of the apoptosis regulators Bax or Trp53 (also known as p53) rescues the survival of neural progenitors and reduces the growth restriction imposed by Aspm deletion. Our data show that Aspm functions to regulate mitosis and to mitigate DNA damage during CGNP cell division, causes microcephaly through progenitor apoptosis when mutated, and sustains tumor growth in medulloblastoma. PMID:26450969

  15. Cerebellar allocentric and action-intentional spatial neglect.

    PubMed

    Milano, Nicholas J; Heilman, Kenneth M

    2014-09-01

    Contralesional hemispatial neglect most often results from lesions in the right posterior temporoparietal cortex. Less commonly, contralesional and ipsilesional neglect are caused by lesions in the frontal lobe. Although unilateral left cerebellar lesions have been reported to cause body-centered (egocentric) ipsilesional neglect, they have not been reported to cause left-side object-centered (allocentric) neglect together with a leftward action-intentional bias. We describe a patient who had these signs of neglect 7 months after a left cerebellar hemorrhage. This 61-year-old right-handed woman reported emotional lability and difficulty walking, frequently bumping into things on her left side. Neurologic examination revealed ocular dysmetria and left-side limb ataxia. Neuropsychological tests showed evidence of neglect. On a clock-drawing test, the patient accurately drew a circle but her number placement deviated to the left side. She showed the same leftward deviation when she tried to draw a circle composed of small triangles. Although her line bisection was normal, on an allocentric task of open-triangle cancellation she was most likely to neglect triangles with a left-side opening. Her performance on this task indicated left allocentric neglect. Her leftward deviation on the clock and figure drawing tasks seems to be a form of an action-intentional grasp, which may have been induced by right frontal dysfunction superimposed on a deficit of global attention. PMID:25237748

  16. Speech prosody in Friedreich's and olivo-ponto cerebellar atrophy

    NASA Astrophysics Data System (ADS)

    Casper, Maureen

    2001-05-01

    A critical issue in the study of speech motor control is the identification of the mechanisms that generate the temporal flow of serially ordered articulatory events. Two staged models of serial ordered events (Lashley, 1951; Lindblom, 1963) claim that time controls events whereas dynamic models predict a relative relation between time and space. Each of these models predicts a different relation between the acoustic measures of formant frequency and segmental duration. The most recent method described herein provides a sensitive index of speech deterioration which is both acoustically robust and phonetically systematic. Both acoustic and magnetic resonance imaging measures were used to describe the speech disturbance in two neurologically distinct groups of cerebellar ataxia: Friedreich's ataxia and olivo-ponto cerebellar ataxia. The speaking task was designed to elicit six different prosodic conditions and four prosodic contrasts. All subjects read the same syllable embedded in a sentence, under six different prosodic conditions. Pair-wise comparisons derived from the six conditions were used to describe (1) final lengthening, (2) phrasal accent, (3) nuclear accent and (4) syllable reduction. An estimate of speech deterioration as determined by individual and normal subects' acoustic values of syllable duration, formant and fundamental frequencies was used in correlation analyses with magnetic resonance imaging ratings.

  17. Cerebellar sequencing: a trick for predicting the future.

    PubMed

    Leggio, M; Molinari, M

    2015-02-01

    "Looking into the future" well depicts one of the most significant concepts in cognitive neuroscience: the brain is constantly predicting future events. Such directedness toward the future has been recognized to be relevant to and beneficial for many aspects of information processing in humans, such as perception, motor and cognitive control, decision-making, theory of mind, and other cognitive processes. Because one of the most adaptive characteristics of the brain is to correct errors, the ability to look into the future represents the best chance to avoid repeating errors. Within the structures that constitute the "predictive brain," the cerebellum has been proposed to have a central function, based on its ability to generate internal models. We suggested that "sequence detection" is the operational mode of the cerebellum in predictive processing. According to this hypothesis, the cerebellum detects and simulates repetitive patterns of temporally or spatially structured events and generates internal models that can be used to make predictions. Consequently, we demonstrate that the cerebellum recognizes serial events as a sequence, detects a sequence violation, and successfully reconstructs the correct sequence of events. Thus, we hypothesize that pattern detection and prediction and processing of anticipation are cerebellum-specific functions within the brain and that the sequence detection hypothesis links the multifarious impairments that are reported in patients with cerebellar damage. We propose that this cerebellar operational mode can advance our understanding of the pathophysiological mechanisms in various clinical conditions, such as schizophrenia and autism. PMID:25331541

  18. Cerebellar-Dependent Eyeblink Conditioning Deficits in Schizophrenia Spectrum Disorders

    PubMed Central

    Forsyth, Jennifer K.; Bolbecker, Amanda R.; Mehta, Crystal S.; Klaunig, Mallory J.; Steinmetz, Joseph E.; O'Donnell, Brian F.; Hetrick, William P.

    2012-01-01

    Accumulating evidence suggests that abnormalities in neural circuitry and timing associated with the cerebellum may play a role in the pathophysiology of schizophrenia. Schizotypal personality disorder (SPD) may be genetically linked to schizophrenia, but individuals with SPD are freer from potential research confounds and may therefore offer insight into psychophysiological correlates of schizophrenia. The present study employed a delay eyeblink conditioning (EBC) procedure to examine cerebellar-dependent learning in schizophrenia, SPD, and healthy control subjects (n = 18 per group) who were matched for age and gender. The conditioned stimulus was a 400-ms tone that coterminated with a 50 ms unconditioned stimulus air puff. Cognitive performance on the Picture Completion, Digit Symbol Coding, Similarities, and Digit Span subscales of the Wechsler Adult Intelligence Scale—Third Edition was also investigated. The schizophrenia and SPD groups demonstrated robust EBC impairment relative to the control subjects; they had significantly fewer conditioned responses (CRs), as well as smaller CR amplitudes. Schizophrenia subjects showed cognitive impairment across subscales compared with SPD and control subjects; SPD subjects showed intermediate performance to schizophrenia and control subjects and performed significantly worse than controls on Picture Completion. Impaired EBC was significantly related to decreased processing speed in schizophrenia spectrum subjects. These findings support the role of altered cortico-cerebellar-thalamic-cortical circuitry in the pathophysiology of schizophrenia spectrum disorders. PMID:21148238

  19. Fluid dynamic lateral slicing of high tensile strength carbon nanotubes.

    PubMed

    Vimalanathan, Kasturi; Gascooke, Jason R; Suarez-Martinez, Irene; Marks, Nigel A; Kumari, Harshita; Garvey, Christopher J; Atwood, Jerry L; Lawrance, Warren D; Raston, Colin L

    2016-01-01

    Lateral slicing of micron length carbon nanotubes (CNTs) is effective on laser irradiation of the materials suspended within dynamic liquid thin films in a microfluidic vortex fluidic device (VFD). The method produces sliced CNTs with minimal defects in the absence of any chemical stabilizers, having broad length distributions centred at ca 190, 160 nm and 171 nm for single, double and multi walled CNTs respectively, as established using atomic force microscopy and supported by small angle neutron scattering solution data. Molecular dynamics simulations on a bent single walled carbon nanotube (SWCNT) with a radius of curvature of order 10 nm results in tearing across the tube upon heating, highlighting the role of shear forces which bend the tube forming strained bonds which are ruptured by the laser irradiation. CNT slicing occurs with the VFD operating in both the confined mode for a finite volume of liquid and continuous flow for scalability purposes. PMID:26965728

  20. Unstable periodic orbits in human epileptic hippocampal slices.

    PubMed

    Pen-Ning Yu; Min-Chi Hsiao; Dong Song; Liu, Charles Y; Heck, Christi N; Millett, David; Berger, Theodore W

    2014-01-01

    Inter-ictal activity is studied in hippocampal slices resected from patients with epilepsy using local field potential recording. Inter-ictal activity in the dentate gyrus (DG) is induced by high-potassium (8 mM), low-magnesium (0.25 mM) aCSF with additional 100 μM 4-aminopyridine(4-AP). The dynamics of the inter-ictal activity is investigated by developing the first return map with inter-pulse intervals. Unstable periodic orbits (UPOs) are detected in the hippocampal slice at the DG area according to both the topological recurrence method and the periodic orbit transform method. Surrogate analysis suggests the presence of UPOs in hippocampal slices from patients with epilepsy. This finding also suggests that inter-ictal activity is a chaotic system and will allow us to apply chaos control techniques to manipulate inter-ictal activity. PMID:25571314