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Sample records for acute cerebellar slices

  1. Acute cerebellar ataxia

    MedlinePlus

    ... Alcohol, medications, and insecticides Bleeding into the cerebellum Multiple sclerosis Strokes of the cerebellum Vaccination ... swelling (inflammation) of the cerebellum (such as from multiple sclerosis) Cerebellar ataxia caused by a recent viral infection ...

  2. Acute cerebellar ataxia, acute cerebellitis, and opsoclonus-myoclonus syndrome.

    PubMed

    Desai, Jay; Mitchell, Wendy G

    2012-11-01

    Acute cerebellar ataxia and acute cerebellitis represent a process characterized by parainfectious, postinfectious, or postvaccination cerebellar inflammation. There is considerable overlap between these entities. The mildest cases of acute cerebellar ataxia represent a benign condition that is characterized by acute truncal and gait ataxia, variably with appendicular ataxia, nystagmus, dysarthria, and hypotonia. It occurs mostly in young children, presents abruptly, and recovers over weeks. Neuroimaging is normal. Severe cases of cerebellitis represent the other end of the spectrum, presenting with acute cerebellar signs often overshadowed by alteration of consciousness, focal neurological deficits, raised intracranial pressure, hydrocephalus, and even herniation. Neuroimaging is abnormal and the prognosis is less favorable than in acute cerebellar ataxia. Acute disseminated encephalomyelitis may be confused with acute cerebellitis when the clinical findings are predominantly cerebellar, but lesions on neuroimaging are usually widespread. Paraneoplastic opsoclonus-myoclonus syndrome is often initially misdiagnosed as acute cerebellar ataxia, but has very specific features, course, and etiopathogensis.

  3. Biosensor measurement of purine release from cerebellar cultures and slices.

    PubMed

    Wall, Mark; Eason, Robert; Dale, Nicholas

    2010-09-01

    We have previously described an action-potential and Ca(2+)-dependent form of adenosine release in the molecular layer of cerebellar slices. The most likely source of the adenosine is the parallel fibres, the axons of granule cells. Using microelectrode biosensors, we have therefore investigated whether cultured granule cells (from postnatal day 7-8 rats) can release adenosine. Although no purine release could be detected in response to focal electrical stimulation, purine (adenosine, inosine or hypoxanthine) release occurred in response to an increase in extracellular K(+) concentration from 3 to 25 mM coupled with addition of 1 mM glutamate. The mechanism of purine release was transport from the cytoplasm via an ENT transporter. This process did not require action-potential firing but was Ca(2+)dependent. The major purine released was not adenosine, but was either inosine or hypoxanthine. In order for inosine/hypoxanthine release to occur, cultures had to contain both granule cells and glial cells; neither cellular component was sufficient alone. Using the same stimulus in cerebellar slices (postnatal day 7-25), it was possible to release purines. The release however was not blocked by ENT blockers and there was a shift in the Ca(2+) dependence during development. This data from cultures and slices further illustrates the complexities of purine release, which is dependent on cellular composition and developmental stage.

  4. Acute cerebellar ataxia and infectious mononucleosis.

    PubMed Central

    Wadhwa, N. K.; Ghose, R. R.

    1983-01-01

    A 28-year-old man, who presented with acute cerebellar ataxia, was found to have haematological features of infectious mononucleosis. There was serological evidence of recent infection with Epstein-Barr virus. It is speculated that cerebellar dysfunction results from virus-induced inflammatory changes within the central nervous system. PMID:6312442

  5. Decreased cerebellar blood flow in postinfectious acute cerebellar ataxia

    PubMed Central

    Nagamitsu, S.; Matsuishi, T.; Ishibashi, M.; Yamashita, Y.; Nishimi, T.; Ichikawa, K.; Yamanishi, K.; Kato, H.

    1999-01-01

    OBJECTIVE—The aim of the present study was to evaluate the regional cerebral blood flow (rCBF) in patients with postinfectious acute cerebellar ataxia using single photon emission computed tomography (SPECT).
METHODS—Five children with postinfectious acute cerebellar ataxia and five control subjects were examined. The distribution of rCBF was measured by SPECT imaging after intravenous administration of 123I-IMP (111 MBq). The rCBF ratio—defined as the ratio of rCBF in the region of interest (ROI) to that in the occipital cortex—was calculated for each cortical and subcortical ROI. The mean rCBF ratio of each region was then compared between the ataxic and control subjects. These patients and all control subjects were also evaluated using MRI.
RESULTS—The rCBF ratio was significantly lower in the cerebellum of the ataxic patients than in the cerebellum of the control subjects (p<0.05). No abnormal cerebellar morphology and no abnormal signal intensities were found on MRI.
CONCLUSION—123I-IMP SPECT clearly demonstrated the decreased rCBF in the cerebellum of all patients with postinfectious acute cerebellar ataxia.

 PMID:10369834

  6. Acute cerebellar ataxia with human parvovirus B19 infection

    PubMed Central

    Shimizu, Y.; Ueno, T.; Komatsu, H.; Takada, H.; Nunoue, T.

    1999-01-01

    A 2 year old boy developed acute cerebellar ataxia in association with erythema infectiosum. During the disease, genomic DNA and antibodies against human parvovirus B19 were detected in serum but not in cerebrospinal fluid. Parvovirus B19 associated acute cerebellar ataxia might occur due to transient vascular reaction in the cerebellum during infection.

 PMID:10325764

  7. Neuroprotection against diisopropylfluorophosphate in acute hippocampal slices

    PubMed Central

    Ferchmin, P. A.; Pérez, Dinely; Cuadrado, Brenda L.; Carrasco, Marimée; Martins, Antonio H.; Eterović, Vesna A.

    2015-01-01

    Diisopropylfluorophosphate (DFP) is an irreversible inhibitor of acetylcholine esterase (AChE) and a surrogate of the organophosphorus (OP) nerve agent sarin. The neurotoxicity of DFP was assessed as a reduction of population spike (PS) area elicited by synaptic stimulation in acute hippocampal slices. Two classical antidotes, atropine, and pralidoxime, and two novel antidotes, 4R-cembranotriene-diol (4R) and a caspase 9 inhibitor, were tested. Atropine, pralidoxime, and 4R significantly protected when applied 30 min after DFP. The caspase inhibitor was neuroprotective when applied 5–10 min before or after DFP, suggesting that early synaptic apoptosis is responsible for the loss of PSs. It is likely that apoptosis starts at the synapses and, if antidotes are not applied, descends to the cell bodies, causing death. The acute slice is a reliable tool for mechanistic studies, and the assessment of neurotoxicity and neuroprotection with PS areas is, in general, pharmacologically congruent with in vivo results and predicts the effect of drugs in vivo. 4R was first found to be neuroprotective in slices and later we demonstrated that 4R is neuroprotective in vivo. The mechanism of neurotoxicity of OPs is not well understood, and there is a need for novel antidotes that could be discovered using acute slices. PMID:26438150

  8. Cerebellar mass as a location of acute lymphoblastic leukaemia.

    PubMed

    Desideri, Ilaria; Canovetti, Silvia; Pesaresi, Ilaria; Caniglia, Michele; Ciancia, Eugenio; Bartolozzi, Carlo; Puglioli, Michele; Cosottini, Mirco

    2014-09-01

    A 22-year-old man with acute lymphoblastic leukaemia was referred to our observation for headache, cervical pain and sopor. A computed tomography study revealed triventricular obstructive hydrocephalus due to a left cerebellar hyperdense mass impinging on the fourth ventricle. A magnetic resonance study demonstrated an area of hyperintensity on T2-weighted images, hypointensity on T1, restricted diffusivity and contrast enhancement involving the left hemispherical cerebellar cortex and the vermis and causing cerebellar herniation. After surgical excision of the lesion, histological examination revealed an infiltrate of lymphoblastic leukaemia with B cells. Leukaemic intracranial masses are rare. Our report describes a case presenting a cerebellar mass of leukaemic tissue characterized by high cellularity and low apparent diffusion coefficient value comparable to acute ischaemia. Therefore leukaemic intracranial mass has to be considered in the differential diagnosis of cerebellar masses.

  9. Modulatory action of taurine on the release of GABA in cerebellar slices of the guinea pig.

    PubMed

    Namima, M; Okamoto, K; Sakai, Y

    1983-01-01

    For the purpose of demonstrating the action of taurine as a neuromodulator in addition to its suggested neurotransmitter function, the effects of taurine and muscimol on the depolarization-induced Ca-dependent release of [3H] gamma-aminobutyric acid ([3H]GABA) and L-[3H]glutamate in cerebellar slices from guinea pigs were investigated. The release of [3H]GABA was found to be greatly decreased by a GABA agonist, muscimol, and by taurine, but not by glycine. The release of L-[3H]glutamate was little affected by taurine. The release of [3H]GABA, was enhanced by bicuculline and strychnine, but not by picrotoxin, and the suppressive action of muscimol on the GABA release was antagonized by bicuculline, picrotoxin, and strychnine, suggesting the possible existence of presynaptic autoreceptors for GABA in the cerebellum. The suppressive action of taurine on the release of [3H]GABA, on the other hand, was blocked only by bicuculline. These results suggest that taurine reduced the release of [3H]GABA from cerebellar slices by acting on the GABA autoreceptors or, more likely, on other types of receptors that are sensitive to bicuculline. As a possible mechanism for this modulatory action of taurine, the blockade by this amino acid of the influx of Ca2+ into cerebellar tissues was tentatively suggested.

  10. Purkinje cell death after uptake of anti-Yo antibodies in cerebellar slice cultures.

    PubMed

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

    2010-10-01

    Paraneoplastic cerebellar degeneration accompanying gynecological and breast cancers is characteristically accompanied by a serum and cerebrospinal fluid (CSF) antibody response, termed "anti-Yo," which reacts with cytoplasmic proteins of cerebellar Purkinje cells. Because these antibodies interact with cytoplasmic rather than cell surface membrane proteins, their role in causing Purkinje cell death has been questioned. To address this issue, we studied the interaction of anti-Yo antibodies with Purkinje cells in slice (organotypic) cultures of rat cerebellum. We incubated cultures with immunoglobulin G (IgG)-containing anti-Yo antibodies using titers of anti-Yo antibody equivalent to those found in CSF of affected patients. Cultures were then studied in real time and after fixation for potential uptake of antibody and induction of cell death. Anti-Yo antibodies delivered in serum, CSF, or purified IgG were taken up by viable Purkinje cells, accumulated intracellularly, and were associated with cell death. Normal IgG was also taken up by Purkinje cells but did not accumulate and did not affect cell viability. These findings indicate that autoantibodies directed against intracellular Purkinje cell proteins can be taken up to cause cell death and suggest that anti-Yo antibody may be directly involved in the pathogenesis of paraneoplastic cerebellar degeneration.

  11. Cell death and proliferation in acute slices and organotypic cultures of mammalian CNS.

    PubMed

    Lossi, Laura; Alasia, Silvia; Salio, Chiara; Merighi, Adalberto

    2009-08-01

    Analysis of the interplay between cell proliferation and death has been greatly advantaged by the development of CNS slice preparations. In slices, interactions between neurons and neurons and the glial cells are fundamentally preserved in a fashion close to the in vivo situation. In parallel, these preparations offer the possibility of an easy experimental manipulation. Two main types of slices are currently in use: the acute slices, which are short living preparations where the major functions of the intact brain (including neurogenesis) are maintained, and the organotypic cultures, where the maturation and plasticity of neuronal circuitries in relation to naturally occurring neuronal death and/or experimental insults can be followed over several weeks in vitro. We will discuss here the main advantages/disadvantages linked to the use of CNS slices for histological analysis of neuronal proliferation and death, as well as the main findings obtained in the most popular types of preparations, i.e. the cortical, hippocampal, cerebellar and retinal slices.

  12. 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…

  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. Typhoid fever presenting as acute cerebellar ataxia and severe thrombocytopenia.

    PubMed

    Cheong, B M K

    2008-03-01

    Typhoid fever being a systemic infection can present in a multitude of ways, involving various systems. Here we describe a case of typhoid fever presenting with acute cerebellar ataxia and marked thrombocytopenia. This atypical presentation is not common in typhoid fever and can lead to misdiagnosis as well as a delay in the initiation of appropriate therapy. Prompt clinical improvement and the return of platelet counts to normal were noted after the patient was started on IV Ceftriaxone.

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

    PubMed Central

    Bradford, Aaron B.; Mancini, Jayme 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 Ca2+ (Ca2+i) are crucial to proper migration, and MeHg is well known to disrupt CGC Ca2+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 Ca2+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 Ca2+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 Ca2+i dysregulation of CGCs. PMID:26514794

  16. Electrophysiological properties of in vitro Purkinje cell somata in mammalian cerebellar slices.

    PubMed Central

    Llinás, R; Sugimori, M

    1980-01-01

    1. The electrical activity of Purkinje cells was studied in guinea-pig cerebellar slices in vitro. Intracellular recordings from Purkinje cell somata were obtained under direct vision, and antidromic, synaptic and direct electroresponsiveness was demonstrated. Synaptic potentials produced by the activation of the climbing fibre afferent could be reversed by direct membrane depolarization. 2. Input resistance of impaled neurones ranged from 10 to 19 M omega and demonstrated non-linearities in both hyperpolarizing and depolarizing directions. 3. Direct activation of a Purkinje cell indicated that repetitive firing of fast somatic spikes (s.s.) occurs, after a threshold, with a minimum spike frequency of about 30 spikes/sec, resembling the '2-class' response of crab nerve (Hodgkin, 1948). 4. As the amplitude of the stimulus was increased, a second form of electroresponsiveness characterized by depolarizing spike bursts (d.s.b.) was observed and was often accomppanied by momentary inactivation of the s.s. potentials. Upon application of tetrodotoxin (TTX) or removal of Na+ ions from the superfusion fluid, the s.s. potentials were abolished while the burst responses remained intact. However, Ca conductance blockers such as Co, Cd, Mn and D600, or the replacement of Ca by Mg, completely abolish d.s.b.s. 5. If Ca conductance was blocked, or Ca removed from the superfusion fluid without blockage of Na conductance, two types of Na-dependent electroresponsiveness were seen: (a) the s.s. potentials and (b) slow rising all-or-none responses which reached plateau at approximately -15 mV and could last for several seconds. These all-or-none Na-dependent plateau depolarizations outlasted the stimulus and were accompanied by a large increase in membrane conductance. Within certain limits the rate of rise and amplitude of the plateau were independent of stimulus strength. The latency, however, was shortened as stimulus amplitude was increased. These potentials were blocked by TTX

  17. Effects of a naturally occurring neurosteroid on GABAA IPSCs during development in rat hippocampal or cerebellar slices

    PubMed Central

    Cooper, Elizabeth J; Johnston, Graham A R; Edwards, Frances A

    1999-01-01

    The effects of the naturally occurring neurosteroid tetrahydrodeoxycorticosterone (THDOC) on GABAA receptor-mediated miniature, spontaneous and evoked IPSCs was tested using patch-clamp techniques in slices of hippocampus and cerebellum from rats at two developmental stages (≈10 and ≈20 days postnatal). The cells studied were hippocampal granule cells and cerebellar Purkinje and granule cells. Most miniature GABAergic currents (mIPSCs) decayed with two exponentials and neurosteroids caused a ≈4-fold increase in the decay time constant of the second exponential at the highest concentration used (2 μm). Similar effects were seen at high concentrations of THDOC (1-2 μm) in all cell groups tested. No effects were seen on amplitude or rise time of mIPSCs. The effects of THDOC (1 μm) were shown to be stereoselective and rapidly reversible, indicating that the neurosteroid binds to the GABAA receptor, rather than acting genomically. At concentrations of THDOC likely to occur physiologically (50–100 nm), the decay time of IPSCs was also enhanced (25–50 %) in all cerebellar cell groups tested. In contrast, at 100 nm THDOC, seven of 11 hippocampal granule cells were sensitive from the 10 day group but the 20 day hippocampal granule cells showed no significant enhancement in the presence of these lower concentrations of THDOC. The differences in sensitivity of hippocampal and cerebellar cells to THDOC are compared to data reported in the literature on regional development of expression of different receptor subunits in the brain and it is suggested that the progressive relative insensitivity of the 20 day hippocampal cells may depend on increasing expression of the δ subunit of the GABAA receptor and possibly an increase in the α4 subunit. PMID:10581314

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

    PubMed

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

    2001-10-01

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

  19. 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.

  20. Potassium accumulation around individual purkinje cells in cerebellar slices from the guinea-pig.

    PubMed Central

    Hounsgaard, J; Nicholson, C

    1983-01-01

    K+-selective micropipettes were used to measure external K+ concentration [( K+]o) in the immediate vicinity of Purkinje cells in slices from guinea-pig cerebellum. The cells were either spontaneously active or were polarized via a separate intracellular micro-electrode. The level of [K+]o rose by 1-3 mM around the soma and dendrites of Purkinje cells during spike activity. The increases in [K+]o were usually greater during Ca2+-mediated spikes than during Na+-mediated spikes. This was even true at the soma where the Ca2+ spike only invaded electrotonically from the dendrites, in contrast to the Na+ spikes which were generated at the soma. No [K+]o changes were seen in the vicinity of Purkinje cells when the cells were hyperpolarized with current passage nor was any [K+]o change seen during subthreshold depolarizations. In glial cells, however, a hyperpolarizing current reduced [K+]o while a depolarizing current increased [K+]o in a symmetrical manner. When Ba2+ was substituted for Ca2+ in the bathing Ringer solution, prolonged plateau-potential spikes could be evoked from Purkinje cells. These spikes were accompanied by large [K+]o elevations but the plateau potentials outlasted the [K+]o elevations. These experiments suggest that large [K+]o increases can occur in the absence of Ca2+-mediated K+ conductances. Substitution of Mn2+ for Ca2+ in the Ringer solution removed some of the [K+]o increases at the Purkinje cell soma. Addition of tetrodotoxin to normal Ringer solution also reduced, but did not abolish the [K+]o increases at the soma. These experiments confirmed that both Na+ and Ca2+ spikes were involved in the [K+]o change. The diffusion characteristics of the slices were determined by an ionophoretic method using tetramethylammonium and ion-selective micropipettes. The extracellular volume fraction of the slice averaged 0.28 while the tortuosity averaged 1.84. These values were close to those found previously in the intact rat cerebellum. These data were

  1. 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.

  2. Low-threshold Ca2+ currents in dendritic recordings from Purkinje cells in rat cerebellar slice cultures.

    PubMed

    Mouginot, D; Bossu, J L; Gähwiler, B H

    1997-01-01

    Voltage-dependent Ca2+ conductances were investigated in Purkinje cells in rat cerebellar slice cultures using the whole-cell and cell-attached configurations of the patch-clamp technique. In the presence of 0.5 mM Ca2+ in the extracellular solution, the inward current activated with a threshold of -55 +/- 1.5 mV and reached a maximal amplitude of 2.3 +/- 0.4 nA at -31 +/- 2 mV. Decay kinetics revealed three distinct components: a fast (24.6 +/- 2 msec time constant), a slow (304 +/- 46 msec time constant), and a nondecaying component. Rundown of the slow and sustained components of the current, or application of antagonists for the P/Q-type Ca2+ channels, allowed isolation of the fast-inactivating Ca2+ current, which had a threshold for activation of -60 mV and reached a maximal amplitude of 0.7 nA at a membrane potential of -33 mV. Both activation and steady-state inactivation of this fast-inactivating Ca2+ current were described with Boltzmann equations, with half-activation and inactivation at -51 mV and -86 mV, respectively. This Ca2+ current was nifedipine-insensitive, but its amplitude was reduced reversibly by bath-application of NiCl2 and amiloride, thus allowing its identification as a T-type Ca2+ current. Channels with a conductance of 7 pS giving rise to a fast T-type ensemble current (insensitive to omega-Aga-IVA) were localized with a high density on the dendritic membrane. Channel activity responsible for the ensemble current sensitive to omega-Aga-IVA was detected with 10 mM Ba2+ as the charge carrier. These channels were distributed with a high density on dendritic membranes and in rare cases were also seen in somatic membrane patches.

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

    PubMed

    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.

  4. 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

  5. Acute fatal parainfectious cerebellar swelling in two children. A rare or an overlooked situation?

    PubMed

    Roulet Perez, E; Maeder, P; Cotting, J; Eskenazy-Cottier, A C; Deonna, T

    1993-12-01

    We report 2 previously healthy children who developed sudden unexpected respiratory arrest and brain death, during a presumed Epstein-Barr meningitis in one case and a multisystemic infection of unknown etiology in the other. Diffuse swelling of the cerebellum with upward transtentorial and downward tonsillar herniation, shown by brain CT-scan and MRI obtained after the acute event, was the most probable cause of death. Review of CT images performed before or at the onset of deterioration already showed discrete signs of early upward herniation of the cerebellar vermis that were initially overlooked. At autopsy in the first case, an acute lymphomonocytic meningoencephalitis with predominant involvement of the cerebellum was observed. Few similar cases were found in the literature, indicating that acute cerebellar swelling is either a very rare or an unrecognized, possibly preventable cause of death in acute inflammatory or non-inflammatory encephalopathies in children.

  6. Analysis of Spine Motility of Newborn Granule Cells in Acute Brain Slices.

    PubMed

    Tashiro, Ayumu; Zhao, Chunmei; Suh, Hoonkyo; Gage, Fred H

    2015-10-01

    In this protocol, acute brain slices are prepared from mice in which newborn granule cells have been labeled using retroviral vector technology. Using a live-cell imaging stage and confocal microscopy coupled to imaging software, dendritic spines are analyzed.

  7. Spontaneous thrombosis of developmental venous anomaly (DVA) with venous infarct and acute cerebellar ataxia.

    PubMed

    Agarwal, Amit; Kanekar, Sangam; Kalapos, Paul; Vijay, Kanupriya

    2014-08-01

    Developmental venous anomaly (DVA), formally known as venous angioma, is a congenital anatomic variant of the venous drainage of the brain. Although they typically have a benign clinical course and a low symptomatic rate, thrombosis of a drainage vein may occur, leading to potentially debilitating complications. We report a unique case of spontaneous thrombosis of a posterior fossa developmental venous anomaly with cerebellar infarct in a 61-year-old man who presented with acute onset cerebellar ataxia. DVA thrombosis was well-depicted on CT and MR studies. Patient was put on anticoagulant therapy and complete recanalization was seen on follow-up imaging.

  8. 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

    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

  9. Acute post-infectious cerebellar ataxia due to co-infection of human herpesvirus-6 and adenovirus mimicking myositis.

    PubMed

    Naselli, Aldo; Pala, Giovanna; Cresta, Federico; Finetti, Martina; Biancheri, Roberta; Renna, Salvatore

    2014-11-26

    Acute cerebellar ataxia (ACA) is a relatively common neurological disease in children. Most common types of ACA are acute post-infectious (APCA) and acute disseminated encephalomyelitis (ADEM). Less common but important causes include opsoclonus-myoclonus syndrome (OMS) and acute cerebellitis. Cerebellar neoplasms and acute hydrocephalus are additional causes of paediatric ataxia. APCA is the most common cause of ACA in children, comprising about 30-50% of total cases. This is a report about an immunocompetent 4-yrs-old male affected by APCA, due to co-infection by human herpesvirus-6 (HHV-6) and adenovirus, with symptoms mimicking myositis.

  10. Acute Cerebellar Syndrome in Infectious Mononucleosis: Documentation of Two Cases With Epstein-Barr Virus Infection

    PubMed Central

    Kramer, David S.; Smitnik, Loretta M.; John, Kuruvilla; Drake, Miles E.

    1985-01-01

    Acute cerebellar ataxia has been described occasionally with infectious mononucleosis. Two additional cases are reported with serologic identification of Epstein-Barr virus (EBV) infection in blood and cerebrospinal fluid. As with previously described cases, the outcome was benign, and examination and laboratory studies did not indicate diffuse neurologic involvement. Visual and brainstem auditory-evoked responses were normal. Electroencephalograms (EEG) demonstrated 14 and 6 per second positive spikes in both patients. This pattern is considered a normal variant and has been recorded from depth electrodes and reported with deep midline lesions. These cases support the prognosis of benign cerebellar involvement in infectious mononucleosis and suggest that evidence of EBV infection be sought in patients with acute ataxia. The significance of 14/sec and 6/sec positive EEG spikes is uncertain. PMID:2987517

  11. Effect of edaravone on acute brainstem-cerebellar infarction with vertigo and sudden hearing loss.

    PubMed

    Inoue, Yuta; Yabe, Takao; Okada, Kazunari; Nakamura, Yuka

    2014-06-01

    We report 2 cases with acute brainstem and brainstem-cerebellar infarction showed improvement of their signs and symptoms after administration of edaravone. Case 1, a 74-year-old woman who experienced sudden vertigo, also had dysarthria and left hemiplegia. Magnetic resonance imaging (MRI) showed an abnormal region in the right ventrolateral medulla oblongata. The patient's vertigo and hemiplegia improved completely after treatment. Case 2, a 50-year-old man who experienced sudden vertigo and sensorineural hearing loss (SNHL), developed dysarthria after admission. MRI revealed acute infarction in the right cerebellar hemisphere. Magnetic resonance angiography revealed dissection of the basilar artery and occlusion of the right anterior inferior cerebellar artery. The patient's vertigo and hearing remarkably improved. We have described 2 patients whose early symptoms were vertigo and sudden SNHL, but who were later shown to have ischemic lesions of the central nervous system. Edaravone is neuroprotective drug with free radical-scavenging actions. Free radicals in the ear are responsible for ischemic damage. Edaravone, a free radical scavenger, may be useful in the treatment of vertigo and SNHL.

  12. [Acute cerebellar ataxia in a 5-year-old boy. Clinical warnings].

    PubMed

    Mrozińska, M; Horwath, A; Ostoja-Chrzastowski, W

    1998-01-01

    A case of acute cerebellar ataxia caused by ECHO virus 30.5-year-old boy admitted to the Clinic of Gastroenterology and Nutrition in Warsaw, in September, 1996, complaining of headache, dizziness, weakness, somnolence, dysarthria and an unsteady walk. On neurological examination he had imparied coordination, rombergism, generalized hypotonia. There was no history of exposure to contagious diseases, ear discharge, convulsions, trauma. Parents suggested that the child could have swallowed an unidentified pill--toxicological tests ruled out poisoning. The diagnosis is based on the clinical examination and amplification ECHO virus from CSF.

  13. Crossed cerebellar diaschisis in acute ischemic stroke: Impact on morphologic and functional outcome.

    PubMed

    Kunz, Wolfgang G; Sommer, Wieland H; Höhne, Christopher; Fabritius, Matthias P; Schuler, Felix; Dorn, Franziska; Othman, Ahmed E; Meinel, Felix G; von Baumgarten, Louisa; Reiser, Maximilian F; Ertl-Wagner, Birgit; Thierfelder, Kolja M

    2017-01-01

    Crossed cerebellar diaschisis (CCD) is the phenomenon of hypoperfusion and hypometabolism of the contralateral cerebellar hemisphere caused by dysfunction of the related supratentorial region. Our aim was to analyze its influence on morphologic and functional outcome in acute ischemic stroke. Subjects with stroke caused by a large vessel occlusion of the anterior circulation were selected from an initial cohort of 1644 consecutive patients who underwent multiparametric CT including whole-brain CT perfusion. Two experienced readers evaluated the posterior fossa in terms of CCD absence (CCD-) or presence (CCD+). A total of 156 patients formed the study cohort with 102 patients (65.4%) categorized as CCD- and 54 (34.6%) as CCD+. In linear and logistic regression analyses, no significant association between CCD and final infarction volume (β = -0.440, p = 0.972), discharge mRS ≤ 2 (OR = 1.897, p = 0.320), or 90-day mRS ≤ 2 (OR = 0.531, p = 0.492) was detected. CCD+ patients had larger supratentorial cerebral blood flow deficits (median: 164 ml vs. 115 ml; p = 0.001) compared to CCD-patients. Regarding complications, CCD was associated with a higher rate of parenchymal hematomas (OR = 4.793, p = 0.035). In conclusion, CCD is frequently encountered in acute ischemic stroke caused by large vessel occlusion of the anterior circulation. CCD was associated with the occurrence of parenchymal hematoma in the ipsilateral cerebral infarction but did not prove to significantly influence patient outcome.

  14. A composite neurobehavioral test to evaluate acute functional deficits after cerebellar haemorrhage in rats.

    PubMed

    McBride, Devin W; Nowrangi, Derek; Kaur, Harpreet; Wu, Guangyong; Huang, Lei; Lekic, Tim; Tang, Jiping; Zhang, John H

    2017-01-01

    Cerebellar haemorrhage accounts for 5-10% of all intracerebral haemorrhages and leads to severe, long-lasting functional deficits. Currently, there is limited research on this stroke subtype, which may be due to the lack of a suitable composite neuroscoring system specific for cerebellar injury in rodents. The purpose of this study is to develop a comprehensive composite neuroscore test for cerebellar injury using a rat model of cerebellar haemorrhage. Sixty male Sprague-Dawley rats were subjected to either sham surgery or cerebellar haemorrhage. Twenty-four hours post-injury, neurological behaviour was evaluated using 17 cost-effective and easy-to-perform tests, and a composite neuroscore was developed. The composite neuroscore was then used to assess functional recovery over seven days after cerebellar haemorrhage. Differences in the composite neuroscore deficits for the mild and moderate cerebellar haemorrhage models were observed for up to five days post-ictus. Until now, a composite neuroscore for cerebellar injury was not available for rodent studies. Herein, using mild and moderate cerebellar haemorrhage rat models a composite neuroscore for cerebellar injury was developed and used to assess functional deficits after cerebellar haemorrhage. This composite neuroscore may also be useful for other cerebellar injury models.

  15. 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.

  16. Case Report: Acute Cerebellar Thrombosis in an Adult Patient with IgM Nephropathy

    PubMed Central

    Adike, Abimbola; Cherry, Mariyam; Awar, Melina

    2015-01-01

    IgM nephropathy is a relatively rare cause of idiopathic nephrotic syndrome.1 It was initially described by van de Putte,2 then by Cohen and Bhasin in 1978, as a distinctive feature of mesangial proliferative glomerulonephritis.2 It is typically characterized by diffuse IgM deposits on the glomeruli and diffuse mesangial hypercellularity. Little is known about the pathogenesis and treatment of this disease.1,3 We describe a patient who presented with nonspecific symptoms of epigastric pain, nausea, and early satiety. Abdominal imaging and endoscopies were unremarkable. She was found to have significant proteinuria (6.4 g/24 hours), hyperlipidemia, and edema consistent with a diagnosis of nephrotic syndrome. Kidney biopsy was performed and confirmed an IgM nephropathy. Less than 2 weeks after her diagnosis of IgM nephropathy, she presented with an acute cerebellar stroke. Thrombophilia is a well-known complication of nephrotic syndrome, but a review of the literature failed to show an association between IgM nephropathy and acute central nervous system thrombosis. PMID:27057296

  17. Cerebellar haemorrhage mimicking acute peripheral vestibulopathy: the role of the video head impulse test in differential diagnosis.

    PubMed

    Armato, E; Ferri, E; Pinzani, A; Ulmer, E

    2014-08-01

    Dizziness and vertigo without neurological signs are typically due to a peripheral vestibular disease. Although the most common causes are benign, differential diagnosis must include potentially life-threatening central diseases such as cerebrovascular pathologies. A systemic clinical approach needs a careful work-up, bedside examination and appropriate instrumental investigation. The head impulse test (HIT) allows qualitative clinical assessment of canalar function; it has some limitations such as subjective evaluation, mainly in patients with a spontaneous nystagmus. A new device has been recently developed consisting of an infrared video camera (video-HIT) to provide quantitative instrumental assessment of the high-frequency vestibular-ocular reflex (VOR) gain. By reporting a case of cerebellar haemorrhage mimicking an acute peripheral vestibulopathy, the authors suggest that video-HIT may be considered a useful tool in differential diagnosis between vestibular neuritis and cerebellar vascular disease in patients with severe acute vertigo without central signs.

  18. GnRH neuron firing and response to GABA in vitro depend on acute brain slice thickness and orientation.

    PubMed

    Constantin, Stephanie; Piet, Richard; Iremonger, Karl; Hwa Yeo, Shel; Clarkson, Jenny; Porteous, Robert; Herbison, Allan E

    2012-08-01

    The GnRH neurons exhibit long dendrites and project to the median eminence. The aim of the present study was to generate an acute brain slice preparation that enabled recordings to be undertaken from GnRH neurons maintaining the full extent of their dendrites or axons. A thick, horizontal brain slice was developed, in which it was possible to record from the horizontally oriented GnRH neurons located in the anterior hypothalamic area (AHA). In vivo studies showed that the majority of AHA GnRH neurons projected outside the blood-brain barrier and expressed c-Fos at the time of the GnRH surge. On-cell recordings compared AHA GnRH neurons in the horizontal slice (AHAh) with AHA and preoptic area (POA) GnRH neurons in coronal slices [POA coronal (POAc) and AHA coronal (AHAc), respectively]. AHAh GnRH neurons exhibited tighter burst firing compared with other slice orientations. Although α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) excited GnRH neurons in all preparations, γ-aminobutyric acid (GABA) was excitatory in AHAc and POAc but inhibitory in AHAh slices. GABA(A) receptor postsynaptic currents were the same in AHAh and AHAc slices. Intriguingly, direct activation of GABA(A) or GABA(B) receptors respectively stimulated and inhibited GnRH neurons regardless of slice orientation. Subsequent experiments indicated that net GABA effects were determined by differences in the ratio of GABA(A) and GABA(B) receptor-mediated effects in "long" and "short" dendrites of GnRH neurons in the different slice orientations. These studies document a new brain slice preparation for recording from GnRH neurons with their extensive dendrites/axons and highlight the importance of GnRH neuron orientation relative to the angle of brain slicing in studying these neurons in vitro.

  19. Dense arrays of micro-needles for recording and electrical stimulation of neural activity in acute brain slices

    NASA Astrophysics Data System (ADS)

    Gunning, D. E.; Beggs, J. M.; Dabrowski, W.; Hottowy, P.; Kenney, C. J.; Sher, A.; Litke, A. M.; Mathieson, K.

    2013-02-01

    Objective. This paper describes the design, microfabrication, electrical characterization and biological evaluation of a high-density micro-needle array. The array records from and electrically stimulates individual neurons simultaneously in acute slices of brain tissue. Approach. Acute slices, arguably the closest in-vitro model of the brain, have a damaged surface layer. Since electrophysiological recording methods rely heavily on electrode-cell proximity, this layer significantly attenuates the signal amplitude making the use of traditional planar electrodes unsuitable. To penetrate into the tissue, bypassing the tissue surface, and to record and stimulate neural activity in the healthy interior volume of the slice, an array of 61 micro-needles was fabricated. Main results. This device is shown to record extracellular action potentials from individual neurons in acute cortical slices with a signal to noise ratio of up to ˜15:1. Electrical stimulation of individual neurons is achieved with stimulation thresholds of 1.1-2.9 µA. Significance. The novelty of this system is the combination of close needle spacing (60 µm), needle heights of up to 250 µm and small (5-10 µm diameter) electrodes allowing the recording of single unit activity. The array is coupled to a custom-designed readout system forming a powerful electrophysiological tool that permits two-way electrode-cell communication with populations of neurons in acute brain slices.

  20. 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

  1. 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

    2015-09-04

    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.

  2. 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

    2016-06-01

    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.

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

    PubMed Central

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

    2017-01-01

    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

  4. Acute and chronic administration of ibogaine to the rat results in astrogliosis that is not confined to the cerebellar vermis.

    PubMed

    O'Callaghan, J P; Rogers, T S; Rodman, L E; Page, J G

    1996-10-31

    Acute administration of high doses of ibogaine (IBG) to the male rat results in degeneration of Purkinje cells and reactive gliosis in the cerebellar vermis. We examined whether acute and chronic administration of IBG to male and female rats results in gliosis as determined by quantification of the astroglial intermediate filament protein, glial fibrillary acidic protein (GFAP). After acute administration of IBG, rats of both sexes showed dose-related increases in GFAP that were not confined to the cerebellar vermis. After chronic administration of IBG, female, but not male rats, showed large (as much as 200% of control), dose-related increases in GFAP in hippocampus, olfactory bulbs, brain stem and striatum, but not cerebellum. In hippocampus, the cytoskeletal proteins, neurofilament 68 (NF-68) and beta-tubulin were increased in females treated chronically with IBG, findings consistent with a damage-induced sprouting response. Together, the data indicate that IBG damages areas of the brain outside the cerebellum and that the sites damaged are dependent on sex and dosage regimen.

  5. Acute death of astrocytes in blast-exposed rat organotypic hippocampal slice cultures.

    PubMed

    Miller, Anna P; Shah, Alok S; Aperi, Brandy V; Kurpad, Shekar N; Stemper, Brian D; Glavaski-Joksimovic, Aleksandra

    2017-01-01

    Blast traumatic brain injury (bTBI) affects civilians, soldiers, and veterans worldwide and presents significant health concerns. The mechanisms of neurodegeneration following bTBI remain elusive and current therapies are largely ineffective. It is important to better characterize blast-evoked cellular changes and underlying mechanisms in order to develop more effective therapies. In the present study, our group utilized rat organotypic hippocampal slice cultures (OHCs) as an in vitro system to model bTBI. OHCs were exposed to either 138 ± 22 kPa (low) or 273 ± 23 kPa (high) overpressures using an open-ended helium-driven shock tube, or were assigned to sham control group. At 2 hours (h) following injury, we have characterized the astrocytic response to a blast overpressure. Immunostaining against the astrocytic marker glial fibrillary acidic protein (GFAP) revealed acute shearing and morphological changes in astrocytes, including clasmatodendrosis. Moreover, overlap of GFAP immunostaining and propidium iodide (PI) indicated astrocytic death. Quantification of the number of dead astrocytes per counting area in the hippocampal cornu Ammonis 1 region (CA1), demonstrated a significant increase in dead astrocytes in the low- and high-blast, compared to sham control OHCs. However only a small number of GFAP-expressing astrocytes were co-labeled with the apoptotic marker Annexin V, suggesting necrosis as the primary type of cell death in the acute phase following blast exposure. Moreover, western blot analyses revealed calpain mediated breakdown of GFAP. The dextran exclusion additionally indicated membrane disruption as a potential mechanism of acute astrocytic death. Furthermore, although blast exposure did not evoke significant changes in glutamate transporter 1 (GLT-1) expression, loss of GLT-1-expressing astrocytes suggests dysregulation of glutamate uptake following injury. Our data illustrate the profound effect of blast overpressure on astrocytes in OHCs at 2 h

  6. Acute death of astrocytes in blast-exposed rat organotypic hippocampal slice cultures

    PubMed Central

    Miller, Anna P.; Shah, Alok S.; Aperi, Brandy V.; Kurpad, Shekar N.; Stemper, Brian D.; Glavaski-Joksimovic, Aleksandra

    2017-01-01

    Blast traumatic brain injury (bTBI) affects civilians, soldiers, and veterans worldwide and presents significant health concerns. The mechanisms of neurodegeneration following bTBI remain elusive and current therapies are largely ineffective. It is important to better characterize blast-evoked cellular changes and underlying mechanisms in order to develop more effective therapies. In the present study, our group utilized rat organotypic hippocampal slice cultures (OHCs) as an in vitro system to model bTBI. OHCs were exposed to either 138 ± 22 kPa (low) or 273 ± 23 kPa (high) overpressures using an open-ended helium-driven shock tube, or were assigned to sham control group. At 2 hours (h) following injury, we have characterized the astrocytic response to a blast overpressure. Immunostaining against the astrocytic marker glial fibrillary acidic protein (GFAP) revealed acute shearing and morphological changes in astrocytes, including clasmatodendrosis. Moreover, overlap of GFAP immunostaining and propidium iodide (PI) indicated astrocytic death. Quantification of the number of dead astrocytes per counting area in the hippocampal cornu Ammonis 1 region (CA1), demonstrated a significant increase in dead astrocytes in the low- and high-blast, compared to sham control OHCs. However only a small number of GFAP-expressing astrocytes were co-labeled with the apoptotic marker Annexin V, suggesting necrosis as the primary type of cell death in the acute phase following blast exposure. Moreover, western blot analyses revealed calpain mediated breakdown of GFAP. The dextran exclusion additionally indicated membrane disruption as a potential mechanism of acute astrocytic death. Furthermore, although blast exposure did not evoke significant changes in glutamate transporter 1 (GLT-1) expression, loss of GLT-1-expressing astrocytes suggests dysregulation of glutamate uptake following injury. Our data illustrate the profound effect of blast overpressure on astrocytes in OHCs at 2 h

  7. 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.

  8. Electrophysiological and Morphological Characterization of Neuronal Microcircuits in Acute Brain Slices Using Paired Patch-Clamp Recordings

    PubMed Central

    Qi, Guanxiao; Radnikow, Gabriele; Feldmeyer, Dirk

    2015-01-01

    The combination of patch clamp recordings from two (or more) synaptically coupled neurons (paired recordings) in acute brain slice preparations with simultaneous intracellular biocytin filling allows a correlated analysis of their structural and functional properties. With this method it is possible to identify and characterize both pre- and postsynaptic neurons by their morphology and electrophysiological response pattern. Paired recordings allow studying the connectivity patterns between these neurons as well as the properties of both chemical and electrical synaptic transmission. Here, we give a step-by-step description of the procedures required to obtain reliable paired recordings together with an optimal recovery of the neuron morphology. We will describe how pairs of neurons connected via chemical synapses or gap junctions are identified in brain slice preparations. We will outline how neurons are reconstructed to obtain their 3D morphology of the dendritic and axonal domain and how synaptic contacts are identified and localized. We will also discuss the caveats and limitations of the paired recording technique, in particular those associated with dendritic and axonal truncations during the preparation of brain slices because these strongly affect connectivity estimates. However, because of the versatility of the paired recording approach it will remain a valuable tool in characterizing different aspects of synaptic transmission at identified neuronal microcircuits in the brain. PMID:25650985

  9. 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

  10. Effects of normobaric versus hyperbaric oxygen on cell injury induced by oxygen and glucose deprivation in acute brain slices

    PubMed Central

    Chazalviel, Laurent; Blatteau, Jean-Eric; Vallée, Nicolas; Risso, Jean-Jacques; Besnard, Stéphane; Abraini, Jacques H.

    2016-01-01

    Normobaric oxygen (NBO) and hyperbaric oxygen (HBO) are emerging as a possible co-treatment of acute ischemic stroke. Both have been shown to reduce infarct volume, to improve neurologic outcome, to promote endogenous tissue plasminogen activator-induced thrombolysis and cerebral blood flow, and to improve tissue oxygenation through oxygen diffusion in the ischemic areas, thereby questioning the interest of HBO compared to NBO. In the present study, in order to investigate and compare the oxygen diffusion effects of NBO and HBO on acute ischemic stroke independently of their effects at the vascular level, we used acute brain slices exposed to oxygen and glucose deprivation, an ex vivo model of brain ischemia that allows investigating the acute effects of NBO (partial pressure of oxygen (pO2) = 1 atmospheres absolute (ATA) = 0.1 MPa) and HBO (pO2 = 2.5 ATA = 0.25 MPa) through tissue oxygenation on ischemia-induced cell injury as measured by the release of lactate dehydrogenase. We found that HBO, but not NBO, reduced oxygen and glucose deprivation-induced cell injury, indicating that passive tissue oxygenation (i.e. without vascular support) of the brain parenchyma requires oxygen partial pressure higher than 1 ATA. PMID:27867486

  11. Effects of normobaric versus hyperbaric oxygen on cell injury induced by oxygen and glucose deprivation in acute brain slices.

    PubMed

    Chazalviel, Laurent; Blatteau, Jean-Eric; Vallée, Nicolas; Risso, Jean-Jacques; Besnard, Stéphane; Abraini, Jacques H

    2016-01-01

    Normobaric oxygen (NBO) and hyperbaric oxygen (HBO) are emerging as a possible co-treatment of acute ischemic stroke. Both have been shown to reduce infarct volume, to improve neurologic outcome, to promote endogenous tissue plasminogen activator-induced thrombolysis and cerebral blood flow, and to improve tissue oxygenation through oxygen diffusion in the ischemic areas, thereby questioning the interest of HBO compared to NBO. In the present study, in order to investigate and compare the oxygen diffusion effects of NBO and HBO on acute ischemic stroke independently of their effects at the vascular level, we used acute brain slices exposed to oxygen and glucose deprivation, an ex vivo model of brain ischemia that allows investigating the acute effects of NBO (partial pressure of oxygen (pO2) = 1 atmospheres absolute (ATA) = 0.1 MPa) and HBO (pO2 = 2.5 ATA = 0.25 MPa) through tissue oxygenation on ischemia-induced cell injury as measured by the release of lactate dehydrogenase. We found that HBO, but not NBO, reduced oxygen and glucose deprivation-induced cell injury, indicating that passive tissue oxygenation (i.e. without vascular support) of the brain parenchyma requires oxygen partial pressure higher than 1 ATA.

  12. Neuroligins Are Selectively Essential for NMDAR Signaling in Cerebellar Stellate Interneurons

    PubMed Central

    Südhof, Thomas C.

    2016-01-01

    Neuroligins are postsynaptic cell-adhesion molecules that contribute to synapse specification. However, many other postsynaptic cell-adhesion molecules are known and the relative contributions of neuroligins versus other such molecules in different types of synapses and neurons remains largely unknown. Here, we have studied the role of neuroligins in cerebellar stellate interneurons that participate in a well defined circuit that converges on Purkinje cells as the major output neurons of cerebellar cortex. By crossing triple conditional knock-out (cKO) mice targeting all three major neuroligins [neuroligin-1 to neuroligin-3 (NL123)] with parvalbumin-Cre (PV-Cre) transgenic mice, we deleted neuroligins from inhibitory cerebellar interneurons and Purkinje cells, allowing us to study the effects of neuroligin deletions on cerebellar stellate cell synapses by electrophysiology in acute slices. PV-Cre/NL123 cKO mice did not exhibit gross alterations of cerebellar structure or cerebellar interneuron morphology. Strikingly, electrophysiological recordings in stellate cells from these PV-Cre/NL123 cKO mice revealed a large decrease in NMDAR-mediated excitatory synaptic responses, which, in stellate cells, are largely extrasynaptic, without a change in AMPA-receptor-mediated responses. Parallel analyses in PV-Cre/NL1 mice that are single NL1 cKO mice uncovered the same phenotype, demonstrating that NL1 is responsible for recruiting extrasynaptic NMDARs. Moreover, we observed only a modest impairment in inhibitory synaptic responses in stellate cells lacking NL123 despite a nearly complete suppression of inhibitory synaptic transmission in Purkinje cells by the same genetic manipulation. Our results suggest that, unlike other types of neurons investigated, neuroligins are selectively essential in cerebellar stellate interneurons for enabling the function of extrasynaptic NMDARs. SIGNIFICANCE STATEMENT Neuroligins are postsynaptic cell-adhesion molecules genetically linked to

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

    PubMed

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

    2013-09-06

    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.

  14. [Cerebellar hypoplasias].

    PubMed

    Safronova, Marta Maia; Barbot, Clara; Resende Pereira, Jorge

    2010-01-01

    Cerebellar hypoplasias are cerebellar malformations with small but completely formed cerebellum. They can be divided in focal and in diffuse or generalized. It is sometimes difficult to make distinction between cerebellar atrophy (progressive condition) and hipoplasia (not progressive condition). Focal hypoplasias are restricted to one cerebellar hemisphere or to the vermis. Diffuse hypoplasias refer to both cerebellar hemispheres and vermis. If there is associated IVth ventricle enlargement, hypoplasias occur in the context of Dandy-Walker complex, a continuum of posterior fossa cystic anomalies. A revision of cerebellar hypoplasias and associated pathology is done, illustrated with 22 cases tha include focal and diffuse cerebellar hypoplasias, Dandy-Walker malformations and its variant, persistent Blake's pouch cyst, megacisterna magna, PEHO síndrome (progressive encephalopathy with oedema, hipsarrhythmia and optic atrophy), Joubert syndrome, congenital disorder of glycosylation type Ia, pontocerebellar hipoplasias Barth type I and II, diffuse subcortical heterotopia. The imaging finding of structural cerebellar anomalies frequently leads to diagnostic incertainty as the anomalies are mostly unspecific, implying an extenuating analytical and genetic workup. Their knowledge and classification may be useful to decide the patient adjusted laboratorial workup.

  15. Dibucaine Mitigates Spreading Depolarization in Human Neocortical Slices and Prevents Acute Dendritic Injury in the Ischemic Rodent Neocortex

    PubMed Central

    Risher, W. Christopher; Lee, Mark R.; Fomitcheva, Ioulia V.; Hess, David C.; Kirov, Sergei A.

    2011-01-01

    Background Spreading depolarizations that occur in patients with malignant stroke, subarachnoid/intracranial hemorrhage, and traumatic brain injury are known to facilitate neuronal damage in metabolically compromised brain tissue. The dramatic failure of brain ion homeostasis caused by propagating spreading depolarizations results in neuronal and astroglial swelling. In essence, swelling is the initial response and a sign of the acute neuronal injury that follows if energy deprivation is maintained. Choosing spreading depolarizations as a target for therapeutic intervention, we have used human brain slices and in vivo real-time two-photon laser scanning microscopy in the mouse neocortex to study potentially useful therapeutics against spreading depolarization-induced injury. Methodology/Principal Findings We have shown that anoxic or terminal depolarization, a spreading depolarization wave ignited in the ischemic core where neurons cannot repolarize, can be evoked in human slices from pediatric brains during simulated ischemia induced by oxygen/glucose deprivation or by exposure to ouabain. Changes in light transmittance (LT) tracked terminal depolarization in time and space. Though spreading depolarizations are notoriously difficult to block, terminal depolarization onset was delayed by dibucaine, a local amide anesthetic and sodium channel blocker. Remarkably, the occurrence of ouabain-induced terminal depolarization was delayed at a concentration of 1 µM that preserves synaptic function. Moreover, in vivo two-photon imaging in the penumbra revealed that, though spreading depolarizations did still occur, spreading depolarization-induced dendritic injury was inhibited by dibucaine administered intravenously at 2.5 mg/kg in a mouse stroke model. Conclusions/Significance Dibucaine mitigated the effects of spreading depolarization at a concentration that could be well-tolerated therapeutically. Hence, dibucaine is a promising candidate to protect the brain from

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

    PubMed Central

    Phillips, Wiktor S.; Herly, Mikkel; Del Negro, Christopher A.

    2015-01-01

    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

  17. Compression of the medulla oblongata and acute respiratory failure caused by rupture of a thrombosed large aneurysm of the anterior inferior cerebellar artery.

    PubMed

    Oyama, Hirofumi; Kito, Akira; Maki, Hideki; Hattori, Kenichi; Tanahashi, Kuniaki

    2010-01-01

    A 65-year-old female presented with an extremely rare case of a ruptured thrombosed large aneurysm of the anterior inferior cerebellar artery (AICA) in which a local hematoma compressed the medulla oblongata and caused acute respiratory failure. She first presented with dizziness, general fatigue, and nausea 2 months before admission. She was hospitalized for intense general fatigue, nausea, and occipitalgia. Computed tomography and T(1)-weighted magnetic resonance imaging showed a heterogeneous lesion around the right cerebello-medullary cistern. Angiography revealed a fusiform aneurysm of the right AICA. Asphyxia occurred 4 days after admission and the patient underwent an emergency operation. No subarachnoid hematoma was present, but a hematoma around the ruptured portion markedly compressed the medulla oblongata. The medulla oblongata was adequately decompressed after subtotal removal of the aneurysm. The patient's respiratory status and consciousness level recovered after the operation.

  18. Granular Layer Neurons Control Cerebellar Neurovascular Coupling Through an NMDA Receptor/NO-Dependent System.

    PubMed

    Mapelli, Lisa; Gagliano, Giuseppe; Soda, Teresa; Laforenza, Umberto; Moccia, Francesco; D'Angelo, Egidio U

    2017-02-01

    Neurovascular coupling (NVC) is the process whereby neuronal activity controls blood vessel diameter. In the cerebellum, the molecular layer is regarded as the main NVC determinant. However, the granular layer is a region with variable metabolic demand caused by large activity fluctuations that shows a prominent expression of NMDA receptors (NMDARs) and nitric oxide synthase (NOS) and is therefore much more suitable for effective NVC. Here, we show, in the granular layer of acute rat cerebellar slices, that capillary diameter changes rapidly after mossy fiber stimulation. Vasodilation required neuronal NMDARs and NOS stimulation and subsequent guanylyl cyclase activation that probably occurred in pericytes. Vasoconstriction required metabotropic glutamate receptors and CYP ω-hydroxylase, the enzyme regulating 20-hydroxyeicosatetraenoic acid production. Therefore, granular layer capillaries are controlled by the balance between vasodilating and vasoconstricting systems that could finely tune local blood flow depending on neuronal activity changes at the cerebellar input stage.

  19. Cerebellar Ataxia.

    PubMed

    Perlman

    2000-05-01

    There is nothing more discouraging than for a patient to be given a specific diagnosis, then to be told that there is nothing that can be done. Physicians are equally disheartened to see exponential progress being made in the understanding of the pathophysiology of a complex disorder but few direct benefits resulting for their patients. Over the past 5 years, molecular genetic research has completely revolutionized the way in which the progressive cerebellar ataxias are classified and diagnosed, but it has yet to produce effective gene-based, neuroprotective, or neurorestorative therapies. The treatment of cerebellar ataxia remains primarily a neurorehabilitation challenge, employing physical, occupational, speech, and swallowing therapy; adaptive equipment; driver safety training; and nutritional counseling. Modest additional gains are seen with the use of medications that can improve imbalance, incoordination, or dysarthria (amantadine, buspirone, acetazolamide); cerebellar tremor (clonazepam, propranolol); and cerebellar or central vestibular nystagmus (gabapentin, baclofen, clonazepam). Many of the progressive cerebellar syndromes have associated features involving other neurologic systems (eg, spasticity, dystonia or rigidity, resting or rubral tremor, chorea, motor unit weakness or fatigue, autonomic dysfunction, peripheral or posterior column sensory loss, neuropathic pain or cramping, double vision, vision and hearing loss, dementia, and bowel, bladder, and sexual dysfunction), which can impede the treatment of the ataxic symptoms or can worsen with the use of certain drugs. Treatment of the associated features themselves may in turn worsen the ataxia either directly (as side effects of medication) or indirectly (eg, relaxation of lower limb spasticity that was acting as a stabilizer for an ataxic gait). Secondary complications of progressive ataxia can include deconditioning or immobility, weight loss or gain, skin breakdown, recurrent pulmonary and

  20. 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

  1. Specificity of exogenous acetate and glutamate as astrocyte substrates examined in acute brain slices from female mice using methionine sulfoximine (MSO) to inhibit glutamine synthesis.

    PubMed

    Andersen, Jens Velde; McNair, Laura Frendrup; Schousboe, Arne; Waagepetersen, Helle Sønderby

    2017-02-28

    Removal of endogenously released glutamate is mediated primarily by astrocytes and exogenous (13) C-labeled glutamate has been applied to study glutamate metabolism in astrocytes. Likewise, studies have clearly established the relevance of (13) C-labeled acetate as an astrocyte specific metabolic substrate. Recent studies have, however, challenged the arguments used to anchor this astrocyte specificity of acetate and glutamate. The aim of the current study was to evaluate the specificity of acetate and glutamate as astrocyte substrates in brain slices. Acutely isolated hippocampal and cerebral cortical slices from female NMRI mice were incubated in media containing [1,2-(13) C]acetate or [U-(13) C]glutamate, with or without methionine sulfoximine (MSO) to inhibit glutamine synthetase (GS). Tissue extracts were analyzed by gas chromatography-mass spectrometry. Blocking GS abolished the majority of glutamine (13) C-labeling from [1,2-(13) C]acetate as intended. However, (13) C-labeling of GABA was only 40-50% reduced by MSO, suggesting considerable neuronal uptake of acetate. Moreover, labeling of glutamate from [1,2-(13) C]acetate in the presence of MSO exceeded the level probable from exclusive labeling of the astrocytic pool, which likewise suggests neuronal acetate metabolism. Approximately 50% of glutamate was uniformly labeled in slices incubated with [U-(13) C]glutamate in the presence of MSO, suggesting that neurons exhibit substantial uptake of exogenously provided glutamate. © 2017 Wiley Periodicals, Inc.

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

    PubMed

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

    2014-04-01

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

  3. 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

  4. [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.

  5. Ionic mechanisms of autorhythmic firing in rat cerebellar Golgi cells

    PubMed Central

    Elisabetta Cesana, Lia Forti; Mapelli, Jonathan; D'Angelo, Egidio

    2006-01-01

    Although Golgi cells (GoCs), the main type of inhibitory interneuron in the cerebellar granular layer (GL), are thought to play a central role in cerebellar network function, their excitable properties have remained unexplored. GoCs fire rhythmically in vivo and in slices, but it was unclear whether this activity originated from pacemaker ionic mechanisms. We explored this issue in acute cerebellar slices from 3-week-old rats by combining loose cell-attached (LCA) and whole-cell (WC) recordings. GoCs displayed spontaneous firing at 1–10 Hz (room temperature) and 2–20 Hz (35–37°C), which persisted in the presence of blockers of fast synaptic receptors and mGluR and GABAB receptors, thus behaving, in our conditions, as pacemaker neurons. ZD 7288 (20 μm), a potent hyperpolarization-activated current (Ih) blocker, slowed down pacemaker frequency. The role of subthreshold Na+ currents (INa,sub) could not be tested directly, but we observed a robust TTX-sensitive, non-inactivating Na+ current in the subthreshold voltage range. When studying repolarizing currents, we found that retigabine (5 μm), an activator of KCNQ K+ channels generating neuronal M-type K+ (IM) currents, reduced GoC excitability in the threshold region. The KCNQ channel antagonist XE991 (5 μm) did not modify firing, suggesting that GoC IM has low XE991 sensitivity. Spike repolarization was followed by an after-hyperpolarization (AHP) supported by apamin-sensitive Ca2+-dependent K+ currents (Iapa). Block of Iapa decreased pacemaker precision without altering average frequency. We propose that feed-forward depolarization is sustained by Ih and INa,sub, and that delayed repolarizing feedback involves an IM-like current whose properties remain to be characterized. The multiple ionic mechanisms shown here to contribute to GoC pacemaking should provide the substrate for fine regulation of firing frequency and precision, thus influencing the cyclic inhibition exerted by GoCs onto the cerebellar GL

  6. 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

  7. 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.

  8. 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

  9. The Relationship between Membrane Potential and Calcium Dynamics in Glucose-Stimulated Beta Cell Syncytium in Acute Mouse Pancreas Tissue Slices

    PubMed Central

    Miller, Evan W.; Slak Rupnik, Marjan

    2013-01-01

    Oscillatory electrical activity is regarded as a hallmark of the pancreatic beta cell glucose-dependent excitability pattern. Electrophysiologically recorded membrane potential oscillations in beta cells are associated with in-phase oscillatory cytosolic calcium activity ([Ca2+]i) measured with fluorescent probes. Recent high spatial and temporal resolution confocal imaging revealed that glucose stimulation of beta cells in intact islets within acute tissue slices produces a [Ca2+]i change with initial transient phase followed by a plateau phase with highly synchronized [Ca2+]i oscillations. Here, we aimed to correlate the plateau [Ca2+]i oscillations with the oscillations of membrane potential using patch-clamp and for the first time high resolution voltage-sensitive dye based confocal imaging. Our results demonstrated that the glucose-evoked membrane potential oscillations spread over the islet in a wave-like manner, their durations and wave velocities being comparable to the ones for [Ca2+]i oscillations and waves. High temporal resolution simultaneous records of membrane potential and [Ca2+]i confirmed tight but nevertheless limited coupling of the two processes, with membrane depolarization preceding the [Ca2+]i increase. The potassium channel blocker tetraethylammonium increased the velocity at which oscillations advanced over the islet by several-fold while, at the same time, emphasized differences in kinetics of the membrane potential and the [Ca2+]i. The combination of both imaging techniques provides a powerful tool that will help us attain deeper knowledge of the beta cell network. PMID:24324777

  10. 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...

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

    PubMed Central

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

    2008-01-01

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

  12. [Study of cerebellar infarction with isolated vertigo].

    PubMed

    Utsumi, Ai; Enomoto, Hiroyuki; Yamamoto, Kaoru; Kimura, Yu; Koizuka, Izumi; Tsukuda, Mamoru

    2010-07-01

    Isolated vertigo is generally attributed to labyrinthine disease, but may also signal otherwise asymptomatic cerebellar infarction. Of 309 subjects admitted between April 2004 and March 2009 for the single symptom of acute vertigo initially thought to be labyrinthine, four were found to have cerebellar infarction of the posterior inferior cerebellar artery area (PICA). All were over 60 years old and had risk factors including hypertension, diabetes mellitus, arrhythmia, and/or hyperlipidemia. Two had trunk ataxia, with magnetic resonance imaging (MRI) showing infarction within a few days. The other two could walk without apparent trunk ataxia, however, it took 4 to 7 days to find the infarction, mainly through neurological, neurootological, and MRI findings. Neurologically, astasia, dysbasia or trunk ataxia were important signs. Neurootologically, nystagmus and electronystagmographic testing involving eye tracking, saccade, and optokinetic patttens were useful.

  13. Iatrogenic postoperative cerebellar cyst.

    PubMed

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

    2016-12-01

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

  14. 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.

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

    PubMed

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

    2010-01-01

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

  16. [Autosomal recessive cerebellar ataxias].

    PubMed

    Tranchant, Christine; Anheim, Mathieu

    2009-12-01

    Friedreich ataxia is the most frequent recessive cerebral ataxia d should always be researched first. Ataxia with isolated vitamin E deficiency and abetalipoproteinemia have a specific treatment. Associated neurological signs such polyneuroapthy, ophtalmologic or oculomotor signs, pyramidal signs, and cerebellar MRI can lead to the etiological diagnosis. Biological tests should be: vitamin E, cholesterol, alpha-fetoprotein levels, acanthocytes, than phytanic acid, cholestanol, lysosomal enzymes. Numerous autosomal recessive cerebellar ataxia remain without etiology.

  17. Cerebellar Development and Disease

    PubMed Central

    Gleeson, Joseph G.

    2008-01-01

    Recent Advances The molecular control of cell type specification within the developing cerebellum as well as the genetic causes of the most common human developmental cerebellar disorders have long remained mysterious. Recent genetic lineage and loss-of-function data from mice have revealed unique and non-overlapping anatomical origins for GABAergic neurons from ventricular zone precursors and glutamatergic cell from rhombic lip precursors, mirroring distinct origins for these neurotransmitter-specific cell types in the cerebral cortex. Mouse studies elucidating the role of Ptf1a as a cerebellar ventricular zone GABerigic fate switch were actually preceded by the recognition that PTF1A mutations in humans cause cerebellar agenesis, a birth defect of the human cerebellum. Indeed, several genes for congenital human cerebellar malformations have recently been identified, including genes causing Joubert syndrome, Dandy-Walker malformation and Ponto-cerebellar hypoplasia. These studies have pointed to surprisingly complex roles for transcriptional regulation, mitochondrial function and neuronal cilia in patterning, homeostasis and cell proliferation during cerebellar development. Together mouse and human studies are synergistically advancing our understanding of the developmental mechanisms that generate the uniquely complex mature cerebellum. PMID:18513948

  18. 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…

  19. 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.

  20. Abnormal cerebellar morphometry in abstinent adolescent marijuana users

    PubMed Central

    Medina, Krista Lisdahl; Nagel, Bonnie J.; Tapert, Susan F.

    2010-01-01

    Background Functional neuroimaging data from adults have, in general, found frontocerebellar dysfunction associated with acute and chronic marijuana (MJ) use (Loeber & Yurgelun-Todd, 1999). One structural neuroimaging study found reduced cerebellar vermis volume in young adult MJ users with a history of heavy polysubstance use (Aasly et al., 1993). The goal of this study was to characterize cerebellar volume in adolescent chronic MJ users following one month of monitored abstinence. Method Participants were MJ users (n=16) and controls (n=16) aged 16-18 years. Extensive exclusionary criteria included history of psychiatric or neurologic disorders. Drug use history, neuropsychological data, and structural brain scans were collected after 28 days of monitored abstinence. Trained research staff defined cerebellar volumes (including three cerebellar vermis lobes and both cerebellar hemispheres) on high-resolution T1-weighted magnetic resonance images. Results Adolescent MJ users demonstrated significantly larger inferior posterior (lobules VIII-X) vermis volume (p<.009) than controls, above and beyond effects of lifetime alcohol and other drug use, gender, and intracranial volume. Larger vermis volumes were associated with poorer executive functioning (p’s<.05). Conclusions Following one month of abstinence, adolescent MJ users had significantly larger posterior cerebellar vermis volumes than non-using controls. These greater volumes are suggested to be pathological based on linkage to poorer executive functioning. Longitudinal studies are needed to examine typical cerebellar development during adolescence and the influence of marijuana use. PMID:20413277

  1. Asterixis as a Presentation of Cerebellar Ischemic Stroke

    PubMed Central

    Siniscalchi, Antonio; Gallelli, Luca; Di Benedetto, Olindo; De Sarro, Giovambattista

    2012-01-01

    Asterixis is not yet considered a common neurological sign of cerebellum infarction, and the pathogenic mechanism for asterixis remains elusive. We report a 58-year-old male with moderate hypertension who presented to our emergency department for acute headache in both cervical and occipital regions of the left side. About 2 hours later the patient developed ipsilateral asterixis in the upper left limb; 3 days later the asterixis disappeared. Magnetic resonance imaging of the brain disclosed cerebellar infarctions at the left superior cerebellar artery. In conclusion, we observed that a transitory asterixis associated with ipsilateral headache can be an initial clinical manifestation of ipsilateral cerebellar infarctions in the superior cerebellar artery area. PMID:23359270

  2. Acute chest pain in emergency room. Preliminary findings with 40-64-slice CT ECG-gated of the whole chest.

    PubMed

    Coche, E

    2007-01-01

    ECG-gated MDCT of the entire chest represents the latest technical advance in the diagnostic work-up of atypical chest pain. The authors report their preliminary experience with the use of 40 and 64-slice CT in the emergency room and recommend to study only patients with moderate likelihood of coronary artery disease. ECG-gated MDCT of the entire chest will be preferentially performed on 64-slice MDCT rather than 40-slice MDCT because it enable to reduce the scan time (18 seconds versus 28 seconds acquisition time), the volume of contrast medium (82 mL + 15 mL versus 97 mL + 15 mL of highly concentrated contrast agent for a patient of 70 kgs) and radiation exposure (17 mSv versus 19 mSv). Approximately 1500 to 2000 of images are produced and need to be analysed on a dedicated workstation by a radiologist expert in cardiac and thoracic disorders. At the present time, only a few studies exist in the literature showing some promising results but further large clinical studies are needed before to implement such sophisticated protocol in emergency room.

  3. Automated Computer-Assisted Diagnosis of Obstructive Coronary Artery Disease in Emergency Department Patients Undergoing 256-Slice Coronary Computed Tomography Angiography for Acute Chest Pain.

    PubMed

    Hashoul, Sharbell; Gaspar, Tamar; Halon, David A; Lewis, Basil S; Shenkar, Yuval; Jaffe, Ronen; Peled, Nathan; Rubinshtein, Ronen

    2015-10-01

    A 256-slice coronary computed tomography angiography (CCTA) is an accurate method for detection and exclusion of obstructive coronary artery disease (OBS-CAD). However, accurate image interpretation requires expertise and may not be available at all hours. The purpose of this study was to evaluate the usefulness of a fully automated computer-assisted diagnosis (COMP-DIAG) tool for exclusion of OBS-CAD in patients in the emergency department (ED) presenting with chest pain. Three hundred sixty-nine patients in ED without known coronary disease underwent 256-slice CCTA as part of the assessment of chest pain of uncertain origin. COMP-DIAG (CorAnalyzer II) automatically reported presence or exclusion of OBS-CAD (>50% stenosis, ≥1 vessel). Performance characteristics of COMP-DIAG for exclusion and detection of OBS-CAD were determined using expert reading as the reference standard. Seventeen (5%) studies were unassessable by COMP-DIAG software, and 352 patients (1,056 vessels) were therefore available for analysis. COMP-DIAG identified 33% of assessable studies as having OBS-CAD, but the prevalence of OBS-CAD on CCTA was only 18% (66 of 352 patients) by standard expert reading. However, COMP-DIAG correctly identified 61 of the 66 patients (93%) with OBS-CAD with 21 vessels (2%) with OBS-CAD misclassified as negative. In conclusion, compared to expert reading, automated computer-assisted diagnosis using the CorAnalyzer showed high sensitivity but only moderate specificity for detection of obstructive coronary disease in patients in ED who underwent 256-slice CCTA. The high negative predictive value of this computer-assisted algorithm may be useful in the ED setting.

  4. Cbln1 regulates rapid formation and maintenance of excitatory synapses in mature cerebellar Purkinje cells in vitro and in vivo.

    PubMed

    Ito-Ishida, Aya; Miura, Eriko; Emi, Kyoichi; Matsuda, Keiko; Iijima, Takatoshi; Kondo, Tetsuro; Kohda, Kazuhisa; Watanabe, Masahiko; Yuzaki, Michisuke

    2008-06-04

    Although many synapse-organizing molecules have been identified in vitro, their functions in mature neurons in vivo have been mostly unexplored. Cbln1, which belongs to the C1q/tumor necrosis factor superfamily, is the most recently identified protein involved in synapse formation in the mammalian CNS. In the cerebellum, Cbln1 is predominantly produced and secreted from granule cells; cbln1-null mice show ataxia and a severe reduction in the number of synapses between Purkinje cells and parallel fibers (PFs), the axon bundle of granule cells. Here, we show that application of recombinant Cbln1 specifically and reversibly induced PF synapse formation in dissociated cbln1-null Purkinje cells in culture. Cbln1 also rapidly induced electrophysiologically functional and ultrastructurally normal PF synapses in acutely prepared cbln1-null cerebellar slices. Furthermore, a single injection of recombinant Cbln1 rescued severe ataxia in adult cbln1-null mice in vivo by completely, but transiently, restoring PF synapses. Therefore, Cbln1 is a unique synapse organizer that is required not only for the normal development of PF-Purkinje cell synapses but also for their maintenance in the mature cerebellum both in vitro and in vivo. Furthermore, our results indicate that Cbln1 can also rapidly organize new synapses in adult cerebellum, implying its therapeutic potential for cerebellar ataxic disorders.

  5. 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.

  6. 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.

  7. Neurochondrin is a neuronal target antigen in autoimmune cerebellar degeneration

    PubMed Central

    Miske, Ramona; Gross, Catharina C.; Scharf, Madeleine; Golombeck, Kristin S.; Hartwig, Marvin; Bhatia, Urvashi; Schulte-Mecklenbeck, Andreas; Bönte, Kathrin; Strippel, Christine; Schöls, Ludger; Synofzik, Matthis; Lohmann, Hubertus; Dettmann, Inga Madeleine; Deppe, Michael; Mindorf, Swantje; Warnecke, Tobias; Denno, Yvonne; Teegen, Bianca; Probst, Christian; Brakopp, Stefanie; Wandinger, Klaus-Peter; Wiendl, Heinz; Stöcker, Winfried; Meuth, Sven G.

    2016-01-01

    Objective: To report on a novel neuronal target antigen in 3 patients with autoimmune cerebellar degeneration. Methods: Three patients with subacute to chronic cerebellar ataxia and controls underwent detailed clinical and neuropsychological assessment together with quantitative high-resolution structural MRI. Sera and CSF were subjected to comprehensive autoantibody screening by indirect immunofluorescence assay (IFA) and immunoblot. Immunoprecipitation with lysates of hippocampus and cerebellum combined with mass spectrometric analysis was used to identify the autoantigen, which was verified by recombinant expression in HEK293 cells and use in several immunoassays. Multiparameter flow cytometry was performed on peripheral blood and CSF, and peripheral blood was subjected to T-cell receptor spectratyping. Results: Patients presented with a subacute to chronic cerebellar and brainstem syndrome. MRI was consistent with cortical and cerebellar gray matter atrophy associated with subsequent neuroaxonal degeneration. IFA screening revealed strong immunoglobulin G1 reactivity in sera and CSF with hippocampal and cerebellar molecular and granular layers, but not with a panel of 30 recombinantly expressed established neural autoantigens. Neurochondrin was subsequently identified as the target antigen, verified by IFA and immunoblot with HEK293 cells expressing human neurochondrin as well as the ability of recombinant neurochondrin to neutralize the autoantibodies' tissue reaction. Immune phenotyping revealed intrathecal accumulation and activation of B and T cells during the acute but not chronic phase of the disease. T-cell receptor spectratyping suggested an antigen-specific T-cell response accompanying the formation of antineurochondrin autoantibodies. No such neurochondrin reactivity was found in control cohorts of various neural autoantibody-associated neurologic syndromes, relapsing-remitting multiple sclerosis, cerebellar type of multiple system atrophy, hereditary

  8. Genetics Home Reference: lissencephaly with cerebellar hypoplasia

    MedlinePlus

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

  9. Acute hypercapnic hyperoxia stimulates reactive species production in the caudal solitary complex of rat brain slices but does not induce oxidative stress.

    PubMed

    Ciarlone, Geoffrey E; Dean, Jay B

    2016-12-01

    Central CO2 chemoreceptive neurons in the caudal solitary complex (cSC) are stimulated by hyperoxia via a free radical mechanism. Hyperoxia has been shown to increase superoxide and nitric oxide in the cSC, but it remains unknown how changes in Pco2 during hyperoxia affect the production of O2-dependent reactive oxygen and nitrogen species (RONS) downstream that can lead to increased levels of oxidative and nitrosative stress, cellular excitability, and, potentially, dysfunction. We used real-time fluorescence microscopy in rat brain slices to determine how hyperoxia and hypercapnic acidosis (HA) modulate one another in the production of key RONS, as well as colorimetric assays to measure levels of oxidized and nitrated lipids and proteins. We also examined the effects of CO2 narcosis and hypoxia before euthanasia and brain slice harvesting, as these neurons are CO2 sensitive and hypothesized to employ CO2/H(+) mechanisms that exacerbate RONS production and potentially oxidative stress. Our findings show that hyperoxia ± HA increases the production of peroxynitrite and its derivatives, whereas increases in Fenton chemistry are most prominent during hyperoxia + HA. Using CO2 narcosis before euthanasia modulates cellular sensitivity to HA postmortem and enhances the magnitude of the peroxynitrite pathway, but blunts the activity of Fenton chemistry. Overall, hyperoxia and HA do not result in increased production of markers of oxidative and nitrosative stress as expected. We postulate this is due to antioxidant and proteosomal removal of damaged lipids and proteins to maintain cell viability and avoid death during protracted hyperoxia.

  10. [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.

  11. Imaging calcium waves in cerebellar Bergmann glia.

    PubMed

    Beierlein, Michael

    2013-01-01

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

  12. Childhood Cerebellar Ataxia

    PubMed Central

    Fogel, Brent L.

    2012-01-01

    Childhood presentations of ataxia, an impairment of balance and coordination caused by damage to or dysfunction of the cerebellum, can often be challenging to diagnose. Presentations tend to be clinically heterogeneous but key considerations may vary based on the child's age at onset, the course of illness, and subtle differences in phenotype. Systematic investigation is recommended for efficient diagnosis. In this review, we outline common etiologies and describe a comprehensive approach to the evaluation of both acquired and genetic cerebellar ataxia in children. PMID:22764177

  13. Crossed Cerebellar Diaschisis

    PubMed Central

    Han, Shuguang; Wang, Xiaopeng; Xu, Kai; Hu, Chunfeng

    2016-01-01

    Abstract Crossed cerebellar diaschisis (CCD) describes a depression of oxidative metabolism glucose and blood flow in the cerebellum secondary to a supratentorial lesion in the contralateral cerebral hemisphere. PET/MR has the potential to become a powerful tool for demonstrating and imaging intracranial lesions .We herein report 3 cases of CCD imaging using a tri-modality PET/CT–MR set-up for investigating the value of adding MRI rather than CT to PET in clinical routine. We describe 3 patients with CCD and neurological symptoms in conjunction with abnormal cerebral fluorodeoxyglucose (FDG) positron emission tomography/computed tomography-magnetic resonance imaging (PET/CT–MR) manifestations including arterial spin-labeling (ASL) and T2-weighted images. In all, 18FDG-PET/CT detected positive FDG uptake in supratentorial lesions, and hypometabolism with atrophy in the contralateral cerebellum. More than that, hybrid PET/MRI provided a more accurate anatomic localization and ASL indicated disruption of the cortico-ponto-cerebellar pathway. Using pathology or long-term clinical follow-up to confirm the PET and ASL findings, the supratentorial lesions of the 3 patients were respectively diagnosed with cerebral infarction, recurrent glioma, and metastasis. The reports emphasize the significance of multimodality radiological examinations. Multimodality imaging contributes to proper diagnosis, management, and follow-up of supratentorial lesions with CCD. PMID:26765477

  14. Evaluation of biventricular ejection fraction with ECG-gated 16-slice CT: preliminary findings in acute pulmonary embolism in comparison with radionuclide ventriculography.

    PubMed

    Coche, Emmanuel; Vlassenbroek, Alain; Roelants, Véronique; D'Hoore, William; Verschuren, Franck; Goncette, Louis; Maldague, Baudouin

    2005-07-01

    This study aimed to assess the feasibility of cardiac global function evaluation during a whole-chest multi-slice CT (MSCT) acquisition in patients referred for suspicion of pulmonary embolism (PE), and to compare the results with planar equilibrium radionuclide ventriculography (ERNA). Ten consecutive haemodynamically stable patients (six female, four male; mean age 69.7 years; heart rate 65-99 bpm) with suspicion of PE underwent an MSCT and ERNA within a 6 h period. CT acquisition was performed after contrast medium injection by using 16x1.5 mm collimation and retrospective ECG gating. Left ventricular (LVEF) and right ventricular (RVEF) ejection fractions were calculated using dedicated three-dimensional software. Relationships between measurements obtained with MSCT and ERNA were assessed using linear regression analysis and reliability of MSCT was assessed with intra-class correlation coefficient. Bland-Altman analysis was performed to calculate limits of agreement between MSCT and ERNA. MSCT was performed successfully in ten patients with a mean acquisition time of 16.5+/-2.8 s. Functional cardiac evaluation was possible on CT for all patients except for one due to poor opacification of right ventricle. Linear regression analysis showed a good correlation between MSCT and ERNA for the LVEF (R=0.91) and the RVEF (R=0.89) measurements. Intra-class correlation was superior for LVEF (0.92) than for the RVEF (0.68). Bland-Altman plots demonstrated that MSCT substantially overestimated the ERNA RVEF. Morphological CT data demonstrated PE in four of ten of patients and alternative diagnoses in five of ten patients. Our study reveals that MSCT with retrospective ECG gating may provide in one modality a morphological and a functional cardiopulmonary evaluation. Comparison with ERNA demonstrated a good correlation for both ventricular ejection fractions.

  15. Gravity-dependent nystagmus and inner-ear dysfunction suggest anterior and posterior inferior cerebellar artery infarct.

    PubMed

    Shaikh, Aasef G; Miller, Benjamin R; Sundararajan, Sophia; Katirji, Bashar

    2014-04-01

    Cerebellar lesions may present with gravity-dependent nystagmus, where the direction and velocity of the drifts change with alterations in head position. Two patients had acute onset of hearing loss, vertigo, oscillopsia, nausea, and vomiting. Examination revealed gravity-dependent nystagmus, unilateral hypoactive vestibulo-ocular reflex (VOR), and hearing loss ipsilateral to the VOR hypofunction. Traditionally, the hypoactive VOR and hearing loss suggest inner-ear dysfunction. Vertigo, nausea, vomiting, and nystagmus may suggest peripheral or central vestibulopathy. The gravity-dependent modulation of nystagmus, however, localizes to the posterior cerebellar vermis. Magnetic resonance imaging in our patients revealed acute cerebellar infarct affecting posterior cerebellar vermis, in the vascular distribution of the posterior inferior cerebellar artery (PICA). This lesion explains the gravity-dependent nystagmus, nausea, and vomiting. Acute onset of unilateral hearing loss and VOR hypofunction could be the manifestation of inner-ear ischemic injury secondary to the anterior inferior cerebellar artery (AICA) compromise. In cases of combined AICA and PICA infarction, the symptoms of peripheral vestibulopathy might masquerade the central vestibular syndrome and harbor a cerebellar stroke. However, the gravity-dependent nystagmus allows prompt identification of acute cerebellar infarct.

  16. Distinct kainate receptor phenotypes in immature and mature mouse cerebellar granule cells

    PubMed Central

    Smith, T Caitlin; Wang, Lu-Yang; Howe, James R

    1999-01-01

    Although glutamate receptors have been shown to be involved in neuronal maturation, a developmental role for kainate-type receptors has not been described. In addition, the single-channel properties of native kainate receptors have not been studied in situ. We have characterized the electrophysiological properties of native kainate receptors of granule cell neurons at two distinct stages in postnatal development, using whole-cell and outside-out patch-clamp recordings in acute cerebellar slices. Kainate-type currents were detected in both immature and mature granule cells. However, noise analysis showed that the apparent unitary conductance of kainate-type channels is significantly higher in proliferating than post-migratory granule cells. The conductance and rectification behaviour of the channels in immature granule cells indicate that they contain unedited GluR5 and GluR6 subunits and are likely to be calcium permeable. Single-channel kainate-type currents were observed in outside-out patches from proliferating granule cells in the external germinal layer. The kinetic behaviour of kainate receptors in immature cells was complex. Openings to multiple conductance levels were observed, although our analysis indicates that the channels spend most of their open time in a 4 pS state. PMID:10226148

  17. 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

  18. Redistribution of crossed cerebellar diaschisis

    SciTech Connect

    Kim, S.M.; Park, C.H.; Intenzo, C.M.; Bell, R.

    1989-04-01

    Crossed cerebellar diaschisis refers to a functional decrease in blood flow to the cerebellar hemisphere contralateral to the infarcted or ischemic cerebral hemisphere. This phenomenon can be depicted using PET as well as using SPECT. This condition, seen on early I-123 IMP brain scans, can show redistribution on the three hour delayed scan, presumably due to normal non-specific amine receptor sites of the affected cerebellum. One such case is reported.

  19. 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

  20. Excitation of Rat Cerebellar Golgi Cells by Ethanol: Further Characterization of the Mechanism

    PubMed Central

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

    2012-01-01

    Background Studies with rodents suggest that acute ethanol exposure impairs information flow through the cerebellar cortex, in part, by increasing GABAergic input to granule cells. Experiments suggest that an increase in the excitability of specialized GABAergic interneurons that regulate granule cell activity (i.e. Golgi cells, GoCs) contributes to this effect. In GoCs, ethanol increases spontaneous action potential firing frequency, decreased the afterhyperpolarization amplitude, and depolarized the membrane potential. Studies suggest that these effects could be mediated by inhibition of the Na+/K+ ATPase. The purpose of this study was to characterize the potential role of other GoC conductances in the mechanism of action of ethanol. Methods Computer modeling techniques and patch-clamp electrophysiological recordings with acute slices from rat cerebella were used for these studies. Results Computer modeling suggested that modulation of subthreshold Na+ channels, hyperpolarization activated currents and several K+ conductances could explain some but not all actions of ethanol on GoCs. Electrophysiological studies did not find evidence consistent with a contribution of these conductances. Quinidine, a non-selective blocker of several types of channels (including several K+ channels) that also antagonizes the Na+/K+ ATPase, reduced the effect of ethanol on GoC firing. Conclusions These findings lend further support to the conclusion that ethanol increases GoC excitability via modulation of the Na+/K+ ATPase, and suggest that a quinidine-sensitive K+ channel may also play a role in the mechanism of action of ethanol. PMID:22004123

  1. Silhouette-Slice Theorems

    DTIC Science & Technology

    1987-03-20

    with standard expressions of spherical trigonometry is sinr)0 = cos0 sini//0 (4.37) which is consistent with the results obtained previously with...theorems for discrete transforms. However, sampling questions inlroduce difficult obstacles in the develop- ment of a discrete theory. First, sampling...additional obstacle to discrete represen- tations of the CT. An example of qualitative predication of the shape of silhouettes with the Silhouette-Slice

  2. Chronic THC intake modifies fundamental cerebellar functions

    PubMed Central

    Stella, Nephi

    2013-01-01

    Delta9-tetrahydrocannabinol (THC), the principal bioactive component in the Cannabis plant, is truly a captivating drug. Acute and chronic THC intake produces a spectrum of biological effects ranging from transient psychotropic effects to prolonged medicinal benefits, many of which have been fostered for centuries by our society. In the July 2013 issue of the JCI, Cutando et al. combined mouse genetics with classic mouse behavioral analysis to deepen our understanding of the physiological consequence of subchronic THC intake on eyeblink reflexes, a fundamental neuronal adaptive response, revealing that this regimen leads to downregulation of the cannabinoid CB1 receptor (referred to as CB1 in the Cutando et al. article) in cerebellar stress fibers and the activation of microglia, raising provocative new questions about the safety profile of regimented THC intake. PMID:23863631

  3. 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

  4. Integration of Purkinje cell inhibition by cerebellar nucleo-olivary neurons.

    PubMed

    Najac, Marion; Raman, Indira M

    2015-01-14

    Neurons in the cerebellar cortex, cerebellar nuclei, and inferior olive (IO) form a trisynaptic loop critical for motor learning. IO neurons excite Purkinje cells via climbing fibers and depress their parallel fiber inputs. Purkinje cells inhibit diverse cells in the cerebellar nuclei, including small GABAergic nucleo-olivary neurons that project to the IO. To investigate how these neurons integrate synaptic signals from Purkinje cells, we retrogradely labeled nucleo-olivary cells in the contralateral interpositus and lateral nuclei with cholera toxin subunit B-Alexa Fluor 488 and recorded their electrophysiological properties in cerebellar slices from weanling mice. Nucleo-olivary cells fired action potentials over a relatively narrow dynamic range (maximal rate, ∼ 70 spikes/s), unlike large cells that project to premotor areas (maximal rate, ∼ 400 spikes/s). GABA(A) receptor-mediated IPSCs evoked by electrical or optogenetic stimulation of Purkinje cells were more than 10-fold slower in nucleo-olivary cells (decay time, ∼ 25 ms) than in large cells (∼ 2 ms), and repetitive stimulation at 20-150 Hz evoked greatly summating IPSCs. Nucleo-olivary firing rates varied inversely with IPSP frequency, and the timing of Purkinje IPSPs and nucleo-olivary spikes was uncorrelated. These attributes contrast with large cells, whose brief IPSCs and rapid firing rates can permit well timed postinhibitory spiking. Thus, the intrinsic and synaptic properties of these two projection neurons from the cerebellar nuclei tailor them for differential integration and transmission of their Purkinje cell input.

  5. 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.

  6. 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.

  7. Orthostatic tremor: a cerebellar pathology?

    PubMed

    Gallea, Cécile; 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

    2016-08-01

    SEE MUTHURAMAN ET AL DOI101093/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.

  8. Linking oscillations in cerebellar circuits

    PubMed Central

    Courtemanche, Richard; Robinson, Jennifer C.; Aponte, Daniel I.

    2013-01-01

    In many neuroscience fields, the study of local and global rhythmicity has been receiving increasing attention. These network influences could directly impact on how neuronal groups interact together, organizing for different contexts. The cerebellar cortex harbors a variety of such local circuit rhythms, from the rhythms in the cerebellar cortex per se, or those dictated from important afferents. We present here certain cerebellar oscillatory phenomena that have been recorded in rodents and primates. Those take place in a range of frequencies: from the more known oscillations in the 4–25 Hz band, such as the olivocerebellar oscillatory activity and the granule cell layer oscillations, to the more recently reported slow (<1 Hz oscillations), and the fast (>150 Hz) activity in the Purkinje cell layer. Many of these oscillations appear spontaneously in the circuits, and are modulated by behavioral imperatives. We review here how those oscillations are recorded, some of their modulatory mechanisms, and also identify some of the cerebellar nodes where they could interact. A particular emphasis has been placed on how these oscillations could be modulated by movement and certain neuropathological manifestations. Many of those oscillations could have a definite impact on the way information is processed in the cerebellum and how it interacts with other structures in a variety of contexts. PMID:23908606

  9. 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…

  10. System for slicing wafers

    NASA Technical Reports Server (NTRS)

    1982-01-01

    A newly patented process for slicing silicon wafers that has distinct advantages over methods now widely used is described. The primary advantage of the new system is that it allows the efficient slicing of a number of ingots simultaneously at high speed. The cutting action is performed mechanically, most often with diamond particles that are transported to the cutting zone by a fluid vehicle or have been made an integral part of the blade by plating or impregnation. The new system uses a multiple or ganged band saw, arranged and spaced so that each side, or length, segment of a blade element, or loop, provides a cutting function. Each blade is maintained precisely in position by guides as it enters and leaves each ingot. The cutting action is performed with a conventional abrasive slurry composed of diamond grit suspended in an oil- or water-based vehicle. The distribution system draws the slurry from the supply reservoir and pumps it to the injection tubes to supply it to each side of each ingot. A flush system is provided at the outer end of the work-station zone. In order to reduce potential damage, a pneumatically driven flushing fluid is provided.

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

    PubMed Central

    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

  12. 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.

  13. 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

  14. Cochlear implantation following cerebellar surgery.

    PubMed

    Saeed, Shahad; Mawman, Deborah; Green, Kevin

    2011-08-01

    Cochlear implantation in patients with known central nervous system conditions can result in wide-ranging outcomes. The aim of this study is to report two cases of cochlear implantation outcomes in patients with acquired cerebellar ataxia following cerebellar surgery. The first is a female implanted with the Nucleus 24 implant in September 2000 and the second is a male implanted with a MED-EL Sonata Flexsoft electro-acoustic stimulation in July 2009. Programming these patients resulted in significant non-auditory stimulation which resulted in less than optimum map fittings. The patients did not gain any open set speech perception benefit although both of them gained an awareness of sound with the device. However, patient 2 elected to become a non-user because of the limited benefit.

  15. Regular Patterns in Cerebellar Purkinje Cell Simple Spike Trains

    PubMed Central

    Shin, Soon-Lim; Hoebeek, Freek E.; Schonewille, Martijn; De Zeeuw, Chris I.; Aertsen, Ad; De Schutter, Erik

    2007-01-01

    Background Cerebellar Purkinje cells (PC) in vivo are commonly reported to generate irregular spike trains, documented by high coefficients of variation of interspike-intervals (ISI). In strong contrast, they fire very regularly in the in vitro slice preparation. We studied the nature of this difference in firing properties by focusing on short-term variability and its dependence on behavioral state. Methodology/Principal Findings Using an analysis based on CV2 values, we could isolate precise regular spiking patterns, lasting up to hundreds of milliseconds, in PC simple spike trains recorded in both anesthetized and awake rodents. Regular spike patterns, defined by low variability of successive ISIs, comprised over half of the spikes, showed a wide range of mean ISIs, and were affected by behavioral state and tactile stimulation. Interestingly, regular patterns often coincided in nearby Purkinje cells without precise synchronization of individual spikes. Regular patterns exclusively appeared during the up state of the PC membrane potential, while single ISIs occurred both during up and down states. Possible functional consequences of regular spike patterns were investigated by modeling the synaptic conductance in neurons of the deep cerebellar nuclei (DCN). Simulations showed that these regular patterns caused epochs of relatively constant synaptic conductance in DCN neurons. Conclusions/Significance Our findings indicate that the apparent irregularity in cerebellar PC simple spike trains in vivo is most likely caused by mixing of different regular spike patterns, separated by single long intervals, over time. We propose that PCs may signal information, at least in part, in regular spike patterns to downstream DCN neurons. PMID:17534435

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

    PubMed

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

    2003-01-01

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

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

    PubMed

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

    2012-03-01

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

  18. Genetics Home Reference: VLDLR-associated cerebellar hypoplasia

    MedlinePlus

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

  19. Inpatient Rehabilitation Performance of Patients with Paraneoplastic Cerebellar Degeneration

    PubMed Central

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

    2014-01-01

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

  20. Infantile intracranial aneurysm of the superior cerebellar artery.

    PubMed

    Del Santo, Molly Ann; Cordina, Steve Mario

    2016-03-03

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

  1. Infantile intracranial aneurysm of the superior cerebellar artery.

    PubMed

    Del Santo, Molly Ann; Cordina, Steve Mario

    2016-02-29

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

  2. Orexins excite neurons of the rat cerebellar nucleus interpositus via orexin 2 receptors in vitro.

    PubMed

    Yu, Lei; Zhang, Xiao-Yang; Zhang, Jun; Zhu, Jing-Ning; Wang, Jian-Jun

    2010-03-01

    Orexins are newfound hypothalamic neuropeptides implicated in the regulation of feeding behavior, sleep-wakefulness cycle, nociception, addiction, emotions, as well as narcolepsy. However, little is known about roles of orexins in motor control. Therefore, the present study was designed to investigate the effect of orexins on neuronal activity in the cerebellum, an important subcortical center for motor control. In this study, perfusing slices with orexin A (100 nM-1 microM) or orexin B (100 nM-1 microM) both produced neurons in the rat cerebellar interpositus nucleus (IN) a concentration-dependent excitatory response (96/143, 67.1%). Furthermore, both of the excitations induced by orexin A and B were not blocked by the low-Ca(2+)/high-Mg(2+) medium (n = 8), supporting a direct postsynaptic action of the peptides. Highly selective orexin 1 receptor antagonist SB-334867 did not block the excitatory response of cerebellar IN neurons to orexins (n = 22), but [Ala(11), D-Leu(15)] orexin B, a highly selective orexin 2 receptor (OX(2)R) agonist, mimicked the excitatory effect of orexins on the cerebellar neurons (n = 18). These results demonstrate that orexins excite the cerebellar IN neurons through OX(2)R and suggest that the central orexinergic nervous system may actively participate in motor control through its modulation on one of the final outputs of the spinocerebellum.

  3. 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.

  4. Ethanol attenuates sensory stimulus-evoked responses in cerebellar granule cells via activation of GABA(A) receptors in vivo in mice.

    PubMed

    Wu, Guang; Liu, Heng; Jin, Juan; Hong, Lan; Lan, Yan; Chu, Chun-Ping; Qiu, De-Lai

    2014-02-21

    Acute alcohol intoxication affects cerebellar motor regulation possibly by altering the transfer and integration of external information in cerebellar cortical neurons, resulting in a dysfunction of cerebellar motor regulation or a cerebellar atexia. However, the synaptic mechanisms of ethanol induced impairments of sensory information processing in cerebellar cortical neurons are not fully understand. In the present study, we used electrophysiological and pharmacological methods to study the effects of ethanol on the sensory stimulation-evoked responses in cerebellar granule cells (GCs) in vivo in urethane anesthetized mice. Air-puff stimulation of the ipsilateral whisker-pad evoked stimulus-on (P1) and stimulus-off responses (P2) in GCs of cerebellar Crus II. Cerebellar surface perfusion of ethanol did not alter the onset latency of the sensory stimulation-evoked responses, but reversible reduced the amplitude of P1 and P2. The ethanol-induced reduction of the GCs sensory responses was concentration-dependent. In the presence of ethanol, the mean half-width, area under curve, rise Tau and decay Tau of P1 were significantly decreased. Blockade of gamma-aminobutyric acid type A (GABA(A)) receptors activity induced an increase in amplitude of P1, and abolished the ethanol induced inhibition of the GCs sensory responses. These results indicate that ethanol inhibits the tactile evoked responses in cerebellar GCs through enhancement of GABA(A) receptors activity.

  5. Altered cerebellar feedback projections in Asperger syndrome.

    PubMed

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

    2008-07-15

    It has been proposed that the biological basis of autism spectrum disorder includes cerebellar 'disconnection'. However, direct in vivo evidence in support of this is lacking. Here, the microstructural integrity of cerebellar white matter in adults with Asperger syndrome was studied using diffusion tensor magnetic resonance tractography. Fifteen adults with Asperger syndrome and 16 age-IQ-gender-matched healthy controls underwent diffusion tensor magnetic resonance imaging. For each subject, tract-specific measurements of mean diffusivity and fractional anisotropy were made within the inferior, middle, superior cerebellar peduncles and short intracerebellar fibres. No group differences were observed in mean diffusivity. However, people with Asperger syndrome had significantly lower fractional anisotropy in the short intracerebellar fibres (p<0.001) and right superior cerebellar (output) peduncle (p<0.001) compared to controls; but no difference in the input tracts. Severity of social impairment, as measured by the Autistic Diagnostic Interview, was negatively correlated with diffusion anisotropy in the fibres of the left superior cerebellar peduncle. These findings suggest a vulnerability of specific cerebellar neural pathways in people with Asperger syndrome. The localised abnormalities in the main cerebellar outflow pathway may prevent the cerebral cortex from receiving those cerebellar feedback inputs necessary for a successful adaptive social behaviour.

  6. 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…

  7. 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

  8. 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

  9. Altered regulation of brain-derived neurotrophic factor protein in hippocampus following slice preparation.

    PubMed

    Danzer, S C; Pan, E; Nef, S; Parada, L F; McNamara, J O

    2004-01-01

    Brain-derived neurotrophic factor (BDNF) and its cognate receptor tyrosine kinase B (TrkB) play important roles in regulating survival, structure, and function of CNS neurons. One method of studying the functions of these molecules has utilized in vitro hippocampal slice preparations. An important caveat to using slices, however, is that slice preparation itself might alter the expression of BDNF, thereby confounding experimental results. To address this concern, BDNF immunoreactivity was examined in rodent slices using two different methods of slice preparation. Rapid and anatomically selective regulation of BDNF content followed slice preparation using both methodologies; however, different patterns of altered BDNF immunoreactivity were observed. First, in cultured slices, BDNF content decreased in the dentate molecular layer and increased in the CA3 pyramidal cell layer and the mossy fiber pathway of the hippocampus after 30 min. Furthermore, an initially "punctate" pattern of BDNF labeling observed in the mossy fiber pathway of control sections changed to homogenous labeling of the pathway in vitro. In contrast to these findings, slices prepared as for acute slice physiology exhibited no change in BDNF content in the molecular layer and mossy fiber pathway 30 min after slicing, but exhibited significant increases in the dentate granule and CA3 pyramidal cell layers. These findings demonstrate that BDNF protein content is altered following slice preparation, that different methods of slice preparation produce different patterns of BDNF regulation, and raise the possibility that BDNF release and TrkB activation may also be regulated. These consequences of hippocampal slice preparation may confound analyses of exogenous or endogenous BDNF on hippocampal neuronal structure or function.

  10. 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

  11. Effects of ethanol on sensory stimulus-evoked responses in the cerebellar molecular layer in vivo in mice.

    PubMed

    Cui, Song-Biao; Cui, Bai-Ri; Liu, Heng; Wu, Mao-Cheng; Xu, Yin-Hua; Bian, Jin-Hua; Chu, Chun-Ping; Qiu, De-Lai

    2014-08-08

    Overdose intake of ethanol can impair cerebellar cortical neurons to integrate and transfer external information, resulting in a dysfunction of cerebellar motor regulation or cerebellar ataxia. However, the mechanisms underlying ethanol-impaired transfer of sensory information from cerebellar cortical molecular layer neurons remain unclear. In the present study, we investigated the effects of ethanol on sensory stimulation-evoked responses in the cerebellar molecular layer of urethane-anesthetized mice, by electrophysiological and pharmacological methods. Our results demonstrated that air-puff stimulation (30 ms, 50-60 psi) of the ipsilateral whisker-pad evoked field potential responses in the molecular layer of the cerebellar cortex folium Crus II, which expressed a negative component (N1) followed by a gamma-aminobutyric acid receptor A (GABAA)-mediated positive component (P1). Cerebellar surface perfusion of ethanol between 2 and 5mM did not change the latency of the evoked responses and the amplitude of N1, but enhanced the amplitude and the area under the curve of P1. Interestingly, high concentrations (>20mM) of ethanol induced a significantly decrease in the amplitude and area under the curve of P1. Furthermore, high concentration ethanol (300 mM) significantly decreased the rise in tau and tau decay value of P1, whereas low concentration ethanol (2-5mM) significantly increased these values of P1. Inhibition of GABAA receptor activity reversed P1 and also abolished the effects of ethanol on sensory stimulation-evoked responses. These results indicated that ethanol induced a bidirectional effect on the sensory stimulation-evoked GABAergic responses in the cerebellar cortical molecular layer, suggesting that acute alcohol intake impacted the sensory information processing of cerebellar cortex.

  12. [Memory transfer in cerebellar motor learning].

    PubMed

    Nagao, Soichi

    2012-01-01

    Most of our motor skills are acquired through learning. Experiments of gain adaptation of ocular reflexes have consistently suggested that the memory of adaptation is initially formed in the cerebellar cortex, and is transferred to the cerebellar (vestibular) nuclei for consolidation to long-term memory after repetitions of training. We have recently developed a new system to evaluate the motor learning in human subjects using prism adaptation of hand reaching movement, by referring to the prism adaptation of dart throwing of Martin et al. (1996). In our system, the subject views the small target presented in the touch-panel screen, and touches it with his/her finger without direct visual feedback. After 15-30 trials of touching wearing prisms, an adaptation occurs in healthy subjects: they became able to touch the target correctly. Meanwhile, such an adaptation was impaired in patients of cerebellar disease. We have proposed a model of human prism adaptation that the memory of adaptation is initially encoded in the cerebellar cortex, and is later transferred to the cerebellar nuclei after repetitions of training. The memory in the cerebellar cortex may be formed and extinguished independently of the memory maintained in the cerebellar nuclei, and these two memories work cooperatively.

  13. ZNHIT3 is defective in PEHO syndrome, a severe encephalopathy with cerebellar granule neuron loss.

    PubMed

    Anttonen, Anna-Kaisa; Laari, Anni; Kousi, Maria; Yang, Yawei J; Jääskeläinen, Tiina; Somer, Mirja; Siintola, Eija; Jakkula, Eveliina; Muona, Mikko; Tegelberg, Saara; Lönnqvist, Tuula; Pihko, Helena; Valanne, Leena; Paetau, Anders; Lun, Melody P; Hästbacka, Johanna; Kopra, Outi; Joensuu, Tarja; Katsanis, Nicholas; Lehtinen, Maria K; Palvimo, Jorma J; Lehesjoki, Anna-Elina

    2017-03-01

    Progressive encephalopathy with oedema, hypsarrhythmia, and optic atrophy (PEHO) syndrome is an early childhood onset, severe autosomal recessive encephalopathy characterized by extreme cerebellar atrophy due to almost total granule neuron loss. By combining homozygosity mapping in Finnish families with Sanger sequencing of positional candidate genes and with exome sequencing a homozygous missense substitution of leucine for serine at codon 31 in ZNHIT3 was identified as the primary cause of PEHO syndrome. ZNHIT3 encodes a nuclear zinc finger protein previously implicated in transcriptional regulation and in small nucleolar ribonucleoprotein particle assembly and thus possibly to pre-ribosomal RNA processing. The identified mutation affects a highly conserved amino acid residue in the zinc finger domain of ZNHIT3. Both knockdown and genome editing of znhit3 in zebrafish embryos recapitulate the patients' cerebellar defects, microcephaly and oedema. These phenotypes are rescued by wild-type, but not mutant human ZNHIT3 mRNA, suggesting that the patient missense substitution causes disease through a loss-of-function mechanism. Transfection of cell lines with ZNHIT3 expression vectors showed that the PEHO syndrome mutant protein is unstable. Immunohistochemical analysis of mouse cerebellar tissue demonstrated ZNHIT3 to be expressed in proliferating granule cell precursors, in proliferating and post-mitotic granule cells, and in Purkinje cells. Knockdown of Znhit3 in cultured mouse granule neurons and ex vivo cerebellar slices indicate that ZNHIT3 is indispensable for granule neuron survival and migration, consistent with the zebrafish findings and patient neuropathology. These results suggest that loss-of-function of a nuclear regulator protein underlies PEHO syndrome and imply that establishment of its spatiotemporal interaction targets will be the basis for developing therapeutic approaches and for improved understanding of cerebellar development.

  14. 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.

  15. 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.

  16. 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.

  17. Cystic cerebellar astrocytomas in childhood.

    PubMed

    Griffin, T W; Beaufait, D; Blasko, J C

    1979-07-01

    Thirty-nine patients with low grade cystic cerebellar astrocytomas were treated at the University of Washington and Children's Orthopedic Hospital in Seattle, Washington, between 1955 and 1977; 29 were treated with partial or complete resection alone, and 10 received radiation therapy after various types of surgical procedures. With a mean follow-up time of 7 years, the survival rate for patients who had complete resections of their primary disease was 100%. The relapse-free survival rate was 82%. The relapse-free survival rate for patients treated primarily with partial resection alone was 36%. Postoperative irradiation after partial resection for both primary and recurrent disease resulted in a relapse-free survival rate of 83%. If complete tumor excision is not possible, postoperative radiation therapy is recommended following partial resection.

  18. Morphine-induced changes in cerebral and cerebellar nitric oxide synthase activity.

    PubMed

    Leza, J C; Lizasoain, I; San-Martín-Clark, O; Lorenzo, P

    1995-10-04

    The effect of acute and chronic morphine treatment on nitric oxide (NO) synthase activity (determined by the rate of conversion of [14C]arginine into [14C]citrulline) on mouse brain was studied. Acute morphine treatment induced an increased in Ca2+ -dependent NO synthase in cerebellum. This effect was blocked by coadministration with naloxone. Chronic morphine treatment (by s.c. pellet) also produced an increase in cerebellar NO synthase, with a maximum on the second day of implantation. No significant changes were found in frontal cortex and forebrain during acute or chronic morphine treatment. The relationship between opiate effects and the L-arginine: NO pathway is discussed.

  19. Optogenetic Visualization of Presynaptic Tonic Inhibition of Cerebellar Parallel Fibers

    PubMed Central

    Berglund, Ken; Wen, Lei; Dunbar, Robert L.; Feng, Guoping

    2016-01-01

    Tonic inhibition was imaged in cerebellar granule cells of transgenic mice expressing the optogenetic chloride indicator, Clomeleon. Blockade of GABAA receptors substantially reduced chloride concentration in granule cells due to block of tonic inhibition. This indicates that tonic inhibition is a significant contributor to the resting chloride concentration of these cells. Tonic inhibition was observed not only in granule cell bodies, but also in their axons, the parallel fibers (PFs). This presynaptic tonic inhibition could be observed in slices both at room and physiological temperatures, as well as in vivo, and has many of the same properties as tonic inhibition measured in granule cell bodies. GABA application revealed that PFs possess at least two types of GABAA receptor: one high-affinity receptor that is activated by ambient GABA and causes a chloride influx that mediates tonic inhibition, and a second with a low affinity for GABA that causes a chloride efflux that excites PFs. Presynaptic tonic inhibition regulates glutamate release from PFs because GABAA receptor blockade enhanced both the frequency of spontaneous EPSCs and the amplitude of evoked EPSCs at the PF-Purkinje cell synapse. We conclude that tonic inhibition of PFs could play an important role in regulating information flow though cerebellar synaptic circuits. Such cross talk between phasic and tonic signaling could be a general mechanism for fine tuning of synaptic circuits. SIGNIFICANCE STATEMENT This paper demonstrates that an unconventional form of signaling, known as tonic inhibition, is found in presynaptic terminals and affects conventional synaptic communication. Our results establish the basic characteristics and mechanisms of presynaptic tonic inhibition and show that it occurs in vivo as well as in isolated brain tissue. PMID:27225762

  20. 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)

  1. 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

  2. [Acute vertigo of neurological origin].

    PubMed

    Bruun, Marie; Højgaard, Joan L Sunnleyg; Kondziella, Daniel

    2013-11-04

    Acute vertigo of neurological origin may be caused by haemorrhages and tumours in the posterior fossa and, most frequently, by ischaemic infarction in the vertebrobasilar circulation. Urgent diagnosis is necessary to avoid further ischaemic episodes, herniation due to cerebellar oedema and/or fatal brainstem infarction. The history should focus on accompanying neurological symptoms. However, vertigo with cerebellar lesions may be monosymptomatic and then bedside evaluation of oculomotor function is the key to correct diagnosis. This paper discusses the pathophysiology, symptomatology and clinical evaluation of acute vertigo of neurological origin.

  3. 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.

  4. 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.

  5. Cerebellar globular cells receive monoaminergic excitation and monosynaptic inhibition from Purkinje cells.

    PubMed

    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.

  6. 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.

  7. 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.

  8. Pathogenic Roles of Glutamic Acid Decarboxylase 65 Autoantibodies in Cerebellar Ataxias

    PubMed Central

    Hampe, Christiane S.

    2017-01-01

    Reports suggesting a pathogenic role of autoantibodies directed against glutamic acid decarboxylase 65 (GAD65Abs) in cerebellar ataxias (CAs) are reviewed, and debatable issues such as internalization of antibodies by neurons and roles of epitopes are discussed. GAD65 is one of two enzymes that catalyze the conversion of glutamate to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). A pathogenic role of GAD65Ab in CAs is suggested by in vivo and in vitro studies. (1) Intracerebellar administration of cerebrospinal fluid (CSF) immunoglobulins (IgGs) obtained from GAD65Ab-positive CA patients impairs cerebellar modulation of motor control in rats. (2) CSF IgGs act on terminals of GABAergic neurons and decrease the release of GABA in cerebellar slices from rats and mice. (3) Absorption of GAD65Ab by recombinant GAD65 diminishes the above effects, and monoclonal human GAD65Ab (b78) mimic the effects of CSF IgGs in vivo and in vitro. Studies using GAD65-KO mice confirm that the target molecule is GAD65. (4) Notably, the effects of GAD65Ab depend on the epitope specificity of the monoclonal GAD65Ab. Taken together, these results indicate that epitope-specific GAD65Ab-induced impairment of GABA release is involved in the pathogenesis of GAD65Ab-positive CA and support the early detection of GAD65Ab-associated CA to initiate immunotherapy before irreversible neuronal death in the cerebellum. PMID:28386570

  9. Analysis of distinct short and prolonged components in rebound spiking of deep cerebellar nucleus neurons

    PubMed Central

    Sangrey, Thomas; Jaeger, Dieter

    2010-01-01

    Deep cerebellar nucleus (DCN) neurons show pronounced post-hyperpolarization rebound burst behavior, which may contribute significantly to responses to strong inhibitory inputs from cerebellar cortical Purkinje cells. Thus, rebound behavior could importantly shape the output from the cerebellum. We used whole cell recordings in brain slices to characterize DCN rebound properties and their dependence on hyperpolarization duration and depth. We found that DCN rebounds showed distinct fast and prolonged components, with different stimulus dependence and different underlying currents. The initial depolarization leading into rebound spiking was carried by HCN current, and variable expression of this current could lead to a control of rebound latency. The ensuing fast rebound burst was due to T-type calcium current, as previously described. It was highly variable between cells in strength, and could be expressed fully after short periods of hyperpolarization. In contrast, a subsequent prolonged rebound component required longer and deeper periods of hyperpolarization before it was fully established. We found using voltage-clamp and dynamic clamp analyses that a slowly inactivating persistent sodium current fit the conductance underlying this prolonged rebound component resulting in spike rate increases over several seconds. Overall, our results demonstrate that multiphasic DCN rebound properties could be elicited differentially by different levels of Purkinje cell activation, and thus create a rich repertoire of potential rebound dynamics in the cerebellar control of motor timing. PMID:21039958

  10. 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.

  11. 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.

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

    PubMed

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

    2017-01-11

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

  13. 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

  14. FGF14 regulates the intrinsic excitability of cerebellar Purkinje neurons.

    PubMed

    Shakkottai, Vikram G; Xiao, Maolei; Xu, Lin; Wong, Michael; Nerbonne, Jeanne M; Ornitz, David M; Yamada, Kelvin A

    2009-01-01

    A missense mutation in the fibroblast growth factor 14 (FGF14) gene underlies SCA27, an autosomal dominant spinocerebellar ataxia in humans. Mice with a targeted disruption of the Fgf14 locus (Fgf14(-/-)) develop ataxia resembling human SCA27. We tested the hypothesis that loss of FGF14 affects the firing properties of Purkinje neurons, which play an important role in motor control and coordination. Current clamp recordings from Purkinje neurons in cerebellar slices revealed attenuated spontaneous firing in Fgf14(-/-) neurons. Unlike in the wild type animals, more than 80% of Fgf14(-/-) Purkinje neurons were quiescent and failed to fire repetitively in response to depolarizing current injections. Immunohistochemical examination revealed reduced expression of Nav1.6 protein in Fgf14(-/-) Purkinje neurons. Together, these observations suggest that FGF14 is required for normal Nav1.6 expression in Purkinje neurons, and that the loss of FGF14 impairs spontaneous and repetitive firing in Purkinje neurons by altering the expression of Nav1.6 channels.

  15. Delayed release of neurotransmitter from cerebellar granule cells.

    PubMed

    Atluri, P P; Regehr, W G

    1998-10-15

    At fast chemical synapses the rapid release of neurotransmitter that occurs within a few milliseconds of an action potential is followed by a more sustained elevation of release probability, known as delayed release. Here we characterize the role of calcium in delayed release and test the hypothesis that facilitation and delayed release share a common mechanism. Synapses between cerebellar granule cells and their postsynaptic targets, stellate cells and Purkinje cells, were studied in rat brain slices. Presynaptic calcium transients were measured with calcium-sensitive fluorophores, and delayed release was detected with whole-cell recordings. Calcium influx, presynaptic calcium dynamics, and the number of stimulus pulses were altered to assess their effect on delayed release and facilitation. Following single stimuli, delayed release can be separated into two components: one lasting for tens of milliseconds that is steeply calcium-dependent, the other lasting for hundreds of milliseconds that is driven by low levels of calcium with a nearly linear calcium dependence. The amplitude, calcium dependence, and magnitude of delayed release do not correspond to those of facilitation, indicating that these processes are not simple reflections of a shared mechanism. The steep calcium dependence of delayed release, combined with the large calcium transients observed in these presynaptic terminals, suggests that for physiological conditions delayed release provides a way for cells to influence their postsynaptic targets long after their own action potential activity has subsided.

  16. 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

  17. 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.

  18. Regionalization of the isthmic and cerebellar primordia.

    PubMed

    Narboux-Nême, Nicolas; Louvi, Angeliki; Alexandre, Paula; Wassef, Marion

    2005-01-01

    The complex migrations of neurons born in the dorsal neural tube of the isthmic and rhombomere l (rl) domains complicate the delineation of the cerebellar primordium. We show that Purkinje cells (P) are likely generated over a wide territory before gathering in the future cerebellar primordium under the developing external granular layer. Later expansion of the cerebellum over a restricted ependymal domain could rely on mutual interations between P cells and granule cell progenitors (GCP). P are attracted by GCP and in turn stimulate their proliferation, increasing the surface of the developing cortex. At later stages, regionalization of the developing and adult cerebellar cortex can be detected through regional variations in the distribution of several P cell markers. Whether and how the developmental and adult P subtypes are related is still unknown and it is unclear if they delineate the same sets of cerebellar subdivisions. We provide evidence that the early P regionalization is involved in intrinsic patterning of the cerebellar primordium, in particular it relate to the organization of the corticonuclear connection. We propose that the early P regionalization provides a scaffold to the mature P regionalization but that the development of functional afferent connections induces a period of P plasticity during which the early regional identity of P could be remodeled.

  19. Secondary orthostatic tremor in the setting of cerebellar degeneration.

    PubMed

    Sarva, Harini; Severt, William Lawrence; Jacoby, Nuri; Pullman, Seth L; Saunders-Pullman, Rachel

    2016-05-01

    Orthostatic tremor (OT) and cerebellar ataxia are uncommon and difficult to treat. We present two patients with OT and cerebellar degeneration, one of whom had spinocerebellar ataxia type 2 and a good treatment response.

  20. 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...

  1. [Atrophy of the granular layer of the cerebellar cortex in patients with nonlymphoblastic leukemia treated with cytosine arabinoside].

    PubMed

    Nowacki, P; Dolińska, D; Honczarenko, K; Zyluk, B

    1992-01-01

    The reported analysis comprised 81 patients dying of acute non-lymphoblastic leukaemia type M1, M2, M4 and blastic crises in chronic myelocytic leukaemia. It was observed that the number of cases of cerebellar granular layer atrophy rose markedly in the years 1984-1990 as compared with 1976-1983 (45.4% vs 16.2%). It is suggested that this was due to the introduction of cytostatic treatment schedules with higher doses of cytosine arabinoside (ARAC), especially TAD (6-thioguanine, ARAC, daunorubicin). Cerebellar granular layer atrophy seems to be dependent rather on the cumulative dose of ARAC and not on a single high dose of that drug.

  2. Selective vulnerability of cerebellar granule neuroblasts and their progeny to drugs with abuse liability

    PubMed Central

    Hauser, Kurt F.; Khurdayan, Valeriya K.; Goody, Robin J.; Nath, Avindra; Saria, Alois; Pauly, James R.

    2015-01-01

    Cerebellar development is shaped by the interplay of genetic and numerous environmental factors. Recent evidence suggests that cerebellar maturation is acutely sensitive to drugs with abuse liability including alcohol, opioids, and nicotine. Assuming substance abuse disrupts cerebellar maturation, a central question is to what are the basic mechanisms underlying potential drug-induced developmental defects. Evidence reviewed herein suggests that the maturation of granule neurons and their progeny are intrinsically affected by several classes of substances with abuse liability. Although drug abuse is also likely to target directly other cerebellar neuron and glial types, such as Purkinje cells and Bergmann glia, findings in isolated granule neurons suggest that they are often the principle target for drug actions. Developmental events that are selectively disrupted by drug abuse in granule neurons and/or their neuroblast precursors include proliferation, migration, differentiation (including neurite elaboration and synapse formation), and programmed cell death. Moreover, different classes of drugs act through distinct molecular mechanisms thereby disrupting unique aspects of development. For example, drug-induced perturbations in (i) neurotransmitter biogenesis, (ii) ligand and ion-gated receptor function and their coupling to intracellular effectors, (iii) neurotrophic factor biogenesis and signaling, and (iv) intercellular adhesion are all likely to have significant effects in shaping developmental outcome. In addition to identifying therapeutic strategies for drug abuse intervention, understanding the mechanisms by which drugs affect cellular maturation is likely to provide a better understanding of the neurochemical events that normally shape central nervous system development. PMID:14509568

  3. The cerebellar serotoninergic system and its possible involvement in cerebellar ataxia.

    PubMed

    Trouillas, P

    1993-05-01

    A review concerning the characteristics of the cerebellar serotoninergic system is presented. In rat, cat and oppossum, the perikarya of origin are located in the brain stem raphe nuclei and in other brainstem structures. The projections to the cerebellar layers and deep nuclei include synaptic connections, but also non synaptic terminals, especially in a diffuse cortical plexus. Serotoninergic receptors have been described: 5-HT1B in the molecular layer and 5-HT2 in the inferior olive. Serotonin exerts neurophysiological effects on several target cells, directly or indirectly, presynaptically or postsynaptically. A modulatory effect on Purkinje cells is well documented. In thiamine deprived animals, a specific serotoninergic cerebellar syndrome includes a selective degeneration of the serotoninergic cerebellar system, an increase of the 5-HIAA cerebellar values and an exaggerated serotoninergic turnover. In human heredoataxias (Friedreich's ataxia and cerebellar cortical atrophy), serotoninergic disturbances have been observed in the CSF, including low 5-HIAA values and an increased serotoninergic turnover. Therapeutic results have been obtained with L-5-HTP, a precursor of serotonin, in several conditions presenting cerebellar ataxia. L-5-HTP resistance of olivopontocerebellar atrophies may be explained by the destruction of serotonin-sensitive target cells, especially Purkinje cells.

  4. 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.

  5. 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

  6. Spontaneous recurrent network activity in organotypic rat hippocampal slices.

    PubMed

    Mohajerani, Majid H; Cherubini, Enrico

    2005-07-01

    Organotypic hippocampal slices were prepared from postnatal day 4 rats and maintained in culture for >6 weeks. Cultured slices exhibited from 12 days in vitro spontaneous events which closely resembled giant depolarizing potentials (GDPs) recorded in neonatal hippocampal slices. GDP-like events occurred over the entire hippocampus with a delay of 30-60 ms between two adjacent regions as demonstrated by pair recordings from CA3-CA3, CA3-CA1 and interneurone-CA3 pyramidal cells. As in acute slices, spontaneous recurrent events were generated by the interplay of GABA and glutamate acting on AMPA receptors as they were reversibly blocked by bicuculline and 6,7-dinitroquinoxaline-2,3-dione but not by dl-2-amino-5-phosphonopentaoic acid. The equilibrium potentials for GABA measured in whole cell and gramicidin-perforated patch from interconnected interneurones-CA3 pyramidal cells were -70 and -56 mV, respectively. The resting membrane potential estimated from the reversal of N-methyl-D-aspartate-induced single-channel currents in cell-attach experiments was -75 mV. In spite of its depolarizing action, in the majority of cases GABA was still inhibitory as it blocked the firing of principal cells. The increased level of glutamatergic connectivity certainly contributed to network synchronization and to the development of interictal discharges after prolonged exposure to bicuculline. In spite of its inhibitory action, in a minority of cells GABA was still depolarizing and excitatory as it was able to bring principal cells to fire, suggesting that a certain degree of immaturity is still present in cultured slices. This was in line with the transient bicuculline-induced block of GDPs and with the isoguvacine-induced increase of GDP frequency.

  7. 21 CFR 882.5820 - Implanted cerebellar stimulator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

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

    PubMed

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

    2014-01-09

    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.

  9. Single-shot curved slice imaging.

    PubMed

    Jochimsen, Thies H; Norris, David G

    2002-03-01

    The feasibility of imaging a curved slice with a single-shot technique so that the reconstructed image shows an un-warping of the slice is examined. This could be of practical importance when the anatomical structures of interest can be more efficiently covered with curved slices than with a series of flat planes. One possible example of such a structure is the cortex of the human brain. Functional imaging would especially benefit from this technique because several planar images can be replaced by a few curved slice images. A method is introduced that is based on multidimensional pulses to excite the desired curved slice profile. A GRASE imaging sequence is then applied that is tailored to the k-space representation of the curved slice. This makes it possible to capture the in-plane information of the slice with a single-shot technique. The method presented is limited to slices that are straight along one axis and can be approximated by a polygon. Reconstruction is performed using a simple numeric Fourier integration along the curved slice. This leads to an image that shows the desired un-warped representation of the slice. Experimental results obtained with this method from healthy volunteers are presented and demonstrate the feasibility of the proposed technique.

  10. Precise spatial and temporal control of oxygen within in vitro brain slices via microfluidic gas channels.

    PubMed

    Mauleon, Gerardo; Fall, Christopher P; Eddington, David T

    2012-01-01

    The acute brain slice preparation is an excellent model for studying the details of how neurons and neuronal tissue respond to a variety of different physiological conditions. But open slice chambers ideal for electrophysiological and imaging access have not allowed the precise spatiotemporal control of oxygen in a way that might realistically model stroke conditions. To address this problem, we have developed a microfluidic add-on to a commercially available perfusion chamber that diffuses oxygen throughout a thin membrane and directly to the brain slice. A microchannel enables rapid and efficient control of oxygen and can be modified to allow different regions of the slice to experience different oxygen conditions. Using this novel device, we show that we can obtain a stable and homogeneous oxygen environment throughout the brain slice and rapidly alter the oxygen tension in a hippocampal slice. We also show that we can impose different oxygen tensions on different regions of the slice preparation and measure two independent responses, which is not easily obtainable with current techniques.

  11. 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

  12. Culturing thick brain slices: an interstitial 3D microperfusion system for enhanced viability.

    PubMed

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

    2009-06-15

    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. Organotypic monolayer cultures of nervous tissue. J Neurosci Methods. 1981; 4: 329-342) or a membrane-insert method (up to 1-4 cell layers, <150 microm) (Stoppini L, Buchs PA, Muller D. A simple method for organotypic cultures of neural tissue. J Neurosci Methods 1991; 37: 173-182), 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 600 microm thick) (Hass HL, Schaerer B, Vosmansky M. A simple perfusion chamber for study of nervous tissue slices in vitro. J Neurosci Methods 1979; 1: 323-325; Nicoll RA, Alger BE. A simple chamber for recording from submerged brain slices. J Neurosci Methods 1981; 4: 153-156; Passeraub PA, Almeida AC, Thakor NV. Design, microfabrication and characterization of a microfluidic chamber for the perfusion of brain tissue slices. J Biomed Dev 2003; 5: 147-155). Here, we report a unique interstitial microfluidic perfusion technique to culture thick (700 microm) organotypic brain slices. The design of the custom-made microperfusion chamber facilitates laminar, interstitial perfusion of oxygenated nutrient medium throughout the tissue thickness with concomitant removal of depleted medium

  13. 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…

  14. Anti-Yo antibody-mediated paraneoplastic cerebellar degeneration in a female patient with pleural malignant mesothelioma.

    PubMed

    Tanriverdi, Ozgur; Meydan, Nezih; Barutca, Sabri; Ozsan, Nazan; Gurel, Duygu; Veral, Ali

    2013-05-01

    Paraneoplastic cerebellar degeneration is a rare non-metastatic complication of malignancies. It presents with acute or subacute onset of ataxia, dysarthria and intention tremor. Paraneoplastic cerebellar degeneration is most commonly associated with malignancies of the ovary, breast and lung. The anti-Yo (anti-Purkinje cells) antibodies that specifically damage the Purkinje cells of the cerebellum are found in the serum and cerebrospinal fluid. Anti-Yo-related paraneoplastic cerebellar degeneration is most commonly found in women with gynecological and breast cancers, but it is reported in other malignancies. Patients with paraneoplastic syndromes most often present with neurologic symptoms before an underlying cancer is detected. We report a case of anti-Yo-related paraneoplastic cerebellar degeneration associated with pleural malignant mesothelioma in a 51-year-old female patient. She presented to our department with a 2-week history after the last chemotherapy of progressive dizziness related to head movement, nausea, vomiting, ataxia and unsteady gait. A western blot assay was negative for anti-Hu, anti-Ri, anti-Ma2, anti-CV2 and anti-amphiphysin paraneoplastic antibody markers but positive for anti-Yo. In conclusion, we report a case of paraneoplastic cerebellar degeneration in a patient with pleural malignant mesothelioma because of the rarity of this neurologic presentation after the diagnosis of malignant mesothelioma and of the association with anti-Yo antibodies.

  15. Radiation sterilization and identification of gizzard slices

    NASA Astrophysics Data System (ADS)

    Zhu, S.; Fu, C.; Jiang, W.; Yao, D.; Zhao, K.; Zhang, Y.

    1998-06-01

    An orthogonal test of 4 factors of radiation dose, storage temperature, storage time, and sanitation of cutting places was carried out to optimize the conditions for disinfection of gizzard slices. In the optimized condition, both the sanitary quality and the shelf-life of gizzard slices were improved. To identify irradiated gizzard slices, the sensory change, and the levels of water-soluble nitrogen, amino acid, total volatile basic nitrogen, peroxide value, vitamin C consumption and KMnO 4 consumption were determinated. No significant change was observed except for the color which was light brown on the surface of irradiated slices.

  16. Cerebellar Hypoplasia and Dysmorphia in Neurofibromatosis Type 1.

    PubMed

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

    2015-12-01

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

  17. 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

  18. 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…

  19. 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.

  20. 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

  1. Improving Cerebellar Segmentation with Statistical Fusion.

    PubMed

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

    2016-02-27

    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.

  2. 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

  3. 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).

  4. 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

  5. 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.

  6. 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.

  7. Case report: Rapid improvement of crossed cerebellar diaschisis after intravascular laser irradiation of blood in a case of stroke

    PubMed Central

    Yang, Wan-Hua; Lin, Shiou-Ping; Chang, Shin-Tsu

    2017-01-01

    Abstract Rationale: Crossed cerebellar diaschisis (CCD) is a poor prognostic factor after stroke because without immediate cerebral reperfusion no further improvements in the patient's condition can be achieved. We investigated the clinical effects of intravascular laser irradiation therapy (ILIB) on CCD and evaluated the therapeutic effect in the sub-acute post-stroke stage. Patient concerns: The 77-year-old male with cerebral infarction in the territory of the right anterior cerebral artery only underwent conservative treatment including hydration and aspirin in the acute post-stroke stage. Diagnosis: He was diagnosed as stroke based on the clinical presentations and imaging findings. Intervention: Once the patient was in stable condition, he underwent a daily hour-long ILIB (He-Ne laser) for ten consecutive days during the sub-acute post-stroke stage. Outcomes: We used single-photon emission computed tomography (SPECT) before and after intravascular laser irradiation to detect changes in cerebral and cerebellar perfusion. Then, we compared the two images. CCD was detected using the first SPECT. After intervention by ILIB, the second SPECT showed greater perfusion in the affected cerebellar hemisphere. Lessons: We found that ILIB helped eliminate CCD, which was previously shown to be an untreatable condition using any intervention during the sub-acute post-stroke stage. Stroke patients could therefore greatly benefit from ILIB. PMID:28079797

  8. A probabilistic atlas of the cerebellar white matter.

    PubMed

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

    2016-01-01

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

  9. Structural cerebellar correlates of cognitive and motor dysfunctions in cerebellar degeneration.

    PubMed

    Kansal, Kalyani; Yang, Zhen; Fishman, Ann M; Sair, Haris I; Ying, Sarah H; Jedynak, Bruno M; Prince, Jerry L; Onyike, Chiadi U

    2017-03-01

    See King et al. (doi:10.1093/aww348) for a scientific commentary on this article.Detailed mapping of clinical dysfunctions to the cerebellar lobules in disease populations is necessary to establish the functional significance of lobules implicated in cognitive and motor functions in normal subjects. This study constitutes the first quantitative examination of the lobular correlates of a broad range of cognitive and motor phenomena in cerebellar disease. We analysed cross-sectional data from 72 cases with cerebellar disease and 36 controls without cerebellar disease. Cerebellar lobule volumes were derived from a graph-cut based segmentation algorithm. Sparse partial least squares, a variable selection approach, was used to identify lobules associated with motor function, language, executive function, memory, verbal learning, perceptual organization and visuomotor coordination. Motor dysfunctions were chiefly associated with the anterior lobe and posterior lobule HVI. Confrontation naming, noun fluency, recognition, and perceptual organization did not have cerebellar associations. Verb and phonemic fluency, working memory, cognitive flexibility, immediate and delayed recall, verbal learning, and visuomotor coordination were variably associated with HVI, Crus I, Crus II, HVII B and/or HIX. Immediate and delayed recall also showed associations with the anterior lobe. These findings provide preliminary anatomical evidence for a functional topography of the cerebellum first defined in task-based functional magnetic resonance imaging studies of normal subjects and support the hypotheses that (i) cerebellar efferents target frontal lobe neurons involved in forming action representations and new search strategies; (ii) there is greater involvement of the cerebellum when immediate recall tasks involve more complex verbal stimuli (e.g. longer words versus digits); and (iii) it is involved in spontaneous retrieval of long-term memory. More generally, they provide an anatomical

  10. A neural model of cerebellar learning for arm movement control: cortico-spino-cerebellar dynamics.

    PubMed

    Contreras-Vidal, J L; Grossberg, S; Bullock, D

    1997-01-01

    A neural network model of opponent cerebellar learning for arm movement control is proposed. The model illustrates how a central pattern generator in cortex and basal ganglia, a neuromuscular force controller in spinal cord, and an adaptive cerebellum cooperate to reduce motor variability during multijoint arm movements using mono- and bi-articular muscles. Cerebellar learning modifies velocity commands to produce phasic antagonist bursts at interpositus nucleus cells whose feed-forward action overcomes inherent limitations of spinal feedback control of tracking. Excitation of alpha motoneuron pools, combined with inhibition of their Renshaw cells by the cerebellum, facilitate movement initiation and optimal execution. Transcerebellar pathways are opened by learning through long-term depression (LTD) of parallel fiber-Purkinje cell synapses in response to conjunctive stimulation of parallel fibers and climbing fiber discharges that signal muscle stretch errors. The cerebellar circuitry also learns to control opponent muscles pairs, allowing cocontraction and reciprocal inhibition of muscles. Learning is stable, exhibits load compensation properties, and generalizes better across movement speeds if motoneuron pools obey the size principle. The intermittency of climbing fiber discharges maintains stable learning. Long-term potentiation (LTP) in response to uncorrelated parallel fiber signals enables previously weakened synapses to recover. Loss of climbing fibers, in the presence of LTP, can erode normal opponent signal processing. Simulated lesions of the cerebellar network reproduce symptoms of cerebellar disease, including sluggish movement onsets, poor execution of multijoint plans, and abnormally prolonged endpoint oscillations.

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  12. Crossed Cerebellar Atrophy of the Lateral Cerebellar Nucleus in an Endothelin-1-Induced, Rodent Model of Ischemic Stroke

    PubMed Central

    Chan, Hugh H.; Cooperrider, Jessica L.; Park, Hyun-Joo; Wathen, Connor A.; Gale, John T.; Baker, Kenneth B.; Machado, Andre G.

    2017-01-01

    Crossed cerebellar diaschisis (CCD) is a functional deficit of the cerebellar hemisphere resulting from loss of afferent input consequent to a lesion of the contralateral cerebral hemisphere. It is manifested as a reduction of metabolism and blood flow and, depending on severity and duration, it can result in atrophy, a phenomenon known as crossed cerebellar atrophy (CCA). While CCA has been well-demonstrated in humans, it remains poorly characterized in animal models of stroke. In this study we evaluated the effects of cerebral cortical ischemia on contralateral cerebellar anatomy using an established rodent model of chronic stroke. The effects of cortical ischemia on the cerebellar hemispheres, vermis and deep nuclei were characterized. Intracortical microinjections of endothelin-1 (ET-1) were delivered to the motor cortex of Long Evans rats to induce ischemic stroke, with animals sacrificed 6 weeks later. Naive animals served as controls. Cerebral sections and cerebellar sections including the deep nuclei were prepared for analysis with Nissl staining. Cortical ischemia was associated with significant thickness reduction of the molecular layer at the Crus 1 and parafloccular lobule (PFL), but not in fourth cerebellar lobule (4Cb), as compared to the ipsilesional cerebellar hemisphere. A significant reduction in volume and cell density of the lateral cerebellar nucleus (LCN), the rodent correlate of the dentate nucleus, was also noted. The results highlight the relevance of corticopontocerebellar (CPC) projections for cerebellar metabolism and function, including its direct projections to the LCN. PMID:28261086

  13. Cerebellar Dysfunction in a Patient with HIV.

    PubMed

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

    2014-01-01

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

  14. Marijuana alters the human cerebellar clock.

    PubMed

    O'Leary, Daniel S; Block, Robert I; Turner, Beth M; Koeppel, Julie; Magnotta, Vincent A; Ponto, Laura Boles; Watkins, G Leonard; Hichwa, Richard D; Andreasen, Nancy C

    2003-06-11

    The effects of marijuana on brain perfusion and internal timing were assessed using [15O] water PET in occasional and chronic users. Twelve volunteers who smoked marijuana recreationally about once weekly, and 12 volunteers who smoked daily for a number of years performed a self-paced counting task during PET imaging, before and after smoking marijuana and placebo cigarettes. Smoking marijuana increased rCBF in the ventral forebrain and cerebellar cortex in both groups, but resulted in significantly less frontal lobe activation in chronic users. Counting rate increased after smoking marijuana in both groups, as did a behavioral measure of self-paced tapping, and both increases correlated with rCBF in the cerebellum. Smoking marijuana appears to accelerate a cerebellar clock altering self-paced behaviors.

  15. 5-HT2 presynaptic receptors mediate inhibition of glutamate release from cerebellar mossy fibre terminals.

    PubMed

    Maura, G; Carbone, R; Guido, M; Pestarino, M; Raiteri, M

    1991-09-17

    'Giant' synaptosomes originating from mossy fibre terminals and having sedimentation properties different from those of standard synaptosomes were obtained from rat cerebellum. Exposure of superfused giant synaptosomes to 15 mM KCl caused the release of endogenous glutamate in a largely (about 80%) calcium-dependent manner. The K(+)-evoked overflow of glutamate was inhibited in a concentration-dependent manner by 5-hydroxytryptamine (5-HT) and by the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI), but not by the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). The effects of 5-HT and DOI were quite potent, already reaching significant inhibition (about 25%) at 10 nM. The 5-HT2 receptor antagonist ketanserin counteracted the inhibitory effect of 5-HT. In cerebellar slices, ketanserin increased on its own the calcium-dependent K(+)-evoked release of glutamate and this effect was not prevented by tetrodotoxin (TTX). The results support the idea that cerebellar mossy fibres use glutamate as a transmitter and show that the release of glutamate can be inhibited via presynaptic heteroreceptors of the 5-HT2 type probably localized on the mossy fibre terminals.

  16. Properties and expression of Kv3 channels in cerebellar Purkinje cells.

    PubMed

    Sacco, Tiziana; De Luca, Annarita; Tempia, Filippo

    2006-10-01

    In cerebellar Purkinje cells, Kv3 potassium channels are indispensable for firing at high frequencies. In Purkinje cells from young mice (P4-P7), Kv3 currents, recorded in whole-cell in slices, activated at -30 mV, with rapid activation and deactivation kinetics, and they were partially blocked by blood depressing substance-I (BDS-I, 1 microM). At positive potentials, Kv3 currents were slowly but completely inactivating, while the recovery from inactivation was about eightfold slower, suggesting that a previous firing activity or a small change of the resting potential could in principle accumulate inactivated Kv3 channels, thereby finely tuning Kv3 current availability for subsequent action potentials. Single-cell RT-PCR analysis showed the expression by all Purkinje cells (n=10 for each subunit) of Kv3.1, Kv3.3 and Kv3.4 mRNA, while Kv3.2 was not expressed. These results add to the framework for interpreting the physiological function and the molecular determinants of Kv3 currents in cerebellar Purkinje cells.

  17. Highly 4-aminopyridine sensitive delayed rectifier current modulates the excitability of guinea pig cerebellar Purkinje cells.

    PubMed

    Etzion, Y; Grossman, Y

    2001-08-01

    The effects of low concentrations of 4-aminopyridine (4-AP) on the membrane properties of guinea pig cerebellar Purkinje cells were investigated in slice preparation using intracellular recordings. It was found that 1-10 microM 4-AP did not affect the resting potential or the input resistance of the cells, but reduced markedly the duration of the slowly depolarizing potential (SDP), and thus the latency to the firing of Ca2+ spikes in response to intracellular current pulses. Intradendritic recordings in the presence of tetrodotoxin, Cd2+, and low [Ca2+]o, which blocked all the regenerative responses, exhibited prominent membrane outward rectification in response to depolarizing current pulses. Under these conditions, the SDP was abolished and, in contrast, a slowly developing hyperpolarization was consistently observed. Application of 10 microM 4-AP reduced the outward membrane rectification in a reversible manner, but did not affect the transient hyperpolarization, which is usually attributed to the activation of potassium "A" current. These results demonstrate, for the first time, the presence of a highly 4-AP sensitive delayed rectifier in guinea pig cerebellar Purkinje cells, which prominently affects their excitability. The results also indicate that the slowly depolarizing potential of guinea pig Purkinje cells does not involve inactivation of transient potassium currents, which has been suggested previously as an underlying mechanism for this phenomenon in turtle Purkinje cells.

  18. Mechanisms and functional roles of glutamatergic synapse diversity in a cerebellar circuit

    PubMed Central

    Zampini, Valeria; Liu, Jian K; Diana, Marco A; Maldonado, Paloma P; Brunel, Nicolas; Dieudonné, Stéphane

    2016-01-01

    Synaptic currents display a large degree of heterogeneity of their temporal characteristics, but the functional role of such heterogeneities remains unknown. We investigated in rat cerebellar slices synaptic currents in Unipolar Brush Cells (UBCs), which generate intrinsic mossy fibers relaying vestibular inputs to the cerebellar cortex. We show that UBCs respond to sinusoidal modulations of their sensory input with heterogeneous amplitudes and phase shifts. Experiments and modeling indicate that this variability results both from the kinetics of synaptic glutamate transients and from the diversity of postsynaptic receptors. While phase inversion is produced by an mGluR2-activated outward conductance in OFF-UBCs, the phase delay of ON UBCs is caused by a late rebound current resulting from AMPAR recovery from desensitization. Granular layer network modeling indicates that phase dispersion of UBC responses generates diverse phase coding in the granule cell population, allowing climbing-fiber-driven Purkinje cell learning at arbitrary phases of the vestibular input. DOI: http://dx.doi.org/10.7554/eLife.15872.001 PMID:27642013

  19. Cerebellar secretin modulates eyeblink classical conditioning

    PubMed Central

    Fuchs, Jason R.; Robinson, Gain M.; Dean, Aaron M.; Schoenberg, Heidi E.; Williams, Michael R.; Morielli, Anthony D.

    2014-01-01

    We have previously shown that intracerebellar infusion of the neuropeptide secretin enhances the acquisition phase of eyeblink conditioning (EBC). Here, we sought to test whether endogenous secretin also regulates EBC and to test whether the effect of exogenous and endogenous secretin is specific to acquisition. In Experiment 1, rats received intracerebellar infusions of the secretin receptor antagonist 5-27 secretin or vehicle into the lobulus simplex of cerebellar cortex immediately prior to sessions 1–3 of acquisition. Antagonist-infused rats showed a reduction in the percentage of eyeblink CRs compared with vehicle-infused rats. In Experiment 2, rats received intracerebellar infusions of secretin or vehicle immediately prior to sessions 1–2 of extinction. Secretin did not significantly affect extinction performance. In Experiment 3, rats received intracerebellar infusions of 5-27 secretin or vehicle immediately prior to sessions 1–2 of extinction. The secretin antagonist did not significantly affect extinction performance. Together, our current and previous results indicate that both exogenous and endogenous cerebellar secretin modulate acquisition, but not extinction, of EBC. We have previously shown that (1) secretin reduces surface expression of the voltage-gated potassium channel α-subunit Kv1.2 in cerebellar cortex and (2) intracerebellar infusions of a Kv1.2 blocker enhance EBC acquisition, much like secretin. Kv1.2 is almost exclusively expressed in cerebellar cortex at basket cell–Purkinje cell pinceaus and Purkinje cell dendrites; we propose that EBC-induced secretin release from PCs modulates EBC acquisition by reducing surface expression of Kv1.2 at one or both of these sites. PMID:25403455

  20. Decreased tonic inhibition in cerebellar granule cells causes motor dysfunction in a mouse model of Angelman syndrome.

    PubMed

    Egawa, Kiyoshi; Kitagawa, Kyoko; Inoue, Koichi; Takayama, Masakazu; Takayama, Chitoshi; Saitoh, Shinji; Kishino, Tatsuya; Kitagawa, Masatoshi; Fukuda, Atsuo

    2012-12-05

    Angelman syndrome is a neurodevelopmental disorder caused by loss of function of the UBE3A gene encoding a ubiquitin E3 ligase. Motor dysfunction is a characteristic feature of Angelman syndrome, but neither the mechanisms of action nor effective therapeutic strategies have yet been elucidated. We report that tonic inhibition is specifically decreased in cerebellar granule cells of Ube3a-deficient mice, a model of Angelman syndrome. As a mechanism underlying this decrease in tonic inhibition, we show that Ube3a controls degradation of γ-aminobutyric acid (GABA) transporter 1 (GAT1) and that deficiency of Ube3a induces a surplus of GAT1 that results in a decrease in GABA concentrations in the extrasynaptic space. Administering low doses of 4,5,6,7-tetrahydroisothiazolo-[5,4-c]pyridin-3-ol (THIP), a selective extrasynaptic GABA(A) receptor agonist, improves the abnormal firing properties of a population of Purkinje cells in cerebellar brain slices and reduces cerebellar ataxia in Ube3a-deficient mice in vivo. These results suggest that pharmacologically increasing tonic inhibition may be a useful strategy for alleviating motor dysfunction in Angelman syndrome.

  1. AROUSAL FROM SLICES TO HUMANS

    PubMed Central

    Kezunovic, N.; Simon, C.; Hyde, J.; Smith, K.; Beck, P.; Odle, A.

    2012-01-01

    Most psychiatric and neurological disorders exhibit sleep disorders, and in some cases presage the disease. Study of the control of sleep and waking has the potential for making a major impact on a number of disorders, making translational neuroscience research on this area critical. One element of the reticular activating system (RAS) is the pedunculopontine nucleus (PPN), which is the cholinergic arm of the RAS, and projects to the thalamus to trigger thalamocortical rhythms and to the brainstem to modulate muscle tone and locomotion. We developed a research program using brainstem slices containing the PPN to tell us about the cellular and molecular organization of this region. In addition, we developed the P13 midlatency auditory evoked potential, which is generated by PPN outputs, preparation in freely moving rats. This allows the study of PPN cellular and molecular mechanisms at the level of the whole animal. We also study the P50 midlatency auditory evoked potential, which is the human equivalent of the rodent P13 potential, allowing us to study processes detected in vitro, confirmed in the whole animal, and tested in humans. This translational research program led to the discovery of a novel mechanism of sleep-wake control, pointing the way to a number of new clinical applications in the development of novel stimulants and anesthetics. PMID:22639732

  2. Autism and cerebellar dysfunction: Evidence from animal models.

    PubMed

    Tsai, Peter T

    2016-10-01

    Autism is a prevalent neurodevelopmental disorder whose origins are not well understood. Cerebellar involvement has been implicated in the pathogenesis of autism spectrum disorders with increasing evidence from both clinical studies and animal models supporting an important role for cerebellar dysfunction in autism spectrum disorders. This article discusses the various cerebellar contributions to autism spectrum disorders. Both clinical and preclinical studies are discussed and future research directions highlighted.

  3. Cerebro-cerebellar circuits in autism spectrum disorder.

    PubMed

    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.

  4. 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

  5. Unusually severe food poisoning from vanilla slices.

    PubMed Central

    Fenton, P. A.; Dobson, K. W.; Eyre, A.; McKendrick, M. W.

    1984-01-01

    Thirty six people suffered from severe vomiting and diarrhoea 15 min to 3 h after eating vanilla slices from the same bakery. Five patients were admitted to hospital, and one developed unusual skin lesions after admission. Staphylococcus aureus was isolated in large numbers from vanilla slices of the same batch as those giving rise to symptoms, and from five faecal specimens obtained from affected persons. Bacillus cereus and Bacillus subtilis were also isolated from the slices. Unbaked custard provides an ideal environment for bacterial multiplication, especially when (as on this occasion) the ambient temperature is persistently high. PMID:6438231

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

    PubMed

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

    2009-12-15

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

  7. Overview of a new slicing method: Fixed Abrasive Slicing Technique (FAST)

    NASA Technical Reports Server (NTRS)

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

    1982-01-01

    The fixed abrasive slicing technique (FAST) was developed to slice silicon ingots more effectively. It was demonstrated that 25 wafers/cm can be sliced from 10 cm diameter and 19 wafers/cm from 15 cm diameter ingots. This was achieved with a combination of machine development and wire-blade development programs. Correlation was established between cutting effectiveness and high surface speeds. A high speed slicer was designed and fabricated for FAST slicing. Wirepack life of slicing three 10 cm diameter ingots was established. Electroforming techniques were developed to control widths and prolong life of wire-blades. Economic analysis indicates that the projected add-on price of FAST slicing is compatible with the DOE price allocation to meet the 1986 cost goals.

  8. Field experience with various slicing methods

    NASA Technical Reports Server (NTRS)

    Yoo, H. I.

    1982-01-01

    Wafer slicing using internal diameter (ID) saw, multiblade slurry (MBS) saw and multiwire slurry (MWS) saw techniques were evaluated. Wafer parameters such as bow, taper, and roughness which may not be important factors for solar cell fabrication, were considerably better for ID saw than those of the MBS and MWS saw. Analysis of add-on slicing cost indicated that machine productivity seems to be a major limiting factor for ID saw, while expendible material costs are a major factor for both MBS and MWS saw. Slicing experience indicated that the most important factors controling final wafer cost are: (1) silicon cost (wafer thickness + kerf loss); (2) add-on slicing cost, and (3) mechanical yield. There is a very strong interaction between these parameters, suggesting a necessity of optimization of these parameters.

  9. 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)

  10. 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.

  11. Test and Evaluation of Program Slicing Tools

    DTIC Science & Technology

    2012-12-19

    and engineering databases. Berzins received BS, MS, EE, and PhD degrees from MIT and has been on the faculty at the University of Texas and the...slice. C. Existing Tools A thesis (Lim & Ben Kahia, 2011) was done at the Naval Postgraduate School (NPS) in which the students tried to find a...reduction of testing effort (Unpublished master’s thesis ). Naval Postgraduate School, Monterey, CA. Weiser, M. (1984). Program slicing. IEEE

  12. Organotypic slice culture of embryonic brain tissue.

    PubMed

    Daza, Ray A M; Englund, Chris; Hevner, Robert F

    2007-12-01

    INTRODUCTIONThis protocol describes how to dissect, assemble, and cultivate mouse embryonic (E) brain tissue from age E11.5 to E18.5 (days) for organotypic slice culture. These preparations can be used for a variety of assays and studies including coculture of different brain regions, cell migration assays, axon guidance assays, and DNA electroporation experiments. During electroporation, an electric current is applied to the surface of a specific target area of the brain slice in order to open holes in the plasma membrane and introduce a plasmid of coding DNA. The floating slice-on-membrane construct helps to preserve the structural integrity of the brain slices, while maintaining easy experimental access and optimal viability. Experiments can be monitored in living slices (e.g., with confocal imaging), and further studies can be completed using slices that have been fixed and cryosectioned at the end of the experiment. Any region of embryonic brain or spinal tissue can be used in this protocol.

  13. HEPES prevents edema in rat brain slices.

    PubMed

    MacGregor, D G; Chesler, M; Rice, M E

    2001-05-11

    Brain slices gain water when maintained in bicarbonate-buffered artificial cerebro-spinal fluid (ACSF) at 35 degrees C. We previously showed that this edema is linked to glutamate receptor activation and oxidative stress. An additional factor that may contribute to swelling is acidosis, which arises from high CO2 tension in brain slices. To examine the role of acidosis in slice edema, we added N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) to osmotically balanced ACSF (HEPES-ACSF), thereby increasing buffering capacity beyond that provided by bicarbonate/CO2. Water gain was markedly inhibited in HEPES-ACSF. After 3 h incubation in HEPES-ACSF at 35 degrees C, water gain was limited to that of fresh slices after 1 h recovery in ACSF at room temperature. The effect of HEPES in decreasing slice water gain was concentration dependent from 0.3 to 20 mM. The inhibition of water gain by HEPES suggests that tissue acidosis is a contributing factor in brain slice edema.

  14. Ethanol affects NMDA receptor signaling at climbing fiber-Purkinje cell synapses in mice and impairs cerebellar LTD.

    PubMed

    He, Qionger; Titley, Heather; Grasselli, Giorgio; Piochon, Claire; Hansel, Christian

    2013-03-01

    Ethanol profoundly influences cerebellar circuit function and motor control. It has recently been demonstrated that functional N-methyl-(D)-aspartate (NMDA) receptors are postsynaptically expressed at climbing fiber (CF) to Purkinje cell synapses in the adult cerebellum. Using whole cell patch-clamp recordings from mouse cerebellar slices, we examined whether ethanol can affect NMDA receptor signaling in mature Purkinje cells. NMDA receptor-mediated currents were isolated by bath application of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzol[f]quinoxaline (NBQX). The remaining (D)-2-amino-5-phosphonovaleric acid ((D)-APV)-sensitive current was reduced by ethanol at concentrations as low as 10 mM. At a concentration of 50 mM ethanol, the blockade of (D)-APV-sensitive CF-excitatory postsynaptic currents was significantly stronger. Ethanol also altered the waveform of CF-evoked complex spikes by reducing the afterdepolarization. This effect was not seen when NMDA receptors were blocked by (D)-APV before ethanol wash-in. In contrast to CF synaptic transmission, parallel fiber (PF) synaptic inputs were not affected by ethanol. Finally, ethanol (10 mM) impaired long-term depression (LTD) at PF to Purkinje cell synapses as induced under control conditions by paired PF and CF activity. However, LTD induced by pairing PF stimulation with depolarizing voltage steps (substituting for CF activation) was not blocked by ethanol. These observations suggest that the sensitivity of cerebellar circuit function and plasticity to low concentrations of ethanol may be caused by an ethanol-mediated impairment of NMDA receptor signaling at CF synapses onto cerebellar Purkinje cells.

  15. BONLAC: A Combinatorial Proteomic Technique to Measure Stimulus-induced Translational Profiles in Brain Slices

    PubMed Central

    Bowling, Heather; Bhattacharya, Aditi; Zhang, Guoan; Lebowitz, Joseph Z.; Alam, Danyal; Smith, Peter T.; Kirshenbaum, Kent; Neubert, Thomas A.; Vogel, Christine; Chao, Moses V.; Klann, Eric

    2015-01-01

    Stimulus-triggered protein synthesis is critical for brain health and function. However, due to technical hurdles, de novo neuronal translation is predominantly studied in cultured cells, whereas electrophysiological and circuit analyses often are performed in brain slices. The different properties of these two experimental systems create an information gap about stimulus-induced alterations in the expression of new proteins in mature circuits. To address this, we adapted two existing techniques, BONCAT and SILAC, to a combined proteomic technique, BONLAC, for use in acute adult hippocampal slices. Using BDNF-induced protein synthesis as a proof of concept, we found alterations in expression of proteins involved in neurotransmission, trafficking, and cation binding that differed from those found in a similar screen in cultured neurons. Our results indicate important differences between cultured neurons and slices, and suggest that BONLAC could be used to dissect proteomic changes underlying synaptic events in adult circuits. PMID:26205778

  16. 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

  17. An integrator circuit in cerebellar cortex.

    PubMed

    Maex, Reinoud; Steuber, Volker

    2013-09-01

    The brain builds dynamic models of the body and the outside world to predict the consequences of actions and stimuli. A well-known example is the oculomotor integrator, which anticipates the position-dependent elasticity forces acting on the eye ball by mathematically integrating over time oculomotor velocity commands. Many models of neural integration have been proposed, based on feedback excitation, lateral inhibition or intrinsic neuronal nonlinearities. We report here that a computational model of the cerebellar cortex, a structure thought to implement dynamic models, reveals a hitherto unrecognized integrator circuit. In this model, comprising Purkinje cells, molecular layer interneurons and parallel fibres, Purkinje cells were able to generate responses lasting more than 10 s, to which both neuronal and network mechanisms contributed. Activation of the somatic fast sodium current by subthreshold voltage fluctuations was able to maintain pulse-evoked graded persistent activity, whereas lateral inhibition among Purkinje cells via recurrent axon collaterals further prolonged the responses to step and sine wave stimulation. The responses of Purkinje cells decayed with a time-constant whose value depended on their baseline spike rate, with integration vanishing at low (< 1 per s) and high rates (> 30 per s). The model predicts that the apparently fast circuit of the cerebellar cortex may control the timing of slow processes without having to rely on sensory feedback. Thus, the cerebellar cortex may contain an adaptive temporal integrator, with the sensitivity of integration to the baseline spike rate offering a potential mechanism of plasticity of the response time-constant.

  18. Neocortical networks entrain neuronal circuits in cerebellar cortex

    PubMed Central

    Roš, Hana; Sachdev, Robert N. S.; Yu, Yuguo; Šestan, Nenad; McCormick, David A.

    2011-01-01

    Activity in neocortex is often characterized by synchronized oscillations of neurons and networks, resulting in the generation of a local field potential and electroencephalogram. Do the neuronal networks of the cerebellum also generate synchronized oscillations and are they under the influence of those in the neocortex? Here we show that in the absence of any overt external stimulus, the cerebellar cortex generates a slow oscillation that is correlated with that of the neocortex. Disruption of the neocortical slow oscillation abolishes the cerebellar slow oscillation, whereas blocking cerebellar activity has no overt effect on the neocortex. We provide evidence that the cerebellar slow oscillation results in part from the activation of granule, Golgi, and Purkinje neurons. In particular, we show that granule and Golgi cells discharge trains of single spikes, and Purkinje cells generate complex spikes, during the Up state of the slow oscillation. Purkinje cell simple spiking is weakly related to the cerebellar and neocortical slow oscillation in a minority of cells. Our results indicate that the cerebellum generates rhythmic network activity that can be recorded as an LFP in the anesthetized animal, which is driven by synchronized oscillations of the neocortex. Furthermore, we show that correlations between neocortical and cerebellar LFPs persist in the awake animal, indicating that neocortical circuits modulate cerebellar neurons in a similar fashion in natural behavioral states. Thus, the projection neurons of the neocortex collectively exert a driving and modulatory influence on cerebellar network activity. PMID:19692605

  19. [Clinical study of two cases of traumatic cerebellar injury].

    PubMed

    Yokota, H; Nakazawa, S; Kobayashi, S; Taniguchi, Y; Yukihide, T

    1990-01-01

    Two cases of traumatic cerebellar injury complicated with a traumatic medial longitudinal fasciculus (MLF) syndrome or cerebellar mutism were reported, and the cause of these mechanisms was discussed: Case 1: A 9-year-old boy who struck his head in the occipital region during an automobile accident was operated on for a delayed traumatic intracerebellar hematoma. The operation improved the level of his consciousness but MLF syndrome was noticed. The mechanism of traumatic MLF syndrome was discussed in relation to vascular injury and to neurovascular friction. The outcome of the syndrome including our case, which recovered spontaneously, seemed to support the theory of neurovascular injury. Case 2: A 6-year-old boy who struck his head in the temporooccipital region during an automobile accident was admitted to our hospital without conciousness. On admission, contusion of the temporal lobe and left cerebellar hemisphere was demonstrated by a computerized tomography (CT) and magnetic resonance imaging (MRI). A mute state (cerebellar mutism) was recognized after his recovery of consciousness. The cause of the cerebellar mutism was thought to be an injury of the cerebellar vermis or left cerebellar hemisphere. The findings of CT scan and MRI in our case suggested that the cause of the cerebellar mutism was the contusion of these areas.

  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. 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.

  2. Nuclear shrinkage in live mouse hippocampal slices.

    PubMed

    Kasischke, K; Büchner, M; Ludolph, A C; Riepe, M W

    2001-05-01

    Brain slices are used extensively for biochemical, electrophysiological and molecular investigations. However, only the time frame for electrophysiological and biochemical investigations has as yet been defined. The goal of the present study was to investigate the time course of nuclear structure in live brain slices. Hippocampal slices (300 microm) were prepared from male CD1 mice (25-30 g), stained with Hoechst 33342 (10 microM), calcein-AM (2 microM) and ethidium homodimer (4 microM), and imaged with single- and dual-photon microscopy. The volume of CA1 pyramidal cell nuclei decreased from 759+/-229 microm3 in 40-50 microm depth 25 min after preparation to 453+/-169 microm3 (P<0.001) after 60 min, 315+/-112 microm3 (P<0.001) after 120 min and 128+/-71 microm3 (P<0.001) after 8 h. Similar results were obtained on a prolonged time scale in 70-80 microm depth and with an accelerated time scale in 20-30 microm depth. Live-dead staining showed that cell damage is progressing from the surface to deeper layers of the slices in a time-dependent fashion. We conclude that nuclei of CA1 hippocampal pyramidal cells show a time- and depth-dependent shrinkage converging 8 h after slice preparation to a volume of 90-130 microm; in any depth between 20 and 80 microm. The nucleus in the superficial 80 microm of each side appears dysfunctional even at times suitable for electrophysiological and biochemical experimentation in hippocampal slices. Molecular analysis of cell regulation in brain slices may, therefore, be time-dependently distorted by progressing cell death in at least half of the tissue under investigation.

  3. Distinct critical cerebellar subregions for components of verbal working memory

    PubMed Central

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

    2014-01-01

    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 cognitive performance and cerebellar integrity in a specific degeneration of the cerebellar cortex: Spinocerebellar Ataxia type 6 (SCA6). The results demonstrate a critical relationship between verbal working memory and grey matter density in superior (bilateral lobules VI and crus I of lobule VII) and inferior (bilateral lobules VIIIa and VIIIb, and right lobule IX) parts of the cerebellum. We demonstrate that distinct cerebellar regions subserve different components of the prevalent psychological model for verbal working memory based on a phonological loop. The work confirms the involvement of the cerebellum in verbal working memory and defines specific subsystems for this within the cerebellum. PMID:22133495

  4. Preterm cerebellar growth impairment after postnatal exposure to glucocorticoids

    PubMed Central

    Tam, Emily W. Y.; Chau, Vann; Ferriero, Donna M.; Barkovich, A. James; Poskitt, Kenneth J.; Studholme, Colin; Fok, Eric D.-Y.; Grunau, Ruth E.; Glidden, David V.; Miller, Steven P.

    2012-01-01

    With improving survival rates of preterm newborns, adverse cognitive outcomes are increasingly recognized. Adverse cognitive outcomes are associated with decreased cerebellar volumes, and modifiable risk factors for these adverse outcomes should be identified. Animal models demonstrate reduced preterm cerebellar growth after exposure to glucocorticoids. Preterm neonates were prospectively studied with serial MRI examinations near birth and again near term-equivalent age. Adjusting for associated clinical factors, antenatal bethamethasone was not associated with changes in cerebellar volume. Postnatal exposure to clinically routine doses of hydrocortisone or dexamethasone were associated with impaired cerebellar, but not cerebral, growth. Modifying postnatal risk factors for impaired cerebellar development, and particularly glucocorticoid exposure, may help to decrease risk for adverse neurological outcome after preterm birth. PMID:22013125

  5. 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

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

    PubMed

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

    2014-09-01

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

  7. 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

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

    PubMed

    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.

  9. Low nanomolar serotonin inhibits the glutamate receptor/nitric oxide/cyclic GMP pathway in slices from adult rat cerebellum.

    PubMed

    Maura, G; Guadagnin, A; Raiteri, M

    1995-09-01

    The function of serotonin afferents to the cerebellum has been investigated by monitoring the effects of serotoninergic drugs on the production of cyclic GMP elicited in cerebellar slices by activation of ionotropic glutamate receptors. Exposure of adult rat cerebellar slices to N-methyl-D-aspartate (1 nM to 1 microM) or to (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA; 1 nM to 10 microM) elicited concentration-dependent and saturable rises in the levels of cyclic GMP. These responses were blocked by selective antagonists at the N-methyl-D-aspartate or AMPA receptors and by inhibiting nitric oxide synthase, but were insensitive to tetrodotoxin. When tested between 0.1 and 10 nM, serotonin, the serotonin1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin and the serotonin2 receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane inhibited, concentration-dependently, the cyclic GMP responses evoked by near-maximal (0.1 microM) concentrations of N-methyl-D-aspartate or AMPA. The EC50 values (concentrations causing half-maximal effect) ranged between 0.7 and 2.1 nM. The actions of serotonin were totally abolished by methiothepin, a mixed-type serotonin receptor antagonist. Thus, the serotonergic cerebellar afferents may exert a potent inhibitory control on the excitatory transmission mediated by N-methyl-D-aspartate and AMPA receptors; the inhibition occurs through both serotonin1A and serotonin2 receptors. As the glutamate receptor-dependent cyclic GMP responses involve production of nitric oxide, a diffusible activator of guanylate cyclase, the above inhibitory serotonin receptors may have multiple localization.(ABSTRACT TRUNCATED AT 250 WORDS)

  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. 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.

  12. Crossed cerebellar diaschisis in ischemic stroke: a study of regional cerebral blood flow by /sup 133/Xe inhalation and single photon emission computerized tomography

    SciTech Connect

    Meneghetti, G.; Vorstrup, S.; Mickey, B.; Lindewald, H.; Lassen, N.A.

    1984-06-01

    Seventy measurements of CBF were performed in 12 stroke patients by /sup 133/Xe inhalation and a rapidly rotating single photon emission computerized tomograph. CBF was measured every other day during the acute phase and at 2- and 6-month follow-up visits. A persistent contralateral cerebellar blood flow depression was evident in five patients with severe hemispheric low flow areas, which correlated with large, hypodense lesions on the computerized tomographic scan. In a sixth patient with a small, deep infarct, a transient crossed cerebellar low flow was observed, while the clinical symptoms persisted. It is concluded from this serial study that crossed cerebellar diaschisis is a common finding in completed stroke. It is probably caused by disconnection of the corticopontine pathways, a disconnection that tends to persist. The phenomenon is in fact less variable than the stroke-related CBF changes in the infarcted hemisphere, in which a period of relative hyperemia is frequently seen.

  13. Comparative Visualization of Ensembles Using Ensemble Surface Slicing

    PubMed Central

    Alabi, Oluwafemi S.; Wu, Xunlei; Harter, Jonathan M.; Phadke, Madhura; Pinto, Lifford; Petersen, Hannah; Bass, Steffen; Keifer, Michael; Zhong, Sharon; Healey, Chris; Taylor, Russell M.

    2012-01-01

    By definition, an ensemble is a set of surfaces or volumes derived from a series of simulations or experiments. Sometimes the series is run with different initial conditions for one parameter to determine parameter sensitivity. The understanding and identification of visual similarities and differences among the shapes of members of an ensemble is an acute and growing challenge for researchers across the physical sciences. More specifically, the task of gaining spatial understanding and identifying similarities and differences between multiple complex geometric data sets simultaneously has proved challenging. This paper proposes a comparison and visualization technique to support the visual study of parameter sensitivity. We present a novel single-image view and sampling technique which we call Ensemble Surface Slicing (ESS). ESS produces a single image that is useful for determining differences and similarities between surfaces simultaneously from several data sets. We demonstrate the usefulness of ESS on two real-world data sets from our collaborators. PMID:23560167

  14. Cerebellar dentate nuclei lesions alter prefrontal cortex dendritic spine morphology.

    PubMed

    Bauer, David J; Peterson, Todd C; Swain, Rodney A

    2014-01-28

    Anatomical tracing studies in primates have revealed neural tracts from the cerebellar dentate nuclei to prefrontal cortex, implicating a cerebellar role in nonmotor processes. Experiments in rats examining the functional role of this cerebellothalamocortical pathway have demonstrated the development of visuospatial and motivational deficits following lesions of the dentate nuclei, in the absence of motor impairment. These behavioral deficits possibly occur due to structural modifications of the cerebral cortex secondary to loss of cerebellar input. The current study characterized morphological alterations in prefrontal cortex important for visuospatial and motivational processes following bilateral cerebellar dentate nuclei lesions. Rats received either bilateral electrolytic cerebellar dentate nuclei lesions or sham surgery followed by a 30-day recovery. Randomly selected Golgi-impregnated neurons in prefrontal cortex were examined for analysis. Measures of branch length and spine density revealed no differences between lesioned and sham rats in either apical or basilar arbors; however, the proportion of immature to mature spines significantly decreased in lesioned rats as compared to sham controls, with reductions of 33% in the basilar arbor and 28% in the apical arbor. Although expected pruning of branches and spines did not occur, the results are consistent with the hypothesis that cerebellar lesions influence prefrontal morphology and support the possibility that functional deficits following cerebellar dentate nuclei lesions are related to prefrontal morphological alteration.

  15. Ultrashort pulse laser slicing of semiconductor crystal

    NASA Astrophysics Data System (ADS)

    Kim, Eunho; Shimotsuma, Yasuhiko; Sakakura, Masaaki; Miura, Kiyotaka

    2016-07-01

    Meanwhile, by the convention wire-saw technique, it is difficult to slice off a thin wafer from bulk SiC crystal without the reserving space for cutting. In this study, we have achieved exfoliation of 4H-SiC single crystal by femtosecond laser induced slicing method. By using this, the exfoliated surface with the root-mean-square roughness of 3 μm and the cutting-loss thickness smaller than 30 μm was successfully demonstrated. We have also observed the nanostructure on the exfoliated surface in SiC crystal.

  16. 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.

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

    PubMed Central

    Koh, Eun-Jeong; Park, Jung-Soo

    2017-01-01

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

  18. Cerebellar Mutism Following Closed Head Injury in a Child

    PubMed Central

    Kariyattil, Rajeev; Rahim, Mohamed I. A.; Muthukuttiparambil, Unnikrishnan

    2015-01-01

    Cerebellar mutism is a rare occurrence following paediatric trauma. Although it is quite common after posterior fossa surgery in children, this phenomenon has rarely been reported following other insults, such as trauma, and its pathophysiology remains poorly understood. We report a seven-year-old child who presented to the casualty department of Sultan Qaboos University Hospital in Muscat, Oman, in May 2013 with a traumatic right cerebellar contusion. The child presented with clinical features of cerebellar mutism but underwent a rapid and spontaneous recovery. The possible mechanism of this occurrence is discussed. PMID:25685374

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

    PubMed

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

    2014-06-01

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

  20. 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.

  1. Classically conditioned postural reflex in cerebellar patients.

    PubMed

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

    2004-09-01

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

  2. The ESO Slice Project (ESP) redshift survey.

    NASA Astrophysics Data System (ADS)

    Vettolani, G.; Zucca, E.; Cappi, A.; Merighi, R.; Mignoli, M.; Stirpe, G.; Zamorani, G.; MacGillivray, H.; Collins, C.; Balkowski, C.; Cayatte, V.; Maurogordato, S.; Proust, D.; Chincarini, G.; Guzzo, L.; Maccagni, D.; Scaramella, R.; Blanchard, A.; Ramella, M.

    The ESO Slice Project (ESP) is a galaxy redshift survey over about 30 square degrees, in a region near the South Galactic Pole. The survey is nearly complete to the limiting magnitude bj = 19.4 and consists of more than three thousands galaxies with reliable redshift determination.

  3. 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…

  4. nem_slice ver. 3.34

    SciTech Connect

    HUTCHINSON, SCOTT; STJOHN, MATTHEW; SJAARDEMA, GREGORY; HENNIGAN, GARY; SHADID, JOHN; DEVINE, KAREN

    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.

  5. 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…

  6. Memory impairment following right cerebellar infarction: a case study.

    PubMed

    Nakamoto, Fumiko Kusunoki; Tsutsumiuchi, Michiko; Maeda, Meiko Hashimoto; Uesaka, Yoshikazu; Takeda, Katsuhiko

    2015-01-01

    We reported a patient with a right cerebellar infarction who showed anterograde amnesia. Cognitive dysfunction caused by cerebellar lesions was called cerebellar cognitive affective syndrome, and deactivation of the contralateral prefrontal cortex function due to disconnections of cerebello-cerebral fiber tracts have been hypothesized as mechanism underlying the syndrome. The episodic memory impairment, however, could not be supported by the same mechanism because the prefrontal lesions cannot cause amnesia syndrome. The feature of the impairment of our patient was similar to that of diencephalic amnesia, and a single photon emission computed tomography study showed a relative hypoperfusion in the right cerebellar hemisphere and left anterior thalamus. We considered that the memory deficit was caused by the dysfunction of the thalamus, which is a relay center of the cerebello-cerebral connectivity network.

  7. Past, Present and Future Therapeutics for Cerebellar Ataxias

    PubMed Central

    Marmolino, D; Manto, M

    2010-01-01

    Cerebellar ataxias are a group of disabling neurological disorders. Patients exhibit a cerebellar syndrome and can also present with extra-cerebellar deficits, namely pigmentary retinopathy, extrapyramidal movement disorders, pyramidal signs, cortical symptoms (seizures, cognitive impairment/behavioural symptoms), and peripheral neuropathy. Recently, deficits in cognitive operations have been unraveled. Cerebellar ataxias are heterogeneous both at the phenotypic and genotypic point of view. Therapeutical trials performed during these last 4 decades have failed in most cases, in particular because drugs were not targeting a deleterious pathway, but were given to counteract putative defects in neurotransmission. The identification of the causative mutations of many hereditary ataxias, the development of relevant animal models and the recent identifications of the molecular mechanisms underlying ataxias are impacting on the development of new drugs. We provide an overview of the pharmacological treatments currently used in the clinical practice and we discuss the drugs under development. PMID:20808545

  8. Hypocupremia: A Possible Association with Late Cortical Cerebellar Atrophy

    PubMed Central

    Mittal, Shivam Om; Machado, Duarte G.

    2014-01-01

    Background We report a patient, diagnosed with late cortical cerebellar atrophy, who had persistent low serum copper levels. Case report A 48-year-old male developed progressive difficulty with balance, frequent falls, and dysarthric speech, which worsened over a short time span. He had an extensive ataxia work-up, which was unremarkable except for persistent low serum copper levels despite adequate supplementation. Magnetic resonance imaging of the brain showed marked cerebellar atrophy. The patient experienced progressive worsening of symptoms, which did not improve with either oral or parenteral copper supplementation. Discussion To our knowledge, ours is the first case report of late cortical cerebellar atrophy in the setting of low serum copper levels. The current report should trigger further research in mechanisms leading to copper deficiency and its possible role in cerebellar disease. PMID:25247109

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

    PubMed

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

    2001-04-01

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

  10. 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

  11. 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

  12. Non-invasive cerebellar stimulation--a consensus paper.

    PubMed

    Grimaldi, G; Argyropoulos, G P; Boehringer, A; Celnik, P; Edwards, M J; Ferrucci, R; Galea, J M; Groiss, S J; Hiraoka, K; Kassavetis, P; Lesage, E; Manto, M; Miall, R C; Priori, A; Sadnicka, A; Ugawa, Y; Ziemann, U

    2014-02-01

    The field of neurostimulation of the cerebellum either with transcranial magnetic stimulation (TMS; single pulse or repetitive (rTMS)) or transcranial direct current stimulation (tDCS; anodal or cathodal) is gaining popularity in the scientific community, in particular because these stimulation techniques are non-invasive and provide novel information on cerebellar functions. There is a consensus amongst the panel of experts that both TMS and tDCS can effectively influence cerebellar functions, not only in the motor domain, with effects on visually guided tracking tasks, motor surround inhibition, motor adaptation and learning, but also for the cognitive and affective operations handled by the cerebro-cerebellar circuits. Verbal working memory, semantic associations and predictive language processing are amongst these operations. Both TMS and tDCS modulate the connectivity between the cerebellum and the primary motor cortex, tuning cerebellar excitability. Cerebellar TMS is an effective and valuable method to evaluate the cerebello-thalamo-cortical loop functions and for the study of the pathophysiology of ataxia. In most circumstances, DCS induces a polarity-dependent site-specific modulation of cerebellar activity. Paired associative stimulation of the cerebello-dentato-thalamo-M1 pathway can induce bidirectional long-term spike-timing-dependent plasticity-like changes of corticospinal excitability. However, the panel of experts considers that several important issues still remain unresolved and require further research. In particular, the role of TMS in promoting cerebellar plasticity is not established. Moreover, the exact positioning of electrode stimulation and the duration of the after effects of tDCS remain unclear. Future studies are required to better define how DCS over particular regions of the cerebellum affects individual cerebellar symptoms, given the topographical organization of cerebellar symptoms. The long-term neural consequences of non

  13. New illumination technique for IR-video guided patch-clamp recording from neurons in slice cultures on biomembrane.

    PubMed

    Alix, Philippe; Winterer, Jochen; Müller, Wolfgang

    2003-09-30

    Slice cultures on biomembrane are the method of choice for studying Ca2+-dependent plastic changes occurring over several days to weeks. Using IR-differential interference contrast, good visualization of neurons in biomembrane slice cultures has been achieved despite a negative optical effect of the biomembrane, but epifluorescence imaging requires removal of a Wollaston prism and the analyzer. Here, we describe a novel illumination method to overcome this problem. Using optic fiber illumination at a shallow angle from the top of the slice culture, with or without additional illumination from the bottom, we obtained good cellular resolution of neurons in biomembrane slice cultures as well as in acute slices with an infrared-video camera. With this technique, we demonstrate visually guided whole-cell patch-clamp recording of Na+- and K+-currents as well as combination of whole-cell recording with fluorescence imaging of hippocampal and entorhinal cortex neurons in biomembrane slice cultures. Our inexpensive method should prove very useful for studying in vitro effects of long-term manipulations on membrane currents and intracellular Ca2+-signaling.

  14. 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…

  15. Isolated cerebellar toxoplasmosis as a complication of HIV infection.

    PubMed

    Pott, H; Castelo, A

    2013-01-01

    Isolated cerebellar mass lesion is an uncommon presentation of toxoplasmosis. The authors report one rare case in a 50-year-old HIV-infected male patient who presented with clipped speech, gait ataxia and incoordination. The cerebellar toxoplasmosis was suspected based on imaging findings, despite the atypical location. This case highlights the need for a high index of clinical suspicion among HIV-infected patients with neurological manifestations and suspicious neuroimaging findings.

  16. Primary cerebellopontine progressive multifocal leukoencephalopathy diagnosed premortem by cerebellar biopsy.

    PubMed

    Jones, H R; Hedley-Whyte, E T; Freidberg, S R; Kelleher, J E; Krolikowski, J

    1982-02-01

    A subacute progressive cerebellar brainstem syndrome developed in a patient with systemic lupus erythematosus in remission. Cerebellar biopsy documented the diagnosis of progressive multifocal leukoencephalopathy (PML). Data from this patient and 10 others in the literature emphasize the need to consider this diagnosis when ataxia develops in any patient with underlying malignancy, chronic infection, or other disease that involves immunological incompetence. Although the ataxic form of PML is not of nosological relevance, early diagnosis may eventually have therapeutic importance.

  17. Glucose utilization in the inferior cerebellar vermis and ocular myoclonus.

    PubMed

    Yakushiji, Y; Otsubo, R; Hayashi, T; Fukuchi, K; Yamada, N; Hasegawa, Y; Minematsu, K

    2006-07-11

    In a patient with symptomatic ocular myoclonus, the authors observed the regional cerebral metabolic rate of glucose use (rCMRGlu) before and after successful treatment with clonazepam. Even after the symptoms resolved, the rCMRGlu in the hypertrophic olive increased persistently, whereas that in the inferior cerebellar vermis contralateral to the hypertrophic olive decreased. The inferior cerebellar vermis, belonging to the vestibulocerebellar system, may be associated with the generation of symptomatic ocular myoclonus.

  18. Slice stretching effects for maximal slicing of a Schwarzschild black hole

    NASA Astrophysics Data System (ADS)

    Reimann, Bernd

    2005-11-01

    Slice stretching effects such as slice sucking and slice wrapping arise when foliating the extended Schwarzschild spacetime with maximal slices. For arbitrary spatial coordinates these effects are quantified here in the context of boundary conditions where the lapse arises as a linear combination of odd and even lapse. Favourable boundary conditions are then derived which make the overall slice stretching occur late in numerical simulations. Allowing the lapse to become negative, this requirement leads to lapse functions which approach at late times the odd lapse corresponding to the static Schwarzschild metric. Demanding, however, that a numerically favourable lapse remains non-negative, as a result the average of odd and even lapse is obtained. At late times the lapse with zero gradient at the puncture arising for the puncture evolution is precisely of this form. Finally, analytic arguments are given on how slice stretching effects can be avoided. Here the excision technique and the working mechanism of the shift function are studied in detail.

  19. Proprioceptive Localization Deficits in People With Cerebellar Damage.

    PubMed

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

    2017-04-01

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

  20. 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.

  1. Neurodevelopmental Malformations of the Cerebellar Vermis in Genetically Engineered Rats.

    PubMed

    Ramos, Raddy L; Van Dine, Sarah E; Gilbert, Mary E; Leheste, Joerg R; Torres, German

    2015-12-01

    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. Malformations are almost exclusively found along the primary fissure and are indicative of deficits of neuronal migration during cerebellar development. In the present report, we test the prediction that genetically engineered rats on Sprague-Dawley or Long-Evans backgrounds will also exhibit the same cerebellar malformations. Consistent with our hypothesis, we found that three different transgenic lines on two different backgrounds had cerebellar malformations. Heterotopia in transgenic rats had identical cytoarchitecture as that observed in wild-type rats including altered morphology of Bergmann glia. In light of the possibility that heterotopia could affect results from behavioral studies, these data suggest that histological analyses be performed in studies of cerebellar function or development when using genetically engineered rats on these backgrounds in order to have more careful interpretation of experimental findings.

  2. Clumsiness and disturbed cerebellar development: insights from animal experiments.

    PubMed

    Gramsbergen, Albert

    2003-01-01

    Cerebellar functioning has been implied in the fine adjustments of muscle tone, in the coordination and the feed-forward control of movements and posture, as well as in the establishment and performance of motor skills. The cerebellar cortex in mammals develops late in neuro-ontogeny and an extrapolation from experimental results indicates that in the human the proliferation of the granule cells and the development of circuitry in the cerebellar cortex starts only in the last trimester of pregnancy and lasts until beyond the first birthday. This late development makes the cerebellar development particularly vulnerable to situations like an insufficient supply of nutrients, which may follow placental dysfunction, or to side effects of pharmacological treatments like the administration of corticosteroids in the postnatal period. We studied whether such situations might also lead to motor impairments. In rats, the effects of undernutrition during the brain growth spurt were investigated as well as those of corticosteroids administered in a period that is analogous to the 7th to 8th month of pregnancy in the human. Both these interferences affect cerebellar development and our results in rats indicate that they also lead to retardations in the emergence of certain reflexes, as well as to longer lasting motor impairments during locomotion. Extrapolation of these results strongly suggests that a disturbed cerebellar development should be considered as an important etiological factor in clumsiness in human children.

  3. Phonological short-term store impairment after cerebellar lesion: a single case study.

    PubMed

    Chiricozzi, Francesca R; Clausi, Silvia; Molinari, Marco; Leggio, Maria G

    2008-01-01

    The cerebellum is a recent addition to the growing list of cerebral areas involved in the multifaceted structural system that sustains verbal working memory (vWM), but its contribution is still a matter of debate. Here, we present a patient with a selective deficit of vWM resulting from a bilateral cerebellar ischemic lesion. After this acute event, the patient had impaired immediate and delayed word-serial recall and auditory-verbal delayed recognition. The digit span, however, was completely preserved. To investigate the cerebellar contribution to vWM, four experiments addressing the function of different vWM phonological loop components were performed 18 months after the lesion, and results were compared with normative data or, when needed, with a small group of matched controls. In Experiment 1, digit span was assessed with different presentation and response modalities using lists of digits of varying lengths. In Experiment 2, the articulatory rehearsal system was analyzed by measurement of word length and articulatory suppression effects. Experiment 3 was devoted to analyzing the phonological short-term store (ph-STS) by the recency effect, the phonological similarity effect, short-term forgetting, and unattended speech. Data suggested a possible key role of the semantic component of the processed material, which was tested in Experiment 4, in which word and nonword-serial recall with or without interpolating activity were analyzed. The patient showed noticeably reduced scores in the tasks that primarily or exclusively engaged activity of the ph-STS, namely those of Experiment 3, and good performance in the tests that investigated the recirculation of verbal information. This pattern of results implicates the ph-STS as the cognitive locus of the patient's deficit. This report demonstrates a cerebellar role in encoding and/or strengthening the phonological traces in vWM.

  4. 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

  5. Activation of NPY type 5 receptors induces a long-lasting increase in spontaneous GABA release from cerebellar inhibitory interneurons

    PubMed Central

    Dubois, C. J.; Ramamoorthy, P.; Whim, M. D.

    2012-01-01

    Neuropeptide Y (NPY), a widely distributed neuropeptide in the central nervous system, can transiently suppress inhibitory synaptic transmission and alter membrane excitability via Y2 and Y1 receptors (Y2rs and Y1rs), respectively. Although many GABAergic neurons express Y5rs, the functional role of these receptors in inhibitory neurons is not known. Here, we investigated whether activation of Y5rs can modulate inhibitory transmission in cerebellar slices. Unexpectedly, application of NPY triggered a long-lasting increase in the frequency of miniature inhibitory postsynaptic currents in stellate cells. NPY also induced a sustained increase in spontaneous GABA release in cultured cerebellar neurons. When cerebellar cultures were examined for Y5r immunoreactivity, the staining colocalized with that of VGAT, a presynaptic marker for GABAergic cells, suggesting that Y5rs are located in the presynaptic terminals of inhibitory neurons. RT-PCR experiments confirmed the presence of Y5r mRNA in the cerebellum. The NPY-induced potentiation of GABA release was blocked by Y5r antagonists and mimicked by application of a selective peptide agonist for Y5r. Thus Y5r activation is necessary and sufficient to trigger an increase in GABA release. Finally, the potentiation of inhibitory transmission could not be reversed by a Y5r antagonist once it was initiated, consistent with the development of a long-term potentiation. These results indicate that activation of presynaptic Y5rs induces a sustained increase in spontaneous GABA release from inhibitory neurons in contrast to the transient suppression of inhibitory transmission that is characteristic of Y1r and Y2r activation. Our findings thus reveal a novel role of presynaptic Y5rs in inhibitory interneurons in regulating GABA release and suggest that these receptors could play a role in shaping neuronal network activity in the cerebellum. PMID:22190627

  6. Human brain slices for epilepsy research: Pitfalls, solutions and future challenges.

    PubMed

    Jones, Roland S G; da Silva, Anderson Brito; Whittaker, Roger G; Woodhall, Gavin L; Cunningham, Mark O

    2016-02-15

    Increasingly, neuroscientists are taking the opportunity to use live human tissue obtained from elective neurosurgical procedures for electrophysiological studies in vitro. Access to this valuable resource permits unique studies into the network dynamics that contribute to the generation of pathological electrical activity in the human epileptic brain. Whilst this approach has provided insights into the mechanistic features of electrophysiological patterns associated with human epilepsy, it is not without technical and methodological challenges. This review outlines the main difficulties associated with working with epileptic human brain slices from the point of collection, through the stages of preparation, storage and recording. Moreover, it outlines the limitations, in terms of the nature of epileptic activity that can be observed in such tissue, in particular, the rarity of spontaneous ictal discharges, we discuss manipulations that can be utilised to induce such activity. In addition to discussing conventional electrophysiological techniques that are routinely employed in epileptic human brain slices, we review how imaging and multielectrode array recordings could provide novel insights into the network dynamics of human epileptogenesis. Acute studies in human brain slices are ultimately limited by the lifetime of the tissue so overcoming this issue provides increased opportunity for information gain. We review the literature with respect to organotypic culture techniques that may hold the key to prolonging the viability of this material. A combination of long-term culture techniques, viral transduction approaches and electrophysiology in human brain slices promotes the possibility of large scale monitoring and manipulation of neuronal activity in epileptic microcircuits.

  7. The Energy Demand of Fast Neuronal Network Oscillations: Insights from Brain Slice Preparations

    PubMed Central

    Kann, Oliver

    2012-01-01

    Fast neuronal network oscillations in the gamma range (30–100 Hz) in the cerebral cortex have been implicated in higher cognitive functions such as sensual perception, working memory, and, perhaps, consciousness. However, little is known about the energy demand of gamma oscillations. This is mainly caused by technical limitations that are associated with simultaneous recordings of neuronal activity and energy metabolism in small neuronal networks and at the level of mitochondria in vivo. Thus recent studies have focused on brain slice preparations to address the energy demand of gamma oscillations in vitro. Here, reports will be summarized and discussed that combined electrophysiological recordings, oxygen sensor microelectrodes, and live-cell fluorescence imaging in acutely prepared slices and organotypic slice cultures of the hippocampus from both, mouse and rat. These reports consistently show that gamma oscillations can be reliably induced in hippocampal slice preparations by different pharmacological tools. They suggest that gamma oscillations are associated with high energy demand, requiring both rapid adaptation of oxidative energy metabolism and sufficient supply with oxygen and nutrients. These findings might help to explain the exceptional vulnerability of higher cognitive functions during pathological processes of the brain, such as circulatory disturbances, genetic mitochondrial diseases, and neurodegeneration. PMID:22291647

  8. Modulation by K+ channels of action potential-evoked intracellular Ca2+ concentration rises in rat cerebellar basket cell axons

    PubMed Central

    Tan, Y P; Llano, I

    1999-01-01

    Action potential-evoked [Ca2+]i rises in basket cell axons of rat cerebellar slices were studied using two-photon laser scanning microscopy and whole-cell recording, to identify the K+ channels controlling the shape of the axonal action potential. Whole-cell recordings of Purkinje cell IPSCs were used to screen K+ channel subtypes which could contribute to axonal repolarization. α-Dendrotoxin, 4-aminopyridine, charybdotoxin and tetraethylammonium chloride increased IPSC rate and/or amplitude, whereas iberiotoxin and apamin failed to affect the IPSCs. The effects of those K+ channel blockers that enhanced transmitter release on the [Ca2+]i rises elicited in basket cell axons by action potentials fell into three groups: 4-aminopyridine strongly increased action potential-evoked [Ca2+]i; tetraethylammonium and charybdotoxin were ineffective alone but augmented the effects of 4-aminopyridine; α-dendrotoxin had no effect. We conclude that cerebellar basket cells contain at least three pharmacologically distinct K+ channels, which regulate transmitter release through different mechanisms. 4-Aminopyridine-sensitive, α-dendrotoxin-insensitive K+ channels are mainly responsible for repolarization in basket cell presynaptic terminals. K+ channels blocked by charybdotoxin and tetraethylammonium have a minor role in repolarization. α-Dendrotoxin-sensitive channels are not involved in shaping the axonal action potential waveform. The two last types of channels must therefore exert control of synaptic activity through a pathway unrelated to axonal action potential broadening. PMID:10517801

  9. Modulation by K+ channels of action potential-evoked intracellular Ca2+ concentration rises in rat cerebellar basket cell axons.

    PubMed

    Tan, Y P; Llano, I

    1999-10-01

    1. Action potential-evoked [Ca2+]i rises in basket cell axons of rat cerebellar slices were studied using two-photon laser scanning microscopy and whole-cell recording, to identify the K+ channels controlling the shape of the axonal action potential. 2. Whole-cell recordings of Purkinje cell IPSCs were used to screen K+ channel subtypes which could contribute to axonal repolarization. alpha-Dendrotoxin, 4-aminopyridine, charybdotoxin and tetraethylammonium chloride increased IPSC rate and/or amplitude, whereas iberiotoxin and apamin failed to affect the IPSCs. 3. The effects of those K+ channel blockers that enhanced transmitter release on the [Ca2+]i rises elicited in basket cell axons by action potentials fell into three groups: 4-aminopyridine strongly increased action potential-evoked [Ca2+]i; tetraethylammonium and charybdotoxin were ineffective alone but augmented the effects of 4-aminopyridine; alpha-dendrotoxin had no effect. 4. We conclude that cerebellar basket cells contain at least three pharmacologically distinct K+ channels, which regulate transmitter release through different mechanisms. 4-Aminopyridine-sensitive, alpha-dendrotoxin-insensitive K+ channels are mainly responsible for repolarization in basket cell presynaptic terminals. K+ channels blocked by charybdotoxin and tetraethylammonium have a minor role in repolarization. alpha-Dendrotoxin-sensitive channels are not involved in shaping the axonal action potential waveform. The two last types of channels must therefore exert control of synaptic activity through a pathway unrelated to axonal action potential broadening.

  10. Frequency-dependent reliability of spike propagation is function of axonal voltage-gated sodium channels in cerebellar Purkinje cells.

    PubMed

    Yang, Zhilai; Wang, Jin-Hui

    2013-12-01

    The spike propagation on nerve axons, like synaptic transmission, is essential to ensure neuronal communication. The secure propagation of sequential spikes toward axonal terminals has been challenged in the neurons with a high firing rate, such as cerebellar Purkinje cells. The shortfall of spike propagation makes some digital spikes disappearing at axonal terminals, such that the elucidation of the mechanisms underlying spike propagation reliability is crucial to find the strategy of preventing loss of neuronal codes. As the spike propagation failure is influenced by the membrane potentials, this process is likely caused by altering the functional status of voltage-gated sodium channels (VGSC). We examined this hypothesis in Purkinje cells by using pair-recordings at their somata and axonal blebs in cerebellar slices. The reliability of spike propagation was deteriorated by elevating spike frequency. The frequency-dependent reliability of spike propagation was attenuated by inactivating VGSCs and improved by removing their inactivation. Thus, the functional status of axonal VGSCs influences the reliability of spike propagation.

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. Autosomal dominant cerebellar ataxia deafness and narcolepsy.

    PubMed

    Melberg, A; Hetta, J; Dahl, N; Nennesmo, I; Bengtsson, M; Wibom, R; Grant, C; Gustavson, K H; Lundberg, P O

    1995-12-01

    A new autosomal dominant syndrome in a Swedish pedigree is described. Five patients were affected with cerebellar ataxia and sensorineural deafness. Four of these patients had symptoms of narcolepsy. Optic atrophy, other neurological abnormalities and psychiatric symptoms developed with increasing disease duration. Three patients had non-neurological disease in addition, including diabetes mellitus in two and hypertrophic cardiomyopathy in one. Autopsy with neuropathological examination was performed in one case. Molecular studies focused on the short arm of chromosome 6, including the HLA DR2 locus associated with narcolepsy and the (CAG)n repeat at the spinocerebellar ataxia type 1 (SCA1) locus. Biochemical investigation of muscle biopsy of one case indicated mitochondrial dysfunction with selective decrease in ATP production for substrates that normally give the highest rates. The activity of glutamate dehydrogenase was reduced, indicating a low mitochondrial density. We postulate an autosomal dominant genetic factor responsible for this syndrome. Linkage was excluded to HLA DR2, and a normal sized SCA1 repeat was observed. We conclude that a locus predisposing to ataxia, deafness and narcolepsy exists outside this region of chromosome 6.

  17. Understanding and modulating motor learning with Cerebellar stimulation

    PubMed Central

    Celnik, Pablo

    2014-01-01

    Non-invasive brain stimulation techniques are a powerful approach to investigate the physiology and function of the central nervous system. Recent years have seen numerous investigations delivering transcranial magnetic stimulation (TMS) and or transcranial direct current stimulation (tDCS) to the cerebellum to determine its role in motor, cognitive and emotional behaviours. Early studies have shown that it is possible to assess cerebellar-motor cortex (CB-M1) connectivity using a paired-pulse TMS paradigm called cerebellar inhibition (CBI), and indirectly infer the state of cerebellar excitability. Thus, it has been shown that CBI changes proportionally to the magnitude of locomotor learning and in association with reaching adaption tasks. In addition, CBI has been used to demonstrate at a physiological level the effects of applying TMS or tDCS to modulate, up or down, the excitability of cerebellar-M1 connectivity. These studies became the fundamental substrate to newer investigations showing that we can affect motor, cognitive and emotional behaviour when TMS or tDCS targeting the cerebellum is delivered in the context of performance. Furthermore, newer investigations are starting to report the effects of cerebellar non-invasive stimulation to treat symptoms associated with neurological conditions such as stroke and dystonia. Altogether, non-invasive cerebellar stimulation can potentially become a game changer for the management of conditions that affect the cerebellum given the scarcity of current effective therapeutic options. In this brief manuscript, some of the current evidence demonstrating the effects of cerebellar stimulation to modulate motor behaviour and its use to assess physiological processes underlying motor learning are presented. PMID:25283180

  18. Effect of Valsartan on Cerebellar Adrenomedullin System Dysregulation During Hypertension.

    PubMed

    Figueira, Leticia; Israel, Anita

    2017-02-01

    Adrenomedullin (AM) and its receptors components, calcitonin-receptor-like receptor (CRLR), and receptor activity-modifying protein (RAMP1, RAMP2, and RAMP3) are expressed in cerebellum. Cerebellar AM, AM binding sites and receptor components are altered during hypertension, suggesting a role for cerebellar AM in blood pressure regulation. Thus, we assessed the effect of valsartan, on AM and its receptor components expression in the cerebellar vermis of Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Additionally, we evaluated AM action on superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activity, and thiobarbituric acid reactive substances (TBARS) production in cerebellar vermis. Animals were treated with valsartan or vehicle for 11 days. Rats were sacrificed by decapitation; cerebellar vermis was dissected; and AM, CRLR, RAMP1, RAMP2, and RAMP3 expression was quantified by Western blot analysis. CAT, SOD, and GPx activity was determined spectrophotometrically and blood pressure by non-invasive plethysmography. We demonstrate that AM and RAMP2 expression was lower in cerebellum of SHR rats, while CRLR, RAMP1, and RAMP3 expression was higher than those of WKY rats. AM reduced cerebellar CAT, SOD, GPx activities, and TBARS production in WKY rats, but not in SHR rats. Valsartan reduced blood pressure and reversed the altered expression of AM and its receptors components, as well the loss of AM capacity to reduce antioxidant enzyme activity and TBARS production in SHR rats. These findings demonstrate that valsartan is able to reverse the dysregulation of cerebellar adrenomedullinergic system; and they suggest that altered AM system in the cerebellum could represent the primary abnormality leading to hypertension.

  19. 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

  20. Spontaneous cluster activity in the inferior olivary nucleus in brainstem slices from postnatal mice.

    PubMed

    Rekling, Jens C; Jensen, Kristian H R; Jahnsen, Henrik

    2012-04-01

    A distinctive property of the cerebellar system is olivocerebellar modules, where synchronized electrical activity in neurons in the inferior olivary nucleus (IO) evokes organized activity in the cerebellar cortex. However, the exact function of these modules, and how they are developed, is still largely unknown. Here we show that the IO in in vitro slices from postnatal mice spontaneously generates clusters of neurons with synchronous Ca(2+) transients. Neurons in the principal olive (PO), and the vestibular-related dorsomedial cell column (dmcc), showed an age-dependent increase in spontaneous calcium transients. The spatiotemporal activity pattern was occasionally organized in clusters of co-active neighbouring neurons,with regular (16 min-1) and irregular (2-3 min(-1)) repeating cluster activity in the dmcc and PO, respectively. IO clusters had a diameter of 100-170 μm, lasted~1 s, and increased in occurrence from postnatal day P5.5 to P12.5, followed by a sharp drop to near zero at P15.5. IO clusters were overlapping, and comprised nearly identical neurons at some time points, and a varied subset of neurons at others. Some neurons had hub-like properties, being co-active with many other neighbours, and some were co-active with separate clusters at different times. The coherence between calcium transients in IO neurons decreased with Euclidean distance between the cells reaching low values at 100-200 μm distances. Intracellular recordings from IO neurons during cluster formation revealed the presence of spikelet-like potentials, suggesting that electrical coupling between neighbouring IO neurons may serve as a synchronizing mechanism. In conclusion, the IO shows spontaneous cluster activity under in vitro conditions, coinciding with a critical postnatal period in olivocerebellar development. We propose that these clusters may be forerunners of the ensembles of IO neurons shown to be co-active in adult animals spontaneously and during motor acts.

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

    PubMed

    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).

  2. 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

  3. Large-scale, high-resolution electrophysiological imaging of field potentials in brain slices with microelectronic multielectrode arrays

    PubMed Central

    Ferrea, E.; Maccione, A.; Medrihan, L.; Nieus, T.; Ghezzi, D.; Baldelli, P.; Benfenati, F.; Berdondini, L.

    2012-01-01

    Multielectrode arrays (MEAs) are extensively used for electrophysiological studies on brain slices, but the spatial resolution and field of recording of conventional arrays are limited by the low number of electrodes available. Here, we present a large-scale array recording simultaneously from 4096 electrodes used to study propagating spontaneous and evoked network activity in acute murine cortico-hippocampal brain slices at unprecedented spatial and temporal resolution. We demonstrate that multiple chemically induced epileptiform episodes in the mouse cortex and hippocampus can be classified according to their spatio-temporal dynamics. Additionally, the large-scale and high-density features of our recording system enable the topological localization and quantification of the effects of antiepileptic drugs in local neuronal microcircuits, based on the distinct field potential propagation patterns. This novel high-resolution approach paves the way to detailed electrophysiological studies in brain circuits spanning spatial scales from single neurons up to the entire slice network. PMID:23162432

  4. 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.

  5. Effects of Relative Hypoglycemia on LTP and NADH Imaging in Rat Hippocampal Slices

    PubMed Central

    Sadgrove, Matthew P.; Beaver, Christopher J.; Turner, Dennis A.

    2007-01-01

    Cognitive and neuronal impairment in diabetes may be associated with iatrogenic hypoglycemia, particularly at low serum glucose levels (< 3 mM). To evaluate cellular impairment, we assessed acute hippocampal slice functioning during decreased ambient glucose, by monitoring evoked field excitatory post-synaptic potentials (fEPSP), and slice nicotinamide adenine dinucleotide (NADH) fluorescence. The effects of lowered glucose levels (60 min) were analyzed by examining the induction and maintenance of long-term potentiation (LTP), and NADH metabolic imaging in the CA1 region. The basal fEPSP response was reduced by lowered ambient glucose, an effect that was reversible in 2.5 mM glucose, partially reversible in 1.25 mM glucose and irreversible in 0 mM glucose, after 25 min recovery. LTP induction and maintenance declined during glucose restriction, demonstrating reversibly failed maintenance in 5 mM and 2.5 mM ambient glucose, and absent induction in 1.25 mM glucose. Peak NADH levels observed during train-induced biphasic transients were significantly reduced during 1.25 mM and 2.5 mM glucose. Significant functional compromise in our slice model occurred at 2.5 mM ambient glucose, equivalent to <1mM tissue glucose in the slice center, due to diffusion limitations and active glucose utilization. This tissue glucose level correlates with human observations of a serum threshold of <3mM for cognitive impairment, since brain tissue glucose is approximately one third of serum levels. The physiological effects of hypoglycemia in our slice model, assessed through fEPSP, LTP, and NADH responses, replicate closely the in vivo situation, confirming the usefulness of this model in assessing consequences of relative hypoglycemia. PMID:17651706

  6. Citrulline uptake in rat cerebral cortex slices: modulation by Thioacetamide -Induced hepatic failure.

    PubMed

    Zielińska, Magdalena; Obara-Michlewska, Marta; Hilgier, Wojciech; Albrecht, Jan

    2014-12-01

    L-citrulline (Cit) is a co-product of NO synthesis and a direct L-arginine (Arg) precursor for de novo NO synthesis. Acute liver failure (ALF) is associated with increased nitric oxide (NO) and cyclic GMP (cGMP) synthesis in the brain, indirectly implicating a role for active transport of Cit. In the present study we characterized [(3)H]Cit uptake to the cortical brain slices obtained from control rats and rats with thioacetamide (TAA)-induced ALF ("TAA slices"). In both control and TAA slices the uptake was partially Na(+)-dependent and markedly inhibited by substrates of systems L and N, including L-glutamine (Gln), which accumulates in excess in brain during ALF. Cit uptake was not affected by Arg, the y(+)/y(+)L transport system substrate, nor by amino acids taken up by systems A, xc (-)or XAG. The Vmax of the uptake in TAA slices was ~60 % higher than in control slices. Chromatographic (HPLC) analysis revealed a ~30 % increase of Cit concentration in the cerebral cortical homogenates of TAA rats. The activity of argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL), the two enzymes of Cit-NO cycle catalyzing synthesis of Arg, showed an increase in TAA rats, consistent with increased ASS and ASL protein expression, by ~30 and ~20 %, respectively. The increased Cit-NO cycle activity was paralleled by increased expression of mRNA coding for inducible nitric oxide synthase (iNOS). Taken together, the results suggest a role for Cit in the activation of cerebral NO synthesis during ALF.

  7. Experimental demonstration of spectrum-sliced elastic optical path network (SLICE).

    PubMed

    Kozicki, Bartłomiej; Takara, Hidehiko; Tsukishima, Yukio; Yoshimatsu, Toshihide; Yonenaga, Kazushige; Jinno, Masahiko

    2010-10-11

    We describe experimental demonstration of spectrum-sliced elastic optical path network (SLICE) architecture. We employ optical orthogonal frequency-division multiplexing (OFDM) modulation format and bandwidth-variable optical cross-connects (OXC) to generate, transmit and receive optical paths with bandwidths of up to 1 Tb/s. We experimentally demonstrate elastic optical path setup and spectrally-efficient transmission of multiple channels with bit rates ranging from 40 to 140 Gb/s between six nodes of a mesh network. We show dynamic bandwidth scalability for optical paths with bit rates of 40 to 440 Gb/s. Moreover, we demonstrate multihop transmission of a 1 Tb/s optical path over 400 km of standard single-mode fiber (SMF). Finally, we investigate the filtering properties and the required guard band width for spectrally-efficient allocation of optical paths in SLICE.

  8. Calcium channels responsible for potassium-induced transmitter release at rat cerebellar synapses.

    PubMed Central

    Momiyama, A; Takahashi, T

    1994-01-01

    The effects of calcium channel blockers on potassium-induced transmitter release were studied in thin slices of cerebellum from neonatal rats using whole-cell patch clamp methods. Miniature inhibitory postsynaptic currents (mIPSCs) mediated by gamma-aminobutyric acid (GABA) were recorded from deep cerebellar nuclear neurones in the presence of tetrodotoxin. The frequency of mIPSCs was reproducibly increased by a brief application of high-potassium solution. In the presence of the L-type Ca2+ channel blocker nicardipine (10 microM), the potassium-induced increase in mIPSC frequency was suppressed by 49%. Neither the mean amplitude nor the time course of mIPSCs was affected by the blocker. The N-type Ca2+ channel blocker omega-conotoxin GVIA (omega-CgTX, 3 microM) had no effect on the frequency of potassium-induced mIPSCs. The P-type Ca2+ channel blocker omega-Aga-IVA (200 nM) suppressed the potassium-induced increase in mIPSC frequency by 83% without affecting the mean amplitude or time course of mIPSCs. Comparing these data with previous studies of neurally evoked transmission, it is concluded that the Ca2+ channel subtypes responsible for potassium-induced transmitter release may be different from those mediating fast synaptic transmission. PMID:7913967

  9. 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.

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

    PubMed

    Cheron, G; Servais, L; Dan, B

    2008-04-22

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

  11. 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

  12. 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.

  13. Modeling the Generation of Output by the Cerebellar Nuclei

    PubMed Central

    Steuber, Volker; Jaeger, Dieter

    2012-01-01

    Functional aspects of network integration in the cerebellar cortex have been studied experimentally and modeled in much detail ever since the early work by theoreticians such as Marr, Albus and Braitenberg more than 40 years ago. In contrast, much less is known about cerebellar processing at the output stage, namely in the cerebellar nuclei (CN). Here, input from Purkinje cells converges to control CN neuron spiking via GABAergic inhibition, before the output from the CN reaches cerebellar targets such as the brainstem and the motor thalamus. In this article we review modeling studies that address how the CN may integrate cerebellar cortical inputs, and what kind of signals may be transmitted. Specific hypotheses in the literature contrast rate coding and temporal coding of information in the spiking output from the CN. One popular hypothesis states that postinhibitory rebound spiking may be an important mechanism by which Purkinje cell inhibition is turned into CN output spiking, but this hypothesis remains controversial. Rate coding clearly does take place, but in what way it may be augmented by temporal codes remains to be more clearly established. Several candidate mechanisms distinct from rebound spiking are discussed, such as the significance of spike time correlations between Purkinje cell pools to determine CN spike timing, irregularity of Purkinje cell spiking as a determinant of CN firing rate, and shared brief pauses between Purkinje cell pools that may trigger individual CN spikes precisely. PMID:23200193

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

    PubMed

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

    2016-03-01

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

  15. 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

  16. 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.

  17. Mechanical characteristics of native tendon slices for tissue engineering scaffold

    PubMed Central

    Qin, Ting-Wu; Chen, Qingshan; Sun, Yu-Long; Steinmann, Scott P.; Amadio, Peter C.; An, Kai-Nan; Zhao, Chunfeng

    2014-01-01

    The purpose of this study was to characterize the mechanical behavior of tendon slices with different thicknesses. Tendon slices of 100, 200, 300, 400, and 500 μm thickness were mechanically tested. The 300 μm slices were further tested for strength and modulus after 21,000-cycle fatigue testing under different applied strain levels (0, 1, 3, 5, 8, 10, and 12%). The tendon slice structure, morphology, and viability of bone marrow stromal cells (BMSCs) seeded onto the slices were also examined with histology, scanning electron microscopy, and vital cell labeling, respectively. Tendon slices 300 μm or more in thickness had similar ultimate tensile strength and Young's modulus to the intact tendon bundle. A strain of 5% or less did not cause any structural damage, nor did it change the mechanical properties of a 300 μm-thick tendon slice after 21,000-cycle fatigue testing. BMSCs were viable between and on the tendon slices after 2 weeks in tissue culture. This study demonstrated that, if tendon slices are used as a scaffold for tendon tissue engineering, slices 300 μm or more in thickness would be preferable from a mechanical strength point of view. If mechanical stimulation is performed for seeded-cell preparations, 5% strain or less would be appropriate. PMID:22323314

  18. 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

  19. Acetylcholinesterase inhibition reveals endogenous nicotinic modulation of glutamate inputs to CA1 stratum radiatum interneurons in hippocampal slices.

    PubMed

    Alkondon, Manickavasagom; Albuquerque, Edson X; Pereira, Edna F R

    2013-05-01

    The involvement of brain nicotinic acetylcholine receptors (nAChRs) in the neurotoxicological effects of soman, a potent acetylcholinesterase (AChE) inhibitor and a chemical warfare agent, is not clear. This is partly due to a poor understanding of the role of AChE in brain nAChR-mediated functions. To test the hypothesis that AChE inhibition builds sufficient acetylcholine (ACh) in the brain and facilitates nAChR-dependent glutamate transmission, we used whole-cell patch-clamp technique to record spontaneous glutamate excitatory postsynaptic currents (EPSCs) from CA1 stratum radiatum interneurons (SRI) in hippocampal slices. First, the frequency, amplitude and kinetics of EPSCs recorded from slices of control guinea pigs were compared to those recorded from slices of guinea pigs after a single injection of the irreversible AChE inhibitor soman (25.2μg/kg, s.c.). Second, EPSCs were recorded from rat hippocampal slices before and after their superfusion with the reversible AChE inhibitor donepezil (100nM). The frequency of EPSCs was significantly higher in slices taken from guinea pigs 24h but not 7 days after the soman injection than in slices from control animals. In 52% of the rat hippocampal slices tested, bath application of donepezil increased the frequency of EPSCs. Further, exposure to donepezil increased both burst-like and large-amplitude EPSCs, and increased the proportion of short (20-100ms) inter-event intervals. Donepezil's effects were suppressed significantly in presence of 10μM mecamylamine or 10nM methyllycaconitine. These results support the concept that AChE inhibition is able to recruit nAChR-dependent glutamate transmission in the hippocampus and such a mechanism can contribute to the acute neurotoxicological actions of soman.

  20. 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.

  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. Preterm cerebellar growth impairment after postnatal exposure to glucocorticoids.

    PubMed

    Tam, Emily W Y; Chau, Vann; Ferriero, Donna M; Barkovich, A James; Poskitt, Kenneth J; Studholme, Colin; Fok, Eric D-Y; Grunau, Ruth E; Glidden, David V; Miller, Steven P

    2011-10-19

    As survival rates of preterm newborns improve as a result of better medical management, these children increasingly show impaired cognition. These adverse cognitive outcomes are associated with decreases in the volume of the cerebellum. Because animals exhibit reduced preterm cerebellar growth after perinatal exposure to glucocorticoids, we sought to determine whether glucocorticoid exposure and other modifiable factors increased the risk for these adverse outcomes in human neonates. We studied 172 preterm neonatal infants from two medical centers, the University of British Columbia and the University of California, San Francisco, by performing serial magnetic resonance imaging examinations near birth and again near term-equivalent age. After we adjusted for associated clinical factors, antenatal betamethasone was not associated with changes in cerebellar volume. Postnatal exposure to clinically routine doses of hydrocortisone or dexamethasone was associated with impaired cerebellar, but not cerebral, growth. Alterations in treatment after preterm birth, particularly glucocorticoid exposure, may help to decrease risk for adverse neurological outcome after preterm birth.

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

    PubMed

    Sundberg, Maria; Sahin, Mustafa

    2015-12-01

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

  4. 3D morphometric analysis of human fetal cerebellar development.

    PubMed

    Scott, Julia A; Hamzelou, Kia S; Rajagopalan, Vidya; Habas, Piotr A; Kim, Kio; Barkovich, A James; Glenn, Orit A; Studholme, Colin

    2012-09-01

    To date, growth of the human fetal cerebellum has been estimated primarily from linear measurements from ultrasound and 2D magnetic resonance imaging (MRI). In this study, we use 3D analytical methods to develop normative growth trajectories for the cerebellum in utero. We measured cerebellar volume, linear dimensions, and local surface curvature from 3D reconstructed MRI of the human fetal brain (N = 46). We found that cerebellar volume increased approximately 7-fold from 20 to 31 gestational weeks. The better fit of the exponential curve (R (2) = 0.96) compared to the linear curve (R (2) = 0.92) indicated acceleration in growth. Within-subject cerebellar and cerebral volumes were highly correlated (R (2) = 0.94), though the cerebellar percentage of total brain volume increased from approximately 2.4% to 3.7% (R (2) = 0.63). Right and left hemispheric volumes did not significantly differ. Transcerebellar diameter, vermal height, and vermal anterior to posterior diameter increased significantly at constant rates. From the local curvature analysis, we found that expansion along the inferior and superior aspects of the hemispheres resulted in decreased convexity, which is likely due to the physical constraints of the dura surrounding the cerebellum and the adjacent brainstem. The paired decrease in convexity along the inferior vermis and increased convexity of the medial hemisphere represents development of the paravermian fissure, which becomes more visible during this period. In this 3D morphometric analysis of the human fetal cerebellum, we have shown that cerebellar growth is accelerating at a greater pace than the cerebrum and described how cerebellar growth impacts the shape of the structure.

  5. 3D Morphometric Analysis of Human Fetal Cerebellar Development

    PubMed Central

    Hamzelou, Kia S.; Rajagopalan, Vidya; Habas, Piotr A.; Kim, Kio; Barkovich, A. James; Glenn, Orit A.; Studholme, Colin

    2012-01-01

    To date, growth of the human fetal cerebellum has been estimated primarily from linear measurements from ultrasound and 2D magnetic resonance imaging (MRI). In this study, we use 3D analytical methods to develop normative growth trajectories for the cerebellum in utero. We measured cerebellar volume, linear dimensions, and local surface curvature from 3D reconstructed MRI of the human fetal brain (N = 46). We found that cerebellar volume increased approximately 7-fold from 20 to 31 gestational weeks. The better fit of the exponential curve (R2 = 0.96) compared to the linear curve (R2 = 0.92) indicated acceleration in growth. Within-subject cerebellar and cerebral volumes were highly correlated (R2 = 0.94), though the cerebellar percentage of total brain volume increased from approximately 2.4% to 3.7% (R2 = 0.63). Right and left hemispheric volumes did not significantly differ. Transcerebellar diameter, vermal height, and vermal anterior to posterior diameter increased significantly at constant rates. From the local curvature analysis, we found that expansion along the inferior and superior aspects of the hemispheres resulted in decreased convexity, which is likely due to the physical constraints of the dura surrounding the cerebellum and the adjacent brainstem. The paired decrease in convexity along the inferior vermis and increased convexity of the medial hemisphere represents development of the paravermian fissure, which becomes more visible during this period. In this 3D morphometric analysis of the human fetal cerebellum, we have shown that cerebellar growth is accelerating at a greater pace than the cerebrum and described how cerebellar growth impacts the shape of the structure. PMID:22198870

  6. Cerebellar cysts in children: a pattern recognition approach.

    PubMed

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

    2015-06-01

    Cerebellar cysts may be seen in selected genetic disorders and acquired anomalies. Here, we review our experience, excluding cystic tumors and parasitic cysts. The pathogenesis is heterogeneous: Cysts may involve/represent normal structures (e.g., Virchow-Robin spaces), be "destructive" (such as in some types of pontocerebellar hypoplasias), "malformative" (such as in some forms of congenital muscular dystrophies and GPR56-related migration disorders), or "disruptive" (such as in some cerebellar dysplasias). The provided checklist may be useful in deciding targeted diagnostic workup.

  7. Paraneoplastic cerebellar degeneration as a marker of endometrial cancer recurrence.

    PubMed

    Lie, Geoffrey; Morley, Thomas; Chowdhury, Muhammad

    2016-05-18

    An 84-year-old woman developed a cerebellar syndrome having undergone a total abdominal hysterectomy and bilateral salpingo-oophorectomy for endometrial cancer 1 year previously. She was found to be anti-Yo antibody positive and was diagnosed with paraneoplastic cerebellar degeneration (PCD). A subsequent positron emission tomography scan and lymph node biopsy identified recurrence of her endometrial cancer. This case illustrates how PCD can be an indicator of cancer recurrence, underlines the significance of PCD as a prompt to search for underlying malignancy, and highlights the difficulties PCD poses to the clinician in terms of diagnosis and management.

  8. [Type I Chiari malformation associated with cerebellar atrophy. Case report].

    PubMed

    Moscote-Salazar, Luis Rafael; Calderón-Miranda, Willem Guillermo; Alvis-Miranda, Hernando Raphael; Lee-Aguirre, Ángel; Alcalá-Cerra, Gabriel

    2017-01-01

    Chiari malformation is characterized by caudal displacement of the cerebellar tonsils that penetrate into the spinal canal through the foramen magnum, achieving reach the atlas or axis. trunk and any drop of the fourth ventricle is observed. Typically is seen in young adults. In some cases scoliosis and Syringomyelic cavities may occur. The authors present (as far as they know) the first case in the literature with long term follow-up, of a caucasian woman with an unusual form of cerebellar atrophy and Chiari Type I malformation, suffering from weakness in his upper and lower extremities with rapidly progression. The patient was successfully treated with suboccipital decompression and C1 laminectomy.

  9. Symptomatic cerebellar hemorrhage from recurrent hemangioblastoma during delivery. Case report.

    PubMed

    Hayashi, Shigeto; Takeda, Naoya; Komura, Eiji

    2010-01-01

    A 30-year-old woman suffered cerebellar hemorrhage during the delivery of her first child. She had undergone surgical removal of a symptomatic cerebellar hemangioblastoma 6 years previously. Neuroradiological examinations indicated recurrent hemangioblastoma, confirmed by histological examination of the surgical specimen. She was discharged with no neurological deficit. Hemangioblastomas are benign tumors that are curable with surgical removal, but can grow during pregnancy. Women of reproductive age who have been treated for hemangioblastoma need careful long-term follow up, even if they show no signs of lesion recurrence.

  10. [Anatomical and clinical correlations in the cerebellar eredodegeneration].

    PubMed

    Pea, Umberto; de Luca, Francesco; Nicola, Massimiliano; Galli, Luigi

    2003-06-01

    Spinocerebellar hereditary degeneration makes up a heterogeneous group of diseases headed by Strumpell-Lorrain syndrome and Friedreich's disease. They are a heterogeneous group characterized by spasticity and paraplegia and related to demyelinization of the pyramidal tract and of the posterior cordons. During a 4-year period, we studied 14 patients (42-61 years old) suffering cerebellar eredodegeneration (hereditary ataxia). The aim of our work was to correlate anatomopathological findings with clinical signs. The important role played by the cerebellum in vesicosphincterial coordination was shown; in particular severe alteration of the ponto-cerebellar bundles could be cause of the abnormal behaviour of the detrusor.

  11. 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.

  12. 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

  13. Organotypic brain slice cultures: A review.

    PubMed

    Humpel, C

    2015-10-01

    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.

  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. Mixed time slicing in path integral simulations

    NASA Astrophysics Data System (ADS)

    Steele, Ryan P.; Zwickl, Jill; Shushkov, Philip; Tully, John C.

    2011-02-01

    A simple and efficient scheme is presented for using different time slices for different degrees of freedom in path integral calculations. This method bridges the gap between full quantization and the standard mixed quantum-classical (MQC) scheme and, therefore, still provides quantum mechanical effects in the less-quantized variables. Underlying the algorithm is the notion that time slices (beads) may be "collapsed" in a manner that preserves quantization in the less quantum mechanical degrees of freedom. The method is shown to be analogous to multiple-time step integration techniques in classical molecular dynamics. The algorithm and its associated error are demonstrated on model systems containing coupled high- and low-frequency modes; results indicate that convergence of quantum mechanical observables can be achieved with disparate bead numbers in the different modes. Cost estimates indicate that this procedure, much like the MQC method, is most efficient for only a relatively few quantum mechanical degrees of freedom, such as proton transfer. In this regime, however, the cost of a fully quantum mechanical simulation is determined by the quantization of the least quantum mechanical degrees of freedom.

  16. Multilayer PDMS microfluidic chamber for controlling brain slice microenvironment.

    PubMed

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

    2007-07-01

    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 microm) 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.

  17. 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.

  18. 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…

  19. 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.

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

    PubMed

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

    2017-04-01

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

  1. 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

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

    PubMed Central

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

    2017-01-01

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

  3. Whole-Cell Properties of Cerebellar Nuclei Neurons In Vivo.

    PubMed

    Canto, Cathrin B; Witter, Laurens; De Zeeuw, Chris I

    2016-01-01

    Cerebellar nuclei neurons integrate sensorimotor information and form the final output of the cerebellum, projecting to premotor brainstem targets. This implies that, in contrast to specialized neurons and interneurons in cortical regions, neurons within the nuclei encode and integrate complex information that is most likely reflected in a large variation of intrinsic membrane properties and integrative capacities of individual neurons. Yet, whether this large variation in properties is reflected in a heterogeneous physiological cell population of cerebellar nuclei neurons with well or poorly defined cell types remains to be determined. Indeed, the cell electrophysiological properties of cerebellar nuclei neurons have been identified in vitro in young rodents, but whether these properties are similar to the in vivo adult situation has not been shown. In this comprehensive study we present and compare the in vivo properties of 144 cerebellar nuclei neurons in adult ketamine-xylazine anesthetized mice. We found regularly firing (N = 88) and spontaneously bursting (N = 56) neurons. Membrane-resistance, capacitance, spike half-width and firing frequency all widely varied as a continuum, ranging from 9.63 to 3352.1 MΩ, from 6.7 to 772.57 pF, from 0.178 to 1.98 ms, and from 0 to 176.6 Hz, respectively. At the same time, several of these parameters were correlated with each other. Capacitance decreased with membrane resistance (R2 = 0.12, P<0.001), intensity of rebound spiking increased with membrane resistance (for 100 ms duration R2 = 0.1503, P = 0.0011), membrane resistance decreased with membrane time constant (R2 = 0.045, P = 0.031) and increased with spike half-width (R2 = 0.023, P<0.001), while capacitance increased with firing frequency (R2 = 0.29, P<0.001). However, classes of neuron subtypes could not be identified using merely k-clustering of their intrinsic firing properties and/or integrative properties following activation of their Purkinje cell input

  4. Whole-Cell Properties of Cerebellar Nuclei Neurons In Vivo

    PubMed Central

    De Zeeuw, Chris I.

    2016-01-01

    Cerebellar nuclei neurons integrate sensorimotor information and form the final output of the cerebellum, projecting to premotor brainstem targets. This implies that, in contrast to specialized neurons and interneurons in cortical regions, neurons within the nuclei encode and integrate complex information that is most likely reflected in a large variation of intrinsic membrane properties and integrative capacities of individual neurons. Yet, whether this large variation in properties is reflected in a heterogeneous physiological cell population of cerebellar nuclei neurons with well or poorly defined cell types remains to be determined. Indeed, the cell electrophysiological properties of cerebellar nuclei neurons have been identified in vitro in young rodents, but whether these properties are similar to the in vivo adult situation has not been shown. In this comprehensive study we present and compare the in vivo properties of 144 cerebellar nuclei neurons in adult ketamine-xylazine anesthetized mice. We found regularly firing (N = 88) and spontaneously bursting (N = 56) neurons. Membrane-resistance, capacitance, spike half-width and firing frequency all widely varied as a continuum, ranging from 9.63 to 3352.1 MΩ, from 6.7 to 772.57 pF, from 0.178 to 1.98 ms, and from 0 to 176.6 Hz, respectively. At the same time, several of these parameters were correlated with each other. Capacitance decreased with membrane resistance (R2 = 0.12, P<0.001), intensity of rebound spiking increased with membrane resistance (for 100 ms duration R2 = 0.1503, P = 0.0011), membrane resistance decreased with membrane time constant (R2 = 0.045, P = 0.031) and increased with spike half-width (R2 = 0.023, P<0.001), while capacitance increased with firing frequency (R2 = 0.29, P<0.001). However, classes of neuron subtypes could not be identified using merely k-clustering of their intrinsic firing properties and/or integrative properties following activation of their Purkinje cell input

  5. 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.

  6. Thin slices of child personality: Perceptual, situational, and behavioral contributions.

    PubMed

    Tackett, Jennifer L; Herzhoff, Kathrin; Kushner, Shauna C; Rule, Nicholas

    2016-01-01

    The present study examined whether thin-slice ratings of child personality serve as a resource-efficient and theoretically valid measurement of child personality traits. We extended theoretical work on the observability, perceptual accuracy, and situational consistency of childhood personality traits by examining intersource and interjudge agreement, cross-situational consistency, and convergent, divergent, and predictive validity of thin-slice ratings. Forty-five unacquainted independent coders rated 326 children's (ages 8-12) personality in 1 of 15 thin-slice behavioral scenarios (i.e., 3 raters per slice, for over 14,000 independent thin-slice ratings). Mothers, fathers, and children rated children's personality, psychopathology, and competence. We found robust evidence for correlations between thin-slice and mother/father ratings of child personality, within- and across-task consistency of thin-slice ratings, and convergent and divergent validity with psychopathology and competence. Surprisingly, thin-slice ratings were more consistent across situations in this child sample than previously found for adults. Taken together, these results suggest that thin slices are a valid and reliable measure to assess child personality, offering a useful method of measurement beyond questionnaires, helping to address novel questions of personality perception and consistency in childhood.

  7. 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.

  8. [Design and accuracy analysis of upper slicing system of MSCT].

    PubMed

    Jiang, Rongjian

    2013-05-01

    The upper slicing system is the main components of the optical system in MSCT. This paper focuses on the design of upper slicing system and its accuracy analysis to improve the accuracy of imaging. The error of slice thickness and ray center by bearings, screw and control system were analyzed and tested. In fact, the accumulated error measured is less than 1 microm, absolute error measured is less than 10 microm. Improving the accuracy of the upper slicing system contributes to the appropriate treatment methods and success rate of treatment.

  9. Acute Diagnosis and Management of Stroke Presenting Dizziness or Vertigo.

    PubMed

    Lee, Seung-Han; Kim, Ji-Soo

    2015-08-01

    Stroke involving the brainstem and cerebellum frequently presents acute vestibular syndrome. Although vascular vertigo is known to usually accompany other neurologic symptoms and signs, isolated vertigo from small infarcts involving the cerebellum or brainstem has been increasingly recognized. Bedside neuro-otologic examination can reliably differentiate acute vestibular syndrome due to stroke from more benign inner ear disease. Sometimes acute isolated audiovestibular loss may herald impending infarction in the territory of the anterior inferior cerebellar artery. Accurate identification of isolated vascular vertigo is very important because misdiagnosis of acute stroke may result in significant morbidity and mortality.

  10. [Intraabdominal metastasis of cerebellar medulloblastoma through ventriculoperitoneal shunt].

    PubMed

    Carrasco Torrents, R; Sancho, M A; Juliá, V; Montaner, A; Costa, J M; Morales, L

    2001-01-01

    We present a 6-year-old girl with cerebellar medulloblastoma causing obstructive hydrocephalus that was treated by ventriculoperitoneal shunting. The patient subsequently underwent surgical excision of the tumor followed by adjuvant craniospinal radiotherapy. Nine months after shunting, multiple intraabdominal metastatic lesions were found. Although the risk is low, ventriculoperitoneal shunting may facilitate the spread of malignant cells.

  11. Cerebro-cerebellar interactions underlying temporal information processing.

    PubMed

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

    2010-12-01

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

  12. 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…

  13. Transcranial magnetic stimulation in patients with cerebellar stroke.

    PubMed

    Cruz-Martínez, A; Arpa, J

    1997-01-01

    Conduction time of the central motor pathways (CMCT) by transcranial magnetic stimulation (TMS) was performed within the first two weeks in 7 patients with isolated hemicerebellar lesions after stroke. Cerebellar infarcts were small (< 2 cm in diameter) in 5 patients and no brainstem structure was involved in CT studies. The threshold (3 cases) and CMCT (4 cases) were abnormal or asymmetric by stimulation of the motor cortex contralateral to the impaired hemicerebellum. The follow-up study in 2 patients revealed electrophysiological improvement closely related to clinical cerebellar recovery rate. CMCT was significantly longer by cortex stimulation contralateral to the impaired hemicerebellum than by ipsilateral stimulation. Prolonged CMCT was significantly correlated with the rated severity of cerebellar signs. Increased threshold may be due to depressed facilitating action of the deep cerebellar nuclei on contralateral motor cortex. Abnormal CMCT might result in reduced size and increased dispersion of the efferent volleys. Recovery of electrophysiological results could represent in part true potentially reversible functional deficit. Whichever the pathophysiological mechanisms involved, our results demonstrate that the cerebellum dysfunction plays a role in the abnormalities of CMCT elicited by TMS.

  14. The Contribution of Brainstem and Cerebellar Pathways to Auditory Recognition

    PubMed Central

    McLachlan, Neil M.; Wilson, Sarah J.

    2017-01-01

    The cerebellum has been known to play an important role in motor functions for many years. More recently its role has been expanded to include a range of cognitive and sensory-motor processes, and substantial neuroimaging and clinical evidence now points to cerebellar involvement in most auditory processing tasks. In particular, an increase in the size of the cerebellum over recent human evolution has been attributed in part to the development of speech. Despite this, the auditory cognition literature has largely overlooked afferent auditory connections to the cerebellum that have been implicated in acoustically conditioned reflexes in animals, and could subserve speech and other auditory processing in humans. This review expands our understanding of auditory processing by incorporating cerebellar pathways into the anatomy and functions of the human auditory system. We reason that plasticity in the cerebellar pathways underpins implicit learning of spectrotemporal information necessary for sound and speech recognition. Once learnt, this information automatically recognizes incoming auditory signals and predicts likely subsequent information based on previous experience. Since sound recognition processes involving the brainstem and cerebellum initiate early in auditory processing, learnt information stored in cerebellar memory templates could then support a range of auditory processing functions such as streaming, habituation, the integration of auditory feature information such as pitch, and the recognition of vocal communications. PMID:28373850

  15. 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.

  16. Early degeneration of the cerebellar cortex, particularly the granular cells.

    PubMed

    Bugiani, O; Berio, A; Di Stefano, A; Mangiante, G; Mancardi, G L; Leonardi, A

    1978-12-07

    An 8 month old infant, who died of severe gastroenteritis, presented a degeneration of the cerebellar cortex involving cells arising from the outer granular layer as well as Purkinje and Golgi II cells. Residual Purkinje cells showed vacuolar change of the cell body and dendritic abnormalities. Related lesions were atrophy of the inferior olives and degeneration of the mossy fibers.

  17. 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

  18. Caytaxin deficiency disrupts signaling pathways in cerebellar cortex.

    PubMed

    Xiao, J; Gong, S; Ledoux, M S

    2007-01-19

    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 sites 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 reverse transcriptase-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 plasma membrane calcium-dependent 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.

  19. 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…

  20. Cerebellar rTMS disrupts predictive language processing

    PubMed Central

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

    2012-01-01

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

  1. Bilateral cerebellar activation in unilaterally challenged essential tremor.

    PubMed

    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

    2016-01-01

    •We added EMG as an index of tremor intensity to fMRI to study essential tremor.•Block- and tremor-related activations during a unilateral motor task were separated.•Block-related activations were found in the classical motor network.•Tremor-related activations were found in bilateral cerebellar lobules V, VI and VIII.

  2. Arachnodactyly, aminoaciduria, congenital cataracts, cerebellar ataxia, and delayed developmental milestones

    PubMed Central

    Bhaskar, P. A.; Jagannathan, K.; Valmikinathan, K.

    1974-01-01

    Two male cousins are reported with arachnodactyly, selective aminoaciduria, congenital cataracts, cerebellar ataxia, and delayed developmental milestones, and a distant female relative with similar abnormalities. The syndrome is thought to be previously undescribed, though it has resemblances to Marinesco-Sjögren and Marfan's syndromes. Images PMID:4448994

  3. 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

  4. The Contribution of Brainstem and Cerebellar Pathways to Auditory Recognition.

    PubMed

    McLachlan, Neil M; Wilson, Sarah J

    2017-01-01

    The cerebellum has been known to play an important role in motor functions for many years. More recently its role has been expanded to include a range of cognitive and sensory-motor processes, and substantial neuroimaging and clinical evidence now points to cerebellar involvement in most auditory processing tasks. In particular, an increase in the size of the cerebellum over recent human evolution has been attributed in part to the development of speech. Despite this, the auditory cognition literature has largely overlooked afferent auditory connections to the cerebellum that have been implicated in acoustically conditioned reflexes in animals, and could subserve speech and other auditory processing in humans. This review expands our understanding of auditory processing by incorporating cerebellar pathways into the anatomy and functions of the human auditory system. We reason that plasticity in the cerebellar pathways underpins implicit learning of spectrotemporal information necessary for sound and speech recognition. Once learnt, this information automatically recognizes incoming auditory signals and predicts likely subsequent information based on previous experience. Since sound recognition processes involving the brainstem and cerebellum initiate early in auditory processing, learnt information stored in cerebellar memory templates could then support a range of auditory processing functions such as streaming, habituation, the integration of auditory feature information such as pitch, and the recognition of vocal communications.

  5. 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.

  6. 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 882.5820 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5820...

  7. 21 CFR 882.5820 - Implanted cerebellar stimulator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted cerebellar stimulator. 882.5820 Section 882.5820 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5820...

  8. 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 882.5820 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5820...

  9. 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…

  10. 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

  11. 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…

  12. 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.

  13. 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

  14. Spectral slicing X-ray telescope

    NASA Technical Reports Server (NTRS)

    Hoover, R. B.; Shealy, D.; Chao, S.-H.

    1986-01-01

    Layered synthetic microstructure (LSM) X-ray optics is investigated as a system for coupling a conventional glancing incidence X-ray mirror to a high sensitivity X-ray detector. It is shown that, by the use of figured LSM optics, it is possible to magnify the X-ray image produced by the primary mirrors so as to maintain their high inherent spatial resolution. The results of theoretical and design analyses of several spectral slicing X-ray telescope systems that utilize LSM mirrors of hyperboloidal, spherical, ellipsoidal, and constant optical path aspheric configurations are presented. It is shown that the spherical LSM optics are the preferred configuration, yielding subarcsecond performance over the entire field. The Stanford/Marshall Space Flight Center Rocket X-ray Telescope, which will utilize normal incidence LSM optics to couple a Wolter-Schwarzschild primary mirror to high resolution detectors for solar X-ray/EUV studies, is discussed. Design diagrams are included.

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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

  20. Neuroimaging Evidence of Cerebellar Involvement in Premenstrual Dysphoric Disorder

    PubMed Central

    Rapkin, Andrea J.; Berman, Steven M.; Mandelkern, Mark A.; Silverman, Daniel H. S.; Morgan, Melinda; London, Edythe D.

    2010-01-01

    Background Premenstrual dysphoric disorder (PMDD) is a debilitating cyclic disorder that is characterized by affective symptoms, including irritability, depression, and anxiety which arise in the luteal phase of the menstrual cycle and resolve soon after the onset of menses. Despite a prevalence of up to 8% in women of reproductive age, few studies have investigated the brain mechanisms that underlie this disorder. Methods We used positron emission tomography with [18F] fluorodeoxyglucose and self-report questionnaires to assess cerebral glucose metabolism and mood in 12 women with PMDD and 12 healthy comparison subjects in the follicular and late luteal phases of the menstrual cycle. The primary biological endpoint was incorporated regional cerebral radioactivity (scaled to the global mean) as an index of glucose metabolism. Relationships between regional brain activity and mood ratings were assessed. Blood samples were taken before each session for assay of plasma estradiol and progesterone concentrations. Results There were no group differences in hormone levels in either the follicular or late luteal phase, but the groups differed in the effect of menstrual phase on cerebellar activity. Women with PMDD, but not comparison subjects, showed an increase in cerebellar activity (particularly in the right cerebellar vermis) from the follicular phase to the late luteal phase (p = 0.003). In the PMDD group, this increase in cerebellar activity was correlated with worsening of mood (p = 0.018). Conclusions These findings suggest that the midline cerebellar nuclei, which have been implicated in other mood disorders, also contribute to negative mood in PMDD. PMID:21092938

  1. 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.

  2. 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.

  3. Organotypic slice cultures for studies of postnatal neurogenesis.

    PubMed

    Mosa, Adam J; Wang, Sabrina; Tan, Yao Fang; Wojtowicz, J Martin

    2015-03-04

    Here we describe a technique for studying hippocampal postnatal neurogenesis in the rodent brain using the organotypic slice culture technique. This method maintains the characteristic topographical morphology of the hippocampus while allowing direct application of pharmacological agents to the developing hippocampal dentate gyrus. Additionally, slice cultures can be maintained for up to 4 weeks and thus, allow one to study the maturation process of newborn granule neurons. Slice cultures allow for efficient pharmacological manipulation of hippocampal slices while excluding complex variables such as uncertainties related to the deep anatomic location of the hippocampus as well as the blood brain barrier. For these reasons, we sought to optimize organotypic slice cultures specifically for postnatal neurogenesis research.

  4. Acetic acid pretreatment improves the hardness of cooked potato slices.

    PubMed

    Zhao, Wenlin; Shehzad, Hussain; Yan, Shoulei; Li, Jie; Wang, Qingzhang

    2017-08-01

    The effects of acetic acid pretreatment on the texture of cooked potato slices were investigated in this work. Potato slices were pretreated with acetic acid immersion (AAI), distilled water immersion (DWI), or no immersion (NI). Subsequently, the cell wall material of the pretreated samples was isolated and fractioned to evaluate changes in the monosaccharide content and molar mass (MM), and the hardness and microscopic structure of the potato slices in different pretreatments before and after cooking were determined. The results showed that the highest firmness was obtained with more intact structure of the cell wall for cooked potato slices with AAI pretreatment. Furthermore, the MM and sugar ratio demonstrated that the AAI pretreated potato slices contained a higher content of the small molecular polysaccharides of cell walls, especially in the hemicellulose fraction. This work may provide a reference for potato processing.

  5. Organotypic Slice Cultures for Studies of Postnatal Neurogenesis

    PubMed Central

    Mosa, Adam J.; Wang, Sabrina; Tan, Yao Fang; Wojtowicz, J. Martin

    2015-01-01

    Here we describe a technique for studying hippocampal postnatal neurogenesis in the rodent brain using the organotypic slice culture technique. This method maintains the characteristic topographical morphology of the hippocampus while allowing direct application of pharmacological agents to the developing hippocampal dentate gyrus. Additionally, slice cultures can be maintained for up to 4 weeks and thus, allow one to study the maturation process of newborn granule neurons. Slice cultures allow for efficient pharmacological manipulation of hippocampal slices while excluding complex variables such as uncertainties related to the deep anatomic location of the hippocampus as well as the blood brain barrier. For these reasons, we sought to optimize organotypic slice cultures specifically for postnatal neurogenesis research. PMID:25867138

  6. 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.

  7. 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.

  8. Development of cerebellar neurons and glias revealed by in utero electroporation: Golgi-like labeling of cerebellar neurons and glias.

    PubMed

    Kita, Yoshiaki; Kawakami, Koichi; Takahashi, Yoshiko; Murakami, Fujio

    2013-01-01

    Cerebellar cortical functions rely on precisely arranged cytoarchitectures composed of several distinct types of neurons and glias. Studies have indicated that cerebellar excitatory and inhibitory neurons have distinct spatial origins, the upper rhombic lip (uRL) and ventricular zone (VZ), respectively, and that different types of neurons have different birthdates. However, the spatiotemporal relationship between uRL/VZ progenitors and their final phenotype remains poorly understood due to technical limitations. To address this issue, we performed in utero electroporation (IUE) of fluorescent protein plasmids using mouse embryos to label uRL/VZ progenitors at specific developmental stages, and observed labeled cells at maturity. To overcome any potential dilution of the plasmids caused by progenitor division, we also utilized constructs that enable permanent labeling of cells. Cerebellar neurons and glias were labeled in a Golgi-like manner enabling ready identification of labeled cells. Five types of cerebellar neurons, namely Purkinje, Golgi, Lugaro and unipolar brush cells, large-diameter deep nuclei (DN) neurons, and DN astrocytes were labeled by conventional plasmids, whereas plasmids that enable permanent labeling additionally labeled stellate, basket, and granule cells as well as three types of glias. IUE allows us to label uRL/VZ progenitors at different developmental stages. We found that the five types of neurons and DN astrocytes were labeled in an IUE stage-dependent manner, while stellate, basket, granule cells and three types of glias were labeled regardless of the IUE stage. Thus, the results indicate the IUE is an efficient method to track the development of cerebellar cells from uRL/VZ progenitors facing the ventricular lumen. They also indicate that while the generation of the five types of neurons by uRL/VZ progenitors is regulated in a time-dependent manner, the progenitor pool retains multipotency throughout embryonic development.

  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. 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

    2015-09-18

    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.

  11. Cerebellar white matter pathways are associated with reading skills in children and adolescents.

    PubMed

    Travis, Katherine E; Leitner, Yael; Feldman, Heidi M; Ben-Shachar, Michal

    2015-04-01

    Reading is a critical life skill in the modern world. The neural basis of reading incorporates a distributed network of cortical areas and their white matter connections. The cerebellum has also been implicated in reading and reading disabilities. However, little is known about the contribution of cerebellar white matter pathways to major component skills of reading. We used diffusion magnetic resonance imaging (dMRI) with tractography to identify the cerebellar peduncles in a group of 9- to 17-year-old children and adolescents born full term (FT, n = 19) or preterm (PT, n = 26). In this cohort, no significant differences were found between fractional anisotropy (FA) measures of the peduncles in the PT and FT groups. FA of the cerebellar peduncles correlated significantly with measures of decoding and reading comprehension in the combined sample of FT and PT subjects. Correlations were negative in the superior and inferior cerebellar peduncles and positive in the middle cerebellar peduncle. Additional analyses revealed that FT and PT groups demonstrated similar patterns of reading associations within the left superior cerebellar peduncle, middle cerebellar peduncle, and left inferior cerebellar peduncle. Partial correlation analyses showed that distinct sub-skills of reading were associated with FA in segments of different cerebellar peduncles. Overall, the present findings are the first to document associations of microstructure of the cerebellar peduncles and the component skills of reading.

  12. 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

  13. A-Type potassium currents active at subthreshold potentials in mouse cerebellar purkinje cells

    PubMed Central

    Sacco, Tiziana; Tempia, Filippo

    2002-01-01

    Voltage-dependent and calcium-independent K+ currents were whole-cell recorded from cerebellar Purkinje cells in slices. Tetraethylammonium (TEA, 4 mm) application isolated an A-type K+ current (Ik(a)) with a peak amplitude, at +20 mV, of about one third of the total voltage-dependent and calcium-independent K+ current. The Ik(a) activated at about −60 mV, had a V0.5 of activation of −24.9 mV and a V0.5 of inactivation of −69.2 mV. The deactivation time constant at −70 mV was 3.4 ± 0.4 ms, while the activation time constant at +20 mV was 0.9 ± 0.2 ms. The inactivation kinetics was weakly voltage dependent, with two time constants; those at +20 mV were 19.3 ± 3.1 and 97.6 ± 9.8 ms. The recovery from inactivation had two time constants of 60.8 ms (78.4%) and 962.3 ms (21.6%). The Ik(a) was blocked by 4-aminopyridine with an IC50 of 67.6 μM. Agitoxin-2 (2 nm) blocked 17.4 ± 2.1% of the Ik(a). Flecainide completely blocked the Ik(a) with a biphasic effect with IC50 values of 4.4 and 183.2 μM. In current-clamp recordings the duration of evoked action potentials was affected neither by agitoxin-2 (2 nm) nor by flecainide (3 μM), but action potentials that were already broadened by TEA were further prolonged by 4-aminopyridine (100 μM). The amplitude of the hyperpolarisation at the end of depolarising steps was reduced by all these blockers. PMID:12205185

  14. Simultaneous multi-slice excitation by parallel transmission

    PubMed Central

    Poser, Benedikt A.; Anderson, Robert James; Guérin, Bastien; Setsompop, Kawin; Deng, Weiran; Mareyam, Azma; Serano, Peter; Wald, Lawrence L.; Stenger, V. Andrew

    2013-01-01

    Purpose A technique is described for simultaneous multi-slice (SMS) excitation using radiofrequency (RF) parallel transmission (pTX). Methods Spatially distinct slices are simultaneously excited by applying different RF frequencies on groups of elements of a multi-channel transmit array. The localized transmit sensitivities of the coil geometry are thereby exploited to reduce RF power. The method is capable of achieving SMS-excitation using single-slice RF pulses, or multi-band pulses. SMS-pTX is demonstrated using eight-channel parallel RF transmission on a dual-ring pTX coil at 3 T. The effect on B1+ homogeneity and SAR is evaluated experimentally and by simulations. Slice-GRAPPA reconstruction was used for separation of the collapsed slice signals. Results Phantom and in vivo brain data acquired with FLASH and blipped-CAIPIRINHA EPI are presented at SMS excitation factors of two, four and six. We also show that with our pTX coil design, slice placement and binary division of transmitters, SMS-pTX excitations can achieve the same mean flip angles excitations at approximately 30% lower RF power than a conventional SMS approach with multi-band RF pulses. Conclusion The proposed SMS-pTX allows simultaneous multi-slice excitations at reduced RF power by exploiting the local B1+ sensitivities of suitable multi-element pTX arrays. PMID:23716365

  15. Slice Culture Modeling of Central Nervous System (CNS) Viral Infection

    PubMed Central

    Dionne, Kalen R.; Tyler, Kenneth L.

    2016-01-01

    The complexity of the central nervous system (CNS) is not recapitulated in cell culture models. Thin slicing and subsequent culture of CNS tissue has become a valued means to study neuronal and glial biology within the context of the physiologically relevant tissue milieu. Modern membrane-interface slice culturing methodology allows straightforward access to both CNS tissue and feeding medium, enabling experimental manipulations and analyses that would otherwise be impossible in vivo. CNS slices can be successfully maintained in culture for up to several weeks for investigation of evolving pathology and long-term intervention in models of chronic neurologic disease. Herein, membrane-interface slice culture models for studying viral encephalitis and myelitis are detailed, with emphasis on the use of these models for investigation of pathogenesis and evaluation of novel treatment strategies. We describe techniques to (1) generate brain and spinal cord slices from rodent donors, (2) virally infect slices, (3) monitor viral replication, (4) assess virally induced injury/apoptosis, (5) characterize “CNS-specific” cytokine production, and (6) treat slices with cytokines/pharmaceuticals. Although our focus is on CNS viral infection, we anticipate that the described methods can be adapted to address a wide range of investigations within the fields of neuropathology, neuroimmunology, and neuropharmacology. PMID:23975824

  16. Cerebellar deficits and hyperactivity in mice lacking Smad4.

    PubMed

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

    2003-10-24

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

  17. 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

  18. 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.

  19. 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

  20. Cerebellar cognitive affective syndrome presented as severe borderline personality disorder.

    PubMed

    Pesic, Danilo; Peljto, Amir; Lukic, Biljana; Milovanovic, Maja; Svetozarevic, Snezana; Lecic Tosevski, Dusica

    2014-01-01

    An increasing number of findings confirm the significance of cerebellum in affecting regulation and early learning. Most consistent findings refer to association of congenital vermis anomalies with deficits in nonmotor functions of cerebellum. In this paper we presented a young woman who was treated since sixteen years of age for polysubstance abuse, affective instability, and self-harming who was later diagnosed with borderline personality disorder. Since the neurological and neuropsychological reports pointed to signs of cerebellar dysfunction and dysexecutive syndrome, we performed magnetic resonance imaging of brain which demonstrated partially developed vermis and rhombencephalosynapsis. These findings match the description of cerebellar cognitive affective syndrome and show an overlap with clinical manifestations of borderline personality disorder.

  1. Motor training compensates for cerebellar dysfunctions caused by oligodendrocyte ablation

    PubMed Central

    Collin, Ludovic; Usiello, Alessandro; Erbs, Eric; Mathis, Carole; Borrelli, Emiliana

    2004-01-01

    The role played by oligodendrocytes (OLs), the myelinating cells of the CNS, during brain development has not been fully explored. We have addressed this question by inducing a temporal and reversible ablation of OLs on postnatal CNS development. OL ablation in newborn mice leads to a profound alteration in the structure of the cerebellar cortex, which can be progressively rescued by newly generated cells, leading to a delayed myelination. Nevertheless, the temporal shift of the OL proliferation and myelinating program cannot completely compensate for developmental defects, resulting in impaired motor functions in the adult. Strikingly, we show that, despite these abnormalities, epigenetic factors, such as motor training, are able to fully rescue cerebellar-directed motor skills. PMID:14694200

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

    PubMed

    Suarez, H; Caffa, C; Macadar, O

    1992-01-01

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

  3. Slices method to describe ray propagation in inhomogeneous media

    NASA Astrophysics Data System (ADS)

    Aguilar-Gutiérrez, J. F.; Arroyo Carrasco, M. L.; Iturbe-Castillo, M. D.

    2017-01-01

    We describe an alternative method that numerically calculates the trajectory followed by a light ray in rotationally symmetric inhomogeneous media in the paraxial approximation. The medium is divided into thin parallel slices and a radial quadratic refractive index is considered for each slice. The ABCD matrix is calculated in each slice and the trajectory of the ray was obtained. The method is demonstrated considering media with a refractive index distribution used to describe the human eye lens. The results are compared with the exact numerical solution for each particular distribution. In all cases, a good agreement is obtained for the proposed method and the exact numerical solution.

  4. Evidence for distinct cognitive deficits after focal cerebellar lesions

    PubMed Central

    Gottwald, B; Wilde, B; Mihajlovic, Z; Mehdorn, H

    2004-01-01

    Objectives: Anatomical evidence and lesion studies, as well as functional magnetic resonance imaging (fMRI) studies, indicate that the cerebellum contributes to higher cognitive functions. Cerebellar posterior lateral regions seem to be relevant for cognition, while vermal lesions seem to be associated with changes in affect. However, the results remain controversial. Deficits of patients are sometimes still attributed to motor impairment. Methods: We present data from a detailed neuropsychological examination of 21 patients with cerebellar lesions due to tumour or haematoma, and 21 controls matched for age, sex, and years of education. Results: Patients showed deficits in executive function, and in attentional processes such as working memory and divided attention. Further analysis revealed that patients with right-sided lesions were in general more impaired than those with left-sided lesions. Conclusions: Those hypotheses that suggest that lesions of the right cerebellar hemisphere lead to verbal deficits, while those of the left lead to non-verbal deficits, have in part been confirmed. The generally greater impairment of those patients with a right-sided lesion has been interpreted as resulting from the connection of the right cerebellum to the left cerebral hemisphere, which is dominant for language functions and crucial for right hand movements. Motor impairment was correlated with less than half of the cognitive measures, with no stronger tendency for correlation with cognitive tests that require motor responses discernible. The results are discussed on the basis of an assumption that the cerebellum has a predicting and preparing function, indicating that cerebellar lesions lead to a "dysmetria of thought." PMID:15489381

  5. Familial Aggregation of the Cerebellar Signs in Familial Essential Tremor

    PubMed Central

    Louis, Elan D.; Hernandez, Nora; Chen, Karen P.; Naranjo, Kelly V.; Park, Jemin; Clark, Lorraine N.; Ottman, Ruth

    2017-01-01

    Background Although the hallmark feature of essential tremor (ET) is kinetic tremor, patients may exhibit additional motor features (e.g., intention tremor and mild gait ataxia) that are markers of an underlying abnormality of cerebellar function. ET is also a highly familial disorder, but we do not know whether the presence and expression of cerebellar signs are similar across family members. There are simply no published data. The alternative possibility is that these features are not heritable. We tested the specific hypothesis that the presence of cerebellar signs (i.e., intention tremor, tandem gait difficulty) ran in ET families. Methods ET probands and relatives enrolled in a genetic study at Yale and Columbia universities underwent a detailed videotaped neurological examination. Results There were 187 enrollees (59 probands, 128 affected relatives). In a bivariate logistic regression model, the presence of intention tremor in the proband was not a predictor of the presence of intention tremor in the relatives (odds ratio [OR] = 0.60, 95% confidence interval [CI] = 0.28–1.27, p = 0.18). In a similar model, the presence of greater tandem gait difficulty (i.e., a tandem gait score in the upper quartile) in the proband was not a predictor of the presence of such difficulty in the relatives (OR = 1.22, 95% CI = 0.41–3.66, p = 0.73). Discussion The presence of cerebellar signs did not aggregate in families with ET. In the current dataset, these did not seem to be disease features that were heritable. PMID:28176975

  6. 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

  7. Sensitivity of cerebellar glutathione system to neonatal ionizing radiation exposure.

    PubMed

    Di Toro, C G; Di Toro, P A; Zieher, L M; Guelman, L R

    2007-05-01

    Reactive oxygen species (ROS) are relevant components of living organisms that, besides their role in the regulation of different important physiological functions, when present in excess are capable to affect cell oxidative status, leading to damage of cellular molecules and disturbance of normal cell function. ROS accumulation has been associated with a variety of conditions such as neurodegenerative diseases and ionizing radiation exposure. Cell ability to counteract ROS overproduction depends on the capacity of the endogenous antioxidant defenses--which includes the glutathione (GSH) system--to cope with. Since developing central nervous system (CNS) is especially sensitive to ROS-induced damage, the aim of the present work was to evaluate ROS, reduced GSH and oxidized glutathione (GSSG) levels in the cerebellum at different developmental ages after irradiation, in order to test if any changes were induced on these key oxidative stress-related cellular markers that might explain the high cerebellar vulnerability to radiation-induced injury. Since intracellular levels of GSH are maintained by glutathione reductase (GSHr), this enzymatic activity was also evaluated. Newborn Wistar rats were irradiated in their cephalic ends and the different parameters were measured, from 1h to 90 days post-irradiation. Results showed that an early transient increase in ROS levels followed by a decrease in cerebellar weight at 3-5 days post-irradiation were induced. An increase in cerebellar GSH levels was induced at 30 days after irradiation, together with a decrease in GSHr activity. These results support the hypothesis that ROS may represent a marker of damage prior to radiation-induced cell death. In contrast, it would be suggested that GSH system might play a role in the compensatory mechanisms triggered to counteract radiation-induced cerebellar damage.

  8. Endogenous cerebellar neurogenesis in adult mice with progressive ataxia

    PubMed Central

    Kumar, Manoj; Csaba, Zsolt; Peineau, Stéphane; Srivastava, Rupali; Rasika, Sowmyalakshmi; Mani, Shyamala; Gressens, Pierre; El Ghouzzi, Vincent

    2014-01-01

    Objective Transplanting exogenous neuronal progenitors to replace damaged neurons in the adult brain following injury or neurodegenerative disorders and achieve functional amelioration is a realistic goal. However, studies so far have rarely taken into consideration the preexisting inflammation triggered by the disease process that could hamper the effectiveness of transplanted cells. Here, we examined the fate and long-term consequences of human cerebellar granule neuron precursors (GNP) transplanted into the cerebellum of Harlequin mice, an adult model of progressive cerebellar degeneration with early-onset microgliosis. Methods Human embryonic stem cell-derived progenitors expressing Atoh1, a transcription factor key to GNP specification, were generated in vitro and stereotaxically transplanted into the cerebellum of preataxic Harlequin mice. The histological and functional impact of these transplants was followed using immunolabeling and Rotarod analysis. Results Although transplanted GNPs did not survive beyond a few weeks, they triggered the proliferation of endogenous nestin-positive precursors in the leptomeninges that crossed the molecular layer and differentiated into mature neurons. These phenomena were accompanied by the preservation of the granule and Purkinje cell layers and delayed ataxic changes. In vitro neurosphere generation confirmed the enhanced neurogenic potential of the cerebellar leptomeninges of Harlequin mice transplanted with exogenous GNPs. Interpretation The cerebellar leptomeninges of adult mice contain an endogenous neurogenic niche that can be stimulated to yield mature neurons from an as-yet unidentified population of progenitors. The transplantation of human GNPs not only stimulates this neurogenesis, but, despite the potentially hostile environment, leads to neuroprotection and functional amelioration. PMID:25574472

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

    PubMed

    Adorno, Juan Oscar Alarcón; de Andrade, Guilherme Cabral

    2002-12-01

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

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

    PubMed

    Pallud, Johan; Belaïd, Hayat; Aldea, Sorin

    2009-06-01

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

  11. Maternal Postsecondary Education Associated With Improved Cerebellar Growth After Preterm Birth.

    PubMed

    Stiver, Mikaela L; Kamino, Daphne; Guo, Ting; Thompson, Angela; Duerden, Emma G; Taylor, Margot J; Tam, Emily W Y

    2015-10-01

    The preterm cerebellum is vulnerable to impaired development impacting long-term outcome. Preterm newborns (<32 weeks) underwent serial magnetic resonance imaging (MRI) scans. The association between parental education and cerebellar volume at each time point was assessed, adjusting for age at scan. In 26 infants, cerebellar volumes at term (P = .001), but not birth (P = .4), were associated with 2-year volumes. For 1 cm(3) smaller cerebellar volume (4% total volume) at term, the cerebellum was 3.18 cm(3) smaller (3% total volume) by 2 years. Maternal postsecondary education was not associated with cerebellar volume at term (P = .16). Maternal postsecondary education was a significant confounder in the relationship between term and 2-year cerebellar volumes (P = .016), with higher education associated with improved volumes by 2 years. Although preterm birth has been found to be associated with smaller cerebellar volumes at term, maternal postsecondary education is associated with improved growth detectable by 2 years.

  12. Cerebellar cortical degeneration with selective granule cell loss in Bavarian mountain dogs.

    PubMed

    Flegel, T; Matiasek, K; Henke, D; Grevel, V

    2007-08-01

    Three Bavarian mountain dogs aged between 18 and 20 months, not related to each other, were presented with chronic signs of cerebellar dysfunction. On sagittal T2-weighted magnetic resonance imaging brain images, the tentative diagnosis of cerebellar hypoplasia was established based on an enlarged cerebrospinal fluid space around the cerebellum and an increased cerebrospinal fluid signal between the folia. Post-mortem examination was performed in one dog and did show an overall reduction of cerebellar size. On histopathologic examination, a selective loss of cerebellar granule cells with sparing of Purkinje cells was evident. Therefore, the Bavarian mountain dog is a breed where cerebellar cortical degeneration caused by the rather exceptional selective granule cell loss can be seen as cause of chronic, slowly progressive cerebellar dysfunction starting at an age of several months.

  13. Controversies in the neurosurgical management of cerebellar hemorrhage and infarction.

    PubMed

    Amar, Arun Paul

    2012-04-01

    Evidence-based guidelines for the management of hemorrhagic and ischemic cerebellar stroke are sparse, and most available data come from Class III studies. As a result, opinions and practices regarding the nature and role of neurosurgical intervention vary widely. A comprehensive literature review was conducted to adjudicate several contentious issues, such as the difference in the management of cerebellar hemorrhage versus infarction, criteria for imaging to exclude an underlying structural lesion, the value of MRI for patient selection, the role of external ventricular drainage, the indications for operative management, the timing of surgical intervention, and various options of surgical technique, among others. Treatment algorithms proposed in several different studies are compared and contrasted. This analysis is concluded by a summary of the recommendations from the American Stroke Association, which advises that patients with cerebellar hemorrhage who experience neurological deterioration or who have brainstem compression and/or hydrocephalus due to ventricular obstruction should undergo surgical evacuation of the hemorrhage as soon as possible, and that initial treatment of such patients with ventricular drainage alone rather than surgical removal of the hemorrhage is not recommended.

  14. 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

  15. 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.

  16. 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.

  17. Monoaminergic modulation of GABAergic transmission onto cerebellar globular cells.

    PubMed

    Hirono, Moritoshi; Nagao, Soichi; Yanagawa, Yuchio; Konishi, Shiro

    2017-03-11

    Cerebellar Purkinje cells (PCs) project their axon collaterals to underneath of the PC layer and make GABAergic synaptic contacts with globular cells, a subgroup of Lugaro cells. GABAergic transmission derived from the PC axon collaterals is so powerful that it could inhibit globular cells and regulate their firing patterns. However, the physiological properties and implications of the GABAergic synapses on globular cells remain unknown. Using whole-cell patch-clamp recordings from globular cells in the mouse cerebellum, we examined the monoaminergic modulation of GABAergic inputs to these cells. Application of either serotonin (5-HT) or noradrenaline (NA) excited globular cells, thereby leading to their firing. The 5-HT- and NA-induced firing was temporally confined and attenuated by GABAergic transmission, although 5-HT and NA exerted an inhibitory effect on the release of GABA from presynaptic terminals of PC axon collaterals. Agonists for 5-HT1B receptors and α2-adrenoceptors mimicked the 5-HT- and NA-induced suppression of GABAergic activity. Through their differential modulatory actions on the cerebellar inhibitory neural circuits, 5-HT facilitated PC firing, whereas NA suppressed it. These results indicate that 5-HT and NA regulate the membrane excitability of globular cells and PCs through their differential modulation of not only the membrane potential but also GABAergic synaptic circuits. Monoaminergic modulation of the neural connections between globular cells and PCs could play a role in cerebellar motor coordination.

  18. 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.

  19. 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

  20. Junctophilin-mediated channel crosstalk essential for cerebellar synaptic plasticity

    PubMed Central

    Kakizawa, Sho; Kishimoto, Yasushi; Hashimoto, Kouichi; Miyazaki, Taisuke; Furutani, Kazuharu; Shimizu, Hidemi; Fukaya, Masahiro; Nishi, Miyuki; Sakagami, Hiroyuki; Ikeda, Atsushi; Kondo, Hisatake; Kano, Masanobu; Watanabe, Masahiko; Iino, Masamitsu; Takeshima, Hiroshi

    2007-01-01

    Functional crosstalk between cell-surface and intracellular ion channels plays important roles in excitable cells and is structurally supported by junctophilins (JPs) in muscle cells. Here, we report a novel form of channel crosstalk in cerebellar Purkinje cells (PCs). The generation of slow afterhyperpolarization (sAHP) following complex spikes in PCs required ryanodine receptor (RyR)-mediated Ca2+-induced Ca2+ release and the subsequent opening of small-conductance Ca2+-activated K+ (SK) channels in somatodendritic regions. Despite the normal expression levels of these channels, sAHP was abolished in PCs from mutant mice lacking neural JP subtypes (JP-DKO), and this defect was restored by exogenously expressing JPs or enhancing SK channel activation. The stimulation paradigm for inducing long-term depression (LTD) at parallel fiber–PC synapses adversely established long-term potentiation in the JP-DKO cerebellum, primarily due to the sAHP deficiency. Furthermore, JP-DKO mice exhibited impairments of motor coordination and learning, although normal cerebellar histology was retained. Therefore, JPs support the Ca2+-mediated communication between voltage-gated Ca2+ channels, RyRs and SK channels, which modulates the excitability of PCs and is fundamental to cerebellar LTD and motor functions. PMID:17347645

  1. Slice Accelerated Gradient-Echo Spin-Echo Dynamic Susceptibility Contrast Imaging with Blipped CAIPI for Increased Slice Coverage

    PubMed Central

    Eichner, Cornelius; Jafari-Khouzani, Kourosh; Cauley, Stephen; Bhat, Himanshu; Polaskova, Pavlina; Andronesi, Ovidiu C.; Rapalino, Otto; Turner, Robert; Wald, Lawrence L.; Stufflebeam, Steven; Setsompop, Kawin

    2014-01-01

    Purpose To improve slice coverage of gradient echo spin echo (GESE) sequences for dynamic susceptibility contrast (DSC) MRI using a simultaneous-multiple-slice (SMS) method. Methods Data were acquired on 3 Tesla (T) MR scanners with a 32-channel head coil. To evaluate use of SMS for DSC, an SMS GESE sequence with two-fold slice coverage and same temporal sampling was compared with a standard GESE sequence, both with 2× in-plane acceleration. A signal to noise ratio (SNR) comparison was performed on one healthy subject. Additionally, data with Gadolinium injection were collected on three patients with glioblastoma using both sequences, and perfusion analysis was performed on healthy tissues as well as on tumor. Results Retained SNR of SMS DSC is 90% for a gradient echo (GE) and 99% for a spin echo (SE) acquisition, compared with a standard acquisition without slice acceleration. Comparing cerebral blood volume maps, it was observed that the results of standard and SMS acquisitions are comparable for both GE and SE images. Conclusion Two-fold slice accelerated DSC MRI achieves similar SNR and perfusion metrics as a standard acquisition, while allowing a significant increase in slice coverage of the brain. The results also point to a possibility to improve temporal sampling rate, while retaining the same slice coverage. PMID:24285593

  2. Differential Effects of Intraventricular Hemorrhage and White Matter Injury on Preterm Cerebellar Growth

    PubMed Central

    Tam, Emily W.Y.; Miller, Steven P.; Studholme, Colin; Chau, Vann; Glidden, David; Poskitt, Kenneth J.; Ferriero, Donna M.; Barkovich, A. James

    2010-01-01

    Objective To hypothesize that detailed examination of early cerebellar volumes over time would distinguish differences in cerebellar growth associated with intraventricular hemorrhage (IVH) and white matter injury (WMI) in preterm infants. Study design Preterm newborns at the University of California San Francisco (n=57) and the University of British Columbia (n=115) were studied using serial MRI scans near birth and again at near term-equivalent age. Interactive semi-automated tools were used to determine volumes of the cerebellar hemispheres. Results Adjusting for supratentorial brain injury, cerebellar hemorrhage, and study site, cerebellar volume increased 1.7cm3/week postmenstrual age (95% CI 1.6–1.7, P<0.001). More severe supratentorial IVH was associated with slower growth of cerebellar volumes (P<0.001). Volumes by 40 weeks were 1.4 cm3 lower in premature infants with grade 1–2 IVH and 5.4 cm3 lower with grade 3–4 IVH. The same magnitude of decrease was found between ipsilateral and contralateral IVH. No association was found with severity of WMI (P=0.3). Conclusions Early effects of decreased cerebellar volume associated with supratentorial IVH in either hemisphere may be a result of concurrent cerebellar injury or direct effects of subarachnoid blood on cerebellar development. PMID:20961562

  3. Contribution of tonic vibration reflex to the evaluation and diagnosis of cerebellar disorders.

    PubMed Central

    Abbruzzese, G; Abbruzzese, M; Ratto, S; Favale, E

    1982-01-01

    Biceps brachii tonic vibration reflexes were elicited in patients with either focal or diffuse cerebellar damage and spino-cerebellar degenerations. As compared to normal controls, tonic vibration reflex amplitude was reduced in cerebellar patients, particularly in cases with unilateral hemispheric lesion, who exhibited a clear cut tonic vibration reflex asymmetry even when clinical symptoms were mild. These reflexes were absent or very weak in patients with spino-cerebellar degenerations. Muscle vibration induced in most of the patients an enhancement of mild or latent clinical symptoms such as intention tremor, difficulty in muscle relaxation or motor incoordination. PMID:7119815

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

    PubMed

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

    2011-01-01

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

  5. JC virus variant associated with cerebellar atrophy in a patient with AIDS.

    PubMed

    Roux, Damien; Bouldouyre, Marie-Anne; Mercier-Delarue, Séverine; Seilhean, Danielle; Zagdanski, Anne-Marie; Delaugerre, Constance; Simon, François; Molina, Jean-Michel; Legoff, Jerôme

    2011-06-01

    The human polyomavirus JC virus (JCV) is the agent of progressive multifocal leukoencephalopathy (PML). It has also recently been involved in cerebellar atrophy. Factors involved in this entity are elusive. We present a case of a human immunodeficiency virus (HIV)-infected patient with PML and cerebellar atrophy. In addition to a compartmentalization of JCV strains between urine, cerebrospinal fluid, and cerebellum, specific rearrangements in the JCV regulatory region were observed in the cerebellum, resulting in alterations of transcription factor binding sites. Our data underline the importance of searching for JCV in HIV-infected patients with cerebellar disorders and suggest that mutations in the regulatory region may be involved in cerebellar degeneration.

  6. Comparative anatomical studies on the cerebellar nuclei of the pangolins.

    PubMed

    Ishimoto, Y

    1983-01-01

    The configurations and volumes of the cerebellar nuclei of left and right 10 sides of 5 cases of the pangolins (Manis pentadactyla) were examined with sagittal myelin sheath and toluidine blue stained serial sections and reconstruction models based upon these serial sections respectively. The cerebellar nuclei of the pangolins, same as in other mammals can be divided into four nuclei, nucleus medialis (M), nucleus interpositus posterior (P), nucleus interpositus anterior (A) and nucleus lateralis (L). In all cases from medially to laterally, M, P, A and L appear in order and disappear M, A, P and L in order respectively. The volume of each nucleus in the total volume of the cerebellar nuclei is: M; 5.3-7.9% P; 27.1-31.2% A; 17.6-22.9% L; 42.4-46.2% In right and left each cerebellar nuclei significant difference is not recognized as p is less than 0.05. The posterior protuberance of the nucleus medialis protrudes remarkably in 4 cases of No. 1, No. 2, No. 3 and No. 4 but in only 1 case of No. 5 it protrudes slightly. In nucleus interpositus posterior the ventrolateral protuberance protrudes slightly in 4 cases of No. 1, No. 3, No. 4 and No. 5 but in only 1 case of No. 2 it protrudes remarkably. The anterior protuberance protrudes remarkably in all cases and the superior protuberance protrudes remarkably in 3 cases of No. 2, No. 3 and No. 4 but in 2 cases of No. 1 and No. 5 it protrudes slightly. In sulci, sulcus b and sulcus a' are distinct in all cases and sulcus a, sulcus c, sulcus b' and sulcus c' are considerably remarkable. In the toluidine blue stained serial sections, the nucleus medialis is composed of close small nerve cells, nucleus interpositus posterior is composed of the diffuse medium-sized nerve cells, nucleus interpositus anterior is composed of the close medium-sized nerve cells and nucleus lateralis is composed of the diffuse large nerve cells. In projection pictures of each subnuclei to the cerebellar cortex in each directions in the dorsal view

  7. Specific cerebellar activation during Braille reading in blind subjects.

    PubMed

    Gizewski, Elke R; Timmann, Dagmar; Forsting, Michael

    2004-07-01

    The traditional view that the cerebellum is involved only in the control of movements has been changed recently. It has been suggested that the human cerebellum is involved in cognition and language. Likewise, besides cortical activity in sensorimotor and visual areas, an increased global activation of the cerebellum has been revealed during Braille reading in blind subjects. Our purpose was to investigate whether there is cerebellar activation during Braille reading by blind subjects other than sensorimotor activation related to finger movements. Early blind and normal sighted subjects were studied with functional magnetic resonance imaging (fMRI) during Braille reading, tactile discrimination of nonsense dots, dots forming symbols, and finger tapping. The experiments were done in block design. Echo planar imaging sequences were carried out on a 1.5-T MR scanner. All blind individuals reading Braille showed robust activation of the posterior and lateral aspects of cerebellar hemispheral lobules Crus I bilaterally but more predominately on the right side. Additionally, activation was present in the medial cerebellum within lobules IV, V, and VIIIA, predominantly on the right. Discriminating nonsense dots did not reveal any activation of Crus I, but did reveal activation within the medial part of lobules IV, V, and VIIIA, predominately on the right. Analysis of sighted subjects during reading of printed text revealed activation of the posterolateral cerebellar hemisphere in Crus I bilaterally, predominantly on the right. Tactile analysis of dots representing symbols revealed an activation in lobules IV and VIII and in right Crus II but not in Crus I. In conclusion, parts of cerebellar activation during Braille reading in blind subjects (i.e., within lobules IV, V, and VIII) overlap with the known hand representation within the cerebellum and are likely related to the sensorimotor part of the task. Cerebellar activation during Braille reading within bilateral Crus I

  8. Precision of Cavalieri sections and slices with local errors.

    PubMed

    Cruz-Orive, L M

    1999-03-01

    Cavalieri sections--and more recently Cavalieri slices, especially in combination with non-invasive scanning--are widely used to estimate volumes. Physical Cavalieri slices are also increasingly used to estimate neuron numbers via the optical fractionator. In either case, the prediction of the error variance is important to assess optimal sample sizes. The error variance consists of two components, one due to the variation among the true contents of sections or slices, and the other due to local or 'nugget' errors. The latter may arise for instance estimating section areas by point counting discrete particles in slices or disectors. In this paper, a fairly comprehensive set of prediction formulae is presented to separate both variance components.

  9. Skin Diseases Take Big Slice Out of America's Health, Economy

    MedlinePlus

    ... Diseases Take Big Slice Out of America's Health, Economy The sometimes deadly conditions cost $75 billion in ... a major impact on Americans and the U.S. economy, a new report finds. "The impact of skin ...

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. Generalized Fourier slice theorem for cone-beam image reconstruction.

    PubMed

    Zhao, Shuang-Ren; Jiang, Dazong; Yang, Kevin; Yang, Kang

    2015-01-01

    The cone-beam reconstruction theory has been proposed by Kirillov in 1961, Tuy in 1983, Feldkamp in 1984, Smith in 1985, Pierre Grangeat in 1990. The Fourier slice theorem is proposed by Bracewell 1956, which leads to the Fourier image reconstruction method for parallel-beam geometry. The Fourier slice theorem is extended to fan-beam geometry by Zhao in 1993 and 1995. By combining the above mentioned cone-beam image reconstruction theory and the above mentioned Fourier slice theory of fan-beam geometry, the Fourier slice theorem in cone-beam geometry is proposed by Zhao 1995 in short conference publication. This article offers the details of the derivation and implementation of this Fourier slice theorem for cone-beam geometry. Especially the problem of the reconstruction from Fourier domain has been overcome, which is that the value of in the origin of Fourier space is 0/0. The 0/0 type of limit is proper handled. As examples, the implementation results for the single circle and two perpendicular circle source orbits are shown. In the cone-beam reconstruction if a interpolation process is considered, the number of the calculations for the generalized Fourier slice theorem algorithm is O(N^4), which is close to the filtered back-projection method, here N is the image size of 1-dimension. However the interpolation process can be avoid, in that case the number of the calculations is O(N5).

  15. A Developmental Study of the Cerebellar Nucleus in the Catshark, a Basal Gnathostome.

    PubMed

    Pose-Méndez, Sol; Rodríguez-Moldes, Isabel; Candal, Eva; Mazan, Sylvie; Anadón, Ramón

    2017-01-01

    The output of the cerebellar cortex is mainly released via cerebellar nuclei which vary in number and complexity among gnathostomes, extant vertebrates with a cerebellum. Cartilaginous fishes, a basal gnathostome lineage, show a conspicuous, well-organized cerebellar nucleus, unlike ray-finned fishes. To gain insight into the evolution and development of the cerebellar nucleus, we analyzed in the shark Scyliorhinus canicula (a chondrichthyan model species) the developmental expression of several genes coding for transcription factors (ScLhx5,ScLhx9,ScTbr1, and ScEn2) and the distribution of the protein calbindin, since all appear to be involved in cerebellar nuclei patterning in other gnathostomes. Three regions (subventricular, medial or central, and lateral or superficial) became recognizable in the cerebellar nucleus of this shark during development. Present genoarchitectonic and neurochemical data in embryos provide insight into the origin of the cerebellar nucleus in chondrichthyans and support a tripartite mediolateral organization of the cerebellar nucleus, as previously described in adult sharks. Furthermore, the expression pattern of ScLhx5,ScLhx9, and ScTbr1 in this shark, together with that of markers of proliferation, migration, and early differentiation of neurons, is compatible with the hypothesis that, as in mammals, different subsets of cerebellar nucleus neurons are originated from progenitors of 2 different sources: the ventricular zone of the cerebellar plate and the rhombic lip. We also present suggestive evidence that Lhx9 expression is involved in cerebellar nuclei patterning early on in gnathostome evolution, rather than representing an evolutionary innovation of the dentate nucleus in mammals, as previously hypothesized.

  16. Changes in neurotransmitter sensitivity in the mouse neocortical slice following propranolol and theophylline administration.

    PubMed Central

    Mally, J.; Connick, J. H.; Stone, T. W.

    1991-01-01

    1. The mouse neocortical slice has been used to examine the sensitivity of neurones to isoprenaline, 5-hydroxytryptamine (5-HT) and adenosine acutely and following chronic treatment of animals with propranolol or theophylline. 2. While having little effect alone, all three agonists enhanced the d.c. depolarizing potential produced by N-methyl-D-aspartate (NMDA). The effect of (-)-isoprenaline (0.2 microM) was shared by (+)-isoprenaline at the much higher concentration of 10 microM. 3. Superfusion of slices with theophylline or 8-phenyltheophylline blocked responses to adenosine with evidence of selectivity. A single injection of theophylline 24 h before slice preparation did not alter agonist sensitivity, but when administered daily at 100 mg kg-1 for 14 days, the xanthine caused a loss of sensitivity to adenosine and (-)-isoprenaline but not 5-HT. The lower dose of theophylline, 10 mg kg-1 daily, also led to a loss of adenosine responses but no change of sensitivity to the amines. 4. Following the 14 day treatment with theophylline at 100 mg kg-1 daily in two groups of mice, responses to adenosine recovered to control levels after 20 days. 5. Propranolol superfusion blocked responses to both isomers of isoprenaline and 5-HT but did not affect sensitivity to adenosine. 6. Chronic treatment with propranolol at 25 mg kg-1 daily for 14 days induced a loss of sensitivity to (-)-isoprenaline and 5-HT but not adenosine. A lower dose of 5 mg kg-1 daily caused no change in responses to adenosine or 5-HT, but yielded an increased sensitivity to (-)-isoprenaline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1364843

  17. 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.

  18. 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

  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. 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…

  1. Congenital torticollis due to sternomastoid aplasia with unilateral cerebellar hypoplasia: a rare association.

    PubMed

    Kumar, V R Ravi; Sabapathy, S Raja; Duraisami, Vijayagiri

    2012-10-01

    Congenital torticollis is most commonly caused by sternomastoid contracture. Aplasia of sternomastoid muscle causing congenital torticollis, though rare, has been reported. However the association of cerebellar hypoplasia with sternomastoid aplasia is extremely rare. The authors describe a case of congenital torticollis due to absence of the left sternomastoid with ipsilateral cerebellar hypoplasia, confirmed by MRI.

  2. Differential Purkinje cell simple spike activity and pausing behavior related to cerebellar modules

    PubMed Central

    Zhou, Haibo; Voges, Kai; Lin, Zhanmin; Ju, Chiheng

    2015-01-01

    The massive computational capacity of the cerebellar cortex is conveyed by Purkinje cells onto cerebellar and vestibular nuclei neurons through their GABAergic, inhibitory output. This implies that pauses in Purkinje cell simple spike activity are potentially instrumental in cerebellar information processing, but their occurrence and extent are still heavily debated. The cerebellar cortex, although often treated as such, is not homogeneous. Cerebellar modules with distinct anatomical connectivity and gene expression have been described, and Purkinje cells in these modules also differ in firing rate of simple and complex spikes. In this study we systematically correlate, in awake mice, the pausing in simple spike activity of Purkinje cells recorded throughout the entire cerebellum, with their location in terms of lobule, transverse zone, and zebrin-identified cerebellar module. A subset of Purkinje cells displayed long (>500-ms) pauses, but we found that their occurrence correlated with tissue damage and lower temperature. In contrast to long pauses, short pauses (<500 ms) and the shape of the interspike interval (ISI) distributions can differ between Purkinje cells of different lobules and cerebellar modules. In fact, the ISI distributions can differ both between and within populations of Purkinje cells with the same zebrin identity, and these differences are at least in part caused by differential synaptic inputs. Our results suggest that long pauses are rare but that there are differences related to shorter intersimple spike intervals between and within specific subsets of Purkinje cells, indicating a potential further segregation in the activity of cerebellar Purkinje cells. PMID:25717166

  3. 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...

  4. 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…

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

    PubMed

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

    2013-12-01

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

  6. 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.…

  7. Recruitment and interaction of human dendritic and T cells in autologous liver slices experimentally infected with HCV produced in cell culture.

    PubMed

    Nascimbeni, Michelina; Bourdoncle, Pierre; Penna, Christophe; Saunier, Bertrand

    2012-04-30

    Studying the immunological processes taking place during the initial steps of acute hepatitis C virus (HCV) infection has been a challenge in patients. Shin et al. have recently reported that delayed induction, not impaired recruitment of specific CD8(+) T cells, causes the late onset of acute hepatitis C in chimpanzees (Gastroenterology, 2011). However, further elucidation of the underlying mechanisms is difficult in vivo. We made observations consistent with their conclusions in human liver slices inoculated ex vivo with HCV produced in cell culture (HCVcc). Autologous immune cells were purified from blood and differentially stained prior to their incubation with the slices for 2 hours. A two-photon confocal microscopic analysis revealed that many more stained dendritic and T cells contracted interactions within two-day infected slices than non-inoculated ones (p<0.001). While in the first instance some dendritic and T cells entered into closer interactions, they never did in the latter case. These results suggest that ex vivo infection of human liver slices with HCVcc may be useful for gaining experimental insight regarding the immunological processes taking place at early steps of HCV infections.

  8. 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

    2014-08-10

    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.

  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 lesions and prism adaptation in macaque monkeys.

    PubMed

    Baizer, J S; Kralj-Hans, I; Glickstein, M

    1999-04-01

    If a laterally displacing prism is placed in front of one eye of a person or monkey with the other eye occluded, they initially will point to one side of a target that is located directly in front of them. Normally, people and monkeys adapt easily to the displaced vision and correct their aim after a few trials. If the prism then is removed, there is a postadaptation shift in which the subject misses the target and points in the opposite direction for a few trials. We tested five Macaque monkeys for their ability to adapt to a laterally displacing prism and to show the expected postadaptation shift. When tested as normals, all five animals showed the typical pattern of adaptation and postadaptation shift. Like human subjects, the monkeys also showed complete interocular transfer of the adaptation but no transfer of the adaptation between the two arms. When preoperative training and testing was complete, we made lesions of various target areas on the cerebellar cortex. A cerebellar lesion that included the dorsal paraflocculus and uvula abolished completely the normal prism adaptation for the arm ipsilateral to the lesion in one of the five monkeys. The other four animals retained the ability to prism-adapt normally and showed the expected postadaptation shift. In the one case in which the lesion abolished prism adaptation, the damage included Crus I and II, paramedian lobule and the dorsal paraflocculus of the cerebellar hemispheres as well as lobule IX, of the vermis. Thus in this case, the lesion included virtually all the cerebellar cortex that receives mossy-fiber visual information relayed via the pontine nuclei from the cerebral cortex. The other four animals had damage to lobule V, the classical anterior lobe arm area and/or vermian lobules VI/VII, the oculomotor region. When tested postoperatively, some of these animals showed a degree of ataxia equivalent to that of the case in which prism adaptation was affected, but prism adaptation and the

  11. 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.

  12. Understanding Cerebellar Liponeurocytomas: Case Report and Literature Review

    PubMed Central

    Oudrhiri, M. Y.; Raouzi, N.; El Kacemi, I.; El Fatemi, N.; Gana, R.; Maaqili, M. R.; Bellakhdar, F.

    2014-01-01

    Cerebellar liponeurocytomas were recognized in the 2000 WHO 3rd edition of CNS tumors as a distinct grade I pathological entity, a tumor with a more favorable prognosis than medulloblastoma. But reports of long-term recurrences and some possible aggressive behavior led to an upgrade on the latest WHO 4th edition of CNS tumors. The case of a 64-year-old female patient is reported in this paper. More than 30 cases of this lately recognized pathological entity have been reported to date. The diagnostic, radiological, and pathological features associated with this tumor are discussed through a literature review. PMID:24716015

  13. 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 .

  14. 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.

  15. 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

  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.

  17. Somatosensory temporal discrimination threshold is increased in patients with cerebellar atrophy.

    PubMed

    Manganelli, Fiore; Dubbioso, Raffaele; Pisciotta, Chiara; Antenora, Antonella; Nolano, Maria; De Michele, Giuseppe; Filla, Alessandro; Berardelli, Alfredo; Santoro, Lucio

    2013-08-01

    Processing of time in the millisecond range seems to depend on cerebellar function and it can be assessed by using the somatosensory temporal discrimination threshold testing. No studies have yet investigated this temporal discrimination task in patients with cerebellar atrophy. Eleven patients with degenerative cerebellar ataxia and 11 controls underwent somatosensory temporal discrimination threshold evaluation. The degree of cerebellar dysfunction was measured by the International Cooperative Ataxia Rating Scale. Somatosensory temporal discrimination threshold was higher in patients compared to controls for each stimulated site (hand, neck, and eye). Age, disease duration, and International Cooperative Ataxia Rating Scale scores were not correlated to somatosensory temporal discrimination threshold. Somatosensory temporal discrimination threshold is abnormal in patients with cerebellar atrophy. These findings suggest that the cerebellum plays a role in modulating the somatosensory temporal discrimination threshold and confirm the role of cerebellum in the processing of time in the millisecond range.

  18. Anti-Ca/anti-ARHGAP26 antibodies associated with cerebellar atrophy and cognitive decline.

    PubMed

    Doss, Sarah; Nümann, Astrid; Ziegler, Annerose; Siebert, Eberhard; Borowski, Kathrin; Stöcker, Winfried; Prüss, Harald; Wildemann, Brigitte; Endres, Matthias; Jarius, Sven

    2014-02-15

    Recently, we identified a novel Purkinje cell-specific autoantibody (termed anti-Ca) targeting rhoGTPase-activating-protein-26 (ARHGAP26) in a patient with cerebellar ataxia. Here we describe a new case of anti-Ca/ARHGAP26 antibody-positive cerebellar ataxia. Cerebellar ataxia was associated with signs of possible limbic encephalitis in this case. The 24-year-old man presented with subacute pancerebellar ataxia, flattened affect, and cognitive decline. Neuropsychological testing revealed working memory deficits, compromised verbal learning and recall, attention deficits, slowed information processing, interference difficulty, and reduced spatial recognition. MRI showed severe pancerebellar atrophy. Serological examinations revealed high-titre anti-Ca/anti-ARHGAP26 antibodies. The antibodies belonged to the IgG1 subclass and were produced intrathecally. This case further corroborates the association of anti-Ca antibodies with cerebellar ataxia, expands the clinical spectrum, and highlights the necessity of antigen-specific diagnostic testing in immune-mediated cerebellar ataxia.

  19. Novel compound heterozygous mutations in a child with Ataxia-Telangiectasia showing unrelated cerebellar disorders.

    PubMed

    Piane, Maria; Molinaro, Anna; Soresina, Annarosa; Costa, Silvia; Maffeis, Marianna; Germani, Aldo; Pinelli, Lorenzo; Meschini, Roberta; Plebani, Alessandro; Chessa, Luciana; Micheli, Roberto

    2016-12-15

    We report the case of a 6-year-old female patient with Ataxia Telangiectasia, an extremely rare condition, who developed in addition a left cerebellar astrocytoma and a right cerebellar infarction, considered as two independent events. Children with AT have an increased risk of developing cancer, but only few cases of glioma are reported and, at our knowledge, no other case of unrelated cerebellar glioma and cerebellar infarction in with the same AT patient have been described. The molecular analysis of ATM (Ataxia Telangiectasia Mutated) gene showed that the patient is compound heterozygote for two previously unreported mutations: c.3291delC (p.Phe1097fs) at exon 25 and c.8198A>C (p.Gln2733Pro) at exon 58. The role of the identified ATM gene mutations in the pathogenesis of Ataxia Telangiectasia and the coexisting cerebellar disorders is discussed.

  20. 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.

  1. 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.

  2. 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.

  3. A multifunctional pipette for localized drug administration to brain slices.

    PubMed

    Ahemaiti, Aikeremu; Ainla, Alar; Jeffries, Gavin D M; Wigström, Holger; Orwar, Owe; Jesorka, Aldo; Jardemark, Kent

    2013-10-15

    We have developed a superfusion method utilizing an open-volume microfluidic device for administration of pharmacologically active substances to selected areas in brain slices with high spatio-temporal resolution. The method consists of a hydrodynamically confined flow of the active chemical compound, which locally stimulates neurons in brain slices, applied in conjunction with electrophysiological recording techniques to analyze the response. The microfluidic device, which is a novel free-standing multifunctional pipette, allows diverse superfusion experiments, such as testing the effects of different concentrations of drugs or drug candidates on neurons in different cell layers with high positional accuracy, affecting only a small number of cells. We demonstrate herein the use of the method with electrophysiological recordings of pyramidal cells in hippocampal and prefrontal cortex brain slices from rats, determine the dependence of electric responses on the distance of the superfusion device from the recording site, document a multifold gain in solution exchange time as compared to whole slice perfusion, and show that the device is able to store and deliver up to four solutions in a series. Localized solution delivery by means of open-volume microfluidic technology also reduces reagent consumption and tissue culture expenses significantly, while allowing more data to be collected from a single tissue slice, thus reducing the number of laboratory animals to be sacrificed for a study.

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

    PubMed

    Stoodley, Catherine J; MacMore, Jason P; Makris, Nikos; Sherman, Janet C; Schmahmann, Jeremy D

    2016-01-01

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

  5. Cerebellar TMS in Treatment of a Patient with Cerebellar Ataxia: Evidence from Clinical, Biomechanics and Neurophysiological Assessments

    PubMed Central

    Farzan, Faranak; Wu, Yunfen; Manor, Brad; Anastasio, Elana M.; Lough, Matthew; Novak, Vera; Greenstein, Patricia E.; Pascual-Leone, Alvaro

    2013-01-01

    We describe a patient with a probable diagnosis of idiopathic late-onset cerebellar atrophy who shows improvement of limb coordination, speech and gait following 21 days of transcranial magnetic stimulation (TMS) applied to scalp regions presumably corresponding to the cerebellum. This case study provides, for the first time, a quantitative assessment of gait improvement in response to TMS therapy in ataxia, as well as neurophysiological evidence in support of modification of cerebello-cortical interaction that may underlie some of the improvements. PMID:23625327

  6. 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

    2016-03-11

    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.

  7. 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.

  8. Stimulation of Ethylene Production in Apple Tissue Slices by Methionine

    PubMed Central

    Lieberman, Morris; Kunishi, Alice; Mapson, L. W.; Wardale, D. A.

    1966-01-01

    Methionine can induce more than a 100% increase in ethylene production by apple tissue slices. The increased amount of ethylene derives from carbons 3 and 4 of methionine. Only post-climacteric fruit tissues are stimulated by methionine, and stimulation is optimum after 8 months' storage. Copper chelators such as sodium diethyl dithiocarbamate and cuprizone very markedly inhibit ethylene production by tissue slices. Carbon monoxide does not effect ethylene production by the slices. These data suggest that the mechanism for the conversion of methionine to ethylene, in apple tissues, is similar to the previously described model system for producing ethylene from methionine and reduced copper. Therefore, it is suggested that one of the ethylene-forming systems in tissues derives from methionine and proceeds to ethylene via a copper enzyme system which may be a peroxidase. PMID:16656267

  9. Fluid dynamic lateral slicing of high tensile strength carbon nanotubes

    PubMed Central

    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

  10. Drying kinetics and colour change of lemon slices

    NASA Astrophysics Data System (ADS)

    Darvishi, Hosain; Khoshtaghaza, Mohammad H.; Minaei, Saeid

    2014-03-01

    The effect of microwave-convective heating on drying characteristics and colour change of lemon slices was investigated. The drying experiments were carried out at 180, 360, 540 and 720Wand at 22°C, with air velocity of 1ms-1. The values of effective moisture diffusivity were found to be in the range between 1.87 10-8 and 3.95 10-8 m2 s-1, and the activation energy was estimated to be 10.91 Wg-1. The drying data were fitted with ten mathematical models available in the literature. The model describing drying kinetics of lemon slices in the best way was found. The colour change of the dried lemon slices was analysed and considered as a quality index affecting the drying quality of the product. The values of lightness/darkness, yellowness/blueness and hue angle increased, while the value of redness/greenness decreased with increasing microwave power.

  11. 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

  12. Microarchitectural changes during development of the cerebellar cortex.

    PubMed

    Mecha, Miriam; Peña-Melián, Angel L; Blanco, Maria J

    2010-01-01

    The cerebellum is a highly conserved structure in the Central Nervous System (CNS) of vertebrates, and is involved in the coordination of voluntary motor behaviour. Supporting this function, the cerebellar cortex presents a layered structure which requires a precise spatial and temporal coordination of proliferation, migration and differentiation events. One of the characteristics of the developing cortex is the formation of the external granule cell layer (EGL) in the outermost part. The EGL is a highly proliferative transient layer which disappears when cells migrate inwards to form the inner granule cell layer. The balance between proliferation and migration leads to changes in EGL thickness, and might be related to "indentations" observed in the surface of the developing chick cerebellum. We have extended the observation of this feature to quail and mouse, supporting the idea that this phenomenon forms part of the mechanisms of cerebellar morphogenesis. Different factors involved in both mitotic activity and migration were analyzed in this study. Our results indicate that proliferation, more than formation of raphes for cell migration, is involved in the formation of indentations in the EGL. In addition, we show that vessels penetrating from the pial surface divide the EGL into regular regions at the time of the appearance of bulges and furrows. We conclude that indentations are the result of a coincidence in time of both the increase in thickness of the EGL and the establishment of the embryonic vascular pattern, which confers a characteristic transitory morphology to the surface of folia.

  13. Speech prosody in Friedreich's and olivo-ponto cerebellar atrophy

    NASA Astrophysics Data System (ADS)

    Casper, Maureen

    2004-05-01

    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.

  14. Development of the cerebellum and cerebellar neural circuits.

    PubMed

    Hibi, Masahiko; Shimizu, Takashi

    2012-03-01

    The cerebellum, a structure derived from the dorsal part of the most anterior hindbrain, is important for integrating sensory perception and motor control. While the structure and development of the cerebellum have been analyzed most extensively in mammals,recent studies have shown that the anatomy and development of the cerebellum is conserved between mammals and bony fish (teleost) species, including zebrafish. In the mammalian and teleost cerebellum,Purkinje and granule cells serve, respectively, as the major GABAergic and glutamatergic neurons. Purkinje cells originate in the ventricular zone (VZ), and receive inputs from climbing fibers. Granule cells originate in the upper rhombic lip (URL) and receive inputs from mossy fibers. Thus, the teleost cerebellum shares many features with the cerebellum of other vertebrates, and isa good model system for studying cerebellar function and development. The teleost cerebellum also has features that are specific to teleosts or have not been elucidated in mammals, including eurydendroid cells and adult neurogenesis. Furthermore, the neural circuitry in part of the optic tectum and the dorsal hindbrain closely resembles the circuitry of the teleost cerebellum; hence,these are called cerebellum-like structures. Here we describe the anatomy and development of cerebellar neurons and their circuitry, and discuss the possible roles of the cerebellum and cerebellum-like structures in behavior and higher cognitive functions. We also consider the potential use of genetics and novel techniques for studying the cerebellum in zebrafish.

  15. Impaired predictive motor timing in patients with cerebellar disorders.

    PubMed

    Bares, Martin; Lungu, Ovidiu; Liu, Tao; Waechter, Tobias; Gomez, Christopher M; Ashe, James

    2007-06-01

    The ability to precisely time events is essential for both perception and action. There is evidence that the cerebellum is important for the neural representation of time in a variety of behaviors including time perception, the tapping of specific time intervals, and eye-blink conditioning. It has been difficult to assess the contribution of the cerebellum to timing during more dynamic motor behavior because the component movements themselves may be abnormal or any motor deficit may be due to an inability to combine the component movements into a complete action rather than timing per se. Here we investigated the performance of subjects with cerebellar disease in predictive motor timing using a task that involved mediated interception of a moving target, and we tested the effect of movement type (acceleration, deceleration, constant), speed (slow, medium, fast), and angle (0 degrees , 15 degrees and 30 degrees) on performance. The subjects with cerebellar damage were significantly worse at interception than healthy controls even when we controlled for basic motor impairments such as response time. Our data suggest that subjects with damage to the cerebellum have a fundamental problem with predictive motor timing and indicate that the cerebellum plays an essential role in integrating incoming visual information with motor output when making predictions about upcoming actions. The findings demonstrate that the cerebellum may have properties that would facilitate the processing or storage of internal models of motor behavior.

  16. Coordinated scaling of cortical and cerebellar numbers of neurons.

    PubMed

    Herculano-Houzel, Suzana

    2010-01-01

    While larger brains possess concertedly larger cerebral cortices and cerebella, the relative size of the cerebral cortex increases with brain size, but relative cerebellar size does not. In the absence of data on numbers of neurons in these structures, this discrepancy has been used to dispute the hypothesis that the cerebral cortex and cerebellum function and have evolved in concert and to support a trend towards neocorticalization in evolution. However, the rationale for interpreting changes in absolute and relative size of the cerebral cortex and cerebellum relies on the assumption that they reflect absolute and relative numbers of neurons in these structures across all species - an assumption that our recent studies have shown to be flawed. Here I show for the first time that the numbers of neurons in the cerebral cortex and cerebellum are directly correlated across 19 mammalian species of four different orders, including humans, and increase concertedly in a similar fashion both within and across the orders Eulipotyphla (Insectivora), Rodentia, Scandentia and Primata, such that on average a ratio of 3.6 neurons in the cerebellum to every neuron in the cerebral cortex is maintained across species. This coordinated scaling of cortical and cerebellar numbers of neurons provides direct evidence in favor of concerted function, scaling and evolution of these brain structures, and suggests that the common notion that equates cognitive advancement with neocortical expansion should be revisited to consider in its stead the coordinated scaling of neocortex and cerebellum as a functional ensemble.

  17. Coordinated Scaling of Cortical and Cerebellar Numbers of Neurons

    PubMed Central

    Herculano-Houzel, Suzana

    2010-01-01

    While larger brains possess concertedly larger cerebral cortices and cerebella, the relative size of the cerebral cortex increases with brain size, but relative cerebellar size does not. In the absence of data on numbers of neurons in these structures, this discrepancy has been used to dispute the hypothesis that the cerebral cortex and cerebellum function and have evolved in concert and to support a trend towards neocorticalization in evolution. However, the rationale for interpreting changes in absolute and relative size of the cerebral cortex and cerebellum relies on the assumption that they reflect absolute and relative numbers of neurons in these structures across all species – an assumption that our recent studies have shown to be flawed. Here I show for the first time that the numbers of neurons in the cerebral cortex and cerebellum are directly correlated across 19 mammalian species of four different orders, including humans, and increase concertedly in a similar fashion both within and across the orders Eulipotyphla (Insectivora), Rodentia, Scandentia and Primata, such that on average a ratio of 3.6 neurons in the cerebellum to every neuron in the cerebral cortex is maintained across species. This coordinated scaling of cortical and cerebellar numbers of neurons provides direct evidence in favor of concerted function, scaling and evolution of these brain structures, and suggests that the common notion that equates cognitive advancement with neocortical expansion should be revisited to consider in its stead the coordinated scaling of neocortex and cerebellum as a functional ensemble. PMID:20300467

  18. Inhibition promotes long-term potentiation at cerebellar excitatory synapses

    PubMed Central

    Binda, F.; Dorgans, K.; Reibel, S.; Sakimura, K.; Kano, M.; Poulain, B.; Isope, P.

    2016-01-01

    The ability of the cerebellar cortex to learn from experience ensures the accuracy of movements and reflex adaptation, processes which require long-term plasticity at granule cell (GC) to Purkinje neuron (PN) excitatory synapses. PNs also receive GABAergic inhibitory inputs via GCs activation of interneurons; despite the involvement of inhibition in motor learning, its role in long-term plasticity is poorly characterized. Here we reveal a functional coupling between ionotropic GABAA receptors and low threshold CaV3 calcium channels in PNs that sustains calcium influx and promotes long-term potentiation (LTP) at GC to PN synapses. High frequency stimulation induces LTP at GC to PN synapses and CaV3-mediated calcium influx provided that inhibition is intact; LTP is mGluR1, intracellular calcium store and CaV3 dependent. LTP is impaired in CaV3.1 knockout mice but it is nevertheless recovered by strengthening inhibitory transmission onto PNs; promoting a stronger hyperpolarization via GABAA receptor activation leads to an enhanced availability of an alternative Purkinje-expressed CaV3 isoform compensating for the lack of CaV3.1 and restoring LTP. Accordingly, a stronger hyperpolarization also restores CaV3-mediated calcium influx in PNs from CaV3.1 knockout mice. We conclude that by favoring CaV3 channels availability inhibition promotes LTP at cerebellar excitatory synapses. PMID:27641070

  19. Single-slice mapping of ultrashort T 2

    NASA Astrophysics Data System (ADS)

    Kirsch, Stefan; Schad, Lothar R.

    2011-05-01

    In this communication we present a method for single-slice mapping of ultrashort transverse relaxation times T2. The RF pulse sequence consists of a spin echo preparation of the magnetization followed by slice-selective ultrashort echo time (UTE) imaging with radial k-space sampling. In order to keep the minimum echo time as small as possible, avoid out-of-slice contamination and signal contamination due to unwanted echoes, the implemented pulse sequence employs a slice-selective 180° RF refocusing pulse and a 4-step phase cycle. The slice overlap of the two slice-selective RF pulses was investigated. An acceptable Gaussian slice profile could be achieved by adjusting the strength of the two slice-selection gradients. The method was tested on a short T2 phantom consisting of an arrangement of a roll of adhesive tape, an eraser, a piece of modeling dough made of Plasticine®, and a 10% w/w agar gel. The T2 measurements on the phantom revealed exponential signal decays for all samples with T2(adhesive tape) = (0.5 ± 0.1) ms, T2(eraser) = (2.33 ± 0.07) ms, T2(Plasticine®) = (2.8 ± 0.06) ms, and T2(10% agar) = (9.5 ± 0.83) ms. The T2 values obtained by the mapping method show good agreement with the T2 values obtained by a non-selective T2 measurement. For all samples, except the adhesive tape, the effective transverse relaxation time T2∗ was significantly shorter than T2. Depending on the scanner hardware the presented method allows mapping of T2 down to a few hundreds of microseconds. Besides investigating material samples, the presented method can be used to study the rapidly decaying MR-signal from biological tissue (e.g.: bone, cartilage, and tendon) and quadrupolar nuclei (e.g.: 23Na, 35Cl, and 17O).

  20. Classification of CT-brain slices based on local histograms

    NASA Astrophysics Data System (ADS)

    Avrunin, Oleg G.; Tymkovych, Maksym Y.; Pavlov, Sergii V.; Timchik, Sergii V.; Kisała, Piotr; Orakbaev, Yerbol

    2015-12-01

    Neurosurgical intervention is a very complicated process. Modern operating procedures based on data such as CT, MRI, etc. Automated analysis of these data is an important task for researchers. Some modern methods of brain-slice segmentation use additional data to process these images. Classification can be used to obtain this information. To classify the CT images of the brain, we suggest using local histogram and features extracted from them. The paper shows the process of feature extraction and classification CT-slices of the brain. The process of feature extraction is specialized for axial cross-section of the brain. The work can be applied to medical neurosurgical systems.

  1. Emission-line galaxies in the Slice of the Universe

    NASA Technical Reports Server (NTRS)

    Salzer, John J.; Aldering, Gregory S.; Bothun, Gregory D.; Mazzarella, Joseph M.; Lonsdale, Carol J.

    1988-01-01

    The relative spatial distributions of emission-line galaxies (ELGs) and normal galaxies that lie in the sky area covered by the 'Slice' survey (de Lapparent et al., 1986) are considered. ELGs follow the same spatial distribution as found for the Slice galaxies, with the exception that they avoid the Coma cluster. It is pointed out that although the present ELGs are not shown to occur in regions of very low density, the luminosity distribution of the sample is such that luminosity/mass-dependent effects on the spatial distribution would not be noticeable.

  2. Verification of Software Product Lines with Delta-Oriented Slicing

    NASA Astrophysics Data System (ADS)

    Bruns, Daniel; Klebanov, Vladimir; Schaefer, Ina

    Software product line (SPL) engineering is a well-known approach to develop industry-size adaptable software systems. SPL are often used in domains where high-quality software is desirable; the overwhelming product diversity, however, remains a challenge for assuring correctness. In this paper, we present delta-oriented slicing, an approach to reduce the deductive verification effort across an SPL where individual products are Java programs and their relations are described by deltas. On the specification side, we extend the delta language to deal with formal specifications. On the verification side, we combine proof slicing and similarity-guided proof reuse to ease the verification process.

  3. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute cystitis; Acute bladder infection; Acute bacterial cystitis ... cause. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  4. Physiology, morphology and detailed passive models of guinea-pig cerebellar Purkinje cells.

    PubMed Central

    Rapp, M; Segev, I; Yarom, Y

    1994-01-01

    1. Purkinje cells (PCs) from guinea-pig cerebellar slices were physiologically characterized using intracellular techniques. Extracellular caesium ions were used to linearize the membrane properties of PCs near the resting potential. Under these conditions the average input resistance, RN, was 29 M omega, the average system time constant, tau 0, was 82 ms and the average cable length, LN, was 0.59. 2. Three PCs were fully reconstructed following physiological measurements and staining with horseradish peroxidase. Assuming that each spine has an area of 1 micron 2 and that the spine density over the spiny dendrites is ten spines per micrometre length, the total membrane area of each PC is approximately 150,000 microns 2, of which approximately 100,000 microns 2 is in the spines. 3. Detailed passive cable and compartmental models were built for each of the three reconstructed PCs. Computational methods were devised to incorporate globally the huge number of spines into these models. In all three cells the models predict that the specific membrane resistivity, Rm, of the soma is much lower than the dendritic Rm (approximately 500 and approximately 100,000 omega cm2 respectively). The specific membrane capacitance, Cm, is estimated to be 1.5-2 muF cm-2 and the specific cytoplasm resistivity, Ri, is 250 omega cm. 4. The average cable length of the dendrites according to the model is 0.13 lambda, suggesting that under caesium conditions PCs are electrically very compact. Brief somatic spikes, however, are expected to attenuate 30-fold when spreading passively into the dendritic terminals. A simulated 200 Hz train of fast, 90 mV somatic spikes produced a smooth 12 mV steady depolarization at the dendritic terminals. 5. A transient synaptic conductance increase, with a 1 nS peak at 0.5 ms and a driving force of 60 mV, is expected to produce approximately 20 mV peak depolarization at the spine head membrane. This EPSP then attenuates between 200- and 900-fold into the soma

  5. Aneurysm in the anterior inferior cerebellar artery-posterior inferior cerebellar artery variant: Case report and review of literature

    PubMed Central

    Akhtar, Saad; Azeem, Abdul; Jiwani, Amyna; Javed, Gohar

    2016-01-01

    Introduction There are variations in the anatomy of the vertebrobasilar system amongst which the Anterior Inferior Cerebellar Artery-Posterior Inferior Cerebellar Artery (AICA-PICA) variant is thought to have a prevalence of 20–24% (based on retrospective studies). Despite this, aneurysms of the AICA-PICA variant are rare. We present a case of an AICA-PICA aneurysm and discuss its presentation and management, along with a review of literature. Presentation of case We describe the case of a 35 year old female who presented with signs of meningismus. On the basis of radiological imaging it was initially misdiagnosed as a thrombosed arteriovenous malformation (AVM). The patient was eventually discharged with a plan of interval imaging and interventional radiology (if required). The patient presented again with similar signs and symptoms. Re-evaluation of imaging revealed an aneurysm of the AICA-PICA variant which was managed surgically. Discussion Aneurysms of the AICA-PICA variant are rare. The radiological features and surgical management represent a unique clinical entity and are discussed below. Conclusion The prevalence of the AICA-PICA variant might be high but aneurysms in this vessel are rare. The scant knowledge available on this subject makes it a diagnostic difficulty. PMID:27017276

  6. Climate variability around the first Pliocene time slice

    NASA Astrophysics Data System (ADS)

    Prescott, C.; Haywood, A.; Dolan, A. M.; Hunter, S. J.; Tindall, J.; Pope, J. O.; Pickering, S.

    2013-12-01

    Existing data/model comparisons for the mid-Pliocene (Dowsett et al., 2013) have identified specific regions of concordance and discord between climate models and proxy data. One reason for site-specific disagreement is likely related to the time (warm peak) averaged nature of the mid-Pliocene ocean temperatures provided within existing proxy syntheses. To facilitate improved data/model comparisons in the future new proxy sea surface temperature reconstructions will focus on specific time slices within the Pliocene epoch. Haywood et al. (2013) identified an initial time slice for environmental reconstruction and climate modelling centred on an interglacial event at Marine Isotope Stage KM5c (3.205 Ma). Critically, this interval displays a very near to modern orbital configuration simplifying the interpretation of proxy data and the experimental design for climate models. Nevertheless, current limitations of chronology and correlation make it likely that new proxy records will be attributable to a time range around the time slice, and may not always represent the time slice specifically. This introduces an element of uncertainty through orbital forcing around the time slice which can be investigated and quantified within a numerical climate modelling framework. The Hadley Centre Coupled Climate Model Version 3 (HadCM3) has been used to perform a series of orbital forcing sensitivity tests around the identified time slice at MIS KM5c. Simulations every 2 kyr either side of the time slice to a range +/- 20 kyr have been completed. The model results indicate that +/- 20 kyr either side of the time slice, orbital forcing generates a less than 1°C change on global MAT. One exception to this relative stability in climate is seen in the North Atlantic (a region noted for disagreement in existing Pliocene data/model comparisons). Here, ocean surface temperature variations of up to 6°C are predicted. These model responses appear to be linked to changes in ocean circulation

  7. Hyperexcitability in combined entorhinal/hippocampal slices of adult rat after exposure to brain-derived neurotrophic factor.

    PubMed

    Scharfman, H E

    1997-08-01

    Effects of brain-derived neurotrophic factor (BDNF) in area CA3, the dentate gyrus, and medial entorhinal cortex were examined electrophysiologically by bath application of BDNF in slices containing the hippocampus and entorhinal cortex. Bath application of 25-100 ng/ml BDNF for 30-90 min increased responses to single afferent stimuli in selective pathways in the majority of slices. In area CA3, responses to mossy fiber stimulation increased in 73% of slices and entorhinal cortex responses to white matter stimulation increased in 64% of slices. After exposure to BDNF, these areas also demonstrated evidence of hyperexcitability, because responses to repetitive stimulation (1-Hz paired pulses for several s) produced multiple population spikes in response to mossy fiber stimulation in CA3 or multiple field potentials in response to white matter stimulation in the entorhinal cortex. Repetitive field potentials persisted after repetitive stimulation ended and usually were followed by spreading depression. Enhancement of responses to single stimuli and hyperexcitability were never evoked in untreated slices or after bath application of boiled BDNF or cytochrome C. The tyrosine kinase antagonist K252a (2 microM) blocked the effects of BDNF. In area CA3, both the potentiation of responses to single stimuli and hyperexcitability showed afferent specificity, because responses to mossy fiber stimulation were affected but responses to fimbria or Schaffer collateral stimulation were not. In addition, regional specificity was demonstrated in that the dentate gyrus was much less affected. The effects of BDNF in area CA3 were similar to those produced by bath application of low doses of kainic acid, which is thought to modulate glutamate release from mossy fiber terminals by a presynaptic action. These results suggest that BDNF has acute effects on excitability in different areas of the hippocampal-entorhinal circuit. These effects appear to be greatest in areas that are highly

  8. Cadherins in cerebellar development: translation of embryonic patterning into mature functional compartmentalization.

    PubMed

    Redies, Christoph; Neudert, Franziska; Lin, Juntang

    2011-09-01

    Cadherins are cell adhesion molecules with multiple morphogenic functions in brain development, for example, in neuroblast migration and aggregation, axon navigation, neural circuit formation, and synaptogenesis. More than 100 members of the cadherin superfamily are expressed in the developing and mature brain. Most of the cadherins investigated, in particular classic cadherins and δ-protocadherins, are expressed in the cerebellum. For several cadherin subtypes, expression begins at early embryonic stages and persists until mature stages of cerebellar development. At intermediate stages, distinct Purkinje cell clusters exhibit unique rostrocaudal and mediolateral expression profiles for each cadherin. In the chicken, mouse, and other species, the Purkinje cell clusters are separated by intervening raphes of migrating granule cells. This pattern of Purkinje cell clusters/raphes is, at least in part, continuous with the parasagittal striping pattern that is apparent in the mature cerebellar cortex, for example, for zebrin II/aldolase C. Moreover, subregions of the deep cerebellar nuclei, vestibular nuclei and the olivary complex also express cadherins differentially. Neuroanatomical evidence suggests that the nuclear subregions and cortical domains that express the same cadherin subtype are connected to each other, to form neural subcircuits of the cerebellar system. Cadherins thus provide a molecular code that specifies not only embryonic structures but also functional cerebellar compartmentalization. By following the implementation of this code, it can be revealed how mature functional architecture emerges from embryonic patterning during cerebellar development. Dysfunction of some cadherins is associated with psychiatric diseases and developmental impairments and may also affect cerebellar function.

  9. Interhemispheric Connectivity Characterizes Cortical Reorganization in Motor-Related Networks After Cerebellar Lesions.

    PubMed

    De Vico Fallani, Fabrizio; Clausi, Silvia; Leggio, Maria; Chavez, Mario; Valencia, Miguel; Maglione, Anton Giulio; Babiloni, Fabio; Cincotti, Febo; Mattia, Donatella; Molinari, Marco

    2017-04-01

    Although cerebellar-cortical interactions have been studied extensively in animal models and humans using modern neuroimaging techniques, the effects of cerebellar stroke and focal lesions on cerebral cortical processing remain unknown. In the present study, we analyzed the large-scale functional connectivity at the cortical level by combining high-density electroencephalography (EEG) and source imaging techniques to evaluate and quantify the compensatory reorganization of brain networks after cerebellar damage. The experimental protocol comprised a repetitive finger extension task by 10 patients with unilateral focal cerebellar lesions and 10 matched healthy controls. A graph theoretical approach was used to investigate the functional reorganization of cortical networks. Our patients, compared with controls, exhibited significant differences at global and local topological level of their brain networks. An abnormal rise in small-world network efficiency was observed in the gamma band (30-40 Hz) during execution of the task, paralleled by increased long-range connectivity between cortical hemispheres. Our findings show that a pervasive reorganization of the brain network is associated with cerebellar focal damage and support the idea that the cerebellum boosts or refines cortical functions. Clinically, these results suggest that cortical changes after cerebellar damage are achieved through an increase in the interactions between remote cortical areas and that rehabilitation should aim to reshape functional activation patterns. Future studies should determine whether these hypotheses are limited to motor tasks or if they also apply to cerebro-cerebellar dysfunction in general.

  10. Modality specificity in the cerebro-cerebellar neurocircuitry during working memory.

    PubMed

    Ng, H B Tommy; Kao, K-L Cathy; Chan, Y C; Chew, Effie; Chuang, K H; Chen, S H Annabel

    2016-05-15

    Previous studies have suggested cerebro-cerebellar circuitry in working memory. The present fMRI study aims to distinguish differential cerebro-cerebellar activation patterns in verbal and visual working memory, and employs a quantitative analysis to deterimine lateralization of the activation patterns observed. Consistent with Chen and Desmond (2005a,b) predictions, verbal working memory activated a cerebro-cerebellar circuitry that comprised left-lateralized language-related brain regions including the inferior frontal and posterior parietal areas, and subcortically, right-lateralized superior (lobule VI) and inferior cerebellar (lobule VIIIA/VIIB) areas. In contrast, a distributed network of bilateral inferior frontal and inferior temporal areas, and bilateral superior (lobule VI) and inferior (lobule VIIB) cerebellar areas, was recruited during visual working memory. Results of the study verified that a distinct cross cerebro-cerebellar circuitry underlies verbal working memory. However, a neural circuitry involving specialized brain areas in bilateral neocortical and bilateral cerebellar hemispheres subserving visual working memory is observed. Findings are discussed in the light of current models of working memory and data from related neuroimaging studies.

  11. Systemic glycerol decreases neonatal rabbit brain and cerebellar growth independent of intraventricular hemorrhage

    PubMed Central

    Traudt, Christopher M; McPherson, Ron J; Studholme, Colin; Millen, Kathleen J; Juul, Sandra E

    2014-01-01

    Background Cerebellar hypoplasia is common problem for preterm infants, and infants that suffer intraventricular hemorrhage (IVH). To evaluate the effects of IVH on cerebellar growth and development, we used a neonatal rabbit model of systemic glycerol to produce IVH. Methods New Zealand White rabbit kits were surgically delivered 2 d preterm, and treated with i.p. glycerol (3.25 to 6.5 g/kg). Controls were born at term. IVH was documented by ultrasound. Brain MRI volumes, cerebellar foliation, proliferation (Ki-67) and Purkinje cell density were done at two weeks of life. Tissue glycerol and glutathione concentrations were measured. Results Glycerol increased IVH, subarachnoid hemorrhages and mortality in a dose-dependent manner. Total cerebellar volumes, cerebellar foliation and cerebellar proliferation were decreased in a dose-dependent manner. Glycerol accumulated rapidly in blood, brain and liver and was associated with increased glutathione concentration. All of these results were independent of IVH status. Conclusions Cerebellar hypoplasia was induced after glycerol administration in a dose-dependent manner. Given rapid tissue accumulation of glycerol, dose dependent decreased brain growth and lack of IVH effect on measured outcomes we question the validity of this model as glycerol toxicity cannot be ruled out. A more physiologic model of IVH is needed. PMID:24346111

  12. Cerebellar mutism in children: report of six cases and potential mechanisms.

    PubMed

    Koh, S; Turkel, S B; Baram, T Z

    1997-04-01

    Cerebellar mutism is a rare finding associated with resection of posterior fossa tumors or cerebellar hemorrhages. We reviewed the medical records of six children, aged 6 to 12 years, who developed cerebellar mutism after resection of a posterior fossa mass or as a result of posterior fossa trauma. From 1989 to 1994, 210 children underwent posterior fossa resection at our institution, and four developed mutism (an incidence of 1.6%). All four patients had primitive neuroectodermal tumors. The fifth patient experienced trauma, and another patient had an arteriovenous malformation (AVM). In four children, hydrocephalus developed as a result of their tumor or AVM. Four developed cerebellar mutism 24 to 48 hours after surgery or trauma, and one developed cerebellar mutism 5 days after surgery, coincident with hydrocephalus. In one, mutism occurred after a second resection was performed for a recurrence of his posterior fossa tumor. Cerebellar mutism lasted 10 days in one patient and 2 to 8 weeks in the other four. Dysarthria was apparent in four patients during the recovery phase. We suggest trauma to the dentate nucleus and/or its outflow tract, the superior cerebellar peduncle, as a cause of reversible mutism. Because posterior fossa tumors are common in children, mutism should be recognized as an important side effect of surgery.

  13. Relationships between regional cerebellar volume and sensorimotor and cognitive function in young and older adults

    PubMed Central

    Bernard, Jessica A.; Seidler, Rachael D.

    2013-01-01

    The cerebellum has been implicated in both sensorimotor and cognitive function, but is known to undergo volumetric declines with advanced age. Individual differences in regional cerebellar volume may therefore provide insight into performance variability across the lifespan, as has been shown with other brain structures and behaviors. Here, we investigated whether there are regional age differences in cerebellar volume in young and older adults, and whether these volumes explain, in part, individual differences in sensorimotor and cognitive task performance. We found that older adults had smaller cerebellar volume than young adults; specifically, lobules in the anterior cerebellum were more impacted by age. Multiple regression analyses for both age groups revealed associations between sensorimotor task performance in several domains (balance, choice reaction time, and timing) and regional cerebellar volume. There were also relationships with working memory, but none with measures of general cognitive or executive function. Follow-up analyses revealed several differential relationships with age between regional volume and sensorimotor performance. These relationships were predominantly selective to cerebellar regions that have been implicated in cognitive functions. Therefore, it may be the cognitive aspects of sensorimotor task performance that are best explained by individual differences in regional cerebellar volumes. In sum, our results demonstrate the importance of regional cerebellar volume with respect to both sensorimotor and cognitive performance, and we provide additional insight into the role of the cerebellum in age-related performance declines. PMID:23625382

  14. Dissociation of locomotor and cerebellar deficits in a murine Angelman syndrome model

    PubMed Central

    Bruinsma, Caroline F.; Schonewille, Martijn; Gao, Zhenyu; Aronica, Eleonora M.A.; Judson, Matthew C.; Philpot, Benjamin D.; Hoebeek, Freek E.; van Woerden, Geeske M.; De Zeeuw, Chris I.; Elgersma, Ype

    2015-01-01

    Angelman syndrome (AS) is a severe neurological disorder that is associated with prominent movement and balance impairments that are widely considered to be due to defects of cerebellar origin. Here, using the cerebellar-specific vestibulo-ocular reflex (VOR) paradigm, we determined that cerebellar function is only mildly impaired in the Ube3am–/p+ mouse model of AS. VOR phase-reversal learning was singularly impaired in these animals and correlated with reduced tonic inhibition between Golgi cells and granule cells. Purkinje cell physiology, in contrast, was normal in AS mice as shown by synaptic plasticity and spontaneous firing properties that resembled those of controls. Accordingly, neither VOR phase-reversal learning nor locomotion was impaired following selective deletion of Ube3a in Purkinje cells. However, genetic normalization of αCaMKII inhibitory phosphorylation fully rescued locomotor deficits despite failing to improve cerebellar learning in AS mice, suggesting extracerebellar circuit involvement in locomotor learning. We confirmed this hypothesis through cerebellum-specific reinstatement of Ube3a, which ameliorated cerebellar learning deficits but did not rescue locomotor deficits. This double dissociation of locomotion and cerebellar phenotypes strongly suggests that the locomotor deficits of AS mice do not arise from impaired cerebellar cortex function. Our results provide important insights into the etiology of the motor deficits associated with AS. PMID:26485287

  15. Lanthanum-mediated modification of GABAA receptor deactivation, desensitization and inhibitory synaptic currents in rat cerebellar neurons.

    PubMed

    Zhu, W J; Wang, J F; Corsi, L; Vicini, S

    1998-09-15

    1. We investigated La3+ effects on recombinant and native gamma-aminobutyric acid A (GABAA) receptors using rapid agonist applications and on inhibitory synaptic currents (IPSCs) in granule and stellate neurons of rat cerebellar slices. 2. Rapid desensitization of currents elicited by 200 ms pulses of 1 mM GABA to small lifted cells transfected with alpha1beta3gamma2 cDNAs was greatly decreased by the coapplication of 100 microM LaCl3. 3. GABA responses were unaffected when coapplication lasted only 2 ms. In contrast, with LaCl3 pre-perfusion, a significant slowing of deactivation in response to 2 ms applications was observed. LaCl3 pre-perfusion also prolonged the duration of responses to 20 mM taurine. 4. Outside-out patches excised from cells transfected with alpha1beta3gamma2 subunit cDNAs were briefly exposed to a saturating concentration of GABA, eliciting a transient activation of single channel currents with a main conductance of 30 pS. Opening and burst durations increased by pre-equilibration of patches with LaCl3. 5. LaCl3 depressed the peak amplitude without affecting the slow deactivation and desensitization of GABA responses in cells transfected with alpha6beta3gamma2 and alpha6beta3delta cDNAs. No significant difference in La3+ modulation of GABA-gated currents was observed between alpha1beta3gamma2 and alpha1beta3delta receptors. 6. The effects of LaCl3 on deactivation and desensitization of GABA responses observed in nucleated patches excised from rat cerebellar granule and stellate neurons were comparable to those in the cells transfected with alpha1beta3gamma2 cDNAs. In addition, La3+ clearly prolonged the spontaneous IPSC time course without changing the amplitude. 7. Our results indicate that La3+ has a dual action on GABA-gated currents: it decreases desensitization and increases channel opening duration. These actions depend on receptor subunit composition and contribute to the prolongation of IPSCs.

  16. Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice.

    PubMed

    Tsai, Peter T; Hull, Court; Chu, YunXiang; Greene-Colozzi, Emily; Sadowski, Abbey R; Leech, Jarrett M; Steinberg, Jason; Crawley, Jacqueline N; Regehr, Wade G; Sahin, Mustafa

    2012-08-30

    Autism spectrum disorders (ASDs) are highly prevalent neurodevelopmental disorders, but the underlying pathogenesis remains poorly understood. Recent studies have implicated the cerebellum in these disorders, with post-mortem studies in ASD patients showing cerebellar Purkinje cell (PC) loss, and isolated cerebellar injury has been associated with a higher incidence of ASDs. However, the extent of cerebellar contribution to the pathogenesis of ASDs remains unclear. Tuberous sclerosis complex (TSC) is a genetic disorder with high rates of comorbid ASDs that result from mutation of either TSC1 or TSC2, whose protein products dimerize and negatively regulate mammalian target of rapamycin (mTOR) signalling. TSC is an intriguing model to investigate the cerebellar contribution to the underlying pathogenesis of ASDs, as recent studies in TSC patients demonstrate cerebellar pathology and correlate cerebellar pathology with increased ASD symptomatology. Functional imaging also shows that TSC patients with ASDs display hypermetabolism in deep cerebellar structures, compared to TSC patients without ASDs. However, the roles of Tsc1 and the sequelae of Tsc1 dysfunction in the cerebellum have not been investigated so far. Here we show that both heterozygous and homozygous loss of Tsc1 in mouse cerebellar PCs results in autistic-like behaviours, including abnormal social interaction, repetitive behaviour and vocalizations, in addition to decreased PC excitability. Treatment of mutant mice with the mTOR inhibitor, rapamycin, prevented the pathological and behavioural deficits. These findings demonstrate new roles for Tsc1 in PC function and define a molecular basis for a cerebellar contribution to cognitive disorders such as autism.

  17. Restoring cognitive functions using non-invasive brain stimulation techniques in patients with cerebellar disorders.

    PubMed

    Pope, Paul A; Miall, R Chris

    2014-01-01

    Numerous studies have highlighted the possibility of modulating the excitability of cerebro-cerebellar circuits bi-directionally using transcranial electrical brain stimulation, in a manner akin to that observed using magnetic stimulation protocols. It has been proposed that cerebellar stimulation activates Purkinje cells in the cerebellar cortex, leading to inhibition of the dentate nucleus, which exerts a tonic facilitatory drive onto motor and cognitive regions of cortex through a synaptic relay in the ventral-lateral thalamus. Some cerebellar deficits present with cognitive impairments if damage to non-motor regions of the cerebellum disrupts the coupling with cerebral cortical areas for thinking and reasoning. Indeed, white matter changes in the dentato-rubral tract correlate with cognitive assessments in patients with Friedreich ataxia, suggesting that this pathway is one component of the anatomical substrate supporting a cerebellar contribution to cognition. An understanding of the physiology of the cerebro-cerebellar pathway previously helped us to constrain our interpretation of results from two recent studies in which we showed cognitive enhancements in healthy participants during tests of arithmetic after electrical stimulation of the cerebellum, but only when task demands were high. Others studies have also shown how excitation of the prefrontal cortex can enhance performance in a variety of working memory tasks. Thus, future efforts might be guided toward neuro-enhancement in certain patient populations, using what is commonly termed "non-invasive brain stimulation" as a cognitive rehabilitation tool to modulate cerebro-cerebellar circuits, or for stimulation over the cerebral cortex to compensate for decreased cerebellar drive to this region. This article will address these possibilities with a review of the relevant literature covering ataxias and cerebellar cognitive affective disorders, which are characterized by thalamo-cortical disturbances.

  18. Network hyperexcitability in hippocampal slices from Mecp2 mutant mice revealed by voltage-sensitive dye imaging

    PubMed Central

    Calfa, Gaston; Hablitz, John J.

    2011-01-01

    Dysfunctions of neuronal and network excitability have emerged as common features in disorders associated with intellectual disabilities, autism, and seizure activity, all common clinical manifestations of Rett syndrome (RTT), a neurodevelopmental disorder caused by loss-of-function mutations in the transcriptional regulator methyl-CpG-binding protein 2 (MeCP2). Here, we evaluated the consequences of Mecp2 mutation on hippocampal network excitability, as well as synapse structure and function using a combination of imaging and electrophysiological approaches in acute slices. Imaging the amplitude and spatiotemporal spread of neuronal depolarizations with voltage-sensitive dyes (VSD) revealed that the CA1 and CA3 regions of hippocampal slices from symptomatic male Mecp2 mutant mice are highly hyperexcitable. However, only the density of docked synaptic vesicles and the rate of release from the readily releasable pool are impaired in Mecp2 mutant mice, while synapse density and morphology are unaffected. The differences in network excitability were not observed in surgically isolated CA1 minislices, and blockade of GABAergic inhibition enhanced VSD signals to the same extent in Mecp2 mutant and wild-type mice, suggesting that network excitability originates in area CA3. Indeed, extracellular multiunit recordings revealed a higher level of spontaneous firing of CA3 pyramidal neurons in slices from symptomatic Mecp2 mutant mice. The neuromodulator adenosine reduced the amplitude and spatiotemporal spread of VSD signals evoked in CA1 of Mecp2 mutant slices to wild-type levels, suggesting its potential use as an anticonvulsant in RTT individuals. The present results suggest that hyperactive CA3 pyramidal neurons contribute to hippocampal dysfunction and possibly to limbic seizures observed in Mecp2 mutant mice and RTT individuals. PMID:21307327

  19. Direct excitation of inhibitory interneurons by extracellular ATP mediated by P2Y1 receptors in the hippocampal slice.

    PubMed

    Kawamura, Masahito; Gachet, Christian; Inoue, Kazuhide; Kato, Fusao

    2004-12-01

    ATP is an important cell-to-cell signaling molecule mediating the interactions between astrocytes and neurons in the CNS. In the hippocampal slices, ATP suppresses excitatory transmission mostly through activation of adenosine A1 receptors, because the ectoenzyme activity for the extracellular breakdown of ATP to adenosine is high in slice preparations in contrast to culture environments. Because the hippocampus is also rich in the expression of P2 receptors activated specifically by ATP, we examined whether ATP modulates neuronal excitability in the acute slice preparations independently of adenosine receptors. Although ATP decreased the frequency of spontaneously occurring EPSCs in the CA3 pyramidal neurons through activation of adenosine A1 receptors, ATP concurrently increased the frequency of IPSCs in a manner dependent on action potential generation. This effect was mediated by P2Y1 receptors because (1) 2-methylthio-ATP (2meSATP) was the most potent agonist, (2) 2'-deoxy-N6-methyladenosine-3',5'-bisphosphate diammonium (MRS2179) abolished this effect, and (3) this increase in IPSC frequency was not observed in the transgenic mice lacking P2Y1 receptor proteins. Application of 2meSATP elicited MRS2179-sensitive time- and voltage-dependent inward currents in the interneurons, which depolarized the cell to firing threshold. Also, it increased [Ca2+]i in both astrocytes and interneurons, but, unlike the former effect, the latter was entirely dependent on Ca2+ entry. Thus, in hippocampal slices, in addition to activating A1 receptors of the excitatory terminals after being converted to adenosine, ATP activates P2Y1 receptors in the interneurons, which is linked to activation of unidentified excitatory conductance, through mechanisms distinct from those in the astrocytes.

  20. Cyanide-resistant Respiration in Freshly Cut Potato Slices.

    PubMed

    Rychter, A; Janes, H W; Frenkel, C

    1978-04-01

    Treating intact white potato (Solanum tuberosum L.) tuber with ethylene in air or O(2) made it possible to obtain freshly cut slices which exhibit cyanide-resistant respiration. The cyanide-resistant path requires induction in whole tubers. The data also indicate that high O(2) concentration is necessary for the full development of cyanide-resistant respiration.

  1. Stochastic neural network model for spontaneous bursting in hippocampal slices.

    PubMed

    Biswal, B; Dasgupta, C

    2002-11-01

    A biologically plausible, stochastic, neural network model that exhibits spontaneous transitions between a low-activity (normal) state and a high-activity (epileptic) state is studied by computer simulation. Brief excursions of the network to the high-activity state lead to spontaneous population bursting similar to the behavior observed in hippocampal slices bathed in a high-potassium medium. Although the variability of interburst intervals in this model is due to stochasticity, first return maps of successive interburst intervals show trajectories that resemble the behavior expected near unstable periodic orbits (UPOs) of systems exhibiting deterministic chaos. Simulations of the effects of the application of chaos control, periodic pacing, and anticontrol to the network model yield results that are qualitatively similar to those obtained in experiments on hippocampal slices. Estimation of the statistical significance of UPOs through surrogate data analysis also leads to results that resemble those of similar analysis of data obtained from slice experiments and human epileptic activity. These results suggest that spontaneous population bursting in hippocampal slices may be a manifestation of stochastic bistable dynamics, rather than of deterministic chaos. Our results also question the reliability of some of the recently proposed, UPO-based, statistical methods for detecting determinism and chaos in experimental time-series data.

  2. Hemodialysis fistula occlusion: demonstration with 64-slice CT angiography.

    PubMed

    Neyman, Edward G; Johnson, Pamela T; Fishman, Elliot K

    2006-01-01

    The speed and resolution of 64-slice CT have resulted in new applications for CT angiography (CTA) owing to rapid data acquisition during the arterial phase, improved visualization of small vessels, and lengthened anatomic coverage. Extremity CT angiography is one such region. This case report shows the utility of multislice CTA for the evaluation of hemodialysis graft dysfunction.

  3. Blanching, salting and sun drying of different pumpkin fruit slices.

    PubMed

    Workneh, T S; Zinash, A; Woldetsadik, K

    2014-11-01

    The study was aimed at assessing the quality of pumpkin (Cucuribita Spp.) slices that were subjected to pre-drying treatments and drying using two drying methods (uncontrolled sun and oven) fruit accessions. Pre-drying had significant (P ≤ 0.05) effect on the quality of dried pumpkin slices. 10 % salt solution dipped pumpkin fruit slices had good chemical quality. The two-way interaction between drying methods and pre-drying treatments had significant (P ≤ 0.05) effect on chemical qualities. Pumpkin subjected to salt solution dipping treatment and oven dried had higher chemical concentrations. Among the pumpkin fruit accessions, pumpkin accession 8007 had the superior TSS, total sugar and sugar to acid ratio after drying. Among the three pre-drying treatment, salt solution dipping treatment had significant (P ≤ 0.05) effect and the most efficient pre-drying treatment to retain the quality of dried pumpkin fruits without significant chemical quality deterioration. Salt dipping treatment combined with low temperature (60 °C) oven air circulation drying is recommended to maintain quality of dried pumpkin slices. However, since direct sun drying needs extended drying time due to fluctuation in temperature, it is recommended to develop or select best successful solar dryer for use in combination with pre-drying salt dipping or blanching treatments.

  4. Differences in saccade dynamics between spinocerebellar ataxia 2 and late-onset cerebellar ataxias.

    PubMed

    Federighi, Pamela; Cevenini, Gabriele; Dotti, Maria T; Rosini, Francesca; Pretegiani, Elena; Federico, Antonio; Rufa, Alessandra

    2011-03-01

    The cerebellum is implicated in maintaining the saccadic subsystem efficient for vision by minimizing movement inaccuracy and by learning from endpoint errors. This ability is often disrupted in degenerative cerebellar diseases, as demonstrated by saccade kinetic abnormalities. The study of saccades in these patients may therefore provide insights into the neural substrate underlying saccadic motor control. We investigated the different extent of saccade dynamic abnormalities in spinocerebellar ataxia type 2 and late-onset cerebellar ataxias, genetically undefined and with prevalent cerebellar atrophy. Reflexive and voluntary saccades of different amplitude (10°-18°) were studied in seven patients with spinocerebellar ataxia 2, eight patients with late-onset cerebellar ataxia and 25 healthy controls. Quantitative analysis of saccade parameters and measures of saccade accuracy were performed. Detailed neurological, neurophysiological and magnetic resonance imaging assessment was obtained for each patient. Genetic and laboratory screening for spinocerebellar ataxias and other forms of late-onset cerebellar ataxias were also performed. A lower peak saccade velocity and longer duration was observed in patients with spinocerebellar ataxia 2 with respect to those with late-onset cerebellar ataxia and controls. Unlike subjects with spinocerebellar ataxia 2, patients with late-onset cerebellar ataxia showed main sequence relationships to similar saccades made by normal subjects. Saccades were significantly more inaccurate, namely hypometric, in late-onset cerebellar ataxia than in spinocerebellar ataxia 2 and inaccuracy increased with saccade amplitude. The percentage of hypometric primary saccades and of larger secondary corrective saccades were consistently higher in late-onset cerebellar ataxia than in spinocerebellar ataxia 2 and controls. No other significant differences were found between groups. Two different mechanisms were adopted to redirect the fovea as fast

  5. A Case of Multiple System Atrophy-Cerebellar Type Preceded by Dementia

    PubMed Central

    Jang, Eun Hye; Lee, Joo Kyung; Jang, Hyun Jung; Kim, Mi-Jung; Chung, Sun Ju

    2012-01-01

    Multiple system atrophy (MSA) is a sporadic, adult-onset disease characterized by progressive degeneration of nervous systems including cerebellar, pyramidal, extrapyramidal, and autonomic system. Although a few recent studies reported that cognitive impairments could occur in patients with MSA, prominent dementia with progressive decline is not a typical clinical manifestation of MSA. In particular, dementia with MSA-cerebellar type is very rare. We have experienced a patient with 2-year history of severe cognitive impairment, who was finally diagnosed as MSA-cerebellar type. PMID:24868414

  6. Pediatric cerebellar stroke associated with elevated titer of antibodies to β2-glycoprotein.

    PubMed

    Spalice, Alberto; Del Balzo, Francesca; Perla, Francesco Massimo; Papetti, Laura; Nicita, Francesco; Ursitti, Fabiana; Properzi, Enrico

    2011-06-01

    Antibodies to 2-glycoprotein I (anti-2GPI) have been associated with recurrent thrombosis and pregnancy morbidity. However, the prevalence of anti-2GPI in children suffering from cerebral and cerebellar infarction is unknown. We report on a 10-month-old boy who had an ischemic cerebellar stroke, secondary to antiphospholipid syndrome with high titers of immunoglobulin G anti-2GPI (first titer: 132U) anticardiolipin antibodies and lupus anticoagulant tests were negative. All other causes of infarction were excluded. To our knowledge, this is the first reported case of childhood cerebellar ischemic stroke with only anti-2GPI but no antibodies detectable in standard antiphospholipid assays.

  7. Anti-Yo positive paraneoplastic cerebellar degeneration in the setting of cholangiocarcinoma.

    PubMed

    Bruhnding, Aubree; Notch, Derek; Beard, Albertine

    2017-02-01

    Paraneoplastic neurological syndromes are a rare complication of malignancy. Subacute cerebellar ataxia, or paraneoplastic cerebellar degeneration, usually presents in women with a subcate onset of gait instability, followed by progressive limb and trunk ataxia, dysarthria, diplopia, and dysphagia that occurs in the setting of, or precedes the diagnosis of, a gynecologic or breast malignancy and clinically stabilizes within six months. The most common autoantibody associated with PCD is purkinje cell cytoplasmic antibody type 1, also known as anti-Yo. Here we describe the first reported case of a man with anti-Yo positive paraneoplastic cerebellar degeneration in the setting of occult cholangiocarcinoma.

  8. Cerebellar Degeneration as a Rare Paraneoplastic Syndrome in a Child With Hodgkin Lymphoma.

    PubMed

    Avramova, Boryana E; Hristova, Tanya; Yordanova, Maya; Vlahova, Irena; Muchinova, Albena; Bojinova, Veneta; Konstantinov, Dobrin

    2016-08-01

    We report a rare case of cerebellar degeneration as a paraneoplastic syndrome in an 8-year-old boy with Hodgkin lymphoma that presented during first-line treatment. Antibodies against Purkinje cells (anti-Tr antibodies) were detected in the serum of the patient. After successful treatment of the lymphoma, the cerebellar symptoms resolved partially. Childhood presentation of paraneoplastic cerebellar degeneration is extremely rare, with only a few reports in the literature. For this reason, the description of all such cases contributes to the enrichment of the medical knowledge and will improve the diagnosis and the treatment of this complication.

  9. Dysplastic Cerebellar Epilepsy: Complete Seizure Control Following Resection of a Ganglioglioma.

    PubMed

    Martins, William Alves; Paglioli, Eliseu; Hemb, Marta; Palmini, Andre

    2016-08-01

    Subcortical epilepsy has been a controversial issue, partially settled by evidence showing seizure generation in hypothalamic hamartomas and also by reports of seizures caused by cerebellar lesions. We report 4-year-old girl with right hemifacial seizures and autonomic phenomena, in whom MRI showed an irregular mass in the right cerebellar peduncle. Despite several unremarkable video-EEG recordings, seizure origin in the lesion was hypothesized. Complete resection was feasible, histopathology showed a ganglioglioma, and she has been seizure free for 3 years. A fine line separates these developmental tumors from focal cortical dysplasia, and the homogeneous presentation of this entity led us to propose the terminology dysplastic cerebellar epilepsy.

  10. Fan beam image reconstruction with generalized Fourier slice theorem.

    PubMed

    Zhao, Shuangren; Yang, Kang; Yang, Kevin

    2014-01-01

    For parallel beam geometry the Fourier reconstruction works via the Fourier slice theorem (or central slice theorem, projection slice theorem). For fan beam situation, Fourier slice can be extended to a generalized Fourier slice theorem (GFST) for fan-beam image reconstruction. We have briefly introduced this method in a conference. This paper reintroduces the GFST method for fan beam geometry in details. The GFST method can be described as following: the Fourier plane is filled by adding up the contributions from all fanbeam projections individually; thereby the values in the Fourier plane are directly calculated for Cartesian coordinates such avoiding the interpolation from polar to Cartesian coordinates in the Fourier domain; inverse fast Fourier transform is applied to the image in Fourier plane and leads to a reconstructed image in spacial domain. The reconstructed image is compared between the result of the GFST method and the result from the filtered backprojection (FBP) method. The major differences of the GFST and the FBP methods are: (1) The interpolation process are at different data sets. The interpolation of the GFST method is at projection data. The interpolation of the FBP method is at filtered projection data. (2) The filtering process are done in different places. The filtering process of the GFST is at Fourier domain. The filtering process of the FBP method is the ramp filter which is done at projections. The resolution of ramp filter is variable with different location but the filter in the Fourier domain lead to resolution invariable with location. One advantage of the GFST method over the FBP method is in short scan situation, an exact solution can be obtained with the GFST method, but it can not be obtained with the FBP method. The calculation of both the GFST and the FBP methods are at O(N^3), where N is the number of pixel in one dimension.

  11. [Occipital dermal sinus associated to a cerebellar abscess. Case].

    PubMed

    Costa, J M; de Reina, L; Guillén, A; Claramunt, E

    2004-10-01

    Congenital dermal sinuses are tubular tracts which communicate the skin with deeper structures. It is a manifestation of defective separation of the ectoderm and neuroderm. The incidence is 1/2500-3000 births alive. Almost 10 % of congenital dermal sinuses are localized in the occipitocervical region. They are usually asymptomatic, unless an infectious process is concurrent (meningitis, abscess). We are presenting the case of a 12 months girl with unnoticed cutaneous stigmata in the occipital region, who was admitted with a meningeal syndrome and secondary neurological impairment. She had a cerebellar abscess and was treated with decompression by puncture of the abscess and antibiotics. When infection was resolved, congenital dermal sinus was excised. Process solves without morbidity. We reviewed the clinical and therapeutic features in cases reported previously in the literature.

  12. Surface-binding autoantibodies to cerebellar neurons in opsoclonus syndrome.

    PubMed

    Blaes, Franz; Fühlhuber, Verena; Korfei, Martina; Tschernatsch, Marlene; Behnisch, Wolfgang; Rostasy, Kevin; Hero, Barbara; Kaps, Manfred; Preissner, Klaus T

    2005-08-01

    Childhood opsoclonus-myoclonus syndrome can occur with or without