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Sample records for abnormal spontaneous activity

  1. Abnormal spontaneous brain activity in minimal hepatic encephalopathy: resting-state fMRI study

    PubMed Central

    Zhong, Wei-Jia; Zhou, Zhi-Ming; Zhao, Jian-Nong; Wu, Wei; Guo, Da-Jing

    2016-01-01

    PURPOSE We aimed to assess the abnormality of baseline spontaneous brain activity in minimal hepatic encephalopathy (MHE) by amplitude of low frequency fluctuation (ALFF) and fraction ALFF (fALFF). METHODS A total of 14 MHE patients and 14 healthy controls were included in our study. Both ALFF and fALFF of functional magnetic resonance imaging were calculated for statistical analysis. RESULTS Compared with healthy controls, patients with MHE had significantly decreased ALFF in the bilateral medial prefrontal cortex (MPFC), left superior frontal gyrus, right precentral gyrus, left opercular part of inferior frontal gyrus, left gyrus rectus, bilateral precuneus, and the posterior lobe of right cerebellum; and they had significantly decreased fALFF in the bilateral MPFC, right middle frontal gyrus, right superior temporal gyrus, and the posterior lobe of left cerebellum. CONCLUSION ALFF and fALFF changes in many brain regions demonstrate abnormality of the spontaneous neuronal activity in MHE. Especially the impairment of right precuneus and left MPFC may play a critical role in manifestation of MHE. Changes of ALFF and fALFF in the precuneus and the MPFC can be used as a potential marker for MHE. PMID:26742646

  2. Spontaneous occurrence of chromosome abnormality in cats.

    PubMed

    THULINE, H C; NORBY, D W

    1961-08-25

    A syndrome in male cats analogous to chromatin-positive Klinefelter's syndrome in human males has been demonstrated. The physical characteristics which suggested an abnormality of chromosome number in cats were "calico" or "tortoise-shell" coat colors in a male. Buccal mucosal smears were found to have "female-type" patterns in two out of 12 such male cats screened, and these two were found to have a diploid chromosome number of 39 rather than the normal 38. Testicular biopsy performed on one revealed an abnormal pattern; no gonadal tissue was found in the other cat with an abnormal chromosome number. These findings indicate that the cat, in addition to the mouse, is available for experimental study of chromosome number abnormalities. PMID:13776765

  3. Abnormal spontaneous regional brain activity in primary insomnia: a resting-state functional magnetic resonance imaging study

    PubMed Central

    Li, Chao; Ma, Xiaofen; Dong, Mengshi; Yin, Yi; Hua, Kelei; Li, Meng; Li, Changhong; Zhan, Wenfeng; Li, Cheng; Jiang, Guihua

    2016-01-01

    Objective Investigating functional specialization is crucial for a complete understanding of the neural mechanisms of primary insomnia (PI). Resting-state functional magnetic resonance imaging (fMRI) is a useful tool to explore the functional specialization of PI. However, only a few studies have focused on the functional specialization of PI using resting-state fMRI and results of these studies were far from consistent. Thus, the current study aimed to investigate functional specialization of PI using resting-state fMRI with amplitude of low frequency fluctuations (ALFFs) algorithm. Methods In this study, 55 PI patients and 44 healthy controls were included. ALFF values were compared between the two groups using two-sample t-test. The relationship of abnormal ALFF values with clinical characteristics and duration of insomnia was investigated using Pearson’s correlation analysis. Results PI patients showed lower ALFF values in the left orbitofrontal cortex/inferior frontal gyrus, right middle frontal gyrus, left inferior parietal lobule, and bilateral cerebellum posterior lobes, while higher ALFF values in the right middle/inferior temporal that extended to the right occipital lobe. In addition, we found that the duration of PI negatively correlated with ALFF values in the left orbitofrontal cortex/inferior frontal gyrus, and the Pittsburgh Sleep Quality Index score negatively correlated with ALFF values in the left inferior parietal lobule. Conclusion The present study added information to limited studies on functional specialization and provided evidence for hyperarousal hypothesis in PI. PMID:27366068

  4. Hypoglycemia-induced spontaneous unilateral jerking movement in bilateral internal capsule posterior limb abnormalities.

    PubMed

    Nakajima, Nobuhito; Ueda, Masayuki; Nagayama, Hiroshi; Katayama, Yasuo

    2014-03-15

    We report an 89-year-old woman who developed consciousness disturbance associated with marked hypoglycemia, and showed involuntary movements manifested as spontaneous quick-jerking flexion followed by slow relaxation, in the right leg. Diffusion-weighted imaging revealed bilateral hyperintensities in the posterior limbs of the internal capsule (P-IC). She was treated with intravenous glucose supplementation, and her symptoms dramatically improved. The P-IC lesions are common abnormalities on MRI in hypoglycemia, and may cause paralysis. However involuntary movements associated with the lesions are rarely observed. The spontaneous jerking movements observed in this patient might result from transient impairment of the pyramidal tract associated with hypoglycemia. PMID:24411408

  5. Spontaneous network activity and synaptic development

    PubMed Central

    Kerschensteiner, Daniel

    2014-01-01

    Throughout development, the nervous system produces patterned spontaneous activity. Research over the last two decades has revealed a core group of mechanisms that mediate spontaneous activity in diverse circuits. Many circuits engage several of these mechanisms sequentially to accommodate developmental changes in connectivity. In addition to shared mechanisms, activity propagates through developing circuits and neuronal pathways (i.e. linked circuits in different brain areas) in stereotypic patterns. Increasing evidence suggests that spontaneous network activity shapes synaptic development in vivo. Variations in activity-dependent plasticity may explain how similar mechanisms and patterns of activity can be employed to establish diverse circuits. Here, I will review common mechanisms and patterns of spontaneous activity in emerging neural networks and discuss recent insights into their contribution to synaptic development. PMID:24280071

  6. Associative memory model with spontaneous neural activity

    NASA Astrophysics Data System (ADS)

    Kurikawa, Tomoki; Kaneko, Kunihiko

    2012-05-01

    We propose a novel associative memory model wherein the neural activity without an input (i.e., spontaneous activity) is modified by an input to generate a target response that is memorized for recall upon the same input. Suitable design of synaptic connections enables the model to memorize input/output (I/O) mappings equaling 70% of the total number of neurons, where the evoked activity distinguishes a target pattern from others. Spontaneous neural activity without an input shows chaotic dynamics but keeps some similarity with evoked activities, as reported in recent experimental studies.

  7. Abnormal Activity Detection Using Pyroelectric Infrared Sensors

    PubMed Central

    Luo, Xiaomu; Tan, Huoyuan; Guan, Qiuju; Liu, Tong; Zhuo, Hankz Hankui; Shen, Baihua

    2016-01-01

    Healthy aging is one of the most important social issues. In this paper, we propose a method for abnormal activity detection without any manual labeling of the training samples. By leveraging the Field of View (FOV) modulation, the spatio-temporal characteristic of human activity is encoded into low-dimension data stream generated by the ceiling-mounted Pyroelectric Infrared (PIR) sensors. The similarity between normal training samples are measured based on Kullback-Leibler (KL) divergence of each pair of them. The natural clustering of normal activities is discovered through a self-tuning spectral clustering algorithm with unsupervised model selection on the eigenvectors of a modified similarity matrix. Hidden Markov Models (HMMs) are employed to model each cluster of normal activities and form feature vectors. One-Class Support Vector Machines (OSVMs) are used to profile the normal activities and detect abnormal activities. To validate the efficacy of our method, we conducted experiments in real indoor environments. The encouraging results show that our method is able to detect abnormal activities given only the normal training samples, which aims to avoid the laborious and inconsistent data labeling process. PMID:27271632

  8. Abnormal Activity Detection Using Pyroelectric Infrared Sensors.

    PubMed

    Luo, Xiaomu; Tan, Huoyuan; Guan, Qiuju; Liu, Tong; Zhuo, Hankz Hankui; Shen, Baihua

    2016-01-01

    Healthy aging is one of the most important social issues. In this paper, we propose a method for abnormal activity detection without any manual labeling of the training samples. By leveraging the Field of View (FOV) modulation, the spatio-temporal characteristic of human activity is encoded into low-dimension data stream generated by the ceiling-mounted Pyroelectric Infrared (PIR) sensors. The similarity between normal training samples are measured based on Kullback-Leibler (KL) divergence of each pair of them. The natural clustering of normal activities is discovered through a self-tuning spectral clustering algorithm with unsupervised model selection on the eigenvectors of a modified similarity matrix. Hidden Markov Models (HMMs) are employed to model each cluster of normal activities and form feature vectors. One-Class Support Vector Machines (OSVMs) are used to profile the normal activities and detect abnormal activities. To validate the efficacy of our method, we conducted experiments in real indoor environments. The encouraging results show that our method is able to detect abnormal activities given only the normal training samples, which aims to avoid the laborious and inconsistent data labeling process. PMID:27271632

  9. Chromosome abnormalities in chronic active hepatitis

    PubMed Central

    Stefanescu, D. T.; Moanga, M.; Teodorescu, M.; Brucher, J.

    1972-01-01

    An investigation on human peripheral blood lymphocyte chromosomes in chronic active hepatitis was carried out. A higher percentage of chromatid and chromosome lesions was recorded in all patients studied as compared with control groups—normal individuals, healthy subjects who had suffered from acute viral hepatitis, patients with alcoholic liver disease, and patients with mechanical jaundice due to cancer. The possible origin of these abnormalities is discussed. PMID:5076805

  10. Costal bone abnormalities: an unusual cause of spontaneous bilateral breast implant deflation†.

    PubMed

    Brooker, Jack E; Gusenoff, Jeffrey A

    2014-01-01

    Augmentation mammoplasty is the most common aesthetic surgical procedure performed in the USA. Prosthetic failure is a major reason for surgical reintervention. A number of causes for this have been documented, but costal bone abnormalities leading to perforation of the prosthesis are very unusual. We present the case of a woman who experienced spontaneous deflation of both saline implants in close succession, and who was found to have sharp bony spicules on both sides of her chest. Pathology examination reported reactive changes, suggestive of heterotopic bone. Examination of the implants showed no defects besides small punctures on the back wall, which coincided with the position of the spicules of bone. There are a number of possible causes for these bony growths which we examine in turn. The chest wall should be examined in all cases where unexplained implant deflation has occurred. PMID:25535321

  11. Altered Spontaneous Brain Activity in Betel Quid Dependence

    PubMed Central

    Liu, Tao; Li, Jian-jun; Zhao, Zhong-yan; Yang, Guo-shuai; Pan, Meng-jie; Li, Chang-qing; Pan, Su-yue; Chen, Feng

    2016-01-01

    Abstract It has been suggested by the first voxel-based morphometry investigation that betel quid dependence (BQD) individuals are presented with brain structural changes in previous reports, and there may be a neurobiological basis for BQD individuals related to an increased risk of executive dysfunction and disinhibition, subjected to the reward system, cognitive system, and emotion system. However, the effects of BQD on neural activity remain largely unknown. Individuals with impaired cognitive control of behavior often reveal altered spontaneous cerebral activity in resting-state functional magnetic resonance imaging and those changes are usually earlier than structural alteration. Here, we examined BQD individuals (n = 33) and age-, sex-, and education-matched healthy control participants (n = 32) in an resting-state functional magnetic resonance imaging study to observe brain function alterations associated with the severity of BQD. Amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values were both evaluated to stand for spontaneous cerebral activity. Gray matter volumes of these participants were also calculated for covariate. In comparison with healthy controls, BQD individuals demonstrated dramatically decreased ALFF and ReHo values in the prefrontal gurus along with left fusiform, and increased ALFF and ReHo values in the primary motor cortex area, temporal lobe as well as some regions of occipital lobe. The betel quid dependence scores (BQDS) were negatively related to decreased activity in the right anterior cingulate. The abnormal spontaneous cerebral activity revealed by ALFF and ReHo calculation excluding the structural differences in patients with BQD may help us probe into the neurological pathophysiology underlying BQD-related executive dysfunction and disinhibition. Diminished spontaneous brain activity in the right anterior cingulate cortex may, therefore, represent a biomarker of BQD individuals. PMID

  12. Spontaneous Circulation of Confined Active Suspensions

    NASA Astrophysics Data System (ADS)

    Woodhouse, Francis; Goldstein, Raymond

    2012-11-01

    Many active fluid systems encountered in biology are set in total geometric confinement; cytoplasmic streaming is a prominent and ubiquitous example. Using the simple paradigm of a dilute dipolar swimmer suspension, we demonstrate that the two key constraints of circular confinement and fluid incompressibility yield qualitatively new dynamics, effectively quantizing the behaviour regimes. We show analytically that there is an activity threshold for spontaneous auto-circulation and verify this numerically. Long-time non-linear behaviour is investigated via simulations, which reveal steady states displaying nematic defect separation and a high-activity bifurcation to an oscillatory regime.

  13. Spontaneous activity in the developing auditory system.

    PubMed

    Wang, Han Chin; Bergles, Dwight E

    2015-07-01

    Spontaneous electrical activity is a common feature of sensory systems during early development. This sensory-independent neuronal activity has been implicated in promoting their survival and maturation, as well as growth and refinement of their projections to yield circuits that can rapidly extract information about the external world. Periodic bursts of action potentials occur in auditory neurons of mammals before hearing onset. This activity is induced by inner hair cells (IHCs) within the developing cochlea, which establish functional connections with spiral ganglion neurons (SGNs) several weeks before they are capable of detecting external sounds. During this pre-hearing period, IHCs fire periodic bursts of Ca(2+) action potentials that excite SGNs, triggering brief but intense periods of activity that pass through auditory centers of the brain. Although spontaneous activity requires input from IHCs, there is ongoing debate about whether IHCs are intrinsically active and their firing periodically interrupted by external inhibitory input (IHC-inhibition model), or are intrinsically silent and their firing periodically promoted by an external excitatory stimulus (IHC-excitation model). There is accumulating evidence that inner supporting cells in Kölliker's organ spontaneously release ATP during this time, which can induce bursts of Ca(2+) spikes in IHCs that recapitulate many features of auditory neuron activity observed in vivo. Nevertheless, the role of supporting cells in this process remains to be established in vivo. A greater understanding of the molecular mechanisms responsible for generating IHC activity in the developing cochlea will help reveal how these events contribute to the maturation of nascent auditory circuits. PMID:25296716

  14. Spontaneous Oscillations in an Active Matter System

    NASA Astrophysics Data System (ADS)

    Hayes, Robert; Tsang, Boyce; Granick, Steve

    Active matter (which consumes energy to move about) can organize into dynamic structures more interesting than those possible at steady-state. Here we show spontaneous periodic self-assembly in a simple three-component system of water, oil phase, and surfactant at constant room temperature, with emphasis on one model system. Benchtop experiments show that liquid crystal oil droplets spontaneously and collectively oscillate like a `beating heart' for several hours; contract, relax, and subsequently re-contract in a petri dish at a rate of a few `beats' per minute. These oscillations, emergent from the cooperative interaction of the three components, are driven by the competition between positive and negative feedback processes. This illustration of feedback in action reveals a new way to program self-assembled structures to vary with time.

  15. Sloppiness in Spontaneously Active Neuronal Networks

    PubMed Central

    Panas, Dagmara; Amin, Hayder; Maccione, Alessandro; Muthmann, Oliver; van Rossum, Mark; Berdondini, Luca

    2015-01-01

    Various plasticity mechanisms, including experience-dependent, spontaneous, as well as homeostatic ones, continuously remodel neural circuits. Yet, despite fluctuations in the properties of single neurons and synapses, the behavior and function of neuronal assemblies are generally found to be very stable over time. This raises the important question of how plasticity is coordinated across the network. To address this, we investigated the stability of network activity in cultured rat hippocampal neurons recorded with high-density multielectrode arrays over several days. We used parametric models to characterize multineuron activity patterns and analyzed their sensitivity to changes. We found that the models exhibited sloppiness, a property where the model behavior is insensitive to changes in many parameter combinations, but very sensitive to a few. The activity of neurons with sloppy parameters showed faster and larger fluctuations than the activity of a small subset of neurons associated with sensitive parameters. Furthermore, parameter sensitivity was highly correlated with firing rates. Finally, we tested our observations from cell cultures on an in vivo recording from monkey visual cortex and we confirm that spontaneous cortical activity also shows hallmarks of sloppy behavior and firing rate dependence. Our findings suggest that a small subnetwork of highly active and stable neurons supports group stability, and that this endows neuronal networks with the flexibility to continuously remodel without compromising stability and function. PMID:26041916

  16. Spontaneous autoimmune thyroiditis in obese strain chickens: a genetic analysis of target organ abnormalities

    SciTech Connect

    Neu, N.; Hala, K.; Dietrich, H.; Wick, G.

    1985-12-01

    In this study the authors investigated the genetic background of primary abnormalities found in the thyroid gland of Obese strain (OS) chickens with spontaneous autoimmune thyroiditis (SAT), i.e., susceptibility to passively transferred antibodies to thyroglobulin (TgAb) and incomplete suppression of iodine uptake by thyroxine (T4). Several crosses between the B15/B15 subline of OS chickens and the inbred CB line (B12/B12) were done and the progeny was analyzed for thyroiditis after injection of OS serum containing high titers of TgAb. It was found that passive transfer of TgAb increased the lymphoid infiltration in the thyroids of OS chickens, but had no effect on CB birds. A genetic analysis of backcrosses revealed that this trait is, in the case of simple Mendelian inheritance, encoded by at least three recessive genes. The thyroidal T I uptake of these crosses under T4 was also determined and they found that this trait is most probably encoded by only one recessive gene.

  17. Spontaneous circulation of confined active suspensions.

    PubMed

    Woodhouse, Francis G; Goldstein, Raymond E

    2012-10-19

    Many active fluid systems encountered in biology are set in total geometric confinement. Cytoplasmic streaming in plant cells is a prominent and ubiquitous example, in which cargo-carrying molecular motors move along polymer filaments and generate coherent cell-scale flow. When filaments are not fixed to the cell periphery, a situation found both in vivo and in vitro, we observe that the basic dynamics of streaming are closely related to those of a nonmotile stresslet suspension. Under this model, it is demonstrated that confinement makes possible a stable circulating state; a linear stability analysis reveals an activity threshold for spontaneous autocirculation. Numerical analysis of the longtime behavior reveals a phenomenon akin to defect separation in nematic liquid crystals and a high-activity bifurcation to an oscillatory regime. PMID:23215137

  18. Spontaneous Circulation of Confined Active Suspensions

    NASA Astrophysics Data System (ADS)

    Woodhouse, Francis G.; Goldstein, Raymond E.

    2012-10-01

    Many active fluid systems encountered in biology are set in total geometric confinement. Cytoplasmic streaming in plant cells is a prominent and ubiquitous example, in which cargo-carrying molecular motors move along polymer filaments and generate coherent cell-scale flow. When filaments are not fixed to the cell periphery, a situation found both in vivo and in vitro, we observe that the basic dynamics of streaming are closely related to those of a nonmotile stresslet suspension. Under this model, it is demonstrated that confinement makes possible a stable circulating state; a linear stability analysis reveals an activity threshold for spontaneous autocirculation. Numerical analysis of the longtime behavior reveals a phenomenon akin to defect separation in nematic liquid crystals and a high-activity bifurcation to an oscillatory regime.

  19. Alteration of spontaneous brain activity in COPD patients

    PubMed Central

    Zhang, Jiaxing; Chen, Ji; Yu, Qian; Fan, Cunxiu; Zhang, Ran; Lin, Jianzhong; Yang, Tianhe; Fan, Ming

    2016-01-01

    Background and objective Airflow limitation in chronic obstructive pulmonary disease (COPD) results in a decrease in oxygen transport to the brain. The aim of the present study was to explore the alteration of spontaneous brain activity induced by hypoxia in patients with COPD. Patients and methods Twenty-five stable patients with COPD and 25 matching healthy volunteers were investigated. Amplitude of low-frequency fluctuation (ALFF) of blood oxygenation level-dependent signal at resting state in the brain was analyzed using functional magnetic resonance imaging. Results Whole-brain analysis using functional magnetic resonance imaging revealed significant decreases in ALFF in the bilateral posterior cingulate gyri and right lingual gyrus and an increase in ALFF in the left postcentral gyrus of patients with COPD. After controlling for SaO2, patients with COPD only showed an increase in ALFF in the left postcentral gyrus. Region of interest analysis showed a decrease in ALFF in the left precentral gyrus and an increase in ALFF in the left caudate nucleus of patients with COPD. In all subjects, ALFF in the bilateral posterior cingulate gyri and right lingual gyrus showed positive correlations with visual reproduction. Conclusion We demonstrated abnormal spontaneous brain activity of patients with COPD, which may have a pathophysiologic meaning. PMID:27555761

  20. Suppression of Chemically Induced and Spontaneous Mouse Oocyte Activation by AMP-Activated Protein Kinase1

    PubMed Central

    Ya, Ru; Downs, Stephen M.

    2013-01-01

    ABSTRACT Oocyte activation is an important process triggered by fertilization that initiates embryonic development. However, parthenogenetic activation can occur either spontaneously or with chemical treatments. The LT/Sv mouse strain is genetically predisposed to spontaneous activation. LT oocytes have a cell cycle defect and are ovulated at the metaphase I stage instead of metaphase II. A thorough understanding of the female meiosis defects in this strain remains elusive. We have reported that AMP-activated protein kinase (PRKA) has an important role in stimulating meiotic resumption and promoting completion of meiosis I while suppressing premature parthenogenetic activation. Here we show that early activation of PRKA during the oocyte maturation period blocked chemically induced activation in B6SJL oocytes and spontaneous activation in LT/SvEiJ oocytes. This inhibitory effect was associated with high levels of MAPK1/3 activity. Furthermore, stimulation of PRKA partially rescued the meiotic defects of LT/Sv mouse oocytes in concert with correction of abnormal spindle pole localization of PRKA and loss of prolonged spindle assembly checkpoint activity. Altogether, these results confirm a role for PRKA in helping sustain the MII arrest in mature oocytes and suggest that dysfunctional PRKA contributes to meiotic defects in LT/SvEiJ oocytes. PMID:23390161

  1. Abnormal fast activity in infancy with paroxysmal downwards gaze.

    PubMed

    Yoshinaga, Harumi; Kobayashi, Katsuhiro; Endo, Fumika; Ishizaki, Yumiko; Wakai, Mari; Ohtsuka, Yoko

    2009-06-01

    We report here on 8 infants who showed paroxysmal downwards gaze (PDG). The time of initial appearance of PDG ranged from one month to five months (mean: 2.7 months) of corrected age. Seven out of eight patients showed interictal spikes in EEG, so they were started on prophylactic therapy with antiepileptic drugs. In five of the eight patients, PDG ceased, either spontaneously or with antiepileptic drug treatment, by four to eight months of corrected age. Six out of eight patients showed localized spikes and peculiar abnormal fast activity (AFA) in the occipital area and five of these patients later developed West syndrome. These AFA were observed on EEGs recorded at the time of initial PDG appearance, before hypsarrhythmia was observed and before tonic spasms appeared. We were able to exclude the possibility that PDG was a subtle epileptic seizure by confirming the temporal discordance between individual episodes of PDG and AFA with video-EEG monitoring. Yet topographic data showed that AFA in these patients was characteristically located in the occipital area, with a distribution similar to that of the fast activity which accompanied the tonic spasms that later developed in these patients. As a risk factor for developing WS, we propose the clinical symptom of PDG with characteristic occipital AFA visible in the EEG, both of which represent damage to the occipital region including the optic radiation. PMID:18804928

  2. Spontaneous motion in hierarchically assembled active matter

    PubMed Central

    Sanchez, Tim; Chen, Daniel T. N.; DeCamp, Stephen J.; Heymann, Michael; Dogic, Zvonimir

    2012-01-01

    With exquisite precision and reproducibility, cells orchestrate the cooperative action of thousands of nanometer-sized molecular motors to carry out mechanical tasks at much larger length scales, such as cell motility, division and replication1. Besides their biological importance, such inherently non-equilibrium processes are an inspiration for developing biomimetic active materials from microscopic components that consume energy to generate continuous motion2–4. Being actively driven, these materials are not constrained by the laws of equilibrium statistical mechanics and can thus exhibit highly sought-after properties such as autonomous motility, internally generated flows and self-organized beating5–7. Starting from extensile microtubule bundles, we hierarchically assemble active analogs of conventional polymer gels, liquid crystals and emulsions. At high enough concentration, microtubules form a percolating active network characterized by internally driven chaotic flows, hydrodynamic instabilities, enhanced transport and fluid mixing. When confined to emulsion droplets, 3D networks spontaneously adsorb onto the droplet surfaces to produce highly active 2D nematic liquid crystals whose streaming flows are controlled by internally generated fractures and self-healing, as well as unbinding and annihilation of oppositely charged disclination defects. The resulting active emulsions exhibit unexpected properties, such as autonomous motility, which are not observed in their passive analogues. Taken together, these observations exemplify how assemblages of animate microscopic objects exhibit collective biomimetic properties that are starkly different from those found in materials assembled from inanimate building blocks, challenging us to develop a theoretical framework that would allow for a systematic engineering of their far-from-equilibrium material properties. PMID:23135402

  3. Development of a spontaneously active dorsal root ganglia assay using multiwell multielectrode arrays.

    PubMed

    Newberry, Kim; Wang, Shuya; Hoque, Nina; Kiss, Laszlo; Ahlijanian, Michael K; Herrington, James; Graef, John D

    2016-06-01

    In vitro phenotypic assays of sensory neuron activity are important tools for identifying potential analgesic compounds. These assays are typically characterized by hyperexcitable and/or abnormally, spontaneously active cells. Whereas manual electrophysiology experiments provide high-resolution biophysical data to characterize both in vitro models and potential therapeutic modalities (e.g., action potential characteristics, the role of specific ion channels, and receptors), these techniques are hampered by their low throughput. We have established a spontaneously active dorsal root ganglia (DRG) platform using multiwell multielectrode arrays (MEAs) that greatly increase the ability to evaluate the effects of multiple compounds and conditions on DRG excitability within the context of a cellular network. We show that spontaneous DRG firing can be attenuated with selective Na(+) and Ca(2+) channel blockers, as well as enhanced with K(+) channel blockers. In addition, spontaneous activity can be augmented with both the transient receptor potential cation channel subfamily V member 1 agonist capsaicin and the peptide bradykinin and completely blocked with neurokinin receptor antagonists. Finally, we validated the use of this assay by demonstrating that commonly used neuropathic pain therapeutics suppress DRG spontaneous activity. Overall, we have optimized primary rat DRG cells on a multiwell MEA platform to generate and characterize spontaneously active cultures that have the potential to be used as an in vitro phenotypic assay to evaluate potential therapeutics in rodent models of pain. PMID:27052585

  4. Development of Spontaneous Activity in the Avian Hindbrain.

    PubMed

    Momose-Sato, Yoko; Sato, Katsushige

    2016-01-01

    Spontaneous activity in the developing central nervous system occurs before the brain responds to external sensory inputs, and appears in the hindbrain and spinal cord as rhythmic electrical discharges of cranial and spinal nerves. This spontaneous activity recruits a large population of neurons and propagates like a wave over a wide region of the central nervous system. Here, we review spontaneous activity in the chick hindbrain by focusing on this large-scale synchronized activity. Asynchronous activity that is expressed earlier than the above mentioned synchronized activity and activity originating in midline serotonergic neurons are also briefly mentioned. PMID:27570506

  5. Development of Spontaneous Activity in the Avian Hindbrain

    PubMed Central

    Momose-Sato, Yoko; Sato, Katsushige

    2016-01-01

    Spontaneous activity in the developing central nervous system occurs before the brain responds to external sensory inputs, and appears in the hindbrain and spinal cord as rhythmic electrical discharges of cranial and spinal nerves. This spontaneous activity recruits a large population of neurons and propagates like a wave over a wide region of the central nervous system. Here, we review spontaneous activity in the chick hindbrain by focusing on this large-scale synchronized activity. Asynchronous activity that is expressed earlier than the above mentioned synchronized activity and activity originating in midline serotonergic neurons are also briefly mentioned. PMID:27570506

  6. Spectral changes in spontaneous MEG activity across the lifespan

    NASA Astrophysics Data System (ADS)

    Gómez, Carlos; Pérez-Macías, Jose M.; Poza, Jesús; Fernández, Alberto; Hornero, Roberto

    2013-12-01

    Objective. The aim of this study is to explore the spectral patterns of spontaneous magnetoencephalography (MEG) activity across the lifespan. Approach. Relative power (RP) in six frequency bands (delta, theta, alpha, beta-1, beta-2 and gamma) was calculated in a sample of 220 healthy subjects with ages ranging from 7 to 84 years. Main results. A significant RP decrease in low-frequency bands (i.e. delta and theta) and a significant increase in high bands (mainly beta-1 and beta-2) were found from childhood to adolescence. This trend was observed until the sixth decade of life, though only slight changes were found. Additionally, healthy aging was characterized by a power increase in low-frequency bands. Our results show that spectral changes across the lifespan may follow a quadratic relationship in delta, theta, alpha, beta-2 and gamma bands with peak ages being reached around the fifth or sixth decade of life. Significance. Our findings provide original insights into the definition of the ‘normal’ behavior of age-related MEG spectral patterns. Furthermore, our study can be useful for the forthcoming MEG research focused on the description of the abnormalities of different brain diseases in comparison to cognitive decline in normal aging.

  7. Mutations in ASPH Cause Facial Dysmorphism, Lens Dislocation, Anterior-Segment Abnormalities, and Spontaneous Filtering Blebs, or Traboulsi Syndrome

    PubMed Central

    Patel, Nisha; Khan, Arif O.; Mansour, Ahmad; Mohamed, Jawahir Y.; Al-Assiri, Abdullah; Haddad, Randa; Jia, Xiaofei; Xiong, Yong; Mégarbané, André; Traboulsi, Elias I.; Alkuraya, Fowzan S.

    2014-01-01

    We have previously described a syndrome characterized by facial dysmorphism, lens dislocation, anterior-segment abnormalities, and spontaneous filtering blebs (FDLAB, or Traboulsi syndrome). In view of the consanguineous nature of the affected families and the likely autosomal-recessive inheritance pattern of this syndrome, we undertook autozygosity mapping and whole-exome sequencing to identify ASPH as the disease locus, in which we identified two homozygous mutations. ASPH encodes aspartyl/asparaginyl β-hydroxylase (ASPH), which has been found to hydroxylate aspartic acid and asparagine residues on epidermal growth factor (EGF)-domain-containing proteins. The truncating and missense mutations we identified are predicted to severely impair the enzymatic function of ASPH, which suggests a possible link to other forms of ectopia lentis given that many of the genes implicated in this phenotype encode proteins that harbor EGF domains. Developmental analysis of Asph revealed an expression pattern consistent with the proposed link to the human syndrome. Indeed, Asph-knockout mice had a foreshortened snout, which corresponds to the facial abnormalities in individuals with Traboulsi syndrome. These data support a genetic basis for a syndromic form of ectopia lentis and the role of aspartyl hydroxylation in human development. PMID:24768550

  8. Abnormal uterine artery remodelling in the stroke prone spontaneously hypertensive rat

    PubMed Central

    Small, Heather Y.; Morgan, Hannah; Beattie, Elisabeth; Griffin, Sinead; Indahl, Marie; Delles, Christian; Graham, Delyth

    2016-01-01

    Introduction The stroke prone spontaneously hypertensive rat (SHRSP) is an established model of human cardiovascular risk. We sought to characterise the uteroplacental vascular response to pregnancy in this model and determine whether this is affected by the pre-existing maternal hypertension. Methods Doppler ultrasound and myography were utilised to assess uterine artery functional and structural changes pre-pregnancy and at gestational day 18 in SHRSP (untreated and nifedipine treated) and in the normotensive Wistar-Kyoto (WKY) rat. Maternal adaptations to pregnancy were also assessed along with histology and expression of genes involved in oxidative stress in the placenta. Results SHRSP uterine arteries had a pulsatile blood flow and were significantly smaller (70906 ± 3903 μm2 vs. 95656 ± 8524 μm2 cross-sectional area; p < 0.01), had a significant increase in contractile response (57.3 ± 10.5 kPa vs 27.7 ± 1.9 kPa; p < 0.01) and exhibited impaired endothelium-dependent vasorelaxation (58.0 ± 5.9% vs 13.9 ± 4.6%; p < 0.01) compared to WKY. Despite significant blood pressure lowering, nifedipine did not improve uterine artery remodelling, function or blood flow in SHRSP. Maternal plasma sFLT-1/PlGF ratio (5.3 ± 0.3 vs 4.6 ± 0.1; p < 0.01) and the urinary albumin/creatinine ratio (1.9 ± 0.2 vs 0.6 ± 0.1; p < 0.01) was increased in SHRSP vs WKY. The SHRSP placenta had a significant reduction in glycogen cell content and an increase in Hif1α, Sod1 and Vegf. Discussion We conclude that the SHRSP exhibits a number of promising characteristics as a model of spontaneous deficient uteroplacental remodelling that adversely affect pregnancy outcome, independent of pre-existing hypertension. PMID:26612342

  9. Altered Spontaneous Brain Activity in Patients with Hemifacial Spasm: A Resting-State Functional MRI Study

    PubMed Central

    Tu, Ye; Wei, Yongxu; Sun, Kun; Zhao, Weiguo; Yu, Buwei

    2015-01-01

    Resting-state functional magnetic resonance imaging (fMRI) has been used to detect the alterations of spontaneous neuronal activity in various neurological and neuropsychiatric diseases, but rarely in hemifacial spasm (HFS), a nervous system disorder. We used resting-state fMRI with regional homogeneity (ReHo) analysis to investigate changes in spontaneous brain activity of patients with HFS and to determine the relationship of these functional changes with clinical features. Thirty patients with HFS and 33 age-, sex-, and education-matched healthy controls were included in this study. Compared with controls, HFS patients had significantly decreased ReHo values in left middle frontal gyrus (MFG), left medial cingulate cortex (MCC), left lingual gyrus, right superior temporal gyrus (STG) and right precuneus; and increased ReHo values in left precentral gyrus, anterior cingulate cortex (ACC), right brainstem, and right cerebellum. Furthermore, the mean ReHo value in brainstem showed a positive correlation with the spasm severity (r = 0.404, p = 0.027), and the mean ReHo value in MFG was inversely related with spasm severity in HFS group (r = -0.398, p = 0.028). This study reveals that HFS is associated with abnormal spontaneous brain activity in brain regions most involved in motor control and blinking movement. The disturbances of spontaneous brain activity reflected by ReHo measurements may provide insights into the neurological pathophysiology of HFS. PMID:25603126

  10. Spontaneous activity does not predict morphological type in cerebellar interneurons.

    PubMed

    Haar, Shlomi; Givon-Mayo, Ronit; Barmack, Neal H; Yakhnitsa, Vadim; Donchin, Opher

    2015-01-28

    The effort to determine morphological and anatomically defined neuronal characteristics from extracellularly recorded physiological signatures has been attempted with varying success in different brain areas. Recent studies have attempted such classification of cerebellar interneurons (CINs) based on statistical measures of spontaneous activity. Previously, such efforts in different brain areas have used supervised clustering methods based on standard parameterizations of spontaneous interspike interval (ISI) histograms. We worried that this might bias researchers toward positive identification results and decided to take a different approach. We recorded CINs from anesthetized cats. We used unsupervised clustering methods applied to a nonparametric representation of the ISI histograms to identify groups of CINs with similar spontaneous activity and then asked how these groups map onto different cell types. Our approach was a fuzzy C-means clustering algorithm applied to the Kullbach-Leibler distances between ISI histograms. We found that there is, in fact, a natural clustering of the spontaneous activity of CINs into six groups but that there was no relationship between this clustering and the standard morphologically defined cell types. These results proved robust when generalization was tested to completely new datasets, including datasets recorded under different anesthesia conditions and in different laboratories and different species (rats). Our results suggest the importance of an unsupervised approach in categorizing neurons according to their extracellular activity. Indeed, a reexamination of such categorization efforts throughout the brain may be necessary. One important open question is that of functional differences of our six spontaneously defined clusters during actual behavior. PMID:25632121

  11. Abnormal bone mineral density and bone turnover marker expression profiles in patients with primary spontaneous pneumothorax

    PubMed Central

    Yu, Lixin; Hou, Shengcai; Hu, Bin; Zhao, Liqiang; Miao, Jinbai; Wang, Yang; Li, Tong; Zhang, Zhenkui; You, Bin; Pang, Baosen; Liang, Yufang; Zhao, Yi; Hao, Wei

    2016-01-01

    Background To examine the bone mineral density (BMD) and the role of bone biomarkers, including bone formation marker procollagen type I aminoterminal propeptide (PINP) and N-terminal midmolecule fragment osteocalcin (N-MID), bone resorption marker b-C-telopeptides of type I collagen (b-CTX) and tartrate-resistant acid phosphatase 5b (TRACP5b) in the pathogenesis of PSP. Methods Eighty-three consecutive primary spontaneous pneumothorax (PSP) patients (PSP group) and 87 healthy individuals (control group) were enrolled in this study. General data, including gender, age, height, weight, and body mass index (BMI), were recorded. Dual-energy X-ray absorptiometry, electrochemiluminescence immunoassay (ECLIA), and ELISA were used to evaluate bone mineral density and expression levels of bone metabolism markers, including PINP, b-CTX, TRACP5b, N-MID, and 25-hydroxyvitamin D (25-OH VD). Results Mean height was significantly greater in the PSP group compared with the control group, whereas weight and BMI were lower. Patients in the PSP group had significantly lower average bone mineral density, which mainly manifested as osteopenia (11/12, 91.7%); however, only one patient (8.3%) developed osteoporosis. Serum overexpression of PINP, b-CTX, TRACP5b, and N-MID were found in PSP patients. Expression of 25-OH VD was low in PSP patients. Bone resorption markers showed positive linear relationships with bone formation markers in all participants; whereas only TRACP5b expression negatively correlated with 25-OH VD. Expression levels of all bone turnover markers negatively correlated with BMI. Regression analysis identified risk factors of PSP as age, height, weight, and TRACP5b and 25-OH VD expression levels; whereas gender and PINP, b-CTX, and N-MID expression levels were not significantly associated with the onset of PSP. Conclusions It had lower bone mineral density in PSP patients. Bone formation marker PINP, N-MID and bone resorption marker b-CTX, TRACP5b were upregulated in

  12. Determination of the Spontaneous Locomotor Activity in Drosophila melanogaster

    PubMed Central

    Woods, Jared K.; Kowalski, Suzanne; Rogina, Blanka

    2014-01-01

    Drosophila melanogaster has been used as an excellent model organism to study environmental and genetic manipulations that affect behavior. One such behavior is spontaneous locomotor activity. Here we describe our protocol that utilizes Drosophila population monitors and a tracking system that allows continuous monitoring of the spontaneous locomotor activity of flies for several days at a time. This method is simple, reliable, and objective and can be used to examine the effects of aging, sex, changes in caloric content of food, addition of drugs, or genetic manipulations that mimic human diseases. PMID:24747955

  13. Determination of the spontaneous locomotor activity in Drosophila melanogaster.

    PubMed

    Woods, Jared K; Kowalski, Suzanne; Rogina, Blanka

    2014-01-01

    Drosophila melanogaster has been used as an excellent model organism to study environmental and genetic manipulations that affect behavior. One such behavior is spontaneous locomotor activity. Here we describe our protocol that utilizes Drosophila population monitors and a tracking system that allows continuous monitoring of the spontaneous locomotor activity of flies for several days at a time. This method is simple, reliable, and objective and can be used to examine the effects of aging, sex, changes in caloric content of food, addition of drugs, or genetic manipulations that mimic human diseases. PMID:24747955

  14. Effects of unilateral acoustic trauma on tinnitus-related spontaneous activity in the inferior colliculus.

    PubMed

    Ropp, Tessa-Jonne F; Tiedemann, Kerrie L; Young, Eric D; May, Bradford J

    2014-12-01

    This study describes the long-term effects of sound-induced cochlear trauma on spontaneous discharge rates in the central nucleus of the inferior colliculus (ICC). As in previous studies, single-unit recordings in Sprague-Dawley rats revealed pervasive increases in spontaneous discharge rates. Based on differences in their sources of input, it was hypothesized that physiologically defined neural populations of the auditory midbrain would reveal the brainstem sources that dictate ICC hyperactivity. Abnormal spontaneous activity was restricted to target neurons of the ventral cochlear nucleus. Nearly identical patterns of hyperactivity were observed in the contralateral and ipsilateral ICC. The elevation in spontaneous activity extended to frequencies well below and above the region of maximum threshold shift. This lack of frequency organization suggests that ICC hyperactivity may be influenced by regions of the brainstem that are not tonotopically organized. Sound-induced hyperactivity is often observed in animals with behavioral signs of tinnitus. Prior to electrophysiological recording, rats were screened for tinnitus by measuring gap pre-pulse inhibition of the acoustic startle reflex (GPIASR). Rats with positive phenotypes did not exhibit unique patterns of ICC hyperactivity. This ambiguity raises concerns regarding animal behavioral models of tinnitus. If our screening procedures were valid, ICC hyperactivity is observed in animals without behavioral indications of the disorder. Alternatively, if the perception of tinnitus is strictly linked to ongoing ICC hyperactivity, our current behavioral approach failed to provide a reliable assessment of tinnitus state. PMID:25255865

  15. Spontaneous Activity Drives Local Synaptic Plasticity In Vivo.

    PubMed

    Winnubst, Johan; Cheyne, Juliette E; Niculescu, Dragos; Lohmann, Christian

    2015-07-15

    Spontaneous activity fine-tunes neuronal connections in the developing brain. To explore the underlying synaptic plasticity mechanisms, we monitored naturally occurring changes in spontaneous activity at individual synapses with whole-cell patch-clamp recordings and simultaneous calcium imaging in the mouse visual cortex in vivo. Analyzing activity changes across large populations of synapses revealed a simple and efficient local plasticity rule: synapses that exhibit low synchronicity with nearby neighbors (<12 μm) become depressed in their transmission frequency. Asynchronous electrical stimulation of individual synapses in hippocampal slices showed that this is due to a decrease in synaptic transmission efficiency. Accordingly, experimentally increasing local synchronicity, by stimulating synapses in response to spontaneous activity at neighboring synapses, stabilized synaptic transmission. Finally, blockade of the high-affinity proBDNF receptor p75(NTR) prevented the depression of asynchronously stimulated synapses. Thus, spontaneous activity drives local synaptic plasticity at individual synapses in an "out-of-sync, lose-your-link" fashion through proBDNF/p75(NTR) signaling to refine neuronal connectivity. VIDEO ABSTRACT. PMID:26182421

  16. The thermal origin of spontaneous activity in the Limulus photoreceptor

    PubMed Central

    Srebro, Richard; Behbehani, Mahmood

    1972-01-01

    1. Discrete depolarizations of the photoreceptor cell membrane called discrete waves occur spontaneously and in response to illumination in the eye of the horseshoe crab, Limulus. Each light induced discrete wave is caused by the absorption of a single photon. 2. The frequencies of spontaneous and light induced discrete waves were studied at different temperatures from 0 to 25° C using a new method of counting them to avoid errors due to their temporal overlap. 3. The frequency of spontaneous discrete waves followed the Arrhenius relationship with activation energy equal to 48·6 kcal. 4. The frequency of the discrete waves caused by a fixed level of steady illumination was not significantly changed when the temperature of the cell was changed. 5. The relationship of the frequency of spontaneous discrete waves to temperature was compared to a prediction based on the relationship of the quantum relative spectral sensitivity of the Limulus eye to the temperature of the eye. The prediction was in good agreement with observation and suggests that spontaneous discrete waves result from thermally induced cis to trans isomerizations of visual pigment molecules. PMID:5071400

  17. The emergence of spontaneous activity in neuronal cultures

    NASA Astrophysics Data System (ADS)

    Orlandi, J. G.; Alvarez-Lacalle, E.; Teller, S.; Soriano, J.; Casademunt, J.

    2013-01-01

    In vitro neuronal networks of dissociated hippocampal or cortical tissues are one of the most attractive model systems for the physics and neuroscience communities. Cultured neurons grow and mature, develop axons and dendrites, and quickly connect to their neighbors to establish a spontaneously active network within a week. The resulting neuronal network is characterized by a combination of excitatory and inhibitory neurons coupled through synaptic connections that interact in a highly nonlinear manner. The nonlinear behavior emerges from the dynamics of both the neurons' spiking activity and synaptic transmission, together with biological noise. These ingredients give rise to a rich repertoire of phenomena that are still poorly understood, including the emergence and maintenance of periodic spontaneous activity, avalanches, propagation of fronts and synchronization. In this work we present an overview on the rich activity of cultured neuronal networks, and detail the minimal theoretical considerations needed to describe experimental observations.

  18. Synchronization of Spontaneous Active Motility of Hair Cell Bundles

    PubMed Central

    Zhang, Tracy-Ying; Ji, Seung; Bozovic, Dolores

    2015-01-01

    Hair cells of the inner ear exhibit an active process, believed to be crucial for achieving the sensitivity of auditory and vestibular detection. One of the manifestations of the active process is the occurrence of spontaneous hair bundle oscillations in vitro. Hair bundles are coupled by overlying membranes in vivo; hence, explaining the potential role of innate bundle motility in the generation of otoacoustic emissions requires an understanding of the effects of coupling on the active bundle dynamics. We used microbeads to connect small groups of hair cell bundles, using in vitro preparations that maintain their innate oscillations. Our experiments demonstrate robust synchronization of spontaneous oscillations, with either 1:1 or multi-mode phase-locking. The frequency of synchronized oscillation was found to be near the mean of the innate frequencies of individual bundles. Coupling also led to an improved regularity of entrained oscillations, demonstrated by an increase in the quality factor. PMID:26540409

  19. Synchronization of Spontaneous Active Motility of Hair Cell Bundles.

    PubMed

    Zhang, Tracy-Ying; Ji, Seung; Bozovic, Dolores

    2015-01-01

    Hair cells of the inner ear exhibit an active process, believed to be crucial for achieving the sensitivity of auditory and vestibular detection. One of the manifestations of the active process is the occurrence of spontaneous hair bundle oscillations in vitro. Hair bundles are coupled by overlying membranes in vivo; hence, explaining the potential role of innate bundle motility in the generation of otoacoustic emissions requires an understanding of the effects of coupling on the active bundle dynamics. We used microbeads to connect small groups of hair cell bundles, using in vitro preparations that maintain their innate oscillations. Our experiments demonstrate robust synchronization of spontaneous oscillations, with either 1:1 or multi-mode phase-locking. The frequency of synchronized oscillation was found to be near the mean of the innate frequencies of individual bundles. Coupling also led to an improved regularity of entrained oscillations, demonstrated by an increase in the quality factor. PMID:26540409

  20. Spontaneous Division and Motility in Active Nematic Droplets

    NASA Astrophysics Data System (ADS)

    Giomi, Luca; DeSimone, Antonio

    2014-04-01

    We investigate the mechanics of an active droplet endowed with internal nematic order and surrounded by an isotropic Newtonian fluid. Using numerical simulations we demonstrate that, due to the interplay between the active stresses and the defective geometry of the nematic director, this system exhibits two of the fundamental functions of living cells: spontaneous division and motility, by means of self-generated hydrodynamic flows. These behaviors can be selectively activated by controlling a single physical parameter, namely, an active variant of the capillary number.

  1. A spontaneous mutation in the nicotinamide nucleotide transhydrogenase gene of C57BL/6J mice results in mitochondrial redox abnormalities.

    PubMed

    Ronchi, Juliana A; Figueira, Tiago R; Ravagnani, Felipe G; Oliveira, Helena C F; Vercesi, Anibal E; Castilho, Roger F

    2013-10-01

    NADPH is the reducing agent for mitochondrial H2O2 detoxification systems. Nicotinamide nucleotide transhydrogenase (NNT), an integral protein located in the inner mitochondrial membrane, contributes to an elevated mitochondrial NADPH/NADP(+) ratio. This enzyme catalyzes the reduction of NADP(+) at the expense of NADH oxidation and H(+) reentry to the mitochondrial matrix. A spontaneous Nnt mutation in C57BL/6J (B6J-Nnt(MUT)) mice arose nearly 3 decades ago but was only discovered in 2005. Here, we characterize the consequences of the Nnt mutation on the mitochondrial redox functions of B6J-Nnt(MUT) mice. Liver mitochondria were isolated both from an Nnt wild-type C57BL/6 substrain (B6JUnib-Nnt(W)) and from B6J-Nnt(MUT) mice. The functional evaluation of respiring mitochondria revealed major redox alterations in B6J-Nnt(MUT) mice, including an absence of transhydrogenation between NAD and NADP, higher rates of H2O2 release, the spontaneous oxidation of NADPH, the poor ability to metabolize organic peroxide, and a higher susceptibility to undergo Ca(2+)-induced mitochondrial permeability transition. In addition, the mitochondria of B6J-Nnt(MUT) mice exhibited increased oxidized/reduced glutathione ratios as compared to B6JUnib-Nnt(W) mice. Nonetheless, the maximal activity of NADP-dependent isocitrate dehydrogenase, which is a coexisting source of mitochondrial NADPH, was similar between both groups. Altogether, our data suggest that NNT functions as a high-capacity source of mitochondrial NADPH and that its functional loss due to the Nnt mutation results in mitochondrial redox abnormalities, most notably a poor ability to sustain NADP and glutathione in their reduced states. In light of these alterations, the potential drawbacks of using B6J-Nnt(MUT) mice in biomedical research should not be overlooked. PMID:23747984

  2. Spontaneous running activity in male rats - Effect of age

    NASA Technical Reports Server (NTRS)

    Mondon, C. E.; Dolkas, C. B.; Sims, C.; Reaven, G. M.

    1985-01-01

    Variations in the intensity and the patterns of spontaneous running activity in wheel cages were studied in male rats aged 7 weeks to one year. Daily running records were obtained for periods of 12 mo, and 24-hour recordings were made for selected runners in order to study variations in running activity during the day. The data indicate that for rats running over two miles/day, the maximum running intensity can be divided into two groups: a group of high achievers running 8 miles/day; and a group of moderate achievers running 4.8 miles/day. For both groups spontaneous activity reached a maximum after 4-5 weeks. An hourly pattern of running activity during the day was identified in rats of increasing age who averaged 9.0, 4.5, 2.6, and 1.2 miles/day, respectively. Progressive losses were observed in both the speed and the duration of spontaneous running as the rats increased in age, with the intensity of exercise falling below 2 miles/day after 7-8 months of age.

  3. Large-scale cortical correlation structure of spontaneous oscillatory activity

    PubMed Central

    Hipp, Joerg F.; Hawellek, David J.; Corbetta, Maurizio; Siegel, Markus; Engel, Andreas K.

    2013-01-01

    Little is known about the brain-wide correlation of electrophysiological signals. Here we show that spontaneous oscillatory neuronal activity exhibits frequency-specific spatial correlation structure in the human brain. We developed an analysis approach that discounts spurious correlation of signal power caused by the limited spatial resolution of electrophysiological measures. We applied this approach to source estimates of spontaneous neuronal activity reconstructed from magnetoencephalography (MEG). Overall, correlation of power across cortical regions was strongest in the alpha to beta frequency range (8–32 Hz) and correlation patterns depended on the underlying oscillation frequency. Global hubs resided in the medial temporal lobe in the theta frequency range (4–6 Hz), in lateral parietal areas in the alpha to beta frequency range (8–23 Hz), and in sensorimotor areas for higher frequencies (32–45 Hz). Our data suggest that interactions in various large-scale cortical networks may be reflected in frequency specific power-envelope correlations. PMID:22561454

  4. Abnormal patterns of displacement activities: a review and reinterpretation.

    PubMed

    Anselme, Patrick

    2008-09-01

    A series of important theoretical contributions flourished in the years 1950-1970 about displacement activities -- those 'out-of-context' actions expressed by organisms in stressful situations. Nothing really new has appeared thereafter. Although the models address different issues, such as causal factors of displacement, it appears obvious that they do not provide a unified (coherent) approach; they often explain the same phenomena using very different means and turn out to be contradictory on several points. In addition, some problems currently remain unsolved, especially concerning the fact that displacement activities exhibit 'abnormalities' of expression in comparison with the same activities performed in usual context. Each model is here described and criticized in order to evaluate its explanatory power and allow the identification of specific limits. A new, integrative model -- the Anticipatory Dynamics Model (or ADM) -- then attempts to overcome the failures of previous models. The ADM suggests that abnormal patterns of displacement activities result from attentional interference caused by a thwarting experience or conflicting motivations. At least one theoretical prediction of the ADM can be differentiated from that of any other model. PMID:18554824

  5. Memory activation reveals abnormal EEG in preclinical Huntington's disease.

    PubMed

    van der Hiele, Karin; Jurgens, Caroline K; Vein, Alla A; Reijntjes, Robert H A M; Witjes-Ané, Marie-Noëlle W; Roos, Raymund A C; van Dijk, Gert; Middelkoop, Huub A M

    2007-04-15

    The EEG is potentially useful as a marker of early Huntington's disease (HD). In dementia, the EEG during a memory activation challenge showed abnormalities where the resting EEG did not. We investigated whether memory activation also reveals EEG abnormalities in preclinical HD. Sixteen mutation carriers for HD and 13 nonmutation carriers underwent neurological, neuropsychological, MRI and EEG investigations. The EEG was registered during a rest condition, i.e. eyes closed, and a working memory task. In each condition we determined absolute power in the theta (4-8 Hz) and alpha (8-13 Hz) bands and subsequently calculated relative alpha power. The EEG during eyes closed did not differ between groups. The EEG during memory activation showed less relative alpha power in mutation carriers as compared to nonmutation carriers, even though memory performance was similar [F (1,27) = 10.87; P = 0.003]. Absolute powers also showed less alpha power [F (1,27) = 7.02; P = 0.013] but similar theta power. No correlations were found between absolute and relative alpha power on the one hand and neuropsychological scores, motor scores or number of CAG repeats on the other. In conclusion, memory activation reveals functional brain changes in Huntington's disease before clinical signs become overt. PMID:17266047

  6. Recruitment of Perisomatic Inhibition during Spontaneous Hippocampal Activity In Vitro

    PubMed Central

    Molter, Colin; Mehidi, Amine; Szabadics, Janos; Leinekugel, Xavier

    2013-01-01

    It was recently shown that perisomatic GABAergic inhibitory postsynaptic potentials (IPSPs) originating from basket and chandelier cells can be recorded as population IPSPs from the hippocampal pyramidal layer using extracellular electrodes (eIPSPs). Taking advantage of this approach, we have investigated the recruitment of perisomatic inhibition during spontaneous hippocampal activity in vitro. Combining intracellular and extracellular recordings from pyramidal cells and interneurons, we confirm that inhibitory signals generated by basket cells can be recorded extracellularly, but our results suggest that, during spontaneous activity, eIPSPs are mostly confined to the CA3 rather than CA1 region. CA3 eIPSPs produced the powerful time-locked inhibition of multi-unit activity expected from perisomatic inhibition. Analysis of the temporal dynamics of spike discharges relative to eIPSPs suggests significant but moderate recruitment of excitatory and inhibitory neurons within the CA3 network on a 10 ms time scale, within which neurons recruit each other through recurrent collaterals and trigger powerful feedback inhibition. Such quantified parameters of neuronal interactions in the hippocampal network may serve as a basis for future characterisation of pathological conditions potentially affecting the interactions between excitation and inhibition in this circuit. PMID:23805227

  7. Recruitment of Perisomatic Inhibition during Spontaneous Hippocampal Activity In Vitro.

    PubMed

    Beyeler, Anna; Retailleau, Aude; Molter, Colin; Mehidi, Amine; Szabadics, Janos; Leinekugel, Xavier

    2013-01-01

    It was recently shown that perisomatic GABAergic inhibitory postsynaptic potentials (IPSPs) originating from basket and chandelier cells can be recorded as population IPSPs from the hippocampal pyramidal layer using extracellular electrodes (eIPSPs). Taking advantage of this approach, we have investigated the recruitment of perisomatic inhibition during spontaneous hippocampal activity in vitro. Combining intracellular and extracellular recordings from pyramidal cells and interneurons, we confirm that inhibitory signals generated by basket cells can be recorded extracellularly, but our results suggest that, during spontaneous activity, eIPSPs are mostly confined to the CA3 rather than CA1 region. CA3 eIPSPs produced the powerful time-locked inhibition of multi-unit activity expected from perisomatic inhibition. Analysis of the temporal dynamics of spike discharges relative to eIPSPs suggests significant but moderate recruitment of excitatory and inhibitory neurons within the CA3 network on a 10 ms time scale, within which neurons recruit each other through recurrent collaterals and trigger powerful feedback inhibition. Such quantified parameters of neuronal interactions in the hippocampal network may serve as a basis for future characterisation of pathological conditions potentially affecting the interactions between excitation and inhibition in this circuit. PMID:23805227

  8. Altered regional homogeneity of spontaneous brain activity in idiopathic trigeminal neuralgia

    PubMed Central

    Wang, Yanping; Zhang, Xiaoling; Guan, Qiaobing; Wan, Lihong; Yi, Yahui; Liu, Chun-Feng

    2015-01-01

    The pathophysiology of idiopathic trigeminal neuralgia (ITN) has conventionally been thought to be induced by neurovascular compression theory. Recent structural brain imaging evidence has suggested an additional central component for ITN pathophysiology. However, far less attention has been given to investigations of the basis of abnormal resting-state brain activity in these patients. The objective of this study was to investigate local brain activity in patients with ITN and its correlation with clinical variables of pain. Resting-state functional magnetic resonance imaging data from 17 patients with ITN and 19 age- and sex-matched healthy controls were analyzed using regional homogeneity (ReHo) analysis, which is a data-driven approach used to measure the regional synchronization of spontaneous brain activity. Patients with ITN had decreased ReHo in the left amygdala, right parahippocampal gyrus, and left cerebellum and increased ReHo in the right inferior temporal gyrus, right thalamus, right inferior parietal lobule, and left postcentral gyrus (corrected). Furthermore, the increase in ReHo in the left precentral gyrus was positively correlated with visual analog scale (r=0.54; P=0.002). Our study found abnormal functional homogeneity of intrinsic brain activity in several regions in ITN, suggesting the maladaptivity of the process of daily pain attacks and a central role for the pathophysiology of ITN. PMID:26508861

  9. Altered regional homogeneity of spontaneous brain activity in idiopathic trigeminal neuralgia.

    PubMed

    Wang, Yanping; Zhang, Xiaoling; Guan, Qiaobing; Wan, Lihong; Yi, Yahui; Liu, Chun-Feng

    2015-01-01

    The pathophysiology of idiopathic trigeminal neuralgia (ITN) has conventionally been thought to be induced by neurovascular compression theory. Recent structural brain imaging evidence has suggested an additional central component for ITN pathophysiology. However, far less attention has been given to investigations of the basis of abnormal resting-state brain activity in these patients. The objective of this study was to investigate local brain activity in patients with ITN and its correlation with clinical variables of pain. Resting-state functional magnetic resonance imaging data from 17 patients with ITN and 19 age- and sex-matched healthy controls were analyzed using regional homogeneity (ReHo) analysis, which is a data-driven approach used to measure the regional synchronization of spontaneous brain activity. Patients with ITN had decreased ReHo in the left amygdala, right parahippocampal gyrus, and left cerebellum and increased ReHo in the right inferior temporal gyrus, right thalamus, right inferior parietal lobule, and left postcentral gyrus (corrected). Furthermore, the increase in ReHo in the left precentral gyrus was positively correlated with visual analog scale (r=0.54; P=0.002). Our study found abnormal functional homogeneity of intrinsic brain activity in several regions in ITN, suggesting the maladaptivity of the process of daily pain attacks and a central role for the pathophysiology of ITN. PMID:26508861

  10. Tuning PAK Activity to Rescue Abnormal Myelin Permeability in HNPP.

    PubMed

    Hu, Bo; Arpag, Sezgi; Zhang, Xuebao; Möbius, Wiebke; Werner, Hauke; Sosinsky, Gina; Ellisman, Mark; Zhang, Yang; Hamilton, Audra; Chernoff, Jonathan; Li, Jun

    2016-09-01

    Schwann cells in the peripheral nervous systems extend their membranes to wrap axons concentrically and form the insulating sheath, called myelin. The spaces between layers of myelin are sealed by myelin junctions. This tight insulation enables rapid conduction of electric impulses (action potentials) through axons. Demyelination (stripping off the insulating sheath) has been widely regarded as one of the most important mechanisms altering the action potential propagation in many neurological diseases. However, the effective nerve conduction is also thought to require a proper myelin seal through myelin junctions such as tight junctions and adherens junctions. In the present study, we have demonstrated the disruption of myelin junctions in a mouse model (Pmp22+/-) of hereditary neuropathy with liability to pressure palsies (HNPP) with heterozygous deletion of Pmp22 gene. We observed a robust increase of F-actin in Pmp22+/- nerve regions where myelin junctions were disrupted, leading to increased myelin permeability. These abnormalities were present long before segmental demyelination at the late phase of Pmp22+/- mice. Moreover, the increase of F-actin levels correlated with an enhanced activity of p21-activated kinase (PAK1), a molecule known to regulate actin polymerization. Pharmacological inhibition of PAK normalized levels of F-actin, and completely prevented the progression of the myelin junction disruption and nerve conduction failure in Pmp22+/- mice. Our findings explain how abnormal myelin permeability is caused in HNPP, leading to impaired action potential propagation in the absence of demyelination. We call it "functional demyelination", a novel mechanism upstream to the actual stripping of myelin that is relevant to many demyelinating diseases. This observation also provides a potential therapeutic approach for HNPP. PMID:27583434

  11. Spontaneous neuronal activity in insula predicts symptom severity of unmedicated obsessive compulsive disorder adults.

    PubMed

    Zhu, Y; Fan, Q; Zhang, Z; Zhang, H; Tong, S; Li, Y

    2015-01-01

    Emerging evidence has suggested that the pathophysiology of obsessive compulsive disorder (OCD) might involve widely distributed large-scale brain systems. The dysfunction within salience network, which is comprised of dorsal anterior cingulated cortex (dACC) and bilateral insular areas, has been proposed to contribute to OCD onset. The mechanism underlying salience network abnormality remains unclear and it is worthwhile to investigate its clinical relevance using functional neuroimaging approaches. In this study, we performed the spontaneous brain activity measurement using resting-state functional magnetic resonance imaging (fMRI) on unmedicated OCD patients (n=23). Specifically, the amplitude of low frequency (0.01-0.08 Hz) fluctuations (ALFF) was calculated for regions in salience network. The voxel-based Pearson's correlative analysis was conducted to explore the relationship beween ALFF measures and symptom severity for OCD patients. The results showed that the spontaneous neuronal activity in insula was significantly correlated to OCD clinical symptoms, especially compulsive behaviors. Our findings consolidated that the salience network played an important role in the pathogenesis of OCD and the intensity of intrinsic brain activity in insula provided a predictive biomarker for OCD symptom severity. PMID:26737523

  12. Vision Drives Correlated Activity without Patterned Spontaneous Activity in Developing Xenopus Retina

    PubMed Central

    Demas, James A.; Payne, Hannah; Cline, Hollis T.

    2011-01-01

    Developing amphibians need vision to avoid predators and locate food before visual system circuits fully mature. Xenopus tadpoles can respond to visual stimuli as soon as retinal ganglion cells (RGCs) innervate the brain, however, in mammals, chicks and turtles, RGCs reach their central targets many days, or even weeks, before their retinas are capable of vision. In the absence of vision, activity-dependent refinement in these amniote species is mediated by waves of spontaneous activity that periodically spread across the retina, correlating the firing of action potentials in neighboring RGCs. Theory suggests that retinorecipient neurons in the brain use patterned RGC activity to sharpen the retinotopy first established by genetic cues. We find that in both wild type and albino Xenopus tadpoles, RGCs are spontaneously active at all stages of tadpole development studied, but their population activity never coalesces into waves. Even at the earliest stages recorded, visual stimulation dominates over spontaneous activity and can generate patterns of RGC activity similar to the locally correlated spontaneous activity observed in amniotes. In addition, we show that blocking AMPA and NMDA type glutamate receptors significantly decreases spontaneous activity in young Xenopus retina, but that blocking GABAA receptor blockers does not. Our findings indicate that vision drives correlated activity required for topographic map formation. They further suggest that developing retinal circuits in the two major subdivisions of tetrapods, amphibians and amniotes, evolved different strategies to supply appropriately patterned RGC activity to drive visual circuit refinement. PMID:21312343

  13. Chronic electrical stimulation homeostatically decreases spontaneous activity, but paradoxically increases evoked network activity

    PubMed Central

    Goel, Anubhuti

    2013-01-01

    Neural dynamics generated within cortical networks play a fundamental role in brain function. However, the learning rules that allow recurrent networks to generate functional dynamic regimes, and the degree to which these regimes are themselves plastic, are not known. In this study we examined plasticity of network dynamics in cortical organotypic slices in response to chronic changes in activity. Studies have typically manipulated network activity pharmacologically; we used chronic electrical stimulation to increase activity in in vitro cortical circuits in a more physiological manner. Slices were stimulated with “implanted” electrodes for 4 days. Chronic electrical stimulation or treatment with bicuculline decreased spontaneous activity as predicted by homeostatic learning rules. Paradoxically, however, whereas bicuculline decreased evoked network activity, chronic stimulation actually increased the likelihood that evoked stimulation elicited polysynaptic activity, despite a decrease in evoked monosynaptic strength. Furthermore, there was an inverse correlation between spontaneous and evoked activity, suggesting a homeostatic tradeoff between spontaneous and evoked activity. Within-slice experiments revealed that cells close to the stimulated electrode exhibited more evoked polysynaptic activity and less spontaneous activity than cells close to a control electrode. Collectively, our results establish that chronic stimulation changes the dynamic regimes of networks. In vitro studies of homeostatic plasticity typically lack any external input, and thus neurons must rely on “spontaneous” activity to reach homeostatic “set points.” However, in the presence of external input we propose that homeostatic learning rules seem to shift networks from spontaneous to evoked regimes. PMID:23324317

  14. Sympathetic sprouting near sensory neurons after nerve injury occurs preferentially on spontaneously active cells and is reduced by early nerve block

    PubMed Central

    Xie, Wenrui; Strong, Judith Ann; Li, Huiqing; Zhang, Jun-Ming

    2006-01-01

    Some chronic pain conditions are maintained or enhanced by sympathetic activity. In animal models of pathological pain, abnormal sprouting of sympathetic fibers around large- and medium-size sensory neurons is observed in dorsal root ganglia (DRG). Large and medium size cells are also more likely to be spontaneously active, suggesting that sprouting may be related to neuron activity. We previously showed that sprouting could be reduced by systemic or locally applied lidocaine. In the complete sciatic nerve transection model in rats, spontaneous activity initially originates in the injury site; later, the DRG become the major source of spontaneous activity. In this study, spontaneous activity reaching the DRG soma was reduced by early nerve blockade (local perfusion of the transected nerve with TTX for the first 7 days after injury). This significantly reduced sympathetic sprouting. Conversely, increasing spontaneous activity by local nerve perfusion with K+ channel blockers increased sprouting. The hyperexcitability and spontaneous activity of DRG neurons observed in this model were also significantly reduced by early nerve blockade. These effects of early nerve blockade on sprouting, excitability, and spontaneous activity were all observed 4 to 5 weeks after the end of early nerve blockade, indicating that the early period of spontaneous activity in the injured nerve is critical for establishing the more long-lasting pathologies observed in the DRG. Individual spontaneously active neurons, labeled with fluorescent dye, were 5–6 times more likely than quiescent cells to be co-localized with sympathetic fibers, suggesting a highly localized correlation of activity and sprouting. PMID:17065247

  15. Atrial Natriuretic Peptide Inhibits Spontaneous Contractile Activity of Lymph Nodes.

    PubMed

    Lobov, G I; Pan'kova, M N

    2016-06-01

    Atrial natriuretic peptide dose-dependently inhibited spontaneous phase and tonic activity of smooth muscle strips from the capsule of isolated bovine mesenteric lymph nodes. Pretreatment with L-NAME, diclofenac, and methylene blue had practically no effect on the peptide-induced relaxation responses. In contrast, glibenclamide significantly reduced the inhibitory effect of atrial natriuretic peptide. We suppose that the NO-dependent and cyclooxygenase signaling pathways are not involved in implementation of the inhibitory effects of atrial natriuretic peptide. ATP-sensitive K(+)-channels of the smooth muscle cell membrane are the last component in the signaling pathway leading to relaxation of smooth muscles of the lymph node capsule caused by atrial natriuretic peptide; activation of these channels leads to membrane hyperpolarization and smooth muscle relaxation. PMID:27383173

  16. Maternal immune activation and abnormal brain development across CNS disorders.

    PubMed

    Knuesel, Irene; Chicha, Laurie; Britschgi, Markus; Schobel, Scott A; Bodmer, Michael; Hellings, Jessica A; Toovey, Stephen; Prinssen, Eric P

    2014-11-01

    Epidemiological studies have shown a clear association between maternal infection and schizophrenia or autism in the progeny. Animal models have revealed maternal immune activation (mIA) to be a profound risk factor for neurochemical and behavioural abnormalities in the offspring. Microglial priming has been proposed as a major consequence of mIA, and represents a critical link in a causal chain that leads to the wide spectrum of neuronal dysfunctions and behavioural phenotypes observed in the juvenile, adult or aged offspring. Such diversity of phenotypic outcomes in the mIA model are mirrored by recent clinical evidence suggesting that infectious exposure during pregnancy is also associated with epilepsy and, to a lesser extent, cerebral palsy in children. Preclinical research also suggests that mIA might precipitate the development of Alzheimer and Parkinson diseases. Here, we summarize and critically review the emerging evidence that mIA is a shared environmental risk factor across CNS disorders that varies as a function of interactions between genetic and additional environmental factors. We also review ongoing clinical trials targeting immune pathways affected by mIA that may play a part in disease manifestation. In addition, future directions and outstanding questions are discussed, including potential symptomatic, disease-modifying and preventive treatment strategies. PMID:25311587

  17. Active magneto-optical control of spontaneous emission in graphene

    DOE PAGESBeta

    Kort-Kamp, W. J. M.; Amorim, B.; Bastos, G.; Pinheiro, F. A.; Rosa, F. S. S.; Peres, N. M. R.; Farina, C.

    2015-11-13

    In this study, we investigate the spontaneous emission rate of a two-level quantum emitter near a graphene-coated substrate under the influence of an external magnetic field or strain induced pseudomagnetic field. We demonstrate that the application of the magnetic field can substantially increase or decrease the decay rate. We show that a suppression as large as 99% in the Purcell factor is achieved even for moderate magnetic fields. The emitter's lifetime is a discontinuous function of |B|, which is a direct consequence of the occurrence of discrete Landau levels in graphene. We demonstrate that, in the near-field regime, the magneticmore » field enables an unprecedented control of the decay pathways into which the photon/polariton can be emitted. Our findings strongly suggest that a magnetic field could act as an efficient agent for on-demand, active control of light-matter interactions in graphene at the quantum level.« less

  18. Active magneto-optical control of spontaneous emission in graphene

    SciTech Connect

    Kort-Kamp, W. J. M.; Amorim, B.; Bastos, G.; Pinheiro, F. A.; Rosa, F. S. S.; Peres, N. M. R.; Farina, C.

    2015-11-13

    In this study, we investigate the spontaneous emission rate of a two-level quantum emitter near a graphene-coated substrate under the influence of an external magnetic field or strain induced pseudomagnetic field. We demonstrate that the application of the magnetic field can substantially increase or decrease the decay rate. We show that a suppression as large as 99% in the Purcell factor is achieved even for moderate magnetic fields. The emitter's lifetime is a discontinuous function of |B|, which is a direct consequence of the occurrence of discrete Landau levels in graphene. We demonstrate that, in the near-field regime, the magnetic field enables an unprecedented control of the decay pathways into which the photon/polariton can be emitted. Our findings strongly suggest that a magnetic field could act as an efficient agent for on-demand, active control of light-matter interactions in graphene at the quantum level.

  19. Spontaneous chiral symmetry breaking in collective active motion

    NASA Astrophysics Data System (ADS)

    Breier, Rebekka E.; Selinger, Robin L. B.; Ciccotti, Giovanni; Herminghaus, Stephan; Mazza, Marco G.

    2016-02-01

    Chiral symmetry breaking is ubiquitous in biological systems, from DNA to bacterial suspensions. A key unresolved problem is how chiral structures may spontaneously emerge from achiral interactions. We study a simple model of active swimmers in three dimensions that effectively incorporates hydrodynamic interactions. We perform large-scale molecular dynamics simulations (up to 106 particles) and find long-lived metastable collective states that exhibit chiral organization although the interactions are achiral. We elucidate under which conditions these chiral states will emerge and grow to large scales. To explore the complex phase space available to the system, we perform nonequilibrium quenches on a one-dimensional Lebwohl-Lasher model with periodic boundary conditions to study the likelihood of formation of chiral structures.

  20. How Can We Identify Ictal and Interictal Abnormal Activity?

    PubMed Central

    Fisher, Robert S.; Scharfman, Helen E.; deCurtis, Marco

    2015-01-01

    The International League Against Epilepsy (ILAE) defined a seizure as “a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.” This definition has been used since the era of Hughlings Jackson, and does not take into account subsequent advances made in epilepsy and neuroscience research. The clinical diagnosis of a seizure is empirical, based upon constellations of certain signs and symptoms, while simultaneously ruling out a list of potential imitators of seizures. Seizures should be delimited in time, but the borders of ictal (during a seizure), interictal (between seizures) and postictal (after a seizure) often are indistinct. EEG recording is potentially very helpful for confirmation, classification and localization. About a half-dozen common EEG patterns are encountered during seizures. Clinicians rely on researchers to answer such questions as why seizures start, spread and stop, whether seizures involve increased synchrony, the extent to which extra-cortical structures are involved, and how to identify the seizure network and at what points interventions are likely to be helpful. Basic scientists have different challenges in use of the word ‘seizure,’ such as distinguishing seizures from normal behavior, which would seem easy but can be very difficult because some rodents have EEG activity during normal behavior that resembles spike-wave discharge or bursts of rhythmic spiking. It is also important to define when a seizure begins and stops so that seizures can be quantified accurately for pre-clinical studies. When asking what causes seizures, the transition to a seizure and differentiating the pre-ictal, ictal and post-ictal state is also important because what occurs before a seizure could be causal and may warrant further investigation for that reason. These and other issues are discussed by three epilepsy researchers with clinical and basic science expertise. PMID:25012363

  1. Altered Spontaneous Brain Activity in Patients with Acute Spinal Cord Injury Revealed by Resting-State Functional MRI

    PubMed Central

    Zhu, Ling; Wu, Guangyao; Zhou, Xin; Li, Jielan; Wen, Zhi; Lin, Fuchun

    2015-01-01

    Background Previous neuroimaging studies have provided evidence of structural and functional reorganization of brain in patients with chronic spinal cord injury (SCI). However, it remains unknown whether the spontaneous brain activity changes in acute SCI. In this study, we investigated intrinsic brain activity in acute SCI patients using a regional homogeneity (ReHo) analysis based on resting-state functional magnetic resonance imaging. Methods A total of 15 patients with acute SCI and 16 healthy controls participated in the study. The ReHo value was used to evaluate spontaneous brain activity, and voxel-wise comparisons of ReHo were performed to identify brain regions with altered spontaneous brain activity between groups. We also assessed the associations between ReHo and the clinical scores in brain regions showing changed spontaneous brain activity. Results Compared with the controls, the acute SCI patients showed decreased ReHo in the bilateral primary motor cortex/primary somatosensory cortex, bilateral supplementary motor area/dorsal lateral prefrontal cortex, right inferior frontal gyrus, bilateral dorsal anterior cingulate cortex and bilateral caudate; and increased ReHo in bilateral precuneus, the left inferior parietal lobe, the left brainstem/hippocampus, the left cingulate motor area, bilateral insula, bilateral thalamus and bilateral cerebellum. The average ReHo values of the left thalamus and right insula were negatively correlated with the international standards for the neurological classification of spinal cord injury motor scores. Conclusion Our findings indicate that acute distant neuronal damage has an immediate impact on spontaneous brain activity. In acute SCI patients, the ReHo was prominently altered in brain regions involved in motor execution and cognitive control, default mode network, and which are associated with sensorimotor compensatory reorganization. Abnormal ReHo values in the left thalamus and right insula could serve as

  2. Modulation of spontaneous fMRI activity in human visual cortex by behavioral state

    PubMed Central

    Bianciardi, Marta; Fukunaga, Masaki; van Gelderen, Peter; Horovitz, Silvina G.; de Zwart, Jacco A.; Duyn, Jeff H.

    2009-01-01

    The phenomenon of spontaneous fMRI activity is increasingly being exploited to investigate the connectivity of functional networks in human brain with high spatial-resolution. Although mounting evidence points towards a neuronal contribution to this activity, its functional role and dependence on behavioral state remain unclear. In this work, we used BOLD fMRI at 7 T to study the modulation of spontaneous activity in occipital areas by various behavioral conditions, including resting with eyes closed, eyes open with visual fixation, and eyes open with fixation and focal visual stimulation. Spontaneous activity was separated from evoked activity and from signal fluctuations related to cardiac and respiratory cycles. We found that spontaneous activity in visual areas was substantially reduced (amplitude (44%) and coherence (25%)) with the fixation conditions relative to the eyes-closed condition. No significant further modulation was observed when the visual stimulus was added. The observed dependence on behavioral condition suggests that part of spontaneous fMRI signal fluctuations represents neuronal activity. Possible mechanisms for the modulation of spontaneous activity by behavioral state are discussed. The observed linear superposition of spontaneous fMRI activity with focal evoked activity related to visual processing has important implications for fMRI studies, which ideally should take into account the effect of spontaneous activity to properly define brain activations during task conditions. PMID:19028588

  3. Methodological considerations for measuring spontaneous physical activity in rodents

    PubMed Central

    Perez-Leighton, Claudio E.; Billington, Charles J.; Kotz, Catherine M.

    2014-01-01

    When exploring biological determinants of spontaneous physical activity (SPA), it is critical to consider whether methodological factors differentially affect rodents and the measured SPA. We determined whether acclimation time, sensory stimulation, vendor, or chamber size affected measures in rodents with varying propensity for SPA. We used principal component analysis to determine which SPA components (ambulatory and vertical counts, time in SPA, and distance traveled) best described the variability in SPA measurements. We compared radiotelemetry and infrared photobeams used to measure SPA and exploratory activity. Acclimation time, sensory stimulation, vendor, and chamber size independently influenced SPA, and the effect was moderated by the propensity for SPA. A 24-h acclimation period prior to SPA measurement was sufficient for habituation. Principal component analysis showed that ambulatory and vertical measurements of SPA describe different dimensions of the rodent's SPA behavior. Smaller testing chambers and a sensory attenuation cubicle around the chamber reduced SPA. SPA varies between rodents purchased from different vendors. Radiotelemetry and infrared photobeams differ in their sensitivity to detect phenotypic differences in SPA and exploratory activity. These data highlight methodological considerations in rodent SPA measurement and a need to standardize SPA methodology. PMID:24598463

  4. Treatment of abnormal vaginal flora in early pregnancy with clindamycin for the prevention of spontaneous preterm birth: a systematic review and metaanalysis

    PubMed Central

    Lamont, Ronald F.; Nhan-Chang, Chia-Ling; Sobel, Jack D.; Workowski, Kimberly; Conde-Agudelo, Agustin; Romero, Roberto

    2011-01-01

    The purpose of this study was to determine whether the administration of clindamycin to women with abnormal vaginal flora at <22 weeks of gestation reduces the risk of preterm birth and late miscarriage. We conducted a systematic review and metaanalysis of randomized controlled trials of the early administration of clindamycin to women with abnormal vaginal flora at <22 weeks of gestation. Five trials that comprised 2346 women were included. Clindamycin that was administered at <22 weeks of gestation was associated with a significantly reduced risk of preterm birth at <37 weeks of gestation and late miscarriage. There were no overall differences in the risk of preterm birth at <33 weeks of gestation, low birthweight, very low birthweight, admission to neonatal intensive care unit, stillbirth, peripartum infection, and adverse effects. Clindamycin in early pregnancy in women with abnormal vaginal flora reduces the risk of spontaneous preterm birth at <37 weeks of gestation and late miscarriage. There is evidence to justify further randomized controlled trials of clindamycin for the prevention of preterm birth. However, a deeper understanding of the vaginal microbiome, mucosal immunity, and the biology of bacterial vaginosis will be needed to inform the design of such trials. PMID:22071048

  5. Molecular mechanism of spontaneous pigment activation in retinal cones.

    PubMed

    Sampath, Alapakkam P; Baylor, Denis A

    2002-07-01

    Spontaneous current and voltage fluctuations (dark noise) in the photoreceptor cells of the retina limit the ability of the visual system to detect dim light. We recorded the dark current noise of individual salamander L cones. Previous work showed that the dark noise in these cells arises from thermal activation of the visual pigment. From the temperature dependence of the rate of occurrence of elementary noise events, we found an Arrhenius activation energy E(a) of 25 +/- 7 kcal/mol (mean +/- SD). This E(a) is similar to that reported for the thermal isomerization of 11-cis retinal in solution, suggesting that the cone pigment noise results from isomerization of the retinal chromophore. E(a) for the cone noise is similar to that previously reported for the "photon-like" noise of rods, but the preexponential factor is five orders of magnitude higher. To test the hypothesis that thermal isomerization can only occur in molecules whose Schiff base linkage is unprotonated, we changed the pH of the solution bathing the cone outer segment. This had little effect on the rate of occurrence of elementary noise events. The rate was also unchanged when the cone was exposed to Ringer solution made up from heavy water, whose solvent isotope effect should reduce the probability, that the Schiff base nitrogen is naked. PMID:12080111

  6. Fast transient networks in spontaneous human brain activity

    PubMed Central

    Baker, Adam P; Brookes, Matthew J; Rezek, Iead A; Smith, Stephen M; Behrens, Timothy; Probert Smith, Penny J; Woolrich, Mark

    2014-01-01

    To provide an effective substrate for cognitive processes, functional brain networks should be able to reorganize and coordinate on a sub-second temporal scale. We used magnetoencephalography recordings of spontaneous activity to characterize whole-brain functional connectivity dynamics at high temporal resolution. Using a novel approach that identifies the points in time at which unique patterns of activity recur, we reveal transient (100–200 ms) brain states with spatial topographies similar to those of well-known resting state networks. By assessing temporal changes in the occurrence of these states, we demonstrate that within-network functional connectivity is underpinned by coordinated neuronal dynamics that fluctuate much more rapidly than has previously been shown. We further evaluate cross-network interactions, and show that anticorrelation between the default mode network and parietal regions of the dorsal attention network is consistent with an inability of the system to transition directly between two transient brain states. DOI: http://dx.doi.org/10.7554/eLife.01867.001 PMID:24668169

  7. New Perspectives on Spontaneous Brain Activity: Dynamic Networks and Energy Matter

    PubMed Central

    Tozzi, Arturo; Zare, Marzieh; Benasich, April A.

    2016-01-01

    Spontaneous brain activity has received increasing attention as demonstrated by the exponential rise in the number of published article on this topic over the last 30 years. Such “intrinsic” brain activity, generated in the absence of an explicit task, is frequently associated with resting-state or default-mode networks (DMN)s. The focus on characterizing spontaneous brain activity promises to shed new light on questions concerning the structural and functional architecture of the brain and how they are related to “mind”. However, many critical questions have yet to be addressed. In this review, we focus on a scarcely explored area, specifically the energetic requirements and constraints of spontaneous activity, taking into account both thermodynamical and informational perspectives. We argue that the “classical” definitions of spontaneous activity do not take into account an important feature, that is, the critical thermodynamic energetic differences between spontaneous and evoked brain activity. Spontaneous brain activity is associated with slower oscillations compared with evoked, task-related activity, hence it exhibits lower levels of enthalpy and “free-energy” (i.e., the energy that can be converted to do work), thus supporting noteworthy thermodynamic energetic differences between spontaneous and evoked brain activity. Increased spike frequency during evoked activity has a significant metabolic cost, consequently, brain functions traditionally associated with spontaneous activity, such as mind wandering, require less energy that other nervous activities. We also review recent empirical observations in neuroscience, in order to capture how spontaneous brain dynamics and mental function can be embedded in a non-linear dynamical framework, which considers nervous activity in terms of phase spaces, particle trajectories, random walks, attractors and/or paths at the edge of the chaos. This takes us from the thermodynamic free-energy, to the realm

  8. New Perspectives on Spontaneous Brain Activity: Dynamic Networks and Energy Matter.

    PubMed

    Tozzi, Arturo; Zare, Marzieh; Benasich, April A

    2016-01-01

    Spontaneous brain activity has received increasing attention as demonstrated by the exponential rise in the number of published article on this topic over the last 30 years. Such "intrinsic" brain activity, generated in the absence of an explicit task, is frequently associated with resting-state or default-mode networks (DMN)s. The focus on characterizing spontaneous brain activity promises to shed new light on questions concerning the structural and functional architecture of the brain and how they are related to "mind". However, many critical questions have yet to be addressed. In this review, we focus on a scarcely explored area, specifically the energetic requirements and constraints of spontaneous activity, taking into account both thermodynamical and informational perspectives. We argue that the "classical" definitions of spontaneous activity do not take into account an important feature, that is, the critical thermodynamic energetic differences between spontaneous and evoked brain activity. Spontaneous brain activity is associated with slower oscillations compared with evoked, task-related activity, hence it exhibits lower levels of enthalpy and "free-energy" (i.e., the energy that can be converted to do work), thus supporting noteworthy thermodynamic energetic differences between spontaneous and evoked brain activity. Increased spike frequency during evoked activity has a significant metabolic cost, consequently, brain functions traditionally associated with spontaneous activity, such as mind wandering, require less energy that other nervous activities. We also review recent empirical observations in neuroscience, in order to capture how spontaneous brain dynamics and mental function can be embedded in a non-linear dynamical framework, which considers nervous activity in terms of phase spaces, particle trajectories, random walks, attractors and/or paths at the edge of the chaos. This takes us from the thermodynamic free-energy, to the realm of "variational

  9. Spontaneous perceptual facial distortions correlate with ventral occipitotemporal activity.

    PubMed

    Dalrymple, Kirsten A; Davies-Thompson, Jodie; Oruc, Ipek; Handy, Todd C; Barton, Jason J S; Duchaine, Brad

    2014-07-01

    Prosopometamorphopsia is a disorder of face perception in which faces appear distorted to the perceiver. The neural basis of prosopometamorphopsia is unclear, but may involve abnormal activity in face-selective areas in the ventral occipito-temporal pathway. Here we present the case of AS, a 44-year-old woman who reports persistent perceptual distortions of faces with no known cause. AS was presented with facial images and rated the magnitude of her distortions while activity in her core face areas and other areas in the ventral visual pathway was measured using functional magnetic resonance imaging. The magnitude of her distortions was positively correlated with signal changes in the right occipital face area (OFA) and right fusiform face area (FFA), as well as right V1-V3, and right lateral occipital cortex (LOC). There was also a trend for a significant correlation with signal in the left OFA and right inferior frontal gyrus (IFG), but not in the right or left superior temporal sulcus (STS). These results suggest that AS' prosopometamorphopsia reflects anomalous activity in face-processing network, particularly in the ventral occipitotemporal cortex. PMID:24859691

  10. Abnormal fusiform activation during emotional-face encoding assessed with functional magnetic resonance imaging.

    PubMed

    Adleman, Nancy E; Kayser, Reilly R; Olsavsky, Aviva K; Bones, Brian L; Muhrer, Eli J; Fromm, Stephen J; Pine, Daniel S; Zarate, Carlos; Leibenluft, Ellen; Brotman, Melissa A

    2013-05-30

    This functional magnetic resonance imaging study shows that children and adults with bipolar disorder (BD), compared with healthy subjects, exhibit impaired memory for emotional faces and abnormal fusiform activation during encoding. Fusiform activation abnormalities in BD were correlated with mania severity and may therefore represent a trait and state BD biomarker. PMID:23541333

  11. Abnormal fusiform activation during emotional-face encoding in children and adults with bipolar disorder

    PubMed Central

    Adleman, Nancy E.; Kayser, Reilly R.; Olsavsky, Aviva K.; Bones, Brian L.; Muhrer, Eli J.; Fromm, Stephen J.; Pine, Daniel S.; Zarate, Carlos; Leibenluft, Ellen; Brotman, Melissa A.

    2013-01-01

    This fMRI study shows that, compared to healthy subjects, children and adults with bipolar disorder (BD) exhibit impaired memory for emotional faces and abnormal fusiform activation during encoding. Fusiform activation abnormalities in BD were correlated with mania severity and may therefore represent a trait and state BD biomarker. PMID:23541333

  12. A BDNF loop-domain mimetic acutely reverses spontaneous apneas and respiratory abnormalities during behavioral arousal in a mouse model of Rett syndrome

    PubMed Central

    Kron, Miriam; Lang, Min; Adams, Ian T.; Sceniak, Michael; Longo, Frank; Katz, David M.

    2014-01-01

    Reduced levels of brain-derived neurotrophic factor (BDNF) are thought to contribute to the pathophysiology of Rett syndrome (RTT), a severe neurodevelopmental disorder caused by loss-of-function mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). In Mecp2 mutant mice, BDNF deficits have been associated with breathing abnormalities, a core feature of RTT, as well as with synaptic hyperexcitability within the brainstem respiratory network. Application of BDNF can reverse hyperexcitability in acute brainstem slices from Mecp2-null mice, suggesting that therapies targeting BDNF or its receptor, TrkB, could be effective at acute reversal of respiratory abnormalities in RTT. Therefore, we examined the ability of LM22A-4, a small-molecule BDNF loop-domain mimetic and TrkB partial agonist, to modulate synaptic excitability within respiratory cell groups in the brainstem nucleus tractus solitarius (nTS) and to acutely reverse abnormalities in breathing at rest and during behavioral arousal in Mecp2 mutants. Patch-clamp recordings in Mecp2-null brainstem slices demonstrated that LM22A-4 decreases excitability at primary afferent synapses in the nTS by reducing the amplitude of evoked excitatory postsynaptic currents and the frequency of spontaneous and miniature excitatory postsynaptic currents. In vivo, acute treatment of Mecp2-null and -heterozygous mutants with LM22A-4 completely eliminated spontaneous apneas in resting animals, without sedation. Moreover, we demonstrate that respiratory dysregulation during behavioral arousal, a feature of human RTT, is also reversed in Mecp2 mutants by acute treatment with LM22A-4. Together, these data support the hypothesis that reduced BDNF signaling and respiratory dysfunction in RTT are linked, and establish the proof-of-concept that treatment with a small-molecule structural mimetic of a BDNF loop domain and a TrkB partial agonist can acutely reverse abnormal breathing at rest and in response to behavioral arousal

  13. Temporal dynamics of spontaneous MEG activity in brain networks.

    PubMed

    de Pasquale, Francesco; Della Penna, Stefania; Snyder, Abraham Z; Lewis, Christopher; Mantini, Dante; Marzetti, Laura; Belardinelli, Paolo; Ciancetta, Luca; Pizzella, Vittorio; Romani, Gian Luca; Corbetta, Maurizio

    2010-03-30

    Functional MRI (fMRI) studies have shown that low-frequency (<0.1 Hz) spontaneous fluctuations of the blood oxygenation level dependent (BOLD) signal during restful wakefulness are coherent within distributed large-scale cortical and subcortical networks (resting state networks, RSNs). The neuronal mechanisms underlying RSNs remain poorly understood. Here, we describe magnetoencephalographic correspondents of two well-characterized RSNs: the dorsal attention and the default mode networks. Seed-based correlation mapping was performed using time-dependent MEG power reconstructed at each voxel within the brain. The topography of RSNs computed on the basis of extended (5 min) epochs was similar to that observed with fMRI but confined to the same hemisphere as the seed region. Analyses taking into account the nonstationarity of MEG activity showed transient formation of more complete RSNs, including nodes in the contralateral hemisphere. Spectral analysis indicated that RSNs manifest in MEG as synchronous modulation of band-limited power primarily within the theta, alpha, and beta bands-that is, in frequencies slower than those associated with the local electrophysiological correlates of event-related BOLD responses. PMID:20304792

  14. Altered Spontaneous Activity in Patients with Persistent Somatoform Pain Disorder Revealed by Regional Homogeneity

    PubMed Central

    Yan, Chao; Lu, Jing; Li, Xuzhou; Tang, Chaozheng; Fan, Mingxia; Luo, Yanli

    2016-01-01

    Persistent somatoform pain disorder (PSPD) is a mental disorder un-associated with any somatic injury and can cause severe somatosensory and emotional impairments in patients. However, so far, the neuro-pathophysiological mechanism of the functional impairments in PSPD is still unclear. The present study assesses the difference in regional spontaneous activity between PSPD and healthy controls (HC) during a resting state, in order to elucidate the neural mechanisms underlying PSPD. Resting-state functional Magnetic Resonance Imaging data were obtained from 13 PSPD patients and 23 age- and gender-matched HC subjects in this study. Kendall’s coefficient of concordance was used to measure regional homogeneity (ReHo), and a two-sample t-test was subsequently performed to investigate the ReHo difference between PSPD and HC. Additionally, the correlations between the mean ReHo of each survived area and the clinical assessments were further analyzed. Compared with the HC group, patients with PSPD exhibited decreased ReHo in the bilateral primary somatosensory cortex, posterior cerebellum, and occipital lobe, while increased ReHo in the prefrontal cortex (PFC) and default mode network (including the medial PFC, right inferior parietal lobe (IPL), and left supramarginal gyrus). In addition, significant positive correlations were found between the mean ReHo of both right IPL and left supramarginal gyrus and participants’ Self-Rating Anxiety Scale (SAS) scores, and between the mean ReHo of the left middle frontal gyrus and Visual Analogue Scale (VAS) scores. Our results suggest that abnormal spontaneous brain activity in specific brain regions during a resting state may be associated with the dysfunctions in pain, memory and emotional processing commonly observed in patients with PSPD. These findings help us to understand the neural mechanisms underlying PSPD and suggest that the ReHo metric could be used as a clinical marker for PSPD. PMID:26977802

  15. Altered Spontaneous Activity in Patients with Persistent Somatoform Pain Disorder Revealed by Regional Homogeneity.

    PubMed

    Huang, Tianming; Zhao, Zhiyong; Yan, Chao; Lu, Jing; Li, Xuzhou; Tang, Chaozheng; Fan, Mingxia; Luo, Yanli

    2016-01-01

    Persistent somatoform pain disorder (PSPD) is a mental disorder un-associated with any somatic injury and can cause severe somatosensory and emotional impairments in patients. However, so far, the neuro-pathophysiological mechanism of the functional impairments in PSPD is still unclear. The present study assesses the difference in regional spontaneous activity between PSPD and healthy controls (HC) during a resting state, in order to elucidate the neural mechanisms underlying PSPD. Resting-state functional Magnetic Resonance Imaging data were obtained from 13 PSPD patients and 23 age- and gender-matched HC subjects in this study. Kendall's coefficient of concordance was used to measure regional homogeneity (ReHo), and a two-sample t-test was subsequently performed to investigate the ReHo difference between PSPD and HC. Additionally, the correlations between the mean ReHo of each survived area and the clinical assessments were further analyzed. Compared with the HC group, patients with PSPD exhibited decreased ReHo in the bilateral primary somatosensory cortex, posterior cerebellum, and occipital lobe, while increased ReHo in the prefrontal cortex (PFC) and default mode network (including the medial PFC, right inferior parietal lobe (IPL), and left supramarginal gyrus). In addition, significant positive correlations were found between the mean ReHo of both right IPL and left supramarginal gyrus and participants' Self-Rating Anxiety Scale (SAS) scores, and between the mean ReHo of the left middle frontal gyrus and Visual Analogue Scale (VAS) scores. Our results suggest that abnormal spontaneous brain activity in specific brain regions during a resting state may be associated with the dysfunctions in pain, memory and emotional processing commonly observed in patients with PSPD. These findings help us to understand the neural mechanisms underlying PSPD and suggest that the ReHo metric could be used as a clinical marker for PSPD. PMID:26977802

  16. Altered Spontaneous Brain Activity in Betel Quid Dependence: A Resting-state Functional Magnetic Resonance Imaging Study.

    PubMed

    Liu, Tao; Li, Jian-Jun; Zhao, Zhong-Yan; Yang, Guo-Shuai; Pan, Meng-Jie; Li, Chang-Qing; Pan, Su-Yue; Chen, Feng

    2016-02-01

    It has been suggested by the first voxel-based morphometry investigation that betel quid dependence (BQD) individuals are presented with brain structural changes in previous reports, and there may be a neurobiological basis for BQD individuals related to an increased risk of executive dysfunction and disinhibition, subjected to the reward system, cognitive system, and emotion system. However, the effects of BQD on neural activity remain largely unknown. Individuals with impaired cognitive control of behavior often reveal altered spontaneous cerebral activity in resting-state functional magnetic resonance imaging and those changes are usually earlier than structural alteration.Here, we examined BQD individuals (n = 33) and age-, sex-, and education-matched healthy control participants (n = 32) in an resting-state functional magnetic resonance imaging study to observe brain function alterations associated with the severity of BQD. Amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values were both evaluated to stand for spontaneous cerebral activity. Gray matter volumes of these participants were also calculated for covariate.In comparison with healthy controls, BQD individuals demonstrated dramatically decreased ALFF and ReHo values in the prefrontal gurus along with left fusiform, and increased ALFF and ReHo values in the primary motor cortex area, temporal lobe as well as some regions of occipital lobe. The betel quid dependence scores (BQDS) were negatively related to decreased activity in the right anterior cingulate.The abnormal spontaneous cerebral activity revealed by ALFF and ReHo calculation excluding the structural differences in patients with BQD may help us probe into the neurological pathophysiology underlying BQD-related executive dysfunction and disinhibition. Diminished spontaneous brain activity in the right anterior cingulate cortex may, therefore, represent a biomarker of BQD individuals. PMID:26844480

  17. From Spontaneous Motor Activity to Coordinated Behaviour: A Developmental Model

    PubMed Central

    Marques, Hugo Gravato; Bharadwaj, Arjun; Iida, Fumiya

    2014-01-01

    In mammals, the developmental path that links the primary behaviours observed during foetal stages to the full fledged behaviours observed in adults is still beyond our understanding. Often theories of motor control try to deal with the process of incremental learning in an abstract and modular way without establishing any correspondence with the mammalian developmental stages. In this paper, we propose a computational model that links three distinct behaviours which appear at three different stages of development. In order of appearance, these behaviours are: spontaneous motor activity (SMA), reflexes, and coordinated behaviours, such as locomotion. The goal of our model is to address in silico four hypotheses that are currently hard to verify in vivo: First, the hypothesis that spinal reflex circuits can be self-organized from the sensor and motor activity induced by SMA. Second, the hypothesis that supraspinal systems can modulate reflex circuits to achieve coordinated behaviour. Third, the hypothesis that, since SMA is observed in an organism throughout its entire lifetime, it provides a mechanism suitable to maintain the reflex circuits aligned with the musculoskeletal system, and thus adapt to changes in body morphology. And fourth, the hypothesis that by changing the modulation of the reflex circuits over time, one can switch between different coordinated behaviours. Our model is tested in a simulated musculoskeletal leg actuated by six muscles arranged in a number of different ways. Hopping is used as a case study of coordinated behaviour. Our results show that reflex circuits can be self-organized from SMA, and that, once these circuits are in place, they can be modulated to achieve coordinated behaviour. In addition, our results show that our model can naturally adapt to different morphological changes and perform behavioural transitions. PMID:25057775

  18. Mechanisms underlying obesity resistance associated with high spontaneous physical activity

    PubMed Central

    Teske, Jennifer A.; Billington, Charles J.; Kotz, Catherine M.

    2013-01-01

    Obesity resistance due to elevated orexin signaling is accompanied by high levels of spontaneous physical activity (SPA). The behavioral and neural mechanisms underlying this observation have not been fully worked out. We determined the contribution of hypothalamic orexin receptors (OXR) to SPA stimulated by orexin A (OXA), whether OXA-stimulated SPA was secondary to arousal and whether voluntary wheel running led to compensations in 24-h SPA. We further tested whether orexin action on dopamine one receptors (DA1R) in the substantia nigra (SN) plays an important role in generation of SPA. To test this, SPA response was determined in lean and obese rats with cannulae targeted towards the rostral lateral hypothalamus (rLH) or SN. Sleep/wake states were also measured in rats with rLH cannula and EEG/EMG radiotelemetry transmitters. SPA in lean rats was more sensitive to antagonism of the orexin 1 receptor (OX1R) and in the early response to the orexin 2 agonist. OXA increased arousal equally in lean and obese rodents, which is discordant from the greater SPA response in lean rats. Obesity resistant rats ran more and wheel running was directly related to 24-h SPA levels. The OX1R antagonist, SB-334867-A, and the DA1R antagonist, SCH3390, in SN more effectively reduced SPA stimulated by OXA in OR rats. These data suggest OXA-stimulated SPA is not secondary to enhanced arousal, propensity for SPA parallels inclination to run and that orexin action on dopaminergic neurons in SN may participate in mediation of SPA and running wheel activity. PMID:24161277

  19. Cardiac Arrest-Induced Global Brain Hypoxia-Ischemia during Development Affects Spontaneous Activity Organization in Rat Sensory and Motor Thalamocortical Circuits during Adulthood

    PubMed Central

    Shoykhet, Michael; Middleton, Jason W.

    2016-01-01

    Normal maturation of sensory information processing in the cortex requires patterned synaptic activity during developmentally regulated critical periods. During early development, spontaneous synaptic activity establishes required patterns of synaptic input, and during later development it influences patterns of sensory experience-dependent neuronal firing. Thalamocortical neurons occupy a critical position in regulating the flow of patterned sensory information from the periphery to the cortex. Abnormal thalamocortical inputs may permanently affect the organization and function of cortical neuronal circuits, especially if they occur during a critical developmental window. We examined the effect of cardiac arrest (CA)-associated global brain hypoxia-ischemia in developing rats on spontaneous and evoked firing of somatosensory thalamocortical neurons and on large-scale correlations in the motor thalamocortical circuit. The mean spontaneous and sensory-evoked firing rate activity and variability were higher in CA injured rats. Furthermore, spontaneous and sensory-evoked activity and variability were correlated in uninjured rats, but not correlated in neurons from CA rats. Abnormal activity patterns of ventroposterior medial nucleus (VPm) neurons persisted into adulthood. Additionally, we found that neurons in the entopeduncular nucleus (EPN) in the basal ganglia had lower firing rates yet had higher variability and higher levels of burst firing after injury. Correlated levels of power in local field potentials (LFPs) between the EPN and the motor cortex (MCx) were also disrupted by injury. Our findings indicate that hypoxic-ischemic injury during development leads to abnormal spontaneous and sensory stimulus-evoked input patterns from thalamus to cortex. Abnormal thalamic inputs likely permanently and detrimentally affect the organization of cortical circuitry and processing of sensory information. Hypoxic-ischemic injury also leads to abnormal single neuron and

  20. Cardiac Arrest-Induced Global Brain Hypoxia-Ischemia during Development Affects Spontaneous Activity Organization in Rat Sensory and Motor Thalamocortical Circuits during Adulthood.

    PubMed

    Shoykhet, Michael; Middleton, Jason W

    2016-01-01

    Normal maturation of sensory information processing in the cortex requires patterned synaptic activity during developmentally regulated critical periods. During early development, spontaneous synaptic activity establishes required patterns of synaptic input, and during later development it influences patterns of sensory experience-dependent neuronal firing. Thalamocortical neurons occupy a critical position in regulating the flow of patterned sensory information from the periphery to the cortex. Abnormal thalamocortical inputs may permanently affect the organization and function of cortical neuronal circuits, especially if they occur during a critical developmental window. We examined the effect of cardiac arrest (CA)-associated global brain hypoxia-ischemia in developing rats on spontaneous and evoked firing of somatosensory thalamocortical neurons and on large-scale correlations in the motor thalamocortical circuit. The mean spontaneous and sensory-evoked firing rate activity and variability were higher in CA injured rats. Furthermore, spontaneous and sensory-evoked activity and variability were correlated in uninjured rats, but not correlated in neurons from CA rats. Abnormal activity patterns of ventroposterior medial nucleus (VPm) neurons persisted into adulthood. Additionally, we found that neurons in the entopeduncular nucleus (EPN) in the basal ganglia had lower firing rates yet had higher variability and higher levels of burst firing after injury. Correlated levels of power in local field potentials (LFPs) between the EPN and the motor cortex (MCx) were also disrupted by injury. Our findings indicate that hypoxic-ischemic injury during development leads to abnormal spontaneous and sensory stimulus-evoked input patterns from thalamus to cortex. Abnormal thalamic inputs likely permanently and detrimentally affect the organization of cortical circuitry and processing of sensory information. Hypoxic-ischemic injury also leads to abnormal single neuron and

  1. Spontaneous remission of acute myeloid leukemia relapse after hematopoietic cell transplantation in a high-risk patient with 11q23/MLL abnormality.

    PubMed

    Hudecek, Michael; Bartsch, Kristina; Jäkel, Nadja; Heyn, Simone; Pfannes, Roald; Al-Ali, Haifa Kathrin; Cross, Michael; Pönisch, Wolfram; Gerecke, Ulrich; Edelmann, Jeanett; Ittel, Thomas; Niederwieser, Dietger

    2008-01-01

    A 35-year-old female patient was diagnosed with acute myeloid leukemia with multiple genetic aberrations [48 XX, del(3)(q21), +6, t(11;15)(q23;q15), +21] including an 11q23/MLL abnormality. The patient achieved a complete remission after one induction chemotherapy cycle. After three courses of consolidation, a matched unrelated hematopoietic cell transplantation (HCT) was performed. Following an upper respiratory tract infection 7 years after transplant, her blood counts declined to leukocytes of 1 x 10(9)/l, platelets of 51 x 10(9)/l and hemoglobin of 7.5 g/dl. A bone marrow aspirate revealed 55% leukemic blasts carrying the unfavorable genetic aberrations seen at initial diagnosis (11q23/MLL). In the absence of any disease-specific treatment, the leukemic blasts cleared from the bone marrow within 6 days after diagnosis of relapse and peripheral blood counts returned to normal. Molecular analysis of the 11q23/MLL rearrangement was used to evaluate minimal residual disease, which became undetectable in repetitive FISH analyses. This is the first report of spontaneous remission in a patient with initially a multiaberrant leukemic cell clone and a proven 11q23/MLL abnormality at relapse after HCT. PMID:18367831

  2. Spontaneous brain activity observed with functional magnetic resonance imaging as a potential biomarker in neuropsychiatric disorders

    PubMed Central

    Zhou, Yuan; Wang, Kun; Liu, Yong; Song, Ming; Song, Sonya W.

    2010-01-01

    As functional magnetic resonance imaging (fMRI) studies have yielded increasing amounts of information about the brain’s spontaneous activity, they have revealed fMRI’s potential to locate changes in brain hemodynamics that are associated with neuropsychiatric disorders. In this paper, we review studies that support the notion that changes in brain spontaneous activity observed by fMRI can be used as potential biomarkers for diagnosis and treatment evaluation in neuropsychiatric disorders. We first review the methods used to study spontaneous activity from the perspectives of (1) the properties of local spontaneous activity, (2) the spatial pattern of spontaneous activity, and (3) the topological properties of brain networks. We also summarize the major findings associated with major neuropsychiatric disorders obtained using these methods. Then we review the pilot studies that have used spontaneous activity to discriminate patients from normal controls. Finally, we discuss current challenges and potential research directions to further elucidate the clinical use of spontaneous brain activity in neuropsychiatric disorders. PMID:22132039

  3. Analysis of spontaneous MEG activity in mild cognitive impairment using spectral entropies and disequilibrium measures.

    PubMed

    Bruña, Ricardo; Poza, Jesús; Gómez, Carlos; Fernández, Alberto; Hornero, Roberto

    2010-01-01

    The aim of this study was to explore the ability of several spectral entropies and disequilibrium measures to discriminate between spontaneous magnetoencephalographic (MEG) oscillations from 18 mild cognitive impairment (MCI) patients and 24 controls. The Shannon spectral entropy (SSE), Tsallis spectral entropy (TSE), and Rényi spectral entropy (RSE) were calculated from the normalized power spectral density to evaluate the irregularity patterns. In addition, the Euclidean (ED) and Wootters (WD) distances were computed as disequilibrium measures. Results revealed statistically significant lower SSE and TSE(2) values for MCI patients than for controls (p < 0.05) in the right lateral region of the brain. ED also obtained statistically significant lower values for MCI patients than for controls using the (p < 0.05) in the right lateral region of the brain. These findings suggest that MCI is associated with a significant decrease in irregularity of MEG activity. In addition, the highest accuracy of 64.3% was achieved by the SSE. We conclude that measures from information theory can be useful to both characterize abnormal brain dynamics and help in MCI detection. PMID:21097360

  4. Cardiac repolarization abnormalities and increased sympathetic activity in scleroderma.

    PubMed Central

    Ciftci, Orcun; Onat, Ahmet Mesut; Yavuz, Bunyamin; Akdogan, Ali; Aytemir, Kudret; Tokgozoglu, Lale; Sahiner, Levent; Deniz, Ali; Ureten, Kemal; Kizilca, Guler; Calguneri, Meral; Oto, Ali

    2007-01-01

    BACKGROUND: Cardiac involvement in scleroderma is a poor prognostic sign and is usually underdiagnosed, particularly in asymptomatic patient. This paper focuses on QT dynamicity and heart rate variability (HRV) in patients with scleroderma and controls in an attempt to investigate the cardiac autonomic system and ventricular repolarization. METHODS: Sixty patients with scleroderma and 30 age- and sex-matched healthy controls who had no cardiovascular risk factors were included in this study. All patients and the controls underwent a 24-hour holter recording as well as a transthoracic echocardiography. HRV and QT dynamicity parameters were calculated. RESULTS: In HRV analysis, autonomic balance was changed in favor of the sympathetic system in patients with diffuse scleroderma. In QT dynamicity analysis, QT/RR slopes were significantly steeper in patients with diffuse scleroderma compared to patients with limited scleroderma and controls (QTapex/RR: 0.24 +/- 0.16, 0.15 +/- 0.03, 0.14 +/- 0.03 respectively p < 0.001; QTend/RR: 0.26 +/- 0.17, 0.14 +/- 0.04, 0.13 +/- 0.05, respectively p < 0.001). CONCLUSIONS: Patients with diffuse scleroderma may have asymptomatic cardiac repolarization abnormalities and autonomic dysfunction. Our results may indicate that QT dynamicity and HRV can be useful noninvasive methods that may detect impaired state of autonomic balance and cardiac repolarization in patients with diffuse scleroderma. PMID:17393947

  5. DELTAMETHRIN AND PERMETHRIN DECREASE SPONTANEOUS ACTIVITY IN NEURONAL NETWORKS IN VITRO.

    EPA Science Inventory

    Effects of pyrethroid insecticides on spontaneous electrical activity were investigated in primary cultures of cortical or spinal cord neurons grown on microelectrode arrays. Bicuculline (40 ¿M) was utilized to block fast GABAergic transmission, and concentration-dependent effect...

  6. Effects of norepinephrine on spontaneous firing activity of cerebellar Purkinje cells in vivo in mice.

    PubMed

    Guo, Ao; Feng, Jun-Yang; Li, Jia; Ding, Nan; Li, Ying-Jun; Qiu, De-Lai; Piao, Ri-Long; Chu, Chun-Ping

    2016-08-26

    Norepinephrine (NE), from the locus coeruleus (LC), has been supported to affect GABAergic system and parallel fiber (PF)-Purkinje cell (PC) synaptic transmission via adrenoceptor in cerebellum cortex. However, the effects of NE on the spontaneous spike activity of cerebellar PCs in living mouse have not yet been fully understood. We here examined the effects of NE on the spontaneous activity of PC in urethane-anesthetized mice by electrophysiological and pharmacological methods. Cerebellar surface application of NE (2.5-25μM) reduced the PC simple spike (SS) firing rate in a dose-dependent manner. The half-inhibitory concentration (IC50) was 5.97μM. In contrast, NE significantly increased the spontaneous firing rate of molecular layer interneuron (MLI). Application of GABAA receptor antagonist, gabazine (SR95531, 20μM) not only blocked the NE-induced inhibition of PC SS firing but also revealed NE-induced excitation of cerebellar PC. Blocking AMPA receptors activity enhanced NE-induced inhibition of PC spontaneous activity. Moreover, the effects of NE on PC spontaneous activity were abolished by simultaneously blocking GABAA and AMPA receptors activity. These results indicated that NE bidirectional modulated the spontaneous activity of PCs via enhancing both inhibitory inputs from MLIs and excitatory inputs of parallel fibers, but NE-induced enhance of inhibitory inputs overwhelmed the excitatory inputs under in vivo conditions. PMID:27369323

  7. Spontaneous high-gamma band activity reflects functional organization of auditory cortex in the awake macaque.

    PubMed

    Fukushima, Makoto; Saunders, Richard C; Leopold, David A; Mishkin, Mortimer; Averbeck, Bruno B

    2012-06-01

    In the absence of sensory stimuli, spontaneous activity in the brain has been shown to exhibit organization at multiple spatiotemporal scales. In the macaque auditory cortex, responses to acoustic stimuli are tonotopically organized within multiple, adjacent frequency maps aligned in a caudorostral direction on the supratemporal plane (STP) of the lateral sulcus. Here, we used chronic microelectrocorticography to investigate the correspondence between sensory maps and spontaneous neural fluctuations in the auditory cortex. We first mapped tonotopic organization across 96 electrodes spanning approximately two centimeters along the primary and higher auditory cortex. In separate sessions, we then observed that spontaneous activity at the same sites exhibited spatial covariation that reflected the tonotopic map of the STP. This observation demonstrates a close relationship between functional organization and spontaneous neural activity in the sensory cortex of the awake monkey. PMID:22681693

  8. Spontaneous high-gamma band activity reflects functional organization of auditory cortex in the awake macaque

    PubMed Central

    Fukushima, Makoto; Saunders, Richard C.; Leopold, David A.; Mishkin, Mortimer; Averbeck, Bruno B.

    2012-01-01

    Summary In the absence of sensory stimuli, spontaneous activity in the brain has been shown to exhibit organization at multiple spatiotemporal scales. In the macaque auditory cortex, responses to acoustic stimuli are tonotopically organized within multiple, adjacent frequency maps aligned in a caudorostral direction on the supratemporal plane (STP) of the lateral sulcus. Here we used chronic micro-electrocorticography to investigate the correspondence between sensory maps and spontaneous neural fluctuations in the auditory cortex. We first mapped tonotopic organization across 96 electrodes spanning approximately two centimeters along the primary and higher auditory cortex. In separate sessions we then observed that spontaneous activity at the same sites exhibited spatial covariation that reflected the tonotopic map of the STP. This observation demonstrates a close relationship between functional organization and spontaneous neural activity in the sensory cortex of the awake monkey. PMID:22681693

  9. Inflammation meets sensitization--an explanation for spontaneous nociceptor activity?

    PubMed

    Rukwied, Roman; Weinkauf, Benjamin; Main, Maurice; Obreja, Otilia; Schmelz, Martin

    2013-12-01

    Anti-nerve growth factor (anti-NGF) treatment is analgesic in chronic inflammatory pain conditions without reducing inflammation. Hypothesizing that ongoing pain induced by inflammatory mediators is increased by long term sensitization of nociceptors, we combined the non-inflammatory NGF-sensitization model with an inflammatory ultraviolet-B (UV-B) model in human volunteers. UV-B irradiation of the skin presensitized with NGF 3 weeks before intensified the pre-existing NGF hyperalgesia during the inflammatory phase of UV-B and caused spontaneous pain in about 70% of the subjects. Pain levels paralleled the intensity of UVB inflammation. Hyperalgesia recorded on a VAS (0-100) was additive after combined NGF/UV-B treatment versus single NGF or UV-B treatment for mechanical impact and tonic heat stimuli, again paralleling the intensity of the UV-B inflammation. In contrast, ratings to tonic mechanical pressure (100 kPa for 10 seconds, peak VAS 58 ± 7 vs VAS 21 ± 5 [NGF] and VAS 12 ± 3 [UV-B]) and pinprick (150 mN for 5 seconds, peak VAS 33 ± 7 vs VAS 10 ± 2 [NGF] and VAS 8 ± 3 [UV-B]) increased in a supra-additive manner. This supra-additive effect faded 24 hours after irradiation, although heat sensitization remained increased. Hyperalgesia and spontaneous pain coexisted in NGF/UV-B treated skin but did not significantly correlate (r < -0.1 at day 1 and r < 0.2 at day 3). We conclude that NGF can sensitize nociceptive endings such that inflammatory mediators may cause sufficient excitation to provoke spontaneous pain. Our results suggest that neuronal sensitization and level of inflammation represent independent therapeutic targets in chronic inflammatory pain conditions. PMID:23933233

  10. On the spontaneous collective motion of active matter

    PubMed Central

    Wang, Shenshen; Wolynes, Peter G.

    2011-01-01

    Spontaneous directed motion, a hallmark of cell biology, is unusual in classical statistical physics. Here we study, using both numerical and analytical methods, organized motion in models of the cytoskeleton in which constituents are driven by energy-consuming motors. Although systems driven by small-step motors are described by an effective temperature and are thus quiescent, at higher order in step size, both homogeneous and inhomogeneous, flowing and oscillating behavior emerges. Motors that respond with a negative susceptibility to imposed forces lead to an apparent negative-temperature system in which beautiful structures form resembling the asters seen in cell division. PMID:21876141

  11. On the spontaneous collective motion of active matter.

    PubMed

    Wang, Shenshen; Wolynes, Peter G

    2011-09-13

    Spontaneous directed motion, a hallmark of cell biology, is unusual in classical statistical physics. Here we study, using both numerical and analytical methods, organized motion in models of the cytoskeleton in which constituents are driven by energy-consuming motors. Although systems driven by small-step motors are described by an effective temperature and are thus quiescent, at higher order in step size, both homogeneous and inhomogeneous, flowing and oscillating behavior emerges. Motors that respond with a negative susceptibility to imposed forces lead to an apparent negative-temperature system in which beautiful structures form resembling the asters seen in cell division. PMID:21876141

  12. Effective temperature and spontaneous collective motion of active matter

    NASA Astrophysics Data System (ADS)

    Wang, Shenshen; Wolynes, Peter

    2012-02-01

    Spontaneous directed motion, a hallmark of cell biology, is unusual in classical statistical physics. Here we study, using both numerical and analytical methods, organized motion in models of the cytoskeleton in which constituents are driven by energy-consuming motors. Although systems driven by small-step motors are described by an effective temperature and are thus quiescent, at higher order in step size, both homogeneous and inhomogeneous, flowing and oscillating behavior emerges. Motors that respond with a negative susceptibility to imposed forces lead to an apparent negative temperature system in which beautiful structures form resembling the asters seen in cell division.

  13. Increasing Spontaneous Retinal Activity before Eye Opening Accelerates the Development of Geniculate Receptive Fields

    PubMed Central

    Davis, Zachary W.; Chapman, Barbara

    2015-01-01

    Visually evoked activity is necessary for the normal development of the visual system. However, little is known about the capacity for patterned spontaneous activity to drive the maturation of receptive fields before visual experience. Retinal waves provide instructive retinotopic information for the anatomical organization of the visual thalamus. To determine whether retinal waves also drive the maturation of functional responses, we increased the frequency of retinal waves pharmacologically in the ferret (Mustela putorius furo) during a period of retinogeniculate development before eye opening. The development of geniculate receptive fields after receiving these increased neural activities was measured using single-unit electrophysiology. We found that increased retinal waves accelerate the developmental reduction of geniculate receptive field sizes. This reduction is due to a decrease in receptive field center size rather than an increase in inhibitory surround strength. This work reveals an instructive role for patterned spontaneous activity in guiding the functional development of neural circuits. SIGNIFICANCE STATEMENT Patterned spontaneous neural activity that occurs during development is known to be necessary for the proper formation of neural circuits. However, it is unknown whether the spontaneous activity alone is sufficient to drive the maturation of the functional properties of neurons. Our work demonstrates for the first time an acceleration in the maturation of neural function as a consequence of driving patterned spontaneous activity during development. This work has implications for our understanding of how neural circuits can be modified actively to improve function prematurely or to recover from injury with guided interventions of patterned neural activity. PMID:26511250

  14. Memory activation enhances EEG abnormality in mild cognitive impairment.

    PubMed

    van der Hiele, K; Vein, A A; Kramer, C G S; Reijntjes, R H A M; van Buchem, M A; Westendorp, R G J; Bollen, E L E M; van Dijk, J G; Middelkoop, H A M

    2007-01-01

    This exploratory study investigated EEG power changes during memory activation in patients with amnestic mild cognitive impairment (MCI). Twelve MCI patients and 16 age-matched controls underwent EEG registration during two conventional EEG conditions ('eyes closed' and 'eyes open') and three memory conditions ('word memory', 'picture memory' and 'animal fluency'). For all conditions, EEG power in the theta (4-8 Hz), lower alpha (8-10.5 Hz) and upper alpha (10.5-13 Hz) bands were expressed as percentile changes compared to 'eyes closed'. MCI patients showed significantly less decrease in the lower alpha band than controls (p=0.04) during picture memory activation. The word memory task showed a trend towards a similar effect (p=0.09). This study suggests that memory activation reveals EEG differences between MCI patients and controls while conventional EEG conditions do not. PMID:16406153

  15. Ongoing Spontaneous Activity Controls Access to Consciousness: A Neuronal Model for Inattentional Blindness

    PubMed Central

    2005-01-01

    Even in the absence of sensory inputs, cortical and thalamic neurons can show structured patterns of ongoing spontaneous activity, whose origins and functional significance are not well understood. We use computer simulations to explore the conditions under which spontaneous activity emerges from a simplified model of multiple interconnected thalamocortical columns linked by long-range, top-down excitatory axons, and to examine its interactions with stimulus-induced activation. Simulations help characterize two main states of activity. First, spontaneous gamma-band oscillations emerge at a precise threshold controlled by ascending neuromodulator systems. Second, within a spontaneously active network, we observe the sudden “ignition” of one out of many possible coherent states of high-level activity amidst cortical neurons with long-distance projections. During such an ignited state, spontaneous activity can block external sensory processing. We relate those properties to experimental observations on the neural bases of endogenous states of consciousness, and particularly the blocking of access to consciousness that occurs in the psychophysical phenomenon of “inattentional blindness,” in which normal subjects intensely engaged in mental activity fail to notice salient but irrelevant sensory stimuli. Although highly simplified, the generic properties of a minimal network may help clarify some of the basic cerebral phenomena underlying the autonomy of consciousness. PMID:15819609

  16. The MEG topography and the source model of abnormal neural activities associated with brain lesions

    SciTech Connect

    Ueno, S.; Iramina, K.; Ozaki, H.; Harada, K.

    1986-09-01

    A source model is proposed to simulate spatial distributions of abnormal MEG and EEG activities generated by abnormal neural activities such as the delta activity associated with brain tumors. Brain tumor itself is electrically silent and the spherical shell around the tumor might generate abnormal neural activities. The sources of these neural activities are represented by combinations of multiple current dipoles. The head is assumed to be a spherical volume conductor. Electrical potentials and magnetic fields over the surface of the spheres are calculated. The computer simulation shows that the MEG topography and EEG topography vary variously with combinations of location and orientation of the dipoles. In a special case, however, that the dipoles orient in the same direction or orient radially, the spatial patterns of the MEGs and EEGs generated by numerous dipoles are analogous to those generated by single dipoles.

  17. NMDA Receptors Enhance Spontaneous Activity and Promote Neuronal Survival in the Developing Cochlea.

    PubMed

    Zhang-Hooks, YingXin; Agarwal, Amit; Mishina, Masayoshi; Bergles, Dwight E

    2016-01-20

    Spontaneous bursts of activity in developing sensory pathways promote maturation of neurons, refinement of neuronal connections, and assembly of appropriate functional networks. In the developing auditory system, inner hair cells (IHCs) spontaneously fire Ca(2+) spikes, each of which is transformed into a mini-burst of action potentials in spiral ganglion neurons (SGNs). Here we show that NMDARs are expressed in SGN dendritic terminals and play a critical role during transmission of activity from IHCs to SGNs before hearing onset. NMDAR activation enhances glutamate-mediated Ca(2+) influx at dendritic terminals, promotes repetitive firing of individual SGNs in response to each synaptic event, and enhances coincident activity of neighboring SGNs that will eventually encode similar frequencies of sound. Loss of NMDAR signaling from SGNs reduced their survival both in vivo and in vitro, revealing that spontaneous activity in the prehearing cochlea promotes maturation of auditory circuitry through periodic activation of NMDARs in SGNs. PMID:26774161

  18. A role for correlated spontaneous activity in the assembly of neural circuits

    PubMed Central

    Kirkby, Lowry; Sack, Georgeann; Firl, Alana; Feller, Marla B.

    2015-01-01

    Before the onset of sensory transduction, developing neural circuits spontaneously generate correlated activity in distinct spatial and temporal patterns. During this period of patterned activity, sensory maps develop and initial coarse connections are refined, which are critical steps in the establishment of adult neural circuits. Over the last decade there has been substantial evidence that altering the pattern of spontaneous activity disrupts refinement, but the mechanistic understanding of this process remains incomplete. In this review, we discuss recent experimental and theoretical progress towards the process of activity-dependent refinement, focusing on circuits in the visual, auditory and motor systems. While many outstanding questions remain, the combination of several novel approaches have brought us closer to a comprehensive understanding of how complex neural circuits are established by patterned spontaneous activity during development. PMID:24314725

  19. Satellite microglia show spontaneous electrical activity that is uncorrelated with activity of the attached neuron.

    PubMed

    Wogram, Emile; Wendt, Stefan; Matyash, Marina; Pivneva, Tatyana; Draguhn, Andreas; Kettenmann, Helmut

    2016-06-01

    Microglia are innate immune cells of the brain. We have studied a subpopulation of microglia, called satellite microglia. This cell type is defined by a close morphological soma-to-soma association with a neuron, indicative of a direct functional interaction. Indeed, ultrastructural analysis revealed closely attached plasma membranes of satellite microglia and neurons. However, we found no apparent morphological specializations of the contact, and biocytin injection into satellite microglia showed no dye-coupling with the apposed neurons or any other cell. Likewise, evoked local field potentials or action potentials and postsynaptic potentials of the associated neuron did not lead to any transmembrane currents or non-capacitive changes in the membrane potential of the satellite microglia in the cortex and hippocampus. Both satellite and non-satellite microglia, however, showed spontaneous transient membrane depolarizations that were not correlated with neuronal activity. These events could be divided into fast-rising and slow-rising depolarizations, which showed different characteristics in satellite and non-satellite microglia. Fast-rising and slow-rising potentials differed with regard to voltage dependence. The frequency of these events was not affected by the application of tetrodotoxin, but the fast-rising event frequency decreased after application of GABA. We conclude that microglia show spontaneous electrical activity that is uncorrelated with the activity of adjacent neurons. PMID:27060918

  20. Spontaneous regional brain activity links restrained eating to later weight gain among young women.

    PubMed

    Dong, Debo; Jackson, Todd; Wang, Yulin; Chen, Hong

    2015-07-01

    Theory and prospective studies have linked restrained eating (RE) to risk for future weight gain and the onset of obesity, but little is known about resting state neural activity that may underlie this association. To address this gap, resting fMRI was used to test the extent to which spontaneous neural activity in regions associated with inhibitory control and food reward account for potential relations between baseline RE levels and changes in body weight among dieters over a one-year interval. Spontaneous regional activity patterns corresponding to RE were assessed among 50 young women using regional homogeneity (ReHo) analysis, which measured temporal synchronization of spontaneous fluctuations within a food deprivation condition. Analyses indicated higher baseline RE scores predicted more weight gain at a one-year follow-up. Furthermore, food-deprived dieting women with high dietary restraint scores exhibited more spontaneous local activity in brain regions associated with the expectation and valuation for food reward [i.e., orbitofrontal cortex (OFC)/ventromedial prefrontal cortex (VMPFC)] and reduced spontaneous local activity in inhibitory control regions [i.e., bilateral dorsal-lateral prefrontal cortex (DLPFC)] at baseline. Notably, the association between baseline RE and follow-up weight gain was mediated by decreased local synchronization of the right DLPFC in particular and, to a lesser degree, increased local synchronization of the right VMPFC. In conjunction with previous research, these findings highlight possible neural mechanisms underlying the relation between RE and risk for weight gain. PMID:26004091

  1. Spontaneous Activity of Cochlear Hair Cells Triggered by Fluid Secretion Mechanism in Adjacent Support Cells.

    PubMed

    Wang, Han Chin; Lin, Chun-Chieh; Cheung, Rocky; Zhang-Hooks, YingXin; Agarwal, Amit; Ellis-Davies, Graham; Rock, Jason; Bergles, Dwight E

    2015-12-01

    Spontaneous electrical activity of neurons in developing sensory systems promotes their maturation and proper connectivity. In the auditory system, spontaneous activity of cochlear inner hair cells (IHCs) is initiated by the release of ATP from glia-like inner supporting cells (ISCs), facilitating maturation of central pathways before hearing onset. Here, we find that ATP stimulates purinergic autoreceptors in ISCs, triggering Cl(-) efflux and osmotic cell shrinkage by opening TMEM16A Ca(2+)-activated Cl(-) channels. Release of Cl(-) from ISCs also forces K(+) efflux, causing transient depolarization of IHCs near ATP release sites. Genetic deletion of TMEM16A markedly reduces the spontaneous activity of IHCs and spiral ganglion neurons in the developing cochlea and prevents ATP-dependent shrinkage of supporting cells. These results indicate that supporting cells in the developing cochlea have adapted a pathway used for fluid secretion in other organs to induce periodic excitation of hair cells. PMID:26627734

  2. Spontaneous Neuronal Activity in Developing Neocortical Networks: From Single Cells to Large-Scale Interactions

    PubMed Central

    Luhmann, Heiko J.; Sinning, Anne; Yang, Jenq-Wei; Reyes-Puerta, Vicente; Stüttgen, Maik C.; Kirischuk, Sergei; Kilb, Werner

    2016-01-01

    Neuronal activity has been shown to be essential for the proper formation of neuronal circuits, affecting developmental processes like neurogenesis, migration, programmed cell death, cellular differentiation, formation of local and long-range axonal connections, synaptic plasticity or myelination. Accordingly, neocortical areas reveal distinct spontaneous and sensory-driven neuronal activity patterns already at early phases of development. At embryonic stages, when immature neurons start to develop voltage-dependent channels, spontaneous activity is highly synchronized within small neuronal networks and governed by electrical synaptic transmission. Subsequently, spontaneous activity patterns become more complex, involve larger networks and propagate over several neocortical areas. The developmental shift from local to large-scale network activity is accompanied by a gradual shift from electrical to chemical synaptic transmission with an initial excitatory action of chloride-gated channels activated by GABA, glycine and taurine. Transient neuronal populations in the subplate (SP) support temporary circuits that play an important role in tuning early neocortical activity and the formation of mature neuronal networks. Thus, early spontaneous activity patterns control the formation of developing networks in sensory cortices, and disturbances of these activity patterns may lead to long-lasting neuronal deficits. PMID:27252626

  3. Spontaneous Neuronal Activity in Developing Neocortical Networks: From Single Cells to Large-Scale Interactions.

    PubMed

    Luhmann, Heiko J; Sinning, Anne; Yang, Jenq-Wei; Reyes-Puerta, Vicente; Stüttgen, Maik C; Kirischuk, Sergei; Kilb, Werner

    2016-01-01

    Neuronal activity has been shown to be essential for the proper formation of neuronal circuits, affecting developmental processes like neurogenesis, migration, programmed cell death, cellular differentiation, formation of local and long-range axonal connections, synaptic plasticity or myelination. Accordingly, neocortical areas reveal distinct spontaneous and sensory-driven neuronal activity patterns already at early phases of development. At embryonic stages, when immature neurons start to develop voltage-dependent channels, spontaneous activity is highly synchronized within small neuronal networks and governed by electrical synaptic transmission. Subsequently, spontaneous activity patterns become more complex, involve larger networks and propagate over several neocortical areas. The developmental shift from local to large-scale network activity is accompanied by a gradual shift from electrical to chemical synaptic transmission with an initial excitatory action of chloride-gated channels activated by GABA, glycine and taurine. Transient neuronal populations in the subplate (SP) support temporary circuits that play an important role in tuning early neocortical activity and the formation of mature neuronal networks. Thus, early spontaneous activity patterns control the formation of developing networks in sensory cortices, and disturbances of these activity patterns may lead to long-lasting neuronal deficits. PMID:27252626

  4. Quantitative observation and study on rhythmic abnormalities of activities in animals prior to earthquakes

    NASA Astrophysics Data System (ADS)

    Feng, Chungao; Jiang, Jinchang

    1992-11-01

    In this paper, the normal daily activities and abnormal activities related to earthquake premonitory information are given by a quantitative observation and analysis of activities in the sparrow (SR, Passer montanus), budgerigar (BG, Melopsittacus undulatus) and rat (RT, Rattus norvegicus). The results show that the quantitative observation of habitual abnormalities in animals may provide some cues for the short-term earthquake prediction. The normal activity rhythms for the SR and BG are similar, and both present M mode. The high activities occurs during 07h 10h and 15h 16h, respectively, the low activities occurs during 12h 13h, and at night both birds are basically silent. For the RT, the normal rhythmic activity has the middle magnitude during 07h 10h and 17h 18h, the low and high magnitudes occur during 11h 16h and from 19h to 06h at the next day. For the SR, BG and RT, observable abnormal changes of the normal activity rhythm were found before earthquakes. The night activities of the SR and BG were increased noticeably. For the RT the activities during the low magnitude of activities at the day time were also increased. They both are about 300 times greater than the normal activity value. Moreover, the total activity values per day were increased, and were about 2 times of the normal value. The x 2-test shows that the abnormalities of the daily activity rhythm and following increase of the daily activity events are significantly correlated with earthquakes of magnitude over 4.3 in Tangshan seismic area within the region of 200 km distance from the observation station.

  5. Effect of spontaneous activity on stimulus detection in a simple neuronal model.

    PubMed

    Levakova, Marie

    2016-06-01

    It is studied what level of a continuous-valued signal is optimally estimable on the basis of first-spike latency neuronal data. When a spontaneous neuronal activity is present, the first spike after the stimulus onset may be caused either by the stimulus itself, or it may be a result of the prevailing spontaneous activity. Under certain regularity conditions, Fisher information is the inverse of the variance of the best estimator. It can be considered as a function of the signal intensity and then indicates accuracy of the estimation for each signal level. The Fisher information is normalized with respect to the time needed to obtain an observation. The accuracy of signal level estimation is investigated in basic discharge patterns modelled by a Poisson and a renewal process and the impact of the complex interaction between spontaneous activity and a delay of the response is shown. PMID:27106186

  6. Spatial pattern of spontaneous retinal waves instructs retinotopic map refinement more than activity frequency.

    PubMed

    Xu, Hong-Ping; Burbridge, Timothy J; Chen, Ming-Gang; Ge, Xinxin; Zhang, Yueyi; Zhou, Zhimin Jimmy; Crair, Michael C

    2015-06-01

    Spontaneous activity during early development is necessary for the formation of precise neural connections, but it remains uncertain whether activity plays an instructive or permissive role in brain wiring. In the visual system, retinal ganglion cell (RGC) projections to the brain form two prominent sensory maps, one reflecting eye of origin and the other retinotopic location. Recent studies provide compelling evidence supporting an instructive role for spontaneous retinal activity in the development of eye-specific projections, but evidence for a similarly instructive role in the development of retinotopy is more equivocal. Here, we report on experiments in which we knocked down the expression of β2-containing nicotinic acetylcholine receptors (β2-nAChRs) specifically in the retina through a Cre-loxP recombination strategy. Overall levels of spontaneous retinal activity in retina-specific β2-nAChR mutant mice (Rx-β2cKO), examined in vitro and in vivo, were reduced to a degree comparable to that observed in whole animal β2-nAChR mouse mutants (β2KO). However, many residual spontaneous waves in Rx-β2cKO mice displayed local propagating features with strong correlations between nearby but not distant RGCs typical of waves observed in wild-type (WT) but not β2KO mice. We further observed that eye-specific segregation was disrupted in Rx-β2cKO mice, but retinotopy was spared in a competition-dependent manner. These results suggest that propagating patterns of spontaneous retinal waves are essential for normal development of the retinotopic map, even while overall activity levels are significantly reduced, and support an instructive role for spontaneous retinal activity in both eye-specific segregation and retinotopic refinement. PMID:25787992

  7. Spatial pattern of spontaneous retinal waves instructs retinotopic map refinement more than activity frequency

    PubMed Central

    Xu, Hong-Ping; Burbridge, Timothy J.; Chen, Ming-Gang; Ge, Xinxin; Zhang, Yueyi; Zhou, Z. Jimmy; Crair, Michael C.

    2015-01-01

    Spontaneous activity during early development is necessary for the formation of precise neural connections, but it remains uncertain whether activity plays an instructive or permissive role in brain wiring. In the visual system, retinal ganglion cell (RGC) projections to the brain form two prominent sensory maps, one reflecting eye of origin and the other retinotopic location. Recent studies provide compelling evidence supporting an instructive role for spontaneous retinal activity in the development of eye-specific projections, but evidence for a similarly instructive role in the development of retinotopy is more equivocal. Here, we report on experiments in which we knocked down the expression of β2-containing nicotinic acetylcholine receptors (β2-nAChRs) specifically in the retina through a Cre-loxP recombination strategy. Overall levels of spontaneous retinal activity in retina-specific β2-nAChR mutant mice (Rx-β2cKO), examined in vitro and in vivo, were reduced to a degree comparable to that observed in whole animal β2-nAChR mouse mutants (β2KO). However, many residual spontaneous waves in Rx-β2cKO mice displayed local propagating features with strong correlations between nearby but not distant RGCs typical of waves observed in WT, but not β2KO mice. We further observed that eye-specific segregation was disrupted in Rx-β2cKO mice, but retinotopy was spared in a competition-dependent manner. These results suggest that propagating patterns of spontaneous retinal waves are essential for normal development of the retinotopic map, even while overall activity levels are significantly reduced, and support an instructive role for spontaneous retinal activity in both eye-specific segregation and retinotopic refinement. PMID:25787992

  8. Spontaneous motility of passive emulsion droplets in polar active gels.

    PubMed

    De Magistris, G; Tiribocchi, A; Whitfield, C A; Hawkins, R J; Cates, M E; Marenduzzo, D

    2014-10-21

    We study by computer simulations the dynamics of a droplet of passive, isotropic fluid, embedded in a polar active gel. The latter represents a fluid of active force dipoles, which exert either contractile or extensile stresses on their surroundings, modelling for instance a suspension of cytoskeletal filaments and molecular motors. When the polarisation of the active gel is anchored normal to the droplet at its surface, the nematic elasticity of the active gel drives the formation of a hedgehog defect; this defect then drives an active flow which propels the droplet forward. In an extensile gel, motility can occur even with tangential anchoring, which is compatible with a defect-free polarisation pattern. In this case, upon increasing activity the droplet first rotates uniformly, and then undergoes a discontinuous nonequilibrium transition into a translationally motile state, powered by bending deformations in the surrounding active medium. PMID:25156695

  9. Effect of hyperthyroidism on spontaneous physical activity and energy expenditure in rats.

    PubMed

    Levine, James A; Nygren, Jonas; Short, Kevin R; Nair, K Sreekumaran

    2003-01-01

    Thyroid hormone excess is associated with increased energy expenditure. The contributions of increases in spontaneous physical activity and nonexercise activity thermogenesis (NEAT) to this effect have not been defined. To address the hypothesis that hyperthyroidism is associated with increased spontaneous physical activity and NEAT, we rendered rats hyperthyroid by using continuous infusion of high-dose triiodothyronine for 14 days and measured the effects on physical activity and NEAT. On day 14, in the hyperthyroid group the mean +/- SD triiodothyronine concentration was 755 +/- 137 (range 574-919) ng/dl and in the control group 59 +/- 0.5 (58-59) ng/dl. Over the 14-day treatment period, mean spontaneous physical activity increased in the hyperthyroid rats from 24 +/- 7 to 36 +/- 6 activity units (AU)/min; P < 0.001 but did not increase in the controls (23 +/- 7 vs. 22 +/- 4 AU/min). Also, over the 14-day period, daily NEAT increased in the hyperthyroid rats from 8.1 +/- 2.8 to 19.7 +/- 5.0 kcal/day (P < 0.001) but did not increase in the controls (8.7 +/- 3.5 cf 9.4 +/- 1.7 kcal/day; not significant). In conclusion, hyperthyroidism is associated with increased spontaneous physical activity and NEAT. PMID:12486020

  10. Abnormal Baseline Brain Activity in Patients with Pulsatile Tinnitus: A Resting-State fMRI Study

    PubMed Central

    Han, Lv; Zhaohui, Liu; Fei, Yan; Ting, Li; Pengfei, Zhao; Wang, Du; Cheng, Dong; Pengde, Guo; Xiaoyi, Han; Xiao, Wang; Rui, Li; Zhenchang, Wang

    2014-01-01

    Numerous investigations studying the brain functional activity of the tinnitus patients have indicated that neurological changes are important findings of this kind of disease. However, the pulsatile tinnitus (PT) patients were excluded in previous studies because of the totally different mechanisms of the two subtype tinnitus. The aim of this study is to investigate whether altered baseline brain activity presents in patients with PT using resting-state functional magnetic resonance imaging (rs-fMRI) technique. The present study used unilateral PT patients (n = 42) and age-, sex-, and education-matched normal control subjects (n = 42) to investigate the changes in structural and amplitude of low-frequency (ALFF) of the brain. Also, we analyzed the relationships between these changes with clinical data of the PT patients. Compared with normal controls, PT patients did not show any structural changes. PT patients showed significant increased ALFF in the bilateral precuneus, and bilateral inferior frontal gyrus (IFG) and decreased ALFF in multiple occipital areas. Moreover, the increased THI score and PT duration was correlated with increased ALFF in precuneus and bilateral IFG. The abnormalities of spontaneous brain activity reflected by ALFF measurements in the absence of structural changes may provide insights into the neural reorganization in PT patients. PMID:24872895

  11. SEARCH FOR AN 80-ms SPONTANEOUS FISSION ACTIVITY IN BOMBARDMENTS OF 249Bk WITH 15N

    SciTech Connect

    Nitschke, J.M.; Fowler, M.; Ghiorso, A.; Leber, R.E.; Nurmia, M.J.; Somerville, L.P.; Williams, K.E.; Hulet, E.K.; Landrum, J.H.; Lougheed, R.W.; Wild, J.F.; Bemis, Jr., C.E.; Silva, R.J.; Eskola, P.

    1980-01-01

    A rotating drum system was used to search for an 80-ms spontaneous fission (sf) activity in the reaction of {sup 15}N with {sup 249}Bk. No such activity was found beyond a cross section limit of 0.3 {+-} 0.3 nb. A sf activity with a half-life of about 20 ms and a formation cross section of 12 nb at 82 MeV was observed. The identity of this activity has not been determined.

  12. Mechanotransduction and hyperpolarization-activated currents contribute to spontaneous activity in mouse vestibular ganglion neurons.

    PubMed

    Horwitz, Geoffrey C; Risner-Janiczek, Jessica R; Holt, Jeffrey R

    2014-04-01

    The hyperpolarization-activated, cyclic nucleotide-sensitive current, Ih, is present in vestibular hair cells and vestibular ganglion neurons, and is required for normal balance function. We sought to identify the molecular correlates and functional relevance of Ih in vestibular ganglion neurons. Ih is carried by channels consisting of homo- or heteromeric assemblies of four protein subunits from the Hcn gene family. The relative expression of Hcn1-4 mRNA was examined using a quantitative reverse transcription PCR (RT-PCR) screen. Hcn2 was the most highly expressed subunit in vestibular neuron cell bodies. Immunolocalization of HCN2 revealed robust expression in cell bodies of all vestibular ganglion neurons. To characterize Ih in vestibular neuron cell bodies and at hair cell-afferent synapses, we developed an intact, ex vivo preparation. We found robust physiological expression of Ih in 89% of cell bodies and 100% of calyx terminals. Ih was significantly larger in calyx terminals than in cell bodies; however, other biophysical characteristics were similar. Ih was absent in calyces lacking Hcn1 and Hcn2, but small Ih was still present in cell bodies, which suggests expression of an additional subunit, perhaps Hcn4. To determine the contributions of hair cell mechanotransduction and Ih to the firing patterns of calyx terminals, we recorded action potentials in current-clamp mode. Mechanotransduction currents were modulated by hair bundle defection and application of calcium chelators to disrupt tip links. Ih activity was modulated using ZD7288 and cAMP. We found that both hair cell transduction and Ih contribute to the rate and regularity of spontaneous action potentials in the vestibular afferent neurons. We propose that modulation of Ih in vestibular ganglion neurons may provide a mechanism for modulation of spontaneous activity in the vestibular periphery. PMID:24638995

  13. Values-Oriented Public Policy Forums: Active Learning in Abnormal Psychology.

    ERIC Educational Resources Information Center

    Hevern, Vincent W.

    Students in an undergraduate course in abnormal psychology annually employ a cooperative active learning model to conduct a 4- to 6-day, values-oriented public policy forum (PPF) within the class itself on a general topic of concern to the field of mental health. A comprehensive and structured five-phase model for a PPF is detailed for course…

  14. [The influence of persistent crowding on the spontaneous motor activity of the aging rat (author's transl)].

    PubMed

    Kment, A; Hofecker, G; Skalicky, M; Niedermüller, H

    1982-07-01

    In the course of a long-term cohort study of stress and aging, the spontaneous activity of 169 male Sprague-Dawley rats was measured at various ages from 9 to 30 months. 84 animals were submitted to crowding from the age of 5 months onwards by housing them in groups of 12 per Makrolon-IV cage. 85 rats, kept as usual in groups of 6 per makrolon-IV cage, served as a control. Spontaneous activity was assessed by an electronic instrument (Animex Activity Meter), which also enabled us to distinguish between total and large movements. During senescence, the spontaneous activity of the control animals decreased slightly by approximately 20% after the age of 18 months. In addition to the quantitative change, a progressive flattening of the activity rhythm was observed. The animals kept under crowded conditions did not reveal any age-related decrease in spontaneous activity. At an advanced age, this resulted in significantly higher activity values in the crowded group as compared with the controls. The differences appeared even earlier and seemed to be more pronounced in the number of large movements. However, the progressive disappearance of the endogenous rhythm was apparent in both the crowded and the control group. It can be concluded that at least two types of change in the central nervous system may be responsible for the aging-changes in spontaneous activity: one which disintegrates the "time structure" of the organism, and a second one which affects motivational centers. Crowded conditions seem to improve the latter, whereas they have no effect on the aging of the "biological clock". PMID:6126135

  15. Sustained attention to spontaneous thumb sensations activates brain somatosensory and other proprioceptive areas.

    PubMed

    Bauer, Clemens C C; Díaz, José-Luis; Concha, Luis; Barrios, Fernando A

    2014-06-01

    The present experiment was designed to test if sustained attention directed to the spontaneous sensations of the right or left thumb in the absence of any external stimuli is able to activate corresponding somatosensory brain areas. After verifying in 34 healthy volunteers that external touch stimuli to either thumb effectively activate brain contralateral somatosensory areas, and after subtracting attention mechanisms employed in both touch and spontaneous-sensation conditions, fMRI evidence was obtained that the primary somatosensory cortex (specifically left BA 3a/3b) becomes active when an individual is required to attend to the spontaneous sensations of either thumb in the absence of external stimuli. In addition, the left superior parietal cortex, anterior cingulate gyrus, insula, motor and premotor cortex, left dorsolateral prefrontal cortex, Broca's area, and occipital cortices were activated. Moreover, attention to spontaneous-sensations revealed an increased connectivity between BA 3a/3b, superior frontal gyrus (BA 9) and anterior cingulate cortex (BA 32), probably allowing top-down activations of primary somatosensory cortex. We conclude that specific primary somatosensory areas in conjunction with other left parieto-frontal areas are involved in processing proprioceptive and interoceptive bodily information that underlies own body-representations and that these networks and cognitive functions can be modulated by top-down attentional processes. PMID:24727703

  16. The role of cellular coupling in the spontaneous generation of electrical activity in uterine tissue.

    PubMed

    Xu, Jinshan; Menon, Shakti N; Singh, Rajeev; Garnier, Nicolas B; Sinha, Sitabhra; Pumir, Alain

    2015-01-01

    The spontaneous emergence of contraction-inducing electrical activity in the uterus at the beginning of labor remains poorly understood, partly due to the seemingly contradictory observation that isolated uterine cells are not spontaneously active. It is known, however, that the expression of gap junctions increases dramatically in the approach to parturition, by more than one order of magnitude, which results in a significant increase in inter-cellular electrical coupling. In this paper, we build upon previous studies of the activity of electrically excitable smooth muscle cells (myocytes) and investigate the mechanism through which the coupling of these cells to electrically passive cells results in the generation of spontaneous activity in the uterus. Using a recently developed, realistic model of uterine muscle cell dynamics, we investigate a system consisting of a myocyte coupled to passive cells. We then extend our analysis to a simple two-dimensional lattice model of the tissue, with each myocyte being coupled to its neighbors, as well as to a random number of passive cells. We observe that different dynamical regimes can be observed over a range of gap junction conductances: at low coupling strength, corresponding to values measured long before delivery, the activity is confined to cell clusters, while the activity for high coupling, compatible with values measured shortly before delivery, may spread across the entire tissue. Additionally, we find that the system supports the spontaneous generation of spiral wave activity. Our results are both qualitatively and quantitatively consistent with observations from in vitro experiments. In particular, we demonstrate that the increase in inter-cellular electrical coupling observed experimentally strongly facilitates the appearance of spontaneous action potentials that may eventually lead to parturition. PMID:25793276

  17. Brain activity for chronic knee osteoarthritis: dissociating evoked pain from spontaneous pain

    PubMed Central

    Parks, Elle L.; Geha, Paul Y.; Baliki, Marwan N.; Katz, Jeffrey; Schnitzer, Thomas J.; Apkarian, A. Vania

    2011-01-01

    Chronic pain is a hallmark of osteoarthritis (OA), yet little is known about its properties and representation in the brain. Here we use fMRI combined with psychophysics to study knee pain in 14 OA patients and 9 healthy controls. Mechanical painful pressure stimuli were applied to the knee in both groups and ratings of evoked pain and related brain activity examined. We observe that psychophysical properties and brain activation patterns of evoked pain are essentially the same between OA patients and healthy subjects, and between worse and better OA knees. In OA patients, stimulus-related brain activity could be distinguished from brain activity associated with spontaneous pain. The former activated brain regions commonly observed for acute painful stimuli in healthy subjects, while the spontaneous pain of OA engaged prefrontal-limbic regions closely corresponding to areas observed for spontaneous pain in other chronic pain conditions, such as chronic back pain and post-herpetic neuralgia. Arthritis-related clinical characteristics of knee OA also mapped to prefrontal-limbic regions. In a subgroup of patients (n = 6) we examined brain activity changes for a 2-week, repeat measure, cyclooxygenase-2 inhibitor (valdecoxib) therapy. Treatment decreased spontaneous pain for the worse knee and clinical characteristics of OA, and increased blood and csf levels of the drug which correlated positively with prefrontal-limbic brain activity. These findings indicate dissociation between mechanically induced and spontaneous OA knee pain, the latter engaging brain regions involved in emotional assessment of the self, and challenge the standard clinical view regarding the nature of OA pain. PMID:21315627

  18. Abnormal Neural Activation to Faces in the Parents of Children with Autism.

    PubMed

    Yucel, G H; Belger, A; Bizzell, J; Parlier, M; Adolphs, R; Piven, J

    2015-12-01

    Parents of children with an autism spectrum disorder (ASD) show subtle deficits in aspects of social behavior and face processing, which resemble those seen in ASD, referred to as the "Broad Autism Phenotype " (BAP). While abnormal activation in ASD has been reported in several brain structures linked to social cognition, little is known regarding patterns in the BAP. We compared autism parents with control parents with no family history of ASD using 2 well-validated face-processing tasks. Results indicated increased activation in the autism parents to faces in the amygdala (AMY) and the fusiform gyrus (FG), 2 core face-processing regions. Exploratory analyses revealed hyper-activation of lateral occipital cortex (LOC) bilaterally in autism parents with aloof personality ("BAP+"). Findings suggest that abnormalities of the AMY and FG are related to underlying genetic liability for ASD, whereas abnormalities in the LOC and right FG are more specific to behavioral features of the BAP. Results extend our knowledge of neural circuitry underlying abnormal face processing beyond those previously reported in ASD to individuals with shared genetic liability for autism and a subset of genetically related individuals with the BAP. PMID:25056573

  19. Spontaneous neuronal activity as a self-organized critical phenomenon

    NASA Astrophysics Data System (ADS)

    de Arcangelis, L.; Herrmann, H. J.

    2013-01-01

    Neuronal avalanches are a novel mode of activity in neuronal networks, experimentally found in vitro and in vivo, and exhibit a robust critical behaviour. Avalanche activity can be modelled within the self-organized criticality framework, including threshold firing, refractory period and activity-dependent synaptic plasticity. The size and duration distributions confirm that the system acts in a critical state, whose scaling behaviour is very robust. Next, we discuss the temporal organization of neuronal avalanches. This is given by the alternation between states of high and low activity, named up and down states, leading to a balance between excitation and inhibition controlled by a single parameter. During these periods both the single neuron state and the network excitability level, keeping memory of past activity, are tuned by homeostatic mechanisms. Finally, we verify if a system with no characteristic response can ever learn in a controlled and reproducible way. Learning in the model occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. Learning is a truly collective process and the learning dynamics exhibits universal features. Even complex rules can be learned provided that the plastic adaptation is sufficiently slow.

  20. Solar activity cycle and the incidence of foetal chromosome abnormalities detected at prenatal diagnosis

    NASA Astrophysics Data System (ADS)

    Halpern, Gabrielle J.; Stoupel, Eliahu G.; Barkai, Gad; Chaki, Rina; Legum, Cyril; Fejgin, Moshe D.; Shohat, Mordechai

    1995-06-01

    We studied 2001 foetuses during the period of minimal solar activity of solar cycle 21 and 2265 foetuses during the period of maximal solar activity of solar cycle 22, in all women aged 37 years and over who underwent free prenatal diagnosis in four hospitals in the greater Tel Aviv area. There were no significant differences in the total incidence of chromosomal abnormalities or of trisomy between the two periods (2.15% and 1.8% versus 2.34% and 2.12%, respectively). However, the trend of excessive incidence of chromosomal abnormalities in the period of maximal solar activity suggests that a prospective study in a large population would be required to rule out any possible effect of extreme solar activity.

  1. The neurological significance of abnormal natural killer cell activity in chronic toxigenic mold exposures.

    PubMed

    Anyanwu, Ebere; Campbell, Andrew W; Jones, Joseph; Ehiri, John E; Akpan, Akpan I

    2003-11-13

    Toxigenic mold activities produce metabolites that are either broad-spectrum antibiotics or mycotoxins that are cytotoxic. Indoor environmental exposure to these toxigenic molds leads to adverse health conditions with the main outcome measure of frequent neuroimmunologic and behavioral consequences. One of the immune system disorders found in patients presenting with toxigenic mold exposure is an abnormal natural killer cell activity. This paper presents an overview of the neurological significance of abnormal natural killer cell (NKC) activity in chronic toxigenic mold exposure. A comprehensive review of the literature was carried out to evaluate and assess the conditions under which the immune system could be dysfunctionally interfered with leading to abnormal NKC activity and the involvement of mycotoxins in these processes. The functions, mechanism, the factors that influence NKC activities, and the roles of mycotoxins in NKCs were cited wherever necessary. The major presentations are headache, general debilitating pains, nose bleeding, fevers with body temperatures up to 40 degrees C (104 degrees F), cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, vertigo/dizziness, and in some cases, seizures. Although sleep is commonly considered a restorative process that is important for the proper functioning of the immune system, it could be disturbed by mycotoxins. Most likely, mycotoxins exert some rigorous effects on the circadian rhythmic processes resulting in sleep deprivation to which an acute and transient increase in NKC activity is observed. Depression, psychological stress, tissue injuries, malignancies, carcinogenesis, chronic fatigue syndrome, and experimental allergic encephalomyelitis could be induced at very low physiological concentrations by mycotoxin-induced NKC activity. In the light of this review, it is concluded that chronic exposures to toxigenic mold could lead to abnormal NKC activity with a wide range

  2. A Neuroanatomical Basis for the Frequency of Discrete Spontaneous Activities in Schizophrenia

    PubMed Central

    Farrow, Tom F.D; Hunter, Michael D; Wilkinson, Iain D; Spence, Sean A

    2009-01-01

    Limited behavioural repertoire impacts quality of life in chronic schizophrenia. We have previously shown that the amount of movement exhibited by patients with schizophrenia is positively correlated with the volume of left anterior cingulate cortex and that this quantity of movement can be increased by modafinil. However, increased movement in itself may be of limited clinical significance. Hence, we sought to analyse the ‘structure’ of spontaneous movement in patients with schizophrenia and to examine whether the chunking of spontaneous activity has a neuroanatomical basis. ‘Actiwatches’ were used to record spontaneous motor activity over a 20 hour period in sixteen male patients with schizophrenia. Time-series data were analysed for the number of discrete spontaneous activities, which might indicate a degree of structure to ongoing activity. Subjects underwent a whole-brain structural MRI scan. The ‘number of discrete movement epochs’ correlated with volumes of regions within bilateral rostro-ventral putamen and temporal poles. These data suggest that in people with schizophrenia the volume of bilateral putamen may influence the complexity of their behaviours, as distinct from the overall amount of behaviour. The results are presented in the context of a large body of previous research examining the role of the basal ganglia in motor and cognitive pattern generation. PMID:19572020

  3. DELTAMETHRIN AND ESFENVALERATE INHIBIT SPONTANEOUS NETWORK ACTIVITY IN RAT CORTICAL NEURONS IN VITRO.

    EPA Science Inventory

    Understanding pyrethroid actions on neuronal networks will help to establish a mode of action for these compounds, which is needed for cumulative risk decisions under the Food Quality Protection Act of 1996. However, pyrethroid effects on spontaneous activity in networks of inter...

  4. Oncogene activation in spontaneous and chemically induced rodent tumors: implications for risk analysis

    SciTech Connect

    Reynolds, S.H.; Stowers, S.J.; Patterson, R.M.; Maronpot, R.R.; Anderson, M.W.

    1988-06-01

    The validity of rodent tumor end points in assessing the potential hazards of chemical exposure to humans is a somewhat controversial but very important issue since most chemicals are classified as potentially hazardous to humans on the basis of long-term carcinogenesis studies in rodents. The ability to distinguish between genotoxic, cytotoxic, or receptor-mediated promotion effects of chemical treatment would aid in the interpretation of rodent carcinogenesis data. Activated oncogenes in spontaneously occurring and chemically induced rodent tumors were examined and compared as one approach to determine the mechanism by which chemical treatment caused an increased incidence of rodent tumors. Different patterns of activated oncogenes were found not only in spontaneous versus chemically induced mouse liver tumors but also in a variety of spontaneous rat tumors versus chemically induced rat lung tumors. In the absence of cytotoxic effects, it could be argued that the chemicals in question activated protooncogenes by a direct genotoxic mechanism. These results provided a basis for the analysis of activated oncogenes in spontaneous and chemically induced rodent tumors to provide information at a molecular level to aid in the extrapolation of rodent carcinogenesis data to human risk assessment.

  5. Effects of Organophosphorus Flame Retardants on Spontaneous Activity in Neuronal Networks Grown on Microelectrode Arrays

    EPA Science Inventory

    EFFECTS OF ORGANOPHOSPHORUS FLAME RETARDANTS ON SPONTANEOUS ACTIVITY IN NEURONAL NETWORKS GROWN ON MICROELECTRODE ARRAYS TJ Shafer1, K Wallace1, WR Mundy1, M Behl2,. 1Integrated Systems Toxicology Division, NHEERL, USEPA, RTP, NC, USA, 2National Toxicology Program, NIEHS, RTP, NC...

  6. Spontaneous Motion in Hierarchically Assembled Active Cellular Materials

    NASA Astrophysics Data System (ADS)

    Chen, Daniel

    2013-03-01

    With exquisite precision and reproducibility, cells orchestrate the cooperative action of thousands of nanometer-sized molecular motors to carry out mechanical tasks at much larger length scales, such as cell motility, division and replication. Besides their biological importance, such inherently far-from-equilibrium processes are an inspiration for the development of soft materials with highly sought after biomimetic properties such as autonomous motility and self-healing. I will describe our exploration of such a class of biologically inspired soft active materials. Starting from extensile bundles comprised of microtubules and kinesin, we hierarchically assemble active analogs of polymeric gels, liquid crystals and emulsions. At high enough concentration, microtubule bundles form an active gel network capable of generating internally driven chaotic flows that enhance transport and fluid mixing. When confined to emulsion droplets, these 3D networks buckle onto the water-oil interface forming a dense thin film of bundles exhibiting cascades of collective buckling, fracture, and self-healing driven by internally generated stresses from the kinesin clusters. When compressed against surfaces, this active nematic cortex exerts traction stresses that propel the locomotion of the droplet. Taken together, these observations exemplify how assemblies of animate microscopic objects exhibit collective biomimetic properties that are fundamentally distinct from those found in materials assembled from inanimate building blocks. These assemblies, in turn, enable the generation of a new class of materials that exhibit macroscale flow phenomena emerging from nanoscale components.

  7. Biologically Active Polymers from Spontaneous Carotenoid Oxidation: A New Frontier in Carotenoid Activity

    PubMed Central

    Johnston, James B.; Nickerson, James G.; Daroszewski, Janusz; Mogg, Trevor J.; Burton, Graham W.

    2014-01-01

    In animals carotenoids show biological activity unrelated to vitamin A that has been considered to arise directly from the behavior of the parent compound, particularly as an antioxidant. However, the very property that confers antioxidant activity on some carotenoids in plants also confers susceptibility to oxidative transformation. As an alternative, it has been suggested that carotenoid oxidative breakdown or metabolic products could be the actual agents of activity in animals. However, an important and neglected aspect of the behavior of the highly unsaturated carotenoids is their potential to undergo addition of oxygen to form copolymers. Recently we reported that spontaneous oxidation of ß-carotene transforms it into a product dominated by ß-carotene-oxygen copolymers. We now report that the polymeric product is biologically active. Results suggest an overall ability to prime innate immune function to more rapidly respond to subsequent microbial challenges. An underlying structural resemblance to sporopollenin, found in the outer shell of spores and pollen, may allow the polymer to modulate innate immune responses through interactions with the pattern recognition receptor system. Oxygen copolymer formation appears common to all carotenoids, is anticipated to be widespread, and the products may contribute to the health benefits of carotenoid-rich fruits and vegetables. PMID:25360750

  8. Biologically active polymers from spontaneous carotenoid oxidation: a new frontier in carotenoid activity.

    PubMed

    Johnston, James B; Nickerson, James G; Daroszewski, Janusz; Mogg, Trevor J; Burton, Graham W

    2014-01-01

    In animals carotenoids show biological activity unrelated to vitamin A that has been considered to arise directly from the behavior of the parent compound, particularly as an antioxidant. However, the very property that confers antioxidant activity on some carotenoids in plants also confers susceptibility to oxidative transformation. As an alternative, it has been suggested that carotenoid oxidative breakdown or metabolic products could be the actual agents of activity in animals. However, an important and neglected aspect of the behavior of the highly unsaturated carotenoids is their potential to undergo addition of oxygen to form copolymers. Recently we reported that spontaneous oxidation of ß-carotene transforms it into a product dominated by ß-carotene-oxygen copolymers. We now report that the polymeric product is biologically active. Results suggest an overall ability to prime innate immune function to more rapidly respond to subsequent microbial challenges. An underlying structural resemblance to sporopollenin, found in the outer shell of spores and pollen, may allow the polymer to modulate innate immune responses through interactions with the pattern recognition receptor system. Oxygen copolymer formation appears common to all carotenoids, is anticipated to be widespread, and the products may contribute to the health benefits of carotenoid-rich fruits and vegetables. PMID:25360750

  9. Changes of spontaneous oscillatory activity to tonic heat pain.

    PubMed

    Peng, Weiwei; Hu, Li; Zhang, Zhiguo; Hu, Yong

    2014-01-01

    Transient painful stimuli could induce suppression of alpha oscillatory activities and enhancement of gamma oscillatory activities that also could be greatly modulated by attention. Here, we attempted to characterize changes in cortical activities during tonic heat pain perception and investigated the influence of directed/distracted attention on these responses. We collected 5-minute long continuous Electroencephalography (EEG) data from 38 healthy volunteers during four conditions presented in a counterbalanced order: (A) resting condition; (B) innoxious-distracted condition; (C) noxious-distracted condition; (D) noxious-attended condition. The effects of tonic heat pain stimulation and selective attention on oscillatory activities were investigated by comparing the EEG power spectra among the four experimental conditions and assessing the relationship between spectral power difference and subjective pain intensity. The change of oscillatory activities in condition D was characterized by stable and persistent decrease of alpha oscillation power over contralateral-central electrodes and widespread increase of gamma oscillation power, which were even significantly correlated with subjective pain intensity. Since EEG responses in the alpha and gamma frequency band were affected by attention in different manners, they are likely related to different aspects of the multidimensional sensory experience of pain. The observed contralateral-central alpha suppression (conditions D vs. B and D vs. C) may reflect primarily a top-down cognitive process such as attention, while the widespread gamma enhancement (conditions D vs. A) may partly reflect tonic pain processing, representing the summary effects of bottom-up stimulus-related and top-down subject-driven cognitive processes. PMID:24603703

  10. Enhancement of visual responsiveness by spontaneous local network activity in vivo.

    PubMed

    Haider, Bilal; Duque, Alvaro; Hasenstaub, Andrea R; Yu, Yuguo; McCormick, David A

    2007-06-01

    Spontaneous activity within local circuits affects the integrative properties of neurons and networks. We have previously shown that neocortical network activity exhibits a balance between excitatory and inhibitory synaptic potentials, and such activity has significant effects on synaptic transmission, action potential generation, and spike timing. However, whether such activity facilitates or reduces sensory responses has yet to be clearly determined. We examined this hypothesis in the primary visual cortex in vivo during slow oscillations in ketamine-xylazine anesthetized cats. We measured network activity (Up states) with extracellular recording, while simultaneously recording postsynaptic potentials (PSPs) and action potentials in nearby cells. Stimulating the receptive field revealed that spiking responses of both simple and complex cells were significantly enhanced (>2-fold) during network activity, as were spiking responses to intracellular injection of varying amplitude artificial conductance stimuli. Visually evoked PSPs were not significantly different in amplitude during network activity or quiescence; instead, spontaneous depolarization caused by network activity brought these evoked PSPs closer to firing threshold. Further examination revealed that visual responsiveness was gradually enhanced by progressive membrane potential depolarization. These spontaneous depolarizations enhanced responsiveness to stimuli of varying contrasts, resulting in an upward (multiplicative) scaling of the contrast response function. Our results suggest that small increases in ongoing balanced network activity that result in depolarization may provide a rapid and generalized mechanism to control the responsiveness (gain) of cortical neurons, such as occurs during shifts in spatial attention. PMID:17409168

  11. Spontaneous Retinal Activity Mediates Development of Ocular Dominance Columns and Binocular Receptive Fields in V1

    PubMed Central

    Huberman, Andrew D.; Speer, Colenso M.; Chapman, Barbara

    2008-01-01

    Summary The mechanisms that give rise to ocular dominance columns (ODCs) during development are controversial. Early experiments indicated a key role for retinal activity in ODC formation. However, later studies showed that in those early experiments, the retinal activity perturbation was initiated after ODCs had already formed. Moreover, recent studies concluded that early eye removals do not impact ODC segregation. Here we blocked spontaneous retinal activity during the very early stages of ODC development. This permanently disrupted the anatomical organization of ODCs and led to a dramatic increase in receptive field size for binocular cells in primary visual cortex. Our data suggest that early spontaneous retinal activity conveys crucial information about whether thalamocortical axons represent one or the other eye and that this activity mediates binocular competition important for shaping receptive fields in primary visual cortex. PMID:17046688

  12. Spontaneous fast gamma activity in the septal hippocampal region correlates with spatial learning in humans.

    PubMed

    Cornwell, B R; Overstreet, C; Grillon, C

    2014-03-15

    Hippocampal neuronal populations exhibit multiple kinds of activity patterns, from the dominant theta rhythm during active exploration to high-frequency ripple-like activity during periods of relative inactivity. In animals, evidence is rapidly accruing that these high-frequency ripple activity patterns subserve retention of spatial learning performance. In a translational effort to address the possible function of offline hippocampal processes in humans, we measured spontaneous gamma activity during an awake rest period within a virtual spatial learning context. Whole-head magnetoencephalographic (MEG) recordings were taken while healthy participants (N=24) quietly rested (eyes open) between encoding and retrieval phases of a hippocampal-dependent virtual Morris water maze task. Results are that fast gamma activity (80-140 Hz) in the septal or posterior region of the hippocampus (bilaterally) was positively correlated across participants with subsequent within-session spatial learning rate. Fast gamma did not predict initial retrieval performance following rest, failing to provide evidence of a direct link between spontaneous high-frequency activity patterns during awake rest and consolidation of previous spatial memories. The findings nevertheless are consistent with a prospective role for offline human hippocampal processes in spatial learning and indicate that higher spontaneous gamma activity in the septal hippocampal region is related to faster updating of spatial knowledge in familiar virtual surroundings. PMID:24388977

  13. Spontaneous neural activity in the primary visual cortex of retinal degenerated rats.

    PubMed

    Wang, Yi; Chen, Ke; Xu, Ping; Ng, Tsz Kin; Chan, Leanne Lai Hang

    2016-06-01

    Retinal degeneration (RD) models have been widely used to study retinal degenerative diseases for a long time. The biological and electrophysiological presentations of changes in the retina during degeneration progress have been well investigated; thus, the present study is aimed at investigating the electrophysiological effects of RD in the primary visual cortex. We extracellularly recorded the spontaneous neural activities in the primary visual cortex of RD rats. The firing rate, interspike interval (ISI) and Lempel-Ziv (LZ) complexity of spontaneous neural activities were subsequently analyzed. When compared to the control group, it was found that the neurons in primary visual cortex of the RD model fired more frequently. In addition, there was a decrease in LZ complexity of spontaneous neural firing in the RD model. These results suggest that the progress of RD may not only affect the retina itself but also the primary visual cortex, which may result in an unbalanced inhibition-excitation system as well as the decreased arising rate of new patterns of spontaneous activities. PMID:27132087

  14. How does non-random spontaneous activity contribute to brain development?

    PubMed

    Thivierge, Jean-Philippe

    2009-09-01

    Highly non-random forms of spontaneous activity are proposed to play an instrumental role in the early development of the visual system. However, both the fundamental properties of spontaneous activity required to drive map formation, as well as the exact role of this information remain largely unknown. Here, a realistic computational model of spontaneous retinal waves is employed to demonstrate that both the amplitude and frequency of waves may play determining roles in retinocollicular map formation. Furthermore, results obtained with different learning rules show that spike precision in the order of milliseconds may be instrumental to neural development: a rule based on precise spike interactions (spike-timing-dependent plasticity) reduced the density of aberrant projections to the SC to a markedly greater extent than a rule based on interactions at much broader time-scale (correlation-based plasticity). Taken together, these results argue for an important role of spontaneous yet highly non-random activity, along with temporally precise learning rules, in the formation of neural circuits. PMID:19196491

  15. High-content screening assay for identification of chemicals impacting spontaneous activity in zebrafish embryos.

    PubMed

    Raftery, Tara D; Isales, Gregory M; Yozzo, Krystle L; Volz, David C

    2014-01-01

    Although cell-based assays exist, rapid and cost-efficient high-content screening (HCS) assays within intact organisms are needed to support prioritization for developmental neurotoxicity testing in rodents. During zebrafish embryogenesis, spontaneous tail contractions occur from late-segmentation (∼19 h postfertilization, hpf) through early pharyngula (∼29 hpf) and represent the first sign of locomotion. Using transgenic zebrafish (fli1:egfp) that stably express eGFP beginning at ∼14 hpf, we have developed and optimized a 384-well-based HCS assay that quantifies spontaneous activity within single zebrafish embryos after exposure to test chemicals in a concentration-response format. Following static exposure of one embryo per well from 5 to 25 hpf, automated image acquisition procedures and custom analysis protocols were used to quantify total body area and spontaneous activity in live embryos. Survival and imaging success rates across control plates ranged from 87.5 to 100% and 93.3-100%, respectively. Using our optimized procedures, we screened 16 chemicals within the US EPA's ToxCast Phase-I library, and found that exposure to abamectin and emamectin benzoate-both potent avermectins-abolished spontaneous activity in the absence of gross malformations. Overall, compared to existing locomotion-based zebrafish assays conducted later in development, this method provides a simpler discovery platform for identifying potential developmental neurotoxicants. PMID:24328182

  16. Spontaneous Physical Activity Downregulates Pax7 in Cancer Cachexia.

    PubMed

    Coletti, Dario; Aulino, Paola; Pigna, Eva; Barteri, Fabio; Moresi, Viviana; Annibali, Daniela; Adamo, Sergio; Berardi, Emanuele

    2016-01-01

    Emerging evidence suggests that the muscle microenvironment plays a prominent role in cancer cachexia. We recently showed that NF-kB-induced Pax7 overexpression impairs the myogenic potential of muscle precursors in cachectic mice, suggesting that lowering Pax7 expression may be beneficial in cancer cachexia. We evaluated the muscle regenerative potential after acute injury in C26 colon carcinoma tumor-bearing mice and healthy controls. Our analyses confirmed that the delayed muscle regeneration observed in muscles form tumor-bearing mice was associated with a persistent local inflammation and Pax7 overexpression. Physical activity is known to exert positive effects on cachectic muscles. However, the mechanism by which a moderate voluntary exercise ameliorates muscle wasting is not fully elucidated. To verify if physical activity affects Pax7 expression, we hosted control and C26-bearing mice in wheel-equipped cages and we found that voluntary wheel running downregulated Pax7 expression in muscles from tumor-bearing mice. As expected, downregulation of Pax7 expression was associated with a rescue of muscle mass and fiber size. Our findings shed light on the molecular basis of the beneficial effect exerted by a moderate physical exercise on muscle stem cells in cancer cachexia. Furthermore, we propose voluntary exercise as a physiological tool to counteract the overexpression of Pax7 observed in cancer cachexia. PMID:27034684

  17. Spontaneous Physical Activity Downregulates Pax7 in Cancer Cachexia

    PubMed Central

    Aulino, Paola; Barteri, Fabio; Moresi, Viviana; Berardi, Emanuele

    2016-01-01

    Emerging evidence suggests that the muscle microenvironment plays a prominent role in cancer cachexia. We recently showed that NF-kB-induced Pax7 overexpression impairs the myogenic potential of muscle precursors in cachectic mice, suggesting that lowering Pax7 expression may be beneficial in cancer cachexia. We evaluated the muscle regenerative potential after acute injury in C26 colon carcinoma tumor-bearing mice and healthy controls. Our analyses confirmed that the delayed muscle regeneration observed in muscles form tumor-bearing mice was associated with a persistent local inflammation and Pax7 overexpression. Physical activity is known to exert positive effects on cachectic muscles. However, the mechanism by which a moderate voluntary exercise ameliorates muscle wasting is not fully elucidated. To verify if physical activity affects Pax7 expression, we hosted control and C26-bearing mice in wheel-equipped cages and we found that voluntary wheel running downregulated Pax7 expression in muscles from tumor-bearing mice. As expected, downregulation of Pax7 expression was associated with a rescue of muscle mass and fiber size. Our findings shed light on the molecular basis of the beneficial effect exerted by a moderate physical exercise on muscle stem cells in cancer cachexia. Furthermore, we propose voluntary exercise as a physiological tool to counteract the overexpression of Pax7 observed in cancer cachexia. PMID:27034684

  18. Climbing Fiber Regulation of Spontaneous Purkinje Cell Activity and Cerebellum-Dependent Blink Responses123

    PubMed Central

    Bengtsson, Fredrik

    2016-01-01

    Abstract It has been known for a long time that GABAergic Purkinje cells in the cerebellar cortex, as well as their target neurons in the cerebellar nuclei, are spontaneously active. The cerebellar output will, therefore, depend on how input is integrated into this spontaneous activity. It has been shown that input from climbing fibers originating in the inferior olive controls the spontaneous activity in Purkinje cells. While blocking climbing fiber input to the Purkinje cells causes a dramatic increase in the firing rate, increased climbing fiber activity results in reduced Purkinje cell activity. However, the exact calibration of this regulation has not been examined systematically. Here we examine the relation between climbing fiber stimulation frequency and Purkinje cell activity in unanesthetized decerebrated ferrets. The results revealed a gradual suppression of Purkinje cell activity, starting at climbing fiber stimulation frequencies as low as 0.5 Hz. At 4 Hz, Purkinje cells were completely silenced. This effect lasted an average of 2 min after the stimulation rate was reduced to a lower level. We also examined the effect of sustained climbing fiber stimulation on overt behavior. Specifically, we analyzed conditioned blink responses, which are known to be dependent on the cerebellum, while stimulating the climbing fibers at different frequencies. In accordance with the neurophysiological data, the conditioned blink responses were suppressed at stimulation frequencies of ≥4 Hz. PMID:26839917

  19. Increasing Spontaneous Retinal Activity before Eye Opening Accelerates the Development of Geniculate Receptive Fields.

    PubMed

    Davis, Zachary W; Chapman, Barbara; Cheng, Hwai-Jong

    2015-10-28

    Visually evoked activity is necessary for the normal development of the visual system. However, little is known about the capacity for patterned spontaneous activity to drive the maturation of receptive fields before visual experience. Retinal waves provide instructive retinotopic information for the anatomical organization of the visual thalamus. To determine whether retinal waves also drive the maturation of functional responses, we increased the frequency of retinal waves pharmacologically in the ferret (Mustela putorius furo) during a period of retinogeniculate development before eye opening. The development of geniculate receptive fields after receiving these increased neural activities was measured using single-unit electrophysiology. We found that increased retinal waves accelerate the developmental reduction of geniculate receptive field sizes. This reduction is due to a decrease in receptive field center size rather than an increase in inhibitory surround strength. This work reveals an instructive role for patterned spontaneous activity in guiding the functional development of neural circuits. PMID:26511250

  20. Spontaneous activations follow a common developmental course across primary sensory areas in mouse neocortex.

    PubMed

    Frye, Charles G; MacLean, Jason N

    2016-08-01

    Spontaneous propagation of spiking within the local neocortical circuits of mature primary sensory areas is highly nonrandom, engaging specific sets of interconnected and functionally related neurons. These spontaneous activations promise insight into neocortical structure and function, but their properties in the first 2 wk of perinatal development are incompletely characterized. Previously, we have found that there is a minimal numerical sample, on the order of 400 cells, necessary to fully capture mature neocortical circuit dynamics. Therefore we maximized our numerical sample by using two-photon calcium imaging to observe spontaneous activity in populations of up to 1,062 neurons spanning multiple columns and layers in 52 acute coronal slices of mouse neocortex at each day from postnatal day (PND) 3 to PND 15. Slices contained either primary auditory cortex (A1) or somatosensory barrel field (S1BF), which allowed us to compare sensory modalities with markedly different developmental timelines. Between PND 3 and PND 8, populations in both areas exhibited activations of anatomically compact subgroups on the order of dozens of cells. Between PND 9 and PND 13, the spatiotemporal structure of the activity diversified to include spatially distributed activations encompassing hundreds of cells. Sparse activations covering the entire field of view dominated in slices taken on or after PND 14. These and other findings demonstrate that the developmental progression of spontaneous activations from active local modules in the first postnatal week to sparse, intermingled groups of neurons at the beginning of the third postnatal week generalizes across primary sensory areas, consistent with an intrinsic developmental trajectory independent of sensory input. PMID:27146981

  1. Causality-weighted active learning for abnormal event identification based on the topic model

    NASA Astrophysics Data System (ADS)

    Fan, Yawen; Zheng, Shibao; Yang, Hua; Zhang, Chongyang; Su, Hang

    2012-07-01

    Abnormal event identification in crowded scenes is a fundamental task for video surveillance. However, it is still challenging for most current approaches because of the general insufficiency of labeled data for training, particularly for abnormal data. We propose a novel active-supervised joint topic model for learning activity and training sample collection. First, a multi-class topic model is constructed based on the initial training data. Then the remaining unlabeled data stream is surveyed. The system actively decides whether it can label a new sample by itself or if it has to ask a human annotator. After each query, the current model is incrementally updated. To alleviate class imbalance, causality-weighted method is applied to both likelihood and uncertainty sampling for active learning. Furthermore, a combination of a new measure termed query entropy and the overall classification accuracy is used for assessing the model performance. Experimental results on two real-world traffic videos for abnormal event identification tasks demonstrate the effectiveness of the proposed method.

  2. Neural activation abnormalities during self-referential processing in schizophrenia: an fMRI study.

    PubMed

    Liu, Jiacheng; Corbera, Silvia; Wexler, Bruce Edward

    2014-06-30

    Impairments in self-awareness contribute to disability in schizophrenia. Studies have revealed activation abnormalities in schizophrenia in cortical midline structures associated with self-reference. We used functional magnetic resonance imaging to compare activation throughout the brain in people with schizophrenia and healthy controls (Kelly et al., 2002) while they indicated whether trait adjectives described attributes of themselves, their mother or a former president of the United States. Blood oxygenation level dependent signal in each condition was compared to resting fixation. Patients were less likely and slower to endorse positive self-attributes, and more likely and quicker to endorse negative self-attributes than controls. Activation abnormalities reported previously in cortical midline structures were again noted. In addition, patients showed greater signal increases in frontal, temporal gyri and insula, and smaller signal decreases in posterior regions than healthy controls when thinking about themselves. Group differences were less evident when subjects were thinking about their mothers and tended to go in the opposite direction when thinking about a president. Many of the areas showing abnormality have been shown in other studies to differ between patients and controls in structure and with other activation paradigms. We suggest that general neuropathology in schizophrenia alters the neural system configurations associated with self-representation. PMID:24795158

  3. Ionic Mechanisms of Pacemaker Activity in Spontaneously-contracting Atrial HL-1 Cells

    PubMed Central

    Yang, Zhenjiang; Murray, Katherine T.

    2010-01-01

    Although normally absent, spontaneous pacemaker activity can develop in human atrium to promote tachyarrhythmias. HL-1 cells are immortalized atrial cardiomyocytes that contract spontaneously in culture, providing a model system of atrial cell automaticity. Using electrophysiologic recordings and selective pharmacologic blockers, we investigated the ionic basis of automaticity in atrial HL-1 cells. Both the sarcoplasmic reticulum (SR) Ca++ release channel inhibitor ryanodine and the SR Ca++ ATPase inhibitor thapsigargin slowed automaticity, supporting a role for intracellular Ca++ release in pacemaker activity. Additional experiments were performed to examine the effects of ionic currents activating in the voltage range of diastolic depolarization. Inhibition of the hyperpolarization-activated pacemaker current, If, by ivabradine significantly suppressed diastolic depolarization, with modest slowing of automaticity. Block of inward Na+ currents also reduced automaticity, while inhibition of T- and L-type Ca++ currents caused milder effects to slow beat rate. The major outward current in HL-1 cells is the rapidly activating delayed rectifier, IKr. Inhibition of IKr using dofetilide caused marked prolongation of APD and thus spontaneous cycle length. These results demonstrate a mutual role for both intracellular Ca++ release and sarcolemmal ionic currents in controlling automaticity in atrial HL-1 cells. Given that similar internal and membrane-based mechanisms also play a role in sinoatrial nodal cell pacemaker activity, our findings provide evidence for generalized conservation of pacemaker mechanisms among different types of cardiomyocytes. PMID:20881602

  4. Spontaneous cortical activity alternates between motifs defined by regional axonal projections

    PubMed Central

    Mohajerani, Majid H.; Chan, Allen W.; Mohsenvand, Mostafa; LeDue, Jeffrey; Liu, Rui; McVea, David A.; Boyd, Jamie D.; Wang, Yu Tian; Reimers, Mark; Murphy, Timothy H.

    2014-01-01

    In lightly anaesthetized or awake adult mice using millisecond timescale voltage sensitive dye imaging, we show that a palette of sensory-evoked and hemisphere-wide activity motifs are represented in spontaneous activity. These motifs can reflect multiple modes of sensory processing including vision, audition, and touch. Similar cortical networks were found with direct cortical activation using channelrhodopsin-2. Regional analysis of activity spread indicated modality specific sources such as primary sensory areas, and a common posterior-medial cortical sink where sensory activity was extinguished within the parietal association area, and a secondary anterior medial sink within the cingulate/secondary motor cortices for visual stimuli. Correlation analysis between functional circuits and intracortical axonal projections indicated a common framework corresponding to long-range mono-synaptic connections between cortical regions. Maps of intracortical mono-synaptic structural connections predicted hemisphere-wide patterns of spontaneous and sensory-evoked depolarization. We suggest that an intracortical monosynaptic connectome shapes the ebb and flow of spontaneous cortical activity. PMID:23974708

  5. Spontaneous cortical activity alternates between motifs defined by regional axonal projections.

    PubMed

    Mohajerani, Majid H; Chan, Allen W; Mohsenvand, Mostafa; LeDue, Jeffrey; Liu, Rui; McVea, David A; Boyd, Jamie D; Wang, Yu Tian; Reimers, Mark; Murphy, Timothy H

    2013-10-01

    Using millisecond-timescale voltage-sensitive dye imaging in lightly anesthetized or awake adult mice, we show that a palette of sensory-evoked and hemisphere-wide activity motifs are represented in spontaneous activity. These motifs can reflect multiple modes of sensory processing, including vision, audition and touch. We found similar cortical networks with direct cortical activation using channelrhodopsin-2. Regional analysis of activity spread indicated modality-specific sources, such as primary sensory areas, a common posterior-medial cortical sink where sensory activity was extinguished within the parietal association area and a secondary anterior medial sink within the cingulate and secondary motor cortices for visual stimuli. Correlation analysis between functional circuits and intracortical axonal projections indicated a common framework corresponding to long-range monosynaptic connections between cortical regions. Maps of intracortical monosynaptic structural connections predicted hemisphere-wide patterns of spontaneous and sensory-evoked depolarization. We suggest that an intracortical monosynaptic connectome shapes the ebb and flow of spontaneous cortical activity. PMID:23974708

  6. Ionic mechanisms of pacemaker activity in spontaneously contracting atrial HL-1 cells.

    PubMed

    Yang, Zhenjiang; Murray, Katherine T

    2011-01-01

    Although normally absent, spontaneous pacemaker activity can develop in human atrium to promote tachyarrhythmias. HL-1 cells are immortalized atrial cardiomyocytes that contract spontaneously in culture, providing a model system of atrial cell automaticity. Using electrophysiologic recordings and selective pharmacologic blockers, we investigated the ionic basis of automaticity in atrial HL-1 cells. Both the sarcoplasmic reticulum Ca release channel inhibitor ryanodine and the sarcoplasmic reticulum Ca ATPase inhibitor thapsigargin slowed automaticity, supporting a role for intracellular Ca release in pacemaker activity. Additional experiments were performed to examine the effects of ionic currents activating in the voltage range of diastolic depolarization. Inhibition of the hyperpolarization-activated pacemaker current, If, by ivabradine significantly suppressed diastolic depolarization, with modest slowing of automaticity. Block of inward Na currents also reduced automaticity, whereas inhibition of T- and L-type Ca currents caused milder effects to slow beat rate. The major outward current in HL-1 cells is the rapidly activating delayed rectifier, IKr. Inhibition of IKr using dofetilide caused marked prolongation of action potential duration and thus spontaneous cycle length. These results demonstrate a mutual role for both intracellular Ca release and sarcolemmal ionic currents in controlling automaticity in atrial HL-1 cells. Given that similar internal and membrane-based mechanisms also play a role in sinoatrial nodal cell pacemaker activity, our findings provide evidence for generalized conservation of pacemaker mechanisms among different types of cardiomyocytes. PMID:20881602

  7. Glutamatergic system controls synchronization of spontaneous neuronal activity in the murine neonatal entorhinal cortex.

    PubMed

    Unichenko, Petr; Yang, Jeng-Wei; Luhmann, Heiko J; Kirischuk, Sergei

    2015-07-01

    Synchronized spontaneous neuronal activity is a characteristic feature of the developing brain. Rhythmic network discharges in the neonatal medial entorhinal cortex (mEC) in vitro depend on activation of ionotropic glutamate receptors, but spontaneously active neurons are required for their initiation. Field potential recordings revealed synchronized neuronal activity in the mEC in vivo developmentally earlier than in vitro. We suggested that not only ionotropic receptors, but also other components of the glutamatergic system modulate neuronal activity in the mEC. Ca(2+) imaging was used to record neuronal activity in neonatal murine brain slices. Two types of spontaneous events were distinguished: global synchronous discharges (synchronous activity) and asynchronously (not synchronized with global discharges) active cells (asynchronous activity). AMPA receptor blockade strongly reduced the frequency of synchronous discharges, while NMDA receptor inhibition was less effective. AMPA and NMDA receptor blockade or activation of group 2/3 metabotropic glutamate receptors (mGluR2/3) completely suppressed synchronous discharges and increased the number of active cells. Blockade of glutamate transporters with DL-TBOA led to NMDA receptor-mediated hyper-synchronization of neuronal activity. Inhibition of NMDA receptors in the presence of DL-TBOA failed to restore synchronous discharges. The latter were partially reestablished only after blockade of mGluR2/3. We conclude that the glutamatergic system can influence neuronal activity via different receptors/mechanisms. As both NMDA and mGluR2/3 receptors have a high affinity for glutamate, changes in extracellular glutamate levels resulting for instance from glutamate transporter malfunction can balance neuronal activity in the mEC, affecting in turn synapse and network formation. PMID:25163767

  8. Oseltamivir reduces hippocampal abnormal EEG activities after a virus infection (influenza) in isoflurane-anesthetized rats

    PubMed Central

    Cissé, Youssouf; Inoue, Isao; Kido, Hiroshi

    2012-01-01

    Background Oseltamivir phosphate (OP, Tamiflu®) is a widely used drug in the treatment of influenza with fever. However, case reports have associated OP intake with sudden abnormal behaviors. In rats infected by the influenza A virus (IAV), the electroencephalogram (EEG) displayed abnormal high-voltage amplitudes with spikes and theta oscillations at a core temperature of 39.9°C to 41°C. Until now, there has been no information describing the effect of OP on intact brain hippocampal activity of IAV-infected animals during hyperthermia. Objective The aim of the present study was to examine the effect of OP on abnormal EEG activities in the hippocampus using the rat model of influenza-associated encephalopathy. Methods Male Wistar rats aged 3 to 4 weeks were used for the study. Influenza A/WSN/33 strain (1 × 105 plaque forming unit in PBS, 60 µL) was applied intranasally to the rats. To characterize OP effects on the IAV-infected rats, EEG activity was studied more particularly in isoflurane-anesthetized IAV-infected rats during hyperthermia. Results We found that the hippocampal EEG of the OP-administered (10 mg/kg) IAV-infected rats showed significant reduction of the high-voltage amplitudes and spikes, but the theta oscillations, which had been observed only at >40°C in OP non-administered rats, appeared at 38°C core temperature. Atropine (30 mg/kg) blocked the theta oscillations. Conclusion Our data suggest that OP efficiently reduces the abnormal EEG activities after IAV infection during hyperthermia. However, OP administration may stimulate ACh release in rats at normal core temperature.

  9. Examination of Synaptic Vesicle Recycling Using FM Dyes During Evoked, Spontaneous, and Miniature Synaptic Activities

    PubMed Central

    Iwabuchi, Sadahiro; Kakazu, Yasuhiro; Koh, Jin-Young; Goodman, Kirsty M.; Harata, N. Charles

    2014-01-01

    Synaptic vesicles in functional nerve terminals undergo exocytosis and endocytosis. This synaptic vesicle recycling can be effectively analyzed using styryl FM dyes, which reveal membrane turnover. Conventional protocols for the use of FM dyes were designed for analyzing neurons following stimulated (evoked) synaptic activity. Recently, protocols have become available for analyzing the FM signals that accompany weaker synaptic activities, such as spontaneous or miniature synaptic events. Analysis of these small changes in FM signals requires that the imaging system is sufficiently sensitive to detect small changes in intensity, yet that artifactual changes of large amplitude are suppressed. Here we describe a protocol that can be applied to evoked, spontaneous, and miniature synaptic activities, and use cultured hippocampal neurons as an example. This protocol also incorporates a means of assessing the rate of photobleaching of FM dyes, as this is a significant source of artifacts when imaging small changes in intensity. PMID:24747983

  10. Abnormal endothelial tight junctions in active lesions and normal-appearing white matter in multiple sclerosis.

    PubMed

    Plumb, Jonnie; McQuaid, Stephen; Mirakhur, Meenakshi; Kirk, John

    2002-04-01

    Blood-brain barrier (BBB) breakdown, demonstrable in vivo by enhanced MRI is characteristic of new and expanding inflammatory lesions in relapsing-remitting and chronic progressive multiple sclerosis (MS). Subtle leakage may also occur in primary progressive MS. However, the anatomical route(s) of BBB leakage have not been demonstrated. We investigated the possible involvement of interendothelial tight junctions (TJ) by examining the expression of TJ proteins (occludin and ZO-1 ) in blood vessels in active MS lesions from 8 cases of MS and in normal-appearing white (NAWM) matter from 6 cases. Blood vessels (10-50 per frozen section) were scanned using confocal laser scanning microscopy to acquire datasets for analysis. TJ abnormalities manifested as beading, interruption, absence or diffuse cytoplasmic localization of fluorescence, or separation of junctions (putative opening) were frequent (affecting 40% of vessels) in oil-red-O-positive active plaques but less frequent in NAWM (15%), and in normal (< 2%) and neurological controls (6%). Putatively "open" junctions were seen in vessels in active lesions and in microscopically inflamed vessels in NAWM. Dual fluorescence revealed abnormal TJs in vessels with pre-mortem serum protein leakage. Abnormal or open TJs, associated with inflammation may contribute to BBB leakage in enhancing MRI lesions and may also be involved in subtle leakage in non-enhancing focal and diffuse lesions in NAWM. BBB disruption due to tight junctional pathology should be regarded as a significant form of tissue injury in MS, alongside demyelination and axonopathy. PMID:11958369

  11. Working Memory Encoding and Maintenance Deficits in Schizophrenia: Neural Evidence for Activation and Deactivation Abnormalities

    PubMed Central

    Anticevic, Alan; Repovs, Grega; Barch, Deanna M.

    2013-01-01

    Substantial evidence implicates working memory (WM) as a core deficit in schizophrenia (SCZ), purportedly due to primary deficits in dorsolateral prefrontal cortex functioning. Recent findings suggest that SCZ is also associated with abnormalities in suppression of certain regions during cognitive engagement—namely the default mode system—that may further contribute to WM pathology. However, no study has systematically examined activation and suppression abnormalities across both encoding and maintenance phases of WM in SCZ. Twenty-eight patients and 24 demographically matched healthy subjects underwent functional magnetic resonance imaging at 3T while performing a delayed match-to-sample WM task. Groups were accuracy matched to rule out performance effects. Encoding load was identical across subjects to facilitate comparisons across WM phases. We examined activation differences using an assumed model approach at the whole-brain level and within meta-analytically defined WM areas. Despite matched performance, we found regions showing less recruitment during encoding and maintenance for SCZ subjects. Furthermore, we identified 2 areas closely matching the default system, which SCZ subjects failed to deactivate across WM phases. Lastly, activation in prefrontal regions predicted the degree of deactivation for healthy but not SCZ subjects. Current results replicate and extend prefrontal recruitment abnormalities across WM phases in SCZ. Results also indicate deactivation abnormalities across WM phases, possibly due to inefficient prefrontal recruitment. Such regional deactivation may be critical for suppressing sources of interference during WM trace formation. Thus, deactivation deficits may constitute an additional source of impairments, which needs to be further characterized for a complete understanding of WM pathology in SCZ. PMID:21914644

  12. Meclozine Facilitates Proliferation and Differentiation of Chondrocytes by Attenuating Abnormally Activated FGFR3 Signaling in Achondroplasia

    PubMed Central

    Matsushita, Masaki; Kitoh, Hiroshi; Ohkawara, Bisei; Mishima, Kenichi; Kaneko, Hiroshi; Ito, Mikako; Masuda, Akio; Ishiguro, Naoki; Ohno, Kinji

    2013-01-01

    Achondroplasia (ACH) is one of the most common skeletal dysplasias with short stature caused by gain-of-function mutations in FGFR3 encoding the fibroblast growth factor receptor 3. We used the drug repositioning strategy to identify an FDA-approved drug that suppresses abnormally activated FGFR3 signaling in ACH. We found that meclozine, an anti-histamine drug that has long been used for motion sickness, facilitates chondrocyte proliferation and mitigates loss of extracellular matrix in FGF2-treated rat chondrosarcoma (RCS) cells. Meclozine also ameliorated abnormally suppressed proliferation of human chondrosarcoma (HCS-2/8) cells that were infected with lentivirus expressing constitutively active mutants of FGFR3-K650E causing thanatophoric dysplasia, FGFR3-K650M causing SADDAN, and FGFR3-G380R causing ACH. Similarly, meclozine alleviated abnormally suppressed differentiation of ATDC5 chondrogenic cells expressing FGFR3-K650E and -G380R in micromass culture. We also confirmed that meclozine alleviates FGF2-mediated longitudinal growth inhibition of embryonic tibia in bone explant culture. Interestingly, meclozine enhanced growth of embryonic tibia in explant culture even in the absence of FGF2 treatment. Analyses of intracellular FGFR3 signaling disclosed that meclozine downregulates phosphorylation of ERK but not of MEK in FGF2-treated RCS cells. Similarly, meclozine enhanced proliferation of RCS cells expressing constitutively active mutants of MEK and RAF but not of ERK, which suggests that meclozine downregulates the FGFR3 signaling by possibly attenuating ERK phosphorylation. We used the C-natriuretic peptide (CNP) as a potent inhibitor of the FGFR3 signaling throughout our experiments, and found that meclozine was as efficient as CNP in attenuating the abnormal FGFR3 signaling. We propose that meclozine is a potential therapeutic agent for treating ACH and other FGFR3-related skeletal dysplasias. PMID:24324705

  13. Meclozine facilitates proliferation and differentiation of chondrocytes by attenuating abnormally activated FGFR3 signaling in achondroplasia.

    PubMed

    Matsushita, Masaki; Kitoh, Hiroshi; Ohkawara, Bisei; Mishima, Kenichi; Kaneko, Hiroshi; Ito, Mikako; Masuda, Akio; Ishiguro, Naoki; Ohno, Kinji

    2013-01-01

    Achondroplasia (ACH) is one of the most common skeletal dysplasias with short stature caused by gain-of-function mutations in FGFR3 encoding the fibroblast growth factor receptor 3. We used the drug repositioning strategy to identify an FDA-approved drug that suppresses abnormally activated FGFR3 signaling in ACH. We found that meclozine, an anti-histamine drug that has long been used for motion sickness, facilitates chondrocyte proliferation and mitigates loss of extracellular matrix in FGF2-treated rat chondrosarcoma (RCS) cells. Meclozine also ameliorated abnormally suppressed proliferation of human chondrosarcoma (HCS-2/8) cells that were infected with lentivirus expressing constitutively active mutants of FGFR3-K650E causing thanatophoric dysplasia, FGFR3-K650M causing SADDAN, and FGFR3-G380R causing ACH. Similarly, meclozine alleviated abnormally suppressed differentiation of ATDC5 chondrogenic cells expressing FGFR3-K650E and -G380R in micromass culture. We also confirmed that meclozine alleviates FGF2-mediated longitudinal growth inhibition of embryonic tibia in bone explant culture. Interestingly, meclozine enhanced growth of embryonic tibia in explant culture even in the absence of FGF2 treatment. Analyses of intracellular FGFR3 signaling disclosed that meclozine downregulates phosphorylation of ERK but not of MEK in FGF2-treated RCS cells. Similarly, meclozine enhanced proliferation of RCS cells expressing constitutively active mutants of MEK and RAF but not of ERK, which suggests that meclozine downregulates the FGFR3 signaling by possibly attenuating ERK phosphorylation. We used the C-natriuretic peptide (CNP) as a potent inhibitor of the FGFR3 signaling throughout our experiments, and found that meclozine was as efficient as CNP in attenuating the abnormal FGFR3 signaling. We propose that meclozine is a potential therapeutic agent for treating ACH and other FGFR3-related skeletal dysplasias. PMID:24324705

  14. Effect of Exercise Intensity on Spontaneous Physical Activity Energy Expenditure in Overweight Boys: A Crossover Study

    PubMed Central

    Paravidino, Vitor Barreto; Mediano, Mauro Felippe Felix; Hoffman, Daniel J.; Sichieri, Rosely

    2016-01-01

    Objective Evaluate the effect of different exercise intensities on spontaneous physical activity energy expenditure in overweight adolescents. Methods A crossover study was developed with a control session, followed by moderate and vigorous exercise sessions, with six days of monitoring each. Twenty-four adolescents, 11–13 years old, male and overweight were selected. Spontaneous physical activity energy expenditure was assessed by accelerometers. Linear mixed effects models were used to evaluate the differences per session across time. Results Energy expenditure during the 1st hour was different between all three sessions, with averages of 82, 286 and 343 kcal to the control, moderate and vigorous sessions, respectively (p <0.001). The same pattern of difference in energy expenditure between the sessions remained after 24 hours (704 vs 970 vs 1056 kcal, p <0.001). However, energy expenditure during the six days indicates compensation from second to the sixth day, although small differences remained at the end of the 6-day period (5102 vs 5193 vs 5271 kcal, p <0.001). Conclusions A single aerobic session seems to modify the spontaneous physical activities in overweight adolescents but still keeping the vigorous session with higher total energy expenditure during the follow-up period. Despite the observed compensatory effect, the greater energy expenditure observed in both moderate and vigorous exercise sessions indicates that physical activity should be recommended to promote an increased energy expenditure in adolescents. Trial Registration ClinicalTrials.gov NCT 02272088 PMID:26771742

  15. Circuit formation and function in the olfactory bulb of mice with reduced spontaneous afferent activity.

    PubMed

    Lorenzon, Paolo; Redolfi, Nelly; Podolsky, Michael J; Zamparo, Ilaria; Franchi, Sira Angela; Pietra, Gianluca; Boccaccio, Anna; Menini, Anna; Murthy, Venkatesh N; Lodovichi, Claudia

    2015-01-01

    The type of neuronal activity required for circuit development is a matter of significant debate. We addressed this issue by analyzing the topographic organization of the olfactory bulb in transgenic mice engineered to have very little afferent spontaneous activity due to the overexpression of the inwardly rectifying potassium channel Kir2.1 in the olfactory sensory neurons (Kir2.1 mice). In these conditions, the topography of the olfactory bulb was unrefined. Odor-evoked responses were readily recorded in glomeruli with reduced spontaneous afferent activity, although the functional maps were coarser than in controls and contributed to altered olfactory discrimination behavior. In addition, overexpression of Kir2.1 in adults induced a regression of the already refined connectivity to an immature (i.e., coarser) status. Our data suggest that spontaneous activity plays a critical role not only in the development but also in the maintenance of the topography of the olfactory bulb and in sensory information processing. PMID:25568110

  16. Spatiotemporal stability of neonatal rat cardiomyocyte monolayers spontaneous activity is dependent on the culture substrate.

    PubMed

    Boudreau-Béland, Jonathan; Duverger, James Elber; Petitjean, Estelle; Maguy, Ange; Ledoux, Jonathan; Comtois, Philippe

    2015-01-01

    In native conditions, cardiac cells must continuously comply with diverse stimuli necessitating a perpetual adaptation. Polydimethylsiloxane (PDMS) is commonly used in cell culture to study cellular response to changes in the mechanical environment. The aim of this study was to evaluate the impact of using PDMS substrates on the properties of spontaneous activity of cardiomyocyte monolayer cultures. We compared PDMS to the gold standard normally used in culture: a glass substrate. Although mean frequency of spontaneous activity remained unaltered, incidence of reentrant activity was significantly higher in samples cultured on glass compared to PDMS substrates. Higher spatial and temporal instability of the spontaneous rate activation was found when cardiomyocytes were cultured on PDMS, and correlated with decreased connexin-43 and increased CaV3.1 and HCN2 mRNA levels. Compared to cultures on glass, cultures on PDMS were associated with the strongest response to isoproterenol and acetylcholine. These results reveal the importance of carefully selecting the culture substrate for studies involving mechanical stimulation, especially for tissue engineering or pharmacological high-throughput screening of cardiac tissue analog. PMID:26035822

  17. Spatiotemporal Stability of Neonatal Rat Cardiomyocyte Monolayers Spontaneous Activity Is Dependent on the Culture Substrate

    PubMed Central

    Boudreau-Béland, Jonathan; Duverger, James Elber; Petitjean, Estelle; Maguy, Ange; Ledoux, Jonathan; Comtois, Philippe

    2015-01-01

    In native conditions, cardiac cells must continuously comply with diverse stimuli necessitating a perpetual adaptation. Polydimethylsiloxane (PDMS) is commonly used in cell culture to study cellular response to changes in the mechanical environment. The aim of this study was to evaluate the impact of using PDMS substrates on the properties of spontaneous activity of cardiomyocyte monolayer cultures. We compared PDMS to the gold standard normally used in culture: a glass substrate. Although mean frequency of spontaneous activity remained unaltered, incidence of reentrant activity was significantly higher in samples cultured on glass compared to PDMS substrates. Higher spatial and temporal instability of the spontaneous rate activation was found when cardiomyocytes were cultured on PDMS, and correlated with decreased connexin-43 and increased CaV3.1 and HCN2 mRNA levels. Compared to cultures on glass, cultures on PDMS were associated with the strongest response to isoproterenol and acetylcholine. These results reveal the importance of carefully selecting the culture substrate for studies involving mechanical stimulation, especially for tissue engineering or pharmacological high-throughput screening of cardiac tissue analog. PMID:26035822

  18. Spontaneous activation of the NF-kappaB signaling pathway in isolated normal glomeruli.

    PubMed

    Hayakawa, Kunihiro; Meng, Yiman; Hiramatsu, Nobuhiko; Kasai, Ayumi; Yao, Jian; Kitamura, Masanori

    2006-12-01

    In this report, we describe that NF-kappaB is spontaneously activated in isolated, normal glomeruli. Ex vivo incubation of isolated rat glomeruli triggered expression of a NF-kappaB-dependent gene, monocyte chemoattractant protein-1 (MCP-1), in parallel with downregulation of IkappaBalpha and IkappaBbeta proteins and activation of the p65 NF-kappaB subunit. The induction of MCP-1 was also observed in mesangial cells coincubated with isolated glomeruli or exposed to media conditioned by isolated glomeruli (GCM), which was abrogated by inhibition of NF-kappaB. The activation of NF-kappaB by glomerulus-derived factors was confirmed using reporter mesangial cells that produce secreted alkaline phosphatase (SEAP) under the control of the kappaB enhancer element. When the reporter cells were adoptively transferred into normal glomeruli, expression of SEAP mRNA and activity of SEAP were also upregulated in the explanted glomeruli. The molecular weight of factors responsible for activation of NF-kappaB was >50 kDa, and TNF-alpha was identified as one of glomerulus-derived activators. To examine upstream events involved, we focused on MAP kinases that are spontaneously activated in explanted glomeruli. Selective suppression of ERK or p38 MAP kinase significantly attenuated activation of NF-kappaB in mesangial cells triggered by coculture with isolated glomeruli. Interestingly, the suppressive effects by MAP kinase inhibitors were not observed in mesangial cells treated with GCM. These data suggested that NF-kappaB was spontaneously activated in explanted glomeruli via autocrine/paracrine factors including TNF-alpha and that the production of NF-kappaB activators by glomeruli was, at least in part, through MAP kinase pathways. PMID:16705144

  19. Recording of spontaneous activity with photoetched microelectrode surfaces from mouse spinal neurons in culture.

    PubMed

    Gross, G W; Williams, A N; Lucas, J H

    1982-01-01

    A matrix of photoetched gold conductors integrated into the floor of a tissue culture chamber has been used to record from mammalian spinal cord neurons grown on the insulation layer of the multielectrode plate. Spontaneous activity has been monitored from tissue microfragments less than 150 micrometers in diameter and from thin sheets of spinal cell aggregates. Maximum spike amplitudes of 360 microV with signal-to-noise ratios of 8:1 have so far been achieved and the spontaneous activity maintained for several days. Recording electrode impedances measured between 4 and 7 M omega at 1 kHz. Conductor tips were deinsulated with laser pulses that formed shallow craters 2 micrometers deep and 12 micrometers in diameter. Addition of colloidal gold or platimum black was not necessary to achieve satisfactory recordings. PMID:7057675

  20. Effect of anesthesia on spontaneous activity and evoked potentials of the cerebellar cortex.

    PubMed

    Ordek, Gokhan; Groth, Jonathan D; Sahin, Mesut

    2012-01-01

    Cerebellum is a highly organized structure with a crystalline morphology that has always intrigued neuroscientists. Much of the cerebellar research has been conducted in anesthetized animals, particularly using ketamine and xylazine combination. It is not clear how the cerebellar cortical circuitry is affected by anesthesia. In this study, we have recorded spontaneous and evoked potentials from the cerebellar surface with chronically implanted, flexible-substrate, multi-electrode arrays. The frequency contents of the spontaneous activity suggest that ketamine/xylazine anesthesia suppresses most of the components except those below 30 Hz. This preliminary study also showed that multi channels of cerebellar cortical activity can be recorded using flexible multi-electrode arrays in behaving animals, which is very challenging task with single microelectrodes. PMID:23366022

  1. Altered intrinsic regional brain spontaneous activity in patients with comitant strabismus: a resting-state functional MRI study

    PubMed Central

    Huang, Xin; Li, Sheng-Hong; Zhou, Fu-Qing; Zhang, Ying; Zhong, Yu-Lin; Cai, Feng-Qin; Shao, Yi; Zeng, Xian-Jun

    2016-01-01

    Objective To investigate the underlying regional homogeneity (ReHo) of brain-activity abnormalities in patients with comitant strabismus (CS) and their relationship with behavioral performance. Methods Twenty patients with CS (ten men and ten women) and 20 (ten men and ten women) age-, sex-, and education-matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging scans. The ReHo method was used to assess local features of spontaneous brain activities. Patients with CS were distinguished from HCs by receiver operating characteristic curve. Correlation analysis was performed to explore the relationship between the observed mean ReHo values of the different brain areas and behavioral performance. Results Compared to HCs, the patients with CS showed significantly increased ReHo values in the right inferior temporal cortex/fusiform gyrus/cerebellum anterior lobe, right lingual gyrus, and bilateral cingulate gyrus. We did not find any relationship between the observed mean ReHo values of the different brain areas and behavioral performance. Conclusion CS causes dysfunction in many brain regions, which may explain the fusion compensation in CS. PMID:27350747

  2. Abnormal auditory cortical activation in dyslexia 100 msec after speech onset.

    PubMed

    Helenius, Päivi; Salmelin, Riitta; Richardson, Ulla; Leinonen, Seija; Lyytinen, Heikki

    2002-05-15

    Reading difficulties are associated with problems in processing and manipulating speech sounds. Dyslexic individuals seem to have, for instance, difficulties in perceiving the length and identity of consonants. Using magnetoencephalography (MEG), we characterized the spatio-temporal pattern of auditory cortical activation in dyslexia evoked by three types of natural bisyllabic pseudowords (/ata/, /atta/, and /a a/), complex nonspeech sound pairs (corresponding to /atta/ and /a a/) and simple 1-kHz tones. The most robust difference between dyslexic and non-reading-impaired adults was seen in the left supratemporal auditory cortex 100 msec after the onset of the vowel /a/. This N100m response was abnormally strong in dyslexic individuals. For the complex nonspeech sounds and tone, the N100m response amplitudes were similar in dyslexic and nonimpaired individuals. The responses evoked by syllable /ta/ of the pseudoword /atta/ also showed modest latency differences between the two subject groups. The responses evoked by the corresponding nonspeech sounds did not differ between the two subject groups. Further, when the initial formant transition, that is, the consonant, was removed from the syllable /ta/, the N100m latency was normal in dyslexic individuals. Thus, it appears that dyslexia is reflected as abnormal activation of the auditory cortex already 100 msec after speech onset, manifested as abnormal response strengths for natural speech and as delays for speech sounds containing rapid frequency transition. These differences between the dyslexic and nonimpaired individuals also imply that the N100m response codes stimulus-specific features likely to be critical for speech perception. Which features of speech (or nonspeech stimuli) are critical in eliciting the abnormally strong N100m response in dyslexic individuals should be resolved in future studies. PMID:12126501

  3. Bidirectional global spontaneous network activity precedes the canonical unidirectional circuit organization in the developing hippocampus

    PubMed Central

    Shi, Yulin; Ikrar, Taruna; Olivas, Nicholas D; Xu, Xiangmin

    2014-01-01

    Spontaneous network activity is believed to sculpt developing neural circuits. Spontaneous giant depolarizing potentials (GDPs) were first identified with single-cell recordings from rat CA3 pyramidal neurons, but here we identify and characterize a large-scale spontaneous network activity we term global network activation (GNA) in the developing mouse hippocampal slices, which is measured macroscopically by fast voltage-sensitive dye imaging. The initiation and propagation of GNA in the mouse is largely GABA-independent and dominated by glutamatergic transmission via AMPA receptors. Despite the fact that signal propagation in the adult hippocampus is strongly unidirectional through the canonical trisynaptic circuit (dentate gyrus [DG] to CA3 to CA1), spontaneous GNA in the developing hippocampus originates in distal CA3 and propagates both forward to CA1 and backward to DG. Photostimulation-evoked GNA also shows prominent backward propagation in the developing hippocampus from CA3 to DG. Mouse GNA is strongly correlated to electrophysiological recordings of highly localized single-cell and local field potential events. Photostimulation mapping of neural circuitry demonstrates that the enhancement of local circuit connections to excitatory pyramidal neurons occurs over the same time course as GNA and reveals the underlying pathways accounting for GNA backward propagation from CA3 to DG. The disappearance of GNA coincides with a transition to the adult-like unidirectional circuit organization at about 2 weeks of age. Taken together, our findings strongly suggest a critical link between GNA activity and maturation of functional circuit connections in the developing hippocampus. PMID:24357090

  4. Spontaneous epileptiform activity in rat neocortex after controlled cortical impact injury.

    PubMed

    Yang, Lie; Afroz, Sonia; Michelson, Hillary B; Goodman, Jeffrey H; Valsamis, Helen A; Ling, Douglas S F

    2010-08-01

    A hallmark of severe traumatic brain injury (TBI) is the development of post-traumatic epilepsy (PTE). However, the mechanisms underlying PTE remain poorly understood. In this study, we used a controlled cortical impact (CCI) model in rats to examine post-traumatic changes in neocortical excitability. Neocortical slices were prepared from rats at 7-9 days (week 1) and 14-16 days (week 2) after CCI injury. By week 2, we observed a substantial gray matter lesion with a cavity that extended to the hippocampal structure. Fluoro-Jade B staining of slices revealed active neuronal degeneration during weeks 1 and 2. Intracellular and extracellular recordings obtained from layer V revealed evoked and spontaneous epileptiform discharges in neocortices of CCI-injured rats. At week 1, intracellular recordings from pyramidal cells revealed evoked epileptiform firing that was synchronized with population events recorded extracellularly, suggestive of increased excitability. This activity was characterized by bursts of action potentials that were followed by recurrent, repetitive after-discharges. At week 2, both spontaneous and evoked epileptiform firing were recorded in slices from injured rats. The evoked discharges resembled those observed at week 1, but with longer burst durations. Spontaneous activity included prolonged, ictal-like discharges lasting up to 8-10 sec, and briefer interictal-like burst events (<1 sec). These results indicate that during the first 2 weeks following severe CCI injury, there is a progressive development of neocortical hyperexcitability that ultimately leads to spontaneous epileptiform firing, suggesting a rapid epileptogenic process. PMID:20504156

  5. Reconstruction of human brain spontaneous activity based on frequency-pattern analysis of magnetoencephalography data

    PubMed Central

    Llinás, Rodolfo R.; Ustinin, Mikhail N.; Rykunov, Stanislav D.; Boyko, Anna I.; Sychev, Vyacheslav V.; Walton, Kerry D.; Rabello, Guilherme M.; Garcia, John

    2015-01-01

    A new method for the analysis and localization of brain activity has been developed, based on multichannel magnetic field recordings, over minutes, superimposed on the MRI of the individual. Here, a high resolution Fourier Transform is obtained over the entire recording period, leading to a detailed multi-frequency spectrum. Further analysis implements a total decomposition of the frequency components into functionally invariant entities, each having an invariant field pattern localizable in recording space. The method, addressed as functional tomography, makes it possible to find the distribution of magnetic field sources in space. Here, the method is applied to the analysis of simulated data, to oscillating signals activating a physical current dipoles phantom, and to recordings of spontaneous brain activity in 10 healthy adults. In the analysis of simulated data, 61 dipoles are localized with 0.7 mm precision. Concerning the physical phantom the method is able to localize three simultaneously activated current dipoles with 1 mm precision. Spatial resolution 3 mm was attained when localizing spontaneous alpha rhythm activity in 10 healthy adults, where the alpha peak was specified for each subject individually. Co-registration of the functional tomograms with each subject's head MRI localized alpha range activity to the occipital and/or posterior parietal brain region. This is the first application of this new functional tomography to human brain activity. The method successfully provides an overall view of brain electrical activity, a detailed spectral description and, combined with MRI, the localization of sources in anatomical brain space. PMID:26528119

  6. Abnormal brain activation during directed forgetting of negative memory in depressed patients.

    PubMed

    Yang, Wenjing; Chen, Qunlin; Liu, Peiduo; Cheng, Hongsheng; Cui, Qian; Wei, Dongtao; Zhang, Qinglin; Qiu, Jiang

    2016-01-15

    The frequent occurrence of uncontrollable negative thoughts and memories is a troubling aspect of depression. Thus, knowledge on the mechanism underlying intentional forgetting of these thoughts and memories is crucial to develop an effective emotion regulation strategy for depressed individuals. Behavioral studies have demonstrated that depressed participants cannot intentionally forget negative memories. However, the neural mechanism underlying this process remains unclear. In this study, participants completed the directed forgetting task in which they were instructed to remember or forget neutral or negative words. Standard univariate analysis based on the General Linear Model showed that the depressed participants have higher activation in the inferior frontal gyrus (IFG), superior frontal gyrus (SFG), superior parietal gyrus (SPG), and inferior temporal gyrus (ITG) than the healthy individuals. The results indicated that depressed participants recruited more frontal and parietal inhibitory control resources to inhibit the TBF items, but the attempt still failed because of negative bias. We also used the Support Vector Machine to perform multivariate pattern classification based on the brain activation during directed forgetting. The pattern of brain activity in directed forgetting of negative words allowed correct group classification with an overall accuracy of 75% (P=0.012). The brain regions which are critical for this discrimination showed abnormal activation when depressed participants were attempting to forget negative words. These results indicated that the abnormal neural circuitry when depressed individuals tried to forget the negative words might provide neurobiological markers for depression. PMID:26639452

  7. Abnormal neuronal activity in Tourette syndrome and its modulation using deep brain stimulation

    PubMed Central

    Israelashvili, Michal; Loewenstern, Yocheved

    2015-01-01

    Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) as a possible treatment for severe cases. Multiple lines of evidence have linked TS with abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. Neurophysiological data have only recently started to slowly accumulate from multiple sources: noninvasive imaging and electrophysiological techniques, invasive electrophysiological recordings in TS patients undergoing DBS implantation surgery, and animal models of the disorder. These converging sources point to system-level physiological changes throughout the CBG pathway, including both general altered baseline neuronal activity patterns and specific tic-related activity. DBS has been applied to different regions along the motor and limbic pathways, primarily to the globus pallidus internus, thalamic nuclei, and nucleus accumbens. In line with the findings that also draw on the more abundant application of DBS to Parkinson's disease, this stimulation is assumed to result in changes in the neuronal firing patterns and the passage of information through the stimulated nuclei. We present an overview of recent experimental findings on abnormal neuronal activity associated with TS and the changes in this activity following DBS. These findings are then discussed in the context of current models of CBG function in the normal state, during TS, and finally in the wider context of DBS in CBG-related disorders. PMID:25925326

  8. Effect of dimethylbenzanthracene (DMBA) on spontaneous activity in mice during pregnancy and lactation

    SciTech Connect

    Pitkow, H.S.; Rainieri, J.; Dwyer, P.

    1986-03-01

    Our laboratory has reported that DMBA, a carcinogenic polycyclic aromatic hydrocarbon, administered during pregnancy significantly depressed neonatal cerebrum growth and synthesis which was manifested by a retarded learning ability on day 32 post-partum. In order to determine the effects of DMBA on spontaneous movements during pregnancy and lactation, female CF-1C mice (23-25 g; 10 animals/group) were subcutaneously injected with 250 ..mu..g DMBA in 0.1 ml sesame oil on alternate days starting with day 8 of pregnancy to day 7 post-partum (i.e., day 27). On day 9 of pregnancy and on alternate days each female's cage, with pups removed, was individually placed on the stage of a Stoelting Electronic Activity Monitor for ten minutes and spontaneous movements per minute (mv/min) recorded. No significant differences were observed between control (64.1 +/- 7.3 mv/min) and DMBA (52.4 +/- 6.8 mv/min) groups during pregnancy. After parturition the spontaneous movements of the control mice significantly increased averaging 86.4 +/- 13.3 mv/min for days 1 to 7 post-partum, whereas, the DMBA group value decreased significantly averaging 41.8 +/- 3.7 mv/min during this time. Our data suggests that the effects of DMBA were manifested during lactation where it significantly depressed the lactating mother's nervous system and subsequent behavioral activity.

  9. Prophage spontaneous activation promotes DNA release enhancing biofilm formation in Streptococcus pneumoniae.

    PubMed

    Carrolo, Margarida; Frias, Maria João; Pinto, Francisco Rodrigues; Melo-Cristino, José; Ramirez, Mário

    2010-01-01

    Streptococcus pneumoniae (pneumococcus) is able to form biofilms in vivo and previous studies propose that pneumococcal biofilms play a relevant role both in colonization and infection. Additionally, pneumococci recovered from human infections are characterized by a high prevalence of lysogenic bacteriophages (phages) residing quiescently in their host chromosome. We investigated a possible link between lysogeny and biofilm formation. Considering that extracellular DNA (eDNA) is a key factor in the biofilm matrix, we reasoned that prophage spontaneous activation with the consequent bacterial host lysis could provide a source of eDNA, enhancing pneumococcal biofilm development. Monitoring biofilm growth of lysogenic and non-lysogenic pneumococcal strains indicated that phage-infected bacteria are more proficient at forming biofilms, that is their biofilms are characterized by a higher biomass and cell viability. The presence of phage particles throughout the lysogenic strains biofilm development implicated prophage spontaneous induction in this effect. Analysis of lysogens deficient for phage lysin and the bacterial major autolysin revealed that the absence of either lytic activity impaired biofilm development and the addition of DNA restored the ability of mutant strains to form robust biofilms. These findings establish that limited phage-mediated host lysis of a fraction of the bacterial population, due to spontaneous phage induction, constitutes an important source of eDNA for the S. pneumoniae biofilm matrix and that this localized release of eDNA favors biofilm formation by the remaining bacterial population. PMID:21187931

  10. Abnormal Activation of BMP Signaling Causes Myopathy in Fbn2 Null Mice.

    PubMed

    Sengle, Gerhard; Carlberg, Valerie; Tufa, Sara F; Charbonneau, Noe L; Smaldone, Silvia; Carlson, Eric J; Ramirez, Francesco; Keene, Douglas R; Sakai, Lynn Y

    2015-06-01

    Fibrillins are large extracellular macromolecules that polymerize to form the backbone structure of connective tissue microfibrils. Mutations in the gene for fibrillin-1 cause the Marfan syndrome, while mutations in the gene for fibrillin-2 cause Congenital Contractural Arachnodactyly. Both are autosomal dominant disorders, and both disorders affect musculoskeletal tissues. Here we show that Fbn2 null mice (on a 129/Sv background) are born with reduced muscle mass, abnormal muscle histology, and signs of activated BMP signaling in skeletal muscle. A delay in Myosin Heavy Chain 8, a perinatal myosin, was found in Fbn2 null forelimb muscle tissue, consistent with the notion that muscle defects underlie forelimb contractures in these mice. In addition, white fat accumulated in the forelimbs during the early postnatal period. Adult Fbn2 null mice are already known to demonstrate persistent muscle weakness. Here we measured elevated creatine kinase levels in adult Fbn2 null mice, indicating ongoing cycles of muscle injury. On a C57Bl/6 background, Fbn2 null mice showed severe defects in musculature, leading to neonatal death from respiratory failure. These new findings demonstrate that loss of fibrillin-2 results in phenotypes similar to those found in congenital muscular dystrophies and that FBN2 should be considered as a candidate gene for recessive congenital muscular dystrophy. Both in vivo and in vitro evidence associated muscle abnormalities and accumulation of white fat in Fbn2 null mice with abnormally activated BMP signaling. Genetic rescue of reduced muscle mass and accumulation of white fat in Fbn2 null mice was accomplished by deleting a single allele of Bmp7. In contrast to other reports that activated BMP signaling leads to muscle hypertrophy, our findings demonstrate the exquisite sensitivity of BMP signaling to the fibrillin-2 extracellular environment during early postnatal muscle development. New evidence presented here suggests that fibrillin-2 can

  11. Abnormal frontostriatal activity in recently abstinent cocaine users during implicit moral processing.

    PubMed

    Caldwell, Brendan M; Harenski, Carla L; Harenski, Keith A; Fede, Samantha J; Steele, Vaughn R; Koenigs, Michael R; Kiehl, Kent A

    2015-01-01

    Investigations into the neurobiology of moral cognition are often done by examining clinical populations characterized by diminished moral emotions and a proclivity toward immoral behavior. Psychopathy is the most common disorder studied for this purpose. Although cocaine abuse is highly co-morbid with psychopathy and cocaine-dependent individuals exhibit many of the same abnormalities in socio-affective processing as psychopaths, this population has received relatively little attention in moral psychology. To address this issue, the authors used functional magnetic resonance imaging (fMRI) to record hemodynamic activity in 306 incarcerated male adults, stratified into regular cocaine users (n = 87) and a matched sample of non-cocaine users (n = 87), while viewing pictures that did or did not depict immoral actions and determining whether each depicted scenario occurred indoors or outdoors. Consistent with expectations, cocaine users showed abnormal neural activity in several frontostriatial regions during implicit moral picture processing compared to their non-cocaine using peers. This included reduced moral/non-moral picture discrimination in the vACC, vmPFC, lOFC, and left vSTR. Additionally, psychopathy was negatively correlated with activity in an overlapping region of the ACC and right lateralized vSTR. These results suggest that regular cocaine abuse may be associated with affective deficits which can impact relatively high-level processes like moral cognition. PMID:26528169

  12. Abnormal frontostriatal activity in recently abstinent cocaine users during implicit moral processing

    PubMed Central

    Caldwell, Brendan M.; Harenski, Carla L.; Harenski, Keith A.; Fede, Samantha J.; Steele, Vaughn R.; Koenigs, Michael R.; Kiehl, Kent A.

    2015-01-01

    Investigations into the neurobiology of moral cognition are often done by examining clinical populations characterized by diminished moral emotions and a proclivity toward immoral behavior. Psychopathy is the most common disorder studied for this purpose. Although cocaine abuse is highly co-morbid with psychopathy and cocaine-dependent individuals exhibit many of the same abnormalities in socio-affective processing as psychopaths, this population has received relatively little attention in moral psychology. To address this issue, the authors used functional magnetic resonance imaging (fMRI) to record hemodynamic activity in 306 incarcerated male adults, stratified into regular cocaine users (n = 87) and a matched sample of non-cocaine users (n = 87), while viewing pictures that did or did not depict immoral actions and determining whether each depicted scenario occurred indoors or outdoors. Consistent with expectations, cocaine users showed abnormal neural activity in several frontostriatial regions during implicit moral picture processing compared to their non-cocaine using peers. This included reduced moral/non-moral picture discrimination in the vACC, vmPFC, lOFC, and left vSTR. Additionally, psychopathy was negatively correlated with activity in an overlapping region of the ACC and right lateralized vSTR. These results suggest that regular cocaine abuse may be associated with affective deficits which can impact relatively high-level processes like moral cognition. PMID:26528169

  13. A MULTIPLEXED ASSAY FOR DETERMINATION OF NEUROTOXICANT EFFECTS ON SPONTANEOUS NETWORK ACTIVITY AND CELL VIABILITY FROM MICROELECTRODE ARRAYS

    EPA Science Inventory

    AbstractTITLE: A MULTIPLEXED ASSAY FOR DETERMINATION OF NEUROTOXICANT EFFECTS ON SPONTANEOUS NETWORK ACTIVITY AND CELL VIABILITY FROM MICROELECTRODE ARRAYSABSTRACT BODY: Microelectrode array (MEA) recordings are increasingly being used as an in vitro method to detect and characte...

  14. Axonal conduction slowing induced by spontaneous bursting activity in cortical neurons cultured in a microtunnel device.

    PubMed

    Shimba, Kenta; Sakai, Koji; Isomura, Takuya; Kotani, Kiyoshi; Jimbo, Yasuhiko

    2015-01-01

    Recently, axons have been recognized as computational units in neuronal networks that can change their conduction properties along with their firing. However, little is known about the relationship between spontaneous activity and changes in the conduction velocity due to lack of a suitable method. Here, we studied changes in the conduction velocity during bursting activity using a new microfabricated device and the spike sorting method. The propagating action potentials were recorded from axons, which extended through a microtunnel in our device, comprised of a microfabricated chamber and a microelectrode array. By using waveforms recorded from a series of three electrodes along the bottom of a microtunnel, we achieved a sorting accuracy approximately 8.0% higher than that of the conventional one-electrode waveform method. We then demonstrated for the first time that conduction delays increased by 8.0% in action potentials of a mathematically isolated axon during one burst recorded at 10 days in vitro (DIV). Moreover, 79.4% of all clusters showed this conduction slowing during bursting activity at 10 DIV. Finally, we evaluated the days-in-culture dependence of the properties of bursting activity. These results suggest that our method is suitable for evaluating changes in conduction properties induced by spontaneous activity. PMID:25418582

  15. Simple spontaneously active Hebbian learning model: homeostasis of activity and connectivity, and consequences for learning and epileptogenesis.

    PubMed

    Hsu, David; Tang, Aonan; Hsu, Murielle; Beggs, John M

    2007-10-01

    A spontaneously active neural system that is capable of continual learning should also be capable of homeostasis of both firing rate and connectivity. Experimental evidence suggests that both types of homeostasis exist, and that connectivity is maintained at a state that is optimal for information transmission and storage. This state is referred to as the critical state. We present a simple stochastic computational Hebbian learning model that incorporates both firing rate and critical homeostasis, and we explore its stability and connectivity properties. We also examine the behavior of our model with a simulated seizure and with simulated acute deafferentation. We argue that a neural system that is more highly connected than the critical state (i.e., one that is "supercritical") is epileptogenic. Based on our simulations, we predict that the postseizural and postdeafferentation states should be supercritical and epileptogenic. Furthermore, interventions that boost spontaneous activity should be protective against epileptogenesis. PMID:17995028

  16. Normal protein content but abnormally inhibited enzyme activity in muscle carnitine palmitoyltransferase II deficiency.

    PubMed

    Lehmann, Diana; Zierz, Stephan

    2014-04-15

    The biochemical consequences of the disease causing mutations of muscle carnitine palmitoyltransferase II (CPT II) deficiency are still enigmatic. Therefore, CPT II was characterized in muscle biopsies of nine patients with genetically proven muscle CPT II deficiency. Total CPT activity (CPT I+CPT II) of patients was not significantly different from that of controls. Remaining activities upon inhibition by malonyl-CoA and Triton X-100 were significantly reduced in patients. Immunohistochemically CPT II protein was predominantly expressed in type-I-fibers with the same intensity in patients as in controls. Western blot showed the same CPT II staining intensity ratio in patients and controls. CPT I and CPT II protein concentrations estimated by ELISA were not significantly different in patients and in controls. Citrate synthase activity in patients was significantly increased. Total CPT activity significantly correlated with both CPT I and CPT II protein concentrations in patients and controls. This implies (i) that normal total CPT activity in patients with muscle CPT II deficiency is not due to compensatory increase of CPT I activity and that (ii) the mutant CPT II is enzymatically active. The data further support the notion that in muscle CPT II deficiency enzyme activity and protein content are not reduced, but rather abnormally inhibited when fatty acid metabolism is stressed. PMID:24602495

  17. Diabetes-induced myelin abnormalities are associated with an altered lipid pattern: protective effects of LXR activation[S

    PubMed Central

    Cermenati, Gaia; Abbiati, Federico; Cermenati, Solei; Brioschi, Elisabetta; Volonterio, Alessandro; Cavaletti, Guido; Saez, Enrique; De Fabiani, Emma; Crestani, Maurizio; Garcia-Segura, Luis M.; Melcangi, Roberto C.; Caruso, Donatella; Mitro, Nico

    2012-01-01

    Diabetic peripheral neuropathy (DPN) is characterized by myelin abnormalities; however, the molecular mechanisms underlying such deficits remain obscure. To uncover the effects of diabetes on myelin alterations, we have analyzed myelin composition. In a streptozotocin-treated rat model of diabetic neuropathy, analysis of sciatic nerve myelin lipids revealed that diabetes alters myelin's phospholipid, FA, and cholesterol content in a pattern that can modify membrane fluidity. Reduced expression of relevant genes in the FA biosynthetic pathway and decreased levels of the transcriptionally active form of the lipogenic factor sterol-regulatory element binding factor-1c (SREBF-1c) were found in diabetic sciatic nerve. Expression of myelin's major protein, myelin protein zero (P0), was also suppressed by diabetes. In addition, we confirmed that diabetes induces sciatic nerve myelin abnormalities, primarily infoldings that have previously been associated with altered membrane fluidity. In a diabetic setting, synthetic activator of the nuclear receptor liver X receptor (LXR) increased SREBF-1c function and restored myelin lipid species and P0 expression levels to normal. These LXR-modulated improvements were associated with restored myelin structure in sciatic nerve and enhanced performance in functional tests such as thermal nociceptive threshold and nerve conduction velocity. These findings demonstrate an important role for the LXR-SREBF-1c axis in protection from diabetes-induced myelin abnormalities. PMID:22158827

  18. Myofascial trigger points: spontaneous electrical activity and its consequences for pain induction and propagation

    PubMed Central

    2011-01-01

    Active myofascial trigger points are one of the major peripheral pain generators for regional and generalized musculoskeletal pain conditions. Myofascial trigger points are also the targets for acupuncture and/or dry needling therapies. Recent evidence in the understanding of the pathophysiology of myofascial trigger points supports The Integrated Hypothesis for the trigger point formation; however unanswered questions remain. Current evidence shows that spontaneous electrical activity at myofascial trigger point originates from the extrafusal motor endplate. The spontaneous electrical activity represents focal muscle fiber contraction and/or muscle cramp potentials depending on trigger point sensitivity. Local pain and tenderness at myofascial trigger points are largely due to nociceptor sensitization with a lesser contribution from non-nociceptor sensitization. Nociceptor and non-nociceptor sensitization at myofascial trigger points may be part of the process of muscle ischemia associated with sustained focal muscle contraction and/or muscle cramps. Referred pain is dependent on the sensitivity of myofascial trigger points. Active myofascial trigger points may play an important role in the transition from localized pain to generalized pain conditions via the enhanced central sensitization, decreased descending inhibition and dysfunctional motor control strategy. PMID:21439050

  19. Fractal analysis reveals subclasses of neurons and suggests an explanation of their spontaneous activity.

    PubMed

    Favela, Luis H; Coey, Charles A; Griff, Edwin R; Richardson, Michael J

    2016-07-28

    The present work used fractal time series analysis (detrended fluctuation analysis; DFA) to examine the spontaneous activity of single neurons in an anesthetized animal model, specifically, the mitral cells in the rat main olfactory bulb. DFA bolstered previous research in suggesting two subclasses of mitral cells. Although there was no difference in the fractal scaling of the interspike interval series at the shorter timescales, there was a significant difference at longer timescales. Neurons in Group B exhibited fractal, power-law scaled interspike intervals, whereas neurons in Group A exhibited random variation. These results raise questions about the role of these different cells within the olfactory bulb and potential explanations of their dynamics. Specifically, self-organized criticality has been proposed as an explanation of fractal scaling in many natural systems, including neural systems. However, this theory is based on certain assumptions that do not clearly hold in the case of spontaneous neural activity, which likely reflects intrinsic cell dynamics rather than activity driven by external stimulation. Moreover, it is unclear how self-organized criticality might account for the random dynamics observed in Group A, and how these random dynamics might serve some functional role when embedded in the typical activity of the olfactory bulb. These theoretical considerations provide direction for additional experimental work. PMID:27189719

  20. Spontaneous Electrical Activity and Spikes in the Tail of Marine Cercariae

    PubMed Central

    Tolstenkov, O. O.; Zhukovskaya, M. I.; Prokofiev, V. V.; Gustafsson, M. K. S.

    2013-01-01

    Spontaneous electrical activity is recorded in two species of marine cercariae, Cryptocotyle lingua and Himasthla elongata, with different types of swimming—by glass microelectrode recordings. Slow local field potentials (sLFPs) of low amplitude and fast high amplitude action potentials (APs) are found. The shape of the sLFPs is different in the species and correlates with the type of swimming. Fast high amplitude APs are recorded for the first time in cercariae. The limited number of APs included in the swimming pattern of larva suggests a key role for the spiking neurons in initiating the motility pattern in the cercaria and needs further research. PMID:27335850

  1. Different effects of abnormal activation and myocardial disease on left ventricular ejection and filling times

    PubMed Central

    Zhou, Q; Henein, M; Coats, A; Gibson, D

    2000-01-01

    BACKGROUND—Ventricular activation is often abnormal in patients with dilated cardiomyopathy, but its specific effects on timing remain undetermined.
OBJECTIVE—To investigate the use of the ratio of the sum of left ventricular ejection and filling times to the total RR interval (Z ratio) to dissociate the effects of abnormal activation from those of cavity dilatation.
METHODS—Subjects were 20 normal individuals, 11 patients with isolated left bundle branch block (LBBB, QRS duration > 120 ms), 17 with dilated cardiomyopathy and normal activation, and 23 with dilated cardiomyopathy and LBBB. An additional 30 patients (nine with normal ventricular systolic function and 21 with dilated cardiomyopathy) were studied before and after right ventricular pacing. Left ventricular ejection and filling times were measured by pulsed wave Doppler and cavity size by M mode echocardiography.
RESULTS—Z ratio was independent of RR interval in all groups. Mean (SD) Z ratio was 82 (10)% for normal subjects, 66 (10)% for isolated LBBB (p < 0.01 v normal), 77 (7)% for dilated cardiomyopathy without LBBB (NS v normal), and 61 (7)% for dilated cardiomyopathy with LBBB (p < 0.01 v normal). In the nine patients with normal left ventricular size and QRS duration, Z ratio fell from 88 (6)% in sinus rhythm to 77 (10)% with right ventricular pacing (p = 0.26). In the 21 patients with dilated cardiomyopathy and LBBB, Z ratio rose from 59 (10)% in sinus rhythm to 74 (9)% with right ventricular DDD pacing (p < 0.001).
CONCLUSIONS—Z ratio dissociates the effects of abnormal ventricular activation and systolic disease. It also clearly differentiates right ventricular pacing from LBBB. It may thus be useful in comparing the haemodynamic effects of different pacing modes in patients with or without left ventricular disease.


Keywords: dilated cardiomyopathy; pacemaker; left bundle branch block; echocardiography. PMID:10956289

  2. Abnormal proliferation and spontaneous differentiation of myoblasts from a symptomatic female carrier of X-linked Emery-Dreifuss muscular dystrophy.

    PubMed

    Meinke, Peter; Schneiderat, Peter; Srsen, Vlastimil; Korfali, Nadia; Lê Thành, Phú; Cowan, Graeme J M; Cavanagh, David R; Wehnert, Manfred; Schirmer, Eric C; Walter, Maggie C

    2015-02-01

    Emery-Dreifuss muscular dystrophy (EDMD) is a neuromuscular disease characterized by early contractures, slowly progressive muscular weakness and life-threatening cardiac arrhythmia that can develop into cardiomyopathy. In X-linked EDMD (EDMD1), female carriers are usually unaffected. Here we present a clinical description and in vitro characterization of a mildly affected EDMD1 female carrying the heterozygous EMD mutation c.174_175delTT; p.Y59* that yields loss of protein. Muscle tissue sections and cultured patient myoblasts exhibited a mixed population of emerin-positive and -negative cells; thus uneven X-inactivation was excluded as causative. Patient blood cells were predominantly emerin-positive, but considerable nuclear lobulation was observed in non-granulocyte cells - a novel phenotype in EDMD. Both emerin-positive and emerin-negative myoblasts exhibited spontaneous differentiation in tissue culture, though emerin-negative myoblasts were more proliferative than emerin-positive cells. The preferential proliferation of emerin-negative myoblasts together with the high rate of spontaneous differentiation in both populations suggests that loss of functional satellite cells might be one underlying mechanism for disease pathology. This could also account for the slowly developing muscle phenotype. PMID:25454731

  3. Where's the Noise? Key Features of Spontaneous Activity and Neural Variability Arise through Learning in a Deterministic Network.

    PubMed

    Hartmann, Christoph; Lazar, Andreea; Nessler, Bernhard; Triesch, Jochen

    2015-12-01

    Even in the absence of sensory stimulation the brain is spontaneously active. This background "noise" seems to be the dominant cause of the notoriously high trial-to-trial variability of neural recordings. Recent experimental observations have extended our knowledge of trial-to-trial variability and spontaneous activity in several directions: 1. Trial-to-trial variability systematically decreases following the onset of a sensory stimulus or the start of a motor act. 2. Spontaneous activity states in sensory cortex outline the region of evoked sensory responses. 3. Across development, spontaneous activity aligns itself with typical evoked activity patterns. 4. The spontaneous brain activity prior to the presentation of an ambiguous stimulus predicts how the stimulus will be interpreted. At present it is unclear how these observations relate to each other and how they arise in cortical circuits. Here we demonstrate that all of these phenomena can be accounted for by a deterministic self-organizing recurrent neural network model (SORN), which learns a predictive model of its sensory environment. The SORN comprises recurrently coupled populations of excitatory and inhibitory threshold units and learns via a combination of spike-timing dependent plasticity (STDP) and homeostatic plasticity mechanisms. Similar to balanced network architectures, units in the network show irregular activity and variable responses to inputs. Additionally, however, the SORN exhibits sequence learning abilities matching recent findings from visual cortex and the network's spontaneous activity reproduces the experimental findings mentioned above. Intriguingly, the network's behaviour is reminiscent of sampling-based probabilistic inference, suggesting that correlates of sampling-based inference can develop from the interaction of STDP and homeostasis in deterministic networks. We conclude that key observations on spontaneous brain activity and the variability of neural responses can be

  4. Where’s the Noise? Key Features of Spontaneous Activity and Neural Variability Arise through Learning in a Deterministic Network

    PubMed Central

    Hartmann, Christoph; Lazar, Andreea; Nessler, Bernhard; Triesch, Jochen

    2015-01-01

    Even in the absence of sensory stimulation the brain is spontaneously active. This background “noise” seems to be the dominant cause of the notoriously high trial-to-trial variability of neural recordings. Recent experimental observations have extended our knowledge of trial-to-trial variability and spontaneous activity in several directions: 1. Trial-to-trial variability systematically decreases following the onset of a sensory stimulus or the start of a motor act. 2. Spontaneous activity states in sensory cortex outline the region of evoked sensory responses. 3. Across development, spontaneous activity aligns itself with typical evoked activity patterns. 4. The spontaneous brain activity prior to the presentation of an ambiguous stimulus predicts how the stimulus will be interpreted. At present it is unclear how these observations relate to each other and how they arise in cortical circuits. Here we demonstrate that all of these phenomena can be accounted for by a deterministic self-organizing recurrent neural network model (SORN), which learns a predictive model of its sensory environment. The SORN comprises recurrently coupled populations of excitatory and inhibitory threshold units and learns via a combination of spike-timing dependent plasticity (STDP) and homeostatic plasticity mechanisms. Similar to balanced network architectures, units in the network show irregular activity and variable responses to inputs. Additionally, however, the SORN exhibits sequence learning abilities matching recent findings from visual cortex and the network’s spontaneous activity reproduces the experimental findings mentioned above. Intriguingly, the network’s behaviour is reminiscent of sampling-based probabilistic inference, suggesting that correlates of sampling-based inference can develop from the interaction of STDP and homeostasis in deterministic networks. We conclude that key observations on spontaneous brain activity and the variability of neural responses can be

  5. Stimulus-specific adaptation in the inferior colliculus of the mouse: anesthesia and spontaneous activity effects.

    PubMed

    Duque, Daniel; Malmierca, Manuel S

    2015-11-01

    Rapid behavioral responses to unexpected events in the acoustic environment are critical for survival. Stimulus-specific adaptation (SSA) is the process whereby some auditory neurons respond better to rare stimuli than to repetitive stimuli. Most experiments on SSA have been performed under anesthesia, and it is unknown if SSA sensitivity is altered by the anesthetic agent. Only a direct comparison can answer this question. Here, we recorded extracellular single units in the inferior colliculus of awake and anesthetized mice under an oddball paradigm that elicits SSA. Our results demonstrate that SSA is similar, but not identical, in the awake and anesthetized preparations. The differences are mostly due to the higher spontaneous activity observed in the awake animals, which also revealed a high incidence of inhibitory receptive fields. We conclude that SSA is not an artifact of anesthesia and that spontaneous activity modulates neuronal SSA differentially, depending on the state of arousal. Our results suggest that SSA may be especially important when nervous system activity is suppressed during sleep-like states. This may be a useful survival mechanism that allows the organism to respond to danger when sleeping. PMID:25115620

  6. A low-cost system to easily measure spontaneous physical activity in rodents.

    PubMed

    Chabert, Clovis; Bottelin, Pierre; Pison, Christophe; Dubouchaud, Hervé

    2016-05-01

    Spontaneous physical activity (SPA) can be responsible for variations of a lot of physiological parameters at the molecular, cellular, tissue, and systemic levels. It is increasingly recognized that good understanding of a large part of experimental results requires weighting them by SPA in order to reduce variability and thus to decrease the number of animals necessary to conduct a study. However, because of the high cost of this equipment, only a few laboratories are equipped with such equipment to measure the SPA of their animals. Here we present an effective, adaptable, and affordable system to measure SPA in rodents based on video acquisition of the animal in its own environment. We compared results obtained with our system to those collected at the same time with a commercial system of actimetry recording, and we found a high degree of correlation between these two approaches (r = 0.93; P < 0.001). We also were able to detect small variations of SPA induced by a special environment like chronic hypoxia exposure (25% less spontaneous activity compared with animals in normoxia, P < 0.05) or during the circadian cycle (107% more activity during the nocturnal phase compared with the diurnal phase, P < 0.05). PMID:26893032

  7. Accurate means of detecting and characterizing abnormal patterns of ventricular activation by phase image analysis

    SciTech Connect

    Botvinick, E.H.; Frais, M.A.; Shosa, D.W.; O'Connell, J.W.; Pacheco-Alvarez, J.A.; Scheinman, M.; Hattner, R.S.; Morady, F.; Faulkner, D.B.

    1982-08-01

    The ability of scintigraphic phase image analysis to characterize patterns of abnormal ventricular activation was investigated. The pattern of phase distribution and sequential phase changes over both right and left ventricular regions of interest were evaluated in 16 patients with normal electrical activation and wall motion and compared with those in 8 patients with an artificial pacemaker and 4 patients with sinus rhythm with the Wolff-Parkinson-White syndrome and delta waves. Normally, the site of earliest phase angle was seen at the base of the interventricular septum, with sequential change affecting the body of the septum and the cardiac apex and then spreading laterally to involve the body of both ventricles. The site of earliest phase angle was located at the apex of the right ventricle in seven patients with a right ventricular endocardial pacemaker and on the lateral left ventricular wall in one patient with a left ventricular epicardial pacemaker. In each case the site corresponded exactly to the position of the pacing electrode as seen on posteroanterior and left lateral chest X-ray films, and sequential phase changes spread from the initial focus to affect both ventricles. In each of the patients with the Wolff-Parkinson-White syndrome, the site of earliest ventricular phase angle was located, and it corresponded exactly to the site of the bypass tract as determined by endocardial mapping. In this way, four bypass pathways, two posterior left paraseptal, one left lateral and one right lateral, were correctly localized scintigraphically. On the basis of the sequence of mechanical contraction, phase image analysis provides an accurate noninvasive method of detecting abnormal foci of ventricular activation.

  8. On the statistical relationship between solar activity and spontaneous social processes

    NASA Astrophysics Data System (ADS)

    Rodkin, M. V.; Kharin, E. P.

    2014-12-01

    The starting times of mass spontaneous social movements have been compared with temporal changes in solar activity (Wolf numbers) and in the Aa index of geomagnetic activity. It is shown that relatively high values of solar and, hence, geomagnetic activity are typical (on average) of a set of years when social cataclysms began. In addition, the relationship between social activity and geomagnetic activity is expressed somewhat more strongly than with solar activity. Heliogeomagnetic activity itself is not, however, the cause of social conflicts, as is evidenced by the weakness of the statistical relationship and the fact that the time intervals of an extremely large number of social conflicts (the decades of the 1800s, 1910s, and 1990s) occur during periods of a reduced mean level of solar and geomagnetic activity. From an averaged statistical model of the solar-geomagnetic influence on social activity and the current status and forecast of the 24th solar cycle, we can assume that heliogeomagnetic factors will contribute to an increased level of sociopolitical activity at least until the end of 2014 and, possibly, a little longer.

  9. Spontaneous otoacoustic emissions in an active nonlinear cochlear model in the time domain

    NASA Astrophysics Data System (ADS)

    Fruth, Florian; Jülicher, Frank; Lindner, Benjamin

    2015-12-01

    A large fraction of human cochleas emits sounds even in the absence of external stimulation. These so-called spontaneous otoacoustic emissions (SOAEs) are a hallmark of the active nonlinear amplification process taking place in the cochlea. Here, we extend a previously proposed frequency domain model and put forward an active nonlinear one-dimensional model of the cochlea in the time domain describing human SOAEs [5]. In our model, oscillatory elements are close to an instability (Hopf bifurcation), they are subject to dynamical noise and coupled by hydrodynamic, elastic and dissipative interactions. Furthermore, oscillators are subject to a weak spatial irregularity in their activity (normally distributed and exponentially correlated in space) that gives rise to the individuality of each simulated cochlea. Our model captures main statistical features of the distribution of emission frequencies, the distribution of the numbers of emissions per cochlea, and the distribution of the distances between neighboring emissions as were previously measured in experiment [14].

  10. Abnormal Frontostriatal Activity During Unexpected Reward Receipt in Depression and Schizophrenia: Relationship to Anhedonia

    PubMed Central

    Segarra, Nuria; Metastasio, Antonio; Ziauddeen, Hisham; Spencer, Jennifer; Reinders, Niels R; Dudas, Robert B; Arrondo, Gonzalo; Robbins, Trevor W; Clark, Luke; Fletcher, Paul C; Murray, Graham K

    2016-01-01

    Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states. PMID:26708106

  11. Abnormal Frontostriatal Activity During Unexpected Reward Receipt in Depression and Schizophrenia: Relationship to Anhedonia.

    PubMed

    Segarra, Nuria; Metastasio, Antonio; Ziauddeen, Hisham; Spencer, Jennifer; Reinders, Niels R; Dudas, Robert B; Arrondo, Gonzalo; Robbins, Trevor W; Clark, Luke; Fletcher, Paul C; Murray, Graham K

    2016-07-01

    Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states. PMID:26708106

  12. Analysis of spontaneous MEG activity in mild cognitive impairment and Alzheimer's disease using spectral entropies and statistical complexity measures.

    PubMed

    Bruña, Ricardo; Poza, Jesús; Gómez, Carlos; García, María; Fernández, Alberto; Hornero, Roberto

    2012-06-01

    Alzheimer's disease (AD) is the most common cause of dementia. Over the last few years, a considerable effort has been devoted to exploring new biomarkers. Nevertheless, a better understanding of brain dynamics is still required to optimize therapeutic strategies. In this regard, the characterization of mild cognitive impairment (MCI) is crucial, due to the high conversion rate from MCI to AD. However, only a few studies have focused on the analysis of magnetoencephalographic (MEG) rhythms to characterize AD and MCI. In this study, we assess the ability of several parameters derived from information theory to describe spontaneous MEG activity from 36 AD patients, 18 MCI subjects and 26 controls. Three entropies (Shannon, Tsallis and Rényi entropies), one disequilibrium measure (based on Euclidean distance ED) and three statistical complexities (based on Lopez Ruiz-Mancini-Calbet complexity LMC) were used to estimate the irregularity and statistical complexity of MEG activity. Statistically significant differences between AD patients and controls were obtained with all parameters (p < 0.01). In addition, statistically significant differences between MCI subjects and controls were achieved by ED and LMC (p < 0.05). In order to assess the diagnostic ability of the parameters, a linear discriminant analysis with a leave-one-out cross-validation procedure was applied. The accuracies reached 83.9% and 65.9% to discriminate AD and MCI subjects from controls, respectively. Our findings suggest that MCI subjects exhibit an intermediate pattern of abnormalities between normal aging and AD. Furthermore, the proposed parameters provide a new description of brain dynamics in AD and MCI. PMID:22571870

  13. Analysis of spontaneous MEG activity in mild cognitive impairment and Alzheimer's disease using spectral entropies and statistical complexity measures

    NASA Astrophysics Data System (ADS)

    Bruña, Ricardo; Poza, Jesús; Gómez, Carlos; García, María; Fernández, Alberto; Hornero, Roberto

    2012-06-01

    Alzheimer's disease (AD) is the most common cause of dementia. Over the last few years, a considerable effort has been devoted to exploring new biomarkers. Nevertheless, a better understanding of brain dynamics is still required to optimize therapeutic strategies. In this regard, the characterization of mild cognitive impairment (MCI) is crucial, due to the high conversion rate from MCI to AD. However, only a few studies have focused on the analysis of magnetoencephalographic (MEG) rhythms to characterize AD and MCI. In this study, we assess the ability of several parameters derived from information theory to describe spontaneous MEG activity from 36 AD patients, 18 MCI subjects and 26 controls. Three entropies (Shannon, Tsallis and Rényi entropies), one disequilibrium measure (based on Euclidean distance ED) and three statistical complexities (based on Lopez Ruiz-Mancini-Calbet complexity LMC) were used to estimate the irregularity and statistical complexity of MEG activity. Statistically significant differences between AD patients and controls were obtained with all parameters (p < 0.01). In addition, statistically significant differences between MCI subjects and controls were achieved by ED and LMC (p < 0.05). In order to assess the diagnostic ability of the parameters, a linear discriminant analysis with a leave-one-out cross-validation procedure was applied. The accuracies reached 83.9% and 65.9% to discriminate AD and MCI subjects from controls, respectively. Our findings suggest that MCI subjects exhibit an intermediate pattern of abnormalities between normal aging and AD. Furthermore, the proposed parameters provide a new description of brain dynamics in AD and MCI.

  14. Decreased numbers of chemotactic factor receptors in chronic neutropenia with defective chemotaxis: spontaneous recovery from the neutrophil abnormalities during early childhood

    SciTech Connect

    Yasui, K.; Yamazaki, M.; Miyagawa, Y.; Komiyama, A.; Akabane, T.

    1987-05-01

    Childhood chronic neutropenia with decreased numbers of chemotactic factor receptors as well as defective chemotaxis was first demonstrated in an 8-month-old girl. Chemotactic factor receptors on neutrophils were assayed using tritiated N-formyl-methionyl-leucyl-phenylalanine (/sup 3/H-FMLP). The patient's neutrophils had decreased numbers of the receptors: numbers of the receptors were 20,000 (less than 3 SD) as compared with those of control cells of 52,000 +/- 6000 (mean +/- SD) (n = 10). The neutropenia disappeared spontaneously by 28 months of age parallel with the improvement of chemotaxis and increase in numbers of chemotactic factor receptors. These results demonstrate a transient decrease of neutrophil chemotactic factor receptors as one of the pathophysiological bases of a transient defect of neutrophil chemotaxis in this disorder.

  15. Abnormal dynamics of activation of object use information in apraxia: evidence from eyetracking

    PubMed Central

    Lee, Chia-lin; Mirman, Daniel; Buxbaum, Laurel J.

    2014-01-01

    Action representations associated with object use may be incidentally activated during visual object processing, and the time course of such activations may be influenced by lexical-semantic context (e.g., Lee, Middleton, Mirman, Kalénine, & Buxbaum, 2012). In this study we used the “visual world” eye-tracking paradigm to examine whether a deficit in producing skilled object-use actions (apraxia) is associated with abnormalities in incidental activation of action information, and assessed the neuroanatomical substrates of any such deficits. Twenty left hemisphere stroke patients, ten of whom were apraxic, performed a task requiring identification of a named object in a visual display containing manipulation-related and unrelated distractor objects. Manipulation relationships among objects were not relevant to the identification task. Objects were cued with neutral (“S/he saw the….”), or action-relevant (“S/he used the….”) sentences. Non-apraxic participants looked at use-related non-target objects significantly more than at unrelated non-target objects when cued both by neutral and action-relevant sentences, indicating that action information is incidentally activated. In contrast, apraxic participants showed delayed activation of manipulation-based action information during object identification when cued by neutral sentences. The magnitude of delayed activation in the neutral sentence condition was reliably predicted by lower scores on a test of gesture production to viewed objects, as well as by lesion loci in the inferior parietal and posterior temporal lobes. However, when cued by a sentence containing an action verb, apraxic participants showed fixation patterns that were statistically indistinguishable from non-apraxic controls. In support of grounded theories of cognition, these results suggest that apraxia and temporal-parietal lesions may be associated with abnormalities in incidental activation of action information from objects. Further

  16. Triclosan causes spontaneous abortion accompanied by decline of estrogen sulfotransferase activity in humans and mice

    PubMed Central

    Wang, Xiaoli; Chen, Xiaojiao; Feng, Xuejiao; Chang, Fei; Chen, Minjian; Xia, Yankai; Chen, Ling

    2015-01-01

    Triclosan (TCS), an antibacterial agent, is identified in serum and urine of humans. Here, we show that the level of urinary TCS in 28.3% patients who had spontaneous abortion in mid-gestation were increased by 11.3-fold (high-TCS) compared with normal pregnancies. Oral administration of TCS (10 mg/kg/day) in mice (TCS mice) caused an equivalent urinary TCS level as those in the high-TCS abortion patients. The TCS-exposure from gestation day (GD) 5.5 caused dose-dependently fetal death during GD12.5–16.5 with decline of live fetal weight. GD15.5 TCS mice appeared placental thrombus and tissue necrosis with enhancement of platelet aggregation. The levels of placenta and plasma estrogen sulfotransferase (EST) mRNA and protein in TCS mice or high-TCS abortion patients were not altered, but their EST activities were significantly reduced compared to controls. Although the levels of serum estrogen (E2) in TCS mice and high-TCS abortion patients had no difference from controls, their ratio of sulfo-conjugated E2 and unconjugated E2 was reduced. The estrogen receptor antagonist ICI-182,780 prevented the enhanced platelet aggregation and placental thrombosis and attenuated the fetal death in TCS mice. The findings indicate that TCS-exposure might cause spontaneous abortion probably through inhibition of EST activity to produce placental thrombosis. PMID:26666354

  17. Acid-sensing ion channels regulate spontaneous inhibitory activity in the hippocampus: possible implications for epilepsy.

    PubMed

    Ievglevskyi, O; Isaev, D; Netsyk, O; Romanov, A; Fedoriuk, M; Maximyuk, O; Isaeva, E; Akaike, N; Krishtal, O

    2016-08-01

    Acid-sensing ion channels (ASICs) play an important role in numerous functions in the central and peripheral nervous systems ranging from memory and emotions to pain. The data correspond to a recent notion that each neuron and many glial cells of the mammalian brain express at least one member of the ASIC family. However, the mechanisms underlying the involvement of ASICs in neuronal activity are poorly understood. However, there are two exceptions, namely, the straightforward role of ASICs in proton-based synaptic transmission in certain brain areas and the role of the Ca(2+)-permeable ASIC1a subtype in ischaemic cell death. Using a novel orthosteric ASIC antagonist, we have found that ASICs specifically control the frequency of spontaneous inhibitory synaptic activity in the hippocampus. Inhibition of ASICs leads to a strong increase in the frequency of spontaneous inhibitory postsynaptic currents. This effect is presynaptic because it is fully reproducible in single synaptic boutons attached to isolated hippocampal neurons. In concert with this observation, inhibition of the ASIC current diminishes epileptic discharges in a low Mg(2+) model of epilepsy in hippocampal slices and significantly reduces kainate-induced discharges in the hippocampus in vivo Our results reveal a significant novel role for ASICs.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377725

  18. Aberrant spontaneous brain activity in chronic tinnitus patients revealed by resting-state functional MRI

    PubMed Central

    Chen, Yu-Chen; Zhang, Jian; Li, Xiao-Wei; Xia, Wenqing; Feng, Xu; Gao, Bo; Ju, Sheng-Hong; Wang, Jian; Salvi, Richard; Teng, Gao-Jun

    2014-01-01

    Objective The neural mechanisms that give rise to the phantom sound of tinnitus are poorly understood. This study aims to investigate whether aberrant spontaneous brain activity exists in chronic tinnitus patients using resting-state functional magnetic resonance imaging (fMRI) technique. Materials and methods A total of 31 patients with chronic tinnitus patients and 32 healthy age-, sex-, and education-matched healthy controls were prospectively examined. Both groups had normal hearing thresholds. We calculated the amplitude of low-frequency fluctuations (ALFFs) of fMRI signals to measure spontaneous neuronal activity and detect the relationship between fMRI information and clinical data of tinnitus. Results Compared with healthy controls, we observed significant increased ALFF within several selected regions including the right middle temporal gyrus (MTG), right superior frontal gyrus (SFG), and right angular gyrus; decreased ALFF was detected in the left cuneus, right middle occipital gyrus and bilateral thalamus. Moreover, tinnitus distress correlated positively with increased ALFF in right MTG and right SFG; tinnitus duration correlated positively with higher ALFF values in right SFG. Conclusions The present study confirms that chronic tinnitus patients have aberrant ALFF in many brain regions, which is associated with specific clinical tinnitus characteristics. ALFF disturbance in specific brain regions might be used to identify the neuro-pathophysiological mechanisms in chronic tinnitus patients. PMID:25379434

  19. Changes in spontaneous neural activity immediately after an acoustic trauma: implications for neural correlates of tinnitus.

    PubMed

    Noreña, A J; Eggermont, J J

    2003-09-01

    Changes in spontaneous activity, recorded over 15-min periods before, immediately after and within hours after an acute acoustic trauma, were studied in primary auditory cortex of ketamine-anesthetized cats. We focused on the spontaneous firing rate (SFR), the peak cross-correlation coefficient (rho) and burst-firing activity. Multi-units (MUs) were grouped according to characteristic frequency (CF): MUs with a CF below the trauma-tone frequency (TF) were labeled as Be, those with a CF within 1 octave above the TF were labeled as Ab1 and those with a CF more than 1 octave above the TF were labeled as Ab2. Immediately after the trauma, the SFR was not significantly changed. The percentage of time that neurons were bursting, the mean burst duration, the number of spikes per burst and the mean inter-spike interval in a burst were enhanced. rho was locally increased in the Ab1-Ab2 and Ab2-Ab2 groups. A few hours post trauma, the SFR was increased in the Be and Ab2 groups, whereas burst-firing returned to pre-exposure levels. Moreover, rho was elevated in the Be-Ab2, Ab1-Ab2 and Ab2-Ab2 groups; this increase was significantly correlated to the changes in SFR. The results are discussed in the context of a neural correlate of tinnitus. PMID:13679145

  20. STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity

    PubMed Central

    Demaria, Olivier; De Gassart, Aude; Coso, Sanja; Gestermann, Nicolas; Di Domizio, Jeremy; Flatz, Lukas; Gaide, Olivier; Michielin, Olivier; Hwu, Patrick; Petrova, Tatiana V.; Martinon, Fabio; Modlin, Robert L.; Speiser, Daniel E.; Gilliet, Michel

    2015-01-01

    Spontaneous CD8 T-cell responses occur in growing tumors but are usually poorly effective. Understanding the molecular and cellular mechanisms that drive these responses is of major interest as they could be exploited to generate a more efficacious antitumor immunity. As such, stimulator of IFN genes (STING), an adaptor molecule involved in cytosolic DNA sensing, is required for the induction of antitumor CD8 T responses in mouse models of cancer. Here, we find that enforced activation of STING by intratumoral injection of cyclic dinucleotide GMP-AMP (cGAMP), potently enhanced antitumor CD8 T responses leading to growth control of injected and contralateral tumors in mouse models of melanoma and colon cancer. The ability of cGAMP to trigger antitumor immunity was further enhanced by the blockade of both PD1 and CTLA4. The STING-dependent antitumor immunity, either induced spontaneously in growing tumors or induced by intratumoral cGAMP injection was dependent on type I IFNs produced in the tumor microenvironment. In response to cGAMP injection, both in the mouse melanoma model and an ex vivo model of cultured human melanoma explants, the principal source of type I IFN was not dendritic cells, but instead endothelial cells. Similarly, endothelial cells but not dendritic cells were found to be the principal source of spontaneously induced type I IFNs in growing tumors. These data identify an unexpected role of the tumor vasculature in the initiation of CD8 T-cell antitumor immunity and demonstrate that tumor endothelial cells can be targeted for immunotherapy of melanoma. PMID:26607445

  1. Rapid recovery from spontaneous and simultaneous bilateral quadriceps tendon rupture in an active, healthy individual.

    PubMed

    Gaheer, Rajinder Singh; Hawkins, Amanda

    2010-07-01

    Bilateral spontaneous quadriceps rupture is an uncommon injury that is usually seen in association with multiple medical conditions and is frequently misdiagnosed. It is rarely seen in healthy, active individuals. This article presents a case of bilateral simultaneous and spontaneous rupture of the quadriceps tendon in a healthy, athletic, active and highly motivated patient with rapid recovery from injury and return to full sport activity within a relatively short period of time. A 65-year-old healthy man felt both knees give way while walking down stairs at home and collapsed, unable to bear weight. He was fit and well, not on any medications and basic laboratory screening was within normal limits. He was an active sportsman, horse rider, swimmer, and long-distance cyclist, and had completed a half marathon 1 month before his injury. He was diagnosed with bilateral quadriceps tendon ruptures. An ultrasound of both knees confirmed the diagnosis of full-thickness rupture. Surgical repair of both quadriceps tendons was performed 3 days after the injury. Bilateral locking brace in 10 degrees of flexion was used to immobilize both knees and protect the repair for 6 weeks. The patient remained nonweight bearing for 2 weeks, then gradual weight bearing was commenced, with full weight bearing at 6 weeks. Intensive isometric quadriceps exercises were started on the second postoperative day. Immobilization of both knees was maintained for 6 weeks, after which full active range of motion (ROM) was initiated. At 16 weeks after the injury he had bilateral ROM from 0 degrees to 120 degrees flexion, with no extension lag. He was horse riding, playing golf, swimming, and walking distances up to 2 miles at that time. PMID:20608622

  2. Pharmacological evidence for Orai channel activation as a source of cardiac abnormal automaticity.

    PubMed

    Wolkowicz, Paul E; Huang, Jian; Umeda, Patrick K; Sharifov, Oleg F; Tabengwa, Edlue; Halloran, Brian A; Urthaler, Ferdinand; Grenett, Hernan E

    2011-10-01

    Calcium transport through plasma membrane voltage-independent calcium channels is vital for signaling events in non-excitable and excitable cells. Following up on our earlier work, we tested the hypothesis that this type of calcium transport can disrupt myocardial electromechanical stability. Our Western and immunofluorescence analyses show that left atrial and ventricular myocytes express the Orai1 and the Orai3 calcium channels. Adding the Orai activator 2-aminoethoxydiphenyl borate (2-APB) to the superfusate of rat left atria causes these non-automatic muscles to contract spontaneously and persistently at rates of up to 10 Hz, and to produce normal action potentials from normal resting potentials, all in the absence of external stimulation. 2-APB likewise induces such automatic activity in superfused rat left ventricular papillary muscles, and the EC(50)s at which 2-APB induces this activity in both muscles are similar to the concentrations which activate Orais. Importantly, the voltage-independent calcium channel inhibitor 1-[2-(4-methoxyphenyl)-2-[3-(4-methoxyphenyl) propoxy]ethyl-1H-imidazole (SKF-96365) suppresses this automaticity with an IC(50) of 11 ± 0.6 μM in left atria and 6 ± 1.6 μM in papillary muscles. 1-(5-Iodonaphthalene-1-sulfonyl)-hexahydro-1,4-diazepine (ML-7), a second voltage-independent calcium channel inhibitor, and two calmodulin inhibitors also prevent 2-APB automaticity while two calmodulin-dependent protein kinase II inhibitors do not. Thus an activator of the Orai calcium channels provokes a novel type of high frequency automaticity in non-automatic heart muscle. PMID:21745466

  3. Spontaneous Synaptic Activation of Muscarinic Receptors by Striatal Cholinergic Neuron Firing.

    PubMed

    Mamaligas, Aphroditi A; Ford, Christopher P

    2016-08-01

    Cholinergic interneurons (CHIs) play a major role in motor and learning functions of the striatum. As acetylcholine does not directly evoke postsynaptic events at most striatal synapses, it remains unclear how postsynaptic cholinergic receptors encode the firing patterns of CHIs in the striatum. To examine the dynamics of acetylcholine release, we used optogenetics and paired recordings from CHIs and medium spiny neurons (MSNs) virally overexpressing G-protein-activated inwardly rectifying potassium (GIRK) channels. Due to the efficient coupling between endogenous muscarinic receptors and GIRK channels, we found that firing of individual CHIs resulted in monosynaptic spontaneous inhibitory post-synaptic currents (IPSCs) in MSNs. Paired CHI-MSN recordings revealed that the high probability of acetylcholine release at these synapses allowed muscarinic receptors to faithfully encode physiological activity patterns from individual CHIs without failure. These results indicate that muscarinic receptors in striatal output neurons reliably decode CHI firing. PMID:27373830

  4. Spontaneous ordering and vortex states of active fluids in circular confinement

    NASA Astrophysics Data System (ADS)

    Theillard, Maxime; Ezhilan, Barath; Saintillan, David

    2015-11-01

    Recent experimental, theoretical and simulation studies have shown that confinement can profoundly affect self-organization in active suspensions leading to striking features such as directed fluid pumping in planar confinement, formation of steady and spontaneous vortices in radial confinement. Motivated by this, we study the dynamics in a suspension of biologically active particles confined in spherical geometries using a mean-field kinetic theory for which we developed a novel numerical solver. In the case of circular confinement, we conduct a systematic exploration of the entire parameter space and distinguish 3 broad states: no-flow, stable vortex and chaotic and several interesting sub-states. Our efficient numerical framework is also employed to study 3D effects and dynamics in more complex geometries.

  5. Identifying minimal hepatic encephalopathy in cirrhotic patients by measuring spontaneous brain activity.

    PubMed

    Chen, Hua-Jun; Zhang, Ling; Jiang, Long-Feng; Chen, Qiu-Feng; Li, Jun; Shi, Hai-Bin

    2016-08-01

    It has been demonstrated that minimal hepatic encephalopathy (MHE) is associated with aberrant regional intrinsic brain activity in cirrhotic patients. However, few studies have investigated whether altered intrinsic brain activity can be used as a biomarker of MHE among cirrhotic patients. In this study, 36 cirrhotic patients (with MHE, n = 16; without MHE [NHE], n = 20) underwent resting-state functional magnetic resonance imaging (fMRI). Spontaneous brain activity was measured by examining the amplitude of low-frequency fluctuations (ALFF) in the fMRI signal. MHE was diagnosed based on the Psychometric Hepatic Encephalopathy Score (PHES). A two-sample t-test was used to determine the regions of interest (ROIs) in which ALFF differed significantly between the two groups; then, ALFF values within ROIs were selected as classification features. A linear discriminative analysis was used to differentiate MHE patients from NHE patients. The leave-one-out cross-validation method was used to estimate the performance of the classifier. The classification analysis was 80.6 % accurate (81.3 % sensitivity and 80.0 % specificity) in terms of distinguishing between the two groups. Six ROIs were identified as the most discriminative features, including the bilateral medial frontal cortex/anterior cingulate cortex, posterior cingulate cortex/precuneus, left precentral and postcentral gyrus, right lingual gyrus, middle frontal gyrus, and inferior/superior parietal lobule. The ALFF values within ROIs were correlated with PHES in cirrhotic patients. Our findings suggest that altered regional brain spontaneous activity is a useful biomarker for MHE detection among cirrhotic patients. PMID:26886109

  6. The role of spontaneous lipid curvature in the interaction of interfacially active peptides with membranes.

    PubMed

    Koller, Daniel; Lohner, Karl

    2014-09-01

    Research on antimicrobial peptides is in part driven by urgent medical needs such as the steady increase in pathogens being resistant to antibiotics. Despite the wealth of information compelling structure-function relationships are still scarce and thus the interfacial activity model has been proposed to bridge this gap. This model also applies to other interfacially active (membrane active) peptides such as cytolytic, cell penetrating or antitumor peptides. One parameter that is strongly linked to interfacial activity is the spontaneous lipid curvature, which is experimentally directly accessible. We discuss different parameters such as H-bonding, electrostatic repulsion, changes in monolayer surface area and lateral pressure that affect induction of membrane curvature, but also vice versa how membrane curvature triggers peptide response. In addition, the impact of membrane lipid composition on the formation of curved membrane structures and its relevance for diverse mode of action of interfacially active peptides and in turn biological activity are described. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova. PMID:24853655

  7. Inflammasome activation has an important role in the development of spontaneous colitis.

    PubMed

    Zhang, J; Fu, S; Sun, S; Li, Z; Guo, B

    2014-09-01

    Inflammatory bowel disease (IBD) is characterized for dysregulated intestinal inflammation. Conflicting reports have shown that activation of inflammasome could promote or decrease intestinal inflammation in an acute colitis model, whereas the involvement of inflammasome activation in chronic colitis is poorly understood. In this study, we investigated the role of inflammasome activation in the development of chronic intestinal inflammation by utilizing interleukin-10 (IL-10) knockout (KO) mouse as an animal model, which develops chronic colitis resembling human IBD. We demonstrate the causative link between inflammasome activation and the development of chronic intestinal inflammation. Our results show that mature IL-1β protein levels were significantly increased in all colon sections from IL-10-deficient mice compared with that of wild-type mice. We found that inhibition of inflammasome activities with IL-1 receptor antagonist or caspase-1 inhibitors suppressed IL-1β and IL-17 production from inflamed colon explants. Furthermore, blocking inflammasome activation with caspase-1 inhibitor in vivo significantly ameliorated the spontaneous colitis in IL-10 KO mice. Taken together, these observations demonstrate that inflammasome activation promotes the development of chronic intestinal inflammation. PMID:24472848

  8. Consistent abnormalities in metabolic network activity in idiopathic rapid eye movement sleep behaviour disorder

    PubMed Central

    Wu, Ping; Yu, Huan; Peng, Shichun; Dauvilliers, Yves; Wang, Jian; Ge, Jingjie; Zhang, Huiwei; Eidelberg, David

    2014-01-01

    Rapid eye movement sleep behaviour disorder has been evaluated using Parkinson’s disease-related metabolic network. It is unknown whether this disorder is itself associated with a unique metabolic network. 18F-fluorodeoxyglucose positron emission tomography was performed in 21 patients (age 65.0 ± 5.6 years) with idiopathic rapid eye movement sleep behaviour disorder and 21 age/gender-matched healthy control subjects (age 62.5 ± 7.5 years) to identify a disease-related pattern and examine its evolution in 21 hemi-parkinsonian patients (age 62.6 ± 5.0 years) and 16 moderate parkinsonian patients (age 56.9 ± 12.2 years). We identified a rapid eye movement sleep behaviour disorder-related metabolic network characterized by increased activity in pons, thalamus, medial frontal and sensorimotor areas, hippocampus, supramarginal and inferior temporal gyri, and posterior cerebellum, with decreased activity in occipital and superior temporal regions. Compared to the healthy control subjects, network expressions were elevated (P < 0.0001) in the patients with this disorder and in the parkinsonian cohorts but decreased with disease progression. Parkinson’s disease-related network activity was also elevated (P < 0.0001) in the patients with rapid eye movement sleep behaviour disorder but lower than in the hemi-parkinsonian cohort. Abnormal metabolic networks may provide markers of idiopathic rapid eye movement sleep behaviour disorder to identify those at higher risk to develop neurodegenerative parkinsonism. PMID:25338949

  9. Spontaneous oscillations, signal amplification and synchronization in a model of active hair bundle mechanics

    PubMed Central

    Han, Lijuan; Neiman, Alexander B.

    2010-01-01

    We study spontaneous dynamics and signal transduction in a model of active hair bundle mechanics of sensory hair cells. The hair bundle motion is subjected to internal noise resulted from thermal fluctuations and stochastic dynamics of mechano-electrical transduction ion channels. Similar to other studies we found that in the presence of noise the coherence of stochastic oscillations is maximal at a point on the bifurcation diagram away from the Andronov-Hopf bifurcation and is close to the point of maximum sensitivity of the system to weak periodic mechanical perturbations. Despite decoherent effect of noise the stochastic hair bundle oscillations can be synchronized by external periodic force of few pN amplitude in a finite range of control parameters. We then study effects of receptor potential oscillations on mechanics of the hair bundle and show that the hair bundle oscillations can be synchronized by oscillating receptor voltage. Moreover, using a linear model for the receptor potential we show that bi-directional coupling of the hair bundle and the receptor potential results in significant enhancement of the coherence of spontaneous oscillations and of the sensitivity to the external mechanical perturbations. PMID:20481759

  10. Abnormal Motor Activity and Thermoregulation in a Schizophrenia Rat Model for Translational Science

    PubMed Central

    2015-01-01

    Background Schizophrenia is accompanied by altered motor activity and abnormal thermoregulation; therefore, the presence of these symptoms can enhance the face validity of a schizophrenia animal model. The goal was to characterize these parameters in freely moving condition of a new substrain of rats showing several schizophrenia-related alterations. Methods Male Wistar rats were used: the new substrain housed individually (for four weeks) and treated subchronically with ketamine, and naive animals without any manipulations. Adult animals were implanted with E-Mitter transponders intraabdominally to record body temperature and locomotor activity continuously. The circadian rhythm of these parameters and the acute effects of changes in light conditions were analyzed under undisturbed circumstances, and the effects of different interventions (handling, bed changing or intraperitoneal vehicle injection) were also determined. Results Decreased motor activity with fragmented pattern was observed in the new substrain. However, these animals had higher body temperature during the active phase, and they showed wider range of its alterations, too. The changes in light conditions and different interventions produced blunted hyperactivity and altered body temperature responses in the new substrain. Poincaré plot analysis of body temperature revealed enhanced short- and long-term variabilities during the active phase compared to the inactive phase in both groups. Furthermore, the new substrain showed increased short- and long-term variabilities with lower degree of asymmetry suggesting autonomic dysregulation. Conclusions In summary, the new substrain with schizophrenia-related phenomena showed disturbed motor activity and thermoregulation suggesting that these objectively determined parameters can be biomarkers in translational research. PMID:26629908

  11. Detection of abnormal cardiac activity using principal component analysis--a theoretical study.

    PubMed

    Greisas, Ariel; Zafrir, Zohar; Zlochiver, Sharon

    2015-01-01

    Electrogram-guided ablation has been recently developed for allowing better detection and localization of abnormal atrial activity that may be the source of arrhythmogeneity. Nevertheless, no clear indication for the benefit of using electrograms guided ablation over empirical ablation was established thus far, and there is a clear need of improving the localization of cardiac arrhythmogenic targets for ablation. In this paper, we propose a new approach for detection and localization of irregular cardiac activity during ablation procedures that is based on dimension reduction algorithms and principal component analysis (PCA). Using an 8×8 electrode array, our method produces manifolds that allow easy visualization and detection of possible arrhythmogenic ablation targets characterized by irregular conduction. We employ mathematical modeling and computer simulations to demonstrate the feasibility of the new approach for two well established arrhythmogenic sources for irregular conduction--spiral waves and patchy fibrosis. Our results show that the PCA method can differentiate between focal ectopic activity and spiral wave activity, as these two types of activity produce substantially different manifold shapes. Moreover, the technique allows the detection of spiral wave cores and their general meandering and drifting pattern. Fibrotic patches larger than 2 mm(2) could also be visualized using the PCA method, both for quiescent atrial tissue and for tissue exhibiting spiral wave activity. We envision that this method, contingent to further numerical and experimental validation studies in more complex, realistic geometrical configurations and with clinical data, can improve existing atrial ablation mapping capabilities, thus increasing success rates and optimizing arrhythmia management. PMID:25073163

  12. Enhanced spontaneous locomotor activity in bovine GH transgenic mice involves peripheral mechanisms.

    PubMed

    Bohlooly-Y, M; Olsson, B; Gritli-Linde, A; Brusehed, O; Isaksson, O G; Ohlsson, C; Söderpalm, B; Törnell, J; Ola, B

    2001-10-01

    Clinical and experimental studies indicate a role for GH in mechanisms related to anhedonia/hedonia, psychic energy, and reward. Recently we showed that transgenic mice with general overexpression of bovine GH display increased spontaneous locomotor activity. In the present study, we investigated whether this behavioral change is owing to a direct action of GH in the central nervous system or to peripheral GH actions. A transgenic construct, containing the glial fibrillary acidic protein promoter directing specific expression of bovine GH to the central nervous system, was designed. The central nervous system-specific expression of bovine GH in the glial fibrillary acidic protein-bovine GH transgenic mice was confirmed, but no effect on spontaneous locomotor activity was observed. Serum bovine GH levels were increased in glial fibrillary acidic protein-bovine GH transgenic mice but clearly lower than in transgenic mice with general overexpression of bovine GH. In contrast to the transgenic mice with general overexpression of bovine GH, glial fibrillary acidic protein-bovine GH mice did not display any difference in serum IGF-I levels. The levels of free T(3) and the conversion of the free T(4) to free T(3) were only increased in transgenic mice with general overexpression of bovine GH, but serum corticosterone levels were similarly increased in both transgenic models. These results suggest that free T(3) and/or IGF-I, affecting dopamine and serotonin systems in the central nervous system, may mediate the enhanced locomotor activity observed in transgenic mice with general overexpression of bovine GH. PMID:11564723

  13. Membrane Potential Dynamics of Spontaneous and Visually Evoked Gamma Activity in V1 of Awake Mice

    PubMed Central

    Perrenoud, Quentin; Pennartz, Cyriel M. A.; Gentet, Luc J.

    2016-01-01

    Cortical gamma activity (30–80 Hz) is believed to play important functions in neural computation and arises from the interplay of parvalbumin-expressing interneurons (PV) and pyramidal cells (PYRs). However, the subthreshold dynamics underlying its emergence in the cortex of awake animals remain unclear. Here, we characterized the intracellular dynamics of PVs and PYRs during spontaneous and visually evoked gamma activity in layers 2/3 of V1 of awake mice using targeted patch-clamp recordings and synchronous local field potentials (LFPs). Strong gamma activity patterned in short bouts (one to three cycles), occurred when PVs and PYRs were depolarizing and entrained their membrane potential dynamics regardless of the presence of visual stimulation. PV firing phase locked unconditionally to gamma activity. However, PYRs only phase locked to visually evoked gamma bouts. Taken together, our results indicate that gamma activity corresponds to short pulses of correlated background synaptic activity synchronizing the output of cortical neurons depending on external sensory drive. PMID:26890123

  14. Spontaneous activity in the developing gerbil auditory cortex in vivo involves GABAergic transmission

    PubMed Central

    Kotak, Vibhakar C.; Péndola, L. Martín; Rodríguez-Contreras, Adrián

    2012-01-01

    A salient feature of the developing brain is that spontaneous oscillations (SOs) and waves may influence the emergence of synaptic connections. Whilst gamma-amino butyric acid (GABA) produces depolarization and may support SOs in the neurons of developing rodents, it elicits hyperpolarization and diminishes SOs in developing gerbil auditory cortex (ACx). Therefore, we asked whether SOs exist in developing gerbil ACx in vivo and if GABAergic involvement can be manipulated. In vivo extracellular recordings in P3-5 ACx revealed SOs with longer burst durations and shorter inter-event intervals compared to ACx SOs in slices. ACx was then validated by gross anatomical features and lesions created at the in vivo recording site that corresponded with the electrophysiological coordinates of thalamorecipient ACx in slices. Further, NeuroVue Red, a lipophilic dye loaded at the in vivo recording sites, stained anatomically identifiable fiber tracks between the ACx and the auditory thalamus, medial geniculate body (MG). Separately, to chronically perturb GABAergic role in SOs, P2-5 pups were administered daily with GABAA receptor blocker, bicuculline (BIC). We then recorded from P14-17 ACx neurons in slices generated after hearing onset. ACx neurons from BIC-administered pups exhibited spontaneous action potentials in contrast to subthreshold synaptic potentials in neurons from sham-injected animals. Finally, to elucidate whether the gap junction blocker mefloquine (MFQ) previously shown to dampen ACx SOs in slices affected GABAergic transmission, MFQ was acutely applied in P3-5 slices while spontaneous inhibitory postsynaptic currents (sIPSCs) were recorded. Whereas MFQ increased the amplitude and frequency of sIPSCs in ACx neurons, the broad-spectrum gap junction blocker carbenoxolone decreased sIPSC amplitudes only. Together, we show that P2-5 gerbil ACx can endogenously generate SOs in vivo. Persistence of activity in ACx in P14-17 slices from pups administered with BIC at

  15. The effects of nutritional polyunsaturated fatty acids on locomotor activity in spontaneously hypertensive rats.

    PubMed

    Hauser, Joachim; Makulska-Gertruda, Ewelina; Reissmann, Andreas; Sontag, Thomas-A; Tucha, Oliver; Lange, Klaus W

    2014-06-01

    The present study investigated the effects of nutritional omega-3 polyunsaturated fatty acids on locomotor activity in spontaneously hypertensive rats (SHRs), which are used as an animal model of attention-deficit/hyperactivity disorder (ADHD). For 6 weeks, two groups of randomly assigned SHRs received food either enriched with or deficient in omega-3 fatty acids (based on the American Institute of Nutrition-93 G/AIN93G). Using an open field, locomotor activity was subsequently assessed for 6 days. A marked difference in locomotor activity as assessed by the distance travelled in the open field was found between the two groups of rats. In comparison with rats fed with omega-3 fatty acid-enriched food, the animals on the omega-3 fatty acid-deficient diet showed a significantly higher locomotor activity. The present findings demonstrated that nutritional enrichment with omega-3 fatty acids was associated with reduced motor activity in an established animal model of ADHD and support the notion that omega-3 polyunsaturated fatty acids may play a role in the pathophysiology of ADHD. PMID:24415401

  16. Telomerase Activity as a Potential Diagnostic Marker for Triage of Abnormal Pap Smears

    PubMed Central

    Ault, Kevin A.; Allen, Heather K.; Phillips, Stacia L.; Bridget Zimmerman, M.; Klingelhutz, Aloysius J.

    2008-01-01

    Objectives To determine whether there is an association between high levels of telomerase and premalignant cervical disease and to provide a preliminary analysis of telomerase activity as a potential triage strategy. Materials and Methods Premenopausal women were invited to participate in the study during routine gynecologic visits as well as visits where colposcopy was performed. Samples were taken from the cervix using a broom device and placed in cold phosphate-buffered saline. A total of 92 samples were evaluated. Cells were counted and lysed, and a semi-quantitative measure of telomerase activity was determined using a commercially available telomerase enzyme-linked immunosorbent assay kit. The presence of human papillomavirus (HPV) types 16 and 18 was assessed by polymerase chain reaction analysis. One-way analysis of variance was used to test for the association of telomerase activity with cytology, HPV type 16 or 18 status, and colposcopy and/or biopsy findings. Results When telomerase levels were analyzed according to Pap smear results, there were no differences among four groups of cytology findings (normal, atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesion, and high-grade squamous intraepithelial lesion). When colposcopy and/or biopsy results were considered, significantly higher levels of telomerase were detected in cervical intraepithelial neoplasia (CIN) 2,3 samples than in normal Pap smear samples and CIN 1 samples (p = .035). There was no significant difference in telomerase levels between samples that tested positive for HPV type 16 or 18 and those that did not (p = .111). Conclusions Telomerase levels were significantly higher in cytologic samples from women with biopsy-proven CIN 2,3 than in samples from women with normal cytology results or CIN 1. These results warrant larger studies to determine whether telomerase activity may be a useful triage tool for abnormal cytologic findings. PMID:15870530

  17. Abnormal Resting State fMRI Activity Predicts Processing Speed Deficits in First-Episode Psychosis

    PubMed Central

    Argyelan, Miklos; Gallego, Juan A; Robinson, Delbert G; Ikuta, Toshikazu; Sarpal, Deepak; John, Majnu; Kingsley, Peter B; Kane, John; Malhotra, Anil K; Szeszko, Philip R

    2015-01-01

    Little is known regarding the neuropsychological significance of resting state functional magnetic resonance imaging (rs-fMRI) activity early in the course of psychosis. Moreover, no studies have used different approaches for analysis of rs-fMRI activity and examined gray matter thickness in the same cohort. In this study, 41 patients experiencing a first-episode of psychosis (including N=17 who were antipsychotic drug-naive at the time of scanning) and 41 individually age- and sex-matched healthy volunteers completed rs-fMRI and structural MRI exams and neuropsychological assessments. We computed correlation matrices for 266 regions-of-interest across the brain to assess global connectivity. In addition, independent component analysis (ICA) was used to assess group differences in the expression of rs-fMRI activity within 20 predefined publicly available templates. Patients demonstrated lower overall rs-fMRI global connectivity compared with healthy volunteers without associated group differences in gray matter thickness assessed within the same regions-of-interest used in this analysis. Similarly, ICA revealed worse rs-fMRI expression scores across all 20 networks in patients compared with healthy volunteers, with posthoc analyses revealing significant (p<0.05; corrected) abnormalities within the caudate nucleus and planum temporale. Worse processing speed correlated significantly with overall lower global connectivity using the region-of-interest approach and lower expression scores within the planum temporale using ICA. Our findings implicate dysfunction in rs-fMRI activity in first-episode psychosis prior to extensive antipsychotic treatment using different analytic approaches (in the absence of concomitant gray matter structural differences) that predict processing speed. PMID:25567423

  18. Dependence of spontaneous electrical activity and basal prolactin release on nonselective cation channels in pituitary lactotrophs.

    PubMed

    Kučka, M; Kretschmannová, K; Stojilkovic, S S; Zemková, H; Tomić, M

    2012-01-01

    All secretory anterior pituitary cells fire action potentials spontaneously and exhibit a high resting cation conductance, but the channels involved in the background permeability have not been identified. In cultured lactotrophs and immortalized GH(3) cells, replacement of extracellular Na(+) with large organic cations, but not blockade of voltage-gated Na(+) influx, led to an instantaneous hyperpolarization of cell membranes that was associated with a cessation of spontaneous firing. When cells were clamped at -50 mV, which was close to the resting membrane potential in these cells, replacement of bath Na(+) with organic cations resulted in an outward-like current, reflecting an inhibition of the inward holding membrane current and indicating loss of a background-depolarizing conductance. Quantitative RT-PCR analysis revealed the high expression of mRNA transcripts for TRPC1 and much lower expression of TRPC6 in both lactotrophs and GH(3) cells. Very low expression of TRPC3, TRPC4, and TRPC5 mRNA transcripts were also present in pituitary but not GH(3) cells. 2-APB and SKF-96365, relatively selective blockers of TRPC channels, inhibited electrical activity, Ca(2+) influx and prolactin release in a concentration-dependent manner. Gd(3+), a common Ca(2+) channel blocker, and flufenamic acid, an inhibitor of non-selective cation channels, also inhibited electrical activity, Ca(2+) influx and prolactin release. These results indicate that nonselective cation channels, presumably belonging to the TRPC family, contribute to the background depolarizing conductance and firing of action potentials with consequent contribution to Ca(2+) influx and hormone release in lactotrophs and GH(3) cells. PMID:22480423

  19. Resting spontaneous activity in the default mode network predicts performance decline during prolonged attention workload.

    PubMed

    Gui, Danyang; Xu, Sihua; Zhu, Senhua; Fang, Zhuo; Spaeth, Andrea M; Xin, Yuanyuan; Feng, Tingyong; Rao, Hengyi

    2015-10-15

    After continuous and prolonged cognitive workload, people typically show reduced behavioral performance and increased feelings of fatigue, which are known as "time-on-task (TOT) effects". Although TOT effects are pervasive in modern life, their underlying neural mechanisms remain elusive. In this study, we induced TOT effects by administering a 20-min continuous psychomotor vigilance test (PVT) to a group of 16 healthy adults and used resting-state blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to examine spontaneous brain activity changes associated with fatigue and performance. Behaviorally, subjects displayed robust TOT effects, as reflected by increasingly slower reaction times as the test progressed and higher self-reported mental fatigue ratings after the 20-min PVT. Compared to pre-test measurements, subjects exhibited reduced amplitudes of low-frequency fluctuation (ALFF) in the default mode network (DMN) and increased ALFF in the thalamus after the test. Subjects also exhibited reduced anti-correlations between the posterior cingulate cortex (PCC) and right middle prefrontal cortex after the test. Moreover, pre-test resting ALFF in the PCC and medial prefrontal cortex (MePFC) predicted subjects' subsequent performance decline; individuals with higher ALFF in these regions exhibited more stable reaction times throughout the 20-min PVT. These results support the important role of both task-positive and task-negative networks in mediating TOT effects and suggest that spontaneous activity measured by resting-state BOLD fMRI may be a marker of mental fatigue. PMID:26196666

  20. Abnormal activity of corneal cold thermoreceptors underlies the unpleasant sensations in dry eye disease.

    PubMed

    Kovács, Illés; Luna, Carolina; Quirce, Susana; Mizerska, Kamila; Callejo, Gerard; Riestra, Ana; Fernández-Sánchez, Laura; Meseguer, Victor M; Cuenca, Nicolás; Merayo-Lloves, Jesús; Acosta, M Carmen; Gasull, Xavier; Belmonte, Carlos; Gallar, Juana

    2016-02-01

    Dry eye disease (DED) affects >10% of the population worldwide, and it provokes an unpleasant sensation of ocular dryness, whose underlying neural mechanisms remain unknown. Removal of the main lachrymal gland in guinea pigs caused long-term reduction of basal tearing accompanied by changes in the architecture and density of subbasal corneal nerves and epithelial terminals. After 4 weeks, ongoing impulse activity and responses to cooling of corneal cold thermoreceptor endings were enhanced. Menthol (200 μM) first excited and then inactivated this augmented spontaneous and cold-evoked activity. Comparatively, corneal polymodal nociceptors of tear-deficient eyes remained silent and exhibited only a mild sensitization to acidic stimulation, whereas mechanonociceptors were not affected. Dryness-induced changes in peripheral cold thermoreceptor responsiveness developed in parallel with a progressive excitability enhancement of corneal cold trigeminal ganglion neurons, primarily due to an increase of sodium currents and a decrease of potassium currents. In corneal polymodal nociceptor neurons, sodium currents were enhanced whereas potassium currents remain unaltered. In healthy humans, exposure of the eye surface to menthol vapors or to cold air currents evoked unpleasant sensations accompanied by increased blinking frequency that we attributed to cold thermoreceptor stimulation. Notably, stimulation with menthol reduced the ongoing background discomfort of patients with DED, conceivably due to use-dependent inactivation of cold thermoreceptors. Together, these data indicate that cold thermoreceptors contribute importantly to the detection and signaling of ocular surface wetness, and develop under chronic eye dryness conditions an injury-evoked neuropathic firing that seems to underlie the unpleasant sensations experienced by patients with DED. PMID:26675826

  1. Abnormal activity of corneal cold thermoreceptors underlies the unpleasant sensations in dry eye disease

    PubMed Central

    Kovács, Illés; Luna, Carolina; Quirce, Susana; Mizerska, Kamila; Callejo, Gerard; Riestra, Ana; Fernández-Sánchez, Laura; Meseguer, Victor M.; Cuenca, Nicolás; Merayo-Lloves, Jesús; Acosta, M. Carmen; Gasull, Xavier; Belmonte, Carlos; Gallar, Juana

    2015-01-01

    Abstract Dry eye disease (DED) affects >10% of the population worldwide, and it provokes an unpleasant sensation of ocular dryness, whose underlying neural mechanisms remain unknown. Removal of the main lachrymal gland in guinea pigs caused long-term reduction of basal tearing accompanied by changes in the architecture and density of subbasal corneal nerves and epithelial terminals. After 4 weeks, ongoing impulse activity and responses to cooling of corneal cold thermoreceptor endings were enhanced. Menthol (200 μM) first excited and then inactivated this augmented spontaneous and cold-evoked activity. Comparatively, corneal polymodal nociceptors of tear-deficient eyes remained silent and exhibited only a mild sensitization to acidic stimulation, whereas mechanonociceptors were not affected. Dryness-induced changes in peripheral cold thermoreceptor responsiveness developed in parallel with a progressive excitability enhancement of corneal cold trigeminal ganglion neurons, primarily due to an increase of sodium currents and a decrease of potassium currents. In corneal polymodal nociceptor neurons, sodium currents were enhanced whereas potassium currents remain unaltered. In healthy humans, exposure of the eye surface to menthol vapors or to cold air currents evoked unpleasant sensations accompanied by increased blinking frequency that we attributed to cold thermoreceptor stimulation. Notably, stimulation with menthol reduced the ongoing background discomfort of patients with DED, conceivably due to use-dependent inactivation of cold thermoreceptors. Together, these data indicate that cold thermoreceptors contribute importantly to the detection and signaling of ocular surface wetness, and develop under chronic eye dryness conditions an injury-evoked neuropathic firing that seems to underlie the unpleasant sensations experienced by patients with DED. PMID:26675826

  2. Relationship between individual neuron and network spontaneous activity in developing mouse cortex

    PubMed Central

    Barnett, Heather M.; Gjorgjieva, Julijana; Weir, Keiko; Comfort, Cara; Fairhall, Adrienne L.

    2014-01-01

    Spontaneous synchronous activity (SSA) that propagates as electrical waves is found in numerous central nervous system structures and is critical for normal development, but the mechanisms of generation of such activity are not clear. In previous work, we showed that the ventrolateral piriform cortex is uniquely able to initiate SSA in contrast to the dorsal neocortex, which participates in, but does not initiate, SSA (Lischalk JW, Easton CR, Moody WJ. Dev Neurobiol 69: 407–414, 2009). In this study, we used Ca2+ imaging of cultured embryonic day 18 to postnatal day 2 coronal slices (embryonic day 17 + 1–4 days in culture) of the mouse cortex to investigate the different activity patterns of individual neurons in these regions. In the piriform cortex where SSA is initiated, a higher proportion of neurons was active asynchronously between waves, and a larger number of groups of coactive cells was present compared with the dorsal cortex. When we applied GABA and glutamate synaptic antagonists, asynchronous activity and cellular clusters remained, while synchronous activity was eliminated, indicating that asynchronous activity is a result of cell-intrinsic properties that differ between these regions. To test the hypothesis that higher levels of cell-autonomous activity in the piriform cortex underlie its ability to initiate waves, we constructed a conductance-based network model in which three layers differed only in the proportion of neurons able to intrinsically generate bursting behavior. Simulations using this model demonstrated that a gradient of intrinsic excitability was sufficient to produce directionally propagating waves that replicated key experimental features, indicating that the higher level of cell-intrinsic activity in the piriform cortex may provide a substrate for SSA generation. PMID:25185811

  3. Altered temporal variance and neural synchronization of spontaneous brain activity in anesthesia.

    PubMed

    Huang, Zirui; Wang, Zhiyao; Zhang, Jianfeng; Dai, Rui; Wu, Jinsong; Li, Yuan; Liang, Weimin; Mao, Ying; Yang, Zhong; Holland, Giles; Zhang, Jun; Northoff, Georg

    2014-11-01

    Recent studies at the cellular and regional levels have pointed out the multifaceted importance of neural synchronization and temporal variance of neural activity. For example, neural synchronization and temporal variance has been shown by us to be altered in patients in the vegetative state (VS). This finding nonetheless leaves open the question of whether these abnormalities are specific to VS or rather more generally related to the absence of consciousness. The aim of our study was to investigate the changes of inter- and intra-regional neural synchronization and temporal variance of resting state activity in anesthetic-induced unconsciousness state. Applying an intra-subject design, we compared resting state activity in functional magnetic resonance imaging (fMRI) between awake versus anesthetized states in the same subjects. Replicating previous studies, we observed reduced functional connectivity within the default mode network (DMN) and thalamocortical network in the anesthetized state. Importantly, intra-regional synchronization as measured by regional homogeneity (ReHo) and temporal variance as measured by standard deviation (SD) of the BOLD signal were significantly reduced in especially the cortical midline regions, while increased in the lateral cortical areas in the anesthetized state. We further found significant frequency-dependent effects of SD in the thalamus, which showed abnormally high SD in Slow-5 (0.01-0.027 Hz) in the anesthetized state. Our results show for the first time of altered temporal variance of resting state activity in anesthesia. Combined with our findings in the vegetative state, these findings suggest a close relationship between temporal variance, neural synchronization and consciousness. PMID:24867379

  4. Power spectral analysis of autonomic nervous activity in spontaneously hypertensive rats.

    PubMed

    Ju, K; Kubo, T

    1997-01-01

    We studied power spectral analysis of heart rate variability (HRV) in control spontaneously hypertensive rats (SHR) and tourmaline hydroxyl negative ion-treated SHR groups. The power spectrum of HRV in SHR groups was composed of two frequency components; low frequency (LF, 0.005 approximately 1.0 Hz) and high frequency (HF, 1.0 approximately 2.0 Hz) components. The low frequency power (LFP) of HRV spectrum, which indicates sympathetic nervous activity, in negative air ion-treated SHR group was significantly (p < 0.01) smaller than in control SHR group. And also we obtained that the high frequency power (HFP) showing parasympathetic nervous activity in negative air ion-treated SHR group was significantly (p < 0.01) higher than in control SHR group. It could be concluded that hydroxyl negative air ions generated by tourmaline ionizer system decreased the elevated blood pressure, and control the sympathetic nervous activity and the parasympathetic nervous activity in SHR having the elevated blood pressure. PMID:9731382

  5. Reducing abnormal muscle co-activation after stroke using a myoelectric-computer interface: a pilot study

    PubMed Central

    Wright, Zachary A.; Zev Rymer, W.; Slutzky, Marc W.

    2014-01-01

    Background A significant factor in impaired movement caused by stroke is the inability to activate muscles independently. While the pathophysiology behind this abnormal co-activation is not clear, reducing the co-activation could improve overall arm function. A myoelectric computer interface (MCI), which maps EMG signals to cursor movement, could be used as a treatment to help retrain muscle activation patterns. Objective To investigate the use of MCI training to reduce abnormal muscle co-activation in chronic stroke survivors. Methods Five healthy subjects and five stroke survivors with hemiparesis participated in multiple sessions of MCI training. The level of arm impairment in stroke survivors was assessed using the upper extremity portion of Fugl-Meyer Motor Assessment (FMA-UE). Subjects performed isometric activations of up to five muscles. Activation of each muscle was mapped to different directions of cursor movement. The MCI specifically targeted one pair of muscles in each subject for reduction of co-activation. Results Both healthy subjects and stroke survivors learned to reduce abnormal co-activation of the targeted muscles with MCI training. Three out of five stroke survivors exhibited objective reduction in arm impairment as well (improvement in FMA-UE of 3 points in each of these subjects). Conclusions These results suggest that the MCI was an effective tool in directly retraining muscle activation patterns following stroke. PMID:24376069

  6. Interneurons Differentially Contribute to Spontaneous Network Activity in the Developing Hippocampus Dependent on Their Embryonic Lineage

    PubMed Central

    Wester, Jason C.

    2016-01-01

    Spontaneously generated network activity is a hallmark of developing neural circuits, and plays an important role in the formation of synaptic connections. In the rodent hippocampus, this activity is observed in vitro as giant depolarizing potentials (GDPs) during the first postnatal week. Interneurons importantly contribute to GDPs, due to the depolarizing actions of GABA early in development. While they are highly diverse, cortical interneurons can be segregated into two distinct groups based on their embryonic lineage from either the medial or caudal ganglionic eminences (MGE and CGE). There is evidence suggesting CGE-derived interneurons are important for GDP generation; however, their contribution relative to those from the MGE has never been directly tested. Here, we optogenetically inhibited either MGE- or CGE-derived interneurons in a region-specific manner in mouse neonatal hippocampus in vitro. In CA1, where interneurons are the primary source of recurrent excitation, we found that those from the MGE strongly and preferentially contributed to GDP generation. Furthermore, in dual whole-cell patch recordings in neonatal CA1, MGE interneurons formed synaptic connections to and from neighboring pyramidal cells at a much higher rate than those from the CGE. These MGE interneurons were commonly perisomatic targeting, in contrast to those from the CGE, which were dendrite targeting. Finally, inhibiting MGE interneurons in CA1 suppressed GDPs in CA3 and vice versa; conversely, they could also trigger GDPs in CA1 that propagated to CA3 and vice versa. Our data demonstrate a key role for MGE-derived interneurons in both generating and coordinating GDPs across the hippocampus. SIGNIFICANCE STATEMENT During nervous system development, immature circuits internally generate rhythmic patterns of electrical activity that promote the establishment of synaptic connections. Immature interneurons are excitatory rather than inhibitory and actively contribute to the generation

  7. Abnormal autonomic and associated brain activities during rest in autism spectrum disorder.

    PubMed

    Eilam-Stock, Tehila; Xu, Pengfei; Cao, Miao; Gu, Xiaosi; Van Dam, Nicholas T; Anagnostou, Evdokia; Kolevzon, Alexander; Soorya, Latha; Park, Yunsoo; Siller, Michael; He, Yong; Hof, Patrick R; Fan, Jin

    2014-01-01

    Autism spectrum disorders are associated with social and emotional deficits, the aetiology of which are not well understood. A growing consensus is that the autonomic nervous system serves a key role in emotional processes, by providing physiological signals essential to subjective states. We hypothesized that altered autonomic processing is related to the socio-emotional deficits in autism spectrum disorders. Here, we investigated the relationship between non-specific skin conductance response, an objective index of sympathetic neural activity, and brain fluctuations during rest in high-functioning adults with autism spectrum disorder relative to neurotypical controls. Compared with control participants, individuals with autism spectrum disorder showed less skin conductance responses overall. They also showed weaker correlations between skin conductance responses and frontal brain regions, including the anterior cingulate and anterior insular cortices. Additionally, skin conductance responses were found to have less contribution to default mode network connectivity in individuals with autism spectrum disorders relative to controls. These results suggest that autonomic processing is altered in autism spectrum disorders, which may be related to the abnormal socio-emotional behaviours that characterize this condition. PMID:24424916

  8. Abnormal Tc-99m-MDP/GA-67 scan patterns in association with active chronic osteomyelitis

    SciTech Connect

    Tumeh, S.S.; Aliabadi, P.; Weissman, B.; McNeil, B.J.

    1985-05-01

    In this study the authors reviewed data from 136 patients (pts) in order to refine the interpretive criteria used to diagnose active osteomyelitis (AOM) in patients with previous bone disease (e.g., old osteomyelitis, fractures, orthopedic devices excluding prostheses). They evaluated bone (Tc-99mMDP) and gallium 67 studies and obtained followup in all pts. AOM was diagnosed by surgery or biopsy and culture in 49 pts and was excluded by the same criteria in 16 pts. An additional 71 pts had the diagnosis excluded by followup clinical criteria. Five patterns were found. T1: abnormal Tc-99m-MDP, normal Ga-67. T2: diffuse increased uptake of both radiopharmaceuticals with Tc-99m-MDP greater than Ga-67. T3: different geographic distribution, but similar intensities of uptake of both. T4: very similar uptake and distribution of both. T5: Ga-67 exceeded Tc-99m-MDP. The authors conclude that T5 is diagnostic of AOM, T3 and T4 raise the probability of AOM than before scanning, T1 and T2 decrease it.

  9. The fungicide imazalil induces developmental abnormalities and alters locomotor activity during early developmental stages in zebrafish.

    PubMed

    Jin, Yuanxiang; Zhu, Zhihong; Wang, Yueyi; Yang, Enlu; Feng, Xiayan; Fu, Zhengwei

    2016-06-01

    The fungicide imazalil (IMZ) is used extensively to protect vegetable fields, fruit plantations and post-harvest crops from rot. Likely due to its wide-spread use, IMZ is frequently detected in vegetable, fruit, soil and even surface water samples. Even though several previous studies have reported on the neurotoxicity of IMZ, its effects on the neurobehavior of zebrafish have received little attention to date. In this study, we show that the heartbeat and hatchability of zebrafish were significantly influenced by IMZ concentrations of 300 μg L(-1) or higher. Moreover, in zebrafish larvae, locomotor behaviors such as average swimming speed and swimming distance were significantly decreased after exposure to 300 μg L(-1) IMZ for 96 h, and acetylcholinesterase (AChE) expression and activity were consistently inhibited in IMZ-treated fish. Our results further suggest that IMZ could act as a neuroendocrine disruptor by decreasing the expression of neurotoxicity-related genes such as Glial fibrillary acidic protein (Gfap), Myelin basic protein (Mbp) and Sonic hedgehog a (Shha) during early developmental stages of zebrafish. In conclusion, we show that exposure to IMZ has the potential to induce developmental toxicity and locomotor behavior abnormalities during zebrafish development. PMID:27035382

  10. Abnormal autonomic and associated brain activities during rest in autism spectrum disorder

    PubMed Central

    Eilam-Stock, Tehila; Xu, Pengfei; Cao, Miao; Gu, Xiaosi; Van Dam, Nicholas T.; Anagnostou, Evdokia; Kolevzon, Alexander; Soorya, Latha; Park, Yunsoo; Siller, Michael; He, Yong; Hof, Patrick R.

    2014-01-01

    Autism spectrum disorders are associated with social and emotional deficits, the aetiology of which are not well understood. A growing consensus is that the autonomic nervous system serves a key role in emotional processes, by providing physiological signals essential to subjective states. We hypothesized that altered autonomic processing is related to the socio-emotional deficits in autism spectrum disorders. Here, we investigated the relationship between non-specific skin conductance response, an objective index of sympathetic neural activity, and brain fluctuations during rest in high-functioning adults with autism spectrum disorder relative to neurotypical controls. Compared with control participants, individuals with autism spectrum disorder showed less skin conductance responses overall. They also showed weaker correlations between skin conductance responses and frontal brain regions, including the anterior cingulate and anterior insular cortices. Additionally, skin conductance responses were found to have less contribution to default mode network connectivity in individuals with autism spectrum disorders relative to controls. These results suggest that autonomic processing is altered in autism spectrum disorders, which may be related to the abnormal socio-emotional behaviours that characterize this condition. PMID:24424916

  11. Abnormal Ventral and Dorsal Attention Network Activity during Single and Dual Target Detection in Schizophrenia

    PubMed Central

    Jimenez, Amy M.; Lee, Junghee; Wynn, Jonathan K.; Cohen, Mark S.; Engel, Stephen A.; Glahn, David C.; Nuechterlein, Keith H.; Reavis, Eric A.; Green, Michael F.

    2016-01-01

    Early visual perception and attention are impaired in schizophrenia, and these deficits can be observed on target detection tasks. These tasks activate distinct ventral and dorsal brain networks which support stimulus-driven and goal-directed attention, respectively. We used single and dual target rapid serial visual presentation (RSVP) tasks during fMRI with an ROI approach to examine regions within these networks associated with target detection and the attentional blink (AB) in 21 schizophrenia outpatients and 25 healthy controls. In both tasks, letters were targets and numbers were distractors. For the dual target task, the second target (T2) was presented at three different lags after the first target (T1) (lag1 = 100 ms, lag3 = 300 ms, lag7 = 700ms). For both single and dual target tasks, patients identified fewer targets than controls. For the dual target task, both groups showed the expected AB effect with poorer performance at lag 3 than at lags 1 or 7, and there was no group by lag interaction. During the single target task, patients showed abnormally increased deactivation of the temporo-parietal junction (TPJ), a key region of the ventral network. When attention demands were increased during the dual target task, patients showed overactivation of the posterior intraparietal cortex, a key dorsal network region, along with failure to deactivate TPJ. Results suggest inefficient and faulty suppression of salience-oriented processing regions, resulting in increased sensitivity to stimuli in general, and difficulty distinguishing targets from non-targets. PMID:27014135

  12. Orexin A (hypocretin 1) injected into hypothalamic paraventricular nucleus and spontaneous physical activity in rats.

    PubMed

    Kiwaki, Kohji; Kotz, Catherine M; Wang, Chuanfeng; Lanningham-Foster, Lorraine; Levine, James A

    2004-04-01

    In humans, nonexercise activity thermogenesis (NEAT) increases with positive energy balance. The mediator of the interaction between positive energy balance and physical activity is unknown. In this study, we address the hypothesis that orexin A acts in the hypothalamic paraventricular nucleus (PVN) to increase nonfeeding-associated physical activity. PVN-cannulated rats were injected with either orexin A or vehicle during the light and dark cycle. Spontaneous physical activity (SPA) was measured using arrays of infrared activity sensors and night vision videotaped recording (VTR). O(2) consumption and CO(2) production were measured by indirect calorimetry. Feeding behavior was assessed by VTR. Regardless of the time point of injection, orexin A (1 nmol) was associated with dramatic increases in SPA for 2 h after injection (orexin A: 6.27 +/- 1.95 x 10(3) beam break count, n = 24; vehicle: 1.85 +/- 1.13 x 10(3), n = 38). This increase in SPA was accompanied by compatible increase in O(2) consumption. Duration of feeding was increased only when orexin A was injected in the early light phase and accounted for only 3.5 +/- 2.5% of the increased physical activity. In a dose-response experiment, increases in SPA were correlated with dose of orexin A linearly up to 2 nmol. PVN injections of orexin receptor antagonist SB-334867 were associated with decreases in SPA and attenuated the effects of PVN-injected orexin A. Thus orexin A can act in PVN to increase nonfeeding-associated physical activity, suggesting that this neuropeptide might be a mediator of NEAT. PMID:14656716

  13. Abnormal expression of plasminogen activator inhibitors in patients with gestational trophoblastic disease.

    PubMed Central

    Estellés, A.; Grancha, S.; Gilabert, J.; Thinnes, T.; Chirivella, M.; España, F.; Aznar, J.; Loskutoff, D. J.

    1996-01-01

    We previously reported significantly elevated levels of plasminogen activator inhibitor type 1 (PAI-1) in plasma and placenta from pregnant women with severe pre-eclampsia, and pre-eclampsia is a frequent problem in molar pregnancies. As increases in PAI-1 may contribute to the placental alterations that occur in pre-eclampsia, we have begun to investigate changes in PAI-1 as well as PAI-2 and several other components of the fibrinolytic system in patients with trophoblastic disease. Significant increases in plasma PAI-1 and decreases in plasma PAI-2 levels were observed in molar pregnancies when compared with the levels in normal pregnant women of similar gestational age. PAI-1 antigen levels also were increased, and PAI-2 levels were decreased in placenta from women with molar pregnancies compared with placenta obtained by spontaneous abortion. Immunohistochemical analysis revealed strong positive and specific staining of PAI-1 in trophoblastic epithelium in molar pregnancies and relatively weak staining of PAI-2. No association between the distribution of PAI-1 and vitronectin was found, and no specific signal for tissue type PA, urokinase type PA, tumor necrosis factor-alpha, or interleukin-1 was detected. In situ hybridization revealed an increase in PAI-1 but not PAI-2 mRNAs in placenta from molar pregnancies in comparison with placenta from abortions. These results demonstrate increased PAI-1 protein and mRNA in trophoblastic disease and suggest that localized elevated levels of PAI-1 may contribute to the hemostatic problems associated with this disorder. Images Figure 1 Figure 2 Figure 3 PMID:8863672

  14. Abnormal intrinsic brain activity patterns in leukoaraiosis with and without cognitive impairment.

    PubMed

    Li, Chuanming; Yang, Jun; Yin, Xuntao; Liu, Chen; Zhang, Lin; Zhang, Xiaochun; Gui, Li; Wang, Jian

    2015-10-01

    The amplitude of low frequency fluctuations (ALFF) from resting-state functional MRI (rs-fMRI) signals can be used to detect intrinsic spontaneous brain activity and provide valuable insights into the pathomechanism of neural disease. In this study, we recruited 56 patients who had been diagnosed as having mild to severe leukoaraiosis. According to the neuropsychological tests, they were subdivided into a leukoaraiosis with cognitive impairment group (n = 28) and a leukoaraiosis without cognitive impairment group (n = 28). 28 volunteers were included as normal controls. We found that the three groups showed significant differences in ALFF in the brain regions of the right inferior occipital gyrus (IOG_R), left middle temporal gyrus (MTG_L), left precuneus (Pcu_L), right superior frontal gyrus (SFG_R) and right superior occipital gyrus (SOG_R). Compared with normal controls, the leukoaraiosis without cognitive impairment group exhibited significantly increased ALFF in the IOG_R, Pcu_L, SFG_R and SOG_R. While compared with leukoaraiosis without cognitive impairment group, the leukoaraiosis with cognitive impairment group showed significantly decreased ALFF in IOG_R, MTG_L, Pcu_L and SOG_R. A close negative correlation was found between the ALFF values of the MTG_L and the Montreal Cognitive Assessment (MoCA) scores. Our data demonstrate that white matter integrity and cognitive impairment are associated with different amplitude fluctuations of rs-fMRI signals. Leukoaraiosis is related to ALFF increases in IOG_R, Pcu_L, SFG_Orb_R and SOG_R. Decreased ALFF in MTG_L is characteristic of cognitive impairment and may aid in its early detection. PMID:26116811

  15. Minimal model for spontaneous cell polarization and edge activity in oscillating, rotating and migrating cells

    NASA Astrophysics Data System (ADS)

    Raynaud, Franck; Ambühl, Mark E.; Gabella, Chiara; Bornert, Alicia; Sbalzarini, Ivo F.; Meister, Jean-Jacques; Verkhovsky, Alexander B.

    2016-04-01

    How cells break symmetry and organize activity at their edges to move directionally is a fundamental question in cell biology. Physical models of cell motility commonly incorporate gradients of regulatory proteins and/or feedback from the motion itself to describe the polarization of this edge activity. These approaches, however, fail to explain cell behaviour before the onset of polarization. We use polarizing and moving fish epidermal cells as a model system to bridge the gap between cell behaviours before and after polarization. Our analysis suggests a novel and simple principle of self-organizing cell activity, in which local cell-edge dynamics depends on the distance from the cell centre, but not on the orientation with respect to the front-back axis. We validate this principle with a stochastic model that faithfully reproduces a range of cell-migration behaviours. Our findings indicate that spontaneous polarization, persistent motion and cell shape are emergent properties of the local cell-edge dynamics controlled by the distance from the cell centre.

  16. Extended self: spontaneous activation of medial prefrontal cortex by objects that are 'mine'.

    PubMed

    Kim, Kyungmi; Johnson, Marcia K

    2014-07-01

    The concept of extended self refers to the idea that people incorporate self-relevant others or objects into one's sense of self. Initial neural support for the notion of extended self was provided by fMRI evidence that medial prefrontal cortex (MPFC) showed greater activation while people imagined objects belonging to them compared with someone else (Kim & Johnson, 2012). This study investigated whether self-associated objects (i.e. 'mine') subsequently engage MPFC spontaneously when a task does not require explicit self-referential judgments. During fMRI scanning, participants detected 'oddballs' (objects with a specific frame color) intermixed with objects participants had previously imagined belonging to them or to someone else and previously unseen non-oddball objects. There was greater activity in MPFC and posterior cingulate cortex for those 'self-owned' objects that participants were more successful at imagining owning compared with 'other-owned' objects. In addition, change in object preference following the ownership manipulation (a mere ownership effect) was predicted by activity in MPFC. Overall, these results provide neural evidence for the idea that personally relevant external stimuli may be incorporated into one's sense of self. PMID:23696692

  17. Spontaneous oscillations in a model for active control of microvessel diameters

    PubMed Central

    Arciero, J. C.; Secomb, T. W.

    2012-01-01

    A new theory is presented for the origin of spontaneous oscillations in blood vessel diameters that are observed experimentally in the microcirculation. These oscillations, known as vasomotion, involve time-varying contractions of the vascular smooth muscle in the walls of arterioles. It is shown that such oscillations can arise as a result of interactions between the mechanics of the vessel wall and the dynamics of the active contraction of smooth muscle cells in response to circumferential tension in the wall. A theoretical model is developed in which the diameter and the degree of activation in a vessel are dynamic variables. The model includes effects of wall shear stress and oxygen-dependent metabolic signals on smooth muscle activation and is applied to a single vessel and to simplified network structures. The model equations predict limit cycle oscillations for certain ranges of parameters such as wall shear stress, arterial pressure and oxygen consumption rate. Predicted characteristics of the oscillations, including their sensitivity to arterial pressure, are consistent with experimental observations. PMID:21525236

  18. Hypotensive and Angiotensin-Converting Enzyme Inhibitory Activities of Eisenia fetida Extract in Spontaneously Hypertensive Rats

    PubMed Central

    Mao, Shumei; Li, Chengde

    2015-01-01

    Objectives. This study aimed to investigate the antihypertensive effects of an Eisenia fetida extract (EFE) and its possible mechanisms in spontaneously hypertensive rats (SHR rats). Methods. Sixteen-week-old SHR rats and Wistar-Kyoto rats (WKY rats) were used in this study. Rats were, respectively, given EFE (EFE group), captopril (captopril group), or phosphate-buffered saline (PBS) (normal control group and SHR group) for 4 weeks. ACE inhibitory activity of EFE in vitro was determined. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured using a Rat Tail-Cuff Blood Pressure System. Levels of angiotensin II (Ang II), aldosterone (Ald), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1α) in plasma were determined by radioimmunoassay, and serum nitric oxide (NO) concentration was measured by Griess reagent systems. Results. EFE had marked ACE inhibitory activity in vitro (IC50 = 2.5 mg/mL). After the 4-week drug management, SHR rats in EFE group and in captopril group had lower SBP and DBP, lower levels of Ang II and Ald, and higher levels of 6-keto-PGF1α and NO than the SHR rats in SHR group. Conclusion. These results indicate that EFE has hypotensive effects in SHR rats and its effects might be associated with its ACE inhibitory activity. PMID:26798397

  19. The origin of spontaneous electrical activity at the end-plate zone.

    PubMed

    Brown, W F; Varkey, G P

    1981-12-01

    Two types of spontaneous electrical activity are present at the end-plate zone: low-voltage negative potentials that correspond to miniature end-plate potentials, and larger voltage negative-positive potentials. The electrogenic origin of the latter has been uncertain. The origin of these larger potentials was investigated in the rat phrenic nerve diaphragm preparation and in human gastrocnemius muscle just prior to intubation during administration of preoperative anesthesia. In the hemidiaphragm the larger voltage negative-positive potentials were rarely triggered by intracellular or tungsten microelectrodes. The negative-positive potentials, however, were clearly triggered by contact of the concentric needle electrode with muscle hemidiaphragm at the end-plate region. The potentials were abolished by curare. Likewise, the equivalent potentials observed at the human gastrocnemius end-plate zone were blocked by neuromuscular blocking agents. Therefore, these positive-negative discharges represent postsynaptic muscle fiber action potentials and not nerve fiber activity. They were probably presynaptically activated by mechanical irritation of the motor axon terminal and preterminal branches. PMID:6275771

  20. Structure and hypotensive activity relationships of tetrandrine derivatives in stroke-prone spontaneously hypertensive rats.

    PubMed

    Kawashima, K; Hayakawa, T; Miwa, Y; Oohata, H; Suzuki, T; Fujimoto, K; Ogino, T; Chen, Z X

    1990-01-01

    1. Structure and hypotensive activity relationships of tetrandrine (TD), an alkaloid isolated from the Chinese herb Radix stephaniae tetrandrae and its derivatives were investigated in conscious stroke-prone spontaneously hypertensive rats (SHRSP). 2. Derivatives substituted at the 7-O position with various types of alkyl group produced varying degrees of hypotensive effect. 3. While the demethylated derivative, fangchinoline (FC), and its acetylated compound had no effect on blood pressure, 7-O-methyl FC (TD), and 7-O-ethyl and 7-O-isopropyl FC at oral doses of 25 and 50 mg/kg produced a gradual and sustained hypotensive effect without any significant effects on heart rate and plasma renin concentration. 4. Substitution at the 7-O position with longer side chains such as n-propyl, n-butyl and n-pentyl groups reduced both the degree and duration of hypotensive activity. 5. Substitution of N-methyl groups at the 2 and 2' positions with quaternary ammonium or N-oxide attenuated the hypotensive activity. 6. The results of this study suggest a possibility that 7-O-ethyl and 7-O-isopropyl derivatives as well as TD can be considered as potential antihypertensive drugs because of the gradual onset and long duration of their hypotensive action in SHRSP. PMID:2187737

  1. Influence of ovariohysterectomy and deslorelin acetate on the spontaneous activity of the rabbit urinary bladder in vitro.

    PubMed

    Bujok, Jolanta; Wincewicz, Edyta; Czerski, Albert; Zawadzki, Wojciech

    2016-02-01

    Lower urinary tract symptoms are not only a serious health problem but also a substantial sociologic issue affecting human beings and companion animals. Estrogen deficiency is considered an etiologic factor of urinary incontinence in postmenopausal women and spayed female dogs. However, insufficient effectiveness of hormonal therapy has caused an intensive search for new therapeutic options. GnRH analogs have positive clinical effects in neutered female dogs suffering from incontinence, but the mechanism of action is not known. The aim of our study was to determine the effect of long-acting deslorelin acetate on the spontaneous activity of urinary bladder sections from a rabbit model of long-term estrogen deprivation. The study was conducted on 21 female New Zealand White rabbits divided into the following groups: control group, ovariohysterectomized (OHX) group, and ovariohysterectomized group given a deslorelin acetate implant. Urinary bladders were excised immediately after sacrifice, and the spontaneous activity of dorsal and ventral strips of the bladder body was examined in organ bath chambers. The amplitude and frequency of the spontaneous contractions were evaluated. Most of the sections developed spontaneous activity. Ovariohysterectomy caused a decrease in the amplitude of spontaneous contractions of the tissues obtained only from the dorsal part of the bladder body. After OHX, the frequency was higher compared with the control group in both parts of the bladder. Deslorelin acetate did not significantly affect the spontaneous contraction amplitude but caused a decrease in the frequency in the dorsal and ventral parts of the bladder. In conclusion, long-term changes in the levels of hormones and other regulatory substances associated with the reproductive system are related to altered spontaneous activity of the urinary bladder, which may impact the symptoms of urgency and incontinence appearing in women after menopause and in female animals after

  2. Solvent-free synthesis, coating and morphogenesis of conductive polymer materials through spontaneous generation of activated monomers.

    PubMed

    Muramatsu, Ryo; Oaki, Yuya; Kuwabara, Kento; Hayashi, Kosei; Imai, Hiroaki

    2014-10-14

    Synthesis, coating, and morphogenesis of conductive polymers were achieved on a variety of substrates through spontaneous generation of activated monomer vapors under ambient pressure and low temperature conditions. The present approach facilitates the generation of complex hierarchical morphologies and the conductive coating for improvement of electrochemical properties. PMID:25145680

  3. On-off intermittency in time series of spontaneous paroxysmal activity in rats with genetic absence epilepsy

    SciTech Connect

    Hramov, Alexander; Koronovskii, Alexey A.; Midzyanovskaya, I.S.; Sitnikova, E.; Rijn, C.M. van

    2006-12-15

    In the present paper we consider the on-off intermittency phenomena observed in time series of spontaneous paroxysmal activity in rats with genetic absence epilepsy. The method to register and analyze the electroencephalogram with the help of continuous wavelet transform is also suggested.

  4. Long-term effects of barbital on spontaneous activity of rats trained to use the drug as a discriminative stimulus.

    PubMed

    York, J L; Winter, J C

    1975-04-30

    This investigation sought to determine if the discriminative stimulus properties of barbital are reflected in the pattern of spontaneous motor activity induced by the drug. Rats were trained in a Skinner box to discriminate the effects of sodium barbital (80 mg/kg), injected 60 min prior to training, from those of saline. Half of the animals (Group I) were taught the drug discrimination by rewarding them for bar pressing only when they were in the drug condition. The other half of the animals (Group II) were rewarded only in the absence of the effects of barbital. Spontaneous motor activity was monitored during the 20 min period from 40--60 min after injection of the drug or saline. After several months of drug discrimination training, the patterns of spontaneous activity displayed by all animals suggested that the treatments had become conditioned to signal the forthcoming availability or non-availability of food in the Skinner box. The data also suggested that chronic exposure to barbital may induced adaptations which allowed the drug to increase spontaneous motor activity. PMID:1153621

  5. Abnormal activation of calpain and protein kinase Cα promotes a constitutive release of matrix metalloproteinase 9 in peripheral blood mononuclear cells from cystic fibrosis patients.

    PubMed

    Averna, Monica; Bavestrello, Margherita; Cresta, Federico; Pedrazzi, Marco; De Tullio, Roberta; Minicucci, Laura; Sparatore, Bianca; Salamino, Franca; Pontremoli, Sandro; Melloni, Edon

    2016-08-15

    Matrix metalloproteinase 9 (MMP9) is physiologically involved in remodeling the extracellular matrix components but its abnormal release has been observed in several human pathologies. We here report that peripheral blood mononuclear cells (PBMCs), isolated from cystic fibrosis (CF) patients homozygous for F508del-cystic fibrosis transmembrane conductance regulator (CFTR), express constitutively and release at high rate MMP9 due to the alteration in their intracellular Ca(2+) homeostasis. This spontaneous and sustained MMP9 secretion may contribute to the accumulation of this protease in fluids of CF patients. Conversely, in PBMCs isolated from healthy donors, expression and secretion of MMP9 are undetectable but can be evoked, after 12 h of culture, by paracrine stimulation which also promotes an increase in [Ca(2+)]i. We also demonstrate that in both CF and control PBMCs the Ca(2+)-dependent MMP9 secretion is mediated by the concomitant activation of calpain and protein kinase Cα (PKCα), and that MMP9 expression involves extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) phosphorylation. Our results are supported by the fact that either the inhibition of Ca(2+) entry or chelation of [Ca(2+)]i as well as the inhibition of single components of the signaling pathway or the restoration of CFTR activity all promote the reduction of MMP9 secretion. PMID:27349634

  6. An active oscillator model describes the statistics of spontaneous otoacoustic emissions.

    PubMed

    Fruth, Florian; Jülicher, Frank; Lindner, Benjamin

    2014-08-19

    Even in the absence of external stimulation, the cochleas of most humans emit very faint sounds below the threshold of hearing, sounds that are known as spontaneous otoacoustic emissions. They are a signature of the active amplification mechanism in the cochlea. Emissions occur at frequencies that are unique for an individual and change little over time. The statistics of a population of ears exhibit characteristic features such as a preferred relative frequency distance between emissions (interemission intervals). We propose a simplified cochlea model comprising an array of active nonlinear oscillators coupled both hydrodynamically and viscoelastically. The oscillators are subject to a weak spatial disorder that lends individuality to the simulated cochlea. Our model captures basic statistical features of the emissions: distributions of 1), emission frequencies; 2), number of emissions per ear; and 3), interemission intervals. In addition, the model reproduces systematic changes of the interemission intervals with frequency. We show that the mechanism for the preferred interemission interval in our model is the occurrence of synchronized clusters of oscillators. PMID:25140416

  7. Modeling spontaneous activity across an excitable epithelium: Support for a coordination scenario of early neural evolution

    PubMed Central

    de Wiljes, Oltman O.; van Elburg, Ronald A. J.; Biehl, Michael; Keijzer, Fred A.

    2015-01-01

    Internal coordination models hold that early nervous systems evolved in the first place to coordinate internal activity at a multicellular level, most notably the use of multicellular contractility as an effector for motility. A recent example of such a model, the skin brain thesis, suggests that excitable epithelia using chemical signaling are a potential candidate as a nervous system precursor. We developed a computational model and a measure for whole body coordination to investigate the coordinative properties of such excitable epithelia. Using this measure we show that excitable epithelia can spontaneously exhibit body-scale patterns of activation. Relevant factors determining the extent of patterning are the noise level for exocytosis, relative body dimensions, and body size. In smaller bodies whole-body coordination emerges from cellular excitability and bidirectional excitatory transmission alone. Our results show that basic internal coordination as proposed by the skin brain thesis could have arisen in this potential nervous system precursor, supporting that this configuration may have played a role as a proto-neural system and requires further investigation. PMID:26441620

  8. Pharmacological evidence of hypotensive activity of Marrubium vulgare and Foeniculum vulgare in spontaneously hypertensive rat.

    PubMed

    El Bardai, S; Lyoussi, B; Wibo, M; Morel, N

    2001-05-01

    The hypotensive effects of the water extract of Marrubium vulgare L. and Foeniculum vulgare L. were investigated in spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto rats (WKY). Oral administration of Marrubium or Foeniculum extract lowered the systolic blood pressure of SHR but not of WKY. In SHR, Foeniculum but not Marrubium treatment increased water, sodium and potassium excretion. Ex vivo as well as in vitro, Marrubium extract inhibited the contractile responses of rat aorta to noradrenaline and to KCl (100 mM). Inhibition was greater in aorta from SHR compared to WKY and was not affected by the NO synthase inhibitor N-nitro-L-arginine. Vascular effects of Foeniculum extract were less pronounced than those of Marrubium and were blocked by N-nitro-L-arginine. These results indicate that hypotensive activity of Marrubium and Foeniculum extracts seems to be mediated through different pathways: Foeniculum appeared to act mainly as a diuretic and a natriuretic while Marrubium displayed vascular relaxant activity. PMID:11349824

  9. Exploring the spectrum of dynamical regimes and timescales in spontaneous cortical activity.

    PubMed

    Mattia, Maurizio; Sanchez-Vives, Maria V

    2012-06-01

    Rhythms at slow (<1 Hz) frequency of alternating Up and Down states occur during slow-wave sleep states, under deep anaesthesia and in cortical slices of mammals maintained in vitro. Such spontaneous oscillations result from the interplay between network reverberations nonlinearly sustained by a strong synaptic coupling and a fatigue mechanism inhibiting the neurons firing in an activity-dependent manner. Varying pharmacologically the excitability level of brain slices we exploit the network dynamics underlying slow rhythms, uncovering an intrinsic anticorrelation between Up and Down state durations. Besides, a non-monotonic change of Down state duration is also observed, which shrinks the distribution of the accessible frequencies of the slow rhythms. Attractor dynamics with activity-dependent self-inhibition predicts a similar trend even when the system excitability is reduced, because of a stability loss of Up and Down states. Hence, such cortical rhythms tend to display a maximal size of the distribution of Up/Down frequencies, envisaging the location of the system dynamics on a critical boundary of the parameter space. This would be an optimal solution for the system in order to display a wide spectrum of dynamical regimes and timescales. PMID:23730355

  10. An Active Oscillator Model Describes the Statistics of Spontaneous Otoacoustic Emissions

    PubMed Central

    Fruth, Florian; Jülicher, Frank; Lindner, Benjamin

    2014-01-01

    Even in the absence of external stimulation, the cochleas of most humans emit very faint sounds below the threshold of hearing, sounds that are known as spontaneous otoacoustic emissions. They are a signature of the active amplification mechanism in the cochlea. Emissions occur at frequencies that are unique for an individual and change little over time. The statistics of a population of ears exhibit characteristic features such as a preferred relative frequency distance between emissions (interemission intervals). We propose a simplified cochlea model comprising an array of active nonlinear oscillators coupled both hydrodynamically and viscoelastically. The oscillators are subject to a weak spatial disorder that lends individuality to the simulated cochlea. Our model captures basic statistical features of the emissions: distributions of 1), emission frequencies; 2), number of emissions per ear; and 3), interemission intervals. In addition, the model reproduces systematic changes of the interemission intervals with frequency. We show that the mechanism for the preferred interemission interval in our model is the occurrence of synchronized clusters of oscillators. PMID:25140416

  11. Beyond blow-up in excitatory integrate and fire neuronal networks: Refractory period and spontaneous activity.

    PubMed

    Cáceres, María J; Perthame, Benoît

    2014-06-01

    The Network Noisy Leaky Integrate and Fire equation is among the simplest model allowing for a self-consistent description of neural networks and gives a rule to determine the probability to find a neuron at the potential v. However, its mathematical structure is still poorly understood and, concerning its solutions, very few results are available. In the midst of them, a recent result shows blow-up in finite time for fully excitatory networks. The intuitive explanation is that each firing neuron induces a discharge of the others; thus increases the activity and consequently the discharge rate of the full network. In order to better understand the details of the phenomena and show that the equation is more complex and fruitful than expected, we analyze further the model. We extend the finite time blow-up result to the case when neurons, after firing, enter a refractory state for a given period of time. We also show that spontaneous activity may occur when, additionally, randomness is included on the firing potential VF in regimes where blow-up occurs for a fixed value of VF. PMID:24533963

  12. Short-term modulation of cerebellar Purkinje cell activity after spontaneous climbing fiber input.

    PubMed

    Sato, Y; Miura, A; Fushiki, H; Kawasaki, T

    1992-12-01

    1. There are two opposite points of view concerning the way climbing fiber input in a Purkinje cell modifies simple spike (SS) activity transiently: depression versus enhancement of SS activity. The different groups of investigators favored one effect predominating over the other. In the decerebrate unanesthetized cat, we recorded spontaneous activity of single Purkinje cells and investigated time course of SS activity after the complex spike (CS). 2. In the peri-CS time histogram, there was a SS pause lasting, on average, 10.8 ms after onset of the CS in all of the 316 cells recorded. The pause was followed by a rapid increase in SS activity to a maximum, which was on average 175.6% of a pre-CS control level, and a gradual return to around the control level in the majority of the cells recorded (pause-facilitation type, 71.2%). The increase in SS activity was significant (P < 0.01, t test) during 20-100 ms. The SS activity during the 20-100 ms was, on average, 163.7% of the control level. In some cells (pure-pause type, 25.3%), no significant changes were found (P > 0.01) in the post-pause SS firing. In contrast, only 3.5% of the cells (pause-reduction type) showed a significant (P < 0.01) firing decrease (average 54.0% of the control level) lasting 20-60 ms after the pause period. 3. Analysis of the pre-CS time histogram revealed no significant differences (P > 0.01) in the SS activity between pre-CS periods in all of the cells recorded, suggesting that the SS activity enhancement is not due to a coactivated mossy fiber input just preceding the activation of the climbing fiber input. 4. Analysis of the raster diagram revealed variability of individual SS responses after the CS. The probability of occurrence of the increase in SS number during a post-CS period of 0-100 ms with respect to that during a pre-CS period of -100-0 ms in individual raster traces was high (on average 78.2%), medium (57.3%), and low (36.3%) in the pause-facilitation, pure-pause, and pause

  13. Cerebral cortical neurons with activity linked to central neurogenic spontaneous and evoked elevations in cerebral blood flow

    NASA Technical Reports Server (NTRS)

    Golanov, E. V.; Reis, D. J.

    1996-01-01

    We recorded neurons in rat cerebral cortex with activity relating to the neurogenic elevations in regional cerebral blood flow (rCBF) coupled to stereotyped bursts of EEG activity, burst-cerebrovascular wave complexes, appearing spontaneously or evoked by electrical stimulation of rostral ventrolateral medulla (RVL) or fastigial nucleus (FN). Of 333 spontaneously active neurons only 15 (5%), in layers 5-6, consistently (P < 0.05, chi-square) increased their activity during the earliest potential of the complex, approximately 1.3 s before the rise of rCBF, and during the minutes-long elevation of rCBF elicited by 10 s of stimulation of RVL or FN. The results indicate the presence of a small population of neurons in deep cortical laminae whose activity correlates with neurogenic elevations of rCBF. These neurons may function to transduce afferent neuronal signals into vasodilation.

  14. A multimodal assessment of melanin and melanocyte activity in abnormally pigmented hypertrophic scar.

    PubMed

    Travis, Taryn E; Ghassemi, Pejhman; Ramella-Roman, Jessica C; Prindeze, Nicholas J; Paul, Dereck W; Moffatt, Lauren T; Jordan, Marion H; Shupp, Jeffrey W

    2015-01-01

    Using a validated swine model of human scar formation, hyperpigmented and hypopigmented scar samples were examined for their histological and optical properties to help elucidate the mechanisms and characteristics of dyspigmentation. Full-thickness wounds were created on the flanks of red Duroc pigs and allowed to heal. Biopsies from areas of hyperpigmentation, hypopigmentation, and uninjured tissue were fixed and embedded for histological examination using Azure B and primary antibodies to S100B, HMB45, and α-melanocyte-stimulating hormone (α-MSH). Spatial frequency domain imaging (SFDI) was then used to examine the optical properties of scars. Hyperpigmentation was first noticeable in healing wounds around weeks 2 to 3, gradually becoming darker. There was no significant difference in S100B staining for the presence of melanocytes between hyperpigmented and hypopigmented scar samples. Azure B staining of melanin was significantly greater in histological sections from hyperpigmented areas than in sections from both uninjured skin and hypopigmented scar (P < .0001). There was significantly greater staining for α-MSH in hyperpigmented samples compared with hypopigmented samples (P = .0121), and HMB45 staining was positive for melanocytes in hyperpigmented scar. SFDI at a wavelength of 632 nm resulted in an absorption coefficient map correlating with visibly hyperpigmented areas of scars. In a red Duroc model of hypertrophic scar formation, melanocyte number is similar in hyperpigmented and hypopigmented tissues. Hyperpigmented tissues, however, show a greater amount of melanin and α-MSH, along with immunohistochemical evidence of stimulated melanocytes. These observations encourage further investigation of melanocyte stimulation and the inflammatory environment within a wound that may influence melanocyte activity. Additionally, SFDI can be used to identify areas of melanin content in mature, pigmented scars, which may lead to its usefulness in wounds at earlier

  15. Sources of abnormal EEG activity in the presence of brain lesions.

    PubMed

    Fernández-Bouzas, A; Harmony, T; Bosch, J; Aubert, E; Fernández, T; Valdés, P; Silva, J; Marosi, E; Martínez-López, M; Casián, G

    1999-04-01

    In routine clinical EEG, a common origin is assumed for delta and theta rhythms produced by brain lesions. In previous papers, we have provided some experimental support, based on High Resolution qEEG and dipole fitting in the frequency domain, for the hypothesis that delta and theta spectral power have independent origins related to lesion and edema respectively. This paper describes the results obtained with Frequency Domain VARETA (FD-VARETA) in a group of 13 patients with cortical space-occupying lesions, in order to: 1) Test the accuracy of FD-VARETA for the localization of brain lesions, and 2) To provide further support for the independent origin of delta and theta components. FD VARETA is a distributed inverse solution, constrained by the Montreal Neurological Institute probabilistic atlas that estimates the spectra of EEG sources. In all patients, logarithmic transformed source spectra were compared with age-matched normative values, defining the Z source spectrum. Maximum Z values were found in 10 patients within the delta band (1.56 to 3.12 Hz); the spatial extent of these sources in the atlas corresponded with the location of the tumors in the CT. In 2 patients with small metastases and large volumes of edema and in a patient showing only edema, maximum Z values were found between 4.29 and 5.12 Hz. The spatial extent of the sources at these frequencies was within the volume of the edema in the CT. These results provided strong support to the hypothesis that both delta and theta abnormal EEG activities are the counterparts of two different pathophysiological processes. PMID:10358783

  16. Altered spontaneous brain activity patterns in patients with unilateral acute open globe injury using amplitude of low-frequency fluctuation: a functional magnetic resonance imaging study

    PubMed Central

    Tan, Gang; Huang, Xin; Ye, Lei; Wu, An-Hua; He, Li-Xian; Zhong, Yu-Lin; Jiang, Nan; Zhou, Fu-Qing; Shao, Yi

    2016-01-01

    Objective The aim of this study was to evaluate altered spontaneous brain activities in patients with unilateral acute open globe injury (OGI) using amplitude of low-frequency fluctuation (ALFF) method and its relationship with their clinical manifestations. Patients and methods A total of 18 patients with acute OGI (16 males and two females) and 18 healthy controls (HCs, 16 males and two females) closely matched in age, sex, and education were recruited in this study. The ALFF method was used to evaluate the altered spontaneous brain activities. The relationships between the mean ALFF signal values of different brain regions and the clinical features were evaluated by correlation analysis. Acute OGI patients were distinguished from HCs by receiver operating characteristic curve. Results Compared with HCs, acute OGI patients had significantly higher ALFF values in the left cuneus, left middle cingulum cortex, and bilateral precuneus. Furthermore, the age of OGI patients showed a negative correlation with the ALFF signal value of the left middle cingulum cortex (r=−0.557, P=0.016) and a negative correlation with the mean ALFF signal value of the bilateral precuneus (r=−0.746, P<0.001). The ALFF signal value of the bilateral precuneus was negatively correlated with the duration of OGI (r=−0.493, P=0.038) and positively correlated with the vision acuity of the injured eye (r=0.583, P=0.011). Conclusion Acute OGI mainly induces dysfunction in the left cuneus, left middle cingulum cortex, and bilateral precuneus, which may reflect the underlying pathologic mechanisms of abnormal brain activities in OGI patients. PMID:27570455

  17. Spontaneous locomotor activity in late-stage chicken embryos is modified by stretch of leg muscles.

    PubMed

    Bradley, Nina S; Ryu, Young U; Yeseta, Marie C

    2014-03-15

    Chicks initiate bilateral alternating steps several days before hatching and adaptively walk within hours of hatching, but emergence of precocious walking skills is not well understood. One of our aims was to determine whether interactions between environment and movement experience prior to hatching are instrumental in establishing precocious motor skills. However, physiological evidence of proprioceptor development in the chick has yet to be established; thus, one goal of this study was to determine when in embryogenesis proprioception circuits can code changes in muscle length. A second goal was to determine whether proprioception circuits can modulate leg muscle activity during repetitive limb movements for stepping (RLMs). We hypothesized that proprioception circuits code changes in muscle length and/or tension, and modulate locomotor circuits producing RLMs in anticipation of adaptive locomotion at hatching. To this end, leg muscle activity and kinematics were recorded in embryos during normal posture and after fitting one ankle with a restraint that supported the limb in an atypical posture. We tested the hypotheses by comparing leg muscle activity during spontaneous RLMs in control posture and ankle extension restraint. The results indicated that proprioceptors detect changes in muscle length and/or muscle tension 3 days before hatching. Ankle extension restraint produced autogenic excitation of the ankle flexor and reciprocal inhibition of the ankle extensor. Restraint also modified knee extensor activity during RLMs 1 day before hatching. We consider the strengths and limitations of these results and propose that proprioception contributes to precocious locomotor development during the final 3 days before hatching. PMID:24265423

  18. Spontaneously hypertensive rats display reduced microglial activation in response to ischemic stroke and lipopolysaccharide

    PubMed Central

    2012-01-01

    Background For successful translation to clinical stroke studies, the Stroke Therapy Academic Industry Round Table criteria have been proposed. Two important criteria are testing of therapeutic interventions in conscious animals and the presence of a co-morbidity factor. We chose to work with hypertensive rats since hypertension is an important modifiable risk factor for stroke and influences the clinical outcome. We aimed to compare the susceptibility to ischemia in hypertensive rats with those in normotensive controls in a rat model for induction of ischemic stroke in conscious animals. Methods The vasoconstrictor endothelin-1 was stereotactically applied in the vicinity of the middle cerebral artery of control Wistar Kyoto rats (WKYRs) and Spontaneously Hypertensive rats (SHRs) to induce a transient decrease in striatal blood flow, which was measured by the Laser Doppler technique. Infarct size was assessed histologically by Cresyl Violet staining. Sensory-motor functions were measured at several time points using the Neurological Deficit Score. Activation of microglia and astrocytes in the striatum and cortex was investigated by immunohistochemistry using antibodies against CD68/Iba-1 and glial fibrillary acidic protein. Results and conclusions The SHRs showed significantly larger infarct volumes and more pronounced sensory-motor deficits, compared to the WKYRs at 24 h after the insult. However, both differences disappeared between 24 and 72 h. In SHRs, microglia were less susceptible to activation by lipopolysaccharide and there was a reduced microglial activation after induction of ischemic stroke. These quantitative and qualitative differences may be relevant for studying the efficacy of new treatments for stroke in accordance to the Stroke Therapy Academic Industry Round Table criteria. PMID:22647642

  19. Role of spontaneous physical activity in prediction of susceptibility to activity based anorexia in male and female rats

    PubMed Central

    Perez-Leighton, Claudio; Grace, Martha; Billington, Charles J.; Kotz, Catherine M.

    2015-01-01

    Anorexia nervosa (AN) is a chronic eating disorder affecting females and males, defined by body weight loss, higher physical activity levels and restricted food intake. Currently, the commonalities and differences between genders in etiology of AN are not well understood. Animal models of AN, such as activity-based anorexia (ABA), can be helpful in identifying factors determining individual susceptibility to AN. In ABA, rodents are given an access to a running wheel while food restricted, resulting in paradoxical increased physical activity levels and weight loss. Recent studies suggest that different behavioral traits, including voluntary exercise, can predict individual weight loss in ABA. A higher inherent drive for movement can promote development and severity of AN, but this hypothesis remains untested. In rodents and humans, drive for movement is defined as spontaneous physical activity (SPA), which is time spent in low-intensity, non-volitional movements. In this paper, we show that a profile of body weight history and behavioral traits, including SPA, can predict individual weight loss caused by ABA in male and female rats with high accuracy. Analysis of the influence of SPA on ABA susceptibility in males and females rats suggests that either high or low levels of SPA increase the probability of high weight loss in ABA, but with larger effects in males compared to females. These results suggest the same behavioral profile can identify individuals at-risk of AN for both male and female populations and that SPA has predictive value for susceptibility to AN. PMID:24912135

  20. Analysis of spontaneous MEG activity in patients with Alzheimer's disease using spectral entropies.

    PubMed

    Poza, Jesús; Hornero, Roberto; Abásolo, Daniel; Fernández, Alberto; Escudero, Javier

    2007-01-01

    The aim of this study was to explore the ability of several spectral entropies to discriminate between spontaneous magnetoencephalographic (MEG) oscillations from 20 Alzheimer's disease (AD) patients and 21 controls. Hence, the relative spectral power (RSP) in classical frequency bands was calculated from the averaged power spectral density. Given the fact that the RSP can be viewed as a probability distribution function, the Shannon spectral entropy, Tsallis spectral entropy, generalized escort-Tsallis spectral entropy and Rényi spectral entropy were calculated from the RSP. Significant differences for each parameter were assessed with Mann-Whitney U test, whereas classification performance was studied using binary logistic regression. Results revealed an increase in the RSP of control subjects at beta and gamma bands, while AD patients showed an increase in the RSP values at delta and theta bands. Entropies obtained statistically significant lower values for AD patients than for controls. This issue suggests a significant decrease in irregularity of AD patients' MEG activity. PMID:18003432

  1. Sculpting the Intrinsic Modular Organization of Spontaneous Brain Activity by Art

    PubMed Central

    Lin, Chia-Shu; Liu, Yong; Huang, Wei-Yuan; Lu, Chia-Feng; Teng, Shin; Ju, Tzong-Ching; He, Yong; Wu, Yu-Te; Jiang, Tianzi; Hsieh, Jen-Chuen

    2013-01-01

    Artistic training is a complex learning that requires the meticulous orchestration of sophisticated polysensory, motor, cognitive, and emotional elements of mental capacity to harvest an aesthetic creation. In this study, we investigated the architecture of the resting-state functional connectivity networks from professional painters, dancers and pianists. Using a graph-based network analysis, we focused on the art-related changes of modular organization and functional hubs in the resting-state functional connectivity network. We report that the brain architecture of artists consists of a hierarchical modular organization where art-unique and artistic form-specific brain states collectively mirror the mind states of virtuosos. We show that even in the resting state, this type of extraordinary and long-lasting training can macroscopically imprint a neural network system of spontaneous activity in which the related brain regions become functionally and topologically modularized in both domain-general and domain-specific manners. The attuned modularity reflects a resilient plasticity nurtured by long-term experience. PMID:23840527

  2. Visual Learning Alters the Spontaneous Activity of the Resting Human Brain: An fNIRS Study

    PubMed Central

    Niu, Haijing; Li, Hao; Sun, Li; Su, Yongming; Huang, Jing; Song, Yan

    2014-01-01

    Resting-state functional connectivity (RSFC) has been widely used to investigate spontaneous brain activity that exhibits correlated fluctuations. RSFC has been found to be changed along the developmental course and after learning. Here, we investigated whether and how visual learning modified the resting oxygenated hemoglobin (HbO) functional brain connectivity by using functional near-infrared spectroscopy (fNIRS). We demonstrate that after five days of training on an orientation discrimination task constrained to the right visual field, resting HbO functional connectivity and directed mutual interaction between high-level visual cortex and frontal/central areas involved in the top-down control were significantly modified. Moreover, these changes, which correlated with the degree of perceptual learning, were not limited to the trained left visual cortex. We conclude that the resting oxygenated hemoglobin functional connectivity could be used as a predictor of visual learning, supporting the involvement of high-level visual cortex and the involvement of frontal/central cortex during visual perceptual learning. PMID:25243168

  3. Interval shifts in basophil measures correlate with disease activity in chronic spontaneous urticaria.

    PubMed

    Oliver, E T; Sterba, P M; Saini, S S

    2015-05-01

    Chronic spontaneous urticaria (CSU) significantly impacts the quality of life of those affected through symptoms of pruritus and recurrent skin lesions. In active CSU disease, reduced IgE-mediated basophil histamine release (HR) and basopenia are observed. We sought to examine the relationship between interval changes in basophil measures and shifts in patient-reported disease impairment. Simultaneous symptom and basophil evaluations were completed at two sequential study visits, and interval changes in measures were compared between visits for each subject (n = 38). These measures included Skindex-29, current itch and hives scores, total leukocyte histamine content (an indirect measure of blood basophil presence), and basophil HR in response to anti-IgE and formyl-methionine-leucine-phenylalanine. Overall, interval improvements in disease measures in CSU subjects were associated with increased basophil numbers (total leukocyte histamine content) and IgE-mediated HR. This suggests these measures are potential biomarkers for CSU disease improvement and further implicates a role for basophils in CSU. PMID:25631394

  4. Linking inter-individual differences in the perceptual load effect to spontaneous brain activity

    PubMed Central

    Liu, Lu; Tan, Jinfeng; Chen, Antao

    2015-01-01

    Previous researches have widely demonstrated that the interference from peripheral distractor will decrease when the task load is high. However, no study to date has paid attention to the individual differences in perceptual load effect (PLE) and little is known of spontaneous brain activity associated with PLE during resting state. To investigate this issue, we used resting-state functional Magnetic Resonance Imaging (fMRI) to examine the relationship between the amplitude of low-frequency fluctuations (ALFFs) and PLE. The results showed that there were large individual differences in PLE and we found PLE was significantly associated with ALFFs in left inferior temporal gyrus (ITG) and left precentral/postcentral gyrus. The present study suggested that the PLE was measurable, and there were individual differences in this effect. Moreover, these results implicated that: 1) mutual competition for limited capacity, which is involved in visual attention, and 2) response control that is included in behavior response both may contribute to the modulation induced by perceptual load. PMID:26257628

  5. Spontaneous brain activity following fear reminder of fear conditioning by using resting-state functional MRI

    PubMed Central

    Feng, Pan; Zheng, Yong; Feng, Tingyong

    2015-01-01

    Although disrupting reconsolidation may be a promising approach to attenuate or erase the expression of fear memory, it is not clear how the neural state following fear reminder contribute to the following fear extinction. To address this question, we used resting-state functional magnetic resonance imaging (rs-fMRI) to measure spontaneous neuronal activity and functional connectivity (RSFC) following fear reminder. Some brain regions such as dorsal anterior cingulate (dACC) and ventromedial prefrontal cortex (vmPFC) showed increased amplitude of LFF (ALFF) in the fear reminder group than the no reminder group following fear reminder. More importantly, there was much stronger functional connectivity between the amygdala and vmPFC in the fear reminder group than those in the no reminder group. These findings suggest that the strong functional connectivity between vmPFC and amygdala following a fear reminder could serve as a key role in the followed-up fear extinction stages, which may contribute to the erasing of fear memory. PMID:26576733

  6. A system for the determination of planar force vectors from spontaneously active chicken embryos.

    PubMed

    Sharp, Andrew A; Cain, Blake W; Pakiraih, Joanna; Williams, James L

    2014-11-01

    Generally, a combination of kinematic, electromyographic (EMG), and force measurements are used to understand how an organism generates and controls movement. The chicken embryo has been a very useful model system for understanding the early stages of embryonic motility in vertebrates. Unfortunately, the size and delicate nature of embryos makes studies of motility during embryogenesis very challenging. Both kinematic and EMG recordings have been achieved in embryonic chickens, but two-dimensional force vector recordings have not. Here, we describe a dual-axis system for measuring force generated by the leg of embryonic chickens. The system employs two strain gauges to measure planar forces oriented with the plane of motion of the leg. This system responds to forces according to the principles of Pythagorean geometry, which allows a simple computational program to determine the force vector (magnitude and direction) generated during spontaneous motor activity. The system is able to determine force vectors for forces >0.5 mN accurately and allows for simultaneous kinematic and EMG recordings. This sensitivity is sufficient for force vector measurements encompassing most embryonic leg movements in midstage chicken embryos allowing for a more complete understanding of embryonic motility. Variations on this system are discussed to enable nonideal or alternative sensor arrangements and to allow for translation of this approach to other delicate model systems. PMID:25143544

  7. Observation of new spontaneous fission activities from elements 100 to 105

    SciTech Connect

    Somerville, L.P.

    1982-03-01

    Several new Spontaneous Fission (SF) activities have been found. No definite identification could be made for any of the new SF activities; however, half-lives and possible assignments to element-104 isotopes consistent with several cross bombardments include /sup 257/Rf(3.8 s, 14% SF), /sup 258/Rf(13 ms), /sup 259/Rf(approx. 3 s, 8% SF), /sup 260/Rf(approx. 20 ms), and /sup 262/Rf(approx. 50 ms). The 80-ms SF activity claimed by the Dubna group for the discovery of element 104 (/sup 260/104) was not observed. A difficulty exists in the interpretation that /sup 260/Rf is a approx. 20-ms SF activity: in order to be correct, for example, the SF activities with half-lives between 14 and 24 ms produced in the reactions 109- to 119-MeV /sup 18/O + /sup 248/Cm, 88- to 100-MeV /sup 15/N + /sup 249/Bk, and 96-MeV /sup 18/O + /sup 249/Cf must be other nuclides due to their large production cross sections, or the cross sections for production of /sup 260/Rf must be enhanced by unknown mechanisms. Based on calculated total production cross sections a possible approx. 1% electron-capture branch in /sup 258/Lr(4.5 s) to the SF emitter /sup 258/No(1.2 ms) and an upper limit of 0.05% for SF branching in /sup 254/No(55 s) were determined. Other measured half-lives from unknown nuclides produced in respective reactions include approx. 1.6 s (/sup 18/O + /sup 248/CM), indications of a approx. 47-s SF activity (75-MeV /sup 12/C + /sup 249/Cf), and two or more SF activities with 3 s less than or equal to T/sub 1/2/ less than or equal to 60 s (/sup 18/O + /sup 249/Bk). The most exciting conclusion of this work is that if the tentative assignments to even-even element 104 isotopes are correct, there would be a sudden change in the SF half-life systematics at element 104 which has been predicted theoretically and attributed to the disappearance of the second hump of the double-humped fission barrier.

  8. Activation of glycine receptors modulates spontaneous epileptiform activity in the immature rat hippocampus

    PubMed Central

    Chen, Rongqing; Okabe, Akihito; Sun, Haiyan; Sharopov, Salim; Hanganu-Opatz, Ileana L; Kolbaev, Sergei N; Fukuda, Atsuo; Luhmann, Heiko J; Kilb, Werner

    2014-01-01

    While the expression of glycine receptors in the immature hippocampus has been shown, no information about the role of glycine receptors in controlling the excitability in the immature CNS is available. Therefore, we examined the effect of glycinergic agonists and antagonists in the CA3 region of an intact corticohippocampal preparation of the immature (postnatal days 4–7) rat using field potential recordings. Bath application of 100 μm taurine or 10 μm glycine enhanced the occurrence of recurrent epileptiform activity induced by 20 μm 4-aminopyridine in low Mg2+ solution. This proconvulsive effect was prevented by 3 μm strychnine or after incubation with the loop diuretic bumetanide (10 μm), suggesting that it required glycine receptors and an active NKCC1-dependent Cl− accumulation. Application of higher doses of taurine (≥1 mm) or glycine (100 μm) attenuated recurrent epileptiform discharges. The anticonvulsive effect of taurine was also observed in the presence of the GABAA receptor antagonist gabazine and was attenuated by strychnine, suggesting that it was partially mediated by glycine receptors. Bath application of the glycinergic antagonist strychnine (0.3 μm) induced epileptiform discharges. We conclude from these results that in the immature hippocampus, activation of glycine receptors can mediate both pro- and anticonvulsive effects, but that a persistent activation of glycine receptors is required to suppress epileptiform activity. In summary, our study elucidated the important role of glycine receptors in the control of neuronal excitability in the immature hippocampus. PMID:24665103

  9. Metaphase I arrest and spontaneous parthenogenetic activation of strain LTXBO oocytes: chimeric reaggregated ovaries establish primary lesion in oocytes.

    PubMed

    Eppig, J J; Wigglesworth, K; Hirao, Y

    2000-08-01

    Oocytes of strain LT mice, and related strains such as LTXBO, exhibit a high incidence of arrest in the progression of meiosis at metaphase I (MI) and in spontaneous parthenogenetic activation. Activation of these oocytes within the ovary leads to the formation of ovarian teratomas. In this study, the role of the oocyte's companion granulosa cells, the cumulus cells, was investigated using fully grown oocytes matured in vitro after isolation from LTXBO mice. Results showed that the role of cumulus cells in MI arrest is dichotomous. Cumulus cells temporarily helped to sustain MI arrest, but they also promoted a delayed progression to metaphase II. Cumulus cells also promoted parthenogenetic activation that occurred in association with the delayed progression to metaphase II. Next, the question of whether the lesion(s) promoting MI arrest and spontaneous activation is due to defects in the somatic cells or is intrinsic to the oocyte was addressed using chimeric reaggregated ovaries. An improved method for completely exchanging the germ cell and the somatic cell compartments of ovaries from newborn mice is described. These chimeric reaggregated ovaries, grafted beneath the renal capsule of SCID mice, allowed the complete development of LTXBO oocytes to occur in association with somatic cells from control (B6SJLF(1)) ovaries and development of control oocytes in association with LTXBO somatic cells. Oocyte growth and follicular development appeared generally normal in reaggregated ovaries. High incidences of MI arrest and spontaneous activation of LTXBO oocytes occurred regardless of the genotype of the somatic cells. Moreover, there was a low incidence of MI arrest and spontaneous activation of control oocytes, even though they underwent complete development and maturation associated with LTXBO somatic cells. It is concluded that the phenotypes of MI arrest and parthenogenetic activation in LTXBO oocytes are defects caused by lesions intrinsic to the oocyte

  10. Towards an automated selection of spontaneous co-activity maps in functional magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Sourty, Marion; Thoraval, Laurent; Roquet, Daniel; Armspach, Jean-Paul; Foucher, Jack

    2015-03-01

    Functional magnetic resonance imaging allows to assess large scale functional integration of the brain. One of the leading techniques to extract functionally relevant networks is spatial independent component analysis (ICA). Spatial ICA separates independent spatial sources, many of whom are noise or imaging artifacts, whereas some do correspond to functionally relevant Spontaneous co-Activity Maps (SAMs). For research purposes, ICA is generally performed on group data. This strategy is well adapted to uncover commonly shared networks, e.g. resting-state networks, but fails to capture idiosyncratic functional networks which may be related to pathological activity, e.g. epilepsy, hallucinations. To capture these subject specific networks, ICA has to be applied to single subjects using a large number of components, from which a tenth are SAMs. Up to now, SAMs have to be selected manually by an expert based on predefined criteria. We aim to semi-automate the selection process in order to save time. To this end, some approaches have been proposed but none with the near 100 % sensitivity required for clinical purposes. In this paper, we propose a computerized version of the SAM's criteria used by experts, based on frequential and spatial characteristics of functional networks. Here we present a pre-selection method and its results at different resolutions, with different scanners or imaging sequences. While preserving a near 100 % sensitivity, it allows an average of 70 % reduction of components to be classified which save 55% of experts' time. In comparison, group ICA fails to detect about 25% of the SAMs.

  11. Learning to modulate one's own brain activity: the effect of spontaneous mental strategies

    PubMed Central

    Kober, Silvia E.; Witte, Matthias; Ninaus, Manuel; Neuper, Christa; Wood, Guilherme

    2013-01-01

    Using neurofeedback (NF), individuals can learn to modulate their own brain activity, in most cases electroencephalographic (EEG) rhythms. Although a large body of literature reports positive effects of NF training on behavior and cognitive functions, there are hardly any reports on how participants can successfully learn to gain control over their own brain activity. About one third of people fail to gain significant control over their brain signals even after repeated training sessions. The reasons for this failure are still largely unknown. In this context, we investigated the effects of spontaneous mental strategies on NF performance. Twenty healthy participants performed either a SMR (sensorimotor rhythm, 12–15 Hz) based or a Gamma (40–43 Hz) based NF training over ten sessions. After the first and the last training session, they were asked to write down which mental strategy they have used for self-regulating their EEG. After the first session, all participants reported the use of various types of mental strategies such as visual strategies, concentration, or relaxation. After the last NF training session, four participants of the SMR group reported to employ no specific strategy. These four participants showed linear improvements in NF performance over the ten training sessions. In contrast, participants still reporting the use of specific mental strategies in the last NF session showed no changes in SMR based NF performance over the ten sessions. This effect could not be observed in the Gamma group. The Gamma group showed no prominent changes in Gamma power over the NF training sessions, regardless of the mental strategies used. These results indicate that successful SMR based NF performance is associated with implicit learning mechanisms. Participants stating vivid reports on strategies to control their SMR probably overload cognitive resources, which might be counterproductive in terms of increasing SMR power. PMID:24151462

  12. Curcumin attenuates cardiac fibrosis in spontaneously hypertensive rats through PPAR-γ activation

    PubMed Central

    Meng, Zhe; Yu, Xin-hui; Chen, Jun; Li, Ling; Li, Sheng

    2014-01-01

    Aim: To investigate the effects of curcumin (Cur) on cardiac fibrosis in spontaneously hypertensive rats (SHRs) and the mechanisms underlying the anti-fibrotic effect of Cur in rat cardiac fibroblasts (CFs) in vitro. Methods: SHRs were orally treated with Cur (100 mg·kg−1·d−1) or Cur (100 mg·kg−1·d−1) plus the PPAR-γ antagonist GW9662 (1 mg·kg−1·d−1) for 12 weeks. Cultured CFs were treated with angiotensin II (Ang II, 0.1 μmol/L) in vitro. The expression of relevant proteins and mRNAs was analyzed using Western blotting and real-time PCR, respectively. The expression and activity of peroxisome proliferator-activated receptor-γ (PPAR-γ) were detected using Western blotting and a DNA-binding assay, respectively. Results: Treatment of SHRs with Cur significantly decreased systolic blood pressure, blood Ang II concentration, heart weight/body weight ratio and left ventricle weight/body weight ratio, with concurrently decreased expression of connective tissue growth factor (CTGF), plasminogen activator inhibitor (PAI)-1, collagen III (Col III) and fibronectin (FN), and increased expression and activity of PPAR-γ in the left ventricle. Co-treatment with GW9662 partially abrogated the anti-fibrotic effects of Cur in SHRs. Pretreatment of CFs with Cur (5, 10, 20 μmol/L) dose-dependently inhibited Ang II-induced expression of CTGF, PAI-1, Col III and FN, and increased the expression and binding activity of PPAR-γ. Pretreatment with GW9662 partially reversed anti-fibrotic effects of Cur in vitro. Furthermore, pretreatment of CFs with Cur inhibited Ang II-induced expression of transforming growth factor-β1 (TGF-β1) and phosphorylation of Smad2/3, which were reversed by GW9662. Conclusion: Cur attenuates cardiac fibrosis in SHRs and inhibits Ang II-induced production of CTGF, PAI-1 and ECM in CFs in vitro. The crosstalk between PPAR-γ and TGF-β1/Smad2/3 signaling is involved in the anti-fibrotic and anti-proliferative effects of Cur. PMID:25132338

  13. Modulation of spontaneous and odorant-evoked activity of rat olfactory sensory neurons by two anorectic peptides, insulin and leptin.

    PubMed

    Savigner, Agnès; Duchamp-Viret, Patricia; Grosmaitre, Xavier; Chaput, Michel; Garcia, Samuel; Ma, Minghong; Palouzier-Paulignan, Brigitte

    2009-06-01

    In mammals, the sense of smell is modulated by the status of satiety, which is mainly signaled by blood-circulating peptide hormones. However, the underlying mechanisms linking olfaction and food intake are poorly understood. Here we investigated the effects of two anorectic peptides, insulin and leptin, on the functional properties of olfactory sensory neurons (OSNs). Using patch-clamp recordings, we analyzed the spontaneous activity of rat OSNs in an in vitro intact epithelium preparation. Bath perfusion of insulin and leptin significantly increased the spontaneous firing frequency in 91.7% (n = 24) and 75.0% (n = 24) of the cells, respectively. When the activity was electrically evoked, both peptides shortened the latency to the first action potential by approximately 25% and decreased the interspike intervals by approximately 13%. While insulin and leptin enhanced the electrical excitability of OSNs in the absence of odorants, they surprisingly reduced the odorant-induced activity in the olfactory epithelium. Insulin and leptin decreased the peak amplitudes of isoamyl acetate-induced electroolfactogram (EOG) signals to 46 and 38%, respectively. When measured in individual cells by patch-clamp recordings, insulin and leptin decreased odorant-induced transduction currents and receptor potentials. Therefore by increasing the spontaneous activity but reducing the odorant-induced activity of OSNs, an elevated insulin and leptin level (such as after a meal) may result in a decreased global signal-to-noise ratio in the olfactory epithelium, which matches the smell ability to the satiety status. PMID:19297511

  14. Modulation of Spontaneous and Odorant-Evoked Activity of Rat Olfactory Sensory Neurons by Two Anorectic Peptides, Insulin and Leptin

    PubMed Central

    Savigner, Agnès; Duchamp-Viret, Patricia; Grosmaitre, Xavier; Chaput, Michel; Garcia, Samuel; Ma, Minghong; Palouzier-Paulignan, Brigitte

    2009-01-01

    In mammals, the sense of smell is modulated by the status of satiety, which is mainly signaled by blood-circulating peptide hormones. However, the underlying mechanisms linking olfaction and food intake are poorly understood. Here we investigated the effects of two anorectic peptides, insulin and leptin, on the functional properties of olfactory sensory neurons (OSNs). Using patch-clamp recordings, we analyzed the spontaneous activity of rat OSNs in an in vitro intact epithelium preparation. Bath perfusion of insulin and leptin significantly increased the spontaneous firing frequency in 91.7% (n = 24) and 75.0% (n = 24) of the cells, respectively. When the activity was electrically evoked, both peptides shortened the latency to the first action potential by ∼25% and decreased the interspike intervals by ∼13%. While insulin and leptin enhanced the electrical excitability of OSNs in the absence of odorants, they surprisingly reduced the odorant-induced activity in the olfactory epithelium. Insulin and leptin decreased the peak amplitudes of isoamyl acetate-induced electroolfactogram (EOG) signals to 46 and 38%, respectively. When measured in individual cells by patch-clamp recordings, insulin and leptin decreased odorant-induced transduction currents and receptor potentials. Therefore by increasing the spontaneous activity but reducing the odorant-induced activity of OSNs, an elevated insulin and leptin level (such as after a meal) may result in a decreased global signal-to-noise ratio in the olfactory epithelium, which matches the smell ability to the satiety status. PMID:19297511

  15. GABA-A receptor antagonists increase firing, bursting and synchrony of spontaneous activity in neuronal networks grown on microelectrode arrays: a step towards chemical "fingerprinting"

    EPA Science Inventory

    Assessment of effects on spontaneous network activity in neurons grown on MEAs is a proposed method to screen chemicals for potential neurotoxicity. In addition, differential effects on network activity (chemical "fingerprints") could be used to classify chemical modes of action....

  16. Activation of the prostaglandin system in response to sleep loss in healthy humans: Potential mediator of increased spontaneous pain

    PubMed Central

    Haack, Monika; Lee, Erin; Cohen, Daniel; Mullington, Janet M.

    2009-01-01

    Insufficient duration of sleep is a highly prevalent behavioral pattern in society that has been shown to cause an increase in spontaneous pain and sensitivity to noxious stimuli. Prostaglandins (PG), in particular PGE2, are key mediators of inflammation and pain, and we investigated whether PGE2 is a potential mediator in sleep-loss induced changes in nociceptive processing. Twenty-four participants (7 females, age 35. 17.1yrs) stayed for 7 days in the Clinical Research Center. After two baseline days, participants were randomly assigned to either three days of 88 hours of total sleep deprivation (TSD, N=15) or 8 hours of sleep per night (N=9), followed by a night of recovery sleep. Participants rated the intensity of various pain-related symptoms every two hours across waking periods on computerized visual analog scales. PGE2 was measured in 24h-urine collections during baseline and third sleep deprivation day. Spontaneous pain, including headache, muscle pain, stomach pain, generalized body pain, and physical discomfort significantly increased by 5 to 14 units on a 100-unit scale during TSD, compared to the sleep condition. Urinary PGE2 metabolite significantly increased by about 30% in TSD over sleep condition. TSD-induced increase in spontaneous pain, in particular headache and muscle pain, was significantly correlated with increase in PGE2 metabolite. Activation of the PGE2 system appears to be a potential mediator of increased spontaneous pain in response to insufficient sleep. PMID:19560866

  17. Spontaneous motor seizures of rats with kainate-induced epilepsy: effect of time of day and activity state.

    PubMed

    Hellier, J L; Dudek, F E

    1999-05-01

    Kainate treatment in rats can result in a chronic behavioral state that is similar to human temporal lobe epilepsy. We tested the hypothesis that, like some humans with epilepsy, rat with kainate-induced epilepsy have more spontaneous motor seizures during inactivity (i.e. little to no volitional movement, including apparent sleep) than during activity (i.e. apparent volitional movement, as in walking, grooming, eating, etc.). Rats were given intraperitoneal (i.p.) injections of kainate (5 mg/kg) every hour so that class III/IV/V seizures were elicited for > or = 3 h. Seizure behavior was video-monitored (24 h for 5-6 days, n = 32 rats at 3 months and n = 23 rats at 4 months after treatment) to examine the occurrence of seizures as a function of light versus dark (12-12-h light-dark cycle) and inactivity versus activity. Significantly more spontaneous motor seizures occurred during inactive versus active states (82% vs. 18%, P = 0.0001). Although more seizures occurred during the light period than the dark, the difference was not significant (62% vs. 38%, P > 0. 1). These data suggest that the frequency of spontaneous motor seizures in the rat with kainate-induced epilepsy depends primarily on activity state rather than time of day (i.e. time during the light-dark cycle). The effect of inactivity on the occurrence of seizures in the rat with kainate-induced epilepsy appears similar to some forms of human epilepsy. PMID:10232794

  18. Impaired culture generated cytotoxicity with preservation of spontaneous natural killer-cell activity in cartilage-hair hypoplasia

    SciTech Connect

    Pierce, G.F.; Brovall, C.; Schacter, B.Z.; Polmar, S.H.

    1983-06-01

    Recent studies of cartilage-hair hypoplasia (CHH), a form of short-limbed dwarfism, have shown that all affected individuals have a cellular proliferation defect that results in a cellular immunodeficiency. However, only a minority of CHH individuals suffer from severe, life-threatening infections. For this reason, relevant immune defense mechanisms that may be responsible for maintaining intact host defenses in the majority of CHH individuals were studied. Spontaneous and allogeneic culture-induced (mixed lymphocyte response-MLR) specific and nonspecific (NK-like) cytotoxic mechanisms were analyzed and correlated with lymphocyte subpopulations present in CHH and normal individuals. Spontaneous natural-killer (NK) activity was present at or above normal levels, but culture-induced specific cytotoxicity and NK-like cytotoxicity as well as NK-like activity by T cell lines were significantly reduced in CHH individuals. The generation of radiation-resistant cytotoxicity, which normally occurs during allogeneic MLR, was markedly diminished in CHH, and was correlated with the decreased proliferation observed in CHH cultures. Preservation of spontaneous NK activity and loss of all forms of culture-induced cytotoxicity was associated with an increase in the proportion of lymphocytes bearing a thymic independent NK phenotype, and a significant decrease in thymic derived cytolytic T cell sub-populations in CHH individuals. Therefore, an intact cellular cytotoxic effector mechanism has been identified in CHH (i.e., NK activity).

  19. [The blood glucose content in newborn rats depending on level and pattern of spontaneous motor activity].

    PubMed

    Kuznetsov, S V; Selina, E N; Kuznetsova, N N

    2011-01-01

    Earlier we have shown that administration to newborn rats of the pentose phosphate cycle inhibitor hydroquinone leads to a change in intensity and pattern of spontaneous periodic motor activity (SPMA) characteristic of early stages of development. The most typical was the disappearance of the rest period from the near-minute cycle "activity--rest" and the appearance of uninterrupted motor activity. In several cases, especially after 10 days of development, there was noted an enhancement in the SMPA pattern of the motor activity complexes following in the decasecond rhythm. In this study, on the 3-10-day old rats maintained under conditions of free behavior there was studied the blood glucose content in the animals at various periods of the activity-rest cycle. Apart from the SPMA phase, its composition (pattern) characterizing the maturity level and functional state of spinal motor centers was taken into account. In the 3, 7 and 10-day old rats at the rest period, the glucose concentration was established to differ depending on the motor activity pattern. In the case of the decasecond periodicity, it amounts to 5.7 +/- 0.2, 6.3 +/- +/- 0.3, and 7.7 +/- 0.3 mmol/l, while at the minute one--6.1 +/- 0.4, 7.8 +/- 0.3, and 7.8 +/- 0.1 mmol/l. At the moment of bursts of motor excitation, the glucose concentration falls to 5.2 +/- 0.1, 6.1 +/- 0.4, and 7.1 +/- +/- 0.3 mm at the decasecond and to 5.4 +/- 0.5, 6.7 +/- 0.2, and 7.6 +/- 0.3 mmol/l at the near-minute rhythm (for the 3, 7 and 10-day old animals, respectively). The results obtained on the 5-day rat pups differ qualitatively from those observed in other age groups. Thus, the glucose concentration at the rest period amounts to 6.8 +/- 0.2 at the decasecond and to 6.7 +/- 0.4 mmol/l at the nearminute periodicity. At the period of motor excitation accompanied by the presence of the decasecond activity rhythm, the glucose concentration falls to the level of 6.0 +/- 0.2 mmol/l by differing statistically significantly

  20. Methylxanthine-evoked perturbation of spontaneous and evoked activities in isolated newborn rat hippocampal networks.

    PubMed

    Ruangkittisakul, A; Sharopov, S; Kantor, C; Kuribayashi, J; Mildenberger, E; Luhmann, H J; Kilb, W; Ballanyi, K

    2015-08-20

    Treatment of apnea of prematurity with methylxanthines like caffeine, aminophylline or theophylline can evoke hippocampal seizures. However, it is unknown at which interstitial brain concentrations methylxanthines promote such neonatal seizures or interfere with physiological 'early network oscillations' (ENOs) that are considered as pivotal for maturation of hippocampal neural networks. We studied theophylline and caffeine effects on ENOs in CA3 neurons (CA3-ENOs) and CA3 electrical stimulation-evoked monosynaptic CA1 field potentials (CA1-FPs) in sliced and intact hippocampi, respectively, from 8 to 10-days-old rats. Submillimolar doses of theophylline and caffeine, blocking adenosine receptors and phosphodiesterase-4 (PDE4), did not affect CA3-ENOs, ENO-associated cytosolic Ca(2+) transients or CA1-FPs nor did they provoke seizure-like discharges. Low millimolar doses of theophylline (⩾1mM) or caffeine (⩾5mM), blocking GABAA and glycine receptors plus sarcoplasmic-endoplasmic reticulum Ca(2+) ATPase (SERCA)-type Ca(2+) ATPases, evoked seizure-like discharges with no indication of cytosolic Ca(2+) dysregulation. Inhibiting PDE4 with rolipram or glycine receptors with strychnine had no effect on CA3-ENOs and did not occlude seizure-like events as tested with theophylline. GABAA receptor blockade induced seizure-like discharges and occluded theophylline-evoked seizure-like discharges in the slices, but not in the intact hippocampi. In summary, submillimolar methylxanthine concentrations do not acutely affect spontaneous CA3-ENOs or electrically evoked synaptic activities and low millimolar doses are needed to evoke seizure-like discharges in isolated developing hippocampal neural networks. We conclude that mechanisms of methylxanthine-related seizure-like discharges do not involve SERCA inhibition-related neuronal Ca(2+) dysregulation, PDE4 blockade or adenosine and glycine receptor inhibition, whereas GABA(A) receptor blockade may contribute partially. PMID

  1. Identification of abnormal motor cortex activation patterns in children with cerebral palsy by functional near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Khan, Bilal; Tian, Fenghua; Behbehani, Khosrow; Romero, Mario I.; Delgado, Mauricio R.; Clegg, Nancy J.; Smith, Linsley; Reid, Dahlia; Liu, Hanli; Alexandrakis, George

    2010-05-01

    We demonstrate the utility of functional near-infrared spectroscopy (fNIRS) as a tool for physicians to study cortical plasticity in children with cerebral palsy (CP). Motor cortex activation patterns were studied in five healthy children and five children with CP (8.4+/-2.3 years old in both groups) performing a finger-tapping protocol. Spatial (distance from center and area difference) and temporal (duration and time-to-peak) image metrics are proposed as potential biomarkers for differentiating abnormal cortical activation in children with CP from healthy pediatric controls. In addition, a similarity image-analysis concept is presented that unveils areas that have similar activation patterns as that of the maximum activation area, but are not discernible by visual inspection of standard activation images. Metrics derived from the images presenting areas of similarity are shown to be sensitive identifiers of abnormal activation patterns in children with CP. Importantly, the proposed similarity concept and related metrics may be applicable to other studies for the identification of cortical activation patterns by fNIRS.

  2. Identification of abnormal motor cortex activation patterns in children with cerebral palsy by functional near-infrared spectroscopy

    PubMed Central

    Khan, Bilal; Tian, Fenghua; Behbehani, Khosrow; Romero, Mario I.; Delgado, Mauricio R.; Clegg, Nancy J.; Smith, Linsley; Reid, Dahlia; Liu, Hanli; Alexandrakis, George

    2010-01-01

    We demonstrate the utility of functional near-infrared spectroscopy (fNIRS) as a tool for physicians to study cortical plasticity in children with cerebral palsy (CP). Motor cortex activation patterns were studied in five healthy children and five children with CP (8.4±2.3years old in both groups) performing a finger-tapping protocol. Spatial (distance from center and area difference) and temporal (duration and time-to-peak) image metrics are proposed as potential biomarkers for differentiating abnormal cortical activation in children with CP from healthy pediatric controls. In addition, a similarity image-analysis concept is presented that unveils areas that have similar activation patterns as that of the maximum activation area, but are not discernible by visual inspection of standard activation images. Metrics derived from the images presenting areas of similarity are shown to be sensitive identifiers of abnormal activation patterns in children with CP. Importantly, the proposed similarity concept and related metrics may be applicable to other studies for the identification of cortical activation patterns by fNIRS. PMID:20615010

  3. Relationship of spontaneous chemical transformation of arylsulfonylhydrazones of 2-pyridinecarboxaldehyde 1-oxide to anticancer activity.

    PubMed

    Shiba, D A; May, J A; Sartorelli, A C

    1983-05-01

    The arylsulfonyl-hydrazones of 2-pyridinecarboxaldehyde 1-oxide represent a relatively new class of antineoplastic agents with the potential for clinical usefulness. The requirement for spontaneous chemical transformation of these agents to exert anticancer activity was evaluated using as the prototype the most potent member of this class synthesized to date, the 3,4-dimethoxybenzene sulfonylhydrazone of 2-pyridinecarboxaldehyde 1-oxide (3,4-DSP. 3,4-DSP was chemically unstable, decomposing with a half-life of 19 min in 0.01 M potassium phosphate buffer (pH 7.4) at 37 degrees. The major chemical decomposition product was identified as 2-pyridylcarbinol 1-oxide by comparison with the authentic compound. This carbinol is hypothesized to be formed via the intramolecular abstraction of hydrogen from the arylsulfonyl-hydrazone, a process that leads to the release of 3,4-dimethoxybenzenesulfinic acid and the formation of 1-oxidopyridin-2-yldiazomethane, which subsequently reacts with water. The diazomethane intermediate is a potent alkylating agent which, if generated in cells, would have the potential to alkylate nucleophilic groups of biologically important macromolecules. The proposed reactive species was trapped using both 4-(4-nitrobenzyl)pyridine (NBP) and morpholine, and the latter product was characterized by mass spectroscopy. The importance of the chemical formation of an alkylating species to cytotoxicity was demonstrated by studies in which solutions of 3,4-DSP were "aged" prior to addition to L1210 leukemia cells in culture and prior to incubation with NBP. The "aging" of 3,4-DSP for 20 min resulted in a 4-fold decrease in cytotoxicity, and aging for 1 to 3 hr led to complete loss of cytotoxicity. Correspondingly, a 20-min aging period decreased alkylation of NBP by 51%, and 3-hr aging resulted in essentially no alkylation of the nucleophile. Further support for the above proposed chemical activation pathway was provided by correlations between in vitro

  4. Physical Activity Is Linked to Greater Moment-To-Moment Variability in Spontaneous Brain Activity in Older Adults

    PubMed Central

    Burzynska, Agnieszka Z.; Wong, Chelsea N.; Voss, Michelle W.; Cooke, Gillian E.; Gothe, Neha P.; Fanning, Jason; McAuley, Edward; Kramer, Arthur F.

    2015-01-01

    Higher cardiorespiratory fitness (CRF) and physical activity (PA) in old age are associated with greater brain structural and functional integrity, and higher cognitive functioning. However, it is not known how different aspects of lifestyle such as sedentariness, light PA (LI-PA), or moderate-to-vigorous physical activity (MV-PA) relate to neural activity in aging. In addition, it is not known whether the effects of PA on brain function differ or overlap with those of CRF. Here, we objectively measured CRF as oxygen consumption during a maximal exercise test and measured PA with an accelerometer worn for 7 days in 100 healthy but low active older adults (aged 60–80 years). We modeled the relationships between CRF, PA, and brain functional integrity using multivariate partial least squares analysis. As an index of functional brain integrity we used spontaneous moment-to-moment variability in the blood oxygenation level-dependent signal (SDBOLD), known to be associated with better cognitive functioning in aging. We found that older adults who engaged more in LI-PA and MV-PA had greater SDBOLD in brain regions that play a role in integrating segregated functional domains in the brain and benefit from greater CRF or PA, such as precuneus, hippocampus, medial and lateral prefrontal, and temporal cortices. Our results suggest that engaging in higher intensity PA may have protective effects on neural processing in aging. Finally, we demonstrated that older adults with greater overall WM microstructure were those showing more LI-PA and MV-PA and greater SDBOLD. We conclude that SDBOLD is a promising correlate of functional brain health in aging. Future analyses will evaluate whether SDBOLD is modifiable with interventions aimed to increase PA and CRF in older adults. PMID:26244873

  5. Physical Activity Is Linked to Greater Moment-To-Moment Variability in Spontaneous Brain Activity in Older Adults.

    PubMed

    Burzynska, Agnieszka Z; Wong, Chelsea N; Voss, Michelle W; Cooke, Gillian E; Gothe, Neha P; Fanning, Jason; McAuley, Edward; Kramer, Arthur F

    2015-01-01

    Higher cardiorespiratory fitness (CRF) and physical activity (PA) in old age are associated with greater brain structural and functional integrity, and higher cognitive functioning. However, it is not known how different aspects of lifestyle such as sedentariness, light PA (LI-PA), or moderate-to-vigorous physical activity (MV-PA) relate to neural activity in aging. In addition, it is not known whether the effects of PA on brain function differ or overlap with those of CRF. Here, we objectively measured CRF as oxygen consumption during a maximal exercise test and measured PA with an accelerometer worn for 7 days in 100 healthy but low active older adults (aged 60-80 years). We modeled the relationships between CRF, PA, and brain functional integrity using multivariate partial least squares analysis. As an index of functional brain integrity we used spontaneous moment-to-moment variability in the blood oxygenation level-dependent signal (SDBOLD), known to be associated with better cognitive functioning in aging. We found that older adults who engaged more in LI-PA and MV-PA had greater SDBOLD in brain regions that play a role in integrating segregated functional domains in the brain and benefit from greater CRF or PA, such as precuneus, hippocampus, medial and lateral prefrontal, and temporal cortices. Our results suggest that engaging in higher intensity PA may have protective effects on neural processing in aging. Finally, we demonstrated that older adults with greater overall WM microstructure were those showing more LI-PA and MV-PA and greater SDBOLD. We conclude that SDBOLD is a promising correlate of functional brain health in aging. Future analyses will evaluate whether SDBOLD is modifiable with interventions aimed to increase PA and CRF in older adults. PMID:26244873

  6. Intrinsic connectivity of the rat subiculum: II. Properties of synchronous spontaneous activity and a demonstration of multiple generator regions.

    PubMed

    Harris, E; Stewart, M

    2001-07-01

    Brain structures that can generate epileptiform activity possess excitatory interconnections among principal cells and a subset of these neurons that can be spontaneously active ("pacemaker" cells). We describe electrophysiological evidence for excitatory interactions among rat subicular neurons. Subiculum was isolated from presubiculum, CA1, and entorhinal cortex in ventral horizontal slices. Nominally zero magnesium perfusate, picrotoxin (100 microM), or NMDA (20 microM) was used to induce spontaneous firing in subicular neurons. Synchronous population activity and the spread of population events from one end of subiculum to the other in isolated subicular subslices indicate that subicular pyramidal neurons are coupled together by excitatory synapses. Both electrophysiological classes of subicular pyramidal cells (bursting and regular spiking) exhibited synchronous activity, indicating that both cell classes are targets of local excitatory inputs. Burst firing neurons were active in the absence of synchronous activity in field recordings, indicating that these cells may serve as pacemaker neurons for the generation of epileptiform activity in subiculum. Epileptiform events could originate at either proximal or distal segments of the subiculum from ventral horizontal slices. In some slices, events originated in both proximal and distal locations and propagated to the other location. Finally, propagation was supported over axonal paths through the cell layer and in the apical dendritic zone. We conclude that subicular burst firing and regular spiking neurons are coupled by means of glutamatergic synapses. These connections may serve to distribute activity driven by topographically organized inputs and to synchronize subicular cell activity. PMID:11406829

  7. Role of mitochondria in spontaneous rhythmic activity and intracellular calcium waves in the guinea pig gallbladder smooth muscle.

    PubMed

    Balemba, Onesmo B; Bartoo, Aaron C; Nelson, Mark T; Mawe, Gary M

    2008-02-01

    Mitochondrial Ca(2+) handling has been implicated in spontaneous rhythmic activity in smooth muscle and interstitial cells of Cajal. In this investigation we evaluated the effect of mitochondrial inhibitors on spontaneous action potentials (APs), Ca(2+) flashes, and Ca(2+) waves in gallbladder smooth muscle (GBSM). Disruption of the mitochondrial membrane potential with carbonyl cyanide 3-chlorophenylhydrazone, carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone, rotenone, and antimycin A significantly reduced or eliminated APs, Ca(2+) flashes, and Ca(2+) waves in GBSM. Blockade of ATP production with oligomycin did not alter APs or Ca(2+) flashes but significantly reduced Ca(2+) wave frequency. Inhibition of mitochondrial Ca(2+) uptake and Ca(2+) release with Ru360 and CGP-37157, respectively, reduced the frequency of Ca(2+) flashes and Ca(2+) waves in GBSM. Similar to oligomycin, cyclosporin A did not alter AP and Ca(2+) flash frequency but significantly reduced Ca(2+) wave activity. These data suggest that mitochondrial Ca(2+) handling is necessary for the generation of spontaneous electrical activity and may therefore play an important role in gallbladder tone and motility. PMID:18048480

  8. Self-monitoring of spontaneous physical activity and sedentary behavior to prevent weight regain in older adults

    PubMed Central

    Nicklas, Barbara J.; Gaukstern, Jill E.; Beavers, Kristen M.; Newman, Jill C.; Leng, Xiaoyan; Rejeski, W. Jack

    2014-01-01

    Objective This study determined whether adding a self-regulatory intervention (SRI) focused on self-monitoring of spontaneous physical activity and sedentary behavior to a standard weight loss intervention improved maintenance of lost weight. Design and Methods Older (65–79 yrs), obese (BMI=30–40 kg/m2) adults (n=48) were randomized to a five-month weight loss intervention involving a hypocaloric diet (DIET) and aerobic exercise (EX) with or without the SRI to promote spontaneous physical activity and decrease sedentary behavior (SRI+DIET+EX compared to DIET+EX). Following the weight loss phase, both groups transitioned to self-selected diet and exercise behavior during a 5-month follow-up. Throughout the 10-months, the SRI+DIET+EX group utilized real-time accelerometer feedback for self-monitoring. Results There was an overall group by time effect of the SRI (P < 0.01); DIET+EX lost less weight and regained more weight than SRI+DIET+EX. The average weight regain during follow-up was 1.3 kg less in the SRI+DIET+EX group. Individuals in this group maintained ~10% lower weight than baseline compared to those in the DIET+EX group whom maintained ~5% lower weight than baseline. Conclusions Addition of a self-regulatory intervention, designed to increase spontaneous physical activity and decrease sedentary behavior, to a standard weight loss intervention enhances successful maintenance of lost weight. PMID:24585701

  9. Activity-dependent plasticity in the isolated embryonic avian brainstem following manipulations of rhythmic spontaneous neural activity.

    PubMed

    Vincen-Brown, Michael A; Revill, Ann L; Pilarski, Jason Q

    2016-07-15

    When rhythmic spontaneous neural activity (rSNA) first appears in the embryonic chick brainstem and cranial nerve motor axons it is principally driven by nicotinic neurotransmission (NT). At this early age, the nicotinic acetylcholine receptor (nAChR) agonist nicotine is known to critically disrupt rSNA at low concentrations (0.1-0.5μM), which are levels that mimic the blood plasma levels of a fetus following maternal cigarette smoking. Thus, we quantified the effect of persistent exposure to exogenous nicotine on rSNA using an in vitro developmental model. We found that rSNA was eliminated by continuous bath application of exogenous nicotine, but rSNA recovered activity within 6-12h despite the persistent activation and desensitization of nAChRs. During the recovery period rSNA was critically driven by chloride-mediated membrane depolarization instead of nicotinic NT. To test whether this observed compensation was unique to the antagonism of nicotinic NT or whether the loss of spiking behavior also played a role, we eliminated rSNA by lowering overall excitatory drive with a low [K(+)]o superfusate. In this context, rSNA again recovered, although the recovery time was much quicker, and exhibited a lower frequency, higher duration, and an increase in the number of bursts per episode when compared to control embryos. Importantly, we show that the main compensatory response to lower overall excitatory drive, similar to nicotinergic block, is a result of potentiated chloride mediated membrane depolarization. These results support increasing evidence that early neural circuits sense spiking behavior to maintain primordial bioelectric rhythms. Understanding the nature of developmental plasticity in the nervous system, especially versions that preserve rhythmic behaviors following clinically meaningful environmental stimuli, both normal and pathological, will require similar studies to determine the consequences of feedback compensation at more mature chronological ages

  10. CONVULSANT PROPERTIES OF CYCLOTRIMETHYLENETRINITRAMINE (RDX): SPONTANEOUS, AUDIOGENIC, AND AMYGDALOID KINDLED SEIZURE ACTIVITY (JOURNAL VERSION)

    EPA Science Inventory

    Dose-effect and time course relationships were determined for the effects of cyclotrimethylemetrinitramine (RDX) on seizure susceptibility. Male Long Evans rats treated with 0-60 mg/kg RDX, p.o., were monitored for spontaneous seizures during an 8 h interval between dosing and au...

  11. BRAIN ACONITASE ACTIVITY IN SPONTANEOUSLY HYPERTENSIVE (SHR) AND WISTAR-KYOTO (WKY) RATS.

    EPA Science Inventory

    Animal models of susceptibility are critical for human health risk assessment. Previous studies indicate that spontaneously hypertensive (SHR) rats are more sensitive than Wistar-Kyoto (WKY) rats to the cholinesterase (ChE) inhibitors such as carbaryl and chlorpyrifos. This diffe...

  12. Frills, Furbelows and Activated Memory: Syntactically Optional Elements in the Spontaneous Language Production of Bilingual Speakers

    ERIC Educational Resources Information Center

    Fehringer, Carol; Fry, Christina

    2007-01-01

    Previous studies have shown a correlation between working memory (WM) and syntactic complexity (variously defined) in language comprehension. The present study investigates this relationship in spontaneous language production, proposing a novel metric, informed by language development and disorders, where complexity is construed in terms of those…

  13. Increased Activation of the Wnt/β-Catenin Pathway in Spontaneous Hepatocellular Carcinoma Observed in Farnesoid X Receptor Knockout Mice

    PubMed Central

    Wolfe, Andy; Thomas, Ann; Edwards, Genea; Jaseja, Reshma; Guo, Grace L.

    2011-01-01

    Farnesoid X receptor (FXR), the primary bile acid-sensing nuclear receptor, also is known for its anticancer properties. It is known that FXR deficiency in mice results in spontaneous hepatocellular carcinoma (HCC), but the mechanisms are not completely understood. We report that sustained activation of the Wnt/β-catenin pathway is associated with spontaneous HCC in FXR-knockout (KO) mice. HCC development was studied in FXR-KO mice at 3, 8, and 14 months of age. No tumors were observed at either 3 or 8 months, but the presence of HCC was observed in 100% of the FXR-KO mice at the age of 14 months. Further analysis revealed no change in β-catenin activation in the livers of 3-month-old FXR-KO mice, but a moderate increase was observed in 8-month-old FXR-KO mice. β-Catenin activation further increased significantly in 14-month-old tumor-bearing mice. Further analysis revealed that two independent mechanisms might be involved in β-catenin activation in the livers of FXR-KO mice. Activation of canonical Wnt signaling was evident as indicated by increased Wnt4 and dishevelled expression along with glycogen synthase kinase-3β inactivation. We also observed decreased expression of E-cadherin, a known regulator of β-catenin, in FXR-KO mice. The decrease in E-cadherin expression was accompanied by increased expression of its transcriptional repressor, Snail. Consistent with the increased HCC in FXR-KO mice, we observed a significant decrease in FXR expression and activity in human HCC samples. Taken together, these data indicate that a temporal increase in the activation of Wnt/β-catenin is observed during spontaneous HCC development in FXR-KO mice and is potentially critical for tumor development. PMID:21430080

  14. IDENTIFICATION AND THE RELATIONSHIP OF DIFFERENT TYPES OF SPONTANEOUS ACTIVITY IN THE RAT URINARY TRACT: URETER, URINARY BLADDER.

    PubMed

    Kazaryan, K V; Simonyan, L G; Chibukhchyan, R G

    2015-04-01

    Simultaneous recording of spontaneous electrical activity was conducted from the ending areas of the ureter (the zone bordered with pyeloureteral anastomosis and bladder, respectively), as well as of the proximal part of the bladder. Normally the activity of the distal ureter zone is a propagating from the perirenal area action potentials with increased amplitude (100 microV). In these conditions from the bladder were recorded action potentials with relatively lower values of amplitude and frequency rhythm (31.9 microV and 17 min(-1), respectively). Isolation of investigating ureter areas from each other and from the bladder leads to the emergence of spike activity in the peribladder area different from that in norm: in the background of oscillating waves arises the action potential. Isolation of the ureter from the bladder also affects the nature of the initial activity. Of all analyzed parameters of activity change (decrease) only the amplitude and the frequency of action potentials reaching respectively 24.5 microV and 14.2 min(-1). The results indicate the presence of different types of autonomous spontaneous activity in the extreme zones of the ureter and bladder. The adjustment of these activity parameters in the areas can be provided by their relationship with each other. PMID:26336741

  15. Low doses of alcohol potentiate GABA sub B inhibition of spontaneous activity of hippocampal CA1 neurons in vivo

    SciTech Connect

    Criado, J.R.; Thies, R. )

    1991-03-11

    Low doses of alcohol facilitate firing of hippocampal neurons. Such doses also enhance the inhibitory actions of GABA. Alcohol is known to potentiate inhibition via GABA{sub A} receptors. However, the effects of alcohol on GABA{sub B} receptor function are not understood. Spontaneous activity of single units was recorded from CA1 neurons of male rats anesthetized with 1.0% halothane. Electrical recordings and local application of drugs were done with multi-barrel pipettes. CA1 pyramidal neurons fired spontaneous bursts of action potentials. Acute alcohol decreased the interval between bursts, a mild excitatory action. Alcohol also more than doubled the period of complete inhibition produced by local application of both GABA and baclofen. These data suggest that GABA{sub B}-mediated inhibition is also potentiated by low doses of alcohol.

  16. Self-Specific Stimuli Interact Differently than Non-Self-Specific Stimuli with Eyes-Open Versus Eyes-Closed Spontaneous Activity in Auditory Cortex

    PubMed Central

    Qin, Pengmin; Grimm, Simone; Duncan, Niall W.; Holland, Giles; Guo, Jia shen; Fan, Yan; Weigand, Anne; Baudewig, Juergen; Bajbouj, Malek; Northoff, Georg

    2013-01-01

    Previous studies suggest that there may be a distinct relationship between spontaneous neural activity and subsequent or concurrent self-specific stimulus-induced activity. This study aims to test the impact of spontaneous activity as recorded in an eyes-open (EO) resting state as opposed to eyes-closed (EC) on self-specific versus non-self-specific auditory stimulus-induced activity in fMRI. In our first experiment we used self-specific stimuli comprised of the subject’s own name and non-self-specific stimuli comprised of a friend’s name and an unknown name, presented during EO versus EC baselines in a 3 name condition × 2 baseline design. In Experiment 2 we directly measured spontaneous activity in the absence of stimuli during EO versus EC to confirm a modulatory effect of the two baseline conditions in the regions found to show an interaction effect in Experiment 1. Spontaneous activity during EO was significantly higher than during EC in bilateral auditory cortex and non-self-specific names yielded stronger signal changes relative to EO baseline than to EC. In contrast, there was no difference in response to self-specific names relative to EO baseline than to EC despite the difference between spontaneous activity levels. These results support an impact of spontaneous activity on stimulus-induced activity, moreover an impact that depends on the high-level stimulus characteristic of self-specificity. PMID:23908625

  17. Dietary intake and physical activity in a Canadian population sample of male patients with HIV infection and metabolic abnormalities.

    PubMed

    Arendt, Bianca Maria; Aghdassi, Elaheh; Mohammed, Saira Saddia; Fung, Lillia Yan; Jalali, Pegah; Salit, Irving Elliot; Allard, Johane Pierette

    2008-01-01

    Objective was to assess dietary intake and physical activity in a Canadian population sample of male patients with HIV and metabolic abnormalities and to compare the data to Canadian recommendations. Sixty-five HIV-infected men with at least one feature associated with the metabolic syndrome (insulin resistance, dyslipidemia, central obesity, or lipodystrophy) were enrolled. Results from 7-day food records and activity logs were compared to the Dietary Reference Intakes and recommendations of Canada's Physical Activity Guide, respectively. Anthropometric data were also measured. Fifty-two percent of the subjects were overweight, another 15% were obese. However, energy intake (mean+/-SEM) (2153+/-99 kcal/d) was lower than the estimated requirement (2854+/-62 kcal/d; p<0.0001), and 84.5% of the patients reached the recommended minimum of 60 min of mild or 30 min of moderate daily exercise. Intake was adequate for protein, but high for fat and cholesterol in 40% of patients. No patient reached the recommendation for fiber. Intake from diet alone was suboptimal for most micronutrients. Prevalence was highest for low vitamin E (91% of patients) and magnesium (68%) intake, and high sodium intake (72%). In summary, a large proportion of HIV patients with metabolic abnormalities were overweight or obese. However, this was not associated with high energy intake, or reduced physical activity. High fat, low fiber and inadequate micronutrient intakes were prevalent. PMID:18288980

  18. Meiotic abnormalities

    SciTech Connect

    1993-12-31

    Chapter 19, describes meiotic abnormalities. These include nondisjunction of autosomes and sex chromosomes, genetic and environmental causes of nondisjunction, misdivision of the centromere, chromosomally abnormal human sperm, male infertility, parental age, and origin of diploid gametes. 57 refs., 2 figs., 1 tab.

  19. EFFECT OF LASER LIGHT ON MATTER. LASER PLASMAS: Distributed extraction of amplified spontaneous emission from a randomly inhomogeneous active medium

    NASA Astrophysics Data System (ADS)

    Starikov, F. A.

    1993-05-01

    This paper investigates the dynamics of amplified spontaneous x-ray emission escaping from a randomly inhomogeneous plasma active medium through its ends and lateral surface. It is shown that the scattering of radiation by fluctuations in the dielectric permittivity, ɛ˜, can be utilized to extract energy through the lateral surface of the active medium. The radiant intensity is maximal in an off-axis direction in this case. When both regular refraction and scattering by ɛ˜ are operating, the distributed extraction of the light is determined by that effect which has the smaller characteristic length (i.e., the scattering length or the refraction length).

  20. High-Tc superconducting quantum interference device recordings of spontaneous brain activity: Towards high-Tc magnetoencephalography

    NASA Astrophysics Data System (ADS)

    Öisjöen, F.; Schneiderman, J. F.; Figueras, G. A.; Chukharkin, M. L.; Kalabukhov, A.; Hedström, A.; Elam, M.; Winkler, D.

    2012-03-01

    We have performed single- and two-channel high transition temperature (high-Tc) superconducting quantum interference device (SQUID) magnetoencephalography (MEG) recordings of spontaneous brain activity in two healthy human subjects. We demonstrate modulation of two well-known brain rhythms: the occipital alpha rhythm and the mu rhythm found in the motor cortex. We further show that despite higher noise-levels compared to their low-Tc counterparts, high-Tc SQUIDs can be used to detect and record physiologically relevant brain rhythms with comparable signal-to-noise ratios. These results indicate the utility of high-Tc technology in MEG recordings of a broader range of brain activity.

  1. Saccade-related Purkinje cell activity in the oculomotor vermis during spontaneous eye movements in light and darkness.

    PubMed

    Helmchen, C; Büttner, U

    1995-01-01

    Saccade-related Purkinje cells (PCs) were recorded in the oculomotor vermis (lobules VI, VII) during spontaneous eye movements and fast phases of optokinetic and vestibular nystagmus in the light and darkness, from two macaque monkeys. All neurons (n = 46) were spontaneously active and exhibited a saccade-related change of activity with all saccades and fast phases of nystagmus. Four types of neurons were found: most neurons (n = 31) exhibited a saccade-related burst of activity only (VBN); other units (n = 7) showed a burst of activity with a subsequent pause (VBPN); some of the units (n = 5) paused in relation to the saccadic eye movement (pause units, VPN); a few PCs (n = 3) showed a burst of activity in one direction and a pause of activity in the opposite direction. For all neurons, burst activity varied considerably for similar saccades. There were no activity differences between spontaneous saccades and vestibular or optokinetically elicited fast phases of nystagmus. The activity before, during, and after horizontal saccades was quantitatively analyzed. For 24 burst PCs (VBN, VBPN), the burst started before saccade onset in one horizontal direction (preferred direction), on average by 15.3 ms (range 27-5 ms). For all these neurons, burst activity started later in the opposite (non-preferred) direction, on average 4.9 ms (range 20 to -12 ms, P < 0.01) before saccade onset. The preferred direction could be either with ipsilateral (42% of neurons) or contralateral (58%) saccades. Nine burst PCs had similar latencies and burst patterns in both horizontal directions. The onset of burst activity of a minority of PCs (n = 5) lagged saccade onset in all directions. The pause for VBPN neurons started after the end of the saccade and reached a minimum of activity some 40-50 ms after saccade completion. For all saccades and quick phases of nystagmus, burst duration increased with saccade duration. Peak burst activity was not correlated with saccade amplitude or peak

  2. Neuronal Functional Connection Graphs among Multiple Areas of the Rat Somatosensory System during Spontaneous and Evoked Activities

    PubMed Central

    Zippo, Antonio G.; Storchi, Riccardo; Nencini, Sara; Caramenti, Gian Carlo; Valente, Maurizio; Biella, Gabriele Eliseo M.

    2013-01-01

    Small-World Networks (SWNs) represent a fundamental model for the comprehension of many complex man-made and biological networks. In the central nervous system, SWN models have been shown to fit well both anatomical and functional maps at the macroscopic level. However, the functional microscopic level, where the nodes of a network are represented by single neurons, is still poorly understood. At this level, although recent evidences suggest that functional connection graphs exhibit small-world organization, it is not known whether and how these maps, potentially distributed in multiple brain regions, change across different conditions, such as spontaneous and stimulus-evoked activities. We addressed these questions by analyzing the data from simultaneous multi-array extracellular recordings in three brain regions of rats, diversely involved in somatosensory information processing: the ventropostero-lateral thalamic nuclei, the primary somatosensory cortex and the centro-median thalamic nuclei. From both spike and Local Field Potential (LFP) recordings, we estimated the functional connection graphs by using the Normalized Compression Similarity for spikes and the Phase Synchrony for LFPs. Then, by using graph-theoretical statistics, we characterized the functional topology both during spontaneous activity and sensory stimulation. Our main results show that: (i) spikes and LFPs show SWN organization during spontaneous activity; (ii) after stimulation onset, while substantial functional graph reconfigurations occur both in spike and LFPs, small-worldness is nonetheless preserved; (iii) the stimulus triggers a significant increase of inter-area LFP connections without modifying the topology of intra-area functional connections. Finally, investigating computationally the functional substrate that supports the observed phenomena, we found that (iv) the fundamental concept of cell assemblies, transient groups of activating neurons, can be described by small

  3. Neuronal functional connection graphs among multiple areas of the rat somatosensory system during spontaneous and evoked activities.

    PubMed

    Zippo, Antonio G; Storchi, Riccardo; Nencini, Sara; Caramenti, Gian Carlo; Valente, Maurizio; Biella, Gabriele Eliseo M

    2013-01-01

    Small-World Networks (SWNs) represent a fundamental model for the comprehension of many complex man-made and biological networks. In the central nervous system, SWN models have been shown to fit well both anatomical and functional maps at the macroscopic level. However, the functional microscopic level, where the nodes of a network are represented by single neurons, is still poorly understood. At this level, although recent evidences suggest that functional connection graphs exhibit small-world organization, it is not known whether and how these maps, potentially distributed in multiple brain regions, change across different conditions, such as spontaneous and stimulus-evoked activities. We addressed these questions by analyzing the data from simultaneous multi-array extracellular recordings in three brain regions of rats, diversely involved in somatosensory information processing: the ventropostero-lateral thalamic nuclei, the primary somatosensory cortex and the centro-median thalamic nuclei. From both spike and Local Field Potential (LFP) recordings, we estimated the functional connection graphs by using the Normalized Compression Similarity for spikes and the Phase Synchrony for LFPs. Then, by using graph-theoretical statistics, we characterized the functional topology both during spontaneous activity and sensory stimulation. Our main results show that: (i) spikes and LFPs show SWN organization during spontaneous activity; (ii) after stimulation onset, while substantial functional graph reconfigurations occur both in spike and LFPs, small-worldness is nonetheless preserved; (iii) the stimulus triggers a significant increase of inter-area LFP connections without modifying the topology of intra-area functional connections. Finally, investigating computationally the functional substrate that supports the observed phenomena, we found that (iv) the fundamental concept of cell assemblies, transient groups of activating neurons, can be described by small

  4. Spontaneous fragmentation of an alpha-active ceramic: a mechanism for dispersion of solid waste

    SciTech Connect

    Clinard, F.W. Jr.; Rohr, D.L.

    1980-01-01

    Studies underway to characterize spontaneous fragmentation in /sup 238/PuO/sub 2/ and to determine the mechanism(s) responsible are reported. Results reported here show that: spontaneous fragmentation of /sup 238/PuO/sub 2/ generates a wide range of particle sizes, from a few mm to 1000 A or less; the phenomenon may continue with time or may saturate, depending on starting material; the magnitude of the effect is dependent on storage environment. Neither thermal stresses nor lattice damage appear to be solely responsible for fragmentation, but radiolysis of the environment could play an important role. Work is continuing in an effort to identify the controlling factors in this phenomenon.

  5. Inositol-1,4,5-trisphosphate-mediated spontaneous activity in mouse embryonic stem cell-derived cardiomyocytes.

    PubMed

    Kapur, Nidhi; Banach, Kathrin

    2007-06-15

    Embryonic stem cell-derived cardiomyocytes (ESdCs) have been proposed as a source for cardiac cell-replacement therapy. The aim of this study was to determine the Ca2+-handling mechanisms that determine the frequency and duration of spontaneous Ca2+ transients in single ESdCs. With laser scanning confocal microscopy using the Ca2+-sensitive dye Fluo-4/AM, we determined that spontaneous Ca2+ transients in ESdCs at the onset of beating (day 9) depend on Ca2+ entry across the plasma membrane (50%) whereas Ca2+-induced Ca2+ release is the major contributor to Ca2+ transients in ESdCs after 16 days (72%). Likewise, Ca2+ extrusion in 9-day-old ESdCs depends on Na+-Ca2+ exchange (50.0+/-8%) whereas Ca2+ reuptake by the sarco(endo)plasmic Ca2+ ATPase (72+/-5%) dominates in further differentiated cells. Spontaneous Ca2+ transients were suppressed by the inositol-1,4,5-trisphosphate (IP3) receptor (IP3R) blocker 2-aminoethoxydiphenyl borate (2-APB) and the phospholipase C blocker U73122 but continued in the presence of caffeine. Stimulation of IP3 production by phenylephrine or endothelin-1 had a positive chronotropic effect that could be reversed by U73122 and 2-APB. The presence of Ca2+-free solution and block of L-type Ca2+ channels by nifedipine also resulted in a cessation of spontaneous activity. Overall, IP3R-mediated Ca2+ release in ESdCs is translated into a depolarization of the plasma membrane and a whole-cell Ca2+ transient is subsequently induced by voltage-dependent Ca2+ influx. Although ryanodine receptor-mediated Ca2+ release amplifies the IP3R-induced trigger for the Ca2+ transients and modulates its frequencies, it is not a prerequisite for spontaneous activity. The results of this study offer important insight into the role of IP3R-mediated Ca2+ release for pacemaker activity in differentiating cardiomyocytes. PMID:17379641

  6. Glutathione diminishes the anti-tumour activity of 4-hydroperoxycyclophosphamide by stabilising its spontaneous breakdown to alkylating metabolites.

    PubMed Central

    Lee, F. Y.

    1991-01-01

    Evidence was obtained showing that GSH protects against the cytotoxicity of 4-hydroperoxycyclophosphamide (4-OOH-CP) by minimizing the spontaneous fission of 4-hydroxycyclophosphamide (4-OH-CP), its breakdown product, to the ultimate toxic species, phosphoramide mustard (PM). This conclusion was borne out in two series of experiments. The first demonstrated that 4-OH-CP was progressively more stable in aqueous solutions containing increasing concentrations of GSH. The second series of experiments were carried out with tumour cell lines with high (SKOV-3) and low (KHT) GSH contents. The cytotoxicity of 4-OOH-CP, a stable precursor that rapidly gives rise to 4-OH-CP spontaneously under physiological conditions, was enhanced in GSH-depleted SKOV-3 cells, but was unchanged in GSH-depleted KHT cells. It is concluded that the high GSH content of SKOV-3 cells provides a significant protection against 4-OH-CP by limiting the breakdown/activation of 4-OH-CP. Deschloro-4-hydroperoxycyclophosphamide (deschloro-4-OOH-CP), an analogue of 4-OOH-CP that generates acrolein (AC) but not PM in the spontaneous fission reaction, is essentially non-toxic when compared with 4-OOH-CP but is equally potent in depleting GSH. It is postulated that AC may promote the cytotoxicity of the parent 4-OH-CP by depleting cellular GSH. Consequently, the stabilising influence of GSH on 4-OH-CP is removed, leading to increased formation of PM, the ultimate cytotoxic agent. PMID:1989664

  7. Abnormal Brain Activity in Social Reward Learning in Children with Autism Spectrum Disorder: An fMRI Study

    PubMed Central

    Choi, Uk-Su; Kim, Sun-Young; Sim, Hyeon Jeong; Lee, Seo-Young; Park, Sung-Yeon; Jeong, Joon-Sup; Seol, Kyeong In; Yoon, Hyo-Woon; Jhung, Kyungun; Park, Jee-In

    2015-01-01

    Purpose We aimed to determine whether Autism Spectrum Disorder (ASD) would show neural abnormality of the social reward system using functional MRI (fMRI). Materials and Methods 27 ASDs and 12 typically developing controls (TDCs) participated in this study. The social reward task was developed, and all participants performed the task during fMRI scanning. Results ASDs and TDCs with a social reward learning effect were selected on the basis of behavior data. We found significant differences in brain activation between the ASDs and TDCs showing a social reward learning effect. Compared with the TDCs, the ASDs showed reduced activity in the right dorsolateral prefrontal cortex, right orbitofrontal cortex, right parietal lobe, and occipital lobe; however, they showed increased activity in the right parahippocampal gyrus and superior temporal gyrus. Conclusion These findings suggest that there might be neural abnormality of the social reward learning system of ASDs. Although this study has several potential limitations, it presents novel findings in the different neural mechanisms of social reward learning in children with ASD and a possible useful biomarker of high-functioning ASDs. PMID:25837176

  8. Auditory Tones and Foot-Shock Recapitulate Spontaneous Sub-Threshold Activity in Basolateral Amygdala Principal Neurons and Interneurons

    PubMed Central

    Yan, Shanzhi; Stratton, Peter G.; Sullivan, Robert; Crane, James W.; Sah, Pankaj

    2016-01-01

    In quiescent states such as anesthesia and slow wave sleep, cortical networks show slow rhythmic synchronized activity. In sensory cortices this rhythmic activity shows a stereotypical pattern that is recapitulated by stimulation of the appropriate sensory modality. The amygdala receives sensory input from a variety of sources, and in anesthetized animals, neurons in the basolateral amygdala (BLA) show slow rhythmic synchronized activity. Extracellular field potential recordings show that these oscillations are synchronized with sensory cortex and the thalamus, with both the thalamus and cortex leading the BLA. Using whole-cell recording in vivo we show that the membrane potential of principal neurons spontaneously oscillates between up- and down-states. Footshock and auditory stimulation delivered during down-states evokes an up-state that fully recapitulates those occurring spontaneously. These results suggest that neurons in the BLA receive convergent input from networks of cortical neurons with slow oscillatory activity and that somatosensory and auditory stimulation can trigger activity in these same networks. PMID:27171164

  9. Assisting people with multiple disabilities actively correct abnormal standing posture with a Nintendo Wii balance board through controlling environmental stimulation.

    PubMed

    Shih, Ching-Hsiang; Shih, Ching-Tien; Chu, Chiung-Ling

    2010-01-01

    The latest researches adopted software technology turning the Nintendo Wii Balance Board into a high performance change of standing posture (CSP) detector, and assessed whether two persons with multiple disabilities would be able to control environmental stimulation using body swing (changing standing posture). This study extends Wii Balance Board functionality for standing posture correction (i.e., actively adjust abnormal standing posture) to assessed whether two persons with multiple disabilities would be able to actively correct their standing posture by controlling their favorite stimulation on/off using a Wii Balance Board with a newly developed standing posture correcting program (SPCP). The study was performed according to an ABAB design, in which A represented baseline and B represented intervention phases. Data showed that both participants significantly increased time duration of maintaining correct standing posture (TDMCSP) to activate the control system to produce environmental stimulation during the intervention phases. Practical and developmental implications of the findings were discussed. PMID:20381997

  10. Spontaneous locomotor activity and L-DOPA-induced dyskinesia are not linked in 6-OHDA parkinsonian rats

    PubMed Central

    Sgroi, Stefania; Kaelin-Lang, Alain; Capper-Loup, Christine

    2014-01-01

    Bradykinesia (slowness of movement) and other characteristic motor manifestations of Parkinson’s disease (PD) are alleviated by treatment with L-dihydroxyphenylalanine (L-DOPA). Long-term L-DOPA treatment, however, is associated with complications such as motor fluctuations and dyskinesia that severely impair the quality of life. It is unclear whether the effect of L-DOPA on spontaneous motor activity and its dyskinesia-inducing effect share a common mechanism. To investigate the possible connection between these two effects, we analyzed the spontaneous locomotor activity of parkinsonian rats before surgery (unilateral injection of 6-OHDA in the right medial forebrain bundle), before treatment with L-DOPA, during L-DOPA treatment (the “ON” phase), and after the end of L-DOPA treatment (the “OFF” phase). We correlated the severity of dyskinesia (AIM scores) with locomotor responses in the ON/OFF phases of chronic L-DOPA treatment at two different doses. We treated three groups of parkinsonian animals with chronic injections of 8 mg/kg L-DOPA, 6 mg/kg L-DOPA, and saline solution and one group of non-lesioned animals with 8 mg/kg L-DOPA. At the end of the experiment, tyrosine hydroxylase (TH) immunoreactivity was analyzed in the striatum of all parkinsonian rats. We found no correlation between the severity of dyskinesia and spontaneous locomotor activity in the ON or OFF phase of L-DOPA treatment. The only observed correlation was between the pathological rotation induced by L-DOPA at the highest dose and locomotor activity in the ON phase of L-DOPA treatment. In addition, a L-DOPA withdrawal effect was observed, with worse motor performance in the OFF phase than before the start of L-DOPA treatment. These findings suggest that different neural mechanisms underlie the effect of L-DOPA on spontaneous motor activity and its dyskinesia-inducing effect, with a different dose-response relationship for each of these two effects. PMID:25324746

  11. Excitability and responsiveness of rat barrel cortex neurons in the presence and absence of spontaneous synaptic activity in vivo

    PubMed Central

    Altwegg-Boussac, Tristan; Chavez, Mario; Mahon, Séverine; Charpier, Stéphane

    2014-01-01

    The amplitude and temporal dynamics of spontaneous synaptic activity in the cerebral cortex vary as a function of brain states. To directly assess the impact of different ongoing synaptic activities on neocortical function, we performed in vivo intracellular recordings from barrel cortex neurons in rats under two pharmacological conditions generating either oscillatory or tonic synaptic drive. Cortical neurons membrane excitability and firing responses were compared, in the same neurons, before and after complete suppression of background synaptic drive following systemic injection of a high dose of anaesthetic. Compared to the oscillatory state, the tonic pattern resulted in a more depolarized and less fluctuating membrane potential (Vm), a lower input resistance (Rm) and steeper relations of firing frequency versus injected current (F–I). Whatever their temporal dynamics, suppression of background synaptic activities increased mean Vm, without affecting Rm, and induced a rightward shift of F–I curves. Both types of synaptic drive generated a high variability in current-induced firing rate and patterns in cortical neurons, which was much reduced after removal of spontaneous activity. These findings suggest that oscillatory and tonic synaptic patterns differentially facilitate the input–output function of cortical neurons but result in a similar moment-to-moment variability in spike responses to incoming depolarizing inputs. PMID:24732430

  12. Congenital Abnormalities

    MedlinePlus

    ... serious health problems (e.g. Down syndrome ). Single-Gene Abnormalities Sometimes the chromosomes are normal in number, ... blood flow to the fetus impair fetal growth. Alcohol consumption and certain drugs during pregnancy significantly increase ...

  13. Craniofacial Abnormalities

    MedlinePlus

    ... of the skull and face. Craniofacial abnormalities are birth defects of the face or head. Some, like cleft ... palate, are among the most common of all birth defects. Others are very rare. Most of them affect ...

  14. Walking abnormalities

    MedlinePlus

    ... include: Arthritis of the leg or foot joints Conversion disorder (a psychological disorder) Foot problems (such as a ... injuries. For an abnormal gait that occurs with conversion disorder, counseling and support from family members are strongly ...

  15. Chromosome Abnormalities

    MedlinePlus

    ... decade, newer techniques have been developed that allow scientists and doctors to screen for chromosomal abnormalities without using a microscope. These newer methods compare the patient's DNA to a normal DNA ...

  16. Nail abnormalities

    MedlinePlus

    Nail abnormalities are problems with the color, shape, texture, or thickness of the fingernails or toenails. ... Fungus or yeast cause changes in the color, texture, and shape of the nails. Bacterial infection may ...

  17. Loss of inhibitory tone on spinal cord dorsal horn spontaneously and nonspontaneously active neurons in a mouse model of neuropathic pain.

    PubMed

    Medrano, Maria Carmen; Dhanasobhon, Dhanasak; Yalcin, Ipek; Schlichter, Rémy; Cordero-Erausquin, Matilde

    2016-07-01

    Plasticity of inhibitory transmission in the spinal dorsal horn (SDH) is believed to be a key mechanism responsible for pain hypersensitivity in neuropathic pain syndromes. We evaluated this plasticity by recording responses to mechanical stimuli in silent neurons (nonspontaneously active [NSA]) and neurons showing ongoing activity (spontaneously active [SA]) in the SDH of control and nerve-injured mice (cuff model). The SA and NSA neurons represented 59% and 41% of recorded neurons, respectively, and were predominantly wide dynamic range (WDR) in naive mice. Nerve-injured mice displayed a marked decrease in the mechanical threshold of the injured paw. After nerve injury, the proportion of SA neurons was increased to 78%, which suggests that some NSA neurons became SA. In addition, the response to touch (but not pinch) was dramatically increased in SA neurons, and high-threshold (nociceptive specific) neurons were no longer observed. Pharmacological blockade of spinal inhibition with a mixture of GABAA and glycine receptor antagonists significantly increased responses to innocuous mechanical stimuli in SA and NSA neurons from sham animals, but had no effect in sciatic nerve-injured animals, revealing a dramatic loss of spinal inhibitory tone in this situation. Moreover, in nerve-injured mice, local spinal administration of acetazolamide, a carbonic anhydrase inhibitor, restored responses to touch similar to those observed in naive or sham mice. These results suggest that a shift in the reversal potential for anions is an important component of the abnormal mechanical responses and of the loss of inhibitory tone recorded in a model of nerve injury-induced neuropathic pain. PMID:26934510

  18. Altered intrinsic regional brain spontaneous activity and subjective sleep quality in patients with chronic primary insomnia: a resting-state fMRI study

    PubMed Central

    Dai, Xi-Jian; Peng, De-Chang; Gong, Hong-Han; Wan, Ai-Lan; Nie, Xiao; Li, Hai-Jun; Wang, Yi-Xiang J

    2014-01-01

    Study objective To prospectively explore the underlying regional homogeneity (ReHo) brain-activity deficit in patients with chronic primary insomnia (PCPIs) and its relationship with clinical features. Design The ReHo method and Statistical Parametric Mapping 8 software were used to evaluate whether resting-state localized brain activity was modulated between PCPIs and good sleepers (GSs), and correlation analysis between altered regional brain areas and clinical features was calculated. Patients and participants Twenty-four PCPIs (17 females, seven males) and 24 (12 females, 12 males) age-, sex-, and education-matched GSs. Measurements and results PCPIs disturbed subjective sleep quality, split positive mood, and exacerbated negative moods. Compared with GSs, PCPIs showed higher ReHo in left fusiform gyrus, and lower ReHo in bilateral cingulate gyrus and right cerebellum anterior lobe. Compared with female GSs, female PCPIs showed higher ReHo in the left fusiform gyrus and right posterior cingulate, and lower ReHo in the left cerebellum anterior lobe and left superior frontal gyrus. Compared with male GSs, male PCPIs showed higher ReHo in the right temporal lobe and lower ReHo in the bilateral frontal lobe. The fusiform gyrus showed strong positive correlations and the frontal lobe showed negative correlations with the clinical measurements. Conclusion The ReHo analysis is a useful noninvasive imaging tool for the detection of cerebral changes and the indexing of clinical features. The abnormal spontaneous activity areas provided important information on the neural mechanisms underlying emotion and sleep-quality impairment in PCPIs. PMID:25484585

  19. Abnormal error-related antisaccade activation in premanifest and early manifest Huntington disease

    PubMed Central

    Rupp, J.; Dzemidzic, M.; Blekher, T.; Bragulat, V.; West, J.; Jackson, J.; Hui, S.; Wojcieszek, J.; Saykin, A.J.; Kareken, D.; Foroud, T.

    2010-01-01

    Objective Individuals with the trinucleotide CAG expansion (CAG+) that causes Huntington disease (HD) have impaired performance on antisaccade (AS) tasks that require directing gaze in the mirror opposite direction of visual targets. This study aimed to identify the neural substrates underlying altered antisaccadic performance. Method Three groups of participants were recruited: 1) Imminent and early manifest HD (early HD, n=8); 2) premanifest (presymptomatic) CAG+ (preHD, n=10); and 3) CAG unexpanded (CAG−) controls (n=12). All participants completed a uniform study visit that included a neurological evaluation, neuropsychological battery, molecular testing, and functional magnetic resonance imaging during an AS task. The blood oxygenation level dependent (BOLD) response was obtained during saccade preparation and saccade execution for both correct and incorrect responses using regression analysis. Results Significant group differences in BOLD response were observed when comparing incorrect AS to correct AS execution. Specifically, as the percentage of incorrect AS increased, BOLD responses in the CAG− group decreased progressively in a well-documented reward detection network that includes the pre-supplementary motor area and dorsal anterior cingulate cortex. In contrast, AS errors in the preHD and early HD groups lacked this relationship with BOLD signal in the error detection network, and BOLD responses to AS errors were smaller in the two CAG+ groups as compared with the CAG− group. Conclusions These results are the first to suggest that abnormalities in an error-related response network may underlie early changes in AS eye movements in premanifest and early manifest HD. PMID:21401260

  20. Dyslexic brain activation abnormalities in deep and shallow orthographies: A meta-analysis of 28 functional neuroimaging studies.

    PubMed

    Martin, Anna; Kronbichler, Martin; Richlan, Fabio

    2016-07-01

    We used coordinate-based meta-analysis to objectively quantify commonalities and differences of dyslexic functional brain abnormalities between alphabetic languages differing in orthographic depth. Specifically, we compared foci of under- and overactivation in dyslexic readers relative to nonimpaired readers reported in 14 studies in deep orthographies (DO: English) and in 14 studies in shallow orthographies (SO: Dutch, German, Italian, Swedish). The separate meta-analyses of the two sets of studies showed universal reading-related dyslexic underactivation in the left occipitotemporal cortex (including the visual word form area (VWFA)). The direct statistical comparison revealed higher convergence of underactivation for DO compared with SO in bilateral inferior parietal regions, but this abnormality disappeared when foci resulting from stronger dyslexic task-negative activation (i.e., deactivation relative to baseline) were excluded. Higher convergence of underactivation for DO compared with SO was further identified in the left inferior frontal gyrus (IFG) pars triangularis, left precuneus, and right superior temporal gyrus, together with higher convergence of overactivation in the left anterior insula. Higher convergence of underactivation for SO compared with DO was found in the left fusiform gyrus, left temporoparietal cortex, left IFG pars orbitalis, and left frontal operculum, together with higher convergence of overactivation in the left precentral gyrus. Taken together, the findings support the notion of a biological unity of dyslexia, with additional orthography-specific abnormalities and presumably different compensatory mechanisms. The results are discussed in relation to current functional neuroanatomical models of developmental dyslexia. Hum Brain Mapp 37:2676-2699, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:27061464

  1. Hierarchical and homotopic correlations of spontaneous neural activity within the visual cortex of the sighted and blind

    PubMed Central

    Butt, Omar H.; Benson, Noah C.; Datta, Ritobrato; Aguirre, Geoffrey K.

    2015-01-01

    Spontaneous neural activity within visual cortex is synchronized by both monosynaptic, hierarchical connections between visual areas and indirect, network-level activity. We examined the interplay of hierarchical and network connectivity in human visual cortex by measuring the organization of spontaneous neural signals within the visual cortex in total darkness using functional magnetic resonance imaging (fMRI). Twenty-five blind (14 congenital and 11 postnatal) participants with equally severe vision loss and 22 sighted subjects were studied. An anatomical template based on cortical surface topology was used for all subjects to identify the quarter-field components of visual areas V1-V3, and assign retinotopic organization. Cortical visual areas that represent the same quadrant of the visual field were considered to have a hierarchical relationship, while the spatially separated quarters of the same visual area were considered homotopic. Blindness was found to enhance correlations between hierarchical cortical areas as compared to indirect, homotopic areas at both the level of visual areas (p = 0.000031) and fine, retinotopic scale (p = 0.0024). A specific effect of congenital, but not postnatal, blindness was to further broaden the cortico-cortico connections between hierarchical visual areas (p = 0.0029). This finding is consistent with animal studies that observe a broadening of axonal terminal arborization when the visual cortex is deprived of early input. We therefore find separable roles for vision in developing and maintaining the intrinsic neural activity of visual cortex. PMID:25713519

  2. Abnormal vitamin K metabolism in the presence of normal clotting factor activity in factory workers exposed to 4-hydroxycoumarins.

    PubMed

    Park, B K; Choonara, I A; Haynes, B P; Breckenridge, A M; Malia, R G; Preston, F E

    1986-03-01

    The case histories of two patients exposed to the novel anticoagulants brodifacoum and difenacoum are reported. Abnormal vitamin K1 metabolism, as indicated by elevated vitamin K1 2,3-epoxide plasma concentrations after i.v. administration of vitamin K1, could be detected for more than 18 months after exposure to the anticoagulants. There was a marked prolongation of prothrombin time (greater than 50 s) in both cases, at the time of exposure. However, subsequent haematological investigations (prothrombin time and vitamin K-dependent clotting factor activity) have been shown to be normal in both cases for at least 18 months. These cases confirm the long-acting nature of brodifacoum and difenacoum and present an apparent dissociation between the effect of coumarin anticoagulants on vitamin K1 metabolism and clotting factor activity. PMID:3964529

  3. Abnormal vitamin K metabolism in the presence of normal clotting factor activity in factory workers exposed to 4-hydroxycoumarins.

    PubMed Central

    Park, B K; Choonara, I A; Haynes, B P; Breckenridge, A M; Malia, R G; Preston, F E

    1986-01-01

    The case histories of two patients exposed to the novel anticoagulants brodifacoum and difenacoum are reported. Abnormal vitamin K1 metabolism, as indicated by elevated vitamin K1 2,3-epoxide plasma concentrations after i.v. administration of vitamin K1, could be detected for more than 18 months after exposure to the anticoagulants. There was a marked prolongation of prothrombin time (greater than 50 s) in both cases, at the time of exposure. However, subsequent haematological investigations (prothrombin time and vitamin K-dependent clotting factor activity) have been shown to be normal in both cases for at least 18 months. These cases confirm the long-acting nature of brodifacoum and difenacoum and present an apparent dissociation between the effect of coumarin anticoagulants on vitamin K1 metabolism and clotting factor activity. PMID:3964529

  4. Intelligence-related differences in the asymmetry of spontaneous cerebral activity.

    PubMed

    Santarnecchi, Emiliano; Tatti, Elisa; Rossi, Simone; Serino, Vinicio; Rossi, Alessandro

    2015-09-01

    Recent evidence suggests the spontaneous BOLD signal synchronization of corresponding interhemispheric, homotopic regions as a stable trait of human brain physiology, with emerging differences in such organization being also related to some pathological conditions. To understand whether such brain functional symmetries play a role into higher-order cognitive functioning, here we correlated the functional homotopy profiles of 119 healthy subjects with their intelligence level. Counterintuitively, reduced homotopic connectivity in above average-IQ versus average-IQ subjects was observed, with significant reductions in visual and somatosensory cortices, supplementary motor area, rolandic operculum, and middle temporal gyrus, possibly suggesting that a downgrading of interhemispheric talk at rest could be associated with higher cognitive functioning. These regions also showed an increased spontaneous synchrony with medial structures located in ipsi- and contralateral hemispheres, with such pattern being mostly detectable for regions placed in the left hemisphere. The interactions with age and gender have been also tested, with different patterns for subjects above and below 25 years old and less homotopic connectivity in the prefrontal cortex and posterior midline regions in female participants with higher IQ scores. These findings support prior evidence suggesting a functional role for homotopic connectivity in human cognitive expression, promoting the reduction of synchrony between primary sensory regions as a predictor of higher intelligence levels. PMID:26059228

  5. On the Effects on Cortical Spontaneous Activity of the Symmetries of the Network of Pinwheels in Visual Area V1.

    PubMed

    Veltz, Romain; Chossat, Pascal; Faugeras, Olivier

    2015-12-01

    This paper challenges and extends earlier seminal work. We consider the problem of describing mathematically the spontaneous activity of V1 by combining several important experimental observations including (1) the organization of the visual cortex into a spatially periodic network of hypercolumns structured around pinwheels, (2) the difference between short-range and long-range intracortical connections, the first ones being rather isotropic and producing naturally doubly periodic patterns by Turing mechanisms, the second one being patchy, and (3) the fact that the Turing patterns spontaneously produced by the short-range connections and the network of pinwheels have similar periods. By analyzing the PO maps, we are able to classify all possible singular points (the pinwheels) as having symmetries described by a small subset of the wallpaper groups. We then propose a description of the spontaneous activity of V1 using a classical voltage-based neural field model that features isotropic short-range connectivities modulated by non-isotropic long-range connectivities. A key observation is that, with only short-range connections and because the problem has full translational invariance in this case, a spontaneous doubly periodic pattern generates a 2-torus in a suitable functional space which persists as a flow-invariant manifold under small perturbations, for example when turning on the long-range connections. Through a complete analysis of the symmetries of the resulting neural field equation and motivated by a numerical investigation of the bifurcations of their solutions, we conclude that the branches of solutions which are stable over an extended range of parameters are those that correspond to patterns with an hexagonal (or nearly hexagonal) symmetry. The question of which patterns persist when turning on the long-range connections is answered by (1) analyzing the remaining symmetries on the perturbed torus and (2) combining this information with the Poincar

  6. Spontaneous stress fractures of the femoral neck

    SciTech Connect

    Dorne, H.L.; Lander, P.H.

    1985-02-01

    The diagnosis of spontaneous stress fractures of the femoral neck, a form of insufficiency stress fracture, can be missed easily. Patients present with unremitting hip pain without a history of significant trauma or unusual increase in daily activity. The initial radiographic features include osteoporosis, minor alterations of trabecular alignment, minimal extracortical or endosteal reaction, and lucent fracture lines. Initial scintigraphic examinations performed in three of four patients showed focal increased radionuclide uptake in two and no focal abnormality in one. Emphasis is placed on the paucity of early findings. Evaluation of patients with persistent hip pain requires a high degree of clinical suspicion and close follow-up; the sequelae of undetected spontaneous fractures are subcapital fracture with displacement, angular deformity, and a vascular necrosis of the femoral head.

  7. A Cognitive Neuroscience View of Schizophrenic Symptoms: Abnormal Activation of a System for Social Perception and Communication

    PubMed Central

    Wible, Cynthia G.; Preus, Alexander P.; Hashimoto, Ryuichiro

    2009-01-01

    We will review converging evidence that language related symptoms of the schizophrenic syndrome such as auditory verbal hallucinations arise at least in part from processing abnormalities in posterior language regions. These language regions are either adjacent to or overlapping with regions in the (posterior) temporal cortex and temporo-parietal occipital junction that are part of a system for processing social cognition, emotion, and self representation or agency. The inferior parietal and posterior superior temporal regions contain multi-modal representational systems that may also provide rapid feedback and feed-forward activation to unimodal regions such as auditory cortex. We propose that the over-activation of these regions could not only result in erroneous activation of semantic and speech (auditory word) representations, resulting in thought disorder and voice hallucinations, but could also result in many of the other symptoms of schizophrenia. These regions are also part of the so-called “default network”, a network of regions that are normally active; and their activity is also correlated with activity within the hippocampal system. PMID:19809534

  8. γ-Band deficiency and abnormal thalamocortical activity in P/Q-type channel mutant mice

    PubMed Central

    Llinás, Rodolfo R.; Choi, Soonwook; Urbano, Francisco J.; Shin, Hee-Sup

    2007-01-01

    Thalamocortical in vivo and in vitro function was studied in mice lacking P/Q-type calcium channels (CaV2.1), in which N-type calcium channels (CaV2.2) supported central synaptic transmission. Unexpectedly, in vitro patch recordings from thalamic neurons demonstrated no γ-band subthreshold oscillation, and voltage-sensitive dye imaging demonstrated an absence of cortical γ-band-dependent columnar activation involving cortical inhibitory interneuron activity. In vivo electroencephalogram recordings showed persistent absence status and a dramatic reduction of γ-band activity. Pharmacological block of T-type calcium channels (CaV3), although not noticeably affecting normal control animals, left the knockout mice in a coma-like state. Hence, although N-type calcium channels can rescue P/Q-dependent synaptic transmission, P/Q calcium channels are essential in the generation of γ-band activity and resultant cognitive function. PMID:17968008

  9. Up‐modulation of interferon‐γ mediates the enhancement of spontanous cytotoxicity in prolactin‐activated natural killer cells

    PubMed Central

    Matera, L; Contarini, M; Bellone, G; Forno, B; Biglino, A

    1999-01-01

    Prolactin (PRL) has been shown to participate in lymphocyte activation. In particular, the constitutive natural killer (NK) and the lymphokine‐activated killer (LAK) cytotoxicity of CD56+ CD16+ cells is increased by its physiological to supraphysiological concentrations. As PRL has been shown to up‐regulate the production of interferon‐γ (IFN‐γ) by peripheral blood mononuclear cells, we studied its effect on IFN‐γ production by NK cells as a possible mechanism of autocrine activation of cytotoxicity. Released and intracellular IFN‐γ, as well as IFN‐γ mRNA expression, were increased by pituitary and recombinant human PRL, which stimulated optimal NK and LAK cytotoxicity. Treatment with blocking anti‐IFN‐γ monoclonal antibody (mAb) selectively affected PRL‐increased killing of K562 targets, demonstrating that PRL‐mediated enhancement of spontaneous cytotoxicity depends, at least in part, on up‐regulation of IFN‐γ. PMID:10583598

  10. Spontaneous activity in electromyography may differentiate certain benign lower motor neuron disease forms from amyotrophic lateral sclerosis.

    PubMed

    Jokela, Manu E; Jääskeläinen, Satu K; Sandell, Satu; Palmio, Johanna; Penttilä, Sini; Saukkonen, Annamaija; Soikkeli, Raija; Udd, Bjarne

    2015-08-15

    There is limited data on electromyography (EMG) findings in other motor neuron disorders than amyotrophic lateral sclerosis (ALS). We assessed whether the distribution of active denervation detected by EMG, i.e. fibrillations and fasciculations, differs between ALS and slowly progressive motor neuron disorders. We compared the initial EMG findings of 43 clinically confirmed, consecutive ALS patients with those of 41 genetically confirmed Late-onset Spinal Motor Neuronopathy and 14 Spinal and Bulbar Muscular Atrophy patients. Spontaneous activity was more frequently detected in the first dorsal interosseus and deltoid muscles of ALS patients than in patients with the slowly progressive motor neuron diseases. The most important observation was that absent fibrillations in the first dorsal interosseus muscle identified the benign forms with sensitivities of 66%-77% and a specificity of 93%. The distribution of active denervation may help to separate ALS from mimicking disorders at an early stage. PMID:26059445

  11. Detection of abnormal muscle activations during walking following spinal cord injury (SCI).

    PubMed

    Wang, Ping; Low, K H; McGregor, Alison H; Tow, Adela

    2013-04-01

    In order to identify optimal rehabilitation strategies for spinal cord injury (SCI) participants, assessment of impaired walking is required to detect, monitor and quantify movement disorders. In the proposed assessment, ten healthy and seven SCI participants were recruited to perform an over-ground walking test at slow walking speeds. SCI participants were given assistance from physiotherapists, if required, while they were walking. In agreement with other research, larger cadence and smaller step length and swing phase of SCI gait were observed as a result of muscle weakness and resultant gait instability. Muscle activation patterns of seven major leg muscles were collected. The EMG signal was processed by the RMS in frequency domain to represent the muscle activation power, and the distribution of muscle activation was compared between healthy and SCI participants. The alternations of muscle activation within the phases of the gait cycle are highlighted to facilitate our understanding of the underlying muscular activation following SCI. Key differences were observed (p-value=0.0006) in the reduced activation of tibialis anterior (TA) in single stance phase and rectus femoris (RF) in swing phase (p-value=0.0011). We can then conclude that the proposed assessment approach of gait provides valuable information that can be used to target and define therapeutic interventions and their evaluation; hence impacting the functional outcome of SCI individuals. PMID:23396198

  12. Feeling Abnormal: Simulation of Deviancy in Abnormal and Exceptionality Courses.

    ERIC Educational Resources Information Center

    Fernald, Charles D.

    1980-01-01

    Describes activity in which student in abnormal psychology and psychology of exceptional children classes personally experience being judged abnormal. The experience allows the students to remember relevant research, become sensitized to the feelings of individuals classified as deviant, and use caution in classifying individuals as abnormal.…

  13. Abnormal Amygdala and Prefrontal Cortex Activation to Facial Expressions in Pediatric Bipolar Disorder

    PubMed Central

    Garrett, Amy; Reiss, Allan; Howe, Meghan; Kelley, Ryan; Singh, Manpreet; Adleman, Nancy; Karchemskiy, Asya; Chang, Kiki

    2012-01-01

    Objective Previous functional magnetic resonance imaging (fMRI) studies in pediatric bipolar disorder (BD) have reported greater amygdala and less dorsolateral prefrontal cortex (DLPFC) activation to facial expressions compared to healthy controls. The current study investigates whether these differences are associated with the early or late phase of activation, suggesting different temporal characteristics of brain responses. Method Twenty euthymic adolescents with familial BD (14 male) and twenty-one healthy control subjects (13 male) underwent fMRI scanning during presentation of happy, sad, and neutral facial expressions. Whole brain voxel-wise analyses were conducted in SPM5, using a 3-way analysis of variance (ANOVA) with factors group (BD and healthy control [HC]), facial expression (happy, sad, and neutral versus scrambled), and phase (early and late, corresponding to the first and second half of each block of faces). Results There were no significant group differences in task performance, age, gender, or IQ. Significant activation from the Main Effect of Group included greater DLPFC activation in the HC group, and greater amygdala/hippocampal activation in the BD group. The interaction of Group X Phase identified clusters in the superior temporal sulcus/insula and visual cortex, where activation increased from the early to late phase of the block for the BD but not the HC group. Conclusions These findings are consistent with previous studies that suggest deficient prefrontal cortex regulation of heightened amygdala response to emotional stimuli in pediatric BD. Increasing activation over time in superior temporal and visual cortices suggests difficulty processing or disengaging attention from emotional faces in BD. PMID:22840553

  14. Adolescent Binge Drinking Linked to Abnormal Spatial Working Memory Brain Activation: Differential Gender Effects

    PubMed Central

    Squeglia, Lindsay M.; Schweinsburg, Alecia Dager; Pulido, Carmen; Tapert, Susan F.

    2011-01-01

    Background Binge drinking is prevalent during adolescence, and its effect on neurocognitive development is of concern. In adult and adolescent populations, heavy substance use has been associated with decrements in cognitive functioning, particularly on tasks of spatial working memory (SWM). Characterizing the gender-specific influences of heavy episodic drinking on SWM may help elucidate the early functional consequences of drinking on adolescent brain functioning. Methods 40 binge drinkers (13 females, 27 males) and 55 controls (24 females, 31 males) ages 16 to 19, completed neuropsychological testing, substance use interviews, and a spatial working memory task (SWM) during functional magnetic resonance imaging (fMRI). Results Significant binge drinking status x gender interactions were found (p<.05) in 8 brain regions spanning bilateral frontal, anterior cingulate, temporal, and cerebellar cortices. In all regions, female binge drinkers showed less SWM activation than female controls, while male bingers exhibited greater SWM response than male controls. For female binge drinkers, less activation was associated with poorer sustained attention and working memory performances (ps<.025). For male binge drinkers, greater activation was linked to better spatial performance (p<.025). Conclusion Binge drinking during adolescence is associated with gender-specific differences in frontal, temporal, and cerebellar brain activation during a SWM task, which in turn relate to cognitive performance. Activation correlates with neuropsychological performance, strengthening the argument that BOLD activation is both affected by alcohol use and is an important indicator of behavioral functioning. Females may be more vulnerable to the neurotoxic effects of heavy alcohol use during adolescence, while males may be more resilient to the deleterious effects of binge drinking. Future longitudinal research will examine the significance of SWM brain activation as an early neurocognitive

  15. Effects of inspiratory muscle training on exercise capacity and spontaneous physical activity in elderly subjects: a randomized controlled pilot trial.

    PubMed

    Aznar-Lain, S; Webster, A L; Cañete, S; San Juan, A F; López Mojares, L M; Pérez, M; Lucia, A; Chicharro, J L

    2007-12-01

    Inspiratory muscle training (IMT) has been shown to improve exercise capacity in diseased populations. We chose to examine the effects of eight weeks of IMT on exercise capacity and spontaneous physical activity in elderly individuals. Eighteen moderately active elderly subjects (68.1 +/- 6.8 years [mean +/- SD]; range 58 - 78 years) were randomly assigned to either an experimental group (n = 9) or a control group (n = 9) in a double-blind manner. All subjects underwent inspiratory muscle testing, treadmill exercise testing and a four-day measurement period of spontaneous physical activity (using accelerometry) both pre- and post-intervention. The experimental group underwent eight weeks of incremental IMT using a pressure threshold device, while the control group underwent sham training using identical devices. After IMT training, inspiratory muscle strength (mean + 21.5 cm H (2)O; 95 % CI: 9.3, 33.7; p = 0.002), V.O (2peak) (+ 2.8 ml x min (-1) x kg (-1); 95 % CI: 0.5, 5.2; p = 0.022), time to exhaustion during a fixed workload treadmill test (+ 7.1 min; 95 % CI: 1.8, 2.4; p = 0.013) and time engaged in moderate-to-vigorous physical activity (+ 59 min; 95 % CI: 15, 78; p = 0.008) improved. Except for a decline in moderate-to-vigorous physical activity, no significant changes were seen in the control group. Therefore, IMT may be a useful technique for positively influencing exercise capacity and physical activity in elderly individuals. PMID:17534784

  16. Effect of He-Ne laser irradiation on spontaneous contractive activity and basal tone level of rat portal vein

    NASA Astrophysics Data System (ADS)

    Petrishchev, Nikolai N.; Barabanova, Valeria V.; Mikhailova, Irina A.; Chephu, Svetlana G.

    2000-11-01

    To study the effect of He-Ne irradiation (632.8 nm, 15 mW/cm2) on spontaneous contractive activity the fragments of rat portal vein weremounted isometrically in Krebs buffer. Irradiation of vessel fragments by He-Ne laser during 3,5 and 10 min caused the decrease of ton up to 50%, which lasted in postirradiation period (the observation time - 10 min). The frequency of phasic and tonic contractions did not change, but the amplitude increased up to 40% as compared to the initial level. The decreased basal tone level and the increased amplitude of phasic oscillations lasted in postirradiation period. Adding NO synthasa blocator (N - nitro-L-arginine) to Krebs solution before irradiation caused no significant changes mentioned above parameters. Irradiation and coputing of the same parameters of spontaneous contractive activity of vena porta caused no effects, mentioned in the absence of the blocator. From the results it is concluded that the decrease of tone is evoked by the increase of EDRF production and cGMP. The increase of amplitude of phasic and tonic contractions is connected with increase of Ca++ entry in every contraction cycle as a result of membrane Ca++ pool increase.

  17. Association between chronic stress-induced structural abnormalities in Ranvier nodes and reduced oligodendrocyte activity in major depression.

    PubMed

    Miyata, Shingo; Taniguchi, Manabu; Koyama, Yoshihisa; Shimizu, Shoko; Tanaka, Takashi; Yasuno, Fumihiko; Yamamoto, Akihide; Iida, Hidehiro; Kudo, Takashi; Katayama, Taiichi; Tohyama, Masaya

    2016-01-01

    Repeated stressful events are associated with the onset of major depressive disorder (MDD). We previously showed oligodendrocyte (OL)-specific activation of the serum/glucocorticoid-regulated kinase (SGK)1 cascade, increased expression of axon-myelin adhesion molecules, and elaboration of the oligodendrocytic arbor in the corpus callosum of chronically stressed mice. In the current study, we demonstrate that the nodes and paranodes of Ranvier in the corpus callosum were narrower in these mice. Chronic stress also led to diffuse redistribution of Caspr and Kv 1.1 and decreased the activity in white matter, suggesting a link between morphological changes in OLs and inhibition of axonal activity. OL primary cultures subjected to chronic stress resulted in SGK1 activation and translocation to the nucleus, where it inhibited the transcription of metabotropic glutamate receptors (mGluRs). Furthermore, the cAMP level and membrane potential of OLs were reduced by chronic stress exposure. We showed by diffusion tensor imaging that the corpus callosum of patients with MDD exhibited reduced fractional anisotropy, reflecting compromised white matter integrity possibly caused by axonal damage. Our findings suggest that chronic stress disrupts the organization of the nodes of Ranvier by suppressing mGluR activation in OLs, and that specific white matter abnormalities are closely associated with MDD onset. PMID:26976207

  18. Association between chronic stress-induced structural abnormalities in Ranvier nodes and reduced oligodendrocyte activity in major depression

    PubMed Central

    Miyata, Shingo; Taniguchi, Manabu; Koyama, Yoshihisa; Shimizu, Shoko; Tanaka, Takashi; Yasuno, Fumihiko; Yamamoto, Akihide; Iida, Hidehiro; Kudo, Takashi; Katayama, Taiichi; Tohyama, Masaya

    2016-01-01

    Repeated stressful events are associated with the onset of major depressive disorder (MDD). We previously showed oligodendrocyte (OL)-specific activation of the serum/glucocorticoid-regulated kinase (SGK)1 cascade, increased expression of axon-myelin adhesion molecules, and elaboration of the oligodendrocytic arbor in the corpus callosum of chronically stressed mice. In the current study, we demonstrate that the nodes and paranodes of Ranvier in the corpus callosum were narrower in these mice. Chronic stress also led to diffuse redistribution of Caspr and Kv 1.1 and decreased the activity in white matter, suggesting a link between morphological changes in OLs and inhibition of axonal activity. OL primary cultures subjected to chronic stress resulted in SGK1 activation and translocation to the nucleus, where it inhibited the transcription of metabotropic glutamate receptors (mGluRs). Furthermore, the cAMP level and membrane potential of OLs were reduced by chronic stress exposure. We showed by diffusion tensor imaging that the corpus callosum of patients with MDD exhibited reduced fractional anisotropy, reflecting compromised white matter integrity possibly caused by axonal damage. Our findings suggest that chronic stress disrupts the organization of the nodes of Ranvier by suppressing mGluR activation in OLs, and that specific white matter abnormalities are closely associated with MDD onset. PMID:26976207

  19. Activation of a Mitochondrial ATPase Gene Induces Abnormal Seed Development in Arabidopsis

    PubMed Central

    Baek, Kon; Seo, Pil Joon; Park, Chung-Mo

    2011-01-01

    The ATPases associated with various cellular activities (AAA) proteins are widespread in living organisms. Some of the AAA-type ATPases possess metalloprotease activities. Other members constitute the 26S proteasome complexes. In recent years, a few AAA members have been implicated in vesicle-mediated secretion, membrane fusion, cellular organelle biogenesis, and hypersensitive responses (HR) in plants. However, the physiological roles and biochemical activities of plant AAA proteins have not yet been defined at the molecular level, and regulatory mechanisms underlying their functions are largely unknown. In this study, we showed that overexpression of an Arabidopsis gene encoding a mitochondrial AAA protein, ATPase-in-Seed-Development (ASD), induces morphological and anatomical defects in seed maturation. The ASD gene is expressed at a high level during the seed maturation process and in mature seeds but is repressed rapidly in germinating seeds. Transgenic plants overexpressing the ASD gene are morphologically normal. However, seed formation is severely disrupted in the transgenic plants. The ASD gene is induced by abiotic stresses, such as low temperatures and high salinity, in an abscisic acid (ABA)- dependent manner. The ASD protein possesses ATPase activity and is localized into the mitochondria. Our observations suggest that ASD may play a role in seed maturation by influencing mitochondrial function under abiotic stress. PMID:21359673

  20. Abnormal Amygdala and Prefrontal Cortex Activation to Facial Expressions in Pediatric Bipolar Disorder

    ERIC Educational Resources Information Center

    Garrett, Amy S.; Reiss, Allan L.; Howe, Meghan E.; Kelley, Ryan G.; Singh, Manpreet K.; Adleman, Nancy E.; Karchemskiy, Asya; Chang, Kiki D.

    2012-01-01

    Objective: Previous functional magnetic resonance imaging (fMRI) studies in pediatric bipolar disorder (BD) have reported greater amygdala and less dorsolateral prefrontal cortex (DLPFC) activation to facial expressions compared to healthy controls. The current study investigates whether these differences are associated with the early or late…

  1. Abnormal fMRI Activation Pattern during Story Listening in Individuals with Down Syndrome

    ERIC Educational Resources Information Center

    Reynolds Losin, Elizabeth A.; Rivera, Susan M.; O'Hare, Elizabeth D.; Sowell, Elizabeth R.; Pinter, Joseph D.

    2009-01-01

    Down syndrome is characterized by disproportionately severe impairments of speech and language, yet little is known about the neural underpinnings of these deficits. We compared fMRI activation patterns during passive story listening in 9 young adults with Down syndrome and 9 approximately age-matched, typically developing controls. The typically…

  2. Role of abnormal anterior pituitary hormones-growth hormone and prolactin in active systemic lupus erythematosus

    PubMed Central

    Zhu, Xiaohua; Xu, Jinhua; Li, Shujuan; Huang, Wen; Li, Feng

    2015-01-01

    Background: The role of anterior pituitary hormones in systemic lupus erythematosus (SLE) remains controversial. Aims and Objectives: We determined the expression levels of human growth hormone (GH), prolactin (PRL), and their receptors in subjects presenting with SLE, and modulation of disease severity. Materials and methods: Forty-seven subjects and ten healthy controls were assessed for possible association between SLE disease activity and levels of serum PRL, GH and thyrotropin-releasing hormone (TRH). In peripheral blood mononuclear cells (PBMC), specific binding and mRNA expression of receptors for GH (GHR), and PRL (PRLR) were determined by receptor-ligand binding assay (RLBA) and RT-PCR. PBMC of recruited subjects were treated with hPRL and rhGH to assess IgG production and antibodies against dsDNA. Results: In active SLE subjects we found elevated PRL and GH levels. Study subject PBMCs displayed augmented GHR and PRLR protein and mRNA expression. Study subjects also showed a positive correlation in serum PRL levels and specific antibodies against dsDNA, SLE disease activity index (SLEDAI), and proteinuria. However, a negative correlation was found between serum PRL levels and complement component C3. We found a positive correlation between specific binding rates of PRLR and GHR and both SLE activity and dsDNA antibody titers. Enhanced IgG and anti-dsDNA secretion was observed in cultured PBMC stimulated by PRL or GH with/without PHA, PWM, IL-2 or IL-10. In active SLE, a close association was found between augmented PRL and GH levels, expression and specific binding activities of PRLR and GHR, and changes in the specific titer of anti-dsDNA. Conclusion: Anterior pituitary hormones play an important role in the pathogenesis of SLE. High levels of growth hormone (GH) and prolactin (PRL) play a role in pathogenesis of SLE, which is correlated with SLE disease activity and antibodies against dsDNA. The mechanism of GH and PRL in SLE was complicated and should

  3. Redox regulation of apurinic/apyrimidinic endonuclease 1 activity in Long-Evans Cinnamon rats during spontaneous hepatitis.

    PubMed

    Karmahapatra, Soumendra Krishna; Saha, Tapas; Adhikari, Sanjay; Woodrick, Jordan; Roy, Rabindra

    2014-03-01

    The Long-Evans Cinnamon (LEC) rat is an animal model for Wilson's disease. This animal is genetically predisposed to copper accumulation in the liver, increased oxidative stress, accumulation of DNA damage, and the spontaneous development of hepatocellular carcinoma. Thus, this animal model is useful for studying the relationship of endogenous DNA damage to spontaneous carcinogenesis. In this study, we have investigated the apurinic/apyrimidinic endonuclease 1 (APE1)-mediated excision repair of endogenous DNA damage, apurinic/apyrimidinic (AP)-sites, which is highly mutagenic and implicated in human cancer. We found that the activity was reduced in the liver extracts from the acute hepatitis period of LEC rats as compared with extracts from the age-matched Long-Evans Agouti rats. The acute hepatitis period had also a heightened oxidative stress condition as assessed by an increase in oxidized glutathione level and loss of enzyme activity of glyceraldehyde 3-phosphate dehydrogenase, a key redox-sensitive protein in cells. Interestingly, the activity reduction was not due to changes in protein expression but apparently by reversible protein oxidation as the addition of reducing agents to extracts of the liver from acute hepatitis period reactivated APE1 activity and thus, confirmed the oxidation-mediated loss of APE1 activity under increased oxidative stress. These findings show for the first time in an animal model that the repair mechanism of AP-sites is impaired by increased oxidative stress in acute hepatitis via redox regulation which contributed to the increased accumulation of mutagenic AP-sites in liver DNA. PMID:24337968

  4. Abnormal Activation of the Social Brain Network in Children with Autism Spectrum Disorder: An fMRI Study

    PubMed Central

    Kim, Sun-Young; Choi, Uk-Su; Park, Sung-Yeon; Oh, Se-Hong; Yoon, Hyo-Woon; Koh, Yun-Joo; Im, Woo-Young; Park, Jee-In; Song, Dong-Ho

    2015-01-01

    Objective The aim of this study is to investigate abnormal findings of social brain network in Korean children with autism spectrum disorder (ASD) compared with typically developing children (TDC). Methods Functional magnetic resonance imaging (fMRI) was performed to examine brain activations during the processing of emotional faces (happy, fearful, and neutral) in 17 children with ASD, 24 TDC. Results When emotional face stimuli were given to children with ASD, various areas of the social brain relevant to social cognition showed reduced activation. Specifically, ASD children exhibited less activation in the right amygdala (AMY), right superior temporal sulcus (STS) and right inferior frontal gyrus (IFG) than TDC group when fearful faces were shown. Activation of left insular cortex and right IFG in response to happy faces was less in the ASD group. Similar findings were also found in left superior insular gyrus and right insula in case of neutral stimulation. Conclusion These findings suggest that children with ASD have different processing of social and emotional experience at the neural level. In other words, the deficit of social cognition in ASD could be explained by the deterioration of the capacity for visual analysis of emotional faces, the subsequent inner imitation through mirror neuron system (MNS), and the ability to transmit it to the limbic system and to process the transmitted emotion. PMID:25670944

  5. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy.

    PubMed

    Teachey, David T; Rheingold, Susan R; Maude, Shannon L; Zugmaier, Gerhard; Barrett, David M; Seif, Alix E; Nichols, Kim E; Suppa, Erica K; Kalos, Michael; Berg, Robert A; Fitzgerald, Julie C; Aplenc, Richard; Gore, Lia; Grupp, Stephan A

    2013-06-27

    Blinatumomab is a CD19/CD3-bispecific T-cell receptor-engaging (BiTE) antibody with efficacy in refractory B-precursor acute lymphoblastic leukemia. Some patients treated with blinatumomab and other T cell-activating therapies develop cytokine release syndrome (CRS). We hypothesized that patients with more severe toxicity may experience abnormal macrophage activation triggered by the release of cytokines by T-cell receptor-activated cytotoxic T cells engaged by BiTE antibodies and leading to hemophagocytic lymphohistiocytosis (HLH). We prospectively monitored a patient during blinatumomab treatment and observed that he developed HLH. He became ill 36 hours into the infusion with fever, respiratory failure, and circulatory collapse. He developed hyperferritinemia, cytopenias, hypofibrinogenemia, and a cytokine profile diagnostic for HLH. The HLH continued to progress after discontinuation of blinatumomab; however, he had rapid improvement after IL-6 receptor-directed therapy with tocilizumab. Patients treated with T cell-activating therapies, including blinatumomab, should be monitored for HLH, and cytokine-directed therapy may be considered in cases of life-threatening CRS. This trial was registered at www.clinicaltrials.gov as #NCT00103285. PMID:23678006

  6. Spontaneous Fission

    DOE R&D Accomplishments Database

    Segre, Emilio

    1950-11-22

    The first attempt to discover spontaneous fission in uranium was made by [Willard] Libby, who, however, failed to detect it on account of the smallness of effect. In 1940, [K. A.] Petrzhak and [G. N.] Flerov, using more sensitive methods, discovered spontaneous fission in uranium and gave some rough estimates of the spontaneous fission decay constant of this substance. Subsequently, extensive experimental work on the subject has been performed by several investigators and will be quoted in the various sections. [N.] Bohr and [A.] Wheeler have given a theory of the effect based on the usual ideas of penetration of potential barriers. On this project spontaneous fission has been studied for the past several years in an effort to obtain a complete picture of the phenomenon. For this purpose the spontaneous fission decay constants {lambda} have been measured for separated isotopes of the heavy elements wherever possible. Moreover, the number {nu} of neutrons emitted per fission has been measured wherever feasible, and other characteristics of the spontaneous fission process have been studied. This report summarizes the spontaneous fission work done at Los Alamos up to January 1, 1945. A chronological record of the work is contained in the Los Alamos monthly reports.

  7. Abnormal medial temporal activity for bound information during working memory maintenance in patients with schizophrenia.

    PubMed

    Luck, David; Danion, Jean-Marie; Marrer, Corrine; Pham, Bich-Tuy; Gounot, Daniel; Foucher, Jack

    2010-08-01

    Alterations of binding in long-term memory in schizophrenia are well established and occur as a result of aberrant activity in the medial temporal lobe (MTL). In working memory (WM), such a deficit is less clear and the pathophysiological bases remain unstudied. Seventeen patients with schizophrenia and 17 matched healthy controls performed a WM binding task while undergoing functional magnetic resonance imaging. Binding was assessed by contrasting two conditions comprising an equal amount of verbal and spatial information (i.e., three letters and three spatial locations), but differing in the absence or presence of a link between them. In healthy controls, MTL activation was observed for encoding and maintenance of bound information but not for its retrieval. Between-group comparisons revealed that patients with schizophrenia showed MTL hypoactivation during the maintenance phase only. In addition, BOLD signals correlated with behavioral performance in controls but not in patients with schizophrenia. Our results confirm the major role that the MTL plays in the pathophysiology of schizophrenia. Short-term and long-term relational memory deficits in schizophrenia may share common cognitive and functional pathological bases. Our results provide additional information about the episodic buffer that represents an integrative interface between WM and long-term memory. PMID:19693783

  8. IL-6 blockade reverses the abnormal STAT activation of peripheral blood leukocytes from rheumatoid arthritis patients.

    PubMed

    Ortiz, M A; Diaz-Torné, C; Hernández, M V; Reina, D; de la Fuente, D; Castellví, I; Moya, P; Ruiz, J M; Corominas, H; Zamora, C; Cantó, E; Sanmartí, R; Juarez, C; Vidal, S

    2015-06-01

    Considering the interplay of multiple STATs in response to cytokines, we investigated how IL-6 and its blocking affect STAT signaling in rheumatoid arthritis (RA). Leukocytes obtained from RA patients before and after tocilizumab treatment and healthy donors (HDs) were cytokine-stimulated and STAT phosphorylation was analyzed by cytometry. RA patients had significantly fewer pSTAT1+, pSTAT3+, and pSTAT6+ monocytes and pSTAT5+ lymphocytes than HDs. After 24weeks of treatment, percentages of IFNγ-induced pSTAT1+ and IL-10-induced pSTAT3+ monocytes in RA patients increased, reaching levels comparable to HDs. pSTAT1+ and pSTAT3+ cells correlated inversely with RA disease activity index and levels of pSTAT+ cells at baseline were higher in patients with good EULAR response to tocilizumab. IFNγ-induced pSTAT1+ cells correlated inversely with memory T cells and anti-CCP levels. IL-10-induced pSTAT3+ cells correlated with Treg/Teff ratio. Our findings suggest that IL-6 blocking reduces the inflammatory mechanisms through the correction of STAT1 and STAT3 activation status. PMID:25847223

  9. Changes in spontaneous EEG activity indicate a special kind of information processing in concept learning.

    PubMed

    Bösel, R; Mecklinger, A; Stolpe, R

    1990-12-01

    Some findings in the literature suggest that a high amount of spectral power in spontaneous EEG alpha 1 band (7.5-10.0 Hz) may be associated with tasks demanding extensive monitoring of stimulus information and combining features for a match with internal concepts ("exploration"). EEG recordings were obtained from 9 subjects involved in a concept-learning task. They had to match visually presented objects with a concept built up by hypothesis and to respond by pressing a "yes" or "no" key. Epochs of EEG data were analyzed with epoch center-times at 500 and 250 ms before response execution. In the case of "yes" responses, when subjects could match their hypothesis positively with combined features of the presented object increased alpha 1 spectral power was found. Also alpha 1 power was larger immediately after disconfirming feedback than after confirming feedback. Additionally, alpha 2 spectral power (10.5-12.5 Hz) was found to be larger 250 ms after confirming feedback than after disconfirming feedback. It is argued that alpha 1 power seems to reflect those mental processes which are involving in combining features and matching them to a concept in mind. The increase in alpha 2 power after confirming feedback is interpreted in terms of general processing demands imposed during task performance. PMID:2132682

  10. Dipeptidyl peptidase-4 inhibition by gemigliptin prevents abnormal vascular remodeling via NF-E2-related factor 2 activation.

    PubMed

    Choi, Seung Hee; Park, Sungmi; Oh, Chang Joo; Leem, Jaechan; Park, Keun-Gyu; Lee, In-Kyu

    2015-10-01

    Dipeptidyl peptidase-4 (DPP-4) inhibitors exert a potent anti-hyperglycemic effect and reduce cardiovascular risk in type 2 diabetic patients. Several studies have shown that DPP-4 inhibitors including sitagliptin have beneficial effects in atherosclerosis and cardiac infarction involving reactive oxygen species. Here, we show that gemigliptin can directly attenuate the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) via enhanced NF-E2-related factor 2 (Nrf2) activity. Gemigliptin dramatically prevented ligation injury-induced neointimal hyperplasia in mouse carotid arteries. Likewise, the proliferation of primary VSMCs was significantly attenuated by gemigliptin in a dose-dependent manner consistent with a decrease in phospho-Rb, resulting in G1 cell cycle arrest. We found that gemigliptin enhanced Nrf2 activity not only by mRNA expression, but also by increasing Keap1 proteosomal degradation by p62, leading to the induction of Nrf2 target genes such as HO-1 and NQO1. The anti-proliferative role of gemigliptin disappeared with DPP-4 siRNA knockdown, indicating that the endogenous DPP-4 in VSMCs contributed to the effect of gemigliptin. In addition, gemigliptin diminished TNF-α-mediated cell adhesion molecules such as MCP-1 and VCAM-1 and reduced MMP2 activity in VSMCs. Taken together, our data indicate that gemigliptin exerts a preventative effect on the proliferation and migration of VSMCs via Nrf2. PMID:26187356

  11. Accuracy of a Custom Physical Activity and Knee Angle Measurement Sensor System for Patients with Neuromuscular Disorders and Gait Abnormalities

    PubMed Central

    Feldhege, Frank; Mau-Moeller, Anett; Lindner, Tobias; Hein, Albert; Markschies, Andreas; Zettl, Uwe Klaus; Bader, Rainer

    2015-01-01

    Long-term assessment of ambulatory behavior and joint motion are valuable tools for the evaluation of therapy effectiveness in patients with neuromuscular disorders and gait abnormalities. Even though there are several tools available to quantify ambulatory behavior in a home environment, reliable measurement of joint motion is still limited to laboratory tests. The aim of this study was to develop and evaluate a novel inertial sensor system for ambulatory behavior and joint motion measurement in the everyday environment. An algorithm for behavior classification, step detection, and knee angle calculation was developed. The validation protocol consisted of simulated daily activities in a laboratory environment. The tests were performed with ten healthy subjects and eleven patients with multiple sclerosis. Activity classification showed comparable performance to commercially available activPAL sensors. Step detection with our sensor system was more accurate. The calculated flexion-extension angle of the knee joint showed a root mean square error of less than 5° compared with results obtained using an electro-mechanical goniometer. This new system combines ambulatory behavior assessment and knee angle measurement for long-term measurement periods in a home environment. The wearable sensor system demonstrated high validity for behavior classification and knee joint angle measurement in a laboratory setting. PMID:25954954

  12. Kamin Blocking Is Associated with Reduced Medial-Frontal Gyrus Activation: Implications for Prediction Error Abnormality in Schizophrenia

    PubMed Central

    Cross, Benjamin; Corcoran, Rhiannon

    2012-01-01

    The following study used 3-T functional magnetic resonance imaging (fMRI) to investigate the neural signature of Kamin blocking. Kamin blocking is an associative learning phenomenon seen where prior association of a stimulus (A) with an outcome blocks subsequent learning to an added stimulus (B) when both stimuli are later presented together (AB) with the same outcome. While there are a number of theoretical explanations of Kamin blocking, it is widely considered to exemplify the use of prediction error in learning, where learning occurs in proportion to the difference between expectation and outcome. In Kamin blocking as stimulus A fully predicts the outcome no prediction error is generated by the addition of stimulus B to form the compound stimulus AB, hence learning about it is “blocked”. Kamin blocking is disrupted in people with schizophrenia, their relatives and healthy individuals with high psychometrically-defined schizotypy. This disruption supports suggestions that abnormal prediction error is a core deficit that can help to explain the symptoms of schizophrenia. The present study tested 9 healthy volunteers on an f-MRI adaptation of Oades' “mouse in the house task”, the only task measuring Kamin blocking that shows disruption in schizophrenia patients that has been independently replicated. Participant's Kamin blocking scores were found to inversely correlate with Kamin-blocking-related activation within the prefrontal cortex, specifically the medial frontal gyrus. The medial frontal gyrus has been associated with the psychological construct of uncertainty, which we suggest is consistent with disrupted Kamin blocking and demonstrated in people with schizophrenia. These data suggest that the medial frontal gyrus merits further investigation as a potential locus of reduced Kamin blocking and abnormal prediction error in schizophrenia. PMID:23028415

  13. Pterygium epithelium abnormal differentiation related to activation of extracellular signal-regulated kinase signaling pathway in vitro

    PubMed Central

    Peng, Juan; Sha, Xiang-Yin; Liu, Yi; Yang, Rui-Ming; Wen, Ye

    2015-01-01

    AIM To investigate whether the abnormal differentiation of the pterygium epithelium is related to the extracellular signal-regulated kinase (ERK) signaling pathway in vitro. METHODS The expression levels of phosphorylated ERK (P-ERK), keratin family members including K19 and K10 and the ocular master control gene Pax-6 were measured in 16 surgically excised pterygium tissues and 12 eye bank conjunctiva. In colony-forming cell assays, the differences in clone morphology and in K10, K19, P-ERK and Pax-6 expression between the head and body were investigated. When cocultured with the ERK signaling pathway inhibitor PD98059, the changes in clone morphology, colony-forming efficiency, differentiated marker K10, K19 and Pax-6 expression and P-ERK protein expression level were examined by immunoreactivity and Western blot analysis. RESULTS The expression of K19 and Pax-6 decreased in the pterygium, especially in the head. No staining of K10 was found in the normal conjunctiva epithelium, but it was found to be expressed in the superficial cells in the head of the pterygium. Characteristic upregulation of P-ERK was observed by immunohistochemistry. The clone from the head with more differentiated cells in the center expressed more K10, and the clone from the body expressed more K19. The P-ERK protein level increased in the pterygium epithelium compared with conjunctiva and decreased when cocultured with PD98059. The same medium with the ERK inhibitor PD98059 was more effective in promoting clonal growth than conventional medium with 3T3 murine feeder layers. It was observed that the epithelium clone co-cultured with the inhibitor had decreased K10 expression and increased K19 and Pax-6 expression. CONCLUSION We suggest ERK signaling pathway activation might play a role in the pterygium epithelium abnormal differentiation. PMID:26682158

  14. [Congenital foot abnormalities].

    PubMed

    Delpont, M; Lafosse, T; Bachy, M; Mary, P; Alves, A; Vialle, R

    2015-03-01

    The foot may be the site of birth defects. These abnormalities are sometimes suspected prenatally. Final diagnosis depends on clinical examination at birth. These deformations can be simple malpositions: metatarsus adductus, talipes calcaneovalgus and pes supinatus. The prognosis is excellent spontaneously or with a simple orthopedic treatment. Surgery remains outstanding. The use of a pediatric orthopedist will be considered if malposition does not relax after several weeks. Malformations (clubfoot, vertical talus and skew foot) require specialized care early. Clubfoot is characterized by an equine and varus hindfoot, an adducted and supine forefoot, not reducible. Vertical talus combines equine hindfoot and dorsiflexion of the forefoot, which is performed in the midfoot instead of the ankle. Skew foot is suspected when a metatarsus adductus is resistant to conservative treatment. Early treatment is primarily orthopedic at birth. Surgical treatment begins to be considered after walking age. Keep in mind that an abnormality of the foot may be associated with other conditions: malposition with congenital hip, malformations with syndromes, neurological and genetic abnormalities. PMID:25524290

  15. The BTG4 and CAF1 complex prevents the spontaneous activation of eggs by deadenylating maternal mRNAs.

    PubMed

    Pasternak, Michał; Pfender, Sybille; Santhanam, Balaji; Schuh, Melina

    2016-09-01

    Once every menstrual cycle, eggs are ovulated into the oviduct where they await fertilization. The ovulated eggs are arrested in metaphase of the second meiotic division, and only complete meiosis upon fertilization. It is crucial that the maintenance of metaphase arrest is tightly controlled, because the spontaneous activation of the egg would preclude the development of a viable embryo (Zhang et al. 2015 J. Genet. Genomics 42, 477-485. (doi:10.1016/j.jgg.2015.07.004); Combelles et al. 2011 Hum. Reprod. 26, 545-552. (doi:10.1093/humrep/deq363); Escrich et al. 2011 J. Assist. Reprod. Genet. 28, 111-117. (doi:10.1007/s10815-010-9493-5)). However, the mechanisms that control the meiotic arrest in mammalian eggs are only poorly understood. Here, we report that a complex of BTG4 and CAF1 safeguards metaphase II arrest in mammalian eggs by deadenylating maternal mRNAs. As a follow-up of our recent high content RNAi screen for meiotic genes (Pfender et al. 2015 Nature 524, 239-242. (doi:10.1038/nature14568)), we identified Btg4 as an essential regulator of metaphase II arrest. Btg4-depleted eggs progress into anaphase II spontaneously before fertilization. BTG4 prevents the progression into anaphase by ensuring that the anaphase-promoting complex/cyclosome (APC/C) is completely inhibited during the arrest. The inhibition of the APC/C relies on EMI2 (Tang et al. 2010 Mol. Biol. Cell 21, 2589-2597. (doi:10.1091/mbc.E09-08-0708); Ohe et al. 2010 Mol. Biol. Cell 21, 905-913. (doi:10.1091/mbc.E09-11-0974)), whose expression is perturbed in the absence of BTG4. BTG4 controls protein expression during metaphase II arrest by forming a complex with the CAF1 deadenylase and we hypothesize that this complex is recruited to the mRNA via interactions between BTG4 and poly(A)-binding proteins. The BTG4-CAF1 complex drives the shortening of the poly(A) tails of a large number of transcripts at the MI-MII transition, and this wave of deadenylation is essential for the arrest in

  16. [Conjugated variability of spontaneous activity and behavioral response to olfactory stimuli in the taiga tick (Ixodes persulcatus)].

    PubMed

    Romashchenko, A V; Shnaĭder, E P; Petrovskiĭ, D V; Moshkin, M P

    2013-01-01

    According to -the automatic tracing of the movement of ticks in a Petri dish, motivational variability of the spontaneous activity and behavioral response of the taiga tick to olfactory stimuli was analyzed. In the studied sample, two groups of ticks that differ in the movement trajectory in the absence of stimulus were isolated, including ticks that mainly moved on the edge of the dish at maximum accessible height (group 1) and ticks that mainly moved at the bottom and wall of the dish (group 2). It was registered that ticks of group 1 (as opposed to ticks of group 2) demonstrated a pronounced behavioral response to olfactory stimuli (human synthetic pheromones and ammonia) and negative geotaxis. It was established that belonging to these groups depended On the time of day when the testing was performed and did not depend on the physiological age and infectious status. PMID:25510114

  17. An interactive activation and competition model of person knowledge, suggested by proactive interference by traits spontaneously inferred from behaviours.

    PubMed

    Wang, Yuanbo E; Higgins, Nancy C; Uleman, James S; Michaux, Aaron; Vipond, Douglas

    2016-03-01

    People unconsciously and unintentionally make inferences about others' personality traits based on their behaviours. In this study, a classic memory phenomenon - proactive interference (PI) - is for the first time used to detect spontaneous trait inferences. PI should occur when lists of behaviour descriptions, all implying the same trait, are to be remembered. Switching to a new trait should produce 'release' from proactive interference (or RPI). Results from two experiments supported these predictions. PI and RPI effects are consistent with an interactive activation and competition model of person perception (e.g., McNeill & Burton, 2002, J. Exp. Psychol., 55A, 1141), which predicts categorical organization of social behaviours based on personality traits. Advantages of this model are discussed. PMID:26096621

  18. Effects of the imidazobenzodiazepine R015-4513 on the stimulant and depressant actions of ethanol on spontaneous locomotor activity

    SciTech Connect

    Becker, H.C.

    1988-01-01

    The purpose of this study was to investigate the effects of the imidazobenzodiazepine R015-4513, a partial inverse agonist at benzodiazepine (BDZ) receptors, on the stimulant and depressant actions of ethanol in mice. For comparative purposes, another BDZ inverse agonist, FG-7142, was examined as well. Neither R015-4513 nor FG-7142 influenced the low-dose excitatory effects of ethanol on spontaneous locomotor activity. However, both R015-4513 and FG-7142 significantly antagonized the depressant effects of ethanol, and this antagonism was completely reversed by pretreatment with the BDZ receptor antagonist, R015-1788. These data suggest that R015-4513 is capable of antagonizing only some of the behavioral effects of ethanol, and in particular, those responses to ethanol that are mediated by modulation of the GABA/BDZ-chloride channel receptor complex.

  19. Endogenous cholinergic tone modulates spontaneous network level neuronal activity in primary cortical cultures grown on multi-electrode arrays

    PubMed Central

    2013-01-01

    Background Cortical cultures grown long-term on multi-electrode arrays (MEAs) are frequently and extensively used as models of cortical networks in studies of neuronal firing activity, neuropharmacology, toxicology and mechanisms underlying synaptic plasticity. However, in contrast to the predominantly asynchronous neuronal firing activity exhibited by intact cortex, electrophysiological activity of mature cortical cultures is dominated by spontaneous epileptiform-like global burst events which hinders their effective use in network-level studies, particularly for neurally-controlled animat (‘artificial animal’) applications. Thus, the identification of culture features that can be exploited to produce neuronal activity more representative of that seen in vivo could increase the utility and relevance of studies that employ these preparations. Acetylcholine has a recognised neuromodulatory role affecting excitability, rhythmicity, plasticity and information flow in vivo although its endogenous production by cortical cultures and subsequent functional influence upon neuronal excitability remains unknown. Results Consequently, using MEA electrophysiological recording supported by immunohistochemical and RT-qPCR methods, we demonstrate for the first time, the presence of intrinsic cholinergic neurons and significant, endogenous cholinergic tone in cortical cultures with a characterisation of the muscarinic and nicotinic components that underlie modulation of spontaneous neuronal activity. We found that tonic muscarinic ACh receptor (mAChR) activation affects global excitability and burst event regularity in a culture age-dependent manner whilst, in contrast, tonic nicotinic ACh receptor (nAChR) activation can modulate burst duration and the proportion of spikes occurring within bursts in a spatio-temporal fashion. Conclusions We suggest that the presence of significant endogenous cholinergic tone in cortical cultures and the comparability of its modulatory effects

  20. The Dynamics of Cortical Neuronal Activity in the First Minutes after Spontaneous Awakening in Rats and Mice

    PubMed Central

    Vyazovskiy, Vladyslav V.; Cui, Nanyi; Rodriguez, Alexander V.; Funk, Chadd; Cirelli, Chiara; Tononi, Giulio

    2014-01-01

    Study Objective: Upon awakening from sleep, a fully awake brain state is not reestablished immediately, but the origin and physiological properties of the distinct brain state during the first min after awakening are unclear. To investigate whether neuronal firing immediately upon arousal is different from the remaining part of the waking episode, we recorded and analyzed the dynamics of cortical neuronal activity in the first 15 min after spontaneous awakenings in freely moving rats and mice. Design: Intracortical recordings of the local field potential and neuronal activity in freely-moving mice and rats. Setting: Basic sleep research laboratory. Patients or Participants: WKY adult male rats, C57BL/6 adult male mice. Interventions: N/A. Measurements and Results: In both species the average population spiking activity upon arousal was initially low, though substantial variability in the dynamics of firing activity was apparent between individual neurons. A distinct population of neurons was found that was virtually silent in the first min upon awakening. The overall lower population spiking initially after awakening was associated with the occurrence of brief periods of generalized neuronal silence (OFF periods), whose frequency peaked immediately after awakening and then progressively declined. OFF periods incidence upon awakening was independent of ongoing locomotor activity but was sensitive to immediate preceding sleep/wake history. Notably, in both rats and mice if sleep before a waking episode was enriched in rapid eye movement sleep, the incidence of OFF periods was initially higher as compared to those waking episodes preceded mainly by nonrapid eye movement sleep. Conclusion: We speculate that an intrusion of sleep-like patterns of cortical neuronal activity into the wake state immediately after awakening may account for some of the changes in the behavior and cognitive function typical of what is referred to as sleep inertia. Citation: Vyazovskiy VV, Cui

  1. Effect of age and severity of cognitive dysfunction on spontaneous activity in pet dogs - part 2: social responsiveness.

    PubMed

    Rosado, B; González-Martínez, A; Pesini, P; García-Belenguer, S; Palacio, J; Villegas, A; Suárez, M-L; Santamarina, G; Sarasa, M

    2012-11-01

    Changes in social interactions with owners and other dogs are frequently observed in dogs with cognitive dysfunction syndrome (CDS). The aim of this work was to assess the effect of age and severity of CDS on social responsiveness. This is the second part of a 2-part report on spontaneous activity in pet dogs. A human interaction test and a mirror test were administered at baseline and 6 months later to assess social responses to humans and conspecifics, respectively, to four groups of privately-owned dogs: young (n=9), middle-aged (n=9), cognitively unimpaired aged (n=31), and cognitively impaired aged (n=36). The severity of cognitive impairment was considered in the last group and dogs were categorised as having either mild or severe CDS. The influence of the person and the mirror on locomotion and exploratory behaviour was also studied. Dogs were recorded in a testing room and the video recordings were subsequently analysed. Young dogs displayed more interactions involving physical contact with a person. Young and middle-aged dogs showed more vocalisations in response to social isolation. In contrast, aged animals spent more time in front of the mirror. Changes in social responsiveness associated with severe CDS included decreased response to social isolation and human interaction and increased time in front of the mirror, suggesting a deficit in habituation. Testing of spontaneous activity might help to characterise CDS in aged dogs, a condition increasingly diagnosed in veterinary clinics and a potentially useful natural model of Alzheimer's disease in humans. PMID:22578689

  2. Spontaneous flow in polar active fluids: the effect of a phenomenological self propulsion-like term.

    PubMed

    Bonelli, Francesco; Gonnella, Giuseppe; Tiribocchi, Adriano; Marenduzzo, Davide

    2016-01-01

    We present hybrid lattice Boltzmann simulations of extensile and contractile active fluids where we incorporate phenomenologically the tendency of active particles such as cell and bacteria, to move, or swim, along the local orientation. Quite surprisingly, we show that the interplay between alignment and activity can lead to completely different results, according to geometry (periodic boundary conditions or confinement between flat walls) and nature of the activity (extensile or contractile). An interesting generic outcome is that the alignment interaction can transform stationary active patterns into continuously moving ones: the dynamics of these evolving patterns can be oscillatory or chaotic according to the strength of the alignment term. Our results suggest that flow-polarisation alignment can have important consequences on the collective dynamics of active fluids and active gel. PMID:26769011

  3. In vivo functional calcium imaging of induced or spontaneous activity in the fly brain using a GFP-apoaequorin-based bioluminescent approach.

    PubMed

    Minocci, Daiana; Carbognin, Elena; Murmu, Meena Sriti; Martin, Jean-René

    2013-07-01

    Different optical imaging techniques have been developed to study neuronal activity with the goal of deciphering the neural code underlying neurophysiological functions. Because of several constraints inherent in these techniques as well as difficulties interpreting the results, the majority of these studies have been dedicated more to sensory modalities than to the spontaneous activity of the central brain. Recently, a novel bioluminescence approach based on GFP-aequorin (GA) (GFP: Green fluorescent Protein), has been developed, allowing us to functionally record in-vivo neuronal activity. Taking advantage of the particular characteristics of GA, which does not require light excitation, we report that we can record induced and/or the spontaneous Ca(2+)-activity continuously over long periods. Targeting GA to the mushrooms-bodies (MBs), a structure implicated in learning/memory and sleep, we have shown that GA is sensitive enough to detect odor-induced Ca(2+)-activity in Kenyon cells (KCs). It has been possible to reveal two particular peaks of spontaneous activity during overnight recording in the MBs. Other peaks of spontaneous activity have been recorded in flies expressing GA pan-neurally. Similarly, expression in the glial cells has revealed that these cells exhibit a cell-autonomous Ca(2+)-activity. These results demonstrate that bioluminescence imaging is a useful tool for studying Ca(2+)-activity in neuronal and/or glial cells and for functional mapping of the neurophysiological processes in the fly brain. These findings provide a framework for investigating the biological meaning of spontaneous neuronal activity. This article is part of a Special Issue entitled: 12th European Symposium on Calcium. PMID:23287020

  4. Automatic classification of squamosal abnormality in micro-CT images for the evaluation of rabbit fetal skull defects using active shape models

    NASA Astrophysics Data System (ADS)

    Chen, Antong; Dogdas, Belma; Mehta, Saurin; Bagchi, Ansuman; Wise, L. David; Winkelmann, Christopher

    2014-03-01

    High-throughput micro-CT imaging has been used in our laboratory to evaluate fetal skeletal morphology in developmental toxicology studies. Currently, the volume-rendered skeletal images are visually inspected and observed abnormalities are reported for compounds in development. To improve the efficiency and reduce human error of the evaluation, we implemented a framework to automate the evaluation process. The framework starts by dividing the skull into regions of interest and then measuring various geometrical characteristics. Normal/abnormal classification on the bone segments is performed based on identifying statistical outliers. In pilot experiments using rabbit fetal skulls, the majority of the skeletal abnormalities can be detected successfully in this manner. However, there are shape-based abnormalities that are relatively subtle and thereby difficult to identify using the geometrical features. To address this problem, we introduced a model-based approach and applied this strategy on the squamosal bone. We will provide details on this active shape model (ASM) strategy for the identification of squamosal abnormalities and show that this method improved the sensitivity of detecting squamosal-related abnormalities from 0.48 to 0.92.

  5. VEGFR1 Activity Modulates Myeloid Cell Infiltration in Growing Lung Metastases but Is Not Required for Spontaneous Metastasis Formation

    PubMed Central

    Chae, Sung-Suk; Fukumura, Dai; Jain, Rakesh K.

    2009-01-01

    The role of vascular endothelial growth factor receptor 1 (VEGFR1/Flt1) in tumor metastasis remains incompletely characterized. Recent reports suggested that blocking VEGFR1 activity or the interaction with its ligands (VEGF and PlGF) has anti-tumor effects. Moreover, several studies showed that VEGFR1 mediates tumor progression to distant metastasis. All these effects may be exerted indirectly by recruitment of bone marrow-derived cells (BMDCs), such as myeloid cells. We investigated the role of VEGFR1 activity in BMDCs during the pre-metastatic phase, i.e., prior to metastatic nodule formation in mice after surgical removal of the primary tumor. Using pharmacologic blockade or genetic deletion of the tyrosine kinase domain of VEGFR1, we demonstrate that VEGFR1 activity is not required for the infiltration of de novo myeloid BMDCs in the pre-metastatic lungs in two tumor models and in two mouse models. Moreover, in line with emerging clinical observations, we show that blockade of VEGFR1 activity neither prevents nor changes the rate of spontaneous metastasis formation after primary tumor removal. Prevention of metastasis will require further identification and exploration of cellular and molecular pathways that mediate the priming of the metastatic soil. PMID:19763275

  6. Hemodynamic correlates of spontaneous neural activity measured by human whole-head resting state EEG+fNIRS.

    PubMed

    Keles, Hasan Onur; Barbour, Randall L; Omurtag, Ahmet

    2016-09-01

    The brains of awake, resting human subjects display spontaneously occurring neural activity patterns whose magnitude is typically many times greater than those triggered by cognitive or perceptual performance. Evoked and resting state activations affect local cerebral hemodynamic properties through processes collectively referred to as neurovascular coupling. Its investigation calls for an ability to track both the neural and vascular aspects of brain function. We used scalp electroencephalography (EEG), which provided a measure of the electrical potentials generated by cortical postsynaptic currents. Simultaneously we utilized functional near-infrared spectroscopy (NIRS) to continuously monitor hemoglobin concentration changes in superficial cortical layers. The multi-modal signal from 18 healthy adult subjects allowed us to investigate the association of neural activity in a range of frequencies over the whole-head to local changes in hemoglobin concentrations. Our results verified the delayed alpha (8-16Hz) modulation of hemodynamics in posterior areas known from the literature. They also indicated strong beta (16-32Hz) modulation of hemodynamics. Analysis revealed, however, that beta modulation was likely generated by the alpha-beta coupling in EEG. Signals from the inferior electrode sites were dominated by scalp muscle related activity. Our study aimed to characterize the phenomena related to neurovascular coupling observable by practical, cost-effective, and non-invasive multi-modal techniques. PMID:27236081

  7. GABAA and GABAB receptor-mediated effects on the spontaneous activity of the longitudinal layer in cat terminal ileum.

    PubMed

    Pencheva, N; Radomirov, R; Venkova, K

    1991-01-01

    1. GABA and GABAergic agonists-muscimol and (+/-)baclofen changed the spontaneous mechanical activity in isolated cat terminal ileum. 2. GABA at doses ranging from 5 microM to 2 mM produced concentration-dependent biphasic responses consisting of a transient relaxation followed by contractions with a tonic and a phasic components. 3. The GABA-induced relaxation was sensitive to bicuculline and picrotoxinin and was mimicked by muscimol, while the GABA-induced contractions were insensitive to bicuculline and picrotoxinin and were mimicked by (+/-)baclofen. Specific cross desensitization occurred between GABA and muscimol or GABA and (+/-)baclofen. 4. The bicuculline-sensitive relaxation induced by GABA and muscimol was abolished by atropine or tetrodotoxin (TTX), while the bicuculline-insensitive contractions induced by GABA and (+/-)baclofen were not antagonized by atropine or TTX, though they were slightly suppressed. 5. The GABA effects in the longitudinal layer of cat terminal ileum were mediated by the following receptors: -GABAA prejunctional receptors whose activation causes relaxation, probably through an inhibitory action on cholinergic neurons; -GABAB prejunctional receptors whose activation cause contractions; -GABAB postjunctional receptors located on the smooth muscle membrane whose activation induces tonic and phasic contractions. PMID:1646745

  8. Effect of synthetic cannabinoids on spontaneous neuronal activity: Evaluation using Ca(2+) spiking and multi-electrode arrays.

    PubMed

    Tauskela, Joseph S; Comas, Tanya; Hewitt, Melissa; Aylsworth, Amy; Zhao, Xigeng; Martina, Marzia; Costain, Willard J

    2016-09-01

    Activation of cannabinoid receptor 1 (CB1) inhibits synaptic transmission in hippocampal neurons. The goal of this study was to evaluate the ability of benchmark and emerging synthetic cannabinoids to suppress neuronal activity in vitro using two complementary techniques, Ca(2+) spiking and multi-electrode arrays (MEAs). Neuron culture and fluorescence imaging conditions were extensively optimized to provide maximum sensitivity for detection of suppression of neural activity by cannabinoids. The neuronal Ca(2+) spiking frequency was significantly suppressed within 10min by the prototypic aminoalkylindole cannabinoid, WIN 55,212-2 (10µM). Suppression by WIN 55,212-2 was not improved by pharmacological intervention with signaling pathways known to interfere with CB1 signaling. The naphthoylindole CB1 agonist, JWH-018 suppressed Ca(2+) spiking at a lower concentration (2.5µM), and the CB1 antagonist rimonabant (5µM), reversed this suppression. In the MEA assay, the ability of synthetic CB1 agonists to suppress spontaneous electrical activity of hippocampal neurons was evaluated over 80min sessions. All benchmark (WIN 55,212-2, HU-210, CP 55,940 and JWH-018) and emerging synthetic cannabinoids (XLR-11, JWH-250, 5F-PB-22, AB-PINACA and MAM-2201) suppressed neural activity at a concentration of 10µM; furthermore, several of these compounds also significantly suppressed activity at 1µM concentrations. Rimonabant partially reversed spiking suppression of 5F-PB-22 and, to a lesser extent, of MAM-2201, supporting CB1-mediated involvement, although the inactive WIN 55,212-3 also partially suppressed activity. Taken together, synthetic cannabinoid CB1-mediated suppression of neuronal activity was detected using Ca(2+) spiking and MEAs. PMID:27262380

  9. Chromosomal Abnormalities and Schizophrenia

    PubMed Central

    BASSETT, ANNE S.; CHOW, EVA W.C.; WEKSBERG, ROSANNA

    2011-01-01

    Schizophrenia is a common and serious psychiatric illness with strong evidence for genetic causation, but no specific loci yet identified. Chromosomal abnormalities associated with schizophrenia may help to understand the genetic complexity of the illness. This paper reviews the evidence for associations between chromosomal abnormalities and schizophrenia and related disorders. The results indicate that 22q11.2 microdeletions detected by fluorescence in-situ hybridization (FISH) are significantly associated with schizophrenia. Sex chromosome abnormalities seem to be increased in schizophrenia but insufficient data are available to indicate whether schizophrenia or related disorders are increased in patients with sex chromosome aneuploidies. Other reports of chromosomal abnormalities associated with schizophrenia have the potential to be important adjuncts to linkage studies in gene localization. Advances in molecular cytogenetic techniques (i.e., FISH) have produced significant increases in rates of identified abnormalities in schizophrenia, particularly in patients with very early age at onset, learning difficulties or mental retardation, or dysmorphic features. The results emphasize the importance of considering behavioral phenotypes, including adult onset psychiatric illnesses, in genetic syndromes and the need for clinicians to actively consider identifying chromosomal abnormalities and genetic syndromes in selected psychiatric patients. PMID:10813803

  10. Autophagic Signaling and Proteolytic Enzyme Activity in Cardiac and Skeletal Muscle of Spontaneously Hypertensive Rats following Chronic Aerobic Exercise

    PubMed Central

    McMillan, Elliott M.; Paré, Marie-France; Baechler, Brittany L.; Graham, Drew A.; Rush, James W. E.; Quadrilatero, Joe

    2015-01-01

    Hypertension is a cardiovascular disease associated with deleterious effects in skeletal and cardiac muscle. Autophagy is a degradative process essential to muscle health. Acute exercise can alter autophagic signaling. Therefore, we aimed to characterize the effects of chronic endurance exercise on autophagy in skeletal and cardiac muscle of normotensive and hypertensive rats. Male Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) were assigned to a sedentary condition or 6 weeks of treadmill running. White gastrocnemius (WG) of hypertensive rats had higher (p<0.05) caspase-3 and proteasome activity, as well as elevated calpain activity. In addition, skeletal muscle of hypertensive animals had elevated (p<0.05) ATG7 and LC3I protein, LAMP2 mRNA, and cathepsin activity, indicative of enhanced autophagic signaling. Interestingly, chronic exercise training increased (p<0.05) Beclin-1, LC3, and p62 mRNA as well as proteasome activity, but reduced (p<0.05) Beclin-1 and ATG7 protein, as well as decreased (p<0.05) caspase-3, calpain, and cathepsin activity. Left ventricle (LV) of hypertensive rats had reduced (p<0.05) AMPKα and LC3II protein, as well as elevated (p<0.05) p-AKT, p-p70S6K, LC3I and p62 protein, which collectively suggest reduced autophagic signaling. Exercise training had little effect on autophagy-related signaling factors in LV; however, exercise training increased (p<0.05) proteasome activity but reduced (p<0.05) caspase-3 and calpain activity. Our results suggest that autophagic signaling is altered in skeletal and cardiac muscle of hypertensive animals. Regular aerobic exercise can effectively alter the proteolytic environment in both cardiac and skeletal muscle, as well as influence several autophagy-related factors in skeletal muscle of normotensive and hypertensive rats. PMID:25799101

  11. Behavioral Abnormality Induced by Enhanced Hypothalamo-Pituitary-Adrenocortical Axis Activity under Dietary Zinc Deficiency and Its Usefulness as a Model

    PubMed Central

    Takeda, Atsushi; Tamano, Haruna; Nishio, Ryusuke; Murakami, Taku

    2016-01-01

    Dietary zinc deficiency increases glucocorticoid secretion from the adrenal cortex via enhanced hypothalamo-pituitary-adrenocortical (HPA) axis activity and induces neuropsychological symptoms, i.e., behavioral abnormality. Behavioral abnormality is due to the increase in glucocorticoid secretion rather than disturbance of brain zinc homeostasis, which occurs after the increase in glucocorticoid secretion. A major target of glucocorticoids is the hippocampus and their actions are often associated with disturbance of glutamatergic neurotransmission, which may be linked to behavioral abnormality, such as depressive symptoms and aggressive behavior under zinc deficiency. Glucocorticoid-mediated disturbance of glutamatergic neurotransmission in the hippocampus is also involved in the pathophysiology of, not only psychiatric disorders, such as depression, but also neurodegenerative disorders, e.g., Alzheimer’s disease. The evidence suggests that zinc-deficient animals are models for behavioral and psychological symptoms of dementia (BPSD), as well as depression. To understand validity to apply zinc-deficient animals as a behavioral abnormality model, this paper deals with the effect of antidepressive drugs and herbal medicines on hippocampal dysfunctions and behavioral abnormality, which are induced by enhanced HPA axis activity under dietary zinc deficiency. PMID:27438830

  12. Behavioral Abnormality Induced by Enhanced Hypothalamo-Pituitary-Adrenocortical Axis Activity under Dietary Zinc Deficiency and Its Usefulness as a Model.

    PubMed

    Takeda, Atsushi; Tamano, Haruna; Nishio, Ryusuke; Murakami, Taku

    2016-01-01

    Dietary zinc deficiency increases glucocorticoid secretion from the adrenal cortex via enhanced hypothalamo-pituitary-adrenocortical (HPA) axis activity and induces neuropsychological symptoms, i.e., behavioral abnormality. Behavioral abnormality is due to the increase in glucocorticoid secretion rather than disturbance of brain zinc homeostasis, which occurs after the increase in glucocorticoid secretion. A major target of glucocorticoids is the hippocampus and their actions are often associated with disturbance of glutamatergic neurotransmission, which may be linked to behavioral abnormality, such as depressive symptoms and aggressive behavior under zinc deficiency. Glucocorticoid-mediated disturbance of glutamatergic neurotransmission in the hippocampus is also involved in the pathophysiology of, not only psychiatric disorders, such as depression, but also neurodegenerative disorders, e.g., Alzheimer's disease. The evidence suggests that zinc-deficient animals are models for behavioral and psychological symptoms of dementia (BPSD), as well as depression. To understand validity to apply zinc-deficient animals as a behavioral abnormality model, this paper deals with the effect of antidepressive drugs and herbal medicines on hippocampal dysfunctions and behavioral abnormality, which are induced by enhanced HPA axis activity under dietary zinc deficiency. PMID:27438830

  13. Spontaneous L-glutamate release enhancement in rat substantia gelatinosa neurons by (-)-carvone and (+)-carvone which activate different types of TRP channel.

    PubMed

    Kang, Qin; Jiang, Chang-Yu; Fujita, Tsugumi; Kumamoto, Eiichi

    2015-04-10

    Transient receptor potential (TRP) channels in the spinal dorsal horn lamina II (substantia gelatinosa; SG), which are involved in the modulation of nociceptive transmission, have not yet been fully examined in property. Activation of the TRP channels by various plant-derived chemicals results in an increase in the spontaneous release of L-glutamate onto the SG neurons. We examined the effects of a monoterpene ketone (-)-carvone (contained in spearmint) and its stereoisomer (+)-carvone (in caraway) on glutamatergic spontaneous excitatory transmission in SG neurons of adult rat spinal cord slices by using the whole-cell patch-clamp technique. (-)-Carvone and (+)-carvone increased the frequency of spontaneous excitatory postsynaptic current (sEPSC) in a reversible and concentration-dependent manner with a small increase in its amplitude. Half-maximal effective concentrations of (-)-carvone and (+)-carvone in increasing sEPSC frequency were 0.70 mM and 0.72 mM, respectively. The (-)-carvone but not (+)-carvone activity was inhibited by a TRPV1 antagonist capsazepine. On the other hand, the (+)-carvone but not (-)-carvone activity was inhibited by a TRPA1 antagonist HC-030031. These results indicate that (-)-carvone and (+)-carvone activate TRPV1 and TRPA1 channels, respectively, resulting in an increase in spontaneous L-glutamate release onto SG neurons, with almost the same efficacy. Such a difference in TRP activation between the stereoisomers may serve to know the properties of TRP channels in the SG. PMID:25747716

  14. Abnormal cortical sensorimotor activity during "Target" sound detection in subjects with acute acoustic trauma sequelae: an fMRI study.

    PubMed

    Job, Agnès; Pons, Yoann; Lamalle, Laurent; Jaillard, Assia; Buck, Karl; Segebarth, Christoph; Delon-Martin, Chantal

    2012-03-01

    The most common consequences of acute acoustic trauma (AAT) are hearing loss at frequencies above 3 kHz and tinnitus. In this study, we have used functional Magnetic Resonance Imaging (fMRI) to visualize neuronal activation patterns in military adults with AAT and various tinnitus sequelae during an auditory "oddball" attention task. AAT subjects displayed overactivities principally during reflex of target sound detection, in sensorimotor areas and in emotion-related areas such as the insula, anterior cingulate and prefrontal cortex, in premotor area, in cross-modal sensory associative areas, and, interestingly, in a region of the Rolandic operculum that has recently been shown to be involved in tympanic movements due to air pressure. We propose further investigations of this brain area and fine middle ear investigations, because our results might suggest a model in which AAT tinnitus may arise as a proprioceptive illusion caused by abnormal excitability of middle-ear muscle spindles possibly link with the acoustic reflex and associated with emotional and sensorimotor disturbances. PMID:22574285

  15. A Tricholoma matsutake Peptide with Angiotensin Converting Enzyme Inhibitory and Antioxidative Activities and Antihypertensive Effects in Spontaneously Hypertensive Rats

    PubMed Central

    Geng, Xueran; Tian, Guoting; Zhang, Weiwei; Zhao, Yongchang; Zhao, Liyan; Wang, Hexiang; Ng, Tzi Bun

    2016-01-01

    Hypertension is a major risk factor for cardiovascular disease. A crude water extract of the fruiting bodies of a highly prized mushroom Tricholoma matsutakei exerted an antihypertensive action on spontaneously hypertensive rats (SHRs) at a dosage of 400 mg/kg. An angiotensin converting enzyme (ACE) inhibitory peptide with an IC50 of 0.40 μM was purified from the extract and designated as TMP. Its amino acid sequence was elucidated to be WALKGYK through LC-MS/MS analysis. The Lineweaver-Burk plot suggested that TMP was a non-competitive inhibitor of ACE. A short-term assay of antihypertensive activity demonstrated that TMP at the dosage of 25 mg/kg could significantly lower the systolic blood pressure (SBP) of SHRs. TMP exhibited remarkable stability over a wide range of temperatures and pH values. It also demonstrated 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. The aforementioned activities of TMP were corroborated by utilizing the synthetic peptide. Hence T. matsutake can be used as a functional food to help prevent hypertension- associated diseases. PMID:27052674

  16. Abnormal activation of potassium channels in aortic smooth muscle of rats with peritonitis-induced septic shock.

    PubMed

    Kuo, Jiunn-Horng; Chen, Shiu-Jen; Shih, Chih-Chin; Lue, Wei-Ming; Wu, Chin-Chen

    2009-07-01

    This study was conducted to examine the role of membrane hyperpolarization in mediating vascular hyporeactivity induced by cecal ligation and puncture (CLP) in endothelial-denuded strips of rat thoracic aorta ex vivo. The CLP for 18 h elicited a significant fall of blood pressure and a severe vascular hyporeactivity to norepinephrine as seen in severe sepsis. At the end of the in vivo experiments, thoracic aortas were removed from both CLP-treated and control rats. After removal of the endothelium, aortic segments were mounted in myographs for the recording of isometric tension and smooth muscle membrane potential. The membrane potential recording showed that a hyperpolarization was observed in the CLP-treated rats when compared with the control rats. This hyperpolarization was reversed by iberiotoxin (a large-conductance Ca2+-activated K+ channel blocker), 4-aminopyridine (a voltage-dependent K+ channel blocker), barium (an inward rectifier K+ channels blocker), N-(1-adamantyl)-N'-cyclohexyl-4-morpholinecarboxamidine hydrochloride (a pore-forming blocker of adenosine triphosphate (ATP)-sensitive K+ channels [KATP]), or methylene blue (a nonspecific guanylyl cyclase [GC] inhibitor). However, this hyperpolarization was not significantly affected by apamin (a small-conductance Ca2+-activated K+ channel blocker), glibenclamide (a sulfonylurea blocker of KATP), N(omega)-nitro-L-arginine methyl ester (a NOS inhibitor), or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (an NO-sensitive GC inhibitor). In addition, the basal tension of the tissues obtained from CLP rats was increased simultaneously, whereas membrane potential was reversed. In contrast, none of these inhibitors had significant effects on the membrane potential or the basal tension in control tissues. Thus, we provide electrophysiological and functional evidence demonstrating that an abnormal activation of K+ channels in vascular smooth muscle in animals with septic shock induced by CLP. Our observations

  17. Preictal Activity of Subicular, CA1, and Dentate Gyrus Principal Neurons in the Dorsal Hippocampus before Spontaneous Seizures in a Rat Model of Temporal Lobe Epilepsy

    PubMed Central

    Fujita, Satoshi; Toyoda, Izumi; Thamattoor, Ajoy K.

    2014-01-01

    Previous studies suggest that spontaneous seizures in patients with temporal lobe epilepsy might be preceded by increased action potential firing of hippocampal neurons. Preictal activity is potentially important because it might provide new opportunities for predicting when a seizure is about to occur and insight into how spontaneous seizures are generated. We evaluated local field potentials and unit activity of single, putative excitatory neurons in the subiculum, CA1, CA3, and dentate gyrus of the dorsal hippocampus in epileptic pilocarpine-treated rats as they experienced spontaneous seizures. Average action potential firing rates of neurons in the subiculum, CA1, and dentate gyrus, but not CA3, increased significantly and progressively beginning 2–4 min before locally recorded spontaneous seizures. In the subiculum, CA1, and dentate gyrus, but not CA3, 41–57% of neurons displayed increased preictal activity with significant consistency across multiple seizures. Much of the increased preictal firing of neurons in the subiculum and CA1 correlated with preictal theta activity, whereas preictal firing of neurons in the dentate gyrus was independent of theta. In addition, some CA1 and dentate gyrus neurons displayed reduced firing rates preictally. These results reveal that different hippocampal subregions exhibit differences in the extent and potential underlying mechanisms of preictal activity. The finding of robust and significantly consistent preictal activity of subicular, CA1, and dentate neurons in the dorsal hippocampus, despite the likelihood that many seizures initiated in other brain regions, suggests the existence of a broader neuronal network whose activity changes minutes before spontaneous seizures initiate. PMID:25505320

  18. Sexual Activity as a Risk Factor for the Spontaneous Rupture of Cerebral Aneurysms.

    PubMed

    Blanke-Roeser, Constantin; Matschke, Jakob; Püschel, Klaus

    2016-06-01

    Subarachnoid hemorrhages from ruptured cerebral aneurysms have a high clinical relevance and often lead to death. Approximately 2% to 5% of the people worldwide, even of younger age, are said to have aneurysms at cerebral arteries. In many cases, they remain clinically unapparent for decades. However, there are numerous risk factors for the rupture of an aneurysm, including temporary raises of the blood pressure. Such changes of the blood pressure can be induced even by several everyday behaviors. For example, any sort of sexual activities may cause extensive raises of the blood pressure because of several physical and psychological factors. The term "sexual activity" covers sexual intercourse as well as masturbation. In this article, the remarkable case of a 24-year-old woman with a ruptured cerebral aneurysm in the context of masturbation is presented. It is discussed with respect to the possible pathophysiological effects of sexual activity on cerebral aneurysms. PMID:27043460

  19. Reciprocal Effects of Oxidative Stress on Heme Oxygenase Expression and Activity Contributes to Reno-Vascular Abnormalities in EC-SOD Knockout Mice

    PubMed Central

    Kawakami, Tomoko; Puri, Nitin; Sodhi, Komal; Bellner, Lars; Takahashi, Toru; Morita, Kiyoshi; Rezzani, Rita; Oury, Tim D.; Abraham, Nader G.

    2012-01-01

    Heme oxygenase (HO) system is one of the key regulators of cellular redox homeostasis which responds to oxidative stress (ROS) via HO-1 induction. However, recent reports have suggested an inhibitory effect of ROS on HO activity. In light of these conflicting reports, this study was designed to evaluate effects of chronic oxidative stress on HO system and its role in contributing towards patho-physiological abnormalities observed in extracellular superoxide dismutase (EC-SOD, SOD3) KO animals. Experiments were performed in WT and EC-SOD(−/−) mice treated with and without HO inducer, cobalt protoporphyrin (CoPP). EC-SOD(−/−) mice exhibited oxidative stress, renal histopathological abnormalities, elevated blood pressure, impaired endothelial function, reduced p-eNOS, p-AKT and increased HO-1 expression; although, HO activity was significantly (P < 0.05) attenuated along with attenuation of serum adiponectin and vascular epoxide levels (P < 0.05). CoPP, in EC-SOD(−/−) mice, enhanced HO activity (P < 0.05) and reversed aforementioned pathophysiological abnormalities along with restoration of vascular EET, p-eNOS, p-AKT and serum adiponectin levels in these animals. Taken together our results implicate a causative role of insufficient activation of heme-HO-adiponectin system in pathophysiological abnormalities observed in animal models of chronic oxidative stress such as EC-SOD(−/−) mice. PMID:22292113

  20. Abnormalities of AMPK Activation and Glucose Uptake in Cultured Skeletal Muscle Cells from Individuals with Chronic Fatigue Syndrome

    PubMed Central

    Brown, Audrey E.; Jones, David E.; Walker, Mark; Newton, Julia L.

    2015-01-01

    Background Post exertional muscle fatigue is a key feature in Chronic Fatigue Syndrome (CFS). Abnormalities of skeletal muscle function have been identified in some but not all patients with CFS. To try to limit potential confounders that might contribute to this clinical heterogeneity, we developed a novel in vitro system that allows comparison of AMP kinase (AMPK) activation and metabolic responses to exercise in cultured skeletal muscle cells from CFS patients and control subjects. Methods Skeletal muscle cell cultures were established from 10 subjects with CFS and 7 age-matched controls, subjected to electrical pulse stimulation (EPS) for up to 24h and examined for changes associated with exercise. Results In the basal state, CFS cultures showed increased myogenin expression but decreased IL6 secretion during differentiation compared with control cultures. Control cultures subjected to 16h EPS showed a significant increase in both AMPK phosphorylation and glucose uptake compared with unstimulated cells. In contrast, CFS cultures showed no increase in AMPK phosphorylation or glucose uptake after 16h EPS. However, glucose uptake remained responsive to insulin in the CFS cells pointing to an exercise-related defect. IL6 secretion in response to EPS was significantly reduced in CFS compared with control cultures at all time points measured. Conclusion EPS is an effective model for eliciting muscle contraction and the metabolic changes associated with exercise in cultured skeletal muscle cells. We found four main differences in cultured skeletal muscle cells from subjects with CFS; increased myogenin expression in the basal state, impaired activation of AMPK, impaired stimulation of glucose uptake and diminished release of IL6. The retention of these differences in cultured muscle cells from CFS subjects points to a genetic/epigenetic mechanism, and provides a system to identify novel therapeutic targets. PMID:25836975

  1. Spontaneous Activity Associated with Delusions of Schizophrenia in the Left Medial Superior Frontal Gyrus: A Resting-State fMRI Study

    PubMed Central

    Liu, Weibo; Chen, Zhiyu; Zhou, Heshan; Yang, Jinyu; Cohen, Zachary; Zhu, Yihong; Zang, Yufeng

    2015-01-01

    Delusions of schizophrenia have been found to be associated with alterations of some brain regions in structure and task-induced activation. However, the relationship between spontaneously occurring symptoms and spontaneous brain activity remains unclear. In the current study, 14 schizophrenic patients with delusions and 14 healthy controls underwent a resting-state functional magnetic resonance imaging (RS-fMRI) scan. Patients with delusions of schizophrenia patients were rated with Positive and Negative Syndrome Scale (PANSS) and Characteristics of Delusional Rating Scale (CDRS). Regional homogeneity (ReHo) was calculated to measure the local synchronization of the spontaneous activity in a voxel-wise way. A two-sample t-test showed that ReHo of the right anterior cingulate gyrus and left medial superior frontal gyrus were higher in patients, and ReHo of the left superior occipital gyrus was lower, compared to healthy controls. Further, among patients, correlation analysis showed a significant difference between delusion scores of CRDS and ReHo of brain regions. ReHo of the left medial superior frontal gyrus was negatively correlated with patients’ CDRS scores but not with delusional PANSS scores. These results suggested that altered local synchronization of spontaneous brain activity may be related to the pathophysiology of delusion in schizophrenia. PMID:26204264

  2. Effects of a high-fat diet on spontaneous metastasis of Lewis lung carcinoma in plasminogen activator inhibitor-1 deficient and wild-type mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We investigated the effects of plasminogen activator inhibitor-1 (PAI-1) deficiency on spontaneous metastasis of Lewis lung carcinoma (LLC) in PAI-1 deficient (PAI-1-/-) and wildtype mice (C57BL/6J background) fed the AIN93G diet or that diet modified with 45% calories from fat. The high-fat diet i...

  3. Effect of Imperatorin on the Spontaneous Motor Activity of Rat Isolated Jejunum Strips

    PubMed Central

    Mendel, Marta; Skalicka-Woźniak, Krystyna; Chłopecka, Magdalena; Dziekan, Natalia

    2015-01-01

    Imperatorin, a psoralen-type furanocoumarin, is a potent myorelaxant agent acting as a calcium antagonist on vascular smooth muscle. Its effects on other types of smooth muscle remain unknown. Therefore, the aim of this study was to investigate the hypothesized myorelaxant effect of imperatorin on gut motor activity and, possibly, to define the underlying mechanism of action. Imperatorin was made available for pharmacological studies from the fruits of the widely available Angelica officinalis through the application of high-performance countercurrent chromatography (HPCCC). Imperatorin generated reversible relaxation of jejunum strips dose-dependently (1–100 μM). At 25 and 50 μM, imperatorin caused relaxation comparable to the strength of the reaction induced by isoproterenol (Isop) at 0.1 μM. The observed response resulted neither from the activation of soluble guanylate cyclase, nor from β-adrenoreceptor involvement, nor from Ca2+-activated potassium channels. Imperatorin relaxed intestine strips precontracted with high potassium concentration, attenuated the force and duration of K+-induced contractions, and modulated the response of jejunum strips to acetylcholine. The results suggest that imperatorin probably interacts with various Ca2+ influx pathways in intestine smooth muscle. The types of some calcium channels involved in the activity of imperatorin will be examined in a subsequent study. PMID:26236380

  4. Brain Interleukin-1β and the Intrinsic Receptor Antagonist Control Peripheral Toll-Like Receptor 3-Mediated Suppression of Spontaneous Activity in Rats

    PubMed Central

    Yamato, Masanori; Tamura, Yasuhisa; Eguchi, Asami; Kume, Satoshi; Miyashige, Yukiharu; Nakano, Masayuki; Watanabe, Yasuyoshi; Kataoka, Yosky

    2014-01-01

    During acute viral infections such as influenza, humans often experience not only transient fever, but also prolonged fatigue or depressive feelings with a decrease in social activity for days or weeks. These feelings are thought to be due to neuroinflammation in the brain. Recent studies have suggested that chronic neuroinflammation is a precipitating event of various neurological disorders, but the mechanism determining the duration of neuroinflammation has not been elucidated. In this study, neuroinflammation was induced by intraperitoneal injection of polyriboinosinic:polyribocytidylic acid (poly I:C), a Toll-like receptor-3 agonist that mimics viral infection in male Sprague-Dawley rats, and then investigated how the neuroinflammation shift from acute to the chronic state. The rats showed transient fever and prolonged suppression of spontaneous activity for several days following poly I:C injection. NS-398, a cyclooxygenase-2 inhibitor, completely prevented fever, but did not improve spontaneous activity, indicating that suppression of spontaneous activity was not induced by the arachidonate cascade that generated the fever. The animals overexpressed interleukin (IL)-1β and IL-1 receptor antagonist (IL-1ra) in the brain including the cerebral cortex. Blocking the IL-1 receptor in the brain by intracerebroventricular (i.c.v.) infusion of recombinant IL-1ra completely blocked the poly I:C-induced suppression of spontaneous activity and attenuated amplification of brain interferon (IFN)-α expression, which has been reported to produce fatigue-like behavior by suppressing the serotonergic system. Furthermore, i.c.v. infusion of neutralizing antibody for IL-1ra prolonged recovery from suppression of spontaneous activity. Our findings indicated that IL-1β is the key trigger of neuroinflammation and that IL-1ra prevents the neuroinflammation entering the chronic state. PMID:24621600

  5. [GLUCOSE CONTENT FLUCTUATION IN BLOOD OF NEWBORN RATS DEPENDING ON SEASON AND PATTERN OF SPONTANEOUS MOTOR ACTIVITY].

    PubMed

    Kuznetsova, N N; Selina, E N

    2015-01-01

    Earlier we have shown that in newborn rats the glucose level in blood serum changes depending on the pattern of spontaneous periodic motor activity (SPMA). During rest periods, both under dominant decasecond rhythm and under dominant minute rhythm, the glucose level in blood serum is higher than during activity periods. We have also shown that the glucose level in the blood serum rises with age reaching the level of adult animals by day 10. In the present study carried out on 3-10-day-old rats under conditions of free behavior the blood glucose content was investigated in different periods of <activity-rest> cycle during different seasons. It is found that in newborn rats of all ages studied (3-, 5-, 7-, and 10-day-old ones) the lowest glucose concentration in the blood is observed in the winter period. In spring its level increases and in summer reaches the maximum different significantly from the winter and spring levels in all age groups except day 5. In autumn the glucose level decreases and approaches the spring values but it is still different from the winter indices. In 5-day-old rats statistically significant differences of glucose levels in different seasons were not observed. The data obtained provide evidence of seasonal fluctuations of the glucose level in blood serum of newborn rats. At the same time during all seasons except spring the dependence of glucose level on the pattern of motor activity persists. In spring these differences are smoothed. Key words: ontogenesis, motor activity, metabolic factors, glucose, seasonal variations. PMID:26856074

  6. Peritonitis - spontaneous

    MedlinePlus

    ... a catheter used in peritoneal dialysis. Antibiotics may control infection in cases of spontaneous peritonitis with liver or kidney disease. Intravenous therapy can treat dehydration . You may need to stay in the hospital so health care providers can rule out conditions ...

  7. Sardine peptide with angiotensin I-converting enzyme inhibitory activity improves glucose tolerance in stroke-prone spontaneously hypertensive rats.

    PubMed

    Otani, Lila; Ninomiya, Toshio; Murakami, Megumi; Osajima, Katsuhiro; Kato, Hisanori; Murakami, Tetsuo

    2009-10-01

    An enzymatic hydrolysate of sardine protein (sardine peptide, SP) derived from sardine muscle possesses angiotensin I-converting enzyme (ACE) inhibitory activity. In the present study, we investigated the effect of SP on the blood glucose levels in stroke-prone spontaneously hypertensive rats (SHRSPs). Ten-week-old SHRSPs were assigned to three groups. The control group was given tap water for 4 weeks, while the experimental groups were given water containing SP (1 g/kg/d) or an ACE inhibitor, captopril (8 mg/kg/d). Treatment with SP and captopril decreased ACE activity in the kidney, aorta, and mesentery. There were no differences in fasting blood glucose levels among the three groups, whereas SP and captopril administration significantly suppressed the increase in blood glucose after glucose loading in the control SHRSPs. No difference was observed in plasma insulin levels among the three groups. Thus treatment with captopril and ACE-inhibitory sardine peptides ameliorated the glucose tolerance of this rat strain. PMID:19809178

  8. Insulinoma-released exosomes or microparticles are immunostimulatory and can activate autoreactive T cells spontaneously developed in nonobese diabetic mice.

    PubMed

    Sheng, Huiming; Hassanali, Saleema; Nugent, Courtney; Wen, Li; Hamilton-Williams, Emma; Dias, Peter; Dai, Yang D

    2011-08-15

    Exosomes (EXO) are secreted intracellular microparticles that can trigger inflammation and induce Ag-specific immune responses. To test possible roles of EXO in autoimmunity, we isolated small microparticles, mainly EXO, from mouse insulinoma and examined their activities to stimulate the autoimmune responses in NOD mice, a model for human type 1 diabetes. We demonstrate that the EXO contains strong innate stimuli and expresses candidate diabetes autoantigens. They can induce secretion of inflammatory cytokines through a MyD88-dependent pathway, and activate purified APC and result in T cell proliferation. To address whether EXO or the secreted microparticles are possible autoimmune targets causing islet-specific inflammation, we monitored the T cell responses spontaneously developed in prediabetic NOD mice for their reactivity to the EXO, and compared this reactivity between diabetes-susceptible and -resistant congenic mouse strains. We found that older NOD females, which have advanced islet destruction, accumulated more EXO-reactive, IFN-γ-producing lymphocytes than younger females or age-matched males, and that pancreatic lymph nodes from the prediabetic NOD, but not from the resistant mice, were also enriched with EXO-reactive Th1 cells. In vivo, immunization with the EXO accelerates insulitis development in nonobese diabetes-resistant mice. Thus, EXO or small microparticles can be recognized by the diabetes-associated autoreactive T cells, supporting that EXO might be a possible autoimmune target and/or insulitis trigger in NOD or congenic mouse strains. PMID:21734072

  9. Global and structured waves of rs-fMRI signal identified as putative propagation of spontaneous neural activity.

    PubMed

    Amemiya, Shiori; Takao, Hidemasa; Hanaoka, Shohei; Ohtomo, Kuni

    2016-06-01

    Conventional resting-state fMRI (rs-fMRI) studies have focused on investigating the synchronous neural activity in functionally relevant distant regions that are termed as resting-state networks. On the other hand, less is known about the spatiotemporal dynamics of the spontaneous activity of the brain. By examining the characteristics of both rs-fMRI and vascular time lag that was measured using dynamic susceptibility contrast-enhanced perfusion weighted imaging, the present study identifies several structured propagation of the rs-fMRI signal as putative neural streams. Temporal shift of both rs-fMRI and perfusion imaging data in each voxel compared with the averaged whole-brain signal was computed using cross-correlation analysis. In contrast to the uniformity of the vascular time lag across subjects, whole-brain rs-fMRI time lag was estimated to be composed of three independent components. After regression of vascular time lag, independent component analysis was applied to rs-fMRI data. The putative neural streams showed slow propagation of the signal from task-positive regions to main nodes of the default mode network, which may represent a mode of transmission underlying the interactions among the resting-state networks. PMID:27012499

  10. A TTX-sensitive inward sodium current contributes to spontaneous activity in newborn rabbit sino-atrial node cells.

    PubMed Central

    Baruscotti, M; DiFrancesco, D; Robinson, R B

    1996-01-01

    1. Single cells were isolated from the sinus node region of rabbits (2 days old to adult) to study the age-dependent contribution of the sodium current (iNa) to pacemaker activity. 2. Experiments were conducted in 50 mM Na(+)-Ca(2+)-free solution. All newborn cells (2-19 days) exhibited a TTX-sensitive, Mn(2+)-insensitive fast inward Na+ current (peak current density 115.5 +/- 11.9 pA pF-1 at 0 mV). Fifty per cent of young cells (20-40 days) possessed the current, but only one in ten adult cells. Current density decreased with development independently of cell capacitance. 3. Newborn cells exhibited a noticeable window current. With development, the position of the activation curve was shifted in the positive direction, while the inactivation was unaltered, resulting in reduced overlap of the two curves and hence less window current. 4. In newborn cells, 3 microM TTX significantly reduced all measured parameters of spontaneous action potentials, slowing rate by 63%. In contrast, there was no significant effect of TTX on rate or most of the same parameters in adult cells. 5. These results indicate that cells of the sinus node region exhibit a substantial TTX-sensitive current at birth. With development, both the density and frequency of occurrence of this current within the sinus node decrease, as does its contribution to automaticity. PMID:8730579

  11. Biphasic GABA-A receptor-mediated effect on the spontaneous activity of the circular layer in cat terminal ileum.

    PubMed

    Pencheva, N; Radomirov, R

    1993-07-01

    1. The GABA and GABA-A receptor agonist muscimol changed the spontaneous mechanical activity of a circular layer isolated from cat terminal ileum, while the selective GABA-B receptor agonist (+/-)baclofen had no effect. 2. GABA at doses ranging from 1 microM to 2 mM elicited concentration-dependent biphasic responses which consisted of a relaxation followed by contraction, with a tonic and a phasic component. The EC50 values, calculated at 95% confidence limits (CL), were 94.9 microM (83.5-109.8 microM) and 66.0 microM (51.2-75.5 microM) for the relaxation and contractile phases, respectively. 3. The GABA-induced biphasic responses were sensitive to bicuculline and picrotoxinin and were entirely mimicked by muscimol. Bicuculline competitively antagonized the effects of GABA and gave closely similar pA2 values for both phases of these responses--inhibitory and stimulatory. Cross-desensitization occurred only between GABA and muscimol and not between (+/-)baclofen and GABA, or (+/-)baclofen and muscimol. 4. Both bicuculline-sensitive phases evoked by GABA and muscimol were abolished by tetrodotoxin or atropine, but were unaffected by guanethidine or naloxone. 5. The present results suggested that the biphasic GABA effect on the mechanical activity of the circular layer in cat terminal ileum was mediated by prejunctional GABA-A receptors, most probably through an action on the cholinergic pathway. PMID:8224749

  12. Bioactive compounds and antioxidant activity of Rosa canina L. biotypes from spontaneous flora of Transylvania

    PubMed Central

    2013-01-01

    Background The theoretical, but especially the practical values of identifying the biochemical compounds from the Rosa canina L. fruits are of present interest, this aspect being illustrated by the numerous researches. It was reported that the Rosa canina L. fruit, with its high ascorbic acid, phenolics and flavonoids contents, have antioxidant, antimutagenic and anticarcinogenic effects. This study was performed on order to evaluate the amount of the main phytochemicals (vitamin C, total polyphenols, and total flavonoids) content and their antioxidant activity. Results The results obtained revealed that the average amounts of vitamin C within the studied genotypes were: 360.22 mg/100 g frozen pulp (var. transitoria f. ramosissima, altitude 1250 m) and 112.20 mg/100 g frozen pulp (var. assiensis, altitude 440 m), giving a good correlation between the vitamin C content of the rosehip and the altitude. The total polyphenols content varied from 575 mg/100 g frozen pulp (var. transitoria f. ramosissima) to 326 mg/100 g frozen pulp (var. lutetiana f. fallens). The total flavonoids content showed the highest value for var. assiensis variant 163.3 mg/100 g frozen pulp and the lowest value attributed to var. transitoria f. montivaga 101.3 mg/100 g frozen pulp. The antioxidant activity of eight rose hip extracts from wild Transylvania populations was investigated through DPPH method. The antioxidant activity revealed a good correlation only with vitamin C content and total polyphenols. Conclusion Eight Rose hip fruit species were compared taking into consideration the ascorbic acid, total polyphenols, total flavonoids contents and their antioxidant activity. Based on these results, two of the rosehip genotypes that were analysed could be of perspective for these species’ amelioration, due to their content of phytochemicals mentioned above. These varieties are var. transitoria f. ramosissima (Bistrita-Nasaud, Agiesel) and var. transitoria f. montivaga (Bistrita

  13. Amplitude of Low Frequency Fluctuation Abnormalities in Adolescents with Online Gaming Addiction

    PubMed Central

    Cheng, Ping; Yang, Xuejuan; Dong, Tao; Bi, Yanzhi; Xing, Lihong; von Deneen, Karen M.; Yu, Dahua; Liu, Junyu; Liang, Jun; Cheng, Tingting; Qin, Wei; Tian, Jie

    2013-01-01

    The majority of previous neuroimaging studies have demonstrated both structural and task-related functional abnormalities in adolescents with online gaming addiction (OGA). However, few functional magnetic resonance imaging (fMRI) studies focused on the regional intensity of spontaneous fluctuations in blood oxygen level-dependent (BOLD) during the resting state and fewer studies investigated the relationship between the abnormal resting-state properties and the impaired cognitive control ability. In the present study, we employed the amplitude of low frequency fluctuation (ALFF) method to explore the local features of spontaneous brain activity in adolescents with OGA and healthy controls during resting-state. Eighteen adolescents with OGA and 18 age-, education- and gender-matched healthy volunteers participated in this study. Compared with healthy controls, adolescents with OGA showed a significant increase in ALFF values in the left medial orbitofrontal cortex (OFC), the left precuneus, the left supplementary motor area (SMA), the right parahippocampal gyrus (PHG) and the bilateral middle cingulate cortex (MCC). The abnormalities of these regions were also detected in previous addiction studies. More importantly, we found that ALFF values of the left medial OFC and left precuneus were positively correlated with the duration of OGA in adolescents with OGA. The ALFF values of the left medial OFC were also correlated with the color-word Stroop test performance. Our results suggested that the abnormal spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology of OGA. PMID:24223843

  14. Amplitude of low frequency fluctuation abnormalities in adolescents with online gaming addiction.

    PubMed

    Yuan, Kai; Jin, Chenwang; Cheng, Ping; Yang, Xuejuan; Dong, Tao; Bi, Yanzhi; Xing, Lihong; von Deneen, Karen M; Yu, Dahua; Liu, Junyu; Liang, Jun; Cheng, Tingting; Qin, Wei; Tian, Jie

    2013-01-01

    The majority of previous neuroimaging studies have demonstrated both structural and task-related functional abnormalities in adolescents with online gaming addiction (OGA). However, few functional magnetic resonance imaging (fMRI) studies focused on the regional intensity of spontaneous fluctuations in blood oxygen level-dependent (BOLD) during the resting state and fewer studies investigated the relationship between the abnormal resting-state properties and the impaired cognitive control ability. In the present study, we employed the amplitude of low frequency fluctuation (ALFF) method to explore the local features of spontaneous brain activity in adolescents with OGA and healthy controls during resting-state. Eighteen adolescents with OGA and 18 age-, education- and gender-matched healthy volunteers participated in this study. Compared with healthy controls, adolescents with OGA showed a significant increase in ALFF values in the left medial orbitofrontal cortex (OFC), the left precuneus, the left supplementary motor area (SMA), the right parahippocampal gyrus (PHG) and the bilateral middle cingulate cortex (MCC). The abnormalities of these regions were also detected in previous addiction studies. More importantly, we found that ALFF values of the left medial OFC and left precuneus were positively correlated with the duration of OGA in adolescents with OGA. The ALFF values of the left medial OFC were also correlated with the color-word Stroop test performance. Our results suggested that the abnormal spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology of OGA. PMID:24223843

  15. Pathological role of a constitutively active population of alpha(1D)-adrenoceptors in arteries of spontaneously hypertensive rats.

    PubMed

    Gisbert, Regina; Ziani, Khalid; Miquel, Raquel; Noguera, M Antonia; Ivorra, M Dolores; Anselmi, Elsa; D'Ocon, Pilar

    2002-01-01

    1. The role of a constitutively active population of alpha(1D)-adrenoceptors was analysed in arteries obtained from spontaneously hypertensive rats (SHR) and controls (WKY) divided into three groups: young prehypertensive, adult hypertensive, and adult animals chronically treated with captopril (50 mg kg(-1) per day orally) in order to prevent the hypertensive state. 2. In adult SHR, a significant increase in BMY 7378 potency (not in prazosin potency) was observed in aorta, mesenteric artery, and the first and second branches of the small mesenteric arteries with respect to WKY rats. This difference was not observed in iliac and tail arteries, which suggests an increased functional role of alpha(1D)-adrenoceptors only in some vessels of SHR. 3. The increase in the resting tone (IRT) observed in absence of agonist, inhibited by BMY 7378, that represents the constitutively active population of alpha(1D)-adrenoceptors, was also significantly greater in aorta and mesenteric artery from adult SHR. 4. In young and captopril treated adult animals, no differences between strains with respect to BMY 7378 potency, or IRT were observed. 5. The increase in the functional role of alpha(1D)-adrenoceptors and their constitutive activity observed in hypertension is prevented by captopril treatment. The pathological consequence of this change is the slower rate of recovery of the basal tone after removal of an adrenergic stimulus, observed in vessels from hypertensive animals that had shown an increase in the functionality of constitutively active alpha(1D)-adrenoceptors. This change was not observed in prehypertensive or captopril treated animals. PMID:11786496

  16. Pathological role of a constitutively active population of α1D-adrenoceptors in arteries of spontaneously hypertensive rats

    PubMed Central

    Gisbert, Regina; Ziani, Khalid; Miquel, Raquel; Noguera, M Antonia; Ivorra, M Dolores; Anselmi, Elsa; D'Ocon, Pilar

    2002-01-01

    The role of a constitutively active population of α1D-adrenoceptors was analysed in arteries obtained from spontaneously hypertensive rats (SHR) and controls (WKY) divided into three groups: young prehypertensive, adult hypertensive, and adult animals chronically treated with captopril (50 mg kg−1 per day orally) in order to prevent the hypertensive state.In adult SHR, a significant increase in BMY 7378 potency (not in prazosin potency) was observed in aorta, mesenteric artery, and the first and second branches of the small mesenteric arteries with respect to WKY rats. This difference was not observed in iliac and tail arteries, which suggests an increased functional role of α1D-adrenoceptors only in some vessels of SHR.The increase in the resting tone (IRT) observed in absence of agonist, inhibited by BMY 7378, that represents the constitutively active population of α1D-adrenoceptors, was also significantly greater in aorta and mesenteric artery from adult SHR.In young and captopril treated adult animals, no differences between strains with respect to BMY 7378 potency, or IRT were observed.The increase in the functional role of α1D-adrenoceptors and their constitutive activity observed in hypertension is prevented by captopril treatment. The pathological consequence of this change is the slower rate of recovery of the basal tone after removal of an adrenergic stimulus, observed in vessels from hypertensive animals that had shown an increase in the functionality of constitutively active α1D-adrenoceptors. This change was not observed in prehypertensive or captopril treated animals. PMID:11786496

  17. Aerobic exercise training improves oxidative stress and ubiquitin proteasome system activity in heart of spontaneously hypertensive rats.

    PubMed

    de Andrade, Luiz Henrique Soares; de Moraes, Wilson Max Almeida Monteiro; Matsuo Junior, Eduardo Hiroshi; de Orleans Carvalho de Moura, Elizabeth; Antunes, Hanna Karen Moreira; Montemor, Jairo; Antonio, Ednei Luiz; Bocalini, Danilo Sales; Serra, Andrey Jorge; Tucci, Paulo José Ferreira; Brum, Patricia Chakur; Medeiros, Alessandra

    2015-04-01

    The activity of the ubiquitin proteasome system (UPS) and the level of oxidative stress contribute to the transition from compensated cardiac hypertrophy to heart failure in hypertension. Moreover, aerobic exercise training (AET) is an important therapy for the treatment of hypertension, but its effects on the UPS are not completely known. The aim of this study was to evaluate the effect of AET on UPS's activity and oxidative stress level in heart of spontaneously hypertensive rats (SHR). A total of 53 Wistar and SHR rats were randomly divided into sedentary and trained groups. The AET protocol was 5×/week in treadmill for 13 weeks. Exercise tolerance test, non-invasive blood pressure measurement, echocardiographic analyses, and left ventricle hemodynamics were performed during experimental period. The expression of ubiquitinated proteins, 4-hydroxynonenal (4-HNE), Akt, phospho-Akt(ser473), GSK3β, and phospho-GSK3β(ser9) were analyzed by western blotting. The evaluation of lipid hydroperoxide concentration was performed using the xylenol orange method, and the proteasomal chymotrypsin-like activity was measured by fluorimetric assay. Sedentary hypertensive group presented cardiac hypertrophy, unaltered expression of total Akt, phospho-Akt, total GSK3β and phospho-GSK3β, UPS hyperactivity, increased lipid hydroperoxidation as well as elevated expression of 4-HNE but normal cardiac function. In contrast, AET significantly increased exercise tolerance, decreased resting systolic blood pressure and heart rate in hypertensive animals. In addition, the AET increased phospho-Akt expression, decreased phospho-GSK3β, and did not alter the expression of total Akt, total GSK3β, and ubiquitinated proteins, however, significantly attenuated 4-HNE levels, lipid hydroperoxidation, and UPS's activity toward normotensive group levels. Our results provide evidence for the main effect of AET on attenuating cardiac ubiquitin proteasome hyperactivity and oxidative stress in SHR

  18. Chronotype and stability of spontaneous locomotor activity rhythm in BMAL1-deficient mice.

    PubMed

    Pfeffer, Martina; Korf, Horst-Werner; von Gall, Charlotte

    2015-02-01

    Behavior, physiological functions and cognitive performance change over the time of the day. These daily rhythms are either externally driven by rhythmic environmental cues such as the light/dark cycle (masking) or controlled by an internal circadian clock, the suprachiasmatic nucleus (SCN), which can be entrained to the light/dark cycle. Within a given species, there is genetically determined variability in the temporal preference for the onset of the active phase, the chronotype. The chronotype is the phase of entrainment between external and internal time and is largely regulated by the circadian clock. Genetic variations in clock genes and environmental influences contribute to the distribution of chronotypes in a given population. However, little is known about the determination of the chronotype, the stability of the locomotor rhythm and the re-synchronization capacity to jet lag in an animal without a functional endogenous clock. Therefore, we analyzed the chronotype of BMAL1-deficient mice (BMAL1-/-) as well as the effects of repeated experimental jet lag on locomotor activity rhythms. Moreover, light-induced period expression in the retina was analyzed to assess the responsiveness of the circadian light input system. In contrast to wild-type mice, BMAL1-/- showed a significantly later chronotype, adapted more rapidly to both phase advance and delay but showed reduced robustness of rhythmic locomotor activity after repeated phase shifts. However, photic induction of Period in the retina was not different between the two genotypes. Our findings suggest that a disturbed clockwork is associated with a late chronotype, reduced rhythm stability and higher vulnerability to repeated external desynchronization. PMID:25216070

  19. Essential Oil Composition, Antioxidant, Cytotoxic and Antiviral Activities of Teucrium pseudochamaepitys Growing Spontaneously in Tunisia.

    PubMed

    Hammami, Saoussen; Jmii, Habib; El Mokni, Ridha; Khmiri, Abdelbaki; Faidi, Khaled; Dhaouadi, Hatem; El Aouni, Mohamed Hédi; Aouni, Mahjoub; Joshi, Rajesh K

    2015-01-01

    The chemical composition, antioxidant, cytotoxic and antiviral activities of the essential oil obtained by hydrodistillation from the aerial parts of Teucrium pseudochamaepitys (Lamiaceae) collected from Zaghouan province of Tunisia are reported. The essential oil was analyzed by gas chromatography equipped with a flame ionization detector (GC-FID) and gas chromatography coupled with mass spectrometry (GC/MS). Thirty-one compounds were identified representing 88.6% of the total essential oil. Hexadecanoic acid was found to be the most abundant component (26.1%) followed by caryophyllene oxide (6.3%), myristicin (4.9%) and α-cubebene (3.9%). The antioxidant capacity of the oil was measured on the basis of the scavenging activity to the stable 2,2-diphenyl-1-picrylhydrazyl (DPPH). The IC50 value of the oil was evaluated as 0.77 mg·mL(-1). In addition, the essential oil was found to possess moderate cytotoxic effects on the HEp-2 cell line (50% cytotoxic concentration (CC50)=653.6 µg·mL(-1)). The potential antiviral effect was tested against Coxsackievirus B (CV-B), a significant human and mouse pathogen that causes pediatric central nervous system disease, commonly with acute syndromes. The reduction of viral infectivity by the essential oil was measured using a cytopathic (CPE) reduction assay. PMID:26580590

  20. AgI microplate monocrystals with polar {0001} facets: spontaneous photocarrier separation and enhanced photocatalytic activity.

    PubMed

    Kuang, Qin; Zheng, Xiaoli; Yang, Shihe

    2014-02-24

    Elucidating the facet-dependent photocatalytic activity of semiconductor photocatalysts is important in improving the overall efficiency of photocatalysis. Furthermore, combining facet control with selective deposition of oxidation and/or reduction cocatalysts on specific faces of semiconductor photocatalysts is potentially an effective strategy to synergistically optimize the functionality of photocatalysts. In the present study, high-purity wurtzite-type β-AgI platelet microcrystals with polar {0001} facets were prepared by a facile polyvinylpyrrolidone-assisted precipitation reaction. The polar-faceted AgI microplates were used as archetypes to demonstrate preferential diametric migration (i.e., effective separation) of photogenerated electrons and holes along the c axis. Such vectorial electron-hole separation stems from the asymmetric surface structures, which give rise to distinct photoexcited reaction behaviors on the ±(0001) polar facets of wurtzite-type semiconductors. Furthermore, on selective deposition of Ag and MnOx (1.5activity of the AgI microplates in degrading organic pollutants was dramatically enhanced thanks to the broad light-absorption range, strong dye-adsorption ability, and effective spatial separation of photocarriers. PMID:24449437

  1. Disturbances of the VLF/LF radio signal reception at Dobrogea Seismological Observatory due to local abnormal electric activity

    NASA Astrophysics Data System (ADS)

    Moldovan, Iren-Adelina; Toader, Victorin; Dolea, Paul; Biagi, Pier Francesco

    2015-04-01

    The National Institute for Earth Physics, as part of the INFREP initiative, has monitored radio waves emitted by 10 transmitters all over Europe in relation with seismicity in the last 5 years. In Romania a radio receiving system is located in only one site (Dobrogea Seismological Observatory) situated in Eforie Nord, in the Eastern part of Romania. The electro-magnetic field monitored both at the ground and (sub) ionospheric level, in different frequency ranges (VLF/LF) is considered to be promising for earthquake forecasting. Because the abnormal behavior of the VLF/LF recordings that could not be correlated with the tectonic activity of the seismogenic zones crossed by the radio paths, we decided to monitor other two parameters, at the receiving site: the vertical component of the atmospheric electric field, which indicates variations of electrical properties of the near-ground air (Boltek electric field mill), and the atmospheric local conditions (WS-3600 weather station). The zone is also surveyed by seismic devices (seismometers, accelerometers and infrasonic equipment) and GPS/GNSS base stations to emphasize the local tectonic conditions. We obtained in such way a multiple-parameter monitoring system that increases the confidence in observational data and decreases uncertainties regarding the accuracy of the data recorded until now. As we are exploring different parameters we have obtained some conclusions regarding the correlation of the anomalies with their possible causes. The final expectation of the monitoring system regard the chance to take a snapshot of the geophysical medium before, during and after a significant earthquake occurrence and to reveal if there was or wasn't a noticeable trace of the preparatory stage of it. This work was partially supported by a grant of the Romanian National Authority for Scientific Research, Programe for research- Space Technology and Avanced Research - STAR, project number 84/2013, and by the NUCLEU project, PN 09

  2. Heat transfer model to characterize the focal cooling necessary to suppress spontaneous epileptiform activity (Invited Paper)

    NASA Astrophysics Data System (ADS)

    Guerra, Reynaldo G.; Davalos, Rafael V.; Garcia, Paul A.; Rubinsky, Boris; Berger, Mitchel

    2005-04-01

    Epilepsy is characterized by paroxysmal transient disturbances of the electrical activity of the brain. Symptoms are manifested as impairment of motor, sensory, or psychic function with or without loss of consciousness or convulsive seizures. This paper presents an initial post-operative heat transfer analysis of surgery performed on a 41 year-old man with medically intractable Epilepsy. The surgery involved tumor removal and the resection of adjacent epileptogenic tissue. Electrocorticography was performed before resection. Cold saline was applied to the resulting interictal spike foci resulting in transient, complete cessation of spiking. A transient one dimensional semi-infinite finite element model of the surface of the brain was developed to simulate the surgery. An approximate temperature distribution of the perfused brain was developed by applying the bioheat equation. The model quantifies the surface heat flux reached in achieving seizure cessation to within an order of magnitude. Rat models have previously shown that the brain surface temperature range to rapidly terminate epileptogenic activity is 20-24°C. The developed model predicts that a constant heat flux of approximately -13,000W/m2, applied at the surface of the human brain, would achieve a surface temperature in this range in approximately 3 seconds. A parametric study was subsequently performed to characterize the effects of brain metabolism and brain blood perfusion as a function of the determined heat flux. The results of these findings can be used as a first approximation in defining the specifications of a cooling device to suppress seizures in human models.

  3. Long-Range Temporal Correlations in the Spontaneous in vivo Activity of Interneuron in the Mouse Hippocampus

    NASA Astrophysics Data System (ADS)

    Guo, Sheng-Bo; Wang, Ying; Yan, Xing; Lin, Longnian; Tsien, Joe; Huang, De-Shuang

    The spontaneous in vivo firings of neuron in mouse hippocampus are generally considered as neuronal noise, where there is no any correlation in the inter-spike interval (ISI) sequences. In the present study, we investigate the nature of the ISI sequences of neuron in CA1 area of mouse hippocampus. By using the detrended fluctuation analysis (DFA), we calculated the fluctuation or scaling exponent of the ISI sequences. The results indicated that there exists the long-range power-law correlation over large time scale in the ISI sequences. To further investigate the long-range correlation of ISI, we studied the long-range correlation of ISI sequences from different types of neurons in mouse hippocampus, which are four types of interneurons categorized by their firing patterns. Our results show the presence of long-range correlations in the ISI sequence of different types of neurons. Furthermore, the shuffle surrogate data achieved by randomly shuffle the original ISI sequence is used to verify our conclusion. The application of shuffle surrogate shows that the long-range correlation is destroyed by randomly shuffle, which demonstrates that there is actually the long-range correlation in the ISI sequence. Furthermore, we also compare the long-range correlations of ISI sequence when mice are in different behavioral states, slow-wave sleep (SWS) and active exploration (AE). Our results indicated that the ISI sequences exhibit different extent of long-range correlations: the long-range correlation is significantly stronger when mice are in AE than that of ISI sequence when mice are in SWS, which demonstrated that the varied long-range correlations exhibiting in ISIs of interneurons might be associated with activities of neuronal network regulating the ongoing neuronal activity of different interneurons.

  4. Alterations in erythrocyte plasma membrane ATPase activity and adenine nucleotide content in a spontaneously diabetic subline of the Chinese hamster.

    PubMed

    Bettin, D; Klöting, I; Kohnert, K D

    1996-01-01

    The CHIG/Han subline of the Chinese hamster develops noninsulin-dependent diabetes mellitus characterized by hyperinsulinemia and different degrees of glucose intolerance. To study whether these abnormalities could affect transmembrane cation transport activity, we determined membrane ATPase activity and ATP concentrations in red blood cells of diabetes-resistant CHIA and diabetes-susceptible CHIG sublines of the Chinese hamster. Mg(2+)-ATPase activity was increased in red blood cell membranes of diabetic hamsters compared with that of nondiabetic CHIG and the diabetes-resistant CHIA animals and correlated with plasma triglyceride and cholesterol levels. Ca(2+)-ATPase and Na+/K+ATPase activity were not significantly different between diabetic and nondiabetic hamsters, but for the Na+/K(+)-ATPase, Km was decreased and the Vmax value increased in membrane preparations from severely diabetic hamsters. Both ATP and ADP content were lower in erythrocytes from diabetic than nondiabetic hamsters. Independently of the levels of glycemia, AMP concentrations were higher in CHIG than in CHIA hamsters. While ATP/AMP ratios were found to be decreased in erythrocytes from diabetes-susceptible CHIG hamsters compared to the diabetes-resistant CHIA animals, they were significantly correlated with the levels of glycemia. Furthermore, the relationship between blood glucose levels and kidney weight in hamsters of the diabetes-susceptible CHIG subline was such, that severely hyperglycemic animals displayed the greatest increase in kidney wet weight. These results indicate that the progressive metabolic deterioration in the development of noninsulin-dependent diabetes is associated with significant changes in the activity and kinetic parameters of cellular ATPases which could probably indicate early membrane alterations which may eventually result in the late microangiopathic complications of diabetes. PMID:8820985

  5. The brain structure and spontaneous activity baseline of the behavioral bias in trait anxiety.

    PubMed

    Yin, Ping; Zhang, Meng; Hou, Xin; Tan, Yafei; Fu, Yixiao; Qiu, Jiang

    2016-10-01

    Individuals with trait anxiety are often considered to be predisposed to psychiatric disorders. However, there is great heterogeneity in the development of psychiatric disorders in this group of people and the nature of the trait anxiety is still unclear. So, we decided to explore the correlations of brain structure and brain activity with trait anxiety in normal individuals. Specifically, we investigated the correlations between trait anxiety and regional grey matter volume (rGMV) and regional BOLD, using the Amplitude of Low Frequency Fluctuations (ALFF) as an index in 382 university students. The results showed that the level of trait anxiety was negatively correlated with rGMV in the right middle occipital gyrus. This result indicates that individuals with high trait anxiety tend to have less image processing on conscious level. Furthermore, we found that trait anxiety was positively correlated with the ALFF in the bilateral superior frontal gyrus and the right supplementary motor area, and negatively correlated with the ALFF in the cerebellum and the thalamus. These results indicate that individuals with high trait anxiety may be more sensitive to relationships and sensory information. Overall, this study's findings suggest that individuals with high trait anxiety have attenuated image processing on the conscious level, and exhibit stronger induced sensibility and over-processing of relationships, which is a brain imaging precondition for psychiatric disorders. PMID:27340090

  6. Neural activations during visual sequence learning leave a trace in post-training spontaneous EEG.

    PubMed

    Moisello, Clara; Meziane, Hadj Boumediene; Kelly, Simon; Perfetti, Bernardo; Kvint, Svetlana; Voutsinas, Nicholas; Blanco, Daniella; Quartarone, Angelo; Tononi, Giulio; Ghilardi, Maria Felice

    2013-01-01

    Recent EEG studies have shown that implicit learning involving specific cortical circuits results in an enduring local trace manifested as local changes in spectral power. Here we used a well characterized visual sequence learning task and high density-(hd-)EEG recording to determine whether also declarative learning leaves a post-task, local change in the resting state oscillatory activity in the areas involved in the learning process. Thus, we recorded hd-EEG in normal subjects before, during and after the acquisition of the order of a fixed spatial target sequence (VSEQ) and during the presentation of targets in random order (VRAN). We first determined the temporal evolution of spectral changes during VSEQ and compared it to VRAN. We found significant differences in the alpha and theta bands in three main scalp regions, a right occipito-parietal (ROP), an anterior-frontal (AFr), and a right frontal (RFr) area. The changes in frontal theta power during VSEQ were positively correlated with the learning rate. Further, post-learning EEG recordings during resting state revealed a significant increase in alpha power in ROP relative to a pre-learning baseline. We conclude that declarative learning is associated with alpha and theta changes in frontal and posterior regions that occur during the task, and with an increase of alpha power in the occipito-parietal region after the task. These post-task changes may represent a trace of learning and a hallmark of use-dependent plasticity. PMID:23799058

  7. Introducing Co-Activation Pattern Metrics to Quantify Spontaneous Brain Network Dynamics

    PubMed Central

    Chen, Jingyuan E.; Chang, Catie; Greicius, Michael D.; Glover, Gary H.

    2015-01-01

    Recently, fMRI researchers have begun to realize that the brain's intrinsic network patterns may undergo substantial changes during a single resting state (RS) scan. However, despite the growing interest in brain dynamics, metrics that can quantify the variability of network patterns are still quite limited. Here, we first introduce various quantification metrics based on the extension of co-activation pattern (CAP) analysis, a recently proposed point-process analysis that tracks state alternations at each individual time frame and relies on very few assumptions; then apply these proposed metrics to quantify changes of brain dynamics during a sustained 2-back working memory (WM) task compared to rest. We focus on the functional connectivity of two prominent RS networks, the default-mode network (DMN) and executive control network (ECN). We first demonstrate less variability of global Pearson correlations with respect to the two chosen networks using a sliding-window approach during WM task compared to rest; then we show that the macroscopic decrease in variations in correlations during a WM task is also well characterized by the combined effect of a reduced number of dominant CAPs, increased spatial consistency across CAPs, and increased fractional contributions of a few dominant CAPs. These CAP metrics may provide alternative and more straightforward quantitative means of characterizing brain network dynamics than time-windowed correlation analyses. PMID:25662866

  8. The contribution of pre-stimulus neural oscillatory activity to spontaneous response time variability.

    PubMed

    Bompas, Aline; Sumner, Petroc; Muthumumaraswamy, Suresh D; Singh, Krish D; Gilchrist, Iain D

    2015-02-15

    Large variability between individual response times, even in identical conditions, is a ubiquitous property of animal behavior. However, the origins of this stochasticity and its relation to action decisions remain unclear. Here we focus on the state of the perception-action network in the pre-stimulus period and its influence on subsequent saccadic response time and choice in humans. We employ magnetoencephalography (MEG) and a correlational source reconstruction approach to identify the brain areas where pre-stimulus oscillatory activity predicted saccadic response time to visual targets. We find a relationship between future response time and pre-stimulus power, but not phase, in occipital (including V1), parietal, posterior cingulate and superior frontal cortices, consistently across alpha, beta and low gamma frequencies, each accounting for between 1 and 4% of the RT variance. Importantly, these correlations were not explained by deterministic sources of variance, such as experimental factors and trial history. Our results further suggest that occipital areas mainly reflect short-term (trial to trial) stochastic fluctuations, while the frontal contribution largely reflects longer-term effects such as fatigue or practice. Parietal areas reflect fluctuations at both time scales. We found no evidence of lateralization: these effects were indistinguishable in both hemispheres and for both saccade directions, and non-predictive of choice - a finding with fundamental consequences for models of action decision, where independent, not coupled, noise is normally assumed. PMID:25482267

  9. Neural Activations during Visual Sequence Learning Leave a Trace in Post-Training Spontaneous EEG

    PubMed Central

    Moisello, Clara; Meziane, Hadj Boumediene; Kelly, Simon; Perfetti, Bernardo; Kvint, Svetlana; Voutsinas, Nicholas; Blanco, Daniella; Quartarone, Angelo; Tononi, Giulio; Ghilardi, Maria Felice

    2013-01-01

    Recent EEG studies have shown that implicit learning involving specific cortical circuits results in an enduring local trace manifested as local changes in spectral power. Here we used a well characterized visual sequence learning task and high density-(hd-)EEG recording to determine whether also declarative learning leaves a post-task, local change in the resting state oscillatory activity in the areas involved in the learning process. Thus, we recorded hd-EEG in normal subjects before, during and after the acquisition of the order of a fixed spatial target sequence (VSEQ) and during the presentation of targets in random order (VRAN). We first determined the temporal evolution of spectral changes during VSEQ and compared it to VRAN. We found significant differences in the alpha and theta bands in three main scalp regions, a right occipito-parietal (ROP), an anterior-frontal (AFr), and a right frontal (RFr) area. The changes in frontal theta power during VSEQ were positively correlated with the learning rate. Further, post-learning EEG recordings during resting state revealed a significant increase in alpha power in ROP relative to a pre-learning baseline. We conclude that declarative learning is associated with alpha and theta changes in frontal and posterior regions that occur during the task, and with an increase of alpha power in the occipito-parietal region after the task. These post-task changes may represent a trace of learning and a hallmark of use-dependent plasticity. PMID:23799058

  10. The Shape of Uterine Contractions and Labor Progress in the Spontaneous Active Labor

    PubMed Central

    Ebrahimzadeh Zagami, Samira; Golmakani, Nahid; Saadatjoo, Seyyed Ali-Reza; Ghomian, Nayyereh; Baghbani, Behjat

    2015-01-01

    Background Dystocia is the most common indication of primary cesarean section. The most common cause of dystocia is uterine dysfunction. In prolonged labor, more attention is usually paid to the fetus and pelvis rather than to the role of uterine contractions in a delivery. Therefore, we decided to determine the relationship between the labor progress and uterine contractions shapes. Methods In this cross-sectional study, 200 primiparous women participated having a single pregnancy and cephalic presentation. Uterus contractions were recorded using electronic fetal monitoring at the beginning of the active phase of labor (dilatation 3-5 cm) for 30 min. Fall to rise (F:R) ratio was calculated by determining the duration of returning from a contraction peak to its baseline (fall) and the duration of the rise time from baseline to peak (rise) in two groups. The data were analyzed using t-test and Chi-square test. Results In this study, 162 women had a normal delivery and 38 women had a cesarean (CS) delivery due to the lack of labor progress. The average F:R ratio was 1.13±0.193 seconds in the vaginal delivery group and 1.64±0.301 seconds in the CS group. This difference was statistically significant (P<0.001). The frequency of contractions in the vaginal delivery group was more than the CS group (P=0.008). Conclusion Our findings demonstrated that uterine contractions shapes change; and F:R ratio was higher in the group that lacked labor progress. Therefore, contraction shapes can be used to predict the labor progress.   PMID:25821288

  11. Spontaneous otogenic pneumocephalus.

    PubMed

    Mohammed, El Romyssa; Profant, Milan

    2011-06-01

    The diagnosis and management of spontaneous otogenic pneumocephalus with literature review is described. A young sportsman experienced headache and fluctuating mass in his occiput during increased physical activity. A large extradural intracranial pneumocephalus with corresponding emphysema was imaged on a CT scan. Transmastoid identification and plugging of temporal bone defect solved the problem with complete pneumocephalus and emphysema resorption. PMID:21254960

  12. A Case of Multiple Spontaneous Keloid Scars

    PubMed Central

    Jfri, Abdulhadi; Rajeh, Nawal; Karkashan, Eman

    2015-01-01

    Keloid scars result from an abnormal healing response to cutaneous injury or inflammation that extends beyond the borders of the original wound. Spontaneous keloid scars forming in the absence of any previous trauma or surgical procedure are rare. Certain syndromes have been associated with this phenomenon, and few reports have discussed the evidence of single spontaneous keloid scar, which raises the question whether they are really spontaneous. Here, we present a 27-year-old mentally retarded single female with orbital hypertelorism, broad nasal bridge, repaired cleft lip and high-arched palate who presented with progressive multiple spontaneous keloid scars in different parts of her body which were confirmed histologically by the presence of typical keloidal collagen. This report supports the fact that keloid scars can appear spontaneously and are possibly linked to a genetic factor. Furthermore, it describes a new presentation of spontaneous keloid scars in the form of multiple large lesions in different sites of the body. PMID:26351423

  13. Antioxidative activities of 4-hydroxy-3(2H)-furanones and their anti-cataract effect on spontaneous cataract rat (ICR/f).

    PubMed

    Sasaki, T; Yamakoshi, J; Saito, M; Kasai, K; Matsudo, T; Koga, T; Mori, K

    1998-10-01

    We determined the anti-cataract effects and antioxidative activities of four 4-hydroxy-3(2H)-furanones. These four furanones showed similar antioxidative activities in the ferric ion reduction model. 4-Hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF) and 2(or 5)-ethyl-4-hydroxy-5(or 2)-methyl-3(2H)-furanone (EHMF) exhibited a higher suppression effect on lipid peroxidation in human plasma than the other furanones did. The effects of hydroxy furanones on the onset of cataract in spontaneous cataract rat (ICR/f rat) were tested, and it was observed that HDMF and EHMF inhibited cataract formation. These results suggest that the antioxidative activity of HDMF and EHMF against superoxide radicals in lens tissue contributed to inhibiting the onset of spontaneous cataract. PMID:9836421

  14. Detecting resting-state brain activity by spontaneous cerebral blood volume fluctuations using whole brain vascular space occupancy imaging.

    PubMed

    Miao, Xinyuan; Gu, Hong; Yan, Lirong; Lu, Hanzhang; Wang, Danny J J; Zhou, Xiaohong Joe; Zhuo, Yan; Yang, Yihong

    2014-01-01

    Resting-state brain activity has been investigated extensively using BOLD contrast. However, BOLD signal represents the combined effects of multiple physiological processes and its spatial localization is less accurate than that of cerebral blood flow and volume (CBF and CBF, respectively). In this study, we demonstrate that resting-state brain activity can be reliably detected by spontaneous fluctuations of CBV-weighted signal using whole-brain gradient and spin echo (GRASE) based vascular space occupancy (VASO) imaging. Specifically, using independent component analysis, intrinsic brain networks, including default mode, salience, executive control, visual, auditory, and sensorimotor networks were revealed robustly by the VASO technique. We further demonstrate that task-evoked VASO signal aligned well with expected gray matter areas, while blood-oxygenation level dependent (BOLD) signal extended outside of these areas probably due to their different spatial specificity. The improved spatial localization of VASO is consistent with previous studies using animal models. Moreover, we showed that the 3D-GRASE VASO images had reduced susceptibility-induced signal voiding, compared to the BOLD technique. This is attributed to the fact that VASO does not require T2* weighting, thus the acquisition can use a shorter TE and can employ spin-echo scheme. Consequently VASO-based functional connectivity signals were well preserved in brain regions that tend to suffer from signal loss and geometric distortion in BOLD, such as orbital prefrontal cortex. Our study suggests that 3D-GRASE VASO imaging, with its improved spatial specificity and less sensitivity to susceptibility artifacts, may have advantages in resting-state fMRI studies. PMID:24055705

  15. Effects of Severing the Corpus Callosum on Electrical and BOLD Functional Connectivity and Spontaneous Dynamic Activity in the Rat Brain

    PubMed Central

    Magnuson, Matthew E.; Thompson, Garth J.; Pan, Wen-Ju

    2014-01-01

    Abstract Functional networks, defined by synchronous spontaneous blood oxygenation level-dependent (BOLD) oscillations between spatially distinct brain regions, appear to be essential to brain function and have been implicated in disease states, cognitive capacity, and sensing and motor processes. While the topographical extent and behavioral function of these networks has been extensively investigated, the neural functions that create and maintain these synchronizations remain mysterious. In this work callosotomized rodents are examined, providing a unique platform for evaluating the influence of structural connectivity via the corpus callosum on bilateral resting state functional connectivity. Two experimental groups were assessed, a full callosotomy group, in which the corpus callosum was completely sectioned, and a sham callosotomy group, in which the gray matter was sectioned but the corpus callosum remained intact. Results indicated a significant reduction in interhemispheric connectivity in the full callosotomy group as compared with the sham group in primary somatosensory cortex and caudate-putamen regions. Similarly, electrophysiology revealed significantly reduced bilateral correlation in band limited power. Bilateral gamma Band-limited power connectivity was most strongly affected by the full callosotomy procedure. This work represents a robust finding indicating the corpus callosum's influence on maintaining integrity in bilateral functional networks; further, functional magnetic resonance imaging (fMRI) and electrophysiological connectivity share a similar decrease in connectivity as a result of the callosotomy, suggesting that fMRI-measured functional connectivity reflects underlying changes in large-scale coordinated electrical activity. Finally, spatiotemporal dynamic patterns were evaluated in both groups; the full callosotomy rodents displayed a striking loss of bilaterally synchronous propagating waves of cortical activity. PMID:24117343

  16. Role of the locus coeruleus in enhanced orexin A-induced spontaneous physical activity in obesity-resistant rats

    PubMed Central

    Perez-Leighton, Claudio E.; Billington, Charles J.; Kotz, Catherine M.

    2013-01-01

    Orexin/hypocretin terminals innervate noradrenergic locus coeruleus (LC) neurons that project to the prefrontral cortex, which may influence spontaneous physical activity (SPA) and energy balance. Obesity-resistant (OR) rats have higher orexin receptors (OXR) mRNA in the LC and other brain regions, as well as lower adiposity compared with obese rats. These findings led us to hypothesize that orexin activity in the LC is relevant for the OR phenotype. We compared OR rats to Sprague-Dawley rats. We predicted that: 1) brain OXR expression pattern is sufficient to differentiate OR from non-bred Sprague-Dawley rats; 2) nonresting energy expenditure (NREE) and orexin A (OXA)-stimulated SPA after injection in LC would be greater in OR rats; and 3) the effect of OXA on SPA would be greater than its effect on feeding. OXR mRNA from 11 brain sites and the SPA and feeding responses to OXA in the LC were determined. Body composition, basal SPA, and EE were determined. Principal component analysis of the OXR expression pattern differentiates OR and Sprague-Dawley rats and suggests the OXR mRNA in the LC is important in defining the OR phenotype. Compared with Sprague-Dawley rats, OR rats had greater SPA and NREE and lower resting EE and adiposity. SPA responsivity to OXA in the LC was greater in OR rats compared with Sprague-Dawley rats. OXA in the LC did not stimulate feeding in OR or Sprague-Dawley rats. These data suggest that the LC is a prominent site modulating OXA-stimulated SPA, which promotes lower adiposity and higher nonresting EE. PMID:24089383

  17. PYK2 selectively mediates signals for growth versus differentiation in response to stretch of spontaneously active vascular smooth muscle.

    PubMed

    Bhattachariya, Anirban; Turczyńska, Karolina M; Grossi, Mario; Nordström, Ina; Buckbinder, Leonard; Albinsson, Sebastian; Hellstrand, Per

    2014-01-01

    Stretch of vascular smooth muscle stimulates growth and proliferation as well as contraction and expression of contractile/cytoskeletal proteins, all of which are also regulated by calcium-dependent signals. We studied the role of the calcium- and integrin-activated proline-rich tyrosine kinase 2 (PYK2) in stretch-induced responses of the rat portal vein loaded by a hanging weight ex vivo. PYK2 phosphorylation at Tyr-402 was increased both by a 10-min stretch and by organ culture with load over several days. Protein and DNA synthesis were reduced by the novel PYK2 inhibitor PF-4594755 (0.5-1 μmol/L), while still sensitive to stretch. In 3-day organ culture, PF-4594755 caused maintained myogenic spontaneous activity but did not affect contraction in response to high-K(+) (60 mmol/L) or to α1-adrenergic stimulation by cirazoline. Basal and stretch-induced PYK2 phosphorylation in culture were inhibited by PF-4594755, closely mimicking inhibition of non-voltage-dependent calcium influx by 2-APB (30 μmol/L). In contrast, the L-type calcium channel blocker, nifedipine (1 μmol/L) eliminated stretch-induced but not basal PYK2 phosphorylation. Stretch-induced Akt and ERK1/2 phosphorylation was eliminated by PF-4594755. PYK2 inhibition had no effect on mRNA expression of several smooth muscle markers, and stretch-sensitive SM22α synthesis was preserved. Culture of portal vein with the Ang II inhibitor losartan (1 μmol/L) eliminated stretch sensitivity of PYK2 and Akt phosphorylation, but did not affect mRNA expression of smooth muscle markers. The results suggest that PYK2 signaling functionally distinguishes effects of voltage- and non-voltage-dependent calcium influx. A small-molecule inhibitor of PYK2 reduces growth and DNA synthesis but does not affect contractile differentiation of vascular smooth muscle. PMID:25347863

  18. Altered intrinsic regional spontaneous brain activity in patients with optic neuritis: a resting-state functional magnetic resonance imaging study

    PubMed Central

    Shao, Yi; Cai, Feng-Qin; Zhong, Yu-Lin; Huang, Xin; Zhang, Ying; Hu, Pei-Hong; Pei, Chong-Gang; Zhou, Fu-Qing; Zeng, Xian-Jun

    2015-01-01

    Objective To investigate the underlying regional homogeneity (ReHo) in brain-activity deficit in patients with optic neuritis (ON) and its relationship with behavioral performance. Materials and methods In total, twelve patients with ON (four males and eight females) and twelve (four males and eight females) age-, sex-, and education-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. The ReHo method was used to assess the local features of spontaneous brain activity. Correlation analysis was used to explore the relationship between the observed mean ReHo values of the different brain areas and the visual evoked potential (VEP) in patients with ON. Results Compared with the healthy controls, patients with ON showed lower ReHo in the left cerebellum, posterior lobe, left middle temporal gyrus, right insula, right superior temporal gyrus, left middle frontal gyrus, bilateral anterior cingulate cortex, left superior frontal gyrus, right superior frontal gyrus, and right precentral gyrus, and higher ReHo in the cluster of the left fusiform gyrus and right inferior parietal lobule. Meanwhile, we found that the VEP amplitude of the right eye in patients with ON showed a positive correlation with the ReHo signal value of the left cerebellum posterior lobe (r=0.701, P=0.011), the right superior frontal gyrus (r=0.731, P=0.007), and the left fusiform gyrus (r=0.644, P=0.024). We also found that the VEP latency of the right eye in ON showed a positive correlation with the ReHo signal value of the right insula (r=0.595, P=0.041). Conclusion ON may involve dysfunction in the default-mode network, which may reflect the underlying pathologic mechanism. PMID:26715848

  19. Development of spontaneous neuropathy in NF-κBp50-deficient mice by calcineurin-signal involving impaired NF-κB activation

    PubMed Central

    Nakamura-Yanagidaira, Tomoko; Takahashi, Yasuko; Sano, Kenji; Murata, Toshinori

    2011-01-01

    Purpose The transcriptional regulator, nuclear factor-kappa B (NF-κB)/Rel family are involved in neuronal cell death and survival. Previously, we reported that NF-κBp50-deficient (p50-deficient) mice exhibit many features resembling human normal tension glaucoma (NTG). The developmental mechanism of human NTG is not clearly understood, and a radical curative treatment has yet to be established. Our aim is to elucidate the signal cascade which mediates the spontaneous optic neuropathy in p50-deficient mice as a model of NTG. Methods To demonstrate the expression and activation of pro-apoptotic factors, which mediate the death of retinal ganglion cells (RGCs) in p50-deficient mice, western blot (WB) and luciferase reporter assays with retinas from p50-deficient and wild type mice, and cultured RGC-5 cells were performed. Furthermore, we tested the neuroprotective effects of chemical reagents (memantine, lomerizine, and tacrolimus) against N-methyl-D-aspartate (NMDA)-susceptible RGC damage according to in vitro experiments with RGC-5 cells. To elucidate the NF-κB-mediated death signaling, the effects of chemical reagents on spontaneous optic neuropathy were examined by histopathological studies. Results WB experiments and luciferase reporter assays showed that NF-κB-inducible BCL2-associated X protein (Bax) and a pro-apoptotic factor, activated caspase 3 were expressed in the retina of p50-deficient mice as well as NMDA-treated RGC-5 cells. Further, the constitutivelyactivecleaved forms of calcineurin (CaN), which havebeen reported to lead to apoptosis, were detected in the retina of p50-deficient mice as well as NMDA-treated RGC-5 cells. Pre-treatment with tacrolimus markedlyprotected RGC-5 cells from NMDA-induced neurotoxicity, and then both spontaneous RGC death and degenerative changes to the optic nerve in p50-deficient mice were significantlyreduced by the chronic administration of tacrolimus. The experiments with cultured RGC-5 cells supported the results

  20. Unaltered Network Activity and Interneuronal Firing During Spontaneous Cortical Dynamics In Vivo in a Mouse Model of Severe Myoclonic Epilepsy of Infancy

    PubMed Central

    De Stasi, Angela Michela; Farisello, Pasqualina; Marcon, Iacopo; Cavallari, Stefano; Forli, Angelo; Vecchia, Dania; Losi, Gabriele; Mantegazza, Massimo; Panzeri, Stefano; Carmignoto, Giorgio; Bacci, Alberto; Fellin, Tommaso

    2016-01-01

    Severe myoclonic epilepsy of infancy (SMEI) is associated with loss of function of the SCN1A gene encoding the NaV1.1 sodium channel isoform. Previous studies in Scn1a−/+ mice during the pre-epileptic period reported selective reduction in interneuron excitability and proposed this as the main pathological mechanism underlying SMEI. Yet, the functional consequences of this interneuronal dysfunction at the circuit level in vivo are unknown. Here, we investigated whether Scn1a−/+ mice showed alterations in cortical network function. We found that various forms of spontaneous network activity were similar in Scn1a−/+ during the pre-epileptic period compared with wild-type (WT) in vivo. Importantly, in brain slices from Scn1a−/+ mice, the excitability of parvalbumin (PV) and somatostatin (SST) interneurons was reduced, epileptiform activity propagated more rapidly, and complex synaptic changes were observed. However, in vivo, optogenetic reduction of firing in PV or SST cells in WT mice modified ongoing network activities, and juxtasomal recordings from identified PV and SST interneurons showed unaffected interneuronal firing during spontaneous cortical dynamics in Scn1a−/+ compared with WT. These results demonstrate that interneuronal hypoexcitability is not observed in Scn1a−/+ mice during spontaneous activities in vivo and suggest that additional mechanisms may contribute to homeostatic rearrangements and the pathogenesis of SMEI. PMID:26819275

  1. Activation of C-F bonds in fluoroarenes by N-heterocyclic carbenes as an effective route to synthesize abnormal NHC complexes.

    PubMed

    Kim, Youngsuk; Lee, Eunsung

    2016-09-18

    IPr (1a) reacts with octafluorotoluene by an unexpected sequential substitution of fluorides in two separate rings. The resulting tetrasubstituted imidazolium salt was isolated and elaborated into Ag(i) and Au(i) complexes with a novel abnormal NHC ligand. Both IPr (1a) and IMes (1b) were also found to be moderately reactive by nucleophilic substitution of the aromatic C-F bond in a weakly-activated fluoroarene, 1-fluoro-4-trifluoromethylbenzene (5). PMID:27533338

  2. Numerically abnormal chromosome constitutions in humans

    SciTech Connect

    1993-12-31

    Chapter 24, discusses numerically abnormal chromosome constitutions in humans. This involves abnormalities of human chromosome number, including polyploidy (when the number of sets of chromosomes increases) and aneuploidy (when the number of individual normal chromosomes changes). Chapter sections discuss the following chromosomal abnormalities: human triploids, imprinting and uniparental disomy, human tetraploids, hydatidiform moles, anomalies caused by chromosomal imbalance, 13 trisomy (D{sub 1} trisomy, Patau syndrome), 21 trisomy (Down syndrome), 18 trisomy syndrome (Edwards syndrome), other autosomal aneuploidy syndromes, and spontaneous abortions. The chapter concludes with remarks on the nonrandom participation of chromosomes in trisomy. 69 refs., 3 figs., 4 tabs.

  3. Association of exercise training and angiotensin-converting enzyme 2 activator improves baroreflex sensitivity of spontaneously hypertensive rats

    PubMed Central

    Lopes, P.R.; Moreira, M.C.S.; Marques, S.M.; Pinto, I.S.J.; Macedo, L.M.; Silva, C.C.; Freiria-Oliveira, A.H.; Rebelo, A.C.S.; Reis, A.A.S.; Rosa, D.A.; Ferreira-Neto, M.L.; Castro, C.H.; Pedrino, G.R.

    2016-01-01

    The present study sought to determine cardiovascular effects of aerobic training associated with diminazene aceturate (DIZE), an activator of the angiotensin converting enzyme 2, in spontaneously hypertensive rats (SHRs). Male SHRs (280–350 g) were either subjected to exercise training or not (sedentary group). The trained group was subjected to 8 weeks of aerobic training on a treadmill (five times a week, lasting 60 min at an intensity of 50–60% of maximum aerobic speed). In the last 15 days of the experimental protocol, these groups were redistributed into four groups: i) sedentary SHRs with daily treatment of 1 mg/kg DIZE (S+D1); ii) trained SHRs with daily treatment of 1 mg/kg DIZE (T+D1); iii) sedentary SHRs with daily treatment of vehicle (S+V); and iv) trained SHRs with daily treatment of vehicle (T+V). After treatment, SHRs were anesthetized and subjected to artery and femoral vein cannulation prior to the implantation of ECG electrode. After 24 h, mean arterial pressure (MAP) and heart rate (HR) were recorded; the baroreflex sensitivity and the effect of double autonomic blockade (DAB) were evaluated in non-anesthetized SHRs. DIZE treatment improved baroreflex sensitivity in the T+D1 group as compared with the T+V and S+D1 groups. The intrinsic heart rate (IHR) and MAP were reduced in T+D1 group as compared with T+V and S+D1 groups. Hence, we conclude that the association of exercise training with DIZE treatment improved baroreflex function and cardiovascular regulation. PMID:27533767

  4. Association of exercise training and angiotensin-converting enzyme 2 activator improves baroreflex sensitivity of spontaneously hypertensive rats.

    PubMed

    Lopes, P R; Moreira, M C S; Marques, S M; Pinto, I S J; Macedo, L M; Silva, C C; Freiria-Oliveira, A H; Rebelo, A C S; Reis, A A S; Rosa, D A; Ferreira-Neto, M L; Castro, C H; Pedrino, G R

    2016-01-01

    The present study sought to determine cardiovascular effects of aerobic training associated with diminazene aceturate (DIZE), an activator of the angiotensin converting enzyme 2, in spontaneously hypertensive rats (SHRs). Male SHRs (280-350 g) were either subjected to exercise training or not (sedentary group). The trained group was subjected to 8 weeks of aerobic training on a treadmill (five times a week, lasting 60 min at an intensity of 50-60% of maximum aerobic speed). In the last 15 days of the experimental protocol, these groups were redistributed into four groups: i) sedentary SHRs with daily treatment of 1 mg/kg DIZE (S+D1); ii) trained SHRs with daily treatment of 1 mg/kg DIZE (T+D1); iii) sedentary SHRs with daily treatment of vehicle (S+V); and iv) trained SHRs with daily treatment of vehicle (T+V). After treatment, SHRs were anesthetized and subjected to artery and femoral vein cannulation prior to the implantation of ECG electrode. After 24 h, mean arterial pressure (MAP) and heart rate (HR) were recorded; the baroreflex sensitivity and the effect of double autonomic blockade (DAB) were evaluated in non-anesthetized SHRs. DIZE treatment improved baroreflex sensitivity in the T+D1 group as compared with the T+V and S+D1 groups. The intrinsic heart rate (IHR) and MAP were reduced in T+D1 group as compared with T+V and S+D1 groups. Hence, we conclude that the association of exercise training with DIZE treatment improved baroreflex function and cardiovascular regulation. PMID:27533767

  5. Effect of calorie restriction on spontaneous physical activity and body mass in mice divergently selected for basal metabolic rate (BMR).

    PubMed

    Brzęk, Paweł; Gębczyński, Andrzej K; Książek, Aneta; Konarzewski, Marek

    2016-07-01

    Spontaneous physical activity (SPA) represents an important component of daily energy expenditures in animals and humans. Intra-specific variation in SPA may be related to the susceptibility to metabolic disease or obesity. In particular, reduced SPA under conditions of limited food availability may conserve energy and prevent loss of body and fat mass ('thrifty genotype hypothesis'). However, both SPA and its changes during food restriction show wide inter-individual variations. We studied the effect of 30% caloric restriction (CR) on SPA in laboratory mice divergently selected for high (H-BMR) and low (L-BMR) basal metabolic rate. Selection increased SPA in the H-BMR line but did not change it in the L-BMR mice. This effect reflected changes in SPA intensity but not SPA duration. CR increased SPA intensity more strongly in the L-BMR line than in the H-BMR line and significantly modified the temporal variation of SPA. However, the initial between-line differences in SPA were not affected by CR. Loss of body mass during CR did not differ between both lines. Our results show that the H-BMR mice can maintain their genetically determined high SPA under conditions of reduced food intake without sacrificing their body mass. We hypothesize that this pattern may reflect the higher flexibility in the energy budget in the H-BMR line, as we showed previously that mice from this line reduced their BMR during CR. These energy savings may allow for the maintenance of elevated SPA in spite of reduced food intake. We conclude that the effect of CR on SPA is in large part determined by the initial level of BMR, whose variation may account for the lack of universal pattern of behavioural responses to CR. PMID:27090226

  6. Spontaneous circadian fluctuations of prostate specific antigen and prostatic acid phosphatase serum activities in patients with prostatic cancer.

    PubMed

    Mannini, D; Maver, P; Aiello, E; Corrado, G; Vecchi, F; Bellanova, B; Marengo, M

    1988-01-01

    Spontaneous circadian variations of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP), determined simultaneously by radioimmunoassay (RIA), were investigated by multiple sampling, over a 24-hour period, in 32 patients with prostatic cancer. In 29/32 patients (91%), the coefficient of variation of 24-hour values, for either marker, was greater than that of the RIA method at the same range of values; stage D patients showed the greatest spontaneous variability. Fluctuations around the mean of 24-hour values ranged from -65% to +85% for PAP, from -72% to +190% for PSA, occurring random and independently for each marker. Variability was about 20% greater for PSA than for PAP. The existence of spontaneous fluctuations should be considered in multiple marker evaluation of prostatic cancer patients. PMID:2449758

  7. Spontaneous electrical activities at myofascial trigger points at different stages of recovery from injury in a rat model

    PubMed Central

    Huang, Qiang-Min; Lv, Jiao-Jiao; Ruanshi, Qiong-Mei; Liu, Lin

    2015-01-01

    Background Spontaneous electrical activity (SEA) is a feature of myofascial trigger points (MTrPs), which can either be latent or active. However, SEA at different stages of recovery from MTrPs remains unclear. Objective To investigate the temporal changes in the nature of SEA after generation of MTrPs in a rat model. Methods 32 rats were divided into four groups: 24 rats were assigned to experimental groups (EGs), which underwent the MTrP modelling intervention and 8 were allocated to a control group (CG). All EG rats received a blunt strike to the left vastus medialis combined with eccentric exercise for 8 weeks. After modelling, the EG rats were subdivided into three groups with total recovery times of 4, 8 and 12 weeks (EG-4w, EG-8w and EG-12w, respectively). Taut bands (TBs) with and without the presence of active MTrPs were identified in the left hind limb muscles of all rats, verified by SEA and further examined with electromyography recordings. Myoelectrical signals were also categorised into one of five types. Results CG rats had fewer TBs than EG rats and EGs showed variable frequencies of SEA. SEA frequencies were higher in EG-4w than in EG-8w and EG-12w groups (240.57±72.9 vs 168.14±64.5 and 151.63±65.4, respectively, p<0.05) and were significantly greater in all EGs than in the CG (55.75±21.9). Relative to CG rats, amplitudes and durations of electrical potentials in the EG were only increased in the EG-8w and EG-12w groups. Types IV and V myoelectrical signals were never seen in latent MTrPs and type V signals did not occur in EG-4w rats. Conclusions Increasing recovery periods following a MTrP modelling intervention in rats are characterised by different frequencies and amplitudes of SEA from TBs. Trial registration number 2014012. PMID:25971282

  8. Deletion of dopamine D1 and D3 receptors differentially affects spontaneous behaviour and cocaine-induced locomotor activity, reward and CREB phosphorylation.

    PubMed

    Karasinska, Joanna M; George, Susan R; Cheng, Regina; O'Dowd, Brian F

    2005-10-01

    Co-localization of dopamine D1 and D3 receptors in striatal neurons suggests that these two receptors interact at a cellular level in mediating dopaminergic function including psychostimulant-induced behaviour. To study D1 and D3 receptor interactions in cocaine-mediated effects, cocaine-induced locomotion and reward in mice lacking either D1, D3 or both receptors were analysed. Spontaneous locomotor activity was increased in D1-/- and D1-/-D3-/- mice and D1-/-D3-/- mice did not exhibit habituation of spontaneous rearing activity. Cocaine (20 mg/kg) increased locomotor activity in wild-type and D3-/- mice, failed to stimulate activity in D1-/- mice and reduced activity in D1-/-D3-/- mice. In the conditioned place preference, all groups exhibited reward at 5, 10 and 20 mg/kg of cocaine. D1-/-D3-/- mice did not demonstrate preference at 2.5 mg/kg of cocaine although preference was observed in wild-type, D1-/- and D3-/- mice. The transcription factor cAMP-responsive element binding protein (CREB) is activated by phosphorylation in striatal regions following dopamine receptor activation. Striatal pCREB levels following acute cocaine were increased in wild-type and D3-/- mice and decreased in D1-/- and D1-/-D3-/- mice. After repeated administration of 2.5 mg/kg of cocaine, D1-/- mice had lower pCREB levels in caudate-putamen and nucleus accumbens. Our findings suggest that, although spontaneous and cocaine-induced horizontal activity depended mainly on the presence of the D1 receptor, there may be crosstalk between D1 and D3 receptors in rearing habituation and the perception of cocaine reward at low doses of the drug. Furthermore, alterations in pCREB levels were associated with changes in cocaine-induced locomotor activity but not reward. PMID:16197514

  9. PYK2 selectively mediates signals for growth versus differentiation in response to stretch of spontaneously active vascular smooth muscle

    PubMed Central

    Bhattachariya, Anirban; Turczyńska, Karolina M.; Grossi, Mario; Nordström, Ina; Buckbinder, Leonard; Albinsson, Sebastian; Hellstrand, Per

    2014-01-01

    Abstract Stretch of vascular smooth muscle stimulates growth and proliferation as well as contraction and expression of contractile/cytoskeletal proteins, all of which are also regulated by calcium‐dependent signals. We studied the role of the calcium‐ and integrin‐activated proline‐rich tyrosine kinase 2 (PYK2) in stretch‐induced responses of the rat portal vein loaded by a hanging weight ex vivo. PYK2 phosphorylation at Tyr‐402 was increased both by a 10‐min stretch and by organ culture with load over several days. Protein and DNA synthesis were reduced by the novel PYK2 inhibitor PF‐4594755 (0.5–1 μmol/L), while still sensitive to stretch. In 3‐day organ culture, PF‐4594755 caused maintained myogenic spontaneous activity but did not affect contraction in response to high‐K+ (60 mmol/L) or to α1‐adrenergic stimulation by cirazoline. Basal and stretch‐induced PYK2 phosphorylation in culture were inhibited by PF‐4594755, closely mimicking inhibition of non‐voltage‐dependent calcium influx by 2‐APB (30 μmol/L). In contrast, the L‐type calcium channel blocker, nifedipine (1 μmol/L) eliminated stretch‐induced but not basal PYK2 phosphorylation. Stretch‐induced Akt and ERK1/2 phosphorylation was eliminated by PF‐4594755. PYK2 inhibition had no effect on mRNA expression of several smooth muscle markers, and stretch‐sensitive SM22α synthesis was preserved. Culture of portal vein with the Ang II inhibitor losartan (1 μmol/L) eliminated stretch sensitivity of PYK2 and Akt phosphorylation, but did not affect mRNA expression of smooth muscle markers. The results suggest that PYK2 signaling functionally distinguishes effects of voltage‐ and non‐voltage‐dependent calcium influx. A small‐molecule inhibitor of PYK2 reduces growth and DNA synthesis but does not affect contractile differentiation of vascular smooth muscle. PMID:25347863

  10. Frequencies of spontaneous breast development and spontaneous menarche in Turner syndrome in Japan.

    PubMed

    Tanaka, Toshiaki; Igarashi, Yutaka; Ozono, Keiichi; Ohyama, Kenji; Ogawa, Masamichi; Osada, Hisao; Onigata, Kazumichi; Kanzaki, Susumu; Kohno, Hitoshi; Seino, Yoshiki; Takahashi, Hiroaki; Tajima, Toshihiro; Tachibana, Katsuhiko; Tanaka, Hiroyuki; Nishi, Yoshikazu; Hasegawa, Tomonobu; Fujita, Keinosuke; Yorifuji, Tohru; Horikawa, Reiko; Yokoya, Susumu

    2015-10-01

    The Growject® database on human GH treatment in Turner syndrome was analyzed in the Turner Syndrome Research Collaboration, and the relationships of the frequencies of spontaneous breast development and spontaneous menarche with karyotype and GH treatment were investigated. One hundred and three cases started GH treatment with 0.5 IU/kg/ week (0.5 IU group), and their dose was increased to 0.35 mg/kg/wk midway through the treatment course. Another 109 cases started GH at a dose of 0.35 mg/kg/wk (0.35 mg group). Spontaneous breast development was observed in 77 (36.3%) of the 212 patients, and spontaneous menarche occurred in 31 patients (14.6%). The frequency of spontaneous breast development was significantly lower in patients with the 45,X karyotype and significantly higher in patients with a structural abnormality of the second X chromosome. The frequency of spontaneous menarche was significantly higher in patients with mosaicism characterized by X monosomy and a cellular line with no structural abnormality of the X chromosome. No significant differences in frequencies of spontaneous breast development and spontaneous menarche were observed between the two dose groups, indicating that GH treatment does not increase the frequency of spontaneous puberty. PMID:26568657

  11. Frequencies of spontaneous breast development and spontaneous menarche in Turner syndrome in Japan

    PubMed Central

    Tanaka, Toshiaki; Igarashi, Yutaka; Ozono, Keiichi; Ohyama, Kenji; Ogawa, Masamichi; Osada, Hisao; Onigata, Kazumichi; Kanzaki, Susumu; Kohno, Hitoshi; Seino, Yoshiki; Takahashi, Hiroaki; Tajima, Toshihiro; Tachibana, Katsuhiko; Tanaka, Hiroyuki; Nishi, Yoshikazu; Hasegawa, Tomonobu; Fujita, Keinosuke; Yorifuji, Tohru; Horikawa, Reiko; Yokoya, Susumu

    2015-01-01

    Abstract. The Growject® database on human GH treatment in Turner syndrome was analyzed in the Turner Syndrome Research Collaboration, and the relationships of the frequencies of spontaneous breast development and spontaneous menarche with karyotype and GH treatment were investigated. One hundred and three cases started GH treatment with 0.5 IU/kg/ week (0.5 IU group), and their dose was increased to 0.35 mg/kg/wk midway through the treatment course. Another 109 cases started GH at a dose of 0.35 mg/kg/wk (0.35 mg group). Spontaneous breast development was observed in 77 (36.3%) of the 212 patients, and spontaneous menarche occurred in 31 patients (14.6%). The frequency of spontaneous breast development was significantly lower in patients with the 45,X karyotype and significantly higher in patients with a structural abnormality of the second X chromosome. The frequency of spontaneous menarche was significantly higher in patients with mosaicism characterized by X monosomy and a cellular line with no structural abnormality of the X chromosome. No significant differences in frequencies of spontaneous breast development and spontaneous menarche were observed between the two dose groups, indicating that GH treatment does not increase the frequency of spontaneous puberty. PMID:26568657

  12. Functional abnormalities of heparan sulfate in mucopolysaccharidosis-I are associated with defective biologic activity of FGF-2 on human multipotent progenitor cells.

    PubMed

    Pan, Chendong; Nelson, Matthew S; Reyes, Morayma; Koodie, Lisa; Brazil, Joseph J; Stephenson, Elliot J; Zhao, Robert C; Peters, Charles; Selleck, Scott B; Stringer, Sally E; Gupta, Pankaj

    2005-09-15

    In mucopolysaccharidosis-I (MPS-I), alpha-L-iduronidase deficiency leads to progressive heparan sulfate (HS) and dermatan sulfate (DS) glycosaminoglycan (GAG) accumulation. The functional consequences of these accumulated molecules are unknown. HS critically influences tissue morphogenesis by binding to and modulating the activity of several cytokines (eg, fibroblast growth factors [FGFs]) involved in developmental patterning. We recently isolated a multipotent progenitor cell from postnatal human bone marrow, which differentiates into cells of all 3 embryonic lineages. The availability of multipotent progenitor cells from healthy volunteers and patients with MPS-I (Hurler syndrome) provides a unique opportunity to directly examine the functional effects of abnormal HS on cytokine-mediated stem-cell proliferation and survival. We demonstrate here that abnormally sulfated HS in Hurler multipotent progenitor cells perturb critical FGF-2-FGFR1-HS interactions, resulting in defective FGF-2-induced proliferation and survival of Hurler multipotent progenitor cells. Both the mitogenic and survival-promoting activities of FGF-2 were restored by substitution of Hurler HS by normal HS. This perturbation of critical HS-cytokine receptor interactions may represent a mechanism by which accumulated HS contributes to the developmental pathophysiology of Hurler syndrome. Similar mechanisms may operate in the pathogenesis of other diseases where structurally abnormal GAGs accumulate. PMID:15947088

  13. Spontaneous Tumor Lysis Syndrome

    PubMed Central

    Kimple, Michelle E.

    2015-01-01

    Tumor lysis syndrome (TLS) is a known complication of malignancy and its treatment. The incidence varies on malignancy type, but is most common with hematologic neoplasms during cytotoxic treatment. Spontaneous TLS is thought to be rare. This case study is of a 62-year-old female admitted with multisystem organ failure, with subsequent diagnosis of aggressive B cell lymphoma. On admission, laboratory abnormalities included renal failure, elevated uric acid (20.7 mg/dL), and 3+ amorphous urates on urinalysis. Oliguric renal failure persisted despite aggressive hydration and diuretic use, requiring initiation of hemodialysis prior to chemotherapy. Antihyperuricemic therapy and hemodialysis were used to resolve hyperuricemia. However, due to multisystem organ dysfunction syndrome with extremely poor prognosis, the patient ultimately expired in the setting of a terminal ventilator wean. Although our patient did not meet current TLS criteria, she required hemodialysis due to uric acid nephropathy, a complication of TLS. This poses the clinical question of whether adequate diagnostic criteria exist for spontaneous TLS and if the lack of currently accepted guidelines has resulted in the underestimation of its incidence. Allopurinol and rasburicase are commonly used for prevention and treatment of TLS. Although both drugs decrease uric acid levels, allopurinol mechanistically prevents formation of the substrate rasburicase acts to solubilize. These drugs were administered together in our patient, although no established guidelines recommend combined use. This raises the clinical question of whether combined therapy is truly beneficial or, conversely, detrimental to patient outcomes. PMID:26904699

  14. DIFFERENTIAL EFFECTS OF CARBARYL IN BRAIN ACONITASE ACTIVITY IN SPONTANEOUSLY HYPERTENSIVE (SHR) AND WISTAR-KYOTO (WKY) RATS.

    EPA Science Inventory

    Animal models of susceptibility are crucial for quantitative human health risk assessment. Spontaneously hypertensive rats (SHR) have long been used in studies on the etiology and mechanisms of hypertension and are known to be prone to oxidative stress. Previous studies indica...

  15. Abnormal activity of the MAPK- and cAMP-associated signaling pathways in frontal cortical areas in postmortem brain in schizophrenia.

    PubMed

    Funk, Adam J; McCullumsmith, Robert E; Haroutunian, Vahram; Meador-Woodruff, James H

    2012-03-01

    Recent evidence suggests that schizophrenia may result from alterations of integration of signaling mediated by multiple neurotransmitter systems. Abnormalities of associated intracellular signaling pathways may contribute to the pathophysiology of schizophrenia. Proteins and phospho-proteins comprising mitogen activated protein kinase (MAPK) and 3'-5'-cyclic adenosine monophosphate (cAMP)-associated signaling pathways may be abnormally expressed in the anterior cingulate (ACC) and dorsolateral prefrontal cortex (DLPFC) in schizophrenia. Using western blot analysis we examined proteins of the MAPK- and cAMP-associated pathways in these two brain regions. Postmortem samples were used from a well-characterized collection of elderly patients with schizophrenia (ACC=36, DLPFC=35) and a comparison (ACC=33, DLPFC=31) group. Near-infrared intensity of IR-dye labeled secondary antisera bound to targeted proteins of the MAPK- and cAMP-associated signaling pathways was measured using LiCor Odyssey imaging system. We found decreased expression of Rap2, JNK1, JNK2, PSD-95, and decreased phosphorylation of JNK1/2 at T183/Y185 and PSD-95 at S295 in the ACC in schizophrenia. In the DLPFC, we found increased expression of Rack1, Fyn, Cdk5, and increased phosphorylation of PSD-95 at S295 and NR2B at Y1336. MAPK- and cAMP-associated molecules constitute ubiquitous intracellular signaling pathways that integrate extracellular stimuli, modify receptor expression and function, and regulate cell survival and neuroplasticity. These data suggest abnormal activity of the MAPK- and cAMP-associated pathways in frontal cortical areas in schizophrenia. These alterations may underlie the hypothesized hypoglutamatergic function in this illness. Together with previous findings, these data suggest that abnormalities of intracellular signaling pathways may contribute to the pathophysiology of schizophrenia. PMID:22048463

  16. Self-Organization in Active Cytoskeletal Mixtures: Cilia-like Beating of Microtubule Bundles and Spontaneous Bulk Mixing

    NASA Astrophysics Data System (ADS)

    Sanchez, Tim

    This thesis discusses circularization and supercoiling of actin biofilaments, as well as the various examples of self-organization observed in a simple non-equilibrium system of microtubules, motor clusters, and a depletion agent (PEG). When the ends of an actin filament approach each other, annealing can occur, resulting in the assumption of a circular conformation. In order to facilitate this experimentally, we dramatically reduce the space available for the ends to explore by confining the filaments to a quasi-2D region. This is accomplished through the use of a depletion attraction. In addition to the pronounced effects of this topological ring constraint on the statistical fluctuations of the filaments, we also observe a spontaneous supercoiling transition in fluorescently labeled actin rings that is directly driven by illumination. To better understand this transition in natural twist, we investigate real-time twist of a filament trapped between two beads, held by optical traps. The main focus of this graduate work was on the behavior of non-equilibrium in vitro mixtures of microtubules, kinesin motor clusters, and a depletion agent. We observed several striking and distinct examples of self-organization on near-macroscopic length scales, due to the interactions of very simple components. First we investigate the driving mechanism behind the beating of biological cilia and flagella, and find that this beating functionality can be reproduced in our vastly simpler system. This occurs only when minimalist components are reconstituted: motors, biofilaments, elastic links to hold the filaments together, and a basal attachment. Beyond the cooperativity of the motors to produce oscillatory beating in individual bundles, we also observe that active bundles in close proximity can synchronize their beating to produce stable, periodic metachronal waves that propagate along the bundle array. By changing only the length distribution of the microtubules in our system, we

  17. ACTIVE LABOR’ DURATION AND DILATION RATES AMONG LOW-RISK, NULLIPAROUS WOMEN WITH SPONTANEOUS LABOR ONSET: A SYSTEMATIC REVIEW

    PubMed Central

    Neal, Jeremy L.; Lowe, Nancy K.; Ahijevych, Karen L.; Patrick, Thelma E.; Cabbage, Lori A.; Corwin, Elizabeth J.

    2009-01-01

    Objective Laboring women are often admitted to labor units under criteria commonly associated with the onset of active phase labor, i.e., cervical dilatation of 3–5 cm in the presence of regular contractions. Beginning with these criteria through complete dilatation, this systematic review describes labor duration and cervical dilation rates among low-risk, nulliparous women with spontaneous labor onset. Methods Studies published in English (1990–2008) were identified via MEDLINE and CINAHL searches. Data were abstracted and weighted ‘active labor’ durations (i.e., from 3–5 cm through complete dilatation) and linear dilation rates were calculated. Results Eighteen studies (n = 7009) reported mean ‘active labor’ duration. The weighted mean duration was 6.0 hrs and the calculated dilation rate was 1.2 cm/hr. These findings closely parallel those found at the median. At the statistical limits, the weighted ‘active labor’ duration was 13.4 hrs (mean + 2 SD) and the dilation rate was 0.6 cm/hr (mean − 2 SD). Conclusions Nulliparous women with spontaneous labor onset have longer ‘active’ labors and, hence, slower dilation rates than are traditionally associated with active labor when commonly used criteria are applied as the starting point. Revision of existing active labor expectations and/or criteria used to prospectively identify active phase onset is warranted. PMID:20630357

  18. Spontaneous alternation and locomotor activity in three species of marine crabs: green crab (Carcinus maenas), blue crab (Callinectes sapidus), and fiddler crab (Uca pugnax).

    PubMed

    Balcı, Fuat; Ramey-Balcı, Patricia A; Ruamps, Perrine

    2014-02-01

    Spontaneous alternation refers to the tendency of organisms to explore places that they have least recently visited. Our previous work showed that alternation performance of Carcinus maenas (invasive European green crab) was significantly higher than Callinectes sapidus (native blue crab), and chance level performance (Ramey, P. A., Teichman, E., Oleksiak, J., & Balcı, F. [2009]. Spontaneous alternation in marine crabs: Invasive versus native species. Behavioural Processes, 82, 51-55.). In the current study, we first tested the robustness of these findings in the absence of visual cues, longer test durations, and wider maze dimensions. These manipulations enabled us to determine whether these two crab species relied on the visual cues provided during the spontaneous alternation task in our prior work, and allowed for better characterization of their exploratory activity in the maze. Our original findings were reproduced in the present study under these new task conditions, suggesting no role for visual cues during alternation, and emphasizing the robustness and generalizability of the corresponding interspecies differences in alternation performance. We also tested whether the lower alternation performance of C. sapidus also applied to another native crab species, Uca pugnax (fiddler crab). Spontaneous alternation performance of U. pugnax was significantly lower than C. maenas but indistinguishable from C. sapidus. Finally, we examined whether the potentially higher inherent risk-sensitivity of C. sapidus could have contributed to their lower alternation performance by testing C. maenas in the presence of a larger natural predator (stressor). Higher risk sensitivity presumably induced by the stressor led to locomotor activity patterns that better resembled those of C. sapidus, however the resultant reduction in alternation performance was not statistically significant. PMID:24060243

  19. Aspirin-induced AMP-activated protein kinase activation regulates the proliferation of vascular smooth muscle cells from spontaneously hypertensive rats

    SciTech Connect

    Sung, Jin Young; Choi, Hyoung Chul

    2011-05-06

    Highlights: {yields} Aspirin-induced AMPK phosphorylation was greater in VSMC from SHR than WKY. {yields} Aspirin-induced AMPK phosphorylation inhibited proliferation of VSMC from SHR. {yields} Low basal AMPK phosphorylation in SHR elicits increased VSMC proliferation. {yields} Inhibition of AMPK restored decreased VSMC proliferation by aspirin in SHR. {yields} Aspirin exerts anti-proliferative effect through AMPK activation in VSMC from SHR. -- Abstract: Acetylsalicylic acid (aspirin), used to reduce risk of cardiovascular disease, plays an important role in the regulation of cellular proliferation. However, mechanisms responsible for aspirin-induced growth inhibition are not fully understood. Here, we investigated whether aspirin may exert therapeutic effects via AMP-activated protein kinase (AMPK) activation in vascular smooth muscle cells (VSMC) from wistar kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Aspirin increased AMPK and acetyl-CoA carboxylase phosphorylation in a time- and dose-dependent manner in VSMCs from WKY and SHR, but with greater efficacy in SHR. In SHR, a low basal phosphorylation status of AMPK resulted in increased VSMC proliferation and aspirin-induced AMPK phosphorylation inhibited proliferation of VSMCs. Compound C, an AMPK inhibitor, and AMPK siRNA reduced the aspirin-mediated inhibition of VSMC proliferation, this effect was more pronounced in SHR than in WKY. In VSMCs from SHR, aspirin increased p53 and p21 expression and inhibited the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. These results indicate that in SHR VSMCs aspirin exerts anti-proliferative effects through the induction of AMPK phosphorylation.

  20. Secretory activity of the brain and peripheral organs: Spontaneous and stimulated release of noradrenaline in the ontogenesis of rats.

    PubMed

    Bondarenko, N S; Murtazina, A R; Dil'mukhametova, L K; Ikonopistseva, M A; Volina, E V; Ugrumov, M V

    2016-03-01

    Spontaneous and K(+)-stimulated release of noradrenaline from the hypothalamus, adrenal gland, and organ of Zuckerkandl under their flowing incubation was investigated in the perinatal period of ontogenesis of rats. The results suggest that, during the investigated period of ontogenesis, adrenal glands are the main source of noradrenaline in the blood, whereas the contributions of the organ of Zuckerkandl and the brain are not as significant and change during this period. PMID:27193722

  1. Oncoprotein HBXIP Modulates Abnormal Lipid Metabolism and Growth of Breast Cancer Cells by Activating the LXRs/SREBP-1c/FAS Signaling Cascade.

    PubMed

    Zhao, Yu; Li, Hang; Zhang, Yingyi; Li, Leilei; Fang, Runping; Li, Yinghui; Liu, Qian; Zhang, Weiying; Qiu, Liyan; Liu, Fabao; Zhang, Xiaodong; Ye, Lihong

    2016-08-15

    Abnormal lipid metabolism is a hallmark of tumorigenesis. Accumulating evidence demonstrates that fatty acid synthase (FAS, FASN) is a metabolic oncogene that supports the growth and survival of tumor cells and is highly expressed in many cancers. Here, we report that the oncoprotein, hepatitis B X-interacting protein (HBXIP, LAMTOR5) contributes to abnormal lipid metabolism. We show that high expression of HBXIP in 236 breast cancer patients was significantly associated with decreased overall survival and progression-free survival. Interestingly, the expression of HBXIP was positively related to that of FAS in clinical breast cancer tissues, and HBXIP overexpression in breast cancer cells resulted in FAS upregulation. Mechanistically, HBXIP upregulated SREBP-1c (SREBF1), which activates the transcription of FAS, by directly interacting with and coactivating nuclear receptor (NR) liver X receptors (LXR). Physiologically, LXRs are activated via a coactivator containing NR motif in a ligand-dependent manner. However, in breast cancer cells, HBXIP containing the corepressor/nuclear receptor motif with special flanking sequence could coactivate LXRs independent of ligand. Moreover, overexpressed SREBP-1c was able to activate the transcription of HBXIP, forming a positive-feedback loop. Functionally, HBXIP enhanced lipogenesis, resulting in the growth of breast cancer cells in vitro and in vivo Thus, we conclude that the oncoprotein HBXIP contributes to the abnormal lipid metabolism in breast cancer through LXRs/SREBP-1c/FAS signaling, providing new insights into the mechanisms by which cancer cells reprogram lipid metabolism in their favor. Cancer Res; 76(16); 4696-707. ©2016 AACR. PMID:26980761

  2. Electrical Responses and Spontaneous Activity of Human iPS-Derived Neuronal Networks Characterized for 3-month Culture with 4096-Electrode Arrays

    PubMed Central

    Amin, Hayder; Maccione, Alessandro; Marinaro, Federica; Zordan, Stefano; Nieus, Thierry; Berdondini, Luca

    2016-01-01

    The recent availability of human induced pluripotent stem cells (hiPSCs) holds great promise as a novel source of human-derived neurons for cell and tissue therapies as well as for in vitro drug screenings that might replace the use of animal models. However, there is still a considerable lack of knowledge on the functional properties of hiPSC-derived neuronal networks, thus limiting their application. Here, upon optimization of cell culture protocols, we demonstrate that both spontaneous and evoked electrical spiking activities of these networks can be characterized on-chip by taking advantage of the resolution provided by CMOS multielectrode arrays (CMOS-MEAs). These devices feature a large and closely-spaced array of 4096 simultaneously recording electrodes and multi-site on-chip electrical stimulation. Our results show that networks of human-derived neurons can respond to electrical stimulation with a physiological repertoire of spike waveforms after 3 months of cell culture, a period of time during which the network undergoes the expression of developing patterns of spontaneous spiking activity. To achieve this, we have investigated the impact on the network formation and on the emerging network-wide functional properties induced by different biochemical substrates, i.e., poly-dl-ornithine (PDLO), poly-l-ornithine (PLO), and polyethylenimine (PEI), that were used as adhesion promoters for the cell culture. Interestingly, we found that neuronal networks grown on PDLO coated substrates show significantly higher spontaneous firing activity, reliable responses to low-frequency electrical stimuli, and an appropriate level of PSD-95 that may denote a physiological neuronal maturation profile and synapse stabilization. However, our results also suggest that even 3-month culture might not be sufficient for human-derived neuronal network maturation. Taken together, our results highlight the tight relationship existing between substrate coatings and emerging network

  3. Beneficial effects of sodium butyrate in 6-OHDA induced neurotoxicity and behavioral abnormalities: Modulation of histone deacetylase activity.

    PubMed

    Sharma, Sorabh; Taliyan, Rajeev; Singh, Sumel

    2015-09-15

    Parkinson's disease (PD) is the second most common neurodegenerative disorder. Recent studies have investigated the involvement of epigenetic modifications in PD. Histone deacetylase (HDAC) inhibitors have been reported to be beneficial in cognitive and motor deficit states. The present study was designed to investigate the effect of sodium butyrate, a HDAC inhibitor in 6-hydroxydopamine (6-OHDA) - induced experimental PD like symptoms in rats. To produce motor deficit, 6-OHDA was administered unilaterally in the right medial forebrain bundle. Three weeks after 6-OHDA administration, the rats were challenged with apomorphine. Following this, the animals were treated with sodium butyrate (150 and 300 mg/kg i.p.) once daily for 14 days. Movement abnormalities were assessed by battery of behavioral tests. Biochemically, oxidative stress markers, neuroinflammation and dopamine were measured in striatal brain homogenate. Further, to explore the molecular mechanism(s), we measured the level of global H3 histone acetylation and brain derived neurotrophic factor (BDNF). 6-OHDA administration results in significant motor deficit along with reduction in striatal dopamine level. 6-OHDA treated rats showed elevated oxidative stress and neuroinflammatory markers. Treatment with sodium butyrate results in significant attenuation of motor deficits and increased striatal dopamine level. Moreover, sodium butyrate treatment attenuated the oxidative stress and neuroinflammatory markers. These effects occur concurrently with increased global H3 histone acetylation and BDNF levels. Thus, the observed results of the present study are indicative for the therapeutic potential of HDAC inhibitors in PD. PMID:26048426

  4. Comparative study of the antihypertensive activity of Marrubium vulgare and of the dihydropyridine calcium antagonist amlodipine in spontaneously hypertensive rat.

    PubMed

    El Bardai, Sanae; Lyoussi, Badiaa; Wibo, Maurice; Morel, Nicole

    2004-08-01

    Water extract of Marrubium vulgare is widely used as antihypertensive treatment in folk medicine. We have compared the effect of 10-week-long treatment with amlodipine or Marrubium water extract on systolic blood pressure (SBP), cardiovascular remodeling and vascular relaxation in spontaneously hypertensive rats (SHR). Both treatments produced similar decrease in SBP. Amlodipine treatment reduced left ventricle, aortic and mesenteric artery weight. Marrubium treatment had a significant antihypertrophic effect in aorta only. Relaxation to acetylcholine (ACh) of mesenteric artery was improved by Marrubium but not by amlodipine treatment. These results demonstrate that, in addition to its antihypertensive effect, Marrubium water extract improved the impaired endothelial function in SHR. PMID:15554450

  5. Quetiapine Inhibits Microglial Activation by Neutralizing Abnormal STIM1-Mediated Intercellular Calcium Homeostasis and Promotes Myelin Repair in a Cuprizone-Induced Mouse Model of Demyelination

    PubMed Central

    Wang, Hanzhi; Liu, Shubao; Tian, Yanping; Wu, Xiyan; He, Yangtao; Li, Chengren; Namaka, Michael; Kong, Jiming; Li, Hongli; Xiao, Lan

    2015-01-01

    Microglial activation has been considered as a crucial process in the pathogenesis of neuroinflammation and psychiatric disorders. Several antipsychotic drugs (APDs) have been shown to display inhibitory effects on microglial activation in vitro, possibly through the suppression of elevated intracellular calcium (Ca2+) concentration. However, the exact underlying mechanisms still remain elusive. In this study, we aimed to investigate the inhibitory effects of quetiapine (Que), an atypical APD, on microglial activation. We utilized a chronic cuprizone (CPZ)-induced demyelination mouse model to determine the direct effect of Que on microglial activation. Our results showed that treatment with Que significantly reduced recruitment and activation of microglia/macrophage in the lesion of corpus callosum and promoted remyelination after CPZ withdrawal. Our in vitro studies also confirmed the direct effect of Que on lipopolysaccharide (LPS)-induced activation of microglial N9 cells, whereby Que significantly inhibited the release of nitric oxide (NO) and tumor necrosis factor α (TNF-α). Moreover, we demonstrated that pretreatment with Que, neutralized the up-regulation of STIM1 induced by LPS and declined both LPS and thapsigargin (Tg)-induced store-operated Ca2+ entry (SOCE). Finally, we found that pretreatment with Que significantly reduced the translocation of nuclear factor kappa B (NF-κB) p65 subunit from cytoplasm to nuclei in LPS-activated primary microglial cells. Overall, our data suggested that Que may inhibit microglial activation by neutralization of the LPS-induced abnormal STIM1-mediated intercellular calcium homeostasis. PMID:26732345

  6. Food restriction and spontaneous motor activity in male mice: effects of feeding pattern, far-infrared ray and bamboo grass leaf extract.

    PubMed

    Nagasawa, H; Murayama, Y; Ishigame, H

    2001-01-01

    The effects on spontaneous motor activity of the pattern of restricted feeding, far-infrared ray (FIR) irradiation or free access in drinking water containing Sasa Health, a bamboo grass leafextract, were examined in SHN male mice at 2-3 months of age. In mice whose diet was restricted to 60% of the control, fed at 9:00 or 17:00 hours, the level of spontaneous behaviour was elevated 1 hour before the respective feeding time (8:00 or 16:00 hours). The activity was stimulated by FIR in both the control and food-restricted mice, but to a much higher degree in the latter. Treatment with Sasa Health in drinking water lowered the elevated activity level in food-restricted mice. Plasma component levels and organ weights were modulated by FIR or Sasa Health. The findings revealed that, not only the restricted feeding itsel, but also its pattern, significantly affected behaviour and that FIR and Sasa Health modified the deleterious effects of restricted feeding. PMID:11695223

  7. Axolemmal abnormalities in myelin mutants.

    PubMed

    Rosenbluth, J

    1990-01-01

    Evidence is reviewed that the paranodal axoglial junction plays important roles in the differentiation and function of myelinated axons. In myelin-deficient axons, ion flux across the axolemma is greater than that in myelinated fibers because a larger proportion of the axolemma is active during continuous, as opposed to saltatory, conduction. In addition, older myelin-deficient rats that have developed spontaneous seizures display small foci of node-like E-face particle accumulations in CNS axons as well as more diffuse regions of increased particle density and number. Assuming that the E-face particles represent sodium channels, such regions could underlie high sodium current density during activity, low threshold for excitation, and increased extracellular potassium accumulation. Depending on the degree of spontaneous channel opening, they could also represent sites of spontaneous generation of activity. The appearance of seizures and their gradual increase in frequency and severity could represent an increase in the number of such regions. In addition, diminution in the dimensions of the extracellular space during maturation would result in increased extracellular resistance, which, together with increasing axonal diameter, would tend to increase the likelihood of ephaptic interaction among neighboring axons as well as the likelihood of extracellular potassium rises to levels that could cause spontaneous activity. PMID:2268117

  8. Abnormalities in the cellular phase of blood fibrinolytic activity in systemic lupus erythematosus and in venous thromboembolism

    SciTech Connect

    Moroz, L.A.; MacLean, L.D.; Langleben, D.

    1986-09-15

    Fibrinolytic activities of whole blood and plasma were determined by /sup 125/I-fibrin radiometric assay in 16 normal subjects, and in 11 patients with systemic lupus erythematosus (SLE), 14 with progressive systemic sclerosis (PSS), 23 with venous thromboembolic disease, and 20 patients awaiting elective surgery. Mean whole blood and plasma activities for patients with PSS, and for those awaiting elective surgery, were similar to normal values, as was the mean plasma activity in patients with SLE. However, mean whole blood activity in SLE was significantly decreased compared with normals (p less than 0.05), with mean plasma activity accounting for 44% of mean whole blood activity (compared with 17% in normal subjects), representing a 67% decrease in mean calculated cellular phase activity in SLE, when compared with normals. Since the numbers of cells (neutrophils, monocytes) possibly involved in cellular activity were not decreased, the findings suggest a functional defect in fibrinolytic activity of one or more blood cell types in SLE. An additional finding was the participation of the cellular phase as well as the well-known plasma phase of blood in the fibrinolytic response to thromboembolism.

  9. Gene Expression Analyses during Spontaneous Reversal of Cardiomyopathy in Mice with Repressed Nuclear CUG-BP, Elav-Like Family (CELF) Activity in Heart Muscle

    PubMed Central

    Dasgupta, Twishasri; Coram, Ryan J.; Stillwagon, Samantha J.; Ladd, Andrea N.

    2015-01-01

    CUG-BP, Elav-like family (CELF) proteins regulate cell type- and developmental stage-specific alternative splicing in the heart. Repression of CELF-mediated splicing activity via expression of a nuclear dominant negative CELF protein in heart muscle was previously shown to induce dysregulation of alternative splicing, cardiac dysfunction, cardiac hypertrophy, and dilated cardiomyopathy in MHC-CELFΔ transgenic mice. A “mild” line of MHC-CELFΔ mice that expresses a lower level of the dominant negative protein exhibits cardiac dysfunction and myopathy at a young age, but spontaneously recovers normal cardiac function and heart size with age despite the persistence of splicing defects. To the best of our knowledge, this was the first example of a genetically induced cardiomyopathy that spontaneously recovers without intervention. In this study, we explored the basis for this recovery. We examined whether a transcriptional program regulated by serum response factor (SRF) that is dysregulated in juvenile MHC-CELFΔ mice is restored in the mild line with age, and evaluated global changes in gene expression by microarray analyses. We found that differences in gene expression between the mild line and wild type hearts are greatly reduced in older animals, including a partial recovery of SRF target gene expression. We did not find evidence of a new compensatory pathway being activated in the mild line with age, and propose that recovery may occur due to developmental stage-specific compatibility of CELF-dependent splice variants with the cellular environment of the cardiomyocyte. PMID:25894229

  10. Is the self a higher-order or fundamental function of the brain? The "basis model of self-specificity" and its encoding by the brain's spontaneous activity.

    PubMed

    Northoff, Georg

    2016-01-01

    What is the self? This is a question that has long been discussed in (Western) philosophy where the self is traditionally conceived a higher-order function at the apex or pinnacle of all functions. This tradition has been transferred to recent neuroscience where the self is often considered to be a higher-order cognitive function reflected in memory and other high-level judgements. However, other lines of research demonstrate a close and intimate relationship between self-specificity and more basic functions like perceptions, emotions and reward. This paper focuses on the relationship between self-specificity and other basic functions relating to emotions, reward and perception. I propose the basis model that conceives self-specificity as a fundamental feature of the brain's spontaneous activity. This is supported by recent findings showing rest-self overlap in midline regions as well as findings demonstrating that the resting state can predict subsequent degrees of self-specificity. I conclude that such self-specificity in the brain's spontaneous activity may be central in linking the self to either internal or external stimuli. This may also provide the basis for coding the self as subject in relation to internal (i.e., self-consciousness) or external (i.e., phenomenal consciousness) mental events. PMID:26505808

  11. The effects of bepridil, compared with calcium-channel inhibitors and calmodulin antagonists on both spontaneous activity and contractions induced by potassium or phenylephrine in rat portal vein.

    PubMed

    Campbell, J K; Winslow, E; Marshall, R J

    1986-12-16

    Bepridil is known to block calcium channels in some vascular tissues. Recent work has shown that bepridil also antagonises calmodulin. The present study attempted to more fully characterize the vasodilator actions of bepridil by comparing it with the known calcium channel blocking drugs, nifedipine, diltiazem, verapamil and flunarizine, the calmodulin inhibitors, trifluoperazine and W7 and propylmethylenedioxyindene, which is thought to act intracellularly, on rat portal vein. The relative activities of the test drugs were compared on spontaneous activity and on all components of the contractile responses to potassium and phenylephrine. Bepridil inhibited all components of the potassium and phenylephrine responses equally, actions similar to those of the intracellular acting drugs. The exception to this was trifluoperazine which also exerted alpha-adrenoceptor blocking actions. In contrast the calcium channel blocking drugs, with the exception of verapamil, inhibited the tonic component of both spasmogen responses more than the phasic component. Bepridil like the intracellular acting drugs, but unlike the calcium channel blockers, markedly increased the frequency of spontaneous contractions whilst reducing amplitude. It is concluded that the profile of bepridil on rat portal vein more closely resembles that of intracellularly acting drugs than that of classical calcium channel inhibitors. PMID:3493163

  12. Abnormal parathyroid hormone stimulation of 25-hydroxyvitamin D-1 alpha-hydroxylase activity in the hypophosphatemic mouse. Evidence for a generalized defect of vitamin D metabolism.

    PubMed Central

    Nesbitt, T; Drezner, M K; Lobaugh, B

    1986-01-01

    Abnormal regulation of vitamin D metabolism is a feature of X-linked hypophosphatemic rickets in man and of the murine homologue of the disease in the hypophosphatemic (Hyp)-mouse. We previously reported that mutant mice have abnormally low renal 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-hydroxylase) activity for the prevailing degree of hypophosphatemia. To further characterize this defect, we examined whether Hyp-mouse renal 1 alpha-hydroxylase