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Sample records for abnormal spontaneous activity

  1. 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

  2. Spontaneous Activity in Crustacean Neurons

    PubMed Central

    Preston, James B.; Kennedy, Donald

    1962-01-01

    Single units which discharged with regular spontaneous rhythms without intentional stimulation were observed in the ventral nerve cord by intracellular recording close to the sixth abdominal ganglion. These units were divided into two groups: group A units in which interspike intervals varied less than 10 msec.; group B units in which interspike intervals varied within a range of 10 to 30 msec. Group A units maintained "constant" interspike intervals and could not be discharged by sensory inputs, while the majority of group B units could be discharged by appropriate sensory nerve stimulation. Both group A and B units discharged to direct stimulation when the stimulating and recording electrodes were placed in the same ganglionic intersegment, and directly evoked single spikes reset the spontaneous rhythm. In group B units, presynaptic volleys reset the spontaneous rhythm of some units; but in others, synaptically evoked spikes were interpolated within the spontaneous rhythm without resetting. The phenomenon of enhancement could also be demonstrated in spontaneously active units as a result of repetitive stimulation. It is concluded that endogenous pacemaker activity is responsible for much of the regular spontaneous firing observed in crayfish central neurons, and that interaction of evoked responses with such pacemaker sites can produce a variety of effects dependent upon the anatomical relationships between pacemaker and synaptic regions. PMID:14488667

  3. Quantitative analysis of abnormal spontaneous behavior and clinical assessment of the stargazer rat.

    PubMed

    Brock, J W; Truett, G E; Ross, K D; Kloster, C A

    1995-06-01

    A new mutant derived from the Zucker rat strain called stargazer (homozygous stg/stg) displays abnormal behavior that is characterized by pronounced arching of the neck ("stargazing"), rapid circling, and conspicuous hyperactivity. Results of serologic assays performed by two independent diagnostic laboratories have indicated that the abnormal behavior in the stargazer is not the result of a viral or bacterial infection. In this report, different groups of stargazer rats and their normal-behaving littermates (heterozygous stg/+) were assessed with regard to spontaneous behaviors, heart rate, blood pressure, and plasma biochemical profiles. Besides frequent stargazing, the predominant behavioral feature of the stargazers was extreme hyperactivity; they had sevenfold greater activity than the normal littermates (P < 0.05), expressed in the form of rapid ambulation and tail-chasing. The stargazers had significantly greater daily calorie and water consumption, despite being significantly smaller in body weight than the littermates (P < 0.05 for all). However, urine output was not different between the two groups. Heart rate and blood pressure also were not different. Stargazers had significantly lower total triglycerides concentration and lower aminotransferase activity than littermates (P < 0.05 for both), a finding probably related to their smaller body size. It is concluded that stargazer rats are extremely hyperactive but normotensive; heterozygous littermates are behaviorally normal, despite being carriers of the stg gene; and routine diagnostic blood testing revealed no important differences between the stargazers and their unaffected littermates. PMID:7650898

  4. Connective tissue spectrum abnormalities associated with spontaneous cerebrospinal fluid leaks: a prospective study.

    PubMed

    Reinstein, Eyal; Pariani, Mitchel; Bannykh, Serguei; Rimoin, David L; Schievink, Wouter I

    2013-04-01

    We aimed to assess the frequency of connective tissue abnormalities among patients with cerebrospinal fluid (CSF) leaks in a prospective study using a large cohort of patients. We enrolled a consecutive group of 50 patients, referred for consultation because of CSF leak. All patients have been carefully examined for the presence of connective tissue abnormalities, and based on findings, patients underwent genetic testing. Ancillary diagnostic studies included echocardiography, eye exam, and histopathological examinations of skin and dura biopsies in selected patients. We identified nine patients with heritable connective tissue disorders, including Marfan syndrome, Ehlers-Danlos syndrome and other unclassified forms. In seven patients, spontaneous CSF leak was the first noted manifestation of the genetic disorder. We conclude that spontaneous CSF leaks are associated with a spectrum of connective tissue abnormalities and may be the first noted clinical presentation of the genetic disorder. We propose that there is a clinical basis for considering spontaneous CSF leak as a clinical manifestation of heritable connective tissue disorders, and we suggest that patients with CSF leaks should be screened for connective tissue and vascular abnormalities.

  5. 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

  6. 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

  7. Neuronal avalanches in spontaneous activity in vivo.

    PubMed

    Hahn, Gerald; Petermann, Thomas; Havenith, Martha N; Yu, Shan; Singer, Wolf; Plenz, Dietmar; Nikolic, Danko

    2010-12-01

    Many complex systems give rise to events that are clustered in space and time, thereby establishing a correlation structure that is governed by power law statistics. In the cortex, such clusters of activity, called "neuronal avalanches," were recently found in local field potentials (LFPs) of spontaneous activity in acute cortex slices, slice cultures, the developing cortex of the anesthetized rat, and premotor and motor cortex of awake monkeys. At present, it is unclear whether neuronal avalanches also exist in the spontaneous LFPs and spike activity in vivo in sensory areas of the mature brain. To address this question, we recorded spontaneous LFPs and extracellular spiking activity with multiple 4 × 4 microelectrode arrays (Michigan Probes) in area 17 of adult cats under anesthesia. A cluster of events was defined as a consecutive sequence of time bins Δt (1-32 ms), each containing at least one LFP event or spike anywhere on the array. LFP cluster sizes consistently distributed according to a power law with a slope largely above -1.5. In two thirds of the corresponding experiments, spike clusters also displayed a power law that displayed a slightly steeper slope of -1.8 and was destroyed by subsampling operations. The power law in spike clusters was accompanied with stronger temporal correlations between spiking activities of neurons that spanned longer time periods compared with spike clusters lacking power law statistics. The results suggest that spontaneous activity of the visual cortex under anesthesia has the properties of neuronal avalanches.

  8. 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

  9. 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

  10. Neuronal Avalanches in Spontaneous Activity In Vivo

    PubMed Central

    Hahn, Gerald; Petermann, Thomas; Havenith, Martha N.; Yu, Shan; Singer, Wolf; Plenz, Dietmar

    2010-01-01

    Many complex systems give rise to events that are clustered in space and time, thereby establishing a correlation structure that is governed by power law statistics. In the cortex, such clusters of activity, called “neuronal avalanches,” were recently found in local field potentials (LFPs) of spontaneous activity in acute cortex slices, slice cultures, the developing cortex of the anesthetized rat, and premotor and motor cortex of awake monkeys. At present, it is unclear whether neuronal avalanches also exist in the spontaneous LFPs and spike activity in vivo in sensory areas of the mature brain. To address this question, we recorded spontaneous LFPs and extracellular spiking activity with multiple 4 × 4 microelectrode arrays (Michigan Probes) in area 17 of adult cats under anesthesia. A cluster of events was defined as a consecutive sequence of time bins Δt (1–32 ms), each containing at least one LFP event or spike anywhere on the array. LFP cluster sizes consistently distributed according to a power law with a slope largely above –1.5. In two thirds of the corresponding experiments, spike clusters also displayed a power law that displayed a slightly steeper slope of −1.8 and was destroyed by subsampling operations. The power law in spike clusters was accompanied with stronger temporal correlations between spiking activities of neurons that spanned longer time periods compared with spike clusters lacking power law statistics. The results suggest that spontaneous activity of the visual cortex under anesthesia has the properties of neuronal avalanches. PMID:20631221

  11. Meiotic abnormalities underlying pollen sterility in wild potato hybrids and spontaneous populations.

    PubMed

    Larrosa, F H; Maune, J F; Erazzú, L E; Camadro, E L

    2012-01-01

    Wild potato species are widely distributed in the Americas, where they spontaneously grow in very diverse habitats. These species - with low chromosome differentiation - form polyploid series with 2n = 2x, 3x, 4x and 6x (x =12). They are isolated in nature by external and internal hybridisation barriers that can be incomplete, allowing hybridisation in areas of sympatry. Nevertheless, most accessions in germplasm banks, regardless of genetic background of the sampled spontaneous populations, have been assigned specific categories based on morphological characters. To further investigate the extent of hybridisation in the group and for comparative purposes, pollen viability was estimated in (i) artificial hybrids between a commercial cultivar (Calén INTA) of the common potato (tetraploid Solanum tuberosum ssp. tuberosum) and the tetraploid cytotype of the related wild species S. gourlayi, and (ii) samples of plants (accessions) and inflorescences of natural populations from Argentina, tentatively classified as 'presumed hybrids' (S. infundibuliforme-S. gourlayi) and 'species' (S. infundibuliforme, S. gourlayi and S. chacoense). Regardless of origin, 98 out of 103 plants analysed had zero to 70% pollen viability (zero to 40% in eight of them). Pollen grains were of variable size and morphology and, in mostly male sterile plants, the only viable pollen grains were 2n and/or 4n. Furthermore, male sterile plants shared various abnormalities in meiosis I and II (unpaired chromosomes, unequal chromosome distribution, precocious/lagging chromosomes, parallel, tripolar, fused and multiple spindles, unequal size nuclei, dyads, triads and pentads in addition to normal tetrads, among others). These results provide novel evidence to support field observations of early potato botanists on the extent of spontaneous hybridisation in wild Argentinian potato populations, which is not reflected in the current taxonomy and has significant consequences for germplasm conservation and

  12. Spontaneous and induced apoptosis in systemic lupus erythematosus: multiple assays fail to reveal consistent abnormalities.

    PubMed

    Caricchio, R; Cohen, P L

    1999-11-25

    The immunologic basis of systemic lupus erythematosus (SLE) is multifactorial and still elusive. Recent advances in the field of apoptosis have suggested new paradigms for the development of lupus autoimmunity. In the present studies we examined the possibility that individual populations of T and B cells are abnormally resistant to apoptosis or that they stand out in over- or underexpressing Fas. Fas was generally overexpressed in cells freshly isolated from SLE patients but the apoptotic response to FasL was normal. We did not find increased spontaneous ongoing apoptosis in SLE lymphocytes. Normal cleavage of PARP similarly implied that the final biochemical pathway of apoptosis is relatively intact in SLE. Finally we placed special emphasis on the response of SLE patient cells to UV irradiation, especially cells from photosensitive patients, and found no difference in Fas expression. In conclusion our results indicate that SLE patients do not suffer from a major apoptotic abnormality. The results also raise questions concerning the dynamic expression of Fas and the significance of ongoing apoptosis as a risk for autoimmune disease. PMID:10612651

  13. 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.

  14. Sloppiness in spontaneously active neuronal networks.

    PubMed

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

    2015-06-01

    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.

  15. 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

  16. Phorbol ester and spontaneous activity in SHR aorta

    SciTech Connect

    Moisey, D.M.; Cox, R.H.

    1986-03-01

    Thoracic aortas (TA) were excised from 6-week old SHR and WKY. 2mm rings were mounted isometrically at optimum preload. Spontaneous rhythmical activity developed in TA from SHR and had a frequency of 3-4/min with varying periods of quiescence between bursts of activity. The spontaneous activity often produced an increase in tension development which was associated with increased frequency of oscillations. Verapamil (10/sup -7/ M) or Ca/sup + +/-free solution added during the contractile phase resulted in an immediate loss of tension and spontaneous activity. Addition of ouabain (10/sup -4/ M) during the contractile phase of spontaneous activity, increased the frequency of oscillations which appeared to fuse into a tetanus. Spontaneous rhythmical activity was infrequently observed in TA from WKY. However, addition of phorbol 12-myristate-13 acetate (TPA), frequently induced spontaneous rhythmic oscillations associated with tension development in TA from WKY. TPA contracted the SHR TA and increased the frequency of oscillations. SHR TA were more sensitive to TPA than WKY. This study demonstrates (1) spontaneous rhythmical activity, independent of agonist stimulation in TA from 6-week old SHR and (2) TPA induced spontaneous oscillatory activity. The mechanism underlying the spontaneous oscillatory activity may involve membrane coupling events and Na-pump difference between SHR and WKY.

  17. 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

  18. 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

  19. 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

  20. 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

  1. Active acromegaly enhances spontaneous parathyroid hormone pulsatility.

    PubMed

    Mazziotti, Gherardo; Cimino, Vincenzo; De Menis, Ernesto; Bonadonna, Stefania; Bugari, Giovanna; De Marinis, Laura; Veldhuis, Johannes D; Giustina, Andrea

    2006-06-01

    In healthy subjects, parathyroid hormone (PTH) is secreted in a dual fashion, with low-amplitude and high-frequency pulses superimposed on tonic secretion. These 2 components of PTH secretion seem to have different effects on target organs. The aim of our study was to evaluate whether growth hormone excess in acromegaly may modify the spontaneous pulsatility of PTH. Five male patients with newly diagnosed active acromegaly and 8 healthy subjects were evaluated by 3-minute blood sampling for 6 hours. Plasma PTH concentrations were evaluated by multiparameter deconvolution analysis. Plasma PTH release profiles were also subjected to an approximate entropy (ApEn) estimate, which provides an ensemble measure of the serial regularity or orderliness of the release process. In acromegalic patients, baseline serum PTH values were not significantly different from those measured in the healthy subjects, as well as tonic PTH secretion rate, number of bursts, fractional pulsatile PTH secretion, and ApEn ratio. Conversely, PTH pulse half-duration was significantly longer in acromegalic patients vs healthy subjects (11.8+/-0.95 vs 6.9+/-1.6 minutes; P=.05), whereas PTH pulse mass showed a tendency (P=.06) to be significantly greater in acromegalic patients. These preliminary data suggest that growth hormone excess may affect PTH secretory dynamics in patients with acromegaly. Potentially negative bone effects of the modifications of PTH secretory pattern in acromegaly should be investigated.

  2. Brain state-dependent abnormal LFP activity in the auditory cortex of a schizophrenia mouse model

    PubMed Central

    Nakao, Kazuhito; Nakazawa, Kazu

    2014-01-01

    In schizophrenia, evoked 40-Hz auditory steady-state responses (ASSRs) are impaired, which reflects the sensory deficits in this disorder, and baseline spontaneous oscillatory activity also appears to be abnormal. It has been debated whether the evoked ASSR impairments are due to the possible increase in baseline power. GABAergic interneuron-specific NMDA receptor (NMDAR) hypofunction mutant mice mimic some behavioral and pathophysiological aspects of schizophrenia. To determine the presence and extent of sensory deficits in these mutant mice, we recorded spontaneous local field potential (LFP) activity and its click-train evoked ASSRs from primary auditory cortex of awake, head-restrained mice. Baseline spontaneous LFP power in the pre-stimulus period before application of the first click trains was augmented at a wide range of frequencies. However, when repetitive ASSR stimuli were presented every 20 s, averaged spontaneous LFP power amplitudes during the inter-ASSR stimulus intervals in the mutant mice became indistinguishable from the levels of control mice. Nonetheless, the evoked 40-Hz ASSR power and their phase locking to click trains were robustly impaired in the mutants, although the evoked 20-Hz ASSRs were also somewhat diminished. These results suggested that NMDAR hypofunction in cortical GABAergic neurons confers two brain state-dependent LFP abnormalities in the auditory cortex; (1) a broadband increase in spontaneous LFP power in the absence of external inputs, and (2) a robust deficit in the evoked ASSR power and its phase-locking despite of normal baseline LFP power magnitude during the repetitive auditory stimuli. The “paradoxically” high spontaneous LFP activity of the primary auditory cortex in the absence of external stimuli may possibly contribute to the emergence of schizophrenia-related aberrant auditory perception. PMID:25018691

  3. Spontaneous olfactory receptor neuron activity determines follower cell response properties

    PubMed Central

    Joseph, Joby; Dunn, Felice A.; Stopfer, Mark

    2012-01-01

    Noisy or spontaneous activity is common in neural systems and poses a challenge to detecting and discriminating signals. Here we use the locust to answer fundamental questions about noise in the olfactory system: Where does spontaneous activity originate? How is this activity propagated or reduced throughout multiple stages of neural processing? What mechanisms favor the detection of signals despite the presence of spontaneous activity? We found that spontaneous activity long observed in the secondary projection neurons (PNs) originates almost entirely from the primary olfactory receptor neurons (ORNs) rather than from spontaneous circuit interactions in the antennal lobe, and that spontaneous activity in ORNs tonically depolarizes the resting membrane potentials of their target PNs and local neurons (LNs), and indirectly tonically depolarizes tertiary Kenyon cells (KCs). However, because these neurons have different response thresholds, in the absence of odor stimulation, ORNs and PNs display a high spontaneous firing rate but KCs are nearly silent. Finally, we used a simulation of the olfactory network to show that discrimination of signal and noise in the KCs is best when threshold levels are set so that baseline activity in PNs persists. Our results show how the olfactory system benefits from making a signal detection decision after a point of maximal information convergence, e.g., after KCs pool inputs from many PNs. PMID:22357872

  4. 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.

  5. Spontaneous Electrical Activity of Dionaea muscipula.

    PubMed

    Balotin, N M; Dipalma, J R

    1962-12-21

    Instillation of four to six drops of 3-percent saline in the leaf trap of Dionaea muscipula Ellis causes the appearance of a series of spontaneous action potentials. Mechanical stimulation of the sensitive leaf hair elicits only a single response. Immersion in 3-percent, but not in 1-percent, saline effects a loss of weight in Dionaea but not in the leaves of gardenia or geranium.

  6. Abnormal amygdala activation profile in pedophilia.

    PubMed

    Sartorius, Alexander; Ruf, Matthias; Kief, Christine; Demirakca, Traute; Bailer, Josef; Ende, Gabriele; Henn, Fritz A; Meyer-Lindenberg, Andreas; Dressing, Harald

    2008-08-01

    Despite considerable public interest research in neurobiological correlates of pedophilia is scarce. Since amygdala activation is central for emotional valuation, arousal, and salience, we investigated the activation profile of this structure in 10 male subjects with pedophilia (exclusively attracted to boys), all convicted sex-offenders and sentenced to forensic psychiatric treatment along with ten male heterosexual matched controls. We used a sexually non-explicit functional Magnetic Resonance Imaging (fMRI) paradigm with images of men, women, boys or girls randomly embedded in neutral target/non-target geometrical symbols. We applied statistical parametric mapping (SPM2) and SPSS 14 for image processing and analysis. While controls activated significantly less to pictures of children compared to adults, the activation profile was reversed in subjects with pedophilia, who exhibited significantly more activation to children than adults. The highest activation was observed for boys in the patient group, and for women in control participants. Our data show enhanced activation to children's pictures even in an incidental context and suggest the provocative hypothesis that a normally present mechanism for reduced emotional arousal for children relative to adults is reversed in pedophilia, suggesting a neural substrate associated with deviant sexual preference in this condition. More extensive research in this field would be of benefit for both the victims and the offenders.

  7. On the Dynamics of the Spontaneous Activity in Neuronal Networks

    PubMed Central

    Bonifazi, Paolo; Ruaro, Maria Elisabetta; Torre, Vincent

    2007-01-01

    Most neuronal networks, even in the absence of external stimuli, produce spontaneous bursts of spikes separated by periods of reduced activity. The origin and functional role of these neuronal events are still unclear. The present work shows that the spontaneous activity of two very different networks, intact leech ganglia and dissociated cultures of rat hippocampal neurons, share several features. Indeed, in both networks: i) the inter-spike intervals distribution of the spontaneous firing of single neurons is either regular or periodic or bursting, with the fraction of bursting neurons depending on the network activity; ii) bursts of spontaneous spikes have the same broad distributions of size and duration; iii) the degree of correlated activity increases with the bin width, and the power spectrum of the network firing rate has a 1/f behavior at low frequencies, indicating the existence of long-range temporal correlations; iv) the activity of excitatory synaptic pathways mediated by NMDA receptors is necessary for the onset of the long-range correlations and for the presence of large bursts; v) blockage of inhibitory synaptic pathways mediated by GABAA receptors causes instead an increase in the correlation among neurons and leads to a burst distribution composed only of very small and very large bursts. These results suggest that the spontaneous electrical activity in neuronal networks with different architectures and functions can have very similar properties and common dynamics. PMID:17502919

  8. Spatial diversity of spontaneous activity in the cortex

    PubMed Central

    Tan, Andrew Y. Y.

    2015-01-01

    The neocortex is a layered sheet across which a basic organization is thought to widely apply. The variety of spontaneous activity patterns is similar throughout the cortex, consistent with the notion of a basic cortical organization. However, the basic organization is only an outline which needs adjustments and additions to account for the structural and functional diversity across cortical layers and areas. Such diversity suggests that spontaneous activity is spatially diverse in any particular behavioral state. Accordingly, this review summarizes the laminar and areal diversity in cortical activity during fixation and slow oscillations, and the effects of attention, anesthesia and plasticity on the cortical distribution of spontaneous activity. Among questions that remain open, characterizing the spatial diversity in spontaneous membrane potential may help elucidate how differences in circuitry among cortical regions supports their varied functions. More work is also needed to understand whether cortical spontaneous activity not only reflects cortical circuitry, but also contributes to determining the outcome of plasticity, so that it is itself a factor shaping the functional diversity of the cortex. PMID:26441547

  9. How networks communicate: propagation patterns in spontaneous brain activity.

    PubMed

    Mitra, Anish; Raichle, Marcus E

    2016-10-01

    Initially regarded as 'noise', spontaneous (intrinsic) activity accounts for a large portion of the brain's metabolic cost. Moreover, it is now widely known that infra-slow (less than 0.1 Hz) spontaneous activity, measured using resting state functional magnetic resonance imaging of the blood oxygen level-dependent (BOLD) signal, is correlated within functionally defined resting state networks (RSNs). However, despite these advances, the temporal organization of spontaneous BOLD fluctuations has remained elusive. By studying temporal lags in the resting state BOLD signal, we have recently shown that spontaneous BOLD fluctuations consist of remarkably reproducible patterns of whole brain propagation. Embedded in these propagation patterns are unidirectional 'motifs' which, in turn, give rise to RSNs. Additionally, propagation patterns are markedly altered as a function of state, whether physiological or pathological. Understanding such propagation patterns will likely yield deeper insights into the role of spontaneous activity in brain function in health and disease.This article is part of the themed issue 'Interpreting blood oxygen level-dependent: a dialogue between cognitive and cellular neuroscience'. PMID:27574315

  10. Abnormal insulin metabolism by specific organs from rats with spontaneous hypertension

    SciTech Connect

    Mondon, C.E.; Reaven, G.M.; Azhar, S.; Lee, C.M.; Rabkin, R. )

    1989-10-01

    Spontaneously hypertensive rats (SHR) have been shown to be both insulin resistant and hyperinsulinemic after oral glucose administration or infusion of exogenous insulin during an insulin suppression test. To determine if this hyperinsulinemia may be due to decreased removal of insulin, the metabolic clearance (k) of insulin was measured in isolated perfused liver, kidney, and hindlimb skeletal muscle from SHR and Wistar-Kyoto (WKY) control rats. The data indicate that the k for insulin removal by liver was similar in SHR and WKY rats, averaging 287 +/- 18 and 271 +/- 10 microliters.min-1.g-1 liver, respectively. In contrast, the k for insulin removal by hindlimbs from SHR was decreased 37% (P less than 0.001) compared with WKY rats (8.6 +/- 0.5 vs. 13.7 +/- 0.7 microliters.min-1.g-1 muscle), and this decrease was not accompanied by decreased binding of insulin to its receptor in plantaris muscle. Although the removal of insulin by glomerular filtration was similar in SHR and WKY rats (653 +/- 64 microliters/min vs. 665 +/- 90 microliters.min-1.kidney-1), total insulin removal by kidney was significantly lower (P less than 0.05) in SHR (710 +/- 78 microliters/min) compared with WKY rats (962 +/- 67 microliters/min), due to decreased peritubular clearance of insulin in SHR (56 +/- 73 vs. 297 +/- 59 microliters/min, P less than 0.05). These findings suggest that the decreased clearance of insulin in SHR rats was possibly not due to impaired hepatic removal of insulin but rather to decreased removal by skeletal muscle and kidneys.

  11. Presynaptic Spontaneous Activity Enhances the Accuracy of Latency Coding.

    PubMed

    Levakova, Marie; Tamborrino, Massimiliano; Kostal, Lubomir; Lansky, Petr

    2016-10-01

    The time to the first spike after stimulus onset typically varies with the stimulation intensity. Experimental evidence suggests that neural systems use such response latency to encode information about the stimulus. We investigate the decoding accuracy of the latency code in relation to the level of noise in the form of presynaptic spontaneous activity. Paradoxically, the optimal performance is achieved at a nonzero level of noise and suprathreshold stimulus intensities. We argue that this phenomenon results from the influence of the spontaneous activity on the stabilization of the membrane potential in the absence of stimulation. The reported decoding accuracy improvement represents a novel manifestation of the noise-aided signal enhancement. PMID:27557098

  12. 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

  13. Presynaptic Spontaneous Activity Enhances the Accuracy of Latency Coding.

    PubMed

    Levakova, Marie; Tamborrino, Massimiliano; Kostal, Lubomir; Lansky, Petr

    2016-10-01

    The time to the first spike after stimulus onset typically varies with the stimulation intensity. Experimental evidence suggests that neural systems use such response latency to encode information about the stimulus. We investigate the decoding accuracy of the latency code in relation to the level of noise in the form of presynaptic spontaneous activity. Paradoxically, the optimal performance is achieved at a nonzero level of noise and suprathreshold stimulus intensities. We argue that this phenomenon results from the influence of the spontaneous activity on the stabilization of the membrane potential in the absence of stimulation. The reported decoding accuracy improvement represents a novel manifestation of the noise-aided signal enhancement.

  14. 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

  15. Learning shapes spontaneous activity itinerating over memorized states.

    PubMed

    Kurikawa, Tomoki; Kaneko, Kunihiko

    2011-01-01

    Learning is a process that helps create neural dynamical systems so that an appropriate output pattern is generated for a given input. Often, such a memory is considered to be included in one of the attractors in neural dynamical systems, depending on the initial neural state specified by an input. Neither neural activities observed in the absence of inputs nor changes caused in the neural activity when an input is provided were studied extensively in the past. However, recent experimental studies have reported existence of structured spontaneous neural activity and its changes when an input is provided. With this background, we propose that memory recall occurs when the spontaneous neural activity changes to an appropriate output activity upon the application of an input, and this phenomenon is known as bifurcation in the dynamical systems theory. We introduce a reinforcement-learning-based layered neural network model with two synaptic time scales; in this network, I/O relations are successively memorized when the difference between the time scales is appropriate. After the learning process is complete, the neural dynamics are shaped so that it changes appropriately with each input. As the number of memorized patterns is increased, the generated spontaneous neural activity after learning shows itineration over the previously learned output patterns. This theoretical finding also shows remarkable agreement with recent experimental reports, where spontaneous neural activity in the visual cortex without stimuli itinerate over evoked patterns by previously applied signals. Our results suggest that itinerant spontaneous activity can be a natural outcome of successive learning of several patterns, and it facilitates bifurcation of the network when an input is provided.

  16. Learning Shapes Spontaneous Activity Itinerating over Memorized States

    PubMed Central

    Kurikawa, Tomoki; Kaneko, Kunihiko

    2011-01-01

    Learning is a process that helps create neural dynamical systems so that an appropriate output pattern is generated for a given input. Often, such a memory is considered to be included in one of the attractors in neural dynamical systems, depending on the initial neural state specified by an input. Neither neural activities observed in the absence of inputs nor changes caused in the neural activity when an input is provided were studied extensively in the past. However, recent experimental studies have reported existence of structured spontaneous neural activity and its changes when an input is provided. With this background, we propose that memory recall occurs when the spontaneous neural activity changes to an appropriate output activity upon the application of an input, and this phenomenon is known as bifurcation in the dynamical systems theory. We introduce a reinforcement-learning-based layered neural network model with two synaptic time scales; in this network, I/O relations are successively memorized when the difference between the time scales is appropriate. After the learning process is complete, the neural dynamics are shaped so that it changes appropriately with each input. As the number of memorized patterns is increased, the generated spontaneous neural activity after learning shows itineration over the previously learned output patterns. This theoretical finding also shows remarkable agreement with recent experimental reports, where spontaneous neural activity in the visual cortex without stimuli itinerate over evoked patterns by previously applied signals. Our results suggest that itinerant spontaneous activity can be a natural outcome of successive learning of several patterns, and it facilitates bifurcation of the network when an input is provided. PMID:21408170

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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

  2. Neuropathic pain: Early spontaneous afferent activity is the trigger

    PubMed Central

    Xie, Wenrui; Strong, Judith A.; Meij, Johanna T.A.; Zhang, Jun-Ming; Yu, Lei

    2005-01-01

    Intractable neuropathic pain often results from nerve injury. One immediate event in damaged nerve is a sustained increase in spontaneous afferent activity, which has a well-established role in ongoing pain. Using two rat models of neuropathic pain, the CCI and SNI models, we show that local, temporary nerve blockade of this afferent activity permanently inhibits the subsequent development of both thermal hyperalgesia and mechanical allodynia. Timing is critical—the nerve blockade must last at least 3–5 days and is effective if started immediately after nerve injury, but not if started at 10 days after injury when neuropathic pain is already established. Effective nerve blockade also prevents subsequent development of spontaneous afferent activity measured electrophysiologically. Similar results were obtained in both pain models, and with two blockade methods (200 mg of a depot form bupivacaine at the injury site, or perfusion of the injured nerve just proximal to the injury site with TTX). These results indicate that early spontaneous afferent fiber activity is the key trigger for the development of pain behaviors, and suggest that spontaneous activity may be required for many of the later changes in the sensory neurons, spinal cord, and brain observed in neuropathic pain models. Many pre-clinical and clinical studies of pre-emptive analgesia have used much shorter duration of blockade, or have not started immediately after the injury. Our results suggest that effective pre-emptive analgesia can be achieved only when nerve block is administered early after injury and lasts several days. PMID:15964687

  3. [The effect of different motor regimens modulating spontaneous activity on rat behavior].

    PubMed

    Kulikov, V P; Kiselev, V I; Konev, I V

    1993-01-01

    A method was developed of non-stressful modulation of spontaneous motor activity of rats. Restraint of mobility was found to inhibit spontaneous activity. Physiological stimulation of muscle activity by means of complication of food-procuring behaviour was accompanied by increase of spontaneous activity. Physiological stimulation of motor activity was characterized by stability of orienting-exploratory behaviour, emotional reactivity, expression of "freedom response", the best learning and working abilities of the animals. Regimes with imposing or restriction of muscle activity favoured the inhibition of spontaneous activity and the decrease of efficiency of adaptive behaviour. Motor regimes accompanied by increase of spontaneous activity were found to be optimal for adaptive behaviour.

  4. Spontaneous and specific activation of chemical bonds in macromolecular fluids.

    PubMed

    Park, Insun; Shirvanyants, David; Nese, Alper; Matyjaszewski, Krzysztof; Rubinstein, Michael; Sheiko, Sergei S

    2010-09-01

    Mechanical activation of chemical bonds typically involves the application of external forces, which implies a broad distribution of bond tensions. We demonstrate that controlling the flow profile of a macromolecular fluid generates and delineates mechanical force concentration, enabling a hierarchical activation of chemical bonds on different length scales from the macroscopic to the molecular. Bond tension is spontaneously generated within brushlike macromolecules as they spread on a solid substrate. The molecular architecture creates an uneven distribution of tension in the covalent bonds, leading to spatially controlled bond scission. By controlling the flow rate and the gradient of the film pressure, one can sever the flowing macromolecules with high precision. Specific chemical bonds are activated within distinct macromolecules located in a defined area of a thin film. Furthermore, the flow-controlled loading rate enables quantitative analysis of the bond activation parameters.

  5. Brain modularity controls the critical behavior of spontaneous activity

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

    The human brain exhibits a complex structure made of scale-free highly connected modules loosely interconnected by weaker links to form a small-world network. These features appear in healthy patients whereas neurological diseases often modify this structure. An important open question concerns the role of brain modularity in sustaining the critical behaviour of spontaneous activity. Here we analyse the neuronal activity of a model, successful in reproducing on non-modular networks the scaling behaviour observed in experimental data, on a modular network implementing the main statistical features measured in human brain. We show that on a modular network, regardless the strength of the synaptic connections or the modular size and number, activity is never fully scale-free. Neuronal avalanches can invade different modules which results in an activity depression, hindering further avalanche propagation. Critical behaviour is solely recovered if inter-module connections are added, modifying the modular into a more random structure.

  6. 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

  7. 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

  8. Spontaneous and task-evoked brain activity negatively interact

    PubMed Central

    He, Biyu J.

    2013-01-01

    A widely held assumption is that spontaneous and task-evoked brain activity sum linearly, such that the recorded brain response in each single trial is the algebraic sum of the constantly changing ongoing activity and the stereotypical evoked activity. Using functional magnetic resonance imaging (fMRI) signals acquired from normal humans, we show that this assumption is invalid. Across widespread cortices, evoked activity interacts negatively with ongoing activity, such that higher prestimulus baseline results in less activation or more deactivation. As a consequence of this negative interaction, trial-to-trial variability of cortical activity decreases following stimulus onset. We further show that variability reduction follows overlapping but distinct spatial pattern from that of task activation/deactivation and it contains behaviorally relevant information. These results favor an alternative perspective to the traditional dichotomous framework of ongoing and evoked activity – one that views the brain as a nonlinear dynamical system whose trajectory is tighter when performing a task; further, incoming sensory stimuli modulate the brain’s activity in a manner that depends on its initial state. We propose that across-trial variability may provide a new approach to brain mapping in the context of cognitive experiments. PMID:23486941

  9. Copper is an endogenous modulator of neural circuit spontaneous activity

    PubMed Central

    Dodani, Sheel C.; Firl, Alana; Chan, Jefferson; Nam, Christine I.; Aron, Allegra T.; Onak, Carl S.; Ramos-Torres, Karla M.; Paek, Jaeho; Webster, Corey M.; Feller, Marla B.; Chang, Christopher J.

    2014-01-01

    For reasons that remain insufficiently understood, the brain requires among the highest levels of metals in the body for normal function. The traditional paradigm for this organ and others is that fluxes of alkali and alkaline earth metals are required for signaling, but transition metals are maintained in static, tightly bound reservoirs for metabolism and protection against oxidative stress. Here we show that copper is an endogenous modulator of spontaneous activity, a property of functional neural circuitry. Using Copper Fluor-3 (CF3), a new fluorescent Cu+ sensor for one- and two-photon imaging, we show that neurons and neural tissue maintain basal stores of loosely bound copper that can be attenuated by chelation, which define a labile copper pool. Targeted disruption of these labile copper stores by acute chelation or genetic knockdown of the CTR1 (copper transporter 1) copper channel alters the spatiotemporal properties of spontaneous activity in developing hippocampal and retinal circuits. The data identify an essential role for copper neuronal function and suggest broader contributions of this transition metal to cell signaling. PMID:25378701

  10. Copper is an endogenous modulator of neural circuit spontaneous activity.

    PubMed

    Dodani, Sheel C; Firl, Alana; Chan, Jefferson; Nam, Christine I; Aron, Allegra T; Onak, Carl S; Ramos-Torres, Karla M; Paek, Jaeho; Webster, Corey M; Feller, Marla B; Chang, Christopher J

    2014-11-18

    For reasons that remain insufficiently understood, the brain requires among the highest levels of metals in the body for normal function. The traditional paradigm for this organ and others is that fluxes of alkali and alkaline earth metals are required for signaling, but transition metals are maintained in static, tightly bound reservoirs for metabolism and protection against oxidative stress. Here we show that copper is an endogenous modulator of spontaneous activity, a property of functional neural circuitry. Using Copper Fluor-3 (CF3), a new fluorescent Cu(+) sensor for one- and two-photon imaging, we show that neurons and neural tissue maintain basal stores of loosely bound copper that can be attenuated by chelation, which define a labile copper pool. Targeted disruption of these labile copper stores by acute chelation or genetic knockdown of the CTR1 (copper transporter 1) copper channel alters the spatiotemporal properties of spontaneous activity in developing hippocampal and retinal circuits. The data identify an essential role for copper neuronal function and suggest broader contributions of this transition metal to cell signaling.

  11. Spontaneous cortical activity in awake monkeys composed of neuronal avalanches.

    PubMed

    Petermann, Thomas; Thiagarajan, Tara C; Lebedev, Mikhail A; Nicolelis, Miguel A L; Chialvo, Dante R; Plenz, Dietmar

    2009-09-15

    Spontaneous neuronal activity is an important property of the cerebral cortex but its spatiotemporal organization and dynamical framework remain poorly understood. Studies in reduced systems--tissue cultures, acute slices, and anesthetized rats--show that spontaneous activity forms characteristic clusters in space and time, called neuronal avalanches. Modeling studies suggest that networks with this property are poised at a critical state that optimizes input processing, information storage, and transfer, but the relevance of avalanches for fully functional cerebral systems has been controversial. Here we show that ongoing cortical synchronization in awake rhesus monkeys carries the signature of neuronal avalanches. Negative LFP deflections (nLFPs) correlate with neuronal spiking and increase in amplitude with increases in local population spike rate and synchrony. These nLFPs form neuronal avalanches that are scale-invariant in space and time and with respect to the threshold of nLFP detection. This dimension, threshold invariance, describes a fractal organization: smaller nLFPs are embedded in clusters of larger ones without destroying the spatial and temporal scale-invariance of the dynamics. These findings suggest an organization of ongoing cortical synchronization that is scale-invariant in its three fundamental dimensions--time, space, and local neuronal group size. Such scale-invariance has ontogenetic and phylogenetic implications because it allows large increases in network capacity without a fundamental reorganization of the system.

  12. 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

  13. 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

  14. 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.

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

    PubMed Central

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

    2016-01-01

    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

  16. 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

  17. 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.

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

    DOE PAGES

    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

  19. 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.

  20. Altered Spontaneous Brain Activity in Primary Open Angle Glaucoma: A Resting-State Functional Magnetic Resonance Imaging Study

    PubMed Central

    Lin, Fuchun; Chen, Zhiqi; Yan, Xiaoqin; Hao, Yonghong; Zhu, Wenzhen; Zhang, Hong

    2014-01-01

    Background Previous studies demonstrated that primary open angle glaucoma (POAG) is associated with abnormal brain structure; however, little is known about the changes in the local synchronization of spontaneous activity. The main objective of this study was to investigate spontaneous brain activity in patients with POAG using regional homogeneity (ReHo) analysis based on resting state functional magnetic resonance imaging (rs-fMRI). Methodology/Principal Findings Thirty-nine POAG patients and forty-one age- and gender- matched healthy controls were finally included in the study. ReHo values were used to evaluate spontaneous brain activity and whole brain voxel-wise analysis of ReHo was carried out to detect differences by region in spontaneous brain activity between groups. Compared to controls, POAG patients showed increased ReHo in the right dorsal anterior cingulated cortex, the bilateral medial frontal gyrus and the right cerebellar anterior lobe, and decreased ReHo in the bilateral calcarine, bilateral precuneus gryus, bilateral pre/postcentral gyrus, left inferior parietal lobule and left cerebellum posterior lobe. A multiple linear regression analysis was performed to explore the relationships between clinical measures and ReHo by region showed significant group differences in the POAG group. Negative correlations were found between age and the ReHo values of the superior frontal gyrus (r = −0.323, p = 0.045), left calcarine (r = −0.357, p = 0.026) and inferior parietal lobule (r = −0.362, p = 0.024). A negative correlation was found between the ReHo values of the left precuneus and the cumulative mean defect (r = −0.400, p = 0.012). Conclusions POAG was associated with abnormal brain spontaneous activity in some brain regions and such changed regional activity may be associated with clinical parameters. Spontaneous brain activity may play a role in POAG initiation and progression. PMID:24586822

  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. 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.

  3. How can we identify ictal and interictal abnormal activity?

    PubMed

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

    2014-01-01

    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.

  4. 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

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

    PubMed Central

    Sampath, Alapakkam P; Baylor, Denis A

    2002-01-01

    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. Fast transient networks in spontaneous human brain activity.

    PubMed

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

    2014-03-25

    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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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.

  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

    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

  15. 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

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

    PubMed

    Teske, J A; Billington, C J; Kotz, C M

    2014-01-01

    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 (OXRs) 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 the generation of SPA. To test this, SPA response was determined in lean and obese rats with cannulae targeted toward the rostral lateral hypothalamus (rLH) or SN. Sleep/wake states were also measured in rats with rLH cannula and electroencephalogram/electromyogram radiotelemetry transmitters. SPA in lean rats was more sensitive to antagonism of the 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 obesity-resistant 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 the mediation of SPA and running wheel activity.

  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. 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

  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 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

  2. 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...

  3. Associating spontaneous with evoked activity in a neural mass model of visual cortex.

    PubMed

    Nguyen Trong, Manh; Bojak, Ingo; Knösche, Thomas R

    2013-02-01

    Spontaneous activity of the brain at rest frequently has been considered a mere backdrop to the salient activity evoked by external stimuli or tasks. However, the resting state of the brain consumes most of its energy budget, which suggests a far more important role. An intriguing hint comes from experimental observations of spontaneous activity patterns, which closely resemble those evoked by visual stimulation with oriented gratings, except that cortex appeared to cycle between different orientation maps. Moreover, patterns similar to those evoked by the behaviorally most relevant horizontal and vertical orientations occurred more often than those corresponding to oblique angles. We hypothesize that this kind of spontaneous activity develops at least to some degree autonomously, providing a dynamical reservoir of cortical states, which are then associated with visual stimuli through learning. To test this hypothesis, we use a biologically inspired neural mass model to simulate a patch of cat visual cortex. Spontaneous transitions between orientation states were induced by modest modifications of the neural connectivity, establishing a stable heteroclinic channel. Significantly, the experimentally observed greater frequency of states representing the behaviorally important horizontal and vertical orientations emerged spontaneously from these simulations. We then applied bar-shaped inputs to the model cortex and used Hebbian learning rules to modify the corresponding synaptic strengths. After unsupervised learning, different bar inputs reliably and exclusively evoked their associated orientation state; whereas in the absence of input, the model cortex resumed its spontaneous cycling. We conclude that the experimentally observed similarities between spontaneous and evoked activity in visual cortex can be explained as the outcome of a learning process that associates external stimuli with a preexisting reservoir of autonomous neural activity states. Our findings

  4. 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

  5. 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.

  6. 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

  7. Hyperpolarization-activated cation current contributes to spontaneous network activity in developing neocortical cultures.

    PubMed

    Klueva, Julia; Lima, Ana D de; Meis, Susanne; Voigt, Thomas; Munsch, Thomas

    2012-01-01

    The mechanisms underlying spontaneous burst activity (SBA), appearing in networks of embryonic cortical neurons at the end of the first week in vitro, remain elusive. Here we investigated the contribution of the hyperpolarization-activated cation current (I(h)) to SBA in cortical cultures of GAD67-GFP mice. I(h) current could be detected in GFP-positive large GABAergic interneurons (L-INs) and glutamatergic principal neurons (PNs) as early as DIV 5. Under current-clamp conditions, blockers of I(h) current, ZD7288 and Cs⁺, abolished the voltage sag and rebound depolarization. ZD7288 induced a hyperpolarization concomitant with an increase in the membrane input resistance in L-INs and PNs. Voltage-clamp recordings revealed I(h) as slowly activating inward current with a reversal potential close to -50 mV and a mid-activation point around -90 mV. Both, ZD7288 (1-10 μM) and Cs⁺ (1-2 mM) reduced SBA, spontaneous activity-driven Ca²⁺ transients, and frequency as well as amplitude of miniature GABAergic postsynaptic currents. Immunocytochemistry and Western blot demonstrated that HCN1 and HCN2 were the prevalent isoforms of HCN channels expressed in L-INs and PNs. These results suggest an important contribution of HCN channels to the maintenance of SBA in embryonic cortical cultures. PMID:22094222

  8. 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

  9. Short-term Effects of Risperidone Monotherapy on Spontaneous Brain Activity in First-episode Treatment-naïve Schizophrenia Patients: A Longitudinal fMRI Study

    PubMed Central

    Hu, Mao-Lin; Zong, Xiao-Fen; Zheng, Jun-Jie; Pantazatos, Spiro P.; Miller, Jeffrey M.; Li, Zong-Chang; Liao, Yan-Hui; He, Ying; Zhou, Jun; Sang, De-En; Zhao, Hong-Zeng; Lv, Lu-Xian; Tang, Jin-Song; Mann, J. John; Chen, Xiao-Gang

    2016-01-01

    It is unclear whether abnormal spontaneous neural activation patterns found in chronic schizophrenia patients (CSP) are part of the pathogenesis of disease, consequences of chronic illness, or effects of antipsychotic treatment. We performed a longitudinal resting-state functional magnetic resonance imaging (fMRI) study in 42 treatment-naïve first-episode schizophrenia patients (FESP) at baseline and then after 8-weeks of risperidone monotherapy, and compared the findings to 38 healthy volunteers. Spontaneous brain activity was quantified using the fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) and compared between patients and controls. Pretreatment, patients exhibited higher fALFF in left caudate compared with controls. After treatment, patients had elevated fALFF in bilateral putamen and right caudate, and increased ReHo in right caudate and left putamen. Greater increase of fALFF in the left putamen correlated with less improvement in positive symptoms. Thus, abnormalities of spontaneous neural activity in chronic schizophrenia is at least partly due to a medication effect. The observed post-treatment increase in striatal intrinsic activity may reflect counter-therapeutic functional adaptation to dopamine D2 receptor occupancy required for medication effects on psychosis. PMID:27698361

  10. Consequences of abnormal CDK activity in S phase.

    PubMed

    Anda, Silje; Rothe, Christiane; Boye, Erik; Grallert, Beáta

    2016-01-01

    Cyclin Dependent Kinases (CDKs) are important regulators of DNA replication. In this work we have investigated the consequences of increasing or decreasing the CDK activity in S phase. To this end we identified S-phase regulators of the fission yeast CDK, Cdc2, and used appropriate mutants to modulate Cdc2 activity. In fission yeast Mik1 has been thought to be the main regulator of Cdc2 activity in S phase. However, we find that Wee1 has a major function in S phase and thus we used wee1 mutants to investigate the consequences of increased Cdc2 activity. These wee1 mutants display increased replication stress and, particularly in the absence of the S-phase checkpoint, accumulate DNA damage. Notably, more cells incorporate EdU in a wee1(-) strain as compared to wildtype, suggesting altered regulation of DNA replication. In addition, a higher number of cells contain chromatin-bound Cdc45, an indicator of active replication forks. In addition, we found that Cdc25 is required to activate Cdc2 in S phase and used a cdc25 mutant to explore a situation where Cdc2 activity is reduced. Interestingly, a cdc25 mutant has a higher tolerance for replication stress than wild-type cells, suggesting that reduced CDK activity in S phase confers resistance to at least some forms of replication stress. PMID:26918805

  11. Abnormal immune complex processing and spontaneous glomerulonephritis in complement factor H-deficient mice with human complement receptor 1 on erythrocytes.

    PubMed

    Alexander, Jessy J; Hack, Bradley K; Jacob, Alexander; Chang, Anthony; Haas, Mark; Finberg, Robert W; Quigg, Richard J

    2010-09-15

    Complement receptor 1 (CR1) on human erythrocytes (Es) and complement factor H (CFH) on rodent platelets perform immune adherence, which is a function that allows the processing of immune complexes (ICs) bearing C3 by the mononuclear phagocyte system. Similar immune adherence occurs in the glomerular podocyte by CR1 in humans and CFH in rodents. As a model for human IC processing, we studied transgenic mice lacking CFH systemically but with human CR1 on Es. These CR1(hu)Tg/CFH(-/-) mice spontaneously developed proliferative glomerulonephritis, which was accelerated in a chronic serum sickness model by active immunization with heterologous apoferritin. ICs containing Ag, IgG and C3 bound to Es in CR1(hu)Tg/CFH(-/-) mice. In this setting, there was increased IC deposition in glomeruli, attributable to the presence of CR1 on Es, together with the absence of CFH on platelets and podocytes. In the absence of plasma CFH, the accumulated ICs activated complement, which led to spontaneous and chronic serum sickness-induced proliferative glomerulonephritis. These findings illustrate the complexities of complement-dependent IC processing by blood cells and in the glomerulus, and the importance of CFH as a plasma complement regulator.

  12. 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

  13. Spontaneous and Evoked Release Are Independently Regulated at Individual Active Zones

    PubMed Central

    Melom, Jan E.; Akbergenova, Yulia; Gavornik, Jeffrey P.

    2013-01-01

    Neurotransmitter release from synaptic vesicle fusion is the fundamental mechanism for neuronal communication at synapses. Evoked release following an action potential has been well characterized for its function in activating the postsynaptic cell, but the significance of spontaneous release is less clear. Using transgenic tools to image single synaptic vesicle fusion events at individual release sites (active zones) in Drosophila, we characterized the spatial and temporal dynamics of exocytotic events that occur spontaneously or in response to an action potential. We also analyzed the relationship between these two modes of fusion at single release sites. A majority of active zones participate in both modes of fusion, although release probability is not correlated between the two modes of release and is highly variable across the population. A subset of active zones is specifically dedicated to spontaneous release, indicating a population of postsynaptic receptors is uniquely activated by this mode of vesicle fusion. Imaging synaptic transmission at individual release sites also revealed general rules for spontaneous and evoked release, and indicate that active zones with similar release probability can cluster spatially within individual synaptic boutons. These findings suggest neuronal connections contain two information channels that can be spatially segregated and independently regulated to transmit evoked or spontaneous fusion signals. PMID:24174659

  14. 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.

  15. Knockdown of sodium channel NaV1.6 blocks mechanical pain and abnormal bursting activity of afferent neurons in inflamed sensory ganglia.

    PubMed

    Xie, Wenrui; Strong, Judith A; Ye, Ling; Mao, Ju-Xian; Zhang, Jun-Ming

    2013-08-01

    Inflammatory processes in the sensory ganglia contribute to many forms of chronic pain. We previously showed that local inflammation of the lumbar sensory ganglia rapidly leads to prolonged mechanical pain behaviors and high levels of spontaneous bursting activity in myelinated cells. Abnormal spontaneous activity of sensory neurons occurs early in many preclinical pain models and initiates many other pathological changes, but its molecular basis is not well understood. The sodium channel isoform NaV1.6 can underlie repetitive firing and excitatory persistent and resurgent currents. We used in vivo knockdown of this channel via local injection of siRNA to examine its role in chronic pain after local inflammation of the rat lumbar sensory ganglia. In normal dorsal root ganglion (DRG), quantitative polymerase chain reaction showed that cells capable of firing repetitively had significantly higher relative expression of NaV1.6. In inflamed DRG, spontaneously active bursting cells expressed high levels of NaV1.6 immunoreactivity. In vivo knockdown of NaV1.6 locally in the lumbar DRG at the time of DRG inflammation completely blocked development of pain behaviors and abnormal spontaneous activity, while having only minor effects on unmyelinated C cells. Current research on isoform-specific sodium channel blockers for chronic pain is largely focused on NaV1.8 because it is present primarily in unmyelinated C fiber nociceptors, or on NaV1.7 because lack of this channel causes congenital indifference to pain. However, the results suggest that NaV1.6 may be a useful therapeutic target for chronic pain and that some pain conditions may be mediated primarily by myelinated A fiber sensory neurons. PMID:23622763

  16. Knockdown of sodium channel NaV1.6 blocks mechanical pain and abnormal bursting activity of afferent neurons in inflamed sensory ganglia

    PubMed Central

    Xie, Wenrui; Strong, Judith A.; Ye, Ling; Mao, Ju-Xian; Zhang, Jun-Ming

    2013-01-01

    Inflammatory processes in the sensory ganglia contribute to many forms of chronic pain. We previously showed that local inflammation of the lumbar sensory ganglia rapidly leads to prolonged mechanical pain behaviors and high levels of spontaneous bursting activity in myelinated cells. Abnormal spontaneous activity of sensory neurons occurs early in many preclinical pain models, and initiates many other pathological changes, but its molecular basis is not well understood. The sodium channel isoform NaV1.6 can underlie repetitive firing and excitatory persistent and resurgent currents. We used in vivo knockdown of this channel via local injection of siRNA to examine its role in chronic pain following local inflammation of the rat lumbar sensory ganglia. In normal DRG, quantitative PCR showed that cells capable of firing repetitively had significantly higher relative expression of NaV1.6. In inflamed DRG, spontaneously active bursting cells expressed high levels of NaV1.6′ immunoreactivity. In vivo knockdown of NaV1.6 locally in the lumbar DRG at the time of DRG inflammation completely blocked development of pain behaviors and abnormal spontaneous activity, while having only minor effects on unmyelinated C-cells. Current research on isoform-specific sodium channel blockers for chronic pain is largely focused on NaV1.8, because it is present primarily in unmyelinated C fiber nociceptors, or on NaV1.7, because lack of this channel causes congenital indifference to pain. However, the results suggest that NaV1.6 may be a useful therapeutic target for chronic pain, and that some pain conditions may be primarily mediated by myelinated A-fiber sensory neurons. PMID:23622763

  17. 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

  18. 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.

  19. Disruption of Lateral Olivocochlear Neurons With a Dopaminergic Neurotoxin Depresses Spontaneous Auditory Nerve Activity

    PubMed Central

    Le Prell, Colleen G.; Dolan, David F.; Hughes, Larry F.; Altschuler, Richard A.; Shore, Susan E.; Bledsoe, Sanford C.

    2015-01-01

    Neurons of the lateral olivocochlear (LOC) system project from the auditory brainstem to the cochlea, where they synapse on radial dendrites of auditory nerve fibers. Selective LOC disruption depresses sound-evoked auditory nerve activity in the guinea pig, but enhances it in the mouse. Here, LOC disruption depressed spontaneous auditory nerve activity in the guinea pig. Recordings from single auditory nerve fibers revealed a significantly reduced proportion of fibers with the highest spontaneous firing rates (SRs) and an increased proportion of neurons with lower SRs. Ensemble activity, estimated using round window noise, also decreased after LOC disruption. Decreased spontaneous activity after LOC disruption may be a consequence of reduced tonic release of excitatory transmitters from the LOC terminals in guinea pigs. PMID:25175420

  20. Disruption of lateral olivocochlear neurons with a dopaminergic neurotoxin depresses spontaneous auditory nerve activity.

    PubMed

    Le Prell, Colleen G; Dolan, David F; Hughes, Larry F; Altschuler, Richard A; Shore, Susan E; Bledsoe, Sanford C

    2014-10-17

    Neurons of the lateral olivocochlear (LOC) system project from the auditory brainstem to the cochlea, where they synapse on radial dendrites of auditory nerve fibers. Selective LOC disruption depresses sound-evoked auditory nerve activity in the guinea pig, but enhances it in the mouse. Here, LOC disruption depressed spontaneous auditory nerve activity in the guinea pig. Recordings from single auditory nerve fibers revealed a significantly reduced proportion of fibers with the highest spontaneous firing rates (SRs) and an increased proportion of neurons with lower SRs. Ensemble activity, estimated using round window noise, also decreased after LOC disruption. Decreased spontaneous activity after LOC disruption may be a consequence of reduced tonic release of excitatory transmitters from the LOC terminals in guinea pigs. PMID:25175420

  1. Phosphorylation of Complexin by PKA Regulates Activity-Dependent Spontaneous Neurotransmitter Release and Structural Synaptic Plasticity.

    PubMed

    Cho, Richard W; Buhl, Lauren K; Volfson, Dina; Tran, Adrienne; Li, Feng; Akbergenova, Yulia; Littleton, J Troy

    2015-11-18

    Synaptic plasticity is a fundamental feature of the nervous system that allows adaptation to changing behavioral environments. Most studies of synaptic plasticity have examined the regulated trafficking of postsynaptic glutamate receptors that generates alterations in synaptic transmission. Whether and how changes in the presynaptic release machinery contribute to neuronal plasticity is less clear. The SNARE complex mediates neurotransmitter release in response to presynaptic Ca(2+) entry. Here we show that the SNARE fusion clamp Complexin undergoes activity-dependent phosphorylation that alters the basic properties of neurotransmission in Drosophila. Retrograde signaling following stimulation activates PKA-dependent phosphorylation of the Complexin C terminus that selectively and transiently enhances spontaneous release. Enhanced spontaneous release is required for activity-dependent synaptic growth. These data indicate that SNARE-dependent fusion mechanisms can be regulated in an activity-dependent manner and highlight the key role of spontaneous neurotransmitter release as a mediator of functional and structural plasticity.

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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

  9. Abnormal grooming activity in Dab1(scm) (scrambler) mutant mice.

    PubMed

    Strazielle, C; Lefevre, A; Jacquelin, C; Lalonde, R

    2012-07-15

    Dab1(scm) mutant mice, characterized by cell ectopias and degeneration in cerebellum, hippocampus, and neocortex, were compared to non-ataxic controls for different facets of grooming caused by brief water immersions, as well as some non-grooming behaviors. Dab1(scm) mutants were strongly affected in their quantitative functional parameters, exhibiting higher starting latencies before grooming relative to non-ataxic littermates of the A/A strain, fewer grooming bouts, and grooming components of shorter duration, with an unequal regional distribution targeting almost totally the rostral part (head washing and forelimb licking) of the animal. Only bouts of a single grooming element were preserved. The cephalocaudal order of grooming elements appeared less disorganized, mutant and control mice initiating the grooming with head washing and forelimb licking prior to licking posterior parts. However, mutants differed from controls in that all their bouts were incomplete but uninterrupted, although intergroup difference for percentage of the incorrect transitions was not significant. In contrast to grooming, Dab1(scm) mice ambulated for a longer time. During walking episodes, they exhibited more body scratching than controls, possibly to compensate for the lack of licking different body parts. In conjunction with studies with other ataxic mice, these results indicate that the cerebellar cortex affects grooming activity and is consequently involved in executing various components, but not in its sequential organization, which requires other brain regions such as cerebral cortices or basal ganglia.

  10. Exploration of the spontaneous fluctuating activity of single enzyme molecules.

    PubMed

    Schwabe, Anne; Maarleveld, Timo R; Bruggeman, Frank J

    2013-09-01

    Single enzyme molecules display inevitable, stochastic fluctuations in their catalytic activity. In metabolism, for instance, the stochastic activity of individual enzymes is averaged out due to their high copy numbers per single cell. However, many processes inside cells rely on single enzyme activity, such as transcription, replication, translation, and histone modifications. Here we introduce the main theoretical concepts of stochastic single-enzyme activity starting from the Michaelis-Menten enzyme mechanism. Next, we discuss stochasticity of multi-substrate enzymes, of enzymes and receptors with multiple conformational states and finally, how fluctuations in receptor activity arise from fluctuations in signal concentration. This paper aims to introduce the exciting field of single-molecule enzyme kinetics and stochasticity to a wider audience of biochemists and systems biologists.

  11. Spontaneous local variations in ongoing neural activity bias perceptual decisions

    PubMed Central

    Hesselmann, Guido; Kell, Christian A.; Eger, Evelyn; Kleinschmidt, Andreas

    2008-01-01

    Neural variability in responding to identical repeated stimuli has been related to trial-by-trial fluctuations in ongoing activity, yet the neural and perceptual consequences of these fluctuations remain poorly understood. Using functional neuroimaging, we recorded brain activity in subjects who reported perceptual decisions on an ambiguous figure, Rubin's vase-faces picture, which was briefly presented at variable intervals of ≥20 s. Prestimulus activity in the fusiform face area, a cortical region preferentially responding to faces, was higher when subjects subsequently perceived faces instead of the vase. This finding suggests that endogenous variations in prestimulus neuronal activity biased subsequent perceptual inference. Furnishing evidence that evoked sensory responses, we then went on to show that the pre- and poststimulus activity interact in a nonlinear way and the ensuing perceptual decisions depend upon the prestimulus context in which they occur. PMID:18664576

  12. 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.

  13. 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

  14. Putative role of border cells in generating spontaneous morphological activity within Kölliker's organ.

    PubMed

    Dayaratne, M W Nishani; Vlajkovic, Srdjan M; Lipski, Janusz; Thorne, Peter R

    2015-12-01

    Kölliker's organ is a transient epithelial structure, comprising a major part of the organ of Corti during pre-hearing stages of development. The auditory system is spontaneously active during development, which serves to retain and refine neural connections. Kölliker's organ is considered a key candidate for generating such spontaneous activity, most likely through purinergic (P2 receptor) signalling and inner hair cell (IHC) activation. Associated with the spontaneous neural activity, ATP released locally by epithelial cells induces rhythmic morphological changes within Kölliker's organ, the purpose of which is not understood. These changes are accompanied by a shift in cellular refractive index, allowing optical detection of this activity in real-time. Using this principle, we investigated the origin of spontaneous morphological activity within Kölliker's organ. Apical turns of Wistar rat cochleae (P9-11) were dissected, and the purinergic involvement was studied following acute tissue exposure to a P2 receptor agonist (ATPγS) and antagonist (suramin). ATPγS induced a sustained darkening throughout Kölliker's organ, reversed by suramin. This effect was most pronounced in the region closest to the inner hair cells, which also displayed the highest frequency of intrinsic morphological events. Additionally, suramin alone induced swelling of this region, suggesting a tight regulation of cell volume by ATP-mediated mechanisms. Histological analysis of cochlear tissues demonstrates the most profound volume changes in the border cell region immediately adjacent to the IHCs. Together, these results underline the role of purinergic signalling in initiating morphological events within Kölliker's organ, and suggest a key involvement of border cells surrounding IHCs in regulating this spontaneous activity.

  15. 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.

  16. 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

  17. The auditory midbrain of people with tinnitus: abnormal sound-evoked activity revisited.

    PubMed

    Melcher, Jennifer R; Levine, Robert A; Bergevin, Christopher; Norris, Barbara

    2009-11-01

    Sound-evoked fMRI activation of the inferior colliculi (IC) was compared between tinnitus and non-tinnitus subjects matched in threshold (normal), age, depression, and anxiety. Subjects were stimulated with broadband sound in an "on/off" fMRI paradigm with and without on-going sound from the scanner coolant pump. (1) With pump sounds off, the tinnitus group showed greater stimulus-evoked activation of the IC than the non-tinnitus group, suggesting abnormal gain within the auditory pathway of tinnitus subjects. (2) Having pump sounds on reduced activation in the tinnitus, but not the non-tinnitus group. This result suggests response saturation in tinnitus subjects, possibly occurring because abnormal gain increased response amplitude to an upper limit. (3) In contrast to Melcher et al. (2000), the ratio of activation between right and left IC did not differ significantly between tinnitus and non-tinnitus subjects or in a manner dependent on tinnitus laterality. However, new data from subjects imaged previously by Melcher et al. suggest a possible tinnitus subgroup with abnormally asymmetric function of the IC. The present and previous data together suggest elevated responses to sound in the IC are common among those with tinnitus and normal thresholds, while abnormally asymmetric activation is not, even among those with lateralized tinnitus. PMID:19699287

  18. 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.

  19. Localization of spontaneous magnetoencephalographic activity of neonates and fetuses using independent component and Hilbert phase analysis

    PubMed Central

    Vairavan, Srinivasan; Eswaran, Hari; Preissl, Hubert; Wilson, James D.; Haddad, Naim; Lowery, Curtis L.

    2011-01-01

    The fetal magnetoencephalogram (fMEG) is measured in the presence of large interference from maternal and fetal magnetocardiograms (mMCG and fMCG). These cardiac interferences can be attenuated by orthogonal projection (OP) technique of the corresponding spatial vectors. However, the OP technique redistributes the fMEG signal among the channels and also leaves some cardiac residuals (partially attenuated mMCG and fMCG) due to loss of stationarity in the signal. In this paper, we propose a novel way to extract and localize the neonatal and fetal spontaneous brain activity by using independent component analysis (ICA) technique. In this approach, we perform ICA on a small subset of sensors for 1-min duration. The independent components obtained are further investigated for the presence of discontinuous patterns as identified by the Hilbert phase analysis and are used as decision criteria for localizing the spontaneous brain activity. In order to locate the region of highest spontaneous brain activity content, this analysis is performed on the sensor subsets, which are traversed across the entire sensor space. The region of the spontaneous brain activity as identified by the proposed approach correlated well with the neonatal and fetal head location. In addition, the burst duration and the inter-burst interval computed for the identified discontinuous brain patterns are in agreement with the reported values. PMID:21096327

  20. 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...

  1. 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...

  2. 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.

  3. 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.

  4. 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…

  5. Abnormal electromyographic activity of the urethral sphincter, voiding dysfunction, and polycystic ovaries: a new syndrome?

    PubMed

    Fowler, C J; Christmas, T J; Chapple, C R; Parkhouse, H F; Kirby, R S; Jacobs, H S

    1988-12-01

    A potential association between abnormal electromyographic activity--that is, decelerating bursts and complex repetitive discharges--of the urethral sphincter and difficulty in voiding was examined in 57 women with urinary retention. Abnormal electromyographic activity was found in 33. Ultrasonography of the ovaries in 22 of the 33 women showed that 14 had polycystic ovaries. Of the other eight women, two had had oophorectomies, one had shrunken ovaries and ovarian failure, and one had previously undergone oophorectomy and the other ovary could not be seen; in one neither ovary could be seen, and three had ovaries of normal appearance, although two of these women were taking the contraceptive pill. Thirteen of the group had endocrine symptoms and signs characteristic of the polycystic ovary syndrome. Videocystometrography in 17 of the women who were examined by ultrasonography showed low flow rates and high residual volumes of urine after micturition in 12 women who could void, the other five having chronic urinary retention. A speculative hypothesis for the observed association of impaired voiding, abnormal electromyographic activity of the urinary sphincter, and polycystic ovaries is advanced, based on the relative progesterone deficiency that characterises the polycystic ovary syndrome. Progesterone stabilises membranes, and its depletion might permit ephaptic transmission of impulses between muscle fibres in the muscle of the urethral sphincter, giving rise to the abnormal electromyographic activity. This may impair relaxation of the sphincter, resulting in low flow rates of urine, incomplete emptying of the bladder, and, finally, urinary retention.

  6. Erratum to "Noise-induced changes of neuronal spontaneous activity in mice inferior colliculus brain slices".

    PubMed

    Basta, Dietmar; Ernst, Arne

    2005-02-01

    The inferior colliculus (IC) in vivo is reportedly subject to a noise-induced decrease of GABA-related inhibitory synaptic transmission accompanied by an amplitude increase of auditory evoked responses, a widening of tuning curves and a higher neuronal discharge rate at suprathreshold levels. However, other in vivo experiments which demonstrated constant neuronal auditory thresholds or unchanged spontaneous activity in the IC after noise exposure did not confirm those findings. Perhaps this can be the result of complex noise-induced interactions between different central auditory structures. It was, therefore, the aim of the present study to investigate the effects of noise exposure on the spontaneous electrical activity of single neurons in a slice preparation of the isolated mouse IC. Normal hearing mice were exposed to noise (10 kHz center frequency at 115 dB SPL for 3 h) at the age of 21 days under anesthesia (Ketamin/Rompun 10:1). After one week, auditory brainstem response (ABR) recordings and extracellular single-unit recordings from spontaneously active neurons within the IC slice were performed in noise-exposed and in normal hearing control mice. Noise-exposed animals showed a significant ABR threshold shift in the whole tested frequency range and a significant lower neuronal spontaneous activity in all investigated isofrequency laminae compared to controls. In both groups, the firing rate of 80% of IC neurons (approximately) increased significantly during the application of the GABA(A) receptor antagonist Bicucullin (10 microM). The present findings demonstrate a noise-related modulation of spontaneous activity in the IC, which possibly contribute to the generation of noise-induced tinnitus and hearing loss.

  7. Noise-induced changes of neuronal spontaneous activity in mice inferior colliculus brain slices.

    PubMed

    Basta, Dietmar; Ernest, Arne

    2004-09-30

    The inferior colliculus (IC) in vivo is reportedly subject to a noise-induced decrease of GABA-related inhibitory synaptic transmission accompanied by an amplitude increase of auditory evoked responses, a widening of tuning curves and a higher neuronal discharge rate at suprathreshold levels. However, other in vivo experiments which demonstrated constant neuronal auditory thresholds or unchanged spontaneous activity in the IC after noise exposure did not confirm those findings. Perhaps this can be the result of complex noise-induced interactions between different central auditory structures. It was, therefore, the aim of the present study to investigate the effects of noise exposure on the spontaneous electrical activity of single neurons in a slice preparation of the isolated mouse IC. Normal hearing mice were exposed to noise (10 kHz center frequency at 115 dB SPL for 3 h) at the age of 21 days under anesthesia (Ketamin/Rompun 10:1). After one week, auditory brainstem response (ABR) recordings and extracellular single-unit recordings from spontaneously active neurons within the IC slice were performed in noise-exposed and in normal hearing control mice. Noise-exposed animals showed a significant ABR threshold shift in the whole tested frequency range and a significant lower neuronal spontaneous activity in all investigated isofrequency laminae compared to controls. In both groups, the firing rate of 80% of IC neurons (approximately) increased significantly during the application of the GABA(A) receptor antagonist Bicucullin (10 microM). The present findings demonstrate a noise-related modulation of spontaneous activity in the IC, which possibly contribute to the generation of noise-induced tinnitus and hearing loss.

  8. Relative Contributions of Specific Activity Histories and Spontaneous Processes to Size Remodeling of Glutamatergic Synapses

    PubMed Central

    Dvorkin, Roman; Ziv, Noam E.

    2016-01-01

    The idea that synaptic properties are defined by specific pre- and postsynaptic activity histories is one of the oldest and most influential tenets of contemporary neuroscience. Recent studies also indicate, however, that synaptic properties often change spontaneously, even in the absence of specific activity patterns or any activity whatsoever. What, then, are the relative contributions of activity history-dependent and activity history-independent processes to changes synapses undergo? To compare the relative contributions of these processes, we imaged, in spontaneously active networks of cortical neurons, glutamatergic synapses formed between the same axons and neurons or dendrites under the assumption that their similar activity histories should result in similar size changes over timescales of days. The size covariance of such commonly innervated (CI) synapses was then compared to that of synapses formed by different axons (non-CI synapses) that differed in their activity histories. We found that the size covariance of CI synapses was greater than that of non-CI synapses; yet overall size covariance of CI synapses was rather modest. Moreover, momentary and time-averaged sizes of CI synapses correlated rather poorly, in perfect agreement with published electron microscopy-based measurements of mouse cortex synapses. A conservative estimate suggested that ~40% of the observed size remodeling was attributable to specific activity histories, whereas ~10% and ~50% were attributable to cell-wide and spontaneous, synapse-autonomous processes, respectively. These findings demonstrate that histories of naturally occurring activity patterns can direct glutamatergic synapse remodeling but also suggest that the contributions of spontaneous, possibly stochastic, processes are at least as great. PMID:27776122

  9. Introduction of a method for quantitative evaluation of spontaneous motor activity development with age in infants.

    PubMed

    Disselhorst-Klug, Catherine; Heinze, Franziska; Breitbach-Faller, Nico; Schmitz-Rode, Thomas; Rau, Günter

    2012-04-01

    Coordination between perception and action is required to interact with the environment successfully. This is already trained by very young infants who perform spontaneous movements to learn how their body interacts with the environment. The strategies used by the infants for this purpose change with age. Therefore, very early progresses in action control made by the infants can be investigated by monitoring the development of spontaneous motor activity. In this paper, an objective method is introduced, which allows the quantitative evaluation of the development of spontaneous motor activity in newborns. The introduced methodology is based on the acquisition of spontaneous movement trajectories of the feet by 3D movement analysis and subsequent calculation of specific movement parameters from them. With these movement-based parameters, it was possible to provide an objective description of age-dependent developmental steps in healthy newborns younger than 6 months. Furthermore, it has been shown that pathologies like infantile cerebral palsy influence development of motor activity significantly. Since the introduced methodology is objective and quantitative, it is suitable to monitor how newborns train their cognitive processes, which will enable them to cope with their environment by motor interaction.

  10. 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

  11. [Feeding activity, spontaneous activity and body core temperature of saddle-back tamarins (Saguinus fuscicollis)].

    PubMed

    Petry, H

    1991-02-01

    Eating behaviour and spontaneous activity (videometry) as well as deep body temperature (radiotelemetry) of 3 adult Saddle Back Tamarins (Saguinus fuscicollis) were investigated (singly housed, environmental temperature 28 degrees C, relative air humidity 60%, light 6:00-18:00 h, drinking-water and pelleted colony diet ad lib.). The experimental animals (1 female, 2 males; 3-8 years old), born in captivity, showed only some slight individual differences within their inborn species pattern, with regard to the 3 measured parameters. The monkeys were, like wild-living individuals, strictly light-active. They moved in the day-time nearly uninterrupted without special rhythm and slept remarkably deep through the whole night. Food intake occurred during the whole day with varying intensity. The body temperature of the 3 monkeys showed individual daytime-means between 38.8-39.9 degrees C, whereby the temperature fluctuated dependent on their moving activity with a range of about +/- 0.5 degrees C. At night the body temperature of the animals averaged between 35.9-36.6 degrees C.

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

    PubMed

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

    2012-04-01

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

  13. 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

  14. Pre & Postsynaptic Tuning of Action Potential Timing by Spontaneous GABAergic Activity

    PubMed Central

    Caillard, Olivier

    2011-01-01

    Frequency and timing of action potential discharge are key elements for coding and transfer of information between neurons. The nature and location of the synaptic contacts, the biophysical parameters of the receptor-operated channels and their kinetics of activation are major determinants of the firing behaviour of each individual neuron. Ultimately the intrinsic excitability of each neuron determines the input-output function. Here we evaluate the influence of spontaneous GABAergic synaptic activity on the timing of action potentials in Layer 2/3 pyramidal neurones in acute brain slices from the somatosensory cortex of young rats. Somatic dynamic current injection to mimic synaptic input events was employed, together with a simple computational model that reproduce subthreshold membrane properties. Besides the well-documented control of neuronal excitability, spontaneous background GABAergic activity has a major detrimental effect on spike timing. In fact, GABAA receptors tune the relationship between the excitability and fidelity of pyramidal neurons via a postsynaptic (the reversal potential for GABAA activity) and a presynaptic (the frequency of spontaneous activity) mechanism. GABAergic activity can decrease or increase the excitability of pyramidal neurones, depending on the difference between the reversal potential for GABAA receptors and the threshold for action potential. In contrast, spike time jitter can only be increased proportionally to the difference between these two membrane potentials. Changes in excitability by background GABAergic activity can therefore only be associated with deterioration of the reliability of spike timing. PMID:21789249

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. A novel method for counting spontaneous motor activity in the rat.

    PubMed

    Masuo, Y; Matsumoto, Y; Morita, S; Noguchi, J

    1997-10-01

    Motor activity is a good index for studying the effects of pharmacological agents. Previous investigations have measured spontaneous motor activity by counting the number of times that an animal interrupts a magnetic field or photocell beam. Quite recently, a novel activity-monitoring system, Supermex, was developed. In this system, a sensor detects the radiated body heat of an animal. The Supermex method enables an investigator to perform multi-channel measurement at low cost. Any size home cage may be used, as long as its geometry cannot block the beam's contact with the animal. Operation is very simple and sensitivity adjustment is not required after the sensor-mount position and height from the cage floor are fixed. In the present study we first used the Supermex system to examine the effects of intracerebroventricular (i.c.v.) administration of a known stimulant, thyrotropin-releasing hormone (TRH). Our results confirmed the suitability of this system for testing spontaneous motor activity. We further studied the effects of pituitary adenylate cyclase-activating polypeptide (PACAP) and its related peptide, vasoactive intestinal polypeptide (VIP), on spontaneous motor activity.

  20. Neuroelectrical decomposition of spontaneous brain activity measured with functional magnetic resonance imaging.

    PubMed

    Liu, Zhongming; de Zwart, Jacco A; Chang, Catie; Duan, Qi; van Gelderen, Peter; Duyn, Jeff H

    2014-11-01

    Spontaneous activity in the human brain occurs in complex spatiotemporal patterns that may reflect functionally specialized neural networks. Here, we propose a subspace analysis method to elucidate large-scale networks by the joint analysis of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data. The new approach is based on the notion that the neuroelectrical activity underlying the fMRI signal may have EEG spectral features that report on regional neuronal dynamics and interregional interactions. Applying this approach to resting healthy adults, we indeed found characteristic spectral signatures in the EEG correlates of spontaneous fMRI signals at individual brain regions as well as the temporal synchronization among widely distributed regions. These spectral signatures not only allowed us to parcel the brain into clusters that resembled the brain's established functional subdivision, but also offered important clues for disentangling the involvement of individual regions in fMRI network activity.

  1. Examination of synaptic vesicle recycling using FM dyes during evoked, spontaneous, and miniature synaptic activities.

    PubMed

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

    2014-03-31

    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.

  2. 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

  3. Effects of a hydrogen sulfide donor on spontaneous contractile activity of rat stomach and jejunum.

    PubMed

    Shafigullin, M Y; Zefirov, R A; Sabirullina, G I; Zefirov, A L; Sitdikova, G F

    2014-07-01

    We studied the effect of sodium hydrosulfite (NaHS), a donor of hydrogen sulfide (H2S), on spontaneous contractive activity of isolated preparations of rat stomach and jejunum under isometric conditions. NaHS in concentrations of 10-200 μM reduced the amplitude, tonic tension, and frequency of contractions of the preparations. Blockade of K(+) channels with a non-specific antagonist tetraethylammonium (10 mM) increased contraction amplitude in the stomach strip and jejunum segment. The effects of NaHS on all parameters of contractile activity of the stomach and jejunum were fully preserved against the background of tetraethylammonium application. These data suggest that H2S in physiologically relevant concentrations inhibited spontaneous contractile activity of smooth muscle cells in rat stomach and jejunum by reducing the amplitude and frequency of contractions and decreased tonic tension without affecting the function of voltage- and calcium-dependent K(+) channels.

  4. Human embryonic stem cell-derived neuronal cells form spontaneously active neuronal networks in vitro.

    PubMed

    Heikkilä, Teemu J; Ylä-Outinen, Laura; Tanskanen, Jarno M A; Lappalainen, Riikka S; Skottman, Heli; Suuronen, Riitta; Mikkonen, Jarno E; Hyttinen, Jari A K; Narkilahti, Susanna

    2009-07-01

    The production of functional human embryonic stem cell (hESC)-derived neuronal cells is critical for the application of hESCs in treating neurodegenerative disorders. To study the potential functionality of hESC-derived neurons, we cultured and monitored the development of hESC-derived neuronal networks on microelectrode arrays. Immunocytochemical studies revealed that these networks were positive for the neuronal marker proteins beta-tubulin(III) and microtubule-associated protein 2 (MAP-2). The hESC-derived neuronal networks were spontaneously active and exhibited a multitude of electrical impulse firing patterns. Synchronous bursts of electrical activity similar to those reported for hippocampal neurons and rodent embryonic stem cell-derived neuronal networks were recorded from the differentiated cultures until up to 4 months. The dependence of the observed neuronal network activity on sodium ion channels was examined using tetrodotoxin (TTX). Antagonists for the glutamate receptors NMDA [D(-)-2-amino-5-phosphonopentanoic acid] and AMPA/kainate [6-cyano-7-nitroquinoxaline-2,3-dione], and for GABAA receptors [(-)-bicuculline methiodide] modulated the spontaneous electrical activity, indicating that pharmacologically susceptible neuronal networks with functional synapses had been generated. The findings indicate that hESC-derived neuronal cells can generate spontaneously active networks with synchronous communication in vitro, and are therefore suitable for use in developmental and drug screening studies, as well as for regenerative medicine.

  5. The Wiring of Developing Sensory Circuits—From Patterned Spontaneous Activity to Synaptic Plasticity Mechanisms

    PubMed Central

    Leighton, Alexandra H.; Lohmann, Christian

    2016-01-01

    In order to accurately process incoming sensory stimuli, neurons must be organized into functional networks, with both genetic and environmental factors influencing the precise arrangement of connections between cells. Teasing apart the relative contributions of molecular guidance cues, spontaneous activity and visual experience during this maturation is on-going. During development of the sensory system, the first, rough organization of connections is created by molecular factors. These connections are then modulated by the intrinsically generated activity of neurons, even before the senses have become operational. Spontaneous waves of depolarizations sweep across the nervous system, placing them in a prime position to strengthen correct connections and weaken others, shaping synapses into a useful network. A large body of work now support the idea that, rather than being a mere side-effect of the system, spontaneous activity actually contains information which readies the nervous system so that, as soon as the senses become active, sensory information can be utilized by the animal. An example is the neonatal mouse. As soon as the eyelids first open, neurons in the cortex respond to visual information without the animal having previously encountered structured sensory input (Cang et al., 2005b; Rochefort et al., 2011; Zhang et al., 2012; Ko et al., 2013). In vivo imaging techniques have advanced considerably, allowing observation of the natural activity in the brain of living animals down to the level of the individual synapse. New (opto)genetic methods make it possible to subtly modulate the spatio-temporal properties of activity, aiding our understanding of how these characteristics relate to the function of spontaneous activity. Such experiments have had a huge impact on our knowledge by permitting direct testing of ideas about the plasticity mechanisms at play in the intact system, opening up a provocative range of fresh questions. Here, we intend to outline

  6. The Wiring of Developing Sensory Circuits—From Patterned Spontaneous Activity to Synaptic Plasticity Mechanisms

    PubMed Central

    Leighton, Alexandra H.; Lohmann, Christian

    2016-01-01

    In order to accurately process incoming sensory stimuli, neurons must be organized into functional networks, with both genetic and environmental factors influencing the precise arrangement of connections between cells. Teasing apart the relative contributions of molecular guidance cues, spontaneous activity and visual experience during this maturation is on-going. During development of the sensory system, the first, rough organization of connections is created by molecular factors. These connections are then modulated by the intrinsically generated activity of neurons, even before the senses have become operational. Spontaneous waves of depolarizations sweep across the nervous system, placing them in a prime position to strengthen correct connections and weaken others, shaping synapses into a useful network. A large body of work now support the idea that, rather than being a mere side-effect of the system, spontaneous activity actually contains information which readies the nervous system so that, as soon as the senses become active, sensory information can be utilized by the animal. An example is the neonatal mouse. As soon as the eyelids first open, neurons in the cortex respond to visual information without the animal having previously encountered structured sensory input (Cang et al., 2005b; Rochefort et al., 2011; Zhang et al., 2012; Ko et al., 2013). In vivo imaging techniques have advanced considerably, allowing observation of the natural activity in the brain of living animals down to the level of the individual synapse. New (opto)genetic methods make it possible to subtly modulate the spatio-temporal properties of activity, aiding our understanding of how these characteristics relate to the function of spontaneous activity. Such experiments have had a huge impact on our knowledge by permitting direct testing of ideas about the plasticity mechanisms at play in the intact system, opening up a provocative range of fresh questions. Here, we intend to outline

  7. 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

  8. 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

  9. Dopamine activation in Neuroticism as measured by spontaneous eye blink rate.

    PubMed

    Barbato, Giuseppe; Della Monica, Ciro; Costanzo, Antonio; De Padova, Vittoria

    2012-01-18

    Personality dimensions have been associated with different psychobiological systems. However, no agreement exists in literature on a specific role of a single neurotransmitter for each of the dimensions investigated. We studied the relationship of Neuroticism, Extraversion and Psychoticism as assessed by Eysenck Personality Inventory (EPI) with spontaneous eye blink rate (BR), a non-invasive measure of central dopamine activity. A total of sixty-three healthy subjects (40 females, 23 males, mean age 24.2±3.9) were studied. Spontaneous blink rate and time of blink suppression were assessed by EOG measurement. Levels of Extraversion and Neuroticism were inversely correlated. In contrast with previous findings, a significant correlation between blink rate measures and Neuroticism was found. No significant correlation between blink measures and either Extraversion, or Psychoticism were found. The results appear consistent with a lower threshold for activation in neuroticism as suggested by Eysenck's original model.

  10. 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

  11. Modulation of synaptic depression of the calyx of Held synapse by GABAB receptors and spontaneous activity

    PubMed Central

    Wang, Tiantian; Rusu, Silviu I; Hruskova, Bohdana; Turecek, Rostislav; Borst, J Gerard G

    2013-01-01

    The calyx of Held synapse of the medial nucleus of the trapezoid body is a giant axosomatic synapse in the auditory brainstem, which acts as a relay synapse showing little dependence of its synaptic strength on firing frequency. The main mechanism that is responsible for its resistance to synaptic depression is its large number of release sites with low release probability. Here, we investigated the contribution of presynaptic GABAB receptors and spontaneous activity to release probability both in vivo and in vitro in young-adult mice. Maximal activation of presynaptic GABAB receptors by baclofen reduced synaptic output by about 45% in whole-cell voltage clamp slice recordings, which was accompanied by a reduction in short-term depression. A similar reduction in transmission was observed when baclofen was applied in vivo by microiontophoresis during juxtacellular recordings using piggyback electrodes. No significant change in synaptic transmission was observed during application of the GABAB receptor antagonist CGP54626 both during in vivo and slice recordings, suggesting a low ambient GABA concentration. Interestingly, we observed that synapses with a high spontaneous frequency showed almost no synaptic depression during auditory stimulation, whereas synapses with a low spontaneous frequency did depress during noise bursts. Our data thus suggest that spontaneous firing can tonically reduce release probability in vivo. In addition, our data show that the ambient GABA concentration in the auditory brainstem is too low to activate the GABAB receptor at the calyx of Held significantly, but that activation of GABAB receptors can reduce sound-evoked synaptic depression. PMID:23940376

  12. Altered spontaneous neural activity in the occipital face area reflects behavioral deficits in developmental prosopagnosia.

    PubMed

    Zhao, Yuanfang; Li, Jingguang; Liu, Xiqin; Song, Yiying; Wang, Ruosi; Yang, Zetian; Liu, Jia

    2016-08-01

    Individuals with developmental prosopagnosia (DP) exhibit severe difficulties in recognizing faces and to a lesser extent, also exhibit difficulties in recognizing non-face objects. We used fMRI to investigate whether these behavioral deficits could be accounted for by altered spontaneous neural activity. Two aspects of spontaneous neural activity were measured: the intensity of neural activity in a voxel indexed by the fractional amplitude of spontaneous low-frequency fluctuations (fALFF), and the connectivity of a voxel to neighboring voxels indexed by regional homogeneity (ReHo). Compared with normal adults, both the fALFF and ReHo values within the right occipital face area (rOFA) were significantly reduced in DP subjects. Follow-up studies on the normal adults revealed that these two measures indicated further functional division of labor within the rOFA. The fALFF in the rOFA was positively correlated with behavioral performance in recognition of non-face objects, whereas ReHo in the rOFA was positively correlated with processing of faces. When considered together, the altered fALFF and ReHo within the same region (rOFA) may account for the comorbid deficits in both face and object recognition in DPs, whereas the functional division of labor in these two measures helps to explain the relative independency of deficits in face recognition and object recognition in DP. PMID:27475965

  13. 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

  14. Working memory encoding and maintenance deficits in schizophrenia: neural evidence for activation and deactivation abnormalities.

    PubMed

    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.

  15. 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

  16. 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

  17. [Lactate dehydrogenase and Krebs cycle enzyme activity in rat liver during the growth of transplanted and spontaneous tumors].

    PubMed

    Morozkina, T S

    1978-03-01

    Certain distinctions in the mouse and rat liver responses to transplanted and spontaneous tumours have been discovered at the initial periods of their growth. The most pronounced changes (the mosaic distribution of enzymatic activity in the lobe) are observed in the case of spontaneous tumours. Activities the Krebs cycle enzymes, especially of NAD-dependent enzymes are seen inhibited in the tumour-bearing liver at the terminal periods of growth of both spontaneous and transplanted tumours; lactate dehydrogenase activity increases (with the exception of mitochondrial lactate dehydrogenase in the rat liver with transplanted sarcomas). PMID:684845

  18. 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.

  19. 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

  20. Calcitonin Gene-Related Peptide Receptor Blocker Inhibits Spontaneous Activity of Human Ureter.

    PubMed

    Jankovic, Slobodan M; Jankovic, Snezana V; Stojadinovic, Dobrivoje; Stojadinovic, Miroslav; Djuric, Janko M; Stojic, Isidora

    2015-01-01

    Calcitonin gene-related peptide (CGRP) is present in nerve fibers that innervate the human ureter and may have important influence on the motility of this organ. The aim of our study was to investigate whether CGRP could affect the motility of an isolated human ureter. The tension and intraluminal pressure of the isolated ureteral segments were recorded and registered on a personal computer. Both phasic and tonic contractions of the isolated preparations were measured as area under the tension or pressure recordings. CGRP and CGRP fragment 8-37 were separately added to the organ baths in a cumulative way, thereby gradually increasing their concentration in the baths' solution. Alpha-CGRP did not affect either phasic, spontaneous activity or tone of isolated ureteral segments, as measured by both tension and intraluminal pressure. On the other hand, CGRP 8-37 caused concentration-dependent inhibition of spontaneous contractions of the isolated ureteral segments. PMID:26305057

  1. Psychobehavioral validity of self-reported symptoms based on spontaneous physical activity.

    PubMed

    Kim, Jinhyuk; Nakamura, Toru; Kikuchi, Hiroe; Yamamoto, Yoshiharu

    2015-08-01

    A limitation of self-reports is the presence of recall biases including retrospective distortions of the respondents' experiences. To overcome this concern, ecological momentary assessment (EMA) and day reconstruction method (DRM) have recently been developed. Very recently, we reported the psychobehavioral validity of within-individual temporal variations in momentary depressive mood recorded with EMA by examining co-variant properties with spontaneous physical activity as the external criteria. However, the validity of DRM in this context has not been objectively examined yet. Therefore, in this study, we examined the psychobehavioral validity of DRM by examining temporal associations with spontaneous physical activity and then showed the difference from EMA. Twenty-two healthy undergraduates wore a watch-type computer for two consecutive days and recorded self-reported symptoms (fatigue, depressive mood, and anxious mood) by EMA. They also recorded the symptoms afterward according to the series of behavioral episodes they reconstructed (DRM) about the same days. Physical activity was also obtained using an actigraph built into the watch-type computer. Multilevel analysis showed the significant association between depressive mood recorded with EMA and local statistics (mean activity levels calculated from 60 min data length) of physical activity around EMA recordings. However, depressive mood recorded with DRM had no significant association with physical activity. As for fatigue and anxious mood, none of the methods showed significant associations with the local statistics of physical activity. These results imply that depressive mood recorded with EMA would include psychobehavioral information which cannot be captured with DRM.

  2. 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...

  3. Dampening Spontaneous Activity Improves the Light Sensitivity and Spatial Acuity of Optogenetic Retinal Prosthetic Responses.

    PubMed

    Barrett, John Martin; Hilgen, Gerrit; Sernagor, Evelyne

    2016-09-21

    Retinitis pigmentosa is a progressive retinal dystrophy that causes irreversible visual impairment and blindness. Retinal prostheses currently represent the only clinically available vision-restoring treatment, but the quality of vision returned remains poor. Recently, it has been suggested that the pathological spontaneous hyperactivity present in dystrophic retinas may contribute to the poor quality of vision returned by retinal prosthetics by reducing the signal-to-noise ratio of prosthetic responses. Here, we investigated to what extent blocking this hyperactivity can improve optogenetic retinal prosthetic responses. We recorded activity from channelrhodopsin-expressing retinal ganglion cells in retinal wholemounts in a mouse model of retinitis pigmentosa. Sophisticated stimuli, inspired by those used in clinical visual assessment, were used to assess light sensitivity, contrast sensitivity and spatial acuity of optogenetic responses; in all cases these were improved after blocking spontaneous hyperactivity using meclofenamic acid, a gap junction blocker. Our results suggest that this approach significantly improves the quality of vision returned by retinal prosthetics, paving the way to novel clinical applications. Moreover, the improvements in sensitivity achieved by blocking spontaneous hyperactivity may extend the dynamic range of optogenetic retinal prostheses, allowing them to be used at lower light intensities such as those encountered in everyday life.

  4. Dampening Spontaneous Activity Improves the Light Sensitivity and Spatial Acuity of Optogenetic Retinal Prosthetic Responses.

    PubMed

    Barrett, John Martin; Hilgen, Gerrit; Sernagor, Evelyne

    2016-01-01

    Retinitis pigmentosa is a progressive retinal dystrophy that causes irreversible visual impairment and blindness. Retinal prostheses currently represent the only clinically available vision-restoring treatment, but the quality of vision returned remains poor. Recently, it has been suggested that the pathological spontaneous hyperactivity present in dystrophic retinas may contribute to the poor quality of vision returned by retinal prosthetics by reducing the signal-to-noise ratio of prosthetic responses. Here, we investigated to what extent blocking this hyperactivity can improve optogenetic retinal prosthetic responses. We recorded activity from channelrhodopsin-expressing retinal ganglion cells in retinal wholemounts in a mouse model of retinitis pigmentosa. Sophisticated stimuli, inspired by those used in clinical visual assessment, were used to assess light sensitivity, contrast sensitivity and spatial acuity of optogenetic responses; in all cases these were improved after blocking spontaneous hyperactivity using meclofenamic acid, a gap junction blocker. Our results suggest that this approach significantly improves the quality of vision returned by retinal prosthetics, paving the way to novel clinical applications. Moreover, the improvements in sensitivity achieved by blocking spontaneous hyperactivity may extend the dynamic range of optogenetic retinal prostheses, allowing them to be used at lower light intensities such as those encountered in everyday life. PMID:27650332

  5. Dampening Spontaneous Activity Improves the Light Sensitivity and Spatial Acuity of Optogenetic Retinal Prosthetic Responses

    PubMed Central

    Barrett, John Martin; Hilgen, Gerrit; Sernagor, Evelyne

    2016-01-01

    Retinitis pigmentosa is a progressive retinal dystrophy that causes irreversible visual impairment and blindness. Retinal prostheses currently represent the only clinically available vision-restoring treatment, but the quality of vision returned remains poor. Recently, it has been suggested that the pathological spontaneous hyperactivity present in dystrophic retinas may contribute to the poor quality of vision returned by retinal prosthetics by reducing the signal-to-noise ratio of prosthetic responses. Here, we investigated to what extent blocking this hyperactivity can improve optogenetic retinal prosthetic responses. We recorded activity from channelrhodopsin-expressing retinal ganglion cells in retinal wholemounts in a mouse model of retinitis pigmentosa. Sophisticated stimuli, inspired by those used in clinical visual assessment, were used to assess light sensitivity, contrast sensitivity and spatial acuity of optogenetic responses; in all cases these were improved after blocking spontaneous hyperactivity using meclofenamic acid, a gap junction blocker. Our results suggest that this approach significantly improves the quality of vision returned by retinal prosthetics, paving the way to novel clinical applications. Moreover, the improvements in sensitivity achieved by blocking spontaneous hyperactivity may extend the dynamic range of optogenetic retinal prostheses, allowing them to be used at lower light intensities such as those encountered in everyday life. PMID:27650332

  6. Spontaneous Activity, Economy of Activity, and Resistance to Diet-Induced Obesity in Rats Bred for High Intrinsic Aerobic Capacity

    PubMed Central

    Novak, Colleen M.; Escande, Carlos; Burghardt, Paul R.; Zhang, Minzhi; Barbosa, Maria Teresa; Chini, Eduardo N.; Britton, Steven L.; Koch, Lauren G.; Akil, Huda; Levine, James A.

    2010-01-01

    Though obesity is common, some people remain resistant to weight gain even in an obesogenic environment. The propensity to remain lean may be partly associated with high endurance capacity along with high spontaneous physical activity and the energy expenditure of activity, called non-exercise activity thermogenesis (NEAT). Previous studies have shown that high-capacity running rats (HCR) are lean compared to low-capacity runners (LCR), which are susceptible to cardiovascular disease and metabolic syndrome. Here, we examine the effect of diet on spontaneous activity and NEAT, as well as potential mechanisms underlying these traits, in rats selectively bred for high or low intrinsic aerobic endurance capacity. Compared to LCR, HCR were resistant to the sizeable increases in body mass and fat mass induced by a high-fat diet; HCR also had lower levels of circulating leptin. HCR were consistently more active than LCR, and had lower fuel economy of activity, regardless of diet. Nonetheless, both HCR and LCR showed a similar decrease in daily activity levels after high-fat feeding, as well as decreases in hypothalamic orexin-A content. The HCR were more sensitive to the NEAT-activating effects of intra-paraventricular orexin-A compared to LCR, especially after high-fat feeding. Lastly, levels of cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) in the skeletal muscle of HCR were consistently higher than LCR, and the high-fat diet decreased skeletal muscle PEPCK-C in both groups of rats. Differences in muscle PEPCK were not secondary to the differing amount of activity. This suggests the possibility that intrinsic differences in physical activity levels may originate at the level of the skeletal muscle, which could alter brain responsiveness to neuropeptides and other factors that regulate spontaneous daily activity and NEAT. PMID:20350549

  7. 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.

  8. 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

  9. Hydrodynamic instabilities provide a generic route to spontaneous biomimetic oscillations in chemomechanically active filaments

    PubMed Central

    Laskar, Abhrajit; Singh, Rajeev; Ghose, Somdeb; Jayaraman, Gayathri; Kumar, P. B. Sunil; Adhikari, R.

    2013-01-01

    Non-equilibrium processes which convert chemical energy into mechanical motion enable the motility of organisms. Bundles of inextensible filaments driven by energy transduction of molecular motors form essential components of micron-scale motility engines like cilia and flagella. The mimicry of cilia-like motion in recent experiments on synthetic active filaments supports the idea that generic physical mechanisms may be sufficient to generate such motion. Here we show, theoretically, that the competition between the destabilising effect of hydrodynamic interactions induced by force-free and torque-free chemomechanically active flows, and the stabilising effect of nonlinear elasticity, provides a generic route to spontaneous oscillations in active filaments. These oscillations, reminiscent of prokaryotic and eukaryotic flagellar motion, are obtained without having to invoke structural complexity or biochemical regulation. This minimality implies that biomimetic oscillations, previously observed only in complex bundles of active filaments, can be replicated in simple chains of generic chemomechanically active beads. PMID:23752497

  10. Hydrodynamic instabilities provide a generic route to spontaneous biomimetic oscillations in chemomechanically active filaments

    NASA Astrophysics Data System (ADS)

    Laskar, Abhrajit; Singh, Rajeev; Ghose, Somdeb; Jayaraman, Gayathri; Kumar, P. B. Sunil; Adhikari, R.

    2013-06-01

    Non-equilibrium processes which convert chemical energy into mechanical motion enable the motility of organisms. Bundles of inextensible filaments driven by energy transduction of molecular motors form essential components of micron-scale motility engines like cilia and flagella. The mimicry of cilia-like motion in recent experiments on synthetic active filaments supports the idea that generic physical mechanisms may be sufficient to generate such motion. Here we show, theoretically, that the competition between the destabilising effect of hydrodynamic interactions induced by force-free and torque-free chemomechanically active flows, and the stabilising effect of nonlinear elasticity, provides a generic route to spontaneous oscillations in active filaments. These oscillations, reminiscent of prokaryotic and eukaryotic flagellar motion, are obtained without having to invoke structural complexity or biochemical regulation. This minimality implies that biomimetic oscillations, previously observed only in complex bundles of active filaments, can be replicated in simple chains of generic chemomechanically active beads.

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

    PubMed Central

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

    2015-01-01

    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

  12. 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

  13. 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

  14. Probabilistic secretion of quanta: spontaneous release at active zones of varicosities, boutons, and endplates.

    PubMed Central

    Bennett, M R; Gibson, W G; Robinson, J

    1995-01-01

    The amplitude-frequency histogram of spontaneous miniature endplate potentials follows a Gaussian distribution at mature endplates. This distribution gives the mean and variance of the quantum of transmitter. According to the vesicle hypothesis, this quantum is due to exocytosis of the contents of a single synaptic vesicle. Multimodal amplitude-frequency histograms are observed in varying degrees at developing endplates and at peripheral and central synapses, each of which has a specific active zone structure. These multimodal histograms may be due to the near synchronous exocytosis of more than one vesicle. In the present work, a theoretical treatment is given of the rise of intraterminal calcium after the stochastic opening of a calcium channel within a particular active zone geometry. The stochastic interaction of this calcium with the vesicle-associated proteins involved in exocytosis is then used to calculate the probability of quantal secretions from one or several vesicles at each active zone type. It is shown that this procedure can account for multiquantal spontaneous release that may occur at varicosities and boutons, compared with that at the active zones of motor nerve terminals. PMID:7669909

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

    PubMed

    Ge, Hong-You; Fernández-de-Las-Peñas, César; Yue, Shou-Wei

    2011-03-25

    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.

  16. 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

  17. 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

  18. Reproduction of overall spontaneous pain pattern by manual stimulation of active myofascial trigger points in fibromyalgia patients

    PubMed Central

    2011-01-01

    Introduction It has previously been reported that local and referred pain from active myofascial trigger points (MTPs) in the neck and shoulder region contribute to fibromyalgia (FM) pain and that the pain pattern induced from active MTPs can reproduce parts of the spontaneous clinical FM pain pattern. The current study investigated whether the overall spontaneous FM pain pattern can be reproduced by local and referred pain from active MTPs located in different muscles. Methods A spontaneous pain pattern in FM was recorded in 30 FM patients and 30 healthy subjects served as controls. Local and referred pain patterns induced from active (patients) and latent (controls) MTPs were recorded following manual stimulation. The existence of MTPs was confirmed by intramuscular electromyographical registration of spontaneous electrical activity. Results Local and referred pain areas induced from key active MTPs in FM were larger than pain areas from latent MTPs in healthy controls (P < 0.001), but were similar to the overall spontaneous FM pain area in FM (P > 0.05). The induced pain area was positively associated with current spontaneous pain intensity in FM (P < 0.01). The locations of key active MTPs in FM patients were found to have latent MTPs in healthy subjects. The muscles containing key active MTPs in FM are often observed in the muscles of extensor digitorum, trapezius, infraspinatus in the upper part of the body and of quadratus lumborum, gluteus medius in the lower part of the body. Conclusions The overall spontaneous FM pain pattern can be reproduced by mechanical stimulation of active MTPs located in different muscles, suggesting that fibromyalgia pain is largely composed of pain arising from muscle pain and spasm. Targeting active MTPs and related perpetuating factors may be an important strategy in FM pain control. Trial registration ISRCTN ISRCTN43167547. PMID:21426569

  19. 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

  20. Spontaneous symmetry breaking in active droplets provides a generic route to motility

    PubMed Central

    Tjhung, Elsen; Marenduzzo, Davide; Cates, Michael E.

    2012-01-01

    We explore a generic mechanism whereby a droplet of active matter acquires motility by the spontaneous breakdown of a discrete symmetry. The model we study offers a simple representation of a “cell extract” comprising, e.g., a droplet of actomyosin solution. (Such extracts are used experimentally to model the cytoskeleton). Actomyosin is an active gel whose polarity describes the mean sense of alignment of actin fibres. In the absence of polymerization and depolymerization processes (‘treadmilling’), the gel’s dynamics arises solely from the contractile motion of myosin motors; this should be unchanged when polarity is inverted. Our results suggest that motility can arise in the absence of treadmilling, by spontaneous symmetry breaking (SSB) of polarity inversion symmetry. Adapting our model to wall-bound cells in two dimensions, we find that as wall friction is reduced, treadmilling-induced motility falls but SSB-mediated motility rises. The latter might therefore be crucial in three dimensions where frictional forces are likely to be modest. At a supracellular level, the same generic mechanism can impart motility to aggregates of nonmotile but active bacteria; we show that SSB in this (extensile) case leads generically to rotational as well as translational motion. PMID:22797894

  1. 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

  2. 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

  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. Abnormal activation of the motor cortical network in idiopathic scoliosis demonstrated by functional MRI.

    PubMed

    Domenech, Julio; García-Martí, G; Martí-Bonmatí, L; Barrios, C; Tormos, J M; Pascual-Leone, A

    2011-07-01

    The aetiology of idiopathic scoliosis (IS) remains unknown, but there is growing support for the possibility of an underlying neurological disorder. Functional magnetic resonance imaging (fMRI) can characterize the abnormal activation of the sensorimotor brain network in movement disorders and could provide further insights into the neuropathogenesis of IS. Twenty subjects were included in the study; 10 adolescents with IS (mean age of 15.2, 8 girls and 2 boys) and 10 age-matched healthy controls. The average Cobb angle of the primary curve in the IS patients was 35° (range 27°-55°). All participants underwent a block-design fMRI experiment in a 1.5-Tesla MRI scanner to explore cortical activation following a simple motor task. Rest periods alternated with activation periods during which participants were required to open and close their hand at an internally paced rate of approximately 1 Hz. Data were analyzed with Statistical Parametric Mapping (SPM5) including age, sex and laterality as nuisance variables to minimise the presence of bias in the results. Compared to controls, IS patients showed significant increases in blood oxygenation level dependent (BOLD) activity in contralateral supplementary motor area when performing the motor task with either hand. No significant differences were observed when testing between groups in the functional activation in the primary motor cortex, premotor cortex and somatosensory cortex. Additionally, the IS group showed a greater interhemispheric asymmetry index than the control group (0.30 vs. 0.13, p < 0.001). This study demonstrates an abnormal pattern of brain activation in secondary motor areas during movement execution in patients with IS. These findings support the hypothesis that a sensorimotor integration disorder underlies the pathogenesis of IS.

  5. Paliperidone increases spontaneous and evoked firing of mesocortical dopaminergic neurons by activating a hyperpolarization-activated inward current.

    PubMed

    Dong, Haiman; Wang, Qian; Zhu, Dexiao; Gao, Fei; Wang, Hui; Bao, Lihua; Zhang, Jing; Hu, Yanlai; Ding, Zhaoxi; Sun, Jinhao

    2016-10-01

    Mesocortical dopaminergic (DA) subtype neurons specifically project to the prefrontal cortex, which is closely related with schizophrenia. Mesocortical DA neurons have unique physiological characteristics that are different from those of mesostriatal and mesolimbic DA neurons. Paliperidone, an atypical antipsychotic, is currently used to treat schizophrenia and has better therapeutic effects than typical antipsychotics. However, the underlying physiological mechanism remains unclear. To explore the effects of paliperidone on mesocortical DA neuron activity, here, we retrogradely labeled these cells with fluorescent microsphere retrobeads, and the electrophysiological changes were recorded in whole-cell recordings in rat midbrain slices with or without paliperidone. The data showed that paliperidone (20μmol/L) increased the spontaneous firing rates of labeled mesocortical neurons (P<0.05). Moreover, paliperidone also increased the frequency of evoked action potentials by current injection stimulation (P<0.05), whereas the accompanying amplitude decreased. Furthermore, to explore the mechanisms of paliperidone's effect, Ih currents were detected, and the results showed that hyperpolarizing voltage pulses evoked instantaneous Ih inward currents and paliperidone increased the maximum Ih current. In addition, paliperidone decreased the spontaneous inhibitory postsynaptic currents. Thus, paliperidone increased the spontaneous and evoked firing of mesocortical neurons, possibly by activating the Ih inward current and reducing the inhibitory synaptic transmission, which provides an underlying mechanism of paliperidone's application in schizophrenia. PMID:27435059

  6. Respiratory-related discharge pattern of sympathetic nerve activity in the spontaneously hypertensive rat.

    PubMed Central

    Czyzyk-Krzeska, M F; Trzebski, A

    1990-01-01

    1. Synchronization of spontaneous sympathetic discharge during the respiratory cycle was studied in the cervical and renal nerves of vagotomized, normotensive Wistar-Kyoto rats (WKYs) and age-matched spontaneously hypertensive rats (SHRs). Phrenic nerve discharge was used as an index of central inspiratory activity. 2. In normotensive Wistar-Kyoto rats depression of sympathetic activity appeared at the onset of inspiration reaching a minimum at mid-inspiration. Peak maximal sympathetic discharge corresponded to postinspiratory phase; a second increase sometimes appeared in late expiration. Variations of respiratory frequency over wide range of experimental conditions by hypoxia, hyperoxia, hyper- or hypocapnia and transection of carotid sinus nerves did not affect this pattern. 3. In SHRs the respiratory-phase-related timing of sympathetic discharge was variable. In normoxia, the maximal sympathetic activity occurred in late inspiration, preceded by short depression at early inspiration and followed by postinspiratory depression. A second increase in sympathetic activity was observed in mid-expiration. 4. The pattern of respiratory phase modulated sympathetic activity in SHRs was altered by hypoxic stimulation of the peripheral chemoreceptors. The early inspiratory depression of sympathetic activity was substantially prolonged and the maximal sympathetic discharge was shifted from inspiration to early expiration. This effect was abolished after carotid sinus nerves had been cut. 5. Hypercapnic stimulation of central chemoreceptors in SHRs with carotid sinus nerves cut did not influence the timing of the sympathetic activity in relation to the respiratory phase, though the magnitude of rhythmical sympathetic discharges was increased. 6. We discuss the possibility that altered synchronization between central respiratory drive and sympathetic neuronal system may contribute to the neurogenic mechanisms of arterial hypertension in SHRs. PMID:2231403

  7. 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.

  8. 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.

  9. 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

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

    PubMed

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

    2015-12-15

    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.

  11. Multichannel detrended fluctuation analysis reveals synchronized patterns of spontaneous spinal activity in anesthetized cats.

    PubMed

    Rodríguez, Erika E; Hernández-Lemus, Enrique; Itzá-Ortiz, Benjamín A; Jiménez, Ismael; Rudomín, Pablo

    2011-01-01

    The analysis of the interaction and synchronization of relatively large ensembles of neurons is fundamental for the understanding of complex functions of the nervous system. It is known that the temporal synchronization of neural ensembles is involved in the generation of specific motor, sensory or cognitive processes. Also, the intersegmental coherence of spinal spontaneous activity may indicate the existence of synaptic neural pathways between different pairs of lumbar segments. In this study we present a multichannel version of the detrended fluctuation analysis method (mDFA) to analyze the correlation dynamics of spontaneous spinal activity (SSA) from time series analysis. This method together with the classical detrended fluctuation analysis (DFA) were used to find out whether the SSA recorded in one or several segments in the spinal cord of the anesthetized cat occurs either in a random or in an organized manner. Our results are consistent with a non-random organization of the sets of neurons involved in the generation of spontaneous cord dorsum potentials (CDPs) recorded either from one lumbar segment (DFA-α mean = 1.04[Formula: see text]0.09) or simultaneously from several lumbar segments (mDFA-α mean = 1.01[Formula: see text]0.06), where α = 0.5 indicates randomness while α = 0.5 indicates long-term correlations. To test the sensitivity of the mDFA method we also examined the effects of small spinal lesions aimed to partially interrupt connectivity between neighboring lumbosacral segments. We found that the synchronization and correlation between the CDPs recorded from the L5 and L6 segments in both sides of the spinal cord were reduced when a lesion comprising the left dorsal quadrant was performed between the segments L5 and L6 (mDFA-[Formula: see text] = 0.992 as compared to initial conditions mDFA-α = 1.186). The synchronization and correlation were reduced even further after a similar additional right spinal lesion (mDFA-α = 0.924). In contrast

  12. Multichannel detrended fluctuation analysis reveals synchronized patterns of spontaneous spinal activity in anesthetized cats.

    PubMed

    Rodríguez, Erika E; Hernández-Lemus, Enrique; Itzá-Ortiz, Benjamín A; Jiménez, Ismael; Rudomín, Pablo

    2011-01-01

    The analysis of the interaction and synchronization of relatively large ensembles of neurons is fundamental for the understanding of complex functions of the nervous system. It is known that the temporal synchronization of neural ensembles is involved in the generation of specific motor, sensory or cognitive processes. Also, the intersegmental coherence of spinal spontaneous activity may indicate the existence of synaptic neural pathways between different pairs of lumbar segments. In this study we present a multichannel version of the detrended fluctuation analysis method (mDFA) to analyze the correlation dynamics of spontaneous spinal activity (SSA) from time series analysis. This method together with the classical detrended fluctuation analysis (DFA) were used to find out whether the SSA recorded in one or several segments in the spinal cord of the anesthetized cat occurs either in a random or in an organized manner. Our results are consistent with a non-random organization of the sets of neurons involved in the generation of spontaneous cord dorsum potentials (CDPs) recorded either from one lumbar segment (DFA-α mean = 1.04[Formula: see text]0.09) or simultaneously from several lumbar segments (mDFA-α mean = 1.01[Formula: see text]0.06), where α = 0.5 indicates randomness while α = 0.5 indicates long-term correlations. To test the sensitivity of the mDFA method we also examined the effects of small spinal lesions aimed to partially interrupt connectivity between neighboring lumbosacral segments. We found that the synchronization and correlation between the CDPs recorded from the L5 and L6 segments in both sides of the spinal cord were reduced when a lesion comprising the left dorsal quadrant was performed between the segments L5 and L6 (mDFA-[Formula: see text] = 0.992 as compared to initial conditions mDFA-α = 1.186). The synchronization and correlation were reduced even further after a similar additional right spinal lesion (mDFA-α = 0.924). In contrast

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

    PubMed

    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

    2015-12-15

    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.

  14. 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

  15. Spontaneous periodic hypothermia.

    PubMed

    Kloos, R T

    1995-09-01

    Spontaneous periodic hypothermia is a rare syndrome of recurrent, centrally mediated hypothermia without an identifiable systemic cause or brain lesion. Most patients defend a temporarily lowered temperature "set point" during episodes of hypothermia, despite manifesting many well-known systemic consequences of core temperature hypothermia. No case of death directly attributable to an episode of spontaneous periodic hypothermia has been reported, although many of the serious systemic effects of hypothermia have been documented in these cases, so it is not unlikely that death may occur. The syndrome's cause, and that of Shapiro syndrome, remains unknown. Pharmacologic trials to date have been only modestly successful. Anticonvulsant agents, clonidine, and cyproheptadine appear the most likely to succeed, with cyproheptadine being a reasonable first choice. Given that the term "spontaneous periodic hypothermia" describes a syndrome, and not a pathophysiologic mechanism, it is likely to encompass a common eventuality, arrived at via several different pathways. One can postulate mechanisms such as structural abnormalities, trauma, infection, irritation, and degeneration involving strategic locations which create a focus for epileptic or other periodic dysfunction whose scope involves the centers for thermoregulation. The existence of 2 distinct, oppositional thermoregulatory centers would allow for speculation of similar mechanisms accounting for cases of both periodic hypo- and hyperthermia (61). Postmortem data regarding the hypothalamic and surrounding areas from future cases of Shapiro syndrome and spontaneous periodic hypothermia would be of great interest. Further, more sensitive in vivo testing methods are clearly needed. The role of PET or single photon emission computed tomography (SPECT) with technetium 99m-labeled hexamethylpropylene amine oxime (Tc 99m HMPAO) performed acutely during an episode remains to be characterized (64, 103, 105). The term

  16. 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.

  17. 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

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

    PubMed

    Gaheer, Rajinder Singh; Hawkins, Amanda

    2010-07-13

    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.

  19. 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.

  20. [Changes in the brain spontaneous bioelectrical activity during transcranial electrical and electromagnetic stimulation].

    PubMed

    Sharova, E V; Mel'nikov, A V; Novikova, M R; Kulikov, M A; Grechenko, T N; Shekhter, E D; Zaslavskiĭ, A Iu

    2006-01-01

    In order to study systemic brain reactions on transcranial electrical or electromagnetic medical stimulation and specify the neurophysiological criteria of its efficiency, comparative clinical and experimental examination was performed with the analysis of spontaneous bioelectric activity and behavioral or clinical parameters. We examined 6 patients with prolonged posttraumatic unconsciousness states treated with electrical stimulation and 17 intact Wistar rats subjected to electromagnetic stimulation of the brain. The effect of the transcranial stimulation was shown to depend on the initial level of the intercentral interactions of brain bioelectrical activity, estimated by the EEG coherence. Hypersynchronization of biopotentials as the main element of the brain reactivity can be the most useful for the rehabilitation of patients with cerebral pathology in cases of initially lowered level of the intercentral interactions in the absence of pathologically strengthened functional connections.

  1. Proteinase-activated receptor-1 activation presynaptically enhances spontaneous glutamatergic excitatory transmission in adult rat substantia gelatinosa neurons.

    PubMed

    Fujita, T; Liu, T; Nakatsuka, T; Kumamoto, E

    2009-07-01

    Proteinase-activated receptors (PARs) have a unique activation mechanism in that a proteolytically exposed N-terminal region acts as a tethered ligand. A potential impact of PAR on sensory processing has not been fully examined yet. Here we report that synthetic peptides with sequences corresponding to PAR ligands enhance glutamatergic excitatory transmission in substantia gelatinosa (SG) neurons of adult rat spinal cord slices by using the whole cell patch-clamp technique. The frequency of spontaneous excitatory postsynaptic current (EPSC) was increased by PAR-1 agonist SFLLRN-NH2 (by 47% at 1 microM) with small increases by PAR-2 and -4 agonists (SLIGKV-NH2 and GYPGQV-OH, respectively; at >3 microM); there was no change in its amplitude or in holding current at -70 mV. The PAR-1 peptide action was inhibited by PAR-1 antagonist YFLLRNP-OH. TFLLR-NH2, an agonist which is more selective to PAR-1 than SFLLRN-NH2, dose-dependently increased spontaneous EPSC frequency (EC50=0.32 microM). A similar presynaptic effect was produced by PAR-1 activating proteinase thrombin in a manner sensitive to YFLLRNP-OH. The PAR-1 peptide action was resistant to tetrodotoxin and inhibited in Ca2+-free solution. Primary-afferent monosynaptically evoked EPSC amplitudes were unaffected by PAR-1 agonist. These results indicate that PAR-1 activation increases the spontaneous release of L-glutamate onto SG neurons from nerve terminals in a manner dependent on extracellular Ca2+. Considering that sensory processing within the SG plays a pivotal role in regulating nociceptive transmission to the spinal dorsal horn, the PAR-1-mediated glutamatergic transmission enhancement could be involved in a positive modulation of nociceptive transmission. PMID:19420120

  2. 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.

  3. 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

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

    NASA Astrophysics Data System (ADS)

    Han, Lijuan; Neiman, Alexander B.

    2010-04-01

    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 mechanoelectrical 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 bidirectional 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.

  5. 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

  6. 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.

  7. 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

  8. The visual perception of natural motion: abnormal task-related neural activity in DYT1 dystonia.

    PubMed

    Sako, Wataru; Fujita, Koji; Vo, An; Rucker, Janet C; Rizzo, John-Ross; Niethammer, Martin; Carbon, Maren; Bressman, Susan B; Uluğ, Aziz M; Eidelberg, David

    2015-12-01

    Although primary dystonia is defined by its characteristic motor manifestations, non-motor signs and symptoms have increasingly been recognized in this disorder. Recent neuroimaging studies have related the motor features of primary dystonia to connectivity changes in cerebello-thalamo-cortical pathways. It is not known, however, whether the non-motor manifestations of the disorder are associated with similar circuit abnormalities. To explore this possibility, we used functional magnetic resonance imaging to study primary dystonia and healthy volunteer subjects while they performed a motion perception task in which elliptical target trajectories were visually tracked on a computer screen. Prior functional magnetic resonance imaging studies of healthy subjects performing this task have revealed selective activation of motor regions during the perception of 'natural' versus 'unnatural' motion (defined respectively as trajectories with kinematic properties that either comply with or violate the two-thirds power law of motion). Several regions with significant connectivity changes in primary dystonia were situated in proximity to normal motion perception pathways, suggesting that abnormalities of these circuits may also be present in this disorder. To determine whether activation responses to natural versus unnatural motion in primary dystonia differ from normal, we used functional magnetic resonance imaging to study 10 DYT1 dystonia and 10 healthy control subjects at rest and during the perception of 'natural' and 'unnatural' motion. Both groups exhibited significant activation changes across perceptual conditions in the cerebellum, pons, and subthalamic nucleus. The two groups differed, however, in their responses to 'natural' versus 'unnatural' motion in these regions. In healthy subjects, regional activation was greater during the perception of natural (versus unnatural) motion (P < 0.05). By contrast, in DYT1 dystonia subjects, activation was relatively greater

  9. Regional wall motion abnormality in apical ballooning syndrome (Takotsubo/stress cardiomyopathy): importance of biplane left ventriculography for differentiating from spontaneously aborted anterior myocardial infarction.

    PubMed

    Patel, Sandeep M; Lennon, Ryan J; Prasad, Abhiram

    2012-04-01

    Understanding the precise distribution of the regional wall motion abnormality (RWMA) in apical ballooning syndrome (ABS) is important because the cardiomyopathy can mimic an acute anterior ST-elevation myocardial infarction (STEMI). The aim of the study was to quantify the severity and distribution of RWMA in ABS, compare it to anterior STEMI, and correlate with clinical features. RWMA (normal = 1, hypokinetic = 2, akinetic = 3) was quantified from the biplane left ventriculogram using a nine-segment model in 95 ABS and 17 anterior STEMI patients at the time of their presentation. Regional wall motion score index (RWMSI) was higher in ABS [2.1 (1.9, 2.1)] compared to anterior STEMI [2.0 (1.8, 2.0)], P = 0.024]. The region that most clearly differentiated ABS from anterior STEMI was the posterolateral segment (sensitivity 81% and specificity 100%) which was hypocontractile in 81% of ABS, but none of the STEMI patients (P < 0.001). RWMSI in ABS had a modest positive correlation with the troponin T levels (r = 0.23, P = 0.029). Patients with ABS with ST-segment elevation had the highest RWMSI [2.1(2.0, 2.2)], while those with non specific changes had the lowest [1.9 (1.8, 2.1)] (P = 0.007). In conclusion, patients with ABS have greater and more diffuse RWMA compared to anterior STEMI. The presence of systolic dysfunction in the posterolateral segment in the left anterior oblique projection of the left ventriculogram most accurately distinguishes ABS from an anterior STEMI highlighting the utility of biplane angiography for this purpose. The severity of RWMA correlates with the extent of troponin release and ECG abnormality.

  10. 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

  11. Urokinase-type plasminogen activator deficiency has little effect on seizure susceptibility and acquired epilepsy phenotype but reduces spontaneous exploration in mice.

    PubMed

    Rantala, J; Kemppainen, S; Ndode-Ekane, X E; Lahtinen, L; Bolkvadze, Tamuna; Gurevicius, K; Tanila, H; Pitkänen, A

    2015-01-01

    Urokinase-type plasminogen activator (uPA), a serine protease, converts plasminogen to plasmin. Activation of plasmin leads to degradation of the extracellular matrix, which is critical for tissue recovery, angiogenesis, cell migration, and axonal and synaptic plasticity. We hypothesized that uPA deficiency would cause an abnormal neurophenotype and would lead to exacerbated epileptogenesis after brain injury. Wild-type (Wt) and uPA-/- mice underwent a battery of neurologic behavioral tests evaluating general reactivity, spontaneous exploratory activity, motor coordination, pain threshold, fear and anxiety, and memory. We placed particular emphasis on the effect of uPA deficiency on seizure susceptibility, including the response to convulsants (pentylenetetrazol, kainate, or pilocarpine) and kainate-induced epileptogenesis and epilepsy. The uPA-/- mice showed no motor or sensory impairment compared with the Wt mice. Hippocampus-dependent spatial memory also remained intact. The uPA-/- mice, however, exhibited reduced exploratory activity and an enhanced response to a tone stimulus (p<0.05 compared with the Wt mice). The urokinase-type plasminogen activator deficient mice showed no increase in spontaneous or evoked epileptiform electrographic activity. Rather, the response to pilocarpine administration was reduced compared with the Wt mice (p<0.05). Also, the epileptogenesis and the epilepsy phenotype after intrahippocampal kainate injection were similar to those in the Wt mice. Taken together, uPA deficiency led to diminished interest in the environmental surroundings and enhanced emotional reactivity to unexpected aversive stimuli. Urokinase-type plasminogen activator deficiency was not associated with enhanced seizure susceptibility or worsened poststatus epilepticus epilepsy phenotype.

  12. Altered spontaneous activity in antisocial personality disorder revealed by regional homogeneity.

    PubMed

    Tang, Yan; Liu, Wangyong; Chen, Jingang; Liao, Jian; Hu, Dewen; Wang, Wei

    2013-08-01

    There is increasing evidence that antisocial personality disorder (ASPD) stems from brain abnormalities. However, there are only a few studies investigating brain structure in ASPD. The aim of this study was to find regional coherence abnormalities in resting-state functional MRI of ASPD. Thirty-two ASPD individuals and 34 controls underwent a resting-state functional MRI scan. The regional homogeneity (ReHo) approach was used to examine whether ASPD was related to alterations in resting-state neural activity. Support vector machine discriminant analysis was used to evaluate the sensitivity/specificity characteristics of the ReHo index in discriminating between the ASPD individuals and controls. The results showed that, compared with controls, ASPD individuals show lower ReHo in the right cerebellum posterior lobe (Crus1) and the right middle frontal gyrus, as well as higher ReHo in the right middle occipital gyrus (BA 19), left inferior temporal gyrus (BA 37), and right inferior occipital gyrus (cuneus, BA 18). All alternation regions reported a predictive accuracy above 70%. To our knowledge, this study was the first to study the change in regional activity coherence in the resting brain of ASPD individuals. These results not only elucidated the pathological mechanism of ASPD from a resting-state functional viewpoint but also showed that these alterations in ReHo may serve as potential markers for the detection of ASPD.

  13. Resting Spontaneous Activity in the Default Mode Network Predicts Performance Decline during Prolonged Attention Workload

    PubMed Central

    Zhu, Senhua; Fang, Zhuo; Spaeth, Andrea M.; Xin, Yuanyuan; Feng, Tingyong; Rao, Hengyi

    2015-01-01

    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-minute 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-minute 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-minute 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

  14. Two types of mental fatigue affect spontaneous oscillatory brain activities in different ways

    PubMed Central

    2013-01-01

    Background Fatigue has a multi-factorial nature. We examined the effects of two types of mental fatigue on spontaneous oscillatory brain activity using magnetoencephalography (MEG). Methods Participants were randomly assigned to two groups in a single-blinded, crossover fashion to perform two types of mental fatigue-inducing experiments. Each experiment consisted of a 30-min fatigue-inducing 0- or 2-back test session and two evaluation sessions performed just before and after the fatigue-inducing mental task session. Results After the 0-back test, decreased alpha power was indicated in the right angular gyrus and increased levels in the left middle and superior temporal gyrus, left postcentral gyrus, right superior frontal gyrus, left inferior frontal gyrus, and right medial frontal gyrus. After the 2-back test, decreased alpha power was indicated in the right middle and superior frontal gyrus and increased levels in the left inferior parietal and superior parietal lobules, right parahippocampal gyrus, right uncus, left postcentral gyrus, left middle frontal gyrus, and right inferior frontal gyrus. For beta power, increased power following the 0-back test was indicated in the left middle temporal gyrus, left superior frontal gyrus, left cingulate gyrus, and left precentral gyrus. After the 2-back test, decreased power was suggested in the left superior frontal gyrus and increased levels in the left middle temporal gyrus and left inferior parietal lobule. Some of these brain regions might be associated with task performance during the fatigue-inducing trials. Conclusions Two types of mental fatigue may produce different alterations of the spontaneous oscillatory MEG activities. Our findings would provide new perspectives on the neural mechanisms underlying mental fatigue. PMID:23305089

  15. Reduced spontaneous neuronal activity in the insular cortex and thalamus in healthy adults with insomnia symptoms.

    PubMed

    Liu, Chun-Hong; Liu, Cun-Zhi; Zhang, Jihui; Yuan, Zhen; Tang, Li-Rong; Tie, Chang-Le; Fan, Jin; Liu, Qing-Quan

    2016-10-01

    Poor sleep and insomnia have been recognized to be strongly correlated with the development of depression. The exploration of the basic mechanism of sleep disturbance could provide the basis for improved understanding and treatment of insomnia and prevention of depression. In this study, 31 subjects with insomnia symptoms as measured by the Hamilton Rating Scale for Depression (HAMD-17) and 71 age- and gender-matched subjects without insomnia symptoms were recruited to participate in a clinical trial. Using resting-state functional magnetic resonance imaging (rs-fMRI), we examined the alterations in spontaneous brain activity between the two groups. Correlations between the fractional amplitude of low frequency fluctuations (fALFF) and clinical measurements (e.g., insomnia severity and Hamilton Depression Rating Scale [HAMD] scores) were also tested in all subjects. Compared to healthy participants without insomnia symptoms, participants with insomnia symptoms showed a decreased fALFF in the left ventral anterior insula, bilateral posterior insula, left thalamus, and pons but an increased fALFF in the bilateral middle occipital gyrus and right precentral gyrus. More specifically, a significant, negative correlation of fALFF in the left thalamus with early morning awakening scores and HAMD scores in the overall sample was identified. These results suggest that insomnia symptoms are associated with altered spontaneous activity in the brain regions of several important functional networks, including the insular cortex of the salience and the thalamus of the hyperarousal network. The altered fALFF in the left thalamus supports the "hyperarousal theory" of insomnia symptoms, which could serve as a biomarker for insomnia. PMID:27425430

  16. 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

  17. 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

  18. 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.

  19. The basal forebrain modulates spontaneous activity of principal cells in the main olfactory bulb of anesthetized mice

    PubMed Central

    Zhan, Xiping; Yin, Pingbo; Heinbockel, Thomas

    2013-01-01

    Spontaneous activity is an important characteristic of the principal cells in the main olfactory bulb (MOB) for encoding odor information, which is modulated by the basal forebrain. Cholinergic activation has been reported to inhibit all major neuron types in the MOB. In this study, the effect of diagonal band (NDB) stimulation on mitral/tufted (M/T) cell spontaneous activity was examined in anesthetized mice. NDB stimulation increased spontaneous activity in 66 MOB neurons which lasted for 2–35 s before returning to the baseline level. The majority of the effected units showed a decrease of interspike intervals (ISI) at a range of 8–25 ms. Fifty-two percent of NDB stimulation responsive units showed intrinsic rhythmical bursting, which was enhanced temporarily by NDB stimulation, whereas the remaining non-rhythmic units were capable of synchronized bursting. The effect was attenuated by scopolamine in 21 of 27 units tested. Only four NDB units were inhibited by NDB stimulation, an inhibition that lasted less than 10 s. The NDB stimulation responsive neurons appeared to be M/T cells. Our findings demonstrate an NDB excitation effect on M/T neurons that mostly requires muscarinic receptor activation, and is likely due to non-selectivity of electrical stimulation. This suggests that cholinergic and a diverse group of non-cholinergic neurons in the basal forebrain co-ordinately modulate the dynamics of M/T cell spontaneous activity, which is fundamental for odor representation and attentional perception. PMID:24065892

  20. [Effects of reversing the feeding cycle and the light period on the spontaneous activity of the rat (author's transl)].

    PubMed

    Ticca, M

    1976-01-01

    The amount and the circadian distribution of spontaneous activity in the rat are influenced by a number of factors, whose importance and interrelationships are still deeply discussed. In order to check the reliability of previous studies about the effects of meal-eating on the spontaneous activity (wheel running) of rats of our Sprague-Dawley strain, the adjustment to the modifications of the normal day-night cycle and of the normal nocturnal feeding rhythm have been controlled. Reversing the normal light and dark periods caused the rats, after a 24 hours period, to lower and to irregularly distribute their spontaneous activity. Rats shifted their pattern of maximal activity by 12 hours in the new period of darkness in about five days, and showed to have completely fixed the new reversed running habit. Also feeding habits changed in a similar way, but more slowly. The levels of mean daily activity did not change. In a second experiment, rats, received food during light hours, and were deprived during dark hours. Their activity increased considerably and irregularly during dark hours, while a very slight rise of wheel running was shown during light hours. Body weight gain and food consumption were similar to those of the control group. These results slightly differ from those obtained using other rat strains, and are an interesting example of reinforcement of a spontaneous behavior resulting more from the light-dark cycle than from cues provided by food deprivation.

  1. 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

  2. Abnormal activation of the occipital lobes during emotion picture processing in major depressive disorder patients.

    PubMed

    Li, Jianying; Xu, Cheng; Cao, Xiaohua; Gao, Qiang; Wang, Yan; Wang, Yanfang; Peng, Juyi; Zhang, Kerang

    2013-06-25

    A large number of studies have demonstrated that depression patients have cognitive dysfunction. With recently developed brain functional imaging, studies have focused on changes in brain function to investigate cognitive changes. However, there is still controversy regarding abnormalities in brain functions or correlation between cognitive impairment and brain function changes. Thus, it is important to design an emotion-related task for research into brain function changes. We selected positive, neutral, and negative pictures from the International Affective Picture System. Patients with major depressive disorder were asked to judge emotion pictures. In addition, functional MRI was performed to synchronously record behavior data and imaging data. Results showed that the total correct rate for recognizing pictures was lower in patients compared with normal controls. Moreover, the consistency for recognizing pictures for depressed patients was worse than normal controls, and they frequently recognized positive pictures as negative pictures. The consistency for recognizing pictures was negatively correlated with the Hamilton Depression Rating Scale. Functional MRI suggested that the activation of some areas in the frontal lobe, temporal lobe, parietal lobe, limbic lobe, and cerebellum was enhanced, but that the activation of some areas in the frontal lobe, parietal lobe and occipital lobe was weakened while the patients were watching positive and neutral pictures compared with normal controls. The activation of some areas in the frontal lobe, temporal lobe, parietal lobe, and limbic lobe was enhanced, but the activation of some areas in the occipital lobe were weakened while the patients were watching the negative pictures compared with normal controls. These findings indicate that patients with major depressive disorder have negative cognitive disorder and extensive brain dysfunction. Thus, reduced activation of the occipital lobe may be an initiating factor for

  3. Abnormal high-energy phosphate molecule metabolism during regional brain activation in patients with bipolar disorder.

    PubMed

    Yuksel, C; Du, F; Ravichandran, C; Goldbach, J R; Thida, T; Lin, P; Dora, B; Gelda, J; O'Connor, L; Sehovic, S; Gruber, S; Ongur, D; Cohen, B M

    2015-09-01

    Converging evidence suggests bioenergetic abnormalities in bipolar disorder (BD). In the brain, phosphocreatine (PCr) acts a reservoir of high-energy phosphate (HEP) bonds, and creatine kinases (CK) catalyze the transfer of HEP from adenosine triphosphate (ATP) to PCr and from PCr back to ATP, at times of increased need. This study examined the activity of this mechanism in BD by measuring the levels of HEP molecules during a stimulus paradigm that increased local energy demand. Twenty-three patients diagnosed with BD-I and 22 healthy controls (HC) were included. Levels of phosphorus metabolites were measured at baseline and during visual stimulation in the occipital lobe using (31)P magnetic resonance spectroscopy at 4T. Changes in metabolite levels showed different patterns between the groups. During stimulation, HC had significant reductions in PCr but not in ATP, as expected. In contrast, BD patients had significant reductions in ATP but not in PCr. In addition, PCr/ATP ratio was lower at baseline in patients, and there was a higher change in this measure during stimulation. This pattern suggests a disease-related failure to replenish ATP from PCr through CK enzyme catalysis during tissue activation. Further studies measuring the CK flux in BD are required to confirm and extend this finding.

  4. Inhibition of fatty acid oxidation activates transforming growth factor-beta in cerebrospinal fluid and decreases spontaneous motor activity.

    PubMed

    Fujikawa, Teppei; Fujita, Ryo; Iwaki, Yoko; Matsumura, Shigenobu; Fushiki, Tohru; Inoue, Kazuo

    2010-10-01

    We have previously reported that transforming growth factor (TGF)-beta in the cerebrospinal fluid (CSF) is involved in the mechanism underlying the regulation of spontaneous motor activity (SMA) by the central nervous system after exercise. However, it remained unclear what physiological condition triggers the activation of TGF-beta. We hypothesized that the shortage of energy derived from fatty acid (FA) oxidation observed in the early phase of exercise activated TGF-beta in the CSF. To test this hypothesis, we investigated whether mercaptoacetate (MA), an inhibitor of FA oxidation, could induce an activation of TGF-beta in the CSF and a decrease in SMA. Intraperitoneal (i.p.) administration of MA activated TGF-beta in CSF in rats and depressed SMA; 2-deoxyglucose, an inhibitor of carbohydrate oxidation, on the other hand, depressed SMA but failed to activate CSF TGF-beta. Intracisternal administration of anti-TGF-beta antibody abolished the depressive effect of MA on SMA. We also found that the depression of SMA and the activation of TGF-beta in the CSF by i.p. MA administration were eliminated by vagotomy. Our data suggest that TGF-beta in the CSF is activated by the inhibition of FA oxidation via the vagus nerve and that this subsequently induces depression of SMA.

  5. 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

  6. A study of lip movements during spontaneous dialog and its application to voice activity detection.

    PubMed

    Sodoyer, David; Rivet, Bertrand; Girin, Laurent; Savariaux, Christophe; Schwartz, Jean-Luc; Jutten, Christian

    2009-02-01

    This paper presents a quantitative and comprehensive study of the lip movements of a given speaker in different speech/nonspeech contexts, with a particular focus on silences (i.e., when no sound is produced by the speaker). The aim is to characterize the relationship between "lip activity" and "speech activity" and then to use visual speech information as a voice activity detector (VAD). To this aim, an original audiovisual corpus was recorded with two speakers involved in a face-to-face spontaneous dialog, although being in separate rooms. Each speaker communicated with the other using a microphone, a camera, a screen, and headphones. This system was used to capture separate audio stimuli for each speaker and to synchronously monitor the speaker's lip movements. A comprehensive analysis was carried out on the lip shapes and lip movements in either silence or nonsilence (i.e., speech+nonspeech audible events). A single visual parameter, defined to characterize the lip movements, was shown to be efficient for the detection of silence sections. This results in a visual VAD that can be used in any kind of environment noise, including intricate and highly nonstationary noises, e.g., multiple and/or moving noise sources or competing speech signals. PMID:19206891

  7. Electrophysiological study in the infraorbital nerve of the rat: Spontaneous and evoked activity

    NASA Astrophysics Data System (ADS)

    Albarracín, A. L.; Farfán, F. D.; Felice, C. J.

    2007-11-01

    In this work we present some studies in the afferent nerve of the rat vibrissae. Studies on spontaneous activity (SA) in this sensorial system are of long data. Nevertheless, SA recordings in the nerve of a single vibrissa have not been made until present. In this work, we use an algorithm based on signal decomposition with Continuous Wavelet Transform (CWT) to analyse the discharges of two nerves. The action potentials of both nerves were detected and the firing rates were calculated. These results suggest that the firing rate of one vibrissa innervation is low considering that this nerve contains hundred of fibers. In addition, we present preliminary studies suggesting important effects of the hair shaft length in the afferent discharge during the vibrissae movements. The experiments consisted in recording the nerve activity after the vibrissae were sectioned at two different levels. The results showed important differences in the signal energy contents. It suggests that the hair shaft length would produce a differential activation of the mechanoreceptors located in the vibrissae follicle.

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. Prolonged exposure to a low-dose of bisphenol A increases spontaneous motor activity in adult male rats.

    PubMed

    Nojima, Kazuo; Takata, Tomoyo; Masuno, Hiroshi

    2013-07-01

    We investigated the effects of bisphenol A (BPA), an environmental endocrine-disrupting chemical, on spontaneous motor activity in adult male rats. The rats were implanted intraperitoneally with mini-osmotic pumps containing either BPA (50 μg/kg body weight per day) in sesame oil (BPA-treated group) or sesame oil only (vehicle-treated group). Spontaneous motor activity during a 24-h period was measured over 5 days from day 9 to day 13 after implantation using an animal movement analysis system. Spontaneous motor activity during the last 2 h of the dark phase and during the first 1-h of the light phase was increased in the BPA-treated group. Total spontaneous motor activity during the 12-h light phase, but not the 12-h dark phase, was higher in the BPA-treated group than in the vehicle-treated group. These findings suggest that BPA may induce hyperactivity in adult male rats during the 12-h light phase, especially during the 2 h immediately preceding sleep-onset and 1 h immediately following sleep-onset.

  15. Central beta-adrenergic receptors mediate renal nerve activity during stress in conscious spontaneously hypertensive rats.

    PubMed

    Koepke, J P; DiBona, G F

    1985-01-01

    The effects of intracerebroventricular (i.c.v.) administration of beta-adrenergic receptor antagonists (d,l-propranolol or timolol, 30 micrograms in 2 microL of isotonic saline) on the increased renal sympathetic nerve activity and decreased urinary sodium excretion (UNaV) responses to stressful environmental stimulation (air jet to head) in conscious spontaneously hypertensive rats (SHR) were examined. Before i.c.v. d,l-propranolol or timolol, air stress increased renal activity (68% from 10.6 +/- 2.1 and 63% from 8.2 +/- 0.9 integrator resets/min respectively). In contrast, after i.c.v. d,l-propranolol or timolol in the same conscious SHR, air stress had no effect on renal sympathetic nerve activity (+7% from 8.1 +/- 1.7 and +7% from 5.5 +/- 1.0 integrator resets/min respectively). Air stress decreased UNaV in conscious SHR given i.c.v. saline vehicle (25% from 2.8 +/- 0.5 microEq/min/100 g body weight), but had no effect on effective renal plasma flow or glomerular filtration rate. In contrast, after i.c.v. d,l-propranolol or timolol, air stress had no effect on UNaV (0% from 2.8 +/- 0.5 and +9% from 3.3 +/- 0.3 microEq/min/100 g body weight respectively). Mean arterial pressure increased similarly during air stress with i.c.v. saline-vehicle or beta-adrenergic receptor antagonists. Intravenous administration of the same doses of d,l-propranolol or timolol did not prevent the increased renal sympathetic nerve activity or decreased UNaV responses resulting from air stress. These results suggest that central nervous system beta-adrenergic receptors mediate the increased renal sympathetic nerve activity and decreased UNaV responses resulting from stressful environmental stimulation in conscious SHR.

  16. Squid have nociceptors that display widespread long-term sensitization and spontaneous activity after bodily injury.

    PubMed

    Crook, Robyn J; Hanlon, Roger T; Walters, Edgar T

    2013-06-12

    Bodily injury in mammals often produces persistent pain that is driven at least in part by long-lasting sensitization and spontaneous activity (SA) in peripheral branches of primary nociceptors near sites of injury. While nociceptors have been described in lower vertebrates and invertebrates, outside of mammals there is limited evidence for peripheral sensitization of primary afferent neurons, and there are no reports of persistent SA being induced in primary afferents by noxious stimulation. Cephalopod molluscs are the most neurally and behaviorally complex invertebrates, with brains rivaling those of some vertebrates in size and complexity. This has fostered the opinion that cephalopods may experience pain, leading some governments to include cephalopods under animal welfare laws. It is not known, however, if cephalopods possess nociceptors, or whether their somatic sensory neurons exhibit nociceptive sensitization. We demonstrate that squid possess nociceptors that selectively encode noxious mechanical but not heat stimuli, and that show long-lasting peripheral sensitization to mechanical stimuli after minor injury to the body. As in mammals, injury in squid can cause persistent SA in peripheral afferents. Unlike mammals, the afferent sensitization and SA are almost as prominent on the contralateral side of the body as they are near an injury. Thus, while squid exhibit peripheral alterations in afferent neurons similar to those that drive persistent pain in mammals, robust changes far from sites of injury in squid suggest that persistently enhanced afferent activity provides much less information about the location of an injury in cephalopods than it does in mammals.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. Increased renal epithelial na channel expression and activity correlate with elevation of blood pressure in spontaneously hypertensive rats.

    PubMed

    Haloui, Mounsif; Tremblay, Johanne; Seda, Ondrej; Koltsova, Svetlana V; Maksimov, Georgy V; Orlov, Sergei N; Hamet, Pavel

    2013-10-01

    Elevation of blood pressure with age is one of the hallmarks of hypertension in both males and females. This study examined transcriptomic profiles in the kidney of 12-, 40-, and 80-week-old spontaneously hypertensive rats and 4 recombinant inbred strains in search for functional genetic elements supporting temporal dynamics of blood pressure elevation. We found that both in males and females of spontaneously hypertensive rats and hypertensive recombinant inbred strains age-dependent blood pressure increment was accompanied by 50% heightened expression of epithelial sodium channel β- and γ-subunits. Epithelial sodium channel subunit expression correlated positively with blood pressure but correlated negatively with renin expression. Increased epithelial sodium channel activity was observed in cultured epithelial cells isolated from the kidney medulla of 80-week-old spontaneously hypertensive rats but not in age-matched normotensive Wistar Kyoto. This difference remained evident after 24-hour treatment with aldosterone. 22Na uptake in the perfused kidney medulla was increased whereas the urinary Na/K ratio was decreased in old spontaneously hypertensive rats compared with normotensive controls. The difference was eliminated by the administration of epithelial sodium channel inhibitor benzamil. Observations in recombinant inbred strains representing various mixtures of parental hypertensive and normotensive genomes suggest that Scnn1g and Scnn1b genes themselves are not implicated in heightened expression and that the increased expression is neither secondary nor required for a partial elevation of blood pressure in contrast to spontaneously hypertensive rats. We suggest that spontaneously hypertensive rats display an intact negative feed-back between renin-angiotensin-system and epithelial Na channel activity whose upregulated expression is supported by a yet unknown mechanism.

  7. Effect of muscle metaboreflex activation on spontaneous cardiac baroreflex sensitivity during exercise in humans.

    PubMed

    Hartwich, Doreen; Dear, William E; Waterfall, Jessica L; Fisher, James P

    2011-12-15

    We sought to determine whether the activation of metabolically sensitive skeletal muscle afferents (muscle metaboreflex) is a potential mechanism for the decrease in spontaneous cardiac baroreflex sensitivity (cBRS) during exercise in humans. In protocol 1, 15 male subjects (22 ± 1 years) performed steady-state leg cycling at low (26 ± 4 W) and moderate workloads (105 ± 7 W), under free-flow conditions and with partial flow restriction (bilateral thigh cuff inflation at 100 mmHg) to evoke muscle metaboreflex activation during exercise. In protocol 2, rhythmic handgrip exercise at 35% maximum voluntary contraction was performed with progressive upper arm cuff inflation (0, 80, 100 and 120 mmHg) to elicit graded metaboreflex activation. Both protocols were followed by post-exercise ischaemia (PEI) to isolate the muscle metaboreflex. Leg cycling-induced increases in HR and mean BP were augmented by partial flow restriction (P < 0.05 vs. free flow), while HR and mean BP both remained elevated during PEI (P < 0.05 vs. rest). Leg cycling evoked an intensity-dependent decrease in cBRS (16 ± 2, 7 ± 1 and 2 ± 0.2 ms mmHg(-1) at rest, low and moderate workloads, respectively; P < 0.05), which was further reduced with partial flow restriction (by -2.6 ± 0.8 and -0.4 ± 0.1 ms mmHg(-1) at low and moderate workloads). cBRS remained suppressed during PEI following leg cycling with partial flow restriction (4 ± 1 ms mmHg(-1); P < 0.05 vs. rest). cBRS was unchanged during handgrip under free-flow conditions, handgrip with partial flow restriction and PEI following handgrip (P > 0.05 vs. rest). These data indicate that the activation of metabolically sensitive skeletal muscle afferents (muscle metaboreflex) decreases cardiac baroreflex responsiveness during leg cycling exercise in humans.

  8. 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

  9. Control of spontaneous activation of rat oocytes by regulating plasma membrane Na+/Ca2+ exchanger activities.

    PubMed

    Cui, Wei; Zhang, Jie; Zhang, Chuan-Xin; Jiao, Guang-Zhong; Zhang, Min; Wang, Tian-Yang; Luo, Ming-Jiu; Tan, Jing-He

    2013-06-01

    Inhibiting oocyte spontaneous activation (SA) is essential for successful rat cloning by nuclear transfer (NT). This study tested the hypothesis that activities of the Na(+)/Ca(2+) exchanger (NCX) would decrease with oocyte aging and that SA of rat oocytes could be inhibited if the intraoocyte Ca(2+) rises were prevented by activating the NCX through increasing Na(+) concentrations in the culture medium. Elevating Na(+) levels in culture medium by supplementing NaCl inhibited SA of rat oocytes, while maintaining a constant level of maturation-promoting factor and mitogen-activated protein kinase activities. Experiments using the NCX inhibitor bepridil, the Na(+)/K(+)-ATPase inhibitor ouabain, and an assay for intraoocyte Ca(2+) concentrations showed that extracellular Na(+) inhibited rat oocyte SA by enhancing NCX activity and preventing intracellular Ca(2+) rises. Immunohistochemical quantification indicated that the density of NCX1 decreased significantly in aged oocytes that were prone to SA compared with that in freshly ovulated oocytes whose SA rates were low during in vitro culture. Cumulus cell NT showed that sham enucleation caused marked SA in freshly ovulated rat oocytes and that Na(+) supplementation prevented the manipulation-induced SA and improved the in vitro and in vivo development of rat somatic cell NT embryos. Taken together, the results have confirmed our hypothesis that the NCX is active in rat oocytes and its activity decreases with oocyte aging and that activating the NCX by increasing extracellular Na(+) inhibits SA of rat oocytes and improves the development of rat somatic cell NT embryos. These data are also important for understanding the mechanisms of oocyte aging. PMID:23677981

  10. DENTAL MINERALIZATION AND SALIVARY ACTIVITY ARE REDUCED IN OFFSPRING OF SPONTANEOUSLY HYPERTENSIVE RATS (SHR)

    PubMed Central

    Elias, Gracieli Prado; dos Santos, Otoniel Antonio Macedo; Sassaki, Kikue Takebayashi; Delbem, Alberto Carlos Botazzo; Antoniali, Cristina

    2006-01-01

    Several pathologies have been diagnosed in children of hypertensive mothers; however, some studies that evaluated the alterations in their oral health are not conclusive. This study analyzed the salivary gland activity and dental mineralization of offsprings of spontaneously hypertensive rats (SHR). Thirty-day-old SHR males and Wistar rats were studied. The salivary flow was evaluated by injection of pilocarpine, the protein concentration and salivary amylase activity, by the Lowry method and kinetic method at 405 nm, respectively. Enamel and dentin mineralization of the mandibular incisors was quantified with aid of the microhardness meter. The results were analyzed by the ANOVA or Student's t test (p<0.05). It was noticed that the salivary flow rate (0.026 mL/min/100 g ± 0.002) and salivary protein concentration (2.26 mg/mL ± 0.14) of SHR offspring were reduced compared to Wistar normotensive offspring (0.036 mL/min/100 g ± 0.003 and 2.91 mg/mL ± 0.27, respectively), yet there was no alteration in amylase activity (SHR: 242.4 U/mL ± 36.9; Wistar: 163.8 U/mL ± 14.1). Microhardness was lower both in enamel (255.8 KHN ± 2.6) and dentin (59.9 KHN ± 0.8) for the SHR teeth compared to the Wistar teeth (enamel: 328.7 KHN ± 3.3 and dentin: 67.1 KHN ± 1.0). These results suggest that the SHR offspring are more susceptible to development of pathologies impairing oral health, once they presented lesser flow and salivary protein concentration and lower dental mineralization. PMID:19089272

  11. Alterations of Regional Spontaneous Brain Activity and Gray Matter Volume in the Blind

    PubMed Central

    Jiang, Aili; Tian, Jing; Li, Rui; Liu, Yong; Jiang, Tianzi; Qin, Wen; Yu, Chunshui

    2015-01-01

    Visual deprivation can induce alterations of regional spontaneous brain activity (RSBA). However, the effects of onset age of blindness on the RSBA and the association between the alterations of RSBA and brain structure are still unclear in the blind. In this study, we performed resting-state functional and structural magnetic resonance imaging on 50 sighted controls and 91 blind subjects (20 congenitally blind, 27 early blind, and 44 late blind individuals). Compared with the sighted control, we identified increased RSBA in the blind in primary and high-level visual areas and decreased RSBA in brain regions which are ascribed to sensorimotor and salience networks. In contrast, blind subjects exhibited significantly decreased gray matter volume (GMV) in the visual areas, while they exhibited significantly increased GMV in the sensorimotor areas. Moreover, the onset age of blindness was negatively correlated with the GMV of visual areas in blind subjects, whereas it exerted complex influences on the RSBA. Finally, significant negative correlations were shown between RSBA and GMV values. Our results demonstrated system-dependent, inverse alterations in RSBA and GMV after visual deprivation. Furthermore, the onset age of blindness has different effects on the reorganizations in RSBA and GMV. PMID:26568891

  12. 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

  13. Alterations of Regional Spontaneous Brain Activity and Gray Matter Volume in the Blind.

    PubMed

    Jiang, Aili; Tian, Jing; Li, Rui; Liu, Yong; Jiang, Tianzi; Qin, Wen; Yu, Chunshui

    2015-01-01

    Visual deprivation can induce alterations of regional spontaneous brain activity (RSBA). However, the effects of onset age of blindness on the RSBA and the association between the alterations of RSBA and brain structure are still unclear in the blind. In this study, we performed resting-state functional and structural magnetic resonance imaging on 50 sighted controls and 91 blind subjects (20 congenitally blind, 27 early blind, and 44 late blind individuals). Compared with the sighted control, we identified increased RSBA in the blind in primary and high-level visual areas and decreased RSBA in brain regions which are ascribed to sensorimotor and salience networks. In contrast, blind subjects exhibited significantly decreased gray matter volume (GMV) in the visual areas, while they exhibited significantly increased GMV in the sensorimotor areas. Moreover, the onset age of blindness was negatively correlated with the GMV of visual areas in blind subjects, whereas it exerted complex influences on the RSBA. Finally, significant negative correlations were shown between RSBA and GMV values. Our results demonstrated system-dependent, inverse alterations in RSBA and GMV after visual deprivation. Furthermore, the onset age of blindness has different effects on the reorganizations in RSBA and GMV. PMID:26568891

  14. Elastase Activity in Aspergillus fumigatus Can Arise by Random, Spontaneous Mutations

    PubMed Central

    Álvarez-Pérez, Sergio; Blanco, Jose L.; López-Rodas, Victoria; Flores-Moya, Antonio; Costas, Eduardo; García, Marta E.

    2010-01-01

    Aspergillus fumigatus Fresenius has the capacity to degrade elastin (the principal protein of the lungs) and it is considered that elastase activity (EA) is among the most important pathogenicity factors of this mold. In particular, there is a strong correlation between EA in A. fumigatus and invasive aspergillosis. However, EA is not universal in this mold, and it is unknown whether the capacity to degrade elastin is the consequence of physiological mechanisms and/or genetic changes (putative adaptive mutations) induced after the exposure to this substrate or, on the contrary, it is due to random spontaneous mutations that occur under nonselective conditions. In order to discriminate between these possibilities, a Luria-Delbrück fluctuation analysis was carried out on an elastase-negative (EA−) A. fumigatus strain, using as selective factor a culture medium containing elastin as the sole source of nitrogen. Here we show that the EA− → EA+ transformation in A. fumigatus appears by rare, random mutations before the exposure of the strain to selective conditions. This work represents the first experimental evidence of pathogenicity factor acquisition in mycelial fungi by preselective mutation. PMID:21350652

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

    SciTech Connect

    Somerville, L.P.

    1982-01-01

    Several new Spontaneous Fission (SF) activities have been found. Their half-lives and production cross sections in several reactions have been measured by collecting and transporting recoils at known speed past mica track detectors. 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(3.8s, 14% SF), /sup 258/Rf(13 ms), /sup 259/Rf(approx.3s, 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 268/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).

  16. 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.

  17. 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

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

    PubMed

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

    2014-08-01

    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 may 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 that 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.

  19. Possible production of actinide spontaneous fission activities in damped collisions of /sup 209/Bi+/sup 56/Fe

    SciTech Connect

    Viola, V.E. Jr.; Mignerey, A.C.; Breuer, H.; Wolf, K.L.; Glagola, B.G.; Wilcke, W.W.; Schroeder, W.U.; Huizenga, J.R.; Hilscher, D.; Birkelund, J.R.

    1980-07-01

    Results of recent nuclear reaction studies on the /sup 209/Bi+/sup 56/Fe system are analyzed in order to investigate the cross sections for production of spontaneously fissioning species with 90 < or = Z < or = 100. This reaction is nearly identical to those used as the basis for identification of new elements with Z=104 --107, reported to be spontaneous fission emitters. Evidence is presented which indicates that actinide elements are formed with primary yields of the order of millibarns in strongly damped collisions of 464 MeV /sup 56/Fe with /sup 209/Bi. Although strongly depleted by fission competition, final yields of possible spontaneous fission activities /sup 240en-dash244/Am/sup f/, /sup 234en-dash238/Cf, and /sup 242en-dash246/Fm are calculated to be of the order of nanobarns. These results suggest that the spontaneous fission activities observed in similar reactions may be due at least in part to fission decay of actinide elements rather than elements with Z=104 --107.

  20. 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

  1. 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

  2. Maturation promoting factor destabilization facilitates postovulatory aging-mediated abortive spontaneous egg activation in rat.

    PubMed

    Prasad, Shilpa; Koch, Biplob; Chaube, Shail K

    2016-04-01

    The present study was designed to investigate whether destabilization of maturation promoting factor (MPF) leads to postovulatory aging-mediated abortive spontaneous egg activation (SEA). If so, we wished to determine whether changes in Wee-1 as well as Emi2 levels are associated with MPF destabilization during postovulatory aging-mediated abortive SEA in rats eggs aged in vivo. For this purpose, sexually immature female rats were given a single injection (20 IU IM) of pregnant mare serum gonadotropin for 48 h followed by single injection of human chorionic gonadotropin (20 IU). Ovulated eggs were collected after 14, 17, 19 and 21 h post-hCG surge to induce postovulatory aging in vivo. The morphological changes, Wee1, phosphorylation status of cyclin dependent kinase 1(Cdk1), early mitotic inhibitor 2 (Emi2), anaphase promoting complex/cyclosome (APC/C), cyclin B1, mitotic arrest deficient protein (MAD2) levels and Cdk1 activity were analyzed. The increased Wee 1 level triggered phosphorylation of Thr-14/Tyr-15 and dephosphorylation of Thr-161 residues of Cdk1. The decrease of Emi2 level was associated with increased APC/C level and decreased cyclin B1 level. Changes in phosphorylation status of Cdk1 and reduced cyclin B1 level resulted in destabilization of MPF. The destabilized MPF finally led to postovulatory aging-mediated abortive SEA in rat eggs. It was concluded that the increase of Wee 1 but decrease of Emi2 level triggers MPF destabilization and thereby postovulatory aging-mediated abortive SEA in rat eggs. PMID:26991553

  3. 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.

  4. Spontaneous activation of [FeFe]-hydrogenases by an inorganic [2Fe] active site mimic

    PubMed Central

    Esselborn, Julian; Berggren, Gustav; Noth, Jens; Siebel, Judith; Hemschemeier, Anja; Artero, Vincent; Reijerse, Edward; Fontecave, Marc; Lubitz, Wolfgang; Happe, Thomas

    2013-01-01

    Hydrogenases catalyze the formation of hydrogen. The cofactor (H-cluster) of [FeFe]-hydrogenases consists of a [4Fe-4S]-cluster bridged to a unique [2Fe]-subcluster whose biosynthesis in vivo requires hydrogenase-specific maturases. Here we show that a chemical mimic of the [2Fe]-subcluster can reconstitute apo-hydrogenase to full activity, independent of helper proteins. The assembled H-cluster is virtually indistinguishable from the native cofactor. This procedure will be a powerful tool for developing novel artificial H2-producing catalysts. PMID:23934246

  5. Changes in locomotor-activity patterns as a measure of spontaneous morphine withdrawal: no effect of clonidine.

    PubMed

    van der Laan, J W; de Groot, G

    1988-10-01

    The anti-withdrawal action of clonidine was studied in a model of spontaneous morphine withdrawal in rats. After withdrawal the behaviour of the animals was registered continuously for several days. In the initial phase of induction of dependence the locomotor activity was enhanced during daytime. Partial tolerance to this increase developed in the course of 3 weeks. In morphine withdrawn animals the activity decreased strongly at night, and this effect was maximal on the second night after removal of morphine. After four nights the nightly activity was restored. Treatment with clonidine (100 micrograms/kg s.c. twice daily) changed neither the observed decrease in nightly locomotor activity nor other withdrawal symptoms such as a decrease in food intake and loss of body weight. In non-dependent animals clonidine induced a biphasic effect in locomotor activity, i.e. a decrease in the first few hours of the night and an increase in the second part of the night. The latter can be interpreted as a rebound phenomenon occurring after only three injections. It was concluded that clonidine was not effective as an anti-withdrawal compound in a model for spontaneous morphine abstinence. The low incidence of symptoms relating to a hyperactive sympathetic system during spontaneous withdrawal may be an explanation for the absence of an effect of clonidine.

  6. 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....

  7. 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

  8. 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).

  9. Linking inter-individual differences in the conflict adaptation effect to spontaneous brain activity.

    PubMed

    Wang, Ting; Chen, Zhencai; Zhao, Guang; Hitchman, Glenn; Liu, Congcong; Zhao, Xiaoyue; Liu, Yijun; Chen, Antao

    2014-04-15

    Conflict adaptation has been widely researched in normal and clinical populations. There are large individual differences in conflict adaptation, and it has been linked to the schizotypal trait. However, no study to date has examined how individual differences in spontaneous brain activity are related to behavioral conflict adaptation (performance). Resting-state functional magnetic resonance imaging (RS-fMRI) is a promising tool to investigate this issue. The present study evaluated the regional homogeneity (ReHo) of RS-fMRI signals in order to explore the neural basis of individual differences in conflict adaptation across two independent samples comprising a total of 67 normal subjects. A partial correlation analysis was carried out to examine the relationship between ReHo and behavioral conflict adaptation, while controlling for reaction time, standard deviation and flanker interference effects. This analysis was conducted on 39 subjects' data (sample 1); the results showed significant positive correlations in the left dorsolateral prefrontal cortex (DLPFC) and left ventrolateral prefrontal cortex. We then conducted a test-validation procedure on the remaining 28 subjects' data (sample 2) to examine the reliability of the results. Regions of interest were defined based on the correlation results. Regression analysis showed that variability in ReHo values in the DLPFC accounted for 48% of the individual differences in the conflict adaptation effect in sample 2. The present findings provide further support for the importance of the DLPFC in the conflict adaptation process. More importantly, we demonstrated that ReHo of RS-fMRI signals in the DLPFC can predict behavioral performance in conflict adaptation, which provides potential biomarkers for the early detection of cognitive control deterioration.

  10. Osteopontin Deficiency Accelerates Spontaneous Colitis in Mice with Disrupted Gut Microbiota and Macrophage Phagocytic Activity

    PubMed Central

    Toyonaga, Takahiko; Nakase, Hiroshi; Ueno, Satoru; Matsuura, Minoru; Yoshino, Takuya; Honzawa, Yusuke; Itou, Ayako; Namba, Kazuyoshi; Minami, Naoki; Yamada, Satoshi; Koshikawa, Yorimitsu; Uede, Toshimitsu; Chiba, Tsutomu; Okazaki, Kazuichi

    2015-01-01

    Background Osteopontin (OPN) is a multifunctional protein expressed in a variety of tissues and cells. Recent studies revealed increased OPN expression in the inflamed intestinal tissues of patients with inflammatory bowel disease (IBD). The role of OPN in the pathophysiology of IBD, however, remains unclear. Aims To investigate the role of OPN in the development of intestinal inflammation using a murine model of IBD, interleukin-10 knock out (IL-10 KO) mice. Methods We compared the development of colitis between IL-10 KO and OPN/IL-10 double KO (DKO) mice. OPN expression in the colonic tissues of IL-10 KO mice was examined by fluorescence in situ hybridization (FISH) analysis. Enteric microbiota were compared between IL-10 KO and OPN/IL-10 DKO mice by terminal restriction fragment length polymorphism analysis. The effect of OPN on macrophage phagocytic function was evaluated by phagocytosis assay. Results OPN/IL-10 DKO mice had an accelerated onset of colitis compared to IL-10 KO mice. FISH analysis revealed enhanced OPN synthesis in the colonic epithelial cells of IL-10 KO mice. OPN/IL-10 DKO mice had a distinctly different enteric bacterial profile with a significantly lower abundance of Clostridium subcluster XIVa and a greater abundance of Clostridium cluster XVIII compared to IL-10 KO mice. Intracellular OPN deletion in macrophages impaired phagocytosis of fluorescence particle-conjugated Escherichia coli in vitro. Exogenous OPN enhanced phagocytosis by OPN-deleted macrophages when administered at doses of 1 to 100 ng/ml, but not 1000 ng/ml. Conclusions OPN deficiency accelerated the spontaneous development of colitis in mice with disrupted gut microbiota and macrophage phagocytic activity. PMID:26274807

  11. Fission properties of the 1. 5-s spontaneous fission activity produced in bombardmentof /sup 248/Cm with /sup 18/O

    SciTech Connect

    Hoffman, D.C.; Lee, D.; Ghiorso, A.; Nurmia, M.J.; Aleklett, K.; Leino, M.

    1981-08-01

    We have measured the mass and kinetic-energy distributions of fragments from the spontaneous fission of a 1.5-s activity produced in bombardments of /sup 248/Cm with 95-MeV /sup 18/O ions. Its spontaneous fission decay exhibits a very symmetric, narrow (full width at half maximum = 12 mass units) mass distribution, a very high total kinetic energy of 234 +- 2 MeV, and increasing total kinetic energy with increasingly symmetric mass division. Based on its half-life and the similarity of its fission properties to the unique fission properties so far only observed for /sup 258/Fm and /sup 259/Fm, the most likely assignment of this activity is to the known /sup 259/Fm. However, assignment to some as yet undiscovered neutron-rich heavy element isotope such as /sup 260/Md cannot be unequivocally excluded.

  12. 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.

  13. 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

  14. Functional expression of KCNQ (Kv7) channels in guinea pig bladder smooth muscle and their contribution to spontaneous activity

    PubMed Central

    Anderson, U A; Carson, C; Johnston, L; Joshi, S; Gurney, A M; McCloskey, K D

    2013-01-01

    Background and Purpose The aim of the study was to determine whether KCNQ channels are functionally expressed in bladder smooth muscle cells (SMC) and to investigate their physiological significance in bladder contractility. Experimental Approach KCNQ channels were examined at the genetic, protein, cellular and tissue level in guinea pig bladder smooth muscle using RT-PCR, immunofluorescence, patch-clamp electrophysiology, calcium imaging, detrusor strip myography, and a panel of KCNQ activators and inhibitors. Key Results KCNQ subtypes 1–5 are expressed in bladder detrusor smooth muscle. Detrusor strips typically displayed TTX-insensitive myogenic spontaneous contractions that were increased in amplitude by the KCNQ channel inhibitors XE991, linopirdine or chromanol 293B. Contractility was inhibited by the KCNQ channel activators flupirtine or meclofenamic acid (MFA). The frequency of Ca2+-oscillations in SMC contained within bladder tissue sheets was increased by XE991. Outward currents in dispersed bladder SMC, recorded under conditions where BK and KATP currents were minimal, were significantly reduced by XE991, linopirdine, or chromanol, and enhanced by flupirtine or MFA. XE991 depolarized the cell membrane and could evoke transient depolarizations in quiescent cells. Flupirtine (20 μM) hyperpolarized the cell membrane with a simultaneous cessation of any spontaneous electrical activity. Conclusions and Implications These novel findings reveal the role of KCNQ currents in the regulation of the resting membrane potential of detrusor SMC and their important physiological function in the control of spontaneous contractility in the guinea pig bladder. PMID:23586426

  15. Excess of Gβe over Gqαe in vivo prevents dark, spontaneous activity of Drosophila photoreceptors

    PubMed Central

    Elia, Natalie; Frechter, Shahar; Gedi, Yinon; Minke, Baruch; Selinger, Zvi

    2005-01-01

    Drosophila melanogaster photoreceptor cells are capable of detecting single photons. This utmost sensitivity is critically dependent on the maintenance of an exceedingly low, dark, spontaneous activity of photoreceptor cells. However, the underlying mechanisms of this hallmark of phototransduction are not fully understood. An analysis of the Drosophila visual heterotrimeric (αβγ) Gq protein revealed that wild-type Drosophila flies have about a twofold excess of Gβ over Gα subunits of the visual Gq protein. Studies of Gβe mutants in which the excess of Gβ was genetically eliminated showed dramatic dark, spontaneous activity of the photoreceptor cells, whereas concurrent genetic reduction of the Gα subunit, which restored the excess of Gβ, abolished this effect. These results indicate that an excess of Gβ over Gα is a strategy used in vivo for the suppression of spontaneous activity, thereby yielding a high signal to noise ratio, which is characteristic of the photoreceptor light response. This mechanism could be relevant to the regulation of G protein signaling in general. PMID:16260498

  16. 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...

  17. 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…

  18. 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.

  19. 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.

  20. 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

  1. Reduction of CTRP9, a novel anti-platelet adipokine, contributes to abnormal platelet activity in diabetic animals.

    PubMed

    Wang, Wenqing; Lau, Wayne Bond; Wang, Yajing; Ma, Xinliang; Li, Rong

    2016-01-11

    Platelet hyper-reactivity is a crucial cause of accelerated atherosclerosis increasing risk of thrombotic vascular events in diabetic patients. The mechanisms leading to abnormal platelet activity during diabetes are complex and not fully defined. The current study attempted to clarify the role of CTRP9, a novel adiponectin paralog, in enhanced platelet activity and determined whether CTRP9 may inhibit platelet activity. Adult male C57BL/6 J mice were randomized to receive high-fat diet (HFD) or normal diet (ND). 8 weeks after HFD, animals were sacrificed, and both plasma CTRP9 and platelet aggregation were determined. HFD-fed animals increased weight gain significantly, and became hyperglycemic and hyperinsulinemic 8 weeks post-HFD. Compared to ND animals, HFD animals exhibited significantly decreased plasma CTRP9 concentration and increased platelet response to ADP, evidenced by augmented aggregation amplitude, steeper aggregation slope, larger area under the curve, and shorter lag time (P < 0.01). A significant negative correlation between plasma CTRP9 concentration and platelet aggregation amplitude was observed. More importantly, in vitro pre-treatment with CTRP9 significantly inhibited ADP-stimulated platelet activation in platelet samples from both ND and HFD animals. Taken together, our results suggest reduced plasma CTRP9 concentration during diabetes plays a causative role in platelet hyper-activity, contributing to platelet-induced cardiovascular damage during this pathologic condition. Enhancing CTRP9 production and/or exogenous supplementation of CTRP9 may protect against diabetic cardiovascular injury via inhibition of abnormal platelet activity.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. alpha- and beta-adrenergic receptor mechanisms in spontaneous contractile activity of rat ileal longitudinal smooth muscle.

    PubMed

    Seiler, Roland; Rickenbacher, Andreas; Shaw, Sidney; Balsiger, Bruno M

    2005-02-01

    Gastrointestinal motility is influenced by adrenergic modulation. Our aim was to identify specific subtypes of adrenergic receptors involved in inhibitory mechanisms that modulate gut smooth muscle contractile activity. Muscle strips of rat ileal longitudinal muscle were evaluated for spontaneous contractile activity and for equimolar dose-responses (10(-7) to 3 x 10(-5) M) to the adrenergic agents norepinephrine (nonselective agonist), phenylephrine (alpha(1)-agonist), clonidine (alpha(2)-agonist), prenalterol (beta(1)-agonist), ritodrine (beta(2)-agonist), and ZD7114 (beta(3)-agonist) in the presence and absence of tetrodotoxin (nonselective nerve blocker). Norepinephrine (3 x 10(-5) M) inhibited 65 +/- 6% (mean +/- SEM) of spontaneous contractile activity. The same molar dose of ritodrine, phenylephrine, or ZD7114 resulted in less inhibition (46 +/- 7%, 31 +/- 5%, and 39 +/- 3%, respectively; P < 0.05). The calculated molar concentration of ZD7114 needed to induce 50% inhibition was similar to that of norepinephrine, whereas higher concentrations of phenylephrine or ritodrine were required. Clonidine and prenalterol had no effect on contractile activity. Blockade of intramural neural transmission by tetrodotoxin affected the responses to ritodrine and phenylephrine (but not to norepinephrine or ZD7114), suggesting that these agents exert part of their effects via neurally mediated enteric pathways. Our results suggest that adrenergic modulation of contractile activity in the rat ileum is mediated primarily by muscular beta(3)-, beta(2)-, and alpha(1)-receptor mechanisms; the latter two also involve neural pathways. PMID:15694819

  7. A high-fat diet rich in corn oil reduces spontaneous locomotor activity and induces insulin resistance in mice.

    PubMed

    Wong, Chi Kin; Botta, Amy; Pither, Jason; Dai, Chuanbin; Gibson, William T; Ghosh, Sanjoy

    2015-04-01

    Over the last few decades, polyunsaturated fatty acid (PUFA), especially n-6 PUFA, and monounsaturated fatty acid content in 'Western diets' has increased manyfold. Such a dietary shift also parallels rising sedentary behavior and diabetes in the Western world. We queried if a shift in dietary fats could be linked to physical inactivity and insulin insensitivity in mice. Eight-week old female C57/Bl6 mice were fed either high-fat (HF) diets [40% energy corn oil (CO) or isocaloric olive oil (OO) diets] or chow (n=10/group) for 6 weeks, followed by estimation of spontaneous locomotor activity, body composition and in vivo metabolic outcomes. Although lean mass and resting energy expenditure stayed similar in both OO- and CO-fed mice, only CO-fed mice demonstrated reduced spontaneous locomotor activity. Such depressed activity in CO-fed mice was accompanied by a lower respiratory ratio, hyperinsulinemia and impaired glucose disposal following intraperitoneal glucose tolerance and insulin tolerance tests compared to OO-fed mice. Unlike the liver, where both HF diets increased expression of fat oxidation genes like PPARs, the skeletal muscle of CO-fed mice failed to up-regulate such genes, thereby supporting the metabolic insufficiencies observed in these mice. In summary, this study demonstrates a specific contribution of n-6 PUFA-rich oils like CO to the loss of spontaneous physical activity and insulin sensitivity in mice. If these data hold true for humans, this study could provide a novel link between recent increases in dietary n-6 PUFA to sedentary behavior and the development of insulin resistance in the Western world.

  8. Abnormal temporal and parietal magnetic activations during the early stages of theory of mind in schizophrenic patients.

    PubMed

    Vistoli, Damien; Brunet-Gouet, Eric; Lemoalle, Amelia; Hardy-Baylé, Marie-Christine; Passerieux, Christine

    2011-01-01

    Schizophrenia is associated with abnormal cortical activation during theory of mind (ToM), as demonstrated by several fMRI or PET studies. Electrical and temporal characteristics of these abnormalities, especially in the early stages, remain unexplored. Nineteen medicated schizophrenic patients and 21 healthy controls underwent magnetoencephalography (MEG) recording to measure brain response evoked by nonverbal stimuli requiring mentalizing. Three conditions based on comic-strips were contrasted: attribution of intentions to others (AI), physical causality with human characters (PCCH), and physical causality with objects (PCOB). Minimum norm localization was performed in order to select regions of interest (ROIs) within bilateral temporal and parietal regions that showed significant ToM-related activations in the control group. Time-courses of each ROI were compared across group and condition. Reduced cortical activation within the 200 to 600 ms time-window was observed in the selected regions in patients. Significant group by condition interactions (i.e., reduced modulation in patients) were found in right posterior superior temporal sulcus, right temporoparietal junction, and right inferior parietal lobule during attribution of intentions. As in healthy controls, the presence of characters elicited activation in patients' left posterior temporal regions and temporoparietal junction. No group difference on evoked responses' latencies in AI was found. In conclusion, ToM processes in the early stages are functionally impaired in schizophrenia. MEG provides a promising means to refine our knowledge on schizophrenic social cognitive disorders.

  9. 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

  10. 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

  11. 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.

  12. Benzodiazepine modulation of partial agonist efficacy and spontaneously active GABAA receptors supports an allosteric model of modulation

    PubMed Central

    Downing, Scott S; Lee, Yan T; Farb, David H; Gibbs, Terrell T

    2005-01-01

    Benzodiazepines (BZDs) have been used extensively for more than 40 years because of their high therapeutic index and low toxicity. Although BZDs are understood to act primarily as allosteric modulators of GABAA receptors, the mechanism of modulation is not well understood. The applicability of an allosteric model with two binding sites for γ-aminobutyric acid (GABA) and one for a BZD-like modulator was investigated. This model predicts that BZDs should enhance the efficacy of partial agonists. Consistent with this prediction, diazepam increased the efficacy of the GABAA receptor partial agonist kojic amine in chick spinal cord neurons. To further test the validity of the model, the effects of diazepam, flurazepam, and zolpidem were examined using wild-type and spontaneously active mutant α1(L263S)β3γ2 GABAA receptors expressed in HEK-293 cells. In agreement with the predictions of the allosteric model, all three modulators acted as direct agonists for the spontaneously active receptors. The results indicate that BZD-like modulators enhance the amplitude of the GABA response by stabilizing the open channel active state relative to the inactive state by less than 1 kcal, which is similar to the energy of stabilization conferred by a single hydrogen bond. PMID:15912137

  13. 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.

  14. Hox-C9 activates the intrinsic pathway of apoptosis and is associated with spontaneous regression in neuroblastoma.

    PubMed

    Kocak, H; Ackermann, S; Hero, B; Kahlert, Y; Oberthuer, A; Juraeva, D; Roels, F; Theissen, J; Westermann, F; Deubzer, H; Ehemann, V; Brors, B; Odenthal, M; Berthold, F; Fischer, M

    2013-04-11

    Neuroblastoma is an embryonal malignancy of the sympathetic nervous system. Spontaneous regression and differentiation of neuroblastoma is observed in a subset of patients, and has been suggested to represent delayed activation of physiologic molecular programs of fetal neuroblasts. Homeobox genes constitute an important family of transcription factors, which play a fundamental role in morphogenesis and cell differentiation during embryogenesis. In this study, we demonstrate that expression of the majority of the human HOX class I homeobox genes is significantly associated with clinical covariates in neuroblastoma using microarray expression data of 649 primary tumors. Moreover, a HOX gene expression-based classifier predicted neuroblastoma patient outcome independently of age, stage and MYCN amplification status. Among all HOX genes, HOXC9 expression was most prominently associated with favorable prognostic markers. Most notably, elevated HOXC9 expression was significantly associated with spontaneous regression in infant neuroblastoma. Re-expression of HOXC9 in three neuroblastoma cell lines led to a significant reduction in cell viability, and abrogated tumor growth almost completely in neuroblastoma xenografts. Neuroblastoma growth arrest was related to the induction of programmed cell death, as indicated by an increase in the sub-G1 fraction and translocation of phosphatidylserine to the outer membrane. Programmed cell death was associated with the release of cytochrome c from the mitochondria into the cytosol and activation of the intrinsic cascade of caspases, indicating that HOXC9 re-expression triggers the intrinsic apoptotic pathway. Collectively, our results show a strong prognostic impact of HOX gene expression in neuroblastoma, and may point towards a role of Hox-C9 in neuroblastoma spontaneous regression.

  15. Chloride-sensitive MEQ fluorescence in chick embryo motoneurons following manipulations of chloride and during spontaneous network activity.

    PubMed

    Chub, Nikolai; Mentis, George Z; O'donovan, Michael J

    2006-01-01

    Intracellular Cl(-) ([Cl(-)](in)) homeostasis is thought to be an important regulator of spontaneous activity in the spinal cord of the chick embryo. We investigated this idea by visualizing the variations of [Cl(-)](in) in motoneurons retrogradely labeled with the Cl-sensitive dye 6-methoxy-N-ethylquinolinium iodide (MEQ) applied to cut muscle nerves in the isolated E10-E12 spinal cord. This labeling procedure obviated the need for synthesizing the reduced, cell-permeable dihydro-MEQ (DiH-MEQ). The specificity of motoneuron labeling was confirmed using retrograde co-labeling with Texas Red Dextran and immunocytochemistry for choline acetyltransferase (ChAT). In MEQ-labeled motoneurons, the GABA(A) receptor agonist isoguvacine (100 muM) increased somatic and dendritic fluorescence by 7.4 and 16.7%, respectively. The time course of this fluorescence change mirrored that of the depolarization recorded from the axons of the labeled motoneurons. Blockade of the inward Na(+)/K(-)/2Cl(-) co-transporter (NKCC1) with bumetanide (20 microM) or with a low-Na(+) bath solution (12 mM), increased MEQ fluorescence by 5.3 and 11.4%, respectively, consistent with a decrease of [Cl(-)](in). After spontaneous episodes of activity, MEQ fluorescence increased and then declined to the pre-episode level during the interepisode interval. The largest fluorescence changes occurred over motoneuron dendrites (19.7%) with significantly smaller changes (5.2%) over somata. Collectively, these results show that retrogradely loaded MEQ can be used to detect [Cl(-)](in) in motoneurons, that the bumetanide-sensitive NKCC1 co-transporter is at least partially responsible for the elevated [Cl(-)](in) of developing motoneurons, and that dendritic [Cl(-)](in) decreases during spontaneous episodes and recovers during the inter-episode interval, presumably due to the action of NKCC1. PMID:16192339

  16. 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

  17. 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.

  18. Treatment with melatonin after status epilepticus attenuates seizure activity and neuronal damage but does not prevent the disturbance in diurnal rhythms and behavioral alterations in spontaneously hypertensive rats in kainate model of temporal lobe epilepsy.

    PubMed

    Petkova, Zlatina; Tchekalarova, Jana; Pechlivanova, Daniela; Moyanova, Slavianka; Kortenska, Lidia; Mitreva, Rumiana; Popov, Deyan; Markova, Petya; Lozanov, Valentin; Atanasova, Dimitrina; Lazarov, Nikolai; Stoynev, Alexander

    2014-02-01

    Melatonin is involved in the control of circadian and seasonal rhythmicity, possesses potent antioxidant activity, and exerts a neuroprotective and anticonvulsant effect. Spontaneously hypertensive rats (SHRs) are widely accepted as an experimental model of essential hypertension with hyperactivity, deficient sustained attention, and alterations in circadian autonomic profiles. The purpose of the present study was to determine whether melatonin treatment during epileptogenesis can prevent the deleterious consequences of status epilepticus (SE) in SHRs in the kainate (KA) model of temporal lobe of epilepsy (TLE). Spontaneous recurrent seizures (SRSs) were EEG- and video-recorded during and after the treatment protocol. Melatonin (10mg/kg diluted in drinking water, 8weeks) increased the seizure-latent period, decreased the frequency of SRSs, and attenuated the circadian rhythm of seizure activity in SHRs. However, melatonin was unable to affect the disturbed diurnal rhythms and behavioral changes associated with epilepsy, including the decreased anxiety level, depression, and impaired spatial memory. Melatonin reduced neuronal damage specifically in the CA1 area of the hippocampus and piriform cortex and decreased hippocampal serotonin (5-HT) levels both in control and epileptic SHRs. Although long-term melatonin treatment after SE shows a potential to attenuate seizure activity and neuronal loss, it is unable to restore epilepsy-associated behavioral abnormalities in SHRs. PMID:24440891

  19. Treatment with melatonin after status epilepticus attenuates seizure activity and neuronal damage but does not prevent the disturbance in diurnal rhythms and behavioral alterations in spontaneously hypertensive rats in kainate model of temporal lobe epilepsy.

    PubMed

    Petkova, Zlatina; Tchekalarova, Jana; Pechlivanova, Daniela; Moyanova, Slavianka; Kortenska, Lidia; Mitreva, Rumiana; Popov, Deyan; Markova, Petya; Lozanov, Valentin; Atanasova, Dimitrina; Lazarov, Nikolai; Stoynev, Alexander

    2014-02-01

    Melatonin is involved in the control of circadian and seasonal rhythmicity, possesses potent antioxidant activity, and exerts a neuroprotective and anticonvulsant effect. Spontaneously hypertensive rats (SHRs) are widely accepted as an experimental model of essential hypertension with hyperactivity, deficient sustained attention, and alterations in circadian autonomic profiles. The purpose of the present study was to determine whether melatonin treatment during epileptogenesis can prevent the deleterious consequences of status epilepticus (SE) in SHRs in the kainate (KA) model of temporal lobe of epilepsy (TLE). Spontaneous recurrent seizures (SRSs) were EEG- and video-recorded during and after the treatment protocol. Melatonin (10mg/kg diluted in drinking water, 8weeks) increased the seizure-latent period, decreased the frequency of SRSs, and attenuated the circadian rhythm of seizure activity in SHRs. However, melatonin was unable to affect the disturbed diurnal rhythms and behavioral changes associated with epilepsy, including the decreased anxiety level, depression, and impaired spatial memory. Melatonin reduced neuronal damage specifically in the CA1 area of the hippocampus and piriform cortex and decreased hippocampal serotonin (5-HT) levels both in control and epileptic SHRs. Although long-term melatonin treatment after SE shows a potential to attenuate seizure activity and neuronal loss, it is unable to restore epilepsy-associated behavioral abnormalities in SHRs.

  20. 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.

  1. 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

  2. Increased excitability and spontaneous activity of rat sensory neurons following in vitro stimulation of sympathetic fiber sprouts in the isolated dorsal root ganglion

    PubMed Central

    Xie, Wenrui; Strong, Judith A.; Zhang, Jun-Ming

    2010-01-01

    Many chronic pain conditions including complex regional pain syndrome are exacerbated by sympathetic activity. In animal models, sympathetic fibers sprout into the dorsal root ganglia (DRG) after peripheral nerve injury, forming abnormal connections with sensory neurons. However, functional studies of sympathetic-sensory connections have been limited largely to in vivo studies. This study describes a new method for studying sympathetic-sensory connections in an isolated whole DRG preparation in the rat spinal nerve ligation (SNL) model. Three days after ligation of the ventral ramus of the spinal nerve (SNL), sympathetic fibers sprouting into the DRG were observed to originate largely in the intact dorsal ramus of the spinal nerve, which at the lumbar level is a small branch of the spinal nerve separating from the ventral ramus near the intervertebral foramen. In whole DRG isolated 3 days after SNL, microelectrode recordings of sensory neurons showed that repeated stimulation of the dorsal ramus enhanced spontaneous activity in large and medium diameter neurons, and reduced rheobase in large neurons. These effects, which were slow and long-lasting, were attributed to stimulation of the sympathetic sprouts because: stimulation had no effect in uninjured DRG; and effects could be reduced or eliminated by a “cocktail” of antagonists of norepinephrine and ATP receptors, by pretreatment with the sympathetic release blocker bretylium, or by pre-cutting the grey ramus through which sympathetic fibers coursed to the ligated DRG. The latter treatment, a relatively minimal form of sympathectomy, was also highly effective in reducing mechanical pain ipsilateral to the SNL. PMID:20800969

  3. Transcriptional activation by TAL1 and FUS-CHOP proteins expressed in acute malignancies as a result of chromosomal abnormalities.

    PubMed Central

    Sánchez-García, I; Rabbitts, T H

    1994-01-01

    Proteins that appear to participate in transcriptional control of gene expression are increasingly implicated in leukemias and malignant solid tumors. We report here that the N-terminal domains of the proteins TAL1 (ectopically activated in T-cell acute leukemias after chromosomal abnormalities caused by V-D-J recombinase error) (V, variable; D, diversity; J, joining) and FUS-CHOP (a liposarcoma tumor-specific fusion protein that is produced as a result of a chromosomal translocation) can function as transcription activators of specific responsive reporter genes. The result with TAL1 provides evidence that transcriptional activation can be mediated by a gene activated by translocation in T-cell acute leukemias. In the case of the liposarcoma, transactivation by the FUS-CHOP protein occurs because the FUS transcriptional activation domain is added to the DNA-binding CHOP protein normally lacking such activity. Therefore, the association of transcriptional activation and DNA-binding elements is a common consequence in proteins activated or newly created as fusion proteins after chromosomal translocations in acute leukemias and in malignant solid tumors. Images PMID:8058726

  4. 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 ...

  5. 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 ...

  6. 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 ...

  7. Nail abnormalities

    MedlinePlus

    Beau's lines; Fingernail abnormalities; Spoon nails; Onycholysis; Leukonychia; Koilonychia; Brittle nails ... Just like the skin, the fingernails tell a lot about your health: ... the fingernail. These lines can occur after illness, injury to ...

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. Effects of turbidity on the spontaneous and prey-searching activity of juvenile Atlantic cod (Gadus morhua).

    PubMed

    Meager, Justin J; Batty, Robert S

    2007-11-29

    Increasing turbidity in coastal waters in the North Atlantic and adjacent seas has raised concerns about impacts on Atlantic cod (Gadus morhua) using these areas as nurseries. A previous experiment (Meager et al. 2005 Can. J. Fish. Aquat. Sci. 62, 1978-1984) has shown that turbidity (up to 28 beam attenuation m-1) had little effect on the foraging rate of juvenile cod. Although this was attributed to cod using chemoreception in conjunction with vision to locate prey, foraging rates may also be maintained by increased activity. Higher activity, however, is energetically costly and may offset benefits from increased foraging return. We examined the effects of turbidity on prey searching and spontaneous activity of juvenile cod in the laboratory, by measuring activity with and without prey cues. Activity of juvenile cod was nonlinearly affected by turbidity and was lower at intermediate turbidity, regardless of the presence of prey odour. Activity increased over time when prey odour was present and decreased when absent, but the effects of prey odour were similar across all turbidity levels. Position in the tank was unaffected by turbidity or prey odour. Reduced activity at intermediate turbidities is likely to offset longer prey-search times. At high turbidity (greater than 17m-1), both longer prey-search times and higher activity indicate that increased energetic costs are probable.

  15. Anatomically realistic multiscale models of normal and abnormal gastrointestinal electrical activity

    PubMed Central

    Cheng, Leo K; Komuro, Rie; Austin, Travis M; Buist, Martin L; Pullan, Andrew J

    2007-01-01

    One of the major aims of the International Union of Physiological Sciences (IUPS) Physiome Project is to develop multiscale mathematical and computer models that can be used to help understand human health. We present here a small facet of this broad plan that applies to the gastrointestinal system. Specifically, we present an anatomically and physiologically based modelling framework that is capable of simulating normal and pathological electrical activity within the stomach and small intestine. The continuum models used within this framework have been created using anatomical information derived from common medical imaging modalities and data from the Visible Human Project. These models explicitly incorporate the various smooth muscle layers and networks of interstitial cells of Cajal (ICC) that are known to exist within the walls of the stomach and small bowel. Electrical activity within individual ICCs and smooth muscle cells is simulated using a previously published simplified representation of the cell level electrical activity. This simulated cell level activity is incorporated into a bidomain representation of the tissue, allowing electrical activity of the entire stomach or intestine to be simulated in the anatomically derived models. This electrical modelling framework successfully replicates many of the qualitative features of the slow wave activity within the stomach and intestine and has also been used to investigate activity associated with functional uncoupling of the stomach. PMID:17457969

  16. Anatomically realistic multiscale models of normal and abnormal gastrointestinal electrical activity.

    PubMed

    Cheng, Leo K; Komuro, Rie; Austin, Travis M; Buist, Martin L; Pullan, Andrew J

    2007-03-01

    One of the major aims of the International Union of Physiological Sciences (IUPS) Physiome Project is to develop multiscale mathematical and computer models that can be used to help understand human health. We present here a small facet of this broad plan that applies to the gastrointestinal system. Specifically, we present an anatomically and physiologically based modelling framework that is capable of simulating normal and pathological electrical activity within the stomach and small intestine. The continuum models used within this framework have been created using anatomical information derived from common medical imaging modalities and data from the Visible Human Project. These models explicitly incorporate the various smooth muscle layers and networks of interstitial cells of Cajal (ICC) that are known to exist within the walls of the stomach and small bowel. Electrical activity within individual ICCs and smooth muscle cells is simulated using a previously published simplified representation of the cell level electrical activity. This simulated cell level activity is incorporated into a bidomain representation of the tissue, allowing electrical activity of the entire stomach or intestine to be simulated in the anatomically derived models. This electrical modelling framework successfully replicates many of the qualitative features of the slow wave activity within the stomach and intestine and has also been used to investigate activity associated with functional uncoupling of the stomach.

  17. 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

  18. 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

  19. 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.…

  20. Immunosuppressive activity of human amniotic fluid of normal and abnormal pregnancies.

    PubMed

    Shohat, B; Faktor, J M

    1988-01-01

    Twenty specimens of amniotic fluid (AF) obtained between week 16 and 18 of gestation from normal pregnant women and six specimens from pregnant women in which trisomia of chromosome 21 was found were tested for immunosuppressive activity. Incubation of normal human donor lymphocytes with 0.2-1 mL of AF from normal pregnant women for one hour at 37 degrees C was sufficient for induction of significant inhibition of the ability of these cells to induce a local xenogeneic graft-versus-host reaction (GVHR) as well as inhibition of E and E-active rosette formation, the GVHR being the most sensitive test. On the other hand, amniotic fluid obtained from the six pregnant women in which trisomia of chromosome 21 was found showed no inhibitory activity in either the E or E-active rosette formation, nor in the local xenogeneic graft-versus-host reaction. AF from all the women tested was found to have no effect on phenotype expression of the lymphocytes, as tested by the monoclonal antibodies OKT4+ and OKT8+, nor on B-lymphocytes, as tested by surface immunoglobulins. No correlation was found between the alpha-fetoprotein levels in the sera of those women and the immunosuppressive activity. These findings indicate that genetic defects of the conceptus are not limited to the embryo but may affect the composition of immunosuppressive components present in normal amniotic fluid.

  1. Signal transduction of aortic and carotid sinus baroreceptors is not modified by central command during spontaneous motor activity in decerebrate cats.

    PubMed

    Matsukawa, Kanji; Ishii, Kei; Kadowaki, Akito; Ishida, Tomoko; Idesako, Mitsuhiro; Liang, Nan

    2014-05-15

    Our laboratory has suggested that central command provides selective inhibition of the cardiomotor component of aortic baroreflex at the start of exercise, preserving carotid sinus baroreflex. It is postulated that central command may modify the signal transduction of aortic baroreceptors, so as to decrease aortic baroreceptor input to the cardiovascular centers, and, thereby, can cause the selective inhibition of aortic baroreflex. To test the hypothesis, we directly analyzed the responses in multifiber aortic nerve activity (AoNA) and carotid sinus nerve activity (CsNA) during spontaneous motor activity in decerebrate, paralyzed cats. The increases of 62-104% in mean AoNA and CsNA were found during spontaneous motor activity, in proportion to a rise of 35 ± 3 mmHg (means ± SE) in mean arterial blood pressure (MAP), and had an attenuating tendency by restraining heart rate (HR) at the lower intrinsic frequency of 154 ± 6 beats/min. Brief occlusion of the abdominal aorta was conducted before and during spontaneous motor activity to produce a mechanically evoked increase in MAP and, thereby, to examine the stimulus-response relationship of arterial baroreceptors. Although the sensitivity of the MAP-HR baroreflex curve was markedly blunted during spontaneous motor activity, the stimulus-response relationships of AoNA and CsNA were not influenced by spontaneous motor activity, irrespective of the absence or presence of the HR restraint. Thus, it is concluded that aortic and carotid sinus baroreceptors can code beat-by-beat blood pressure during spontaneous motor activity in decerebrate cats and that central command is unlikely to modulate the signal transduction of arterial baroreceptors.

  2. What is the importance of abnormal "background" activity in seizure generation?

    PubMed

    Staba, Richard J; Worrell, Gregory A

    2014-01-01

    Investigations of interictal epileptiform spikes and seizures have played a central role in the study of epilepsy. The background EEG activity, however, has received less attention. In this chapter we discuss the characteristic features of the background activity of the brain when individuals are at rest and awake (resting wake) and during sleep. The characteristic rhythms of the background EEG are presented, and the presence of 1/f (β) behavior of the EEG power spectral density is discussed and its possible origin and functional significance. The interictal EEG findings of focal epilepsy and the impact of interictal epileptiform spikes on cognition are also discussed. PMID:25012365

  3. 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

  4. 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…

  5. 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…

  6. 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

  7. Abnormal functional activation during a simple word repetition task: A PET study of adult dyslexics.

    PubMed

    McCrory, E; Frith, U; Brunswick, N; Price, C

    2000-09-01

    Eight dyslexic subjects, impaired on a range of tasks requiring phonological processing, were matched for age and general ability with six control subjects. Participants were scanned using positron emission tomography (PET) during three conditions: repeating real words, repeating pseudowords, and rest. In both groups, speech repetition relative to rest elicited widespread bilateral activation in areas associated with auditory processing of speech; there were no significant differences between words and pseudowords. However, irrespective of word type, the dyslexic group showed less activation than the control group in the right superior temporal and right post-central gyri and also in the left cerebellum. Notably, the right anterior superior temporal cortex (Brodmann's area 22 [BA 22]) was less activated in each of the eight dyslexic subjects, compared to each of the six control subjects. This deficit appears to be specific to auditory repetition as it was not detected in a previous study of reading which used the same sets of stimuli (Brunswick, N., McCrory, E., Price, C., Frith, C.D., & Frith, U. [1999]. Explicit and implicit processing of words and pseudowords by adult developmental dyslexics: A search for Wernicke's Wortschatz? Brain, 122, 1901-1917). This implies that the observed neural manifestation of developmental dyslexia is task-specific (i.e., functional rather than structural). Other studies of normal subjects indicate that attending to the phonetic structure of speech leads to a decrease in right-hemisphere processing. Lower right hemisphere activation in the dyslexic group may therefore indicate less processing of non-phonetic aspects of speech, allowing greater salience to be accorded to phonological aspects of attended speech. PMID:11054918

  8. 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

  9. Spontaneous oscillatory activity in rd1 mouse retina is transferred from ON pathway to OFF pathway via glycinergic synapse.

    PubMed

    Poria, Deepak; Dhingra, Narender K

    2015-01-15

    Retinal ganglion cells (RGCs) spike randomly in the dark and carry information about visual stimuli to the brain via specific spike patterns. However, following photoreceptor loss, both ON and OFF type of RGCs exhibit spontaneous oscillatory spike activity, which reduces the quality of information they can carry. Furthermore, it is not clear how the oscillatory activity would interact with the experimental treatment approaches designed to produce artificial vision. The oscillatory activity is considered to originate in ON-cone bipolar cells, AII amacrine cells, and/or their synaptic interactions. However, it is unknown how the oscillatory activity is generated in OFF RGCs. We tested the hypothesis that oscillatory activity is transferred from the ON pathway to the OFF pathway via the glycinergic AII amacrine cells. Using extracellular loose-patch and whole cell patch recordings, we recorded oscillatory activity in ON and OFF RGCs and studied their response to strychnine, a specific glycine receptor blocker. The cells were labeled with a fluorescent dye, and their dendritic stratification in inner plexiform layer was studied using confocal microscopy. Application of strychnine resulted in abolition of the oscillatory burst activity in OFF RGCs but not in ON RGCs, implying that oscillatory activity is generated in ON pathway and is transferred to OFF pathway, likely via the glycinergic AII amacrine cells. We found oscillatory activity in RGCs as early as postnatal day 12 in rd1 mouse, when rod degeneration has started but cones are still intact. This suggests that the oscillatory activity in rd1 mouse retina originates in rod pathway.

  10. Role of PKC and RhoA/ROCK pathways in the spontaneous phasic activity in the rectal smooth muscle.

    PubMed

    Singh, Jagmohan; Rattan, Satish

    2013-04-15

    The role of PKC and RhoA/ROCK pathways in the phasic activities in the rectal smooth muscles (RSM) in the basal state is not known. We examined this issue by determining the effects of PKC inhibitors (calphostin C and Gö-6850) and a ROCK inhibitor (Y-27632) on the slow-rate (~3/min) and fast-rate (~25/min) phasic activities. We also examined the corresponding signal transduction cascades and the PKC and ROCK enzymatic activities in the RSM in the basal state. PKC inhibition with calphostin C and Gö-6850 (10(-5) M) caused a significant decrease (~25%) in slow-rate (but not fast-rate) phasic activity (monitored by frequency and amplitude of contractions) of the RSM. Conversely, ROCK inhibition with Y-27632 (10(-5) M) caused a significant decrease not only in slow-rate, but also fast-rate, phasic activity caused by ROCK inhibition in the RSM. Western blot analysis revealed that the PKC inhibition-induced decrease in RSM phasic activity was associated with decreases in PKCα translocation, phosphorylated (Thr(38)) PKC-potentiated inhibitor (CPI-17), and phosphorylated (Thr(18)/Ser(19)) 20-kDa myosin regulatory light chain. Conversely, decreases in the phasic activity in the RSM by ROCK inhibition were accompanied by the additional decrease in phosphorylated (Thr(696)) myosin phosphatase target subunit 1. Data show that while PKC and RhoA/ROCK pathways play a significant role in slow-rate high-amplitude spontaneous phasic activity, only the RhoA/ROCK pathway primarily mediates fast-rate low-amplitude phasic activity, in the RSM. Such knowledge is important in the understanding of the pathophysiology of large intestinal motility disorders. Relative contributions of the PKC vs. the RhoA/ROCK pathway in the phasic activity remain to be determined.

  11. The BTG4 and CAF1 complex prevents the spontaneous activation of eggs by deadenylating maternal mRNAs

    PubMed Central

    Pfender, Sybille; Santhanam, Balaji

    2016-01-01

    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

  12. 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

  13. 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.

  14. [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.

  15. 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

  16. 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

  17. 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

  18. Changes in correlation between spontaneous activity of dorsal horn neurones lead to differential recruitment of inhibitory pathways in the cat spinal cord

    PubMed Central

    Chávez, D; Rodríguez, E; Jiménez, I; Rudomin, P

    2012-01-01

    Simultaneous recordings of cord dorsum potentials along the lumbo-sacral spinal cord of the anaesthetized cat revealed the occurrence of spontaneous synchronous negative (n) and negative–positive (np) cord dorsum potentials (CDPs). The npCDPs, unlike the nCDPs, appeared preferentially associated with spontaneous negative dorsal root potentials (DRPs) resulting from primary afferent depolarization. Spontaneous npCDPs recorded in preparations with intact neuroaxis or after spinalization often showed a higher correlation than the nCDPs recorded from the same pair of segments. The acute section of the sural and superficial peroneal nerves further increased the correlation between paired sets of npCDPs and reduced the correlation between the nCDPs recorded from the same pair of segments. It is concluded that the spontaneous nCDPs and npCDPs are produced by the activation of interconnected sets of dorsal horn neurones located in Rexed's laminae III–IV and bilaterally distributed along the lumbo-sacral spinal cord. Under conditions of low synchronization in the activity of this network of neurones there would be a preferential activation of the intermediate nucleus interneurones mediating Ib non-reciprocal postsynaptic inhibition. Increased synchronization in the spontaneous activity of this ensemble of dorsal horn neurones would recruit the interneurones mediating primary afferent depolarization and presynaptic inhibition and, at the same time, reduce the activation of pathways mediating Ib postsynaptic inhibition. Central control of the synchronization in the spontaneous activity of dorsal horn neurones and its modulation by cutaneous inputs is envisaged as an effective mechanism for the selection of alternative inhibitory pathways during the execution of specific motor or sensory tasks. PMID:22271870

  19. 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

  20. Ovariectomy augments hypertension through rho-kinase activation in the brain stem in female spontaneously hypertensive rats.

    PubMed

    Ito, Koji; Hirooka, Yoshitaka; Kimura, Yoshikuni; Sagara, Yoji; Sunagawa, Kenji

    2006-10-01

    Estrogen protects against increases in arterial pressure (AP) by acting on blood vessels and on cardiovascular centers in the brain. The mechanisms underlying the effects of estrogen in the brain stem, however, are not clear. The aim of the present study was to determine whether ovariectomy affects AP via the Rho/Rho-kinase pathway in the brain stem. We performed bilateral ovariectomy in 12-week-old female spontaneously hypertensive rats. AP and heart rate (HR), measured using radiotelemetry in awake rats, were increased in ovariectomized rats compared with control rats (mean AP: 163+/-3 versus 144+/-4 mm Hg; HR: 455+/-4 versus 380+/-6 bpm). Continuous intracisternal infusion of Y-27632 significantly attenuated the ovariectomy-induced increase in AP and HR (mean AP: 137+/-6 versus 163+/-3 mm Hg; HR: 379+/-10 versus 455+/-4 bpm). In addition, we confirmed the increase of Rho-kinase activity in the brain stem in ovariectomized rats, and the increase was attenuated by intracisternal infusion of Y-27632 via the phosphorylated ezrin, radixin, and moesin (ERM) family, which are Rho-kinase target proteins. Furthermore, angiotensin II type 1 receptor expression in the brain stem was significantly greater in ovariectomized rats than in control rats, and the increase was partially reduced by intracisternal infusion of Y-27632. In a separate group of animals, we confirmed that the serum and cerebrospinal fluid 17beta-estradiol concentrations decreased in ovariectomized rats. These results suggest that depletion of endogenous estrogen by ovariectomy, at least in part, induces hypertension in female spontaneously hypertensive rats via activation of the renin-angiotensin system and the Rho/Rho-kinase pathway in the brain stem.

  1. Implications of perennial saline springs for abnormally high fluid pressures and active thrusting in western California

    SciTech Connect

    Unruh, J.R.; Davisson, M.L.; Criss, R.E.; Moores, E.M. )

    1992-05-01

    Perennial saline springs in the Rumsey Hills area, southwestern Sacramento Valley, California, locally discharge at high elevations and near ridgetops. The springs are cold, are commonly associated with natural gas seeps, and typically emerge along west-vergent thrust faults. Stable isotope analyses indicate that the spring waters are similar to oil-field formation fluids and they have had a significant residence time in the subsurface at moderate temperatures. The nonmeteoric character of the springs demonstrates that they are not being fed by perched water tables. The authors propose that these subsurface formation waters are being forced to the surface by anomalously high porefluid pressures. The Rumsey Hills area is one of Quaternary uplift, thrusting, and crustal shortening, and prospect wells drilled there have encountered anomalously high fluid pressures at shallow depths. They attribute these high fluid pressures to active tectonic compression and shortening of Cretaceous marine sedimentary rocks. The widespread occurrence of anomalously high pore-fluid pressures and perennial saline springs in the Coast Ranges and western Great Valley suggests that much of western California may be characterized as a seismically active, overpressured thrust belt. The emergence of formation waters along thrust faults further suggests that patterns of subsurface fluid flow in western California may be similar to those in overpressured accretionary prisms, and that excess fluid pressures may also play a role in the distribution of seismicity.

  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. Population calcium imaging of spontaneous respiratory and novel motor activity in the facial nucleus and ventral brainstem in newborn mice.

    PubMed

    Persson, Karin; Rekling, Jens C

    2011-05-15

    The brainstem contains rhythm and pattern forming circuits, which drive cranial and spinal motor pools to produce respiratory and other motor patterns. Here we used calcium imaging combined with nerve recordings in newborn mice to reveal spontaneous population activity in the ventral brainstem and in the facial nucleus. In Fluo-8AM loaded brainstem-spinal cord preparations, respiratory activity on cervical nerves was synchronized with calcium signals at the ventrolateral brainstem surface. Individual ventrolateral neurons at the level of the parafacial respiratory group showed perfect or partial synchrony with respiratory nerve bursts. In brainstem-spinal cord preparations, cut at the level of the mid-facial nucleus, calcium signals were recorded in the dorsal, lateral and medial facial subnuclei during respiratory activity. Strong activity initiated in the dorsal subnucleus, followed by activity in lateral and medial subnuclei. Whole-cell recordings from facial motoneurons showed weak respiratory drives, and electrical field potential recordings confirmed respiratory drive to particularly the dorsal and lateral subnuclei. Putative facial premotoneurons showed respiratory-related calcium signals, and were predominantly located dorsomedial to the facial nucleus. A novel motor activity on facial, cervical and thoracic nerves was synchronized with calcium signals at the ventromedial brainstem extending from the level of the facial nucleus to the medulla–spinal cord border. Cervical dorsal root stimulation induced similar ventromedial activity. The medial facial subnucleus showed calcium signals synchronized with this novel motor activity on cervical nerves, and cervical dorsal root stimulation induced similar medial facial subnucleus activity. In conclusion, the dorsal and lateral facial subnuclei are strongly respiratory-modulated, and the brainstem contains a novel pattern forming circuit that drives the medial facial subnucleus and cervical motor pools.

  4. 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

  5. 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.

  6. Differential effect of central command on aortic and carotid sinus baroreceptor-heart rate reflexes at the onset of spontaneous, fictive motor activity.

    PubMed

    Matsukawa, Kanji; Ishii, Kei; Kadowaki, Akito; Liang, Nan; Ishida, Tomoko

    2012-08-15

    Our laboratory has reported that central command blunts the sensitivity of the aortic baroreceptor-heart rate (HR) reflex at the onset of voluntary static exercise in conscious cats and spontaneous contraction in decerebrate cats. The purpose of this study was to examine whether central command attenuates the sensitivity of the carotid sinus baroreceptor-HR reflex at the onset of spontaneous, fictive motor activity in paralyzed, decerebrate cats. We confirmed that aortic nerve (AN)-stimulation-induced bradycardia was markedly blunted to 26 ± 4.4% of the control (21 ± 1.3 beats/min) at the onset of spontaneous motor activity. Although the baroreflex bradycardia by electrical stimulation of the carotid sinus nerve (CSN) was suppressed (P < 0.05) to 86 ± 5.6% of the control (38 ± 1.2 beats/min), the inhibitory effect of spontaneous motor activity was much weaker (P < 0.05) with CSN stimulation than with AN stimulation. The baroreflex bradycardia elicited by brief occlusion of the abdominal aorta was blunted to 36% of the control (36 ± 1.6 beats/min) during spontaneous motor activity, suggesting that central command is able to inhibit the cardiomotor sensitivity of arterial baroreflexes as the net effect. Mechanical stretch of the triceps surae muscle never affected the baroreflex bradycardia elicited by AN or CSN stimulation and by aortic occlusion, suggesting that muscle mechanoreflex did not modify the cardiomotor sensitivity of aortic and carotid sinus baroreflex. Since the inhibitory effect of central command on the carotid baroreflex pathway, associated with spontaneous motor activity, was much weaker compared with the aortic baroreflex pathway, it is concluded that central command does not force a generalized modulation on the whole pathways of arterial baroreflexes but provides selective inhibition for the cardiomotor component of the aortic baroreflex.

  7. 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

  8. Accuracy of a custom physical activity and knee angle measurement sensor system for patients with neuromuscular disorders and gait abnormalities.

    PubMed

    Feldhege, Frank; Mau-Moeller, Anett; Lindner, Tobias; Hein, Albert; Markschies, Andreas; Zettl, Uwe Klaus; Bader, Rainer

    2015-05-06

    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.

  9. 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

  10. 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.

  11. Fatigue in multiple sclerosis is associated with abnormal cortical activation to voluntary movement--EEG evidence.

    PubMed

    Leocani, L; Colombo, B; Magnani, G; Martinelli-Boneschi, F; Cursi, M; Rossi, P; Martinelli, V; Comi, G

    2001-06-01

    Converging evidence is consistent with the view that fatigue in Multiple Sclerosis is independent from pyramidal tract involvement, suggesting a possible involvement of frontal areas. During voluntary movement, changes of the EEG rhythms can be observed over sensorimotor areas. Event-related desynchronization (ERD) of the 10 and 20 Hz frequency bands occurs during motor planning and execution and is followed after movement termination by event-related synchronization (ERS), expressing cortical idling or inhibition. We evaluated the pattern of cortical activation to voluntary movement in MS patients complaining of fatigue assessed using the Fatigue Severity Scale. Fifteen MS patients complaining of fatigue, 18 MS patients without fatigue, and 14 normal controls were studied. The two patients groups were similar for age, sex, disease duration, and were not disabled (score <1.5 at the Expanded Disability Status Scale). Twenty-nine channel EEG was recorded during about 60 self-paced extensions of the right thumb. The onset latency and amount of the contralateral sensorimotor (C3 electrode) 10 and 18--22 Hz ERD were similar in the three groups. ERD was more widespread anteriorly in the fatigue group compared with normal controls (P < 0.01 over Fz electrode). Postmovement contralateral sensorimotor 18--22 Hz ERS was significantly lower in fatigue MS patients compared with normal subjects (P < 0.005) and with nonfatigue MS patients (P = 0.02). These findings are consistent with a central origin of fatigue in MS and indicate cortical dysfunction even during a simple motor task, resulting in hyperactivity during movement execution and failure of the inhibitory mechanisms intervening after movement termination. PMID:11352624

  12. [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

  13. Correlation properties of spontaneous motor activity in healthy infants: a new computer-assisted method to evaluate neurological maturation.

    PubMed

    Waldmeier, Sandra; Grunt, Sebastian; Delgado-Eckert, Edgar; Latzin, Philipp; Steinlin, Maja; Fuhrer, Katharina; Frey, Urs

    2013-06-01

    Qualitative assessment of spontaneous motor activity in early infancy is widely used in clinical practice. It enables the description of maturational changes of motor behavior in both healthy infants and infants who are at risk for later neurological impairment. These assessments are, however, time-consuming and are dependent upon professional experience. Therefore, a simple physiological method that describes the complex behavior of spontaneous movements (SMs) in infants would be helpful. In this methodological study, we aimed to determine whether time series of motor acceleration measurements at 40-44 weeks and 50-55 weeks gestational age in healthy infants exhibit fractal-like properties and if this self-affinity of the acceleration signal is sensitive to maturation. Healthy motor state was ensured by General Movement assessment. We assessed statistical persistence in the acceleration time series by calculating the scaling exponent α via detrended fluctuation analysis of the time series. In hand trajectories of SMs in infants we found a mean α value of 1.198 (95 % CI 1.167-1.230) at 40-44 weeks. Alpha changed significantly (p = 0.001) at 50-55 weeks to a mean of 1.102 (1.055-1.149). Complementary multilevel regression analysis confirmed a decreasing trend of α with increasing age. Statistical persistence of fluctuation in hand trajectories of SMs is sensitive to neurological maturation and can be characterized by a simple parameter α in an automated and observer-independent fashion. Future studies including children at risk for neurological impairment should evaluate whether this method could be used as an early clinical screening tool for later neurological compromise.

  14. Sex Hormones Promote Opposite Effects on ACE and ACE2 Activity, Hypertrophy and Cardiac Contractility in Spontaneously Hypertensive Rats

    PubMed Central

    Dalpiaz, P. L. M.; Lamas, A. Z.; Caliman, I. F.; Ribeiro, R. F.; Abreu, G. R.; Moyses, M. R.; Andrade, T. U.; Gouvea, S. A.; Alves, M. F.; Carmona, A. K.; Bissoli, N. S.

    2015-01-01

    Background There is growing interest in sex differences and RAS components. However, whether gender influences cardiac angiotensin I-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) activity is still unknown. In the present work, we determined the relationship between ACE and ACE2 activity, left ventricular function and gender in spontaneously hypertensive rats (SHRs). Methodology / Principal Findings Twelve-week-old female (F) and male (M) SHRs were divided into 2 experimental groups (n = 7 in each group): sham (S) and gonadectomized (G). Fifty days after gonadectomy, we measured positive and negative first derivatives (dP/dt maximum left ventricle (LV) and dP/dt minimum LV, respectively), hypertrophy (morphometric analysis) and ACE and ACE2 catalytic activity (fluorimetrically). Expression of calcium handling proteins was measured by western blot. Male rats exhibited higher cardiac ACE and ACE2 activity as well as hypertrophy compared to female rats. Orchiectomy decreased the activity of these enzymes and hypertrophy, while ovariectomy increased hypertrophy and ACE2, but did not change ACE activity. For cardiac function, the male sham group had a lower +dP/dt than the female sham group. After gonadectomy, the +dP/dt increased in males and reduced in females. The male sham group had a lower -dP/dt than the female group. After gonadectomy, the -dP/dt increased in the male and decreased in the female groups when compared to the sham group. No difference was observed among the groups in SERCA2a protein expression. Gonadectomy increased protein expression of PLB (phospholamban) and the PLB to SERCA2a ratio in female rats, but did not change in male rats. Conclusion Ovariectomy leads to increased cardiac hypertrophy, ACE2 activity, PLB expression and PLB to SERCA2a ratio, and worsening of hemodynamic variables, whereas in males the removal of testosterone has the opposite effects on RAS components. PMID:26010093

  15. Relation of thyroid hormone abnormalities with subclinical inflammatory activity in patients with type 1 and type 2 diabetes mellitus.

    PubMed

    Moura Neto, Arnaldo; Parisi, Maria Candida Ribeiro; Alegre, Sarah Monte; Pavin, Elizabeth Joao; Tambascia, Marcos Antonio; Zantut-Wittmann, Denise Engelbrecht

    2016-01-01

    Thyroid hormone (TH) abnormalities are common in patients with diabetes mellitus (DM). These thyroid hormone abnormalities have been associated with inflammatory activity in several conditions but this link remains unclear in DM. We assessed the influence of subclinical inflammation in TH metabolism in euthyroid diabetic patients. Cross-sectional study involving 258 subjects divided in 4 groups: 70 patients with T2DM and 55 patients with T1DM and two control groups of 70 and 63 non-diabetic individuals, respectively. Groups were paired by age, sex, and body mass index (BMI). We evaluated the association between clinical and hormonal variables [thyrotropin, reverse T3 (rT3), total and free thyroxine (T4), and triiodothyronine (T3)] with the inflammation markers C-reactive protein (hs-CRP), serum amyloid A (SAA), and interleukin-6 (IL-6). Serum T3 and free T3 were lower in patients with diabetes (all P < 0.001) compared to the control groups. Interleukin-6 showed positive correlations with rT3 in both groups (P < 0.05). IL-6 was independently associated to FT3/rT3 (B = -0.193; 95% CI -0.31; -0.076; P = 0.002) and FT4/rT3 (B = -0.107; 95% CI -0.207; -0.006; P = 0.039) in the T1DM group. In the T2DM group, SAA (B = 0.18; 95% CI 0.089; 0.271; P < 0.001) and hs-CRP (B = -0.069; 95% CI -0.132; -0.007; P = 0.03) predicted FT3 levels. SAA (B = -0.16; 95% CI -0.26; -0.061; P = 0.002) and IL6 (B = 0.123; 95% CI 0.005; 0.241; P = 0.041) were related to FT4/FT3. In DM, differences in TH levels compared to non-diabetic individuals were related to increased subclinical inflammatory activity and BMI. Altered deiodinase activity was probably involved. These findings were independent of sex, age, BMI, and HbA1c levels.

  16. 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

  17. 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

  18. Elevated hepatic gamma-glutamylcysteine synthetase activity and abnormal sulfate levels in liver and muscle tissue may explain abnormal cysteine and glutathione levels in SIV-infected rhesus macaques.

    PubMed

    Gross, A; Hack, V; Stahl-Hennig, C; Dröge, W

    1996-11-20

    To establish whether the low cysteine and glutathione levels in HIV-infected patients and SIV-infected rhesus macaques may be consequences of an abnormal cysteine catabolism, we analyzed sulfate and glutathione levels in macaques. Muscle tissue (m. vastus lateralis and m. gastrocnemius) of SIV-infected macaques (n = 25) had higher sulfate and lower glutathione and glutamate levels than that of uninfected controls (n =9). Hepatic tissue, in contrast, showed decreased sulfate and glutathione disulfide (GSSG) levels, and increased gamma-glutamylcysteine synthetase (gamma-GCS) activity. These findings suggest drainage of the cysteine pool by increased cysteine catabolism in skeletal muscle tissue, and by increased hepatic glutathione biosynthesis. Cachectic macaques also showed increased urea levels and decreased glutamine/urea ratios in the liver, which are obviously related to the abnormal urea excretion and negative nitrogen balance commonly observed in cachexia. As urea production and net glutamine synthesis in the liver are strongly influenced by proton-generating processes, the abnormal hepatic urea production may be the direct consequence of the cysteine deficiency and the decreased catabolic conversion of cysteine into sulfate and protons in the liver.

  19. 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

  20. 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.

  1. Spontaneous Recovery

    ERIC Educational Resources Information Center

    Rescorla, Robert A.

    2004-01-01

    Spontaneous recovery from extinction is one of the most basic phenomena of Pavlovian conditioning. Although it can be studied by using a variety of designs, some procedures are better than others for identifying the involvement of underlying learning processes. A wide range of different learning mechanisms has been suggested as being engaged by…

  2. Vasopressin modulates the spontaneous electrical activity in aortic cells (line A7r5) by acting on three different types of ionic channels.

    PubMed Central

    Van Renterghem, C; Romey, G; Lazdunski, M

    1988-01-01

    A7r5 smooth muscle (aorta) cells have a spontaneous electrical activity. Application of vasopressin produces a hyperpolarization accompanied by an interruption of the spontaneous activity, which is followed by a depolarization associated with a recovery of the spiking activity. Vasopressin action is produced by an action of the peptide on three different types of ionic channels. Vasopressin activates a Ca2+-sensitive K+ conductance, presumably by producing inositol 1,4,5-trisphosphate intracellularly and liberating Ca2+ from internal stores. This activation is transient (0.5-4 min) and is related to the vasopressin-induced hyperpolarization. Intracellular perfusion of inositol trisphosphate triggers by itself a transient K+ current and prevents subsequent activation by vasopressin. Vasopressin inhibits an L-type Ca2+ channel through both protein kinase C activation and a [Ca2+]i-dependent inactivation mechanism triggered by inositol trisphosphate production. The addition of the activation of a Ca2+-sensitive K+ channel and of the inhibition of a voltage-sensitive Ca2+ channel is responsible for the transient blockade of the spontaneous activity. Vasopressin also provokes the activation of an inward current (2-20 min) due to a nonselective channel able to transfer Ca2+, Na+, K+, and Cs+ across the membrane. This effect of the peptide is associated with the depolarization following the hyperpolarization phase. Images PMID:2461570

  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. Effect of Imperatorin on the Spontaneous Motor Activity of Rat Isolated Jejunum Strips.

    PubMed

    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 Ca(2+)-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 Ca(2+) 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.

  5. 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...

  6. 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

  7. [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

  8. Inhibition of spontaneous network activity in neonatal hippocampal slices by energy substrates is not correlated with intracellular acidification.

    PubMed

    Mukhtarov, Marat; Ivanov, Anton; Zilberter, Yuri; Bregestovski, Piotr

    2011-01-01

    Several energy substrates complementary to glucose, including lactate, pyruvate and β-hydroxybutyrate, serve as a fuel for neurons. It was reported recently that these substrates can substantially modulate cortical excitability in neonatal slices. However, complementary energy substrates (CES) can also induce an intracellular acidification when added exogenously. Therefore, action of CES on the neuronal properties governing excitability in neonatal brain slices may be underlain by a change in the cell energy status or by intracellular acidification, or both. Here, we attempt to elucidate these possibilities in neonatal hippocampus by recording neuronal population activity and monitoring intracellular pH. We show that a spontaneous network activity pattern, giant depolarizing potentials (GDPs), characteristic for the neonatal hippocampal slices exposed to artificial cerebrospinal fluid, is strongly inhibited by CES and this effect is unlikely to be caused by a subtle intracellular acidification induced by these compounds. Indeed, a much stronger intracellular acidification in the HCO(3) -free solution inhibited neither the GDP frequency nor the GDP amplitude. Therefore, modulation of neuronal energy homeostasis is the most likely factor underlying the effect of lactate, pyruvate and β-hydroxybutyrate on network excitability in neonatal brain slices.

  9. 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.

  10. 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

  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. Spontaneous inactivation of human tryptase involves conformational changes consistent with conversion of the active site to a zymogen-like structure.

    PubMed

    Selwood, T; McCaslin, D R; Schechter, N M

    1998-09-22

    The conformational changes accompanying spontaneous inactivation and dextran sulfate (DS) mediated reactivation of the serine protease human tryptase were investigated by analysis of (i) intrinsic fluorescence, (ii) inhibitor binding, and (iii) catalytic efficiency. Spontaneous inactivation produced a marked decrease in fluorescence emission intensity that was reversed by the addition of DS. Fluorescence decreases at high (4.0 microM) and low (0.1 microM) tryptase concentrations were similar at early times and coincided with loss of enzymatic activity but deviated significantly from activity loss at later times by showing a difference in the extent of change. The fluorescence losses were best described by a two-step kinetic model in which the major decrease correlated to activity loss (t1/2 of 4.3 min in 0.2 M NaCl, pH 6.8, 30 degrees C) and was followed by a further decrease (t1/2 approximately 60 min) whose extent differed with tryptase concentration. The ability to bind the competitive inhibitor p-aminobenzamidine was reversibly lost upon spontaneous inactivation, providing evidence for conformational changes affecting the major substrate binding site (S1-pocket). Estimation of catalytic efficiency using an active site titrant showed that the specific activity of tryptase remained unchanged upon inactivation and reactivation. Return of enzymatic activity, intrinsic fluorescence, and the S1 pocket appeared to occur in the same time frame (t1/2 approximately 3 min). These studies indicate that spontaneous inactivation involves reversible changes which convert the active site to a nonfunctional state. The association of activity loss with an intrinsic fluorescence decrease and loss of the S1-pocket is consistent with the disruption of a critical ionic bond at the active site. Formation of this ionic bond is the basis of zymogen activation for the chymotrypsin family of serine proteases. PMID:9748324

  13. Chronic baroreflex activation restores spontaneous baroreflex control and variability of heart rate in obesity-induced hypertension.

    PubMed

    Iliescu, Radu; Tudorancea, Ionut; Irwin, Eric D; Lohmeier, Thomas E

    2013-10-01

    The sensitivity of baroreflex control of heart rate is depressed in subjects with obesity hypertension, which increases the risk for cardiac arrhythmias. The mechanisms are not fully known, and there are no therapies to improve this dysfunction. To determine the cardiovascular dynamic effects of progressive increases in body weight leading to obesity and hypertension in dogs fed a high-fat diet, 24-h continuous recordings of spontaneous fluctuations in blood pressure and heart rate were analyzed in the time and frequency domains. Furthermore, we investigated whether autonomic mechanisms stimulated by chronic baroreflex activation and renal denervation-current therapies in patients with resistant hypertension, who are commonly obese-restore cardiovascular dynamic control. Increases in body weight to ∼150% of control led to a gradual increase in mean arterial pressure to 17 ± 3 mmHg above control (100 ± 2 mmHg) after 4 wk on the high-fat diet. In contrast to the gradual increase in arterial pressure, tachycardia, attenuated chronotropic baroreflex responses, and reduced heart rate variability were manifest within 1-4 days on high-fat intake, reaching 130 ± 4 beats per minute (bpm) (control = 86 ± 3 bpm) and ∼45% and <20%, respectively, of control levels. Subsequently, both baroreflex activation and renal denervation abolished the hypertension. However, only baroreflex activation effectively attenuated the tachycardia and restored cardiac baroreflex sensitivity and heart rate variability. These findings suggest that baroreflex activation therapy may reduce the risk factors for cardiac arrhythmias as well as lower arterial pressure.

  14. 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

  15. 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

  16. 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

    2015-11-16

    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.

  17. 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.

  18. 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

  19. Central neuronal responsiveness to sensory ganglion stimulation is correlated with the incidence of spontaneous bioelectric activity in developing spinal cord cultures.

    PubMed

    Corner, M A; Baker, R E

    1987-11-01

    In spinal cord explants co-cultured with dorsal root ganglion cells for 3-4 weeks in a (horse)serum-containing medium, the spread of ganglion-evoked action potentials from monosynaptic innervation sites ("polysynaptic excitability index") was not correlated with the incidence of neuronal "background" discharges. Moreover, chronic exposure of serum-grown cultures to tetrodotoxin (TTX) in a dose sufficient to reversibly block bioelectric activity, failed to significantly affect this index. For explants grown in a chemically defined medium (CDM) similar excitability scores were obtained only if a low level of spontaneous activity was measured. The most active preparations scored considerably higher, with intermediate values being found in the moderately active cultures. Chronic TTX-exposure in developing CDM-grown cultures reduced their excitability scores to the level found in weakly active, untreated, explants despite a normal incidence of spontaneous activity. The present study indicates that low levels of spontaneous activity in untreated explants were associated with a similar sluggishness of DRG-evoked responses as previously observed after chronic treatment with TTX. These results give additional grounds for confidence that this reduced responsiveness of spinal cord neurons to sensory input is indeed attributable to prolonged reduction of centrally generated excitation during development in vitro.

  20. Lysyl oxidase activity contributes to collagen stabilization during liver fibrosis progression and limits spontaneous fibrosis reversal in mice.

    PubMed

    Liu, Susan B; Ikenaga, Naoki; Peng, Zhen-Wei; Sverdlov, Deanna Y; Greenstein, Andrew; Smith, Victoria; Schuppan, Detlef; Popov, Yury

    2016-04-01

    Collagen stabilization through irreversible cross-linking is thought to promote hepatic fibrosis progression and limit its reversibility. However, the mechanism of this process remains poorly defined. We studied the functional contribution of lysyl oxidase (LOX) to collagen stabilization and hepatic fibrosis progression/reversalin vivousing chronic administration of irreversible LOX inhibitor β-aminopropionitrile (BAPN, or vehicle as control) in C57Bl/6J mice with carbon tetrachloride (CCl4)-induced fibrosis. Fibrotic matrix stability was directly assessed using a stepwise collagen extraction assay and fibrotic septae morphometry. Liver cells and fibrosis were studied by histologic, biochemical methods and quantitative real-time reverse-transcription PCR. During fibrosis progression, BAPN administration suppressed accumulation of cross-linked collagens, and fibrotic septae showed widening and collagen fibrils splitting, reminiscent of remodeling signs observed during fibrosis reversal. LOX inhibition attenuated hepatic stellate cell activation markers and promoted F4/80-positive scar-associated macrophage infiltration without an increase in liver injury. In reversal experiments, BAPN-treated fibrotic mice demonstrated accelerated fibrosis reversal after CCl4withdrawal. Our findings demonstrate for the first time that LOX contributes significantly to collagen stabilization in liver fibrosis, promotes fibrogenic activation of attenuated hepatic stellate cells, and limits fibrosis reversal. Our data support the concept of pharmacologic targeting of LOX pathway to inhibit liver fibrosis and promote its resolution.-Liu, S. B., Ikenaga, N., Peng, Z.-W., Sverdlov, D. Y., Greenstein, A., Smith, V., Schuppan, D., Popov, Y. Lysyl oxidase activity contributes to collagen stabilization during liver fibrosis progression and limits spontaneous fibrosis reversal in mice.

  1. Predicting Stroop Effect from Spontaneous Neuronal Activity: A Study of Regional Homogeneity

    PubMed Central

    Liu, Congcong; Chen, Zhencai; Wang, Ting; Tang, Dandan; Hitchman, Glenn; Sun, Jiangzhou; Zhao, Xiaoyue; Wang, Lijun; Chen, Antao

    2015-01-01

    The Stroop effect is one of the most robust and well-studied phenomena in cognitive psychology and cognitive neuroscience. However, little is known about the relationship between intrinsic brain activity and the individual differences of this effect. In the present study, we explored this issue by examining whether resting-state functional magnetic resonance imaging (rs-fMRI) signals could predict individual differences in the Stroop effect of healthy individuals. A partial correlation analysis was calculated to examine the relationship between regional homogeneity (ReHo) and Stroop effect size, while controlling for age, sex, and framewise displacement (FD). The results showed positive correlations in the left inferior frontal gyrus (LIFG), the left insula, the ventral anterior cingulate cortex (vACC), and the medial frontal gyrus (MFG), and negative correlation in the left precentral gyrus (LPG). These results indicate the possible influences of the LIFG, the left insula, and the LPG on the efficiency of cognitive control, and demonstrate that the key nodes of default mode network (DMN) may be important in goal-directed behavior and/or mental effort during cognitive control tasks. PMID:25938442

  2. Spontaneous coronary artery thrombosis in the setting of active lupus mesenteric vasculitis.

    PubMed

    Reddy, Yogesh N V; Sundaram, V; Tam, M; Parikh, S A

    2015-07-01

    A 33-year-old male with systemic lupus erythematosus (SLE) presented with acute abdominal pain and was found to have lupus mesenteric vasculitis on imaging and during exploratory laparotomy. Post laparotomy he continued to have persistent nausea and dyspepsia and an electrocardiogram showed evidence of an inferior ST elevation myocardial infarction (STEMI). Emergency cardiac catheterization showed evidence of thrombotic right coronary artery occlusion. His coronaries were otherwise normal with no evidence of underlying coronary artery disease. Extensive workup with trans-esophageal echo, serologies for antiphospholipid antibody syndrome (APS) and bubble study was negative. This effectively ruled out Libman-Sacks endocarditis, APS-induced arterial thrombus and paradoxical emboli as potential causes of his STEMI. By exclusion of other causes, the etiology of his STEMI was felt to be secondary to in-situ coronary artery thrombosis in the setting of active SLE. To the best of our knowledge, this is the first report of a patient with SLE presenting with both lupus mesenteric vasculitis and in-situ coronary arterial thrombosis in the absence of APS.

  3. Predicting stroop effect from spontaneous neuronal activity: a study of regional homogeneity.

    PubMed

    Liu, Congcong; Chen, Zhencai; Wang, Ting; Tang, Dandan; Hitchman, Glenn; Sun, Jiangzhou; Zhao, Xiaoyue; Wang, Lijun; Chen, Antao

    2015-01-01

    The Stroop effect is one of the most robust and well-studied phenomena in cognitive psychology and cognitive neuroscience. However, little is known about the relationship between intrinsic brain activity and the individual differences of this effect. In the present study, we explored this issue by examining whether resting-state functional magnetic resonance imaging (rs-fMRI) signals could predict individual differences in the Stroop effect of healthy individuals. A partial correlation analysis was calculated to examine the relationship between regional homogeneity (ReHo) and Stroop effect size, while controlling for age, sex, and framewise displacement (FD). The results showed positive correlations in the left inferior frontal gyrus (LIFG), the left insula, the ventral anterior cingulate cortex (vACC), and the medial frontal gyrus (MFG), and negative correlation in the left precentral gyrus (LPG). These results indicate the possible influences of the LIFG, the left insula, and the LPG on the efficiency of cognitive control, and demonstrate that the key nodes of default mode network (DMN) may be important in goal-directed behavior and/or mental effort during cognitive control tasks.

  4. The contribution of pre-stimulus neural oscillatory activity to spontaneous response time variability

    PubMed Central

    Bompas, Aline; Sumner, Petroc; Muthumumaraswamy, Suresh D.; Singh, Krish D.; Gilchrist, Iain D.

    2015-01-01

    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

  5. Fluorescent probes as a tool for cell population tracking in spontaneously active neural networks derived from human pluripotent stem cells.

    PubMed

    Mäkinen, M; Joki, T; Ylä-Outinen, L; Skottman, H; Narkilahti, S; Aänismaa, R

    2013-04-30

    Applications such as 3D cultures and tissue modelling require cell tracking with non-invasive methods. In this work, the suitability of two fluorescent probes, CellTracker, CT, and long chain carbocyanine dye, DiD, was investigated for long-term culturing of labeled human pluripotent stem cell-derived neural cells. We found that these dyes did not affect the cell viability. However, proliferation was decreased in DiD labeled cell population. With both dyes the labeling was stable up to 4 weeks. CT and DiD labeled cells could be co-cultured and, importantly, these mixed populations had their normal ability to form spontaneous electrical network activity. In conclusion, human neural cells can be successfully labeled with these two fluorescent probes without significantly affecting the cell characteristics. These labeled cells could be utilized further in e.g. building controlled neuronal networks for neurotoxicity screening platforms, combining cells with biomaterials for 3D studies, and graft development. PMID:23473797

  6. Sex-related differences in mast cell activity and doxorubicin toxicity: a study in spontaneously hypertensive rats.

    PubMed

    Zhang, Jun; Knapton, Alan; Lipshultz, Steven E; Cochran, Thomas R; Hiraragi, Hajime; Herman, Eugene H

    2014-01-01

    Clinically, girls appear to be more sensitive than boys to the cardiotoxic effects of doxorubicin, whereas the opposite may be true for adults. To identify and characterize potential sex-related differences, adult male and female spontaneously hypertensive rats (SHR; some ovariectomized [OVX]) received 1 mg/kg of doxorubicin or saline iv weekly for 9, 10, or 12 weeks. Weight gain was slower in treated males. Serum concentrations of cholesterol and triglycerides increased and those of albumin decreased in both sexes, but changes were more pronounced in treated males. Treated males had significantly more severe cardiomyopathy scores and higher serum levels of cTnT than females. The increased cardiotoxicity was accompanied by higher numbers of cardiac mast cells (MCs) and percentage of cardiac MCs undergoing degranulation. Doxorubicin-treated OVX animals had significantly increased numbers of cardiac MCs, more severe myocardial lesions, and elevated serum concentrations of cTnT compared to doxorubicin-treated normal female SHR. The severity of cardiac lesions in the OVX female was similar to that observed in doxorubicin-treated males. This study demonstrated the presence of sex-related differences in the cardiotoxic effects elicited by doxorubicin and identified variations in the level of cardiac MC activity as a factor which could possibly contribute to the male-female dissimilarity.

  7. Myelinated Afferents Are Involved in Pathology of the Spontaneous Electrical Activity and Mechanical Hyperalgesia of Myofascial Trigger Spots in Rats

    PubMed Central

    2015-01-01

    Myofascial trigger points (MTrPs) are common causes for chronic pain. Myelinated afferents were considered to be related with muscular pain, and our clinical researches indicated they might participate in the pathology of MTrPs. Here, we applied myofascial trigger spots (MTrSs, equal to MTrPs in human) of rats to further investigate role of myelinated afferents. Modified pyridine-silver staining revealed more nerve endings at MTrSs than non-MTrSs (P < 0.01), and immunohistochemistry with Neurofilament 200 indicated more myelinated afferents existed in MTrSs (P < 0.01). Spontaneous electrical activity (SEA) recordings at MTrSs showed that specific block of myelinated afferents in sciatic nerve with tetrodotoxin (TTX) led to significantly decreased SEA (P < 0.05). Behavioral assessment showed that mechanical pain thresholds (MPTs) of MTrSs were lower than those of non-MTrSs (P < 0.01). Block of myelinated afferents by intramuscular TTX injection increased MPTs of MTrSs significantly (P < 0.01), while MPTs of non-MTrSs first decreased (P < 0.05) and then increased (P > 0.05). 30 min after the injection, MPTs at MTrSs were significantly lower than those of non-MTrSs (P < 0.01). Therefore, we concluded that proliferated myelinated afferents existed at MTrSs, which were closely related to pathology of SEA and mechanical hyperalgesia of MTrSs. PMID:26064165

  8. 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.

  9. 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

  10. 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

  11. Spontaneous production of thymocyte-activating factor by human gingival fibroblasts and its autoregulatory effect on their proliferation.

    PubMed Central

    Ohmori, Y; Hanazawa, S; Amano, S; Miyoshi, T; Hirose, K; Kitano, S

    1987-01-01

    The purpose of this study was to examine whether human gingival fibroblasts produce a cytokine which modulates in immune and inflammatory responses including alterations in connective tissue metabolism in periodontal tissue. We found that a cultured human gingival fibroblast cell line (Gin-1) and freshly isolated human gingival fibroblasts produced thymocyte-activating factor(s), so we called the factor(s) fibroblast-derived thymocyte-activating factor (FTAF). Growth of the producing cell was itself modulated by the factor(s). Gin-1 cells spontaneously produced a significant amount of FTAF in a cell growth-dependent manner. Maximum activity was observed in conditioned medium from stationary-phase cells. The activity in conditioned medium of cultures lacking serum was significantly higher than that in those containing serum. Treatment of Gin-1 cell cultures with cycloheximide, an inhibitor of protein synthesis, markedly inhibited FTAF production. When Gin-1 cells were stimulated by triggering with muramyl dipeptide or sonicated extracts of Bacteroides gingivalis, FTAF production was significantly stimulated. Freshly isolated human gingival fibroblasts from gingival biopsies of healthy donors also produced FTAF which enhanced thymocyte proliferation. Peaks of thymocyte proliferation activity in conditioned medium from Gin-1 cells were observed in fractions having molecular weights of 25,000, 35,000, and 45,000, as determined by Sephadex G-75 column chromatography. The peak fractions (partially purified FTAF) significantly suppressed the proliferation of Gin-1 cells themselves as evaluated by [3H]thymidine uptake. The suppressive effect of partially purified FTAF was, at least partially, mediated by endogenous prostaglandin for the following reasons: addition of indomethacin, and inhibitor of prostaglandin synthesis, abrogated the suppressive effect; partially purified FTAF stimulated the production of prostaglandin E2 by the cells; and the suppression of cell

  12. Spontaneous fission

    SciTech Connect

    Hoffman, D.C.

    1993-09-01

    The spontaneous fission (SF) of the heaviest actinides and the transactinides is of particular interest because of the dramatic changes in properties observed in the region of the heavy fermion isotopes and for still heavier elements. The existing experimental information on SF properties including half-life systematics, fragment kinetic-energy and mass-yield distributions, prompt neutron emission, and gamma emission will be reviewed. Possibility for extending studies of SF properties to other regions are considered and the potential for obtaining additional information about low-energy fission properties is discussed.

  13. 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

  14. 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

    2016-08-01

    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.

  15. 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

  16. Ligand specific variation in cardiac response to stimulation of peroxisome proliferator-activated receptor-alpha in spontaneously hypertensive rat.

    PubMed

    Ismael, Saifudeen; Purushothaman, Sreeja; Harikrishnan, V S; Nair, R Renuka

    2015-08-01

    Left ventricular hypertrophy (LVH) is an independent risk factor for cardiac failure. Reduction of LVH has beneficial effects on the heart. LVH is associated with shift in energy substrate preference from fatty acid to glucose, mediated by down regulation of peroxisome proliferator-activated receptor-alpha (PPAR-α). As long-term dependence on glucose can promote adverse cardiac remodeling, it was hypothesized that, prevention of metabolic shift by averting down regulation of PPAR-α can reduce cardiac remodeling in spontaneously hypertensive rat (SHR). Cardiac response to stimulation of PPAR-α presumably depends on the type of ligand used. Therefore, the study was carried out in SHR, using two different PPAR-α ligands. SHR were treated with either fenofibrate (100 mg/kg/day) or medium-chain triglyceride (MCT) Tricaprylin (5% of diet) for 4 months. Expression of PPAR-α and medium-chain acylCoA dehydrogenase served as markers, for stimulation of PPAR-α. Both ligands stimulated PPAR-α. Decrease of blood pressure was observed only with fenofibrate. LVH was assessed from heart-weight/body weight ratio, histology and brain natriuretic peptide expression. As oxidative stress is linked with hypertrophy, serum and cardiac malondialdehyde and cardiac 3-nitrotyrosine levels were determined. Compared to untreated SHR, LVH and oxidative stress were lower on supplementation with MCT, but higher on treatment with fenofibrate. The observations indicate that reduction of blood pressure is not essentially accompanied by reduction of LVH, and that, progressive cardiac remodeling can be prevented with decrease in oxidative stress. Contrary to the notion that reactivation of PPAR-α is detrimental; the study substantiates that cardiac response to stimulation of PPAR-α is ligand specific. PMID:25976666

  17. 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

  18. 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

  19. 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

  20. Sex-specific 24-h acetylcholine release profile in the medial prefrontal cortex: simultaneous measurement of spontaneous locomotor activity in behaving rats.

    PubMed

    Takase, K; Kimura, F; Yagami, T; Mitsushima, D

    2009-03-01

    The difference in visual object recognition by males and females suggests a sex-specific function in the medial prefrontal cortex (mPFC). In the present study, we performed an in vivo microdialysis study in three groups of rats (males, diestrous females, and proestrous females) to examine the potential sex difference in acetylcholine (ACh) release in the mPFC. The dialysate was automatically collected from the mPFC every 20 min for 24 h under freely moving conditions and the spontaneous locomotor activity was simultaneously monitored. Although ACh release in the mPFC during the dark phase was significantly greater than during the light phase in both sexes, the female rats consistently exhibited a significantly greater mean ACh release than the males. Spontaneous locomotor activity during the dark phase was also significantly greater than during the light phase in both sexes, but the females exhibited significantly greater spontaneous locomotor activity than the males. In addition, both sexes of rats were found to have significant positive correlations between ACh release and spontaneous locomotor activity, but females were found to have significantly greater correlation coefficients than males. Stereological methods were used to examine the number of choline acetyltransferase immunoreactive cells in the nucleus basalis magnocellularis and the horizontal diagonal band of Broca. The number of choline acetyltransferase immunoreactive cells in the nucleus basalis magnocellularis was also greater in females than males, suggesting a contribution to the higher ACh release in females. In contrast, no sex difference in the choline acetyltransferase immunoreactive cells was observed in the horizontal diagonal band of Broca. This is the first report to show a sex difference in the 24-h ACh release profile in the mPFC of behaving rats.

  1. Sex-specific 24-h acetylcholine release profile in the medial prefrontal cortex: simultaneous measurement of spontaneous locomotor activity in behaving rats.

    PubMed

    Takase, K; Kimura, F; Yagami, T; Mitsushima, D

    2009-03-01

    The difference in visual object recognition by males and females suggests a sex-specific function in the medial prefrontal cortex (mPFC). In the present study, we performed an in vivo microdialysis study in three groups of rats (males, diestrous females, and proestrous females) to examine the potential sex difference in acetylcholine (ACh) release in the mPFC. The dialysate was automatically collected from the mPFC every 20 min for 24 h under freely moving conditions and the spontaneous locomotor activity was simultaneously monitored. Although ACh release in the mPFC during the dark phase was significantly greater than during the light phase in both sexes, the female rats consistently exhibited a significantly greater mean ACh release than the males. Spontaneous locomotor activity during the dark phase was also significantly greater than during the light phase in both sexes, but the females exhibited significantly greater spontaneous locomotor activity than the males. In addition, both sexes of rats were found to have significant positive correlations between ACh release and spontaneous locomotor activity, but females were found to have significantly greater correlation coefficients than males. Stereological methods were used to examine the number of choline acetyltransferase immunoreactive cells in the nucleus basalis magnocellularis and the horizontal diagonal band of Broca. The number of choline acetyltransferase immunoreactive cells in the nucleus basalis magnocellularis was also greater in females than males, suggesting a contribution to the higher ACh release in females. In contrast, no sex difference in the choline acetyltransferase immunoreactive cells was observed in the horizontal diagonal band of Broca. This is the first report to show a sex difference in the 24-h ACh release profile in the mPFC of behaving rats. PMID:19162130

  2. Effects of proton radiation on evoked and spontaneous neuronal activity in the hippocampus of APP/PSEN1 transgenic mice

    PubMed Central

    Rudobeck, Emil; Szucs, Attila; Vlkolinsky, Roman

    2014-01-01

    Ground-based studies on space radiation indicate that exposure to charged particle radiation at relatively low doses may impair neuronal functions. Decrements in excitatory synaptic transmission and plasticity in the hippocampus have been previously reported in mouse brains irradiated with iron nuclei, but relatively little is known about the effects of protons on the synaptic activity in the hippocampus. Behavioral and neurophysiological decrements in irradiated subjects are also commonly observed in Alzheimer's disease (AD), and we hypothesized that irradiation with protons may exacerbate AD-like neurodegenerative pathology. We used transgenic (TG) mice with AD-like neurodegeneration to test whether whole-body irradiation with protons (150 MeV; 0.1, 0.5, 1 Gy) accelerates the onset of AD and/or exacerbates synaptic impairments. We measured evoked excitatory synaptic potentials, synaptic plasticity and spontaneous oscillations in hippocampal slices prepared from APP/PSEN1 double TG mice (males only) at 6 and 9 months post-irradiation. Our electrophysiological recordings indicate that most of the radiation-induced synaptic decrements can be observed at 9 months rather than 6 months post-irradiation and they are differently expressed in TG and wild-type (WT) mice. Presynaptic excitability evaluated by the amplitude of fiber volleys was significantly increased in non-irradiated TG mice when compared with non-irradiated WT mice, and irradiation did not cause further alterations. The post-synaptic, dendritic excitability, evaluated by the initial slope of the excitatory post-synaptic potentials (EPSPs), was reduced in TG mice exposed to 0.5 Gy, but increased relative to WT mice at the same dose. Interestingly, the suppressive effect on EPSP in TG mice was not observed at 1 Gy. Post-synaptic firing of action potentials, evaluated by the amplitude of population spikes (PS), was increased in non-irradiated TG mice when compared with WT controls. However, these increases

  3. Nitric oxide synthase activity in blood vessels of spontaneously hypertensive rats: antioxidant protection by gamma-tocotrienol.

    PubMed

    Newaz, M A; Yousefipour, Z; Nawal, N; Adeeb, N

    2003-09-01

    Involvement of free radicals and nitric oxide (NO) has long been implicated to the pathogenesis of essential hypertension. Several studies using antioxidants as the radical scavenger have shown to confer protection against free radical mediated diseases. This study is designed to investigate the role of antioxidant gamma-tocotrienol on endothelial nitric oxide synthase (NOS) activity in spontaneously hypertensive rats (SHR). SHR's were divided into four groups namely untreated SHR (HC), treatment with 15 mg gamma-tocotrienol/kg diet (gammal), 30 mg gamma-tocotrienol/kg diet (gamma2) and 150 mg gamma-tocotrienol/kg diet (gamma3) and studied for three months. Wister Kyoto (WKY) rats were used as the control (C). Blood pressure was recorded every fortnightly by tail plethysmography. Animals were sacrificed and NOS activity in blood vessels was measured by [3H]arginine radioactive assay. Nitrite concentration in plasma was determined by Greis assay and lipid peroxides in the blood vessels by spectrofluorometry. This study showed that gamma-tocotrienol significantly reduced systolic blood pressure (SBP) in SHRs with a maximum reduction in group treated with gamma-tocotrienol 15 mg/kg diet (HC: 210 +/- 9 mmHg, gammal:123 +/- 19 mmHg). Blood vessels from untreated SHR showed a reduced NOS activity compare to that of WKY rats (C: 1.54 +/- 0.26 pmol/mg protein, HC: 0.87 +/- 0.23 pmol/mg protein; p<0.001). Gamma-tocotrienol improves NOS activity in all the groups with more significance in group gamma2 (p<0.001) and gamma3 (p<0.05). Plasma level of nitrite was reduced in SHR from 55 +/- 3 microM/ml in WKY to 26+/-2 muM/ml (p<0.001). Plasma nitrite level was reversed by treatment with gamma-tocotrienol. (gammal: p<0.001, gamma2: p<0.005, gamma3: p<0.001, respectively). In all the treatment groups, NOS activity showed significant negative correlation with blood pressure (gammal: r=-0.716, p<0.05; gamma2: r=-0.709, p<0.05; gamma3: r=-0.789, p<0.05). For plasma nitrite, although

  4. 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.

  5. 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

  6. 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

  7. MR appearance of bilateral, spontaneous patellar tendon rupture in systemic lupus erythematosus.

    PubMed

    Gould, E S; Taylor, S; Naidich, J B; Furie, R; Lane, L

    1987-01-01

    Bilateral spontaneous patellar tendon rupture is an unusual complication in patients with systemic lupus erythematosus. The ability of magnetic resonance to detect these tendon abnormalities is demonstrated.

  8. 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...

  9. 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

  10. 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.

  11. [Comparative study of the pharmacological properties of sultopride sulpiride and other antipsychotic drugs: influence of sultopride, sulpiride and other antipsychotic drugs on spontaneous locomotor activity and changes in locomotor activity induced by apomorphine and clonidine in mice].

    PubMed

    Horikomi, K; Fujita, M

    1986-09-01

    To elucidate pharmacological properties of sultopride and sulpiride, their effects on spontaneous locomotor activity, apomorphine-induced hyper- and hypoactivity, and clonidine-induced hypoactivity in mice were examined by use of a photocell activity meter in comparison with the effects of other antipsychotic drugs. Sultopride did not affect spontaneous locomotor activity, whereas it potentiated apomorphine-induced hyperactivity at low doses and inhibited it at high doses. Sultopride also dose-dependently antagonized apomorphine-induced hypoactivity at limited doses. By contrast, sulpiride, in a wide range of doses, exhibited enhancement of apomorphine-induced hyperactivity and antagonization of apomorphine-induced hypoactivity. Furthermore, the activities of sulpiride were more potent than those of sultopride. Haloperidol and chlorpromazine inhibited spontaneous locomotor activity and apomorphine-induced hyperactivity and slightly antagonized apomorphine-induced hypoactivity. Pimozide increased spontaneous locomotor activity but inhibited it at high doses, while also potentiating apomorphine-induced hyperactivity at small doses and inhibiting it at large doses. Pimozide did not markedly affect apomorphine-induced hypoactivity. None of the drugs studied except for imipramine and yohimbine affected clonidine-induced hypoactivity. These results indicate that sultopride has somewhat different pharmacological properties from those of sulpiride and other antipsychotic drugs. These results also suggest that sultopride would have good therapeutic efficacy in schizophrenic disorders.

  12. 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

  13. 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

  14. 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.

  15. Association of physical activity measured by accelerometer, knee joint abnormalities and cartilage T2-measurements obtained from 3T MRI: Data from the Osteoarthritis Initiative

    PubMed Central

    Kretzschmar, M.; Lin, W.; Nardo, L.; Joseph, G. B.; Dunlop, D. D.; Heilmeier, U.; Nevitt, M. C.; Alizai, H.; McCulloch, C. E.; Lynch, J. A.; Link, T. M.

    2015-01-01

    Objective To study the cross-sectional association between physical activity measured with an accelerometer, structural knee abnormalities and cartilage T2-values assessed with 3T MRI. Methods We included 274 subjects from the Osteoarthritis Initiative cohort without definite radiographic osteoarthritis (KL 0 and 1) and at most mild pain, stiffness and functional limitation in the study knee (WOMAC 0–1), which had not limited their activity due to knee pain. Physical activity was measured over seven days with an ActiGraph GT1M accelerometer. Subjects were categorized by quartile of physical activity based on the average daily minutes of moderate/vigorous activity (mv-PA). MR images of the right knee (at 48-months visit) were assessed for structural abnormalities using a modified WORMS score and for T2-relaxation times derived from segmented cartilage of 4 femorotibial regions and the patella. WORMS-grades and T2-measurements were compared between activity quartiles using a linear regression model. Covariates included age, sex, BMI, knee injury, family history of knee replacement, knee symptoms, hip and ankle pain and daily wear time of the accelerometer. Results Higher mv-PA was associated with increased severity (p=0.0087) and number of lesions of the medial meniscus (p=0.0089) and severity of bone marrow edema lesions (p=0.0053). No association between cartilage lesions and mv-PA was found. T2-values of cartilage (loss, damage, abnormalities) tended to be greater in the higher quartiles of mv-PA, but the differences were non-significant. Conclusion In knees without radiographic osteoarthritis in subjects with no or mild knee pain, higher physical activity levels were associated with increases in meniscal and BMEP lesions. PMID:25777255

  16. Cyclin D1 and E2F-1 immunoreactivity in bone marrow biopsy specimens of multiple myeloma: relationship to proliferative activity, cytogenetic abnormalities and DNA ploidy.

    PubMed

    Wilson, C S; Butch, A W; Lai, R; Medeiros, L J; Sawyer, J R; Barlogie, B; McCourty, A; Kelly, K; Brynes, R K

    2001-03-01

    Cyclin D1, encoded by the CCND1 gene, is immunohistochemically detectable in up to one-third of cases of multiple myeloma (MM). To examine the mechanism of cyclin D1 overexpression, we compared cyclin D1 immunoreactivity with the results of conventional cytogenetics to determine if the t(11;14)(q13;q32) or other abnormalities of 11q11-14 explained cyclin D1 overexpression. Karyotypic abnormalities were found in 45 out of 67 (67%) MM cases; the t(11;14) was present in seven cases (10%). Additional 11q11-14 abnormalities were not identified. The t(11;14) correlated with cyclin D1 upregulation in low to intermediately proliferative MM, but was not present in highly proliferative tumours (assessed using bromodeoxyuridine labelling index). Cyclin D1 indirectly activates the transcription factor E2F-1. In the bone marrow biopsy specimens of MM cases, E2F-1 was concurrently expressed with cyclin D1 (P = 0.001), indicating that cyclin D1 is functional. However, as neither E2F-1 nor cyclin D1 expression correlated with proliferative activity, the speculation that t(11;14) upregulates the CCND1 gene to induce higher proliferation and possibly more aggressive disease is not supported. We conclude that in low to intermediately proliferative MM cases, cyclin D1 is probably upregulated by t(11;14), but an alternative mechanism is more probable in highly proliferative MM.

  17. 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

  18. 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.

  19. 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

  20. The origin of the 900 Hz spectral peak in spontaneous and sound-evoked round-window electrical activity.

    PubMed

    McMahon, Catherine M; Patuzzi, Robert B

    2002-11-01

    We have monitored the spectrum of the (spontaneous) neural noise at the round window (RW) and on the surface of the antero-ventral cochlear nucleus (CN) and the dorsal CN (DCN) of anaesthetised guinea pigs. We have also obtained the average gross extracellular waveform evoked by 20 kHz tone-bursts (0.25 ms and 25 ms) at each of these recording sites, and calculated the spectrum of the average waveforms (SAW). With these tone-bursts, only a small population of neurones in the extreme basal turn of the cochlea near the RW electrode responds, presumably with only a single action potential for each 0.25 ms tone-burst. The RW waveforms recorded between 20 dB and 60 dB SPL were very similar, and are therefore presumably a simple estimate of the shape of the contribution of the firing of a single neurone to the gross RW signal (the unitary potential or UP). In normal animals, the SNN and the SAW were remarkably similar, with peaks at 900 Hz and at 2400 Hz, suggesting that they are not due to neural synchronisation (as suggested previously by others), but are due to an oscillatory waveform produced by each single fibre action potential. Abolition of all spike activity by RW tetrodotoxin left a waveform with only a summating potential and a dendritic potential, and no 900 Hz peak in the SAW or SNN, indicating that the spectral peak is due to neural spiking only. Abolition of the CN contribution to the RW waveforms by CN application of lignocaine or sectioning of the cochlear nerve at the internal meatus (by focal aspiration of the DCN and underlying cochlear nerve) showed that the 900 Hz peak was not simply due to the addition of a delayed and inverted CN contribution: mathematical modelling shows that this would produce a broad spectral peak at about 1200 Hz. Moreover, the 900 Hz spectral peak remains after complete abolition of the CN contribution, although reduced in amplitude. This residual 900 Hz peak can be traced to an oscillation in the gross waveform due to the

  1. Liver transplantation nearly normalizes brain spontaneous activity and cognitive function at 1 month: a resting-state functional MRI study.

    PubMed

    Cheng, Yue; Huang, Lixiang; Zhang, Xiaodong; Zhong, Jianhui; Ji, Qian; Xie, Shuangshuang; Chen, Lihua; Zuo, Panli; Zhang, Long Jiang; Shen, Wen

    2015-08-01

    To investigate the short-term brain activity changes in cirrhotic patients with Liver transplantation (LT) using resting-state functional MRI (fMRI) with regional homogeneity (ReHo) method. Twenty-six cirrhotic patients as transplant candidates and 26 healthy controls were included in this study. The assessment was repeated for a sub-group of 12 patients 1 month after LT. ReHo values were calculated to evaluate spontaneous brain activity and whole brain voxel-wise analysis was carried to detect differences between groups. Correlation analyses were performed to explore the relationship between the change of ReHo with the change of clinical indexes pre- and post-LT. Compared to pre-LT, ReHo values increased in the bilateral inferior frontal gyrus (IFG), right inferior parietal lobule (IPL), right supplementary motor area (SMA), right STG and left middle frontal gyrus (MFG) in patients post-LT. Compared to controls, ReHo values of post-LT patients decreased in the right precuneus, right SMA and increased in bilateral temporal pole, left caudate, left MFG, and right STG. The changes of ReHo in the right SMA, STG and IFG were correlated with change of digit symbol test (DST) scores (P < 0.05 uncorrected). This study found that, at 1 month after LT, spontaneous brain activity of most brain regions with decreased ReHo in pre-LT was substantially improved and nearly normalized, while spontaneous brain activity of some brain regions with increased ReHo in pre-LT continuously increased. ReHo may provide information on the neural mechanisms of LT' effects on brain function.

  2. 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.

  3. 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

  4. Electrical Responses and Spontaneous Activity of Human iPS-Derived Neuronal Networks Characterized for 3-month Culture with 4096-Electrode Arrays.

    PubMed

    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

  5. Electrical Responses and Spontaneous Activity of Human iPS-Derived Neuronal Networks Characterized for 3-month Culture with 4096-Electrode Arrays.

    PubMed

    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

  6. Decreased frequency and activated phenotype of blood CD27 IgD IgM B lymphocytes is a permanent abnormality in systemic lupus erythematosus patients

    PubMed Central

    2010-01-01

    Introduction Systemic lupus erythematosus (SLE) is characterized by B cell hyper-activation and auto-reactivity resulting in pathogenic auto-antibody generation. The phenotypic analysis of blood B cell subsets can be used to understand these alterations. Methods The combined detection of CD19, CD27 and IgD (or IgM) by flow cytometry (FC) analysis delineates five well-defined blood B cell-subsets: naive, switched (S) memory, double negative (DN) memory and CD27 IgD IgM (non-switched memory) B lymphocytes, and plasma cells (PCs). This phenotypic study was performed in 69 consecutive SLE patients and 31 healthy controls. Results SLE patients exhibited several abnormalities in the distribution of these B cell subsets, including elevated levels of DN memory B cells and PCs, and decreased CD27 IgD IgM B cells. Active SLE patients also showed decreased presence of S memory B cells and increased proportions of naive B lymphocytes. Nevertheless, when the patients in remission who did not require treatment were studied separately, the only remaining abnormality was a reduction of the CD27 IgD IgM B cell-subset detectable in most of these patients. The level of reduction of CD27 IgD IgM B cells was associated with elevated values of serum SLE auto-antibodies. Further analysis of this latter B cell-subset specifically showed increased expression of CD80, CD86, CD95, 9G4 idiotype and functional CXCR3 and CXCR4. Conclusions The presence of a reduced blood CD27 IgD IgM B cell-subset, exhibiting an activated state and enriched for auto-reactivity, is a consistent B cell abnormality in SLE. These findings suggest that CD27 IgD IgM B lymphocytes play a role in the pathogenesis of this disease. PMID:20525218

  7. Experimental Investigation on Spontaneously Active Hippocampal Cultures Recorded by Means of High-Density MEAs: Analysis of the Spatial Resolution Effects.

    PubMed

    Maccione, Alessandro; Gandolfo, Mauro; Tedesco, Mariateresa; Nieus, Thierry; Imfeld, Kilian; Martinoia, Sergio; Berdondini, Luca

    2010-01-01

    Based on experiments performed with high-resolution Active Pixel Sensor microelectrode arrays (APS-MEAs) coupled with spontaneously active hippocampal cultures, this work investigates the spatial resolution effects of the neuroelectronic interface on the analysis of the recorded electrophysiological signals. The adopted methodology consists, first, in recording the spontaneous activity at the highest spatial resolution (interelectrode separation of 21 mum) from the whole array of 4096 microelectrodes. Then, the full resolution dataset is spatially downsampled in order to evaluate the effects on raster plot representation, array-wide spike rate (AWSR), mean firing rate (MFR) and mean bursting rate (MBR). Furthermore, the effects of the array-to-network relative position are evaluated by shifting a subset of equally spaced electrodes on the entire recorded area. Results highlight that MFR and MBR are particularly influenced by the spatial resolution provided by the neuroelectronic interface. On high-resolution large MEAs, such analysis better represent the time-based parameterization of the network dynamics. Finally, this work suggest interesting capabilities of high-resolution MEAs for spatial-based analysis in dense and low-dense neuronal preparation for investigating signaling at both local and global neuronal circuitries.

  8. Voluntary exercise contributed to an amelioration of abnormal feeding behavior, locomotor activity and ghrelin production concomitantly with a weight reduction in high fat diet-induced obese rats.

    PubMed

    Mifune, Hiroharu; Tajiri, Yuji; Nishi, Yoshihiro; Hara, Kento; Iwata, Shimpei; Tokubuchi, Ichiro; Mitsuzono, Ryouichi; Yamada, Kentaro; Kojima, Masayasu

    2015-09-01

    In the present study, effects of voluntary exercise in an obese animal model were investigated in relation to the rhythm of daily activity and ghrelin production. Male Sprague-Dawley rats were fed either a high fat diet (HFD) or a chow diet (CD) from four to 16 weeks old. They were further subdivided into either an exercise group (HFD-Ex, CD-Ex) with a running wheel for three days of every other week or sedentary group (HFD-Se, CD-Se). At 16 weeks old, marked increases in body weight and visceral fat were observed in the HFD-Se group, together with disrupted rhythms of feeding and locomotor activity. The induction of voluntary exercise brought about an effective reduction of weight and fat, and ameliorated abnormal rhythms of activity and feeding in the HFD-Ex rats. Wheel counts as voluntary exercise was greater in HFD-Ex rats than those in CD-Ex rats. The HFD-obese had exhibited a deterioration of ghrelin production, which was restored by the induction of voluntary exercise. These findings demonstrated that abnormal rhythms of feeding and locomotor activity in HFD-obese rats were restored by infrequent voluntary exercise with a concomitant amelioration of the ghrelin production and weight reduction. Because ghrelin is related to food anticipatory activity, it is plausible that ghrelin participates in the circadian rhythm of daily activity including eating behavior. A beneficial effect of voluntary exercise has now been confirmed in terms of the amelioration of the daily rhythms in eating behavior and physical activity in an animal model of obesity.

  9. Central command: control of cardiac sympathetic and vagal efferent nerve activity and the arterial baroreflex during spontaneous motor behaviour in animals.

    PubMed

    Matsukawa, Kanji

    2012-01-01

    Feedforward control by higher brain centres (termed central command) plays a role in the autonomic regulation of the cardiovascular system during exercise. Over the past 20 years, workers in our laboratory have used the precollicular-premammillary decerebrate animal model to identify the neural circuitry involved in the CNS control of cardiac autonomic outflow and arterial baroreflex function. Contrary to the traditional idea that vagal withdrawal at the onset of exercise causes the increase in heart rate, central command did not decrease cardiac vagal efferent nerve activity but did allow cardiac sympathetic efferent nerve activity to produce cardiac acceleration. In addition, central command-evoked inhibition of the aortic baroreceptor-heart rate reflex blunted the baroreflex-mediated bradycardia elicited by aortic nerve stimulation, further increasing the heart rate at the onset of exercise. Spontaneous motor activity and associated cardiovascular responses disappeared in animals decerebrated at the midcollicular level. These findings indicate that the brain region including the caudal diencephalon and extending to the rostral mesencephalon may play a role in generating central command. Bicuculline microinjected into the midbrain ventral tegmental area of decerebrate rats produced a long-lasting repetitive activation of renal sympathetic nerve activity that was synchronized with the motor nerve discharge. When lidocaine was microinjected into the ventral tegmental area, the spontaneous motor activity and associated cardiovascular responses ceased. From these findings, we conclude that cerebral cortical outputs trigger activation of neural circuits within the caudal brain, including the ventral tegmental area, which causes central command to augment cardiac sympathetic outflow at the onset of exercise in decerebrate animal models. PMID:21984731

  10. Spontaneous locomotor activity correlates with the degranulation of mast cells in the meninges rather than in the thalamus: disruptive effect of cocaine.

    PubMed

    Larson, Alice A; Thomas, Mark J; McElhose, Alex; Kovács, Katalin J

    2011-06-13

    Mast cells are located in the central nervous system (CNS) of many mammals and stress induces their degranulation. We postulated that mast cells are associated with wakefulness and stimulatory tone in the CNS, as reflected by spontaneous motor activity. Because stress also precipitates drug-seeking behavior in cocaine addicts, we also postulated that cocaine manifests its effects through this relationship. We investigated the influence of single and repeated injections of cocaine on circulating corticosterone, motor activity and degranulation of mast cells in both the thalamus and meninges of mice. Mice were subjected to 5 consecutive days of cocaine or saline followed by a single injection of cocaine or saline 11 days later. Spontaneous locomotor activity was measure for 1h after the final injection before death. Neither a single injection nor prior treatment with cocaine increased motor activity compared to saline-injected controls, however, repeated administration of cocaine induced a significant sensitization to its behavioral effect when delivered 11 days later. In mice that received only saline, motor activity correlated positively with mast cell degranulation in the meninges but not in the thalamus. Cocaine, regardless of the treatment schedule, disrupted this correlation. The concentration of corticosterone did not differ amongst groups and did not correlate with either behavior or mast cell parameters in any group. The correlation between behavioral activity and the mast cell degranulation in the meninges suggests that these parameters are linked. The disruptive effect of cocaine on this relationship indicates a role downstream from mast cells in the regulation of motor activity.

  11. Chromosomal abnormalities as a cause of recurrent abortions in Egypt

    PubMed Central

    El-Dahtory, Faeza Abdel Mogib

    2011-01-01

    BACKGROUND: In 4%-8% of couples with recurrent abortion, at least one of the partners has chromosomal abnormality. Most spontaneous miscarriages which happen in the first and second trimesters are caused by chromosomal abnormalities. These chromosomal abnormalities may be either numerical or structural. MATERIAL AND METHODS: Cytogenetic study was done for 73 Egyptian couples who presented with recurrent abortion at Genetic Unit of Children Hospital, Mansoura University. RESULTS: We found that the frequency of chromosomal abnormalities was not significantly different from that reported worldwide. Chromosomal abnormalities were detected in 9 (6.1%) of 73 couples. Seven of chromosomal abnormalities were structural and two of them were numerical. CONCLUSION: Our results showed that 6.1% of the couples with recurrent abortion had chromosomal abnormalities, with no other abnormalities. We suggest that it is necessary to perform cytogenetic in vestigation for couples who have recurrent abortion. PMID:22090718

  12. 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.

  13. 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

  14. Effect of effective mass and spontaneous polarization on photocatalytic activity of wurtzite and zinc-blende ZnS

    SciTech Connect

    Dong, Ming; Zhang, Jinfeng; Yu, Jiaguo

    2015-10-01

    Semiconductor zinc sulphide (ZnS) has two common phases: hexagonal wurtzite and cubic zinc-blende structures. The crystal structures, energy band structures, density of states (DOS), bond populations, and optical properties of wurtzite and zinc-blende ZnS were investigated by the density functional theory of first-principles. The similar band gaps and DOS of wurtzite and zinc-blende ZnS were found and implied the similarities in crystal structures. However, the distortion of ZnS{sub 4} tetrahedron in wurtzite ZnS resulted in the production of spontaneous polarization and internal electric field, which was beneficial for the transfer and separation of photogenerated electrons and holes.

  15. Plasticity of spontaneous excitatory and inhibitory synaptic activity in morphologically defined vestibular nuclei neurons during early vestibular compensation

    PubMed Central

    Shao, Mei; Hirsch, June C.

    2012-01-01

    After unilateral peripheral vestibular lesions, the brain plasticity underlying early recovery from the static symptoms is not fully understood. Principal cells of the chick tangential nucleus offer a subset of morphologically defined vestibular nuclei neurons to study functional changes after vestibular lesions. Chickens show posture and balance deficits immediately after unilateral vestibular ganglionectomy (UVG), but by 3 days most subjects begin to recover, although some remain uncompensated. With the use of whole cell voltage-clamp, spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) and miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs) were recorded from principal cells in brain slices 1 and 3 days after UVG. One day after UVG, sEPSC frequency increased on the lesion side and remained elevated at 3 days in uncompensated chickens only. Also by 3 days, sIPSC frequency increased on the lesion side in all operated chickens due to major increases in GABAergic events. Significant change also occurred in decay time of the events. To determine whether fluctuations in frequency and kinetics influenced overall excitatory or inhibitory synaptic drive, synaptic charge transfer was calculated. Principal cells showed significant increase in excitatory synaptic charge transfer only on the lesion side of uncompensated chickens. Thus compensation continues when synaptic charge transfer is in balance bilaterally. Furthermore, excessive excitatory drive in principal cells on the lesion side may prevent vestibular compensation. Altogether, this work is important for it defines the time course and excitatory and inhibitory nature of changing spontaneous synaptic inputs to a morphologically defined subset of vestibular nuclei neurons during critical early stages of recovery after UVG. PMID:21957228

  16. 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

  17. Modulation of postsynaptic activities of thalamic lateral geniculate neurons by spontaneous changes in number of retinal inputs in chronic cats. 1. Input-output relations.

    PubMed

    Fourment, A; Hirsch, J C; Marc, M E; Guidet, C

    1984-06-01

    The experiments were designed to explore the role of retinal inputs compared with that of the behavioral state in the modulation of the output of thalamic lateral geniculate neurons during sleep and wakefulness in cats with intact visual pathways. We made the following assumptions: the retinal dark discharge, while showing spontaneous pauses in activity, does not vary with the behavioral state; the optic tract inputs postsynaptically elicit subthreshold activities called S-potentials which in turn generate spikes, the degree of transformation being dependent on the level of alertness. On the basis of these assumptions, it could be expected that changes in retinal input frequency would modify the rate of the S-potentials. Therefore the effect of spontaneous decreases in frequency of S-potentials on the spike rate and pattern was examined in juxta- and intracellular recordings from chronically implanted cats during natural sleep and wakefulness. During quiet wakefulness and light slow-wave sleep, lateral geniculate relay neurons normally displayed numerous S-potentials associated with a moderate firing rate. Many neurons occasionally showed transient reductions in frequency of the S-potentials and an oversimplification of the discharges which combined a decreased rate with a prevalent rhythmical burst pattern. Antidromic responsiveness remained unchanged. The oscillatory periods recurred two to six times without any alteration in the control state level. They were not observed throughout wakefulness and paradoxical sleep, during which neuronal activity combined a high spike rate with a low S-potential rate. The modifications were confirmed by computation of the mean rates and of the inter-event intervals. The transfer ratio (spikes/S-potentials + spikes) significantly increased both during the oscillatory periods poor in S-potentials of quiet wakefulness and during active wakefulness. But the correlation between the transfer ratio and the spike frequency, which was

  18. 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.

  19. Persistent Effects of Peer Rearing on Abnormal and Species-Appropriate Activities but Not Social Behavior in Group-Housed Rhesus Macaques (Macaca mulatta)

    PubMed Central

    Bauer, Sharon A; Baker, Kate C

    2016-01-01

    Nursery rearing of rhesus macaques (Macaca mulatta) alters behaviors but may be necessitated by maternal rejection or death, for research protocols, or for derivation of SPF colonies. The Tulane National Primate Research Center maintains a nursery-reared colony that is free from 9 pathogens as well as a mother-reared colony free from 4 pathogens, thus affording an opportunity to assess the outcomes of differential rearing. Nursery-reared macaques had continuous contact with 2 peers and an artificial surrogate (peer rearing). Focal sampling (432 h) was collected on the behavior of 32 peer-reared and 40 mother-reared subjects (age, 1 to 10 y; immature group, younger than 4 y; adult group 4 y or older). All animals were housed outdoors in like-reared social groups of 3 to 8 macaques. Contrary to expectation, no rearing effects on affiliative or agonistic social behaviors were detected. Compared with mother-reared subjects, peer-reared macaques in both age classes had elevated levels of abnormal appetitive, abnormal self-directed, and eating behaviors and lower levels of locomoting and vigilance (highly alert to activities in surrounding environment); a trend toward reduced foraging was detected. Immature but not adult peer-reared monkeys demonstrated more enrichment-directed behavior and drinking and a trend toward more anxiety-related behavior and inactivity. No new rearing effects were detected in adults that had not been detected in immature subjects. Results suggest that modern peer-rearing practices may not result in inevitable perturbations in aggressive, rank-related, sexual, and emotional behavior. However, abnormal behaviors may be lifelong issues once they appear. PMID:27053567

  20. Reflux esophagitis and hiatal hernia as concomitant abnormality in patients presenting with active duodenal or gastric ulcer: cross-sectional endoscopic study in consecutive patients.

    PubMed

    Loffeld, R J.L.F.; van der Putten, A B.M.M.

    2002-05-01

    BACKGROUND: Follow-up studies have shown that patients with ulcer disease are at risk of developing reflux esophagitis (RE) after successful eradication of Heliobacter pylori. It is still not clear whether this is induced by eradication of H. pylori or whether RE is already present at the time the ulcer is diagnosed. A cross-sectional study was done in consecutive patients suffering from active ulcer disease in order to assess coincidental RE. METHODS: Patients with an active duodenal or gastric ulcer were included in the study. Concomitant RE and the presence of hiatal hernia (HH) were scored. Biopsy specimens were taken for detection of H. pylori. RESULTS: In 375 patients (77%), an active duodenal ulcer was the only abnormality. In 43 patients (8.8%), duodenal ulcer and concomitant RE were present and 69 patients (14.2%) had a duodenal ulcer with concomitant HH. Patients with a duodenal ulcer were significantly younger than patients with concomitant RE or HH. From 374 patients (76.8%) with a duodenal ulcer, biopsy specimens were available for the detection of H. pylori. The majority of duodenal ulcer patients were H. pylori-positive. H. pylori was significantly more often present in patients with an active duodenal ulcer than it was in duodenal ulcer patients suffering from concomitant RE (P=0.04). In 218 patients (76%), a gastric ulcer was the only abnormality. Fifteen patients (5.2%) also had RE and 54 patients (18.8%) had a concomitant HH. There was no difference in H. pylori status in these three groups of patients. CONCLUSIONS: Given the low prevalence of concomitant RE, it is concluded that this condition is likely to occur in a large percentage of patients suffering from H. pylori-positive ulcer disease after successful eradication therapy.

  1. Abnormal brain activation during working memory in children with prenatal exposure to drugs of abuse: the effects of methamphetamine, alcohol, and polydrug exposure.

    PubMed

    Roussotte, Florence F; Bramen, Jennifer E; Nunez, S Christopher; Quandt, Lorna C; Smith, Lynne; O'Connor, Mary J; Bookheimer, Susan Y; Sowell, Elizabeth R

    2011-02-14

    Structural and metabolic abnormalities in fronto-striatal structures have been reported in children with prenatal methamphetamine (MA) exposure. The current study was designed to quantify functional alterations to the fronto-striatal circuit in children with prenatal MA exposure using functional magnetic resonance imaging (fMRI). Because many women who use MA during pregnancy also use alcohol, a known teratogen, we examined 50 children (age range 7-15), 19 with prenatal MA exposure, 15 of whom had concomitant prenatal alcohol exposure (the MAA group), 13 with heavy prenatal alcohol but no MA exposure (ALC group), and 18 unexposed controls (CON group). We hypothesized that MA exposed children would demonstrate abnormal brain activation during a visuospatial working memory (WM) "N-Back" task. As predicted, the MAA group showed less activation than the CON group in many brain areas, including the striatum and frontal lobe in the left hemisphere. The ALC group showed less activation than the MAA group in several regions, including the right striatum. We found an inverse correlation between performance and activity in the striatum in both the CON and MAA groups. However, this relationship was significant in the caudate of the CON group but not the MAA group, and in the putamen of the MAA group but not the CON group. These findings suggest that structural damage in the fronto-striatal circuit after prenatal MA exposure leads to decreased recruitment of this circuit during a WM challenge, and raise the possibility that a rewiring of cortico-striatal networks may occur in children with prenatal MA exposure.

  2. Flibanserin, a drug intended for treatment of hypoactive sexual desire disorder in pre-menopausal women, affects spontaneous motor activity and brain neurochemistry in female rats.

    PubMed

    Ferger, Boris; Shimasaki, Makoto; Ceci, Angelo; Ittrich, Carina; Allers, Kelly A; Sommer, Bernd

    2010-06-01

    Flibanserin, a 5-HT(1A) receptor agonist and 5-HT(2A) receptor antagonist, is being developed for the treatment of hypoactive sexual desire disorder (HSDD) in pre-menopausal women. Here, we investigated the effects of acute administration of flibanserin (15 and 45 mg/kg, p.o.) and the selective 5-HT(1A) receptor agonist (+)-8-OH-DPAT (1 mg/kg, i.p.) on neurotransmitter levels in brain areas of female rats. Specifically, levels of dopamine (DA) and serotonin (5-HT) and neurotransmitter metabolites were examined in prefrontal cortex (PFC), nucleus accumbens, hypothalamus and brain stem using high performance liquid chromatography coupled to electrochemical detection. In addition, spontaneous motor activity was determined in an automated motor activity system. Flibanserin (45 mg/kg) but not (+)-8-OH-DPAT significantly reduced motor activity, when compared to vehicle controls. Specifically, the DA turnover was significantly increased (279%) in the PFC after flibanserin treatment but less pronounced (159%) after 8-OH-DPAT administration. Serotonin tissue levels were not altered in any of the investigated brain regions upon flibanserin treatment. However, flibanserin produced a significant decrease of the major serotonin metabolite 5-hydroxyindoleacetic acid and 5-HT turnover in the PFC, nucleus accumbens, hypothalamus and brain stem similar to (+)-8-OH-DPAT. In conclusion, the present study indicates that flibanserin is able to modulate dopaminergic and serotonergic activity in distinct brain areas. The observed effects in the PFC on dopaminergic markers are different from those induced by (+)-8-OH-DPAT and may contribute to its therapeutic efficacy in HSDD. The effects of flibanserin on spontaneous motor behaviour are in agreement with its receptor profile and underscore that flibanserin is devoid of any locomotor hyperactivity inducing properties.

  3. 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 activity responds normally to other stimulatory and inhibitory controls of enzyme function. We studied stimulation by parathyroid hormone (PTH) using: (a) a calcium-deficient (0.02% Ca) diet to raise endogenous PTH; or (b) 24-h continuous infusion of 0.25 IU/h bovine PTH via osmotic minipump. In both cases enzyme activity of identically treated normal mice increased to greater levels than those attained by Hyp-mice. The relative inability of PTH to stimulate 1 alpha-hydroxylase activity is not a function of the hypophosphatemia in the Hyp-mouse since PTH-infused, phosphate-depleted normal mice sustained a level of enzyme activity greater than that of normal and Hyp-mice. In further studies we investigated inhibition of enzyme activity by using: (a) a calcium-loaded (1.2% Ca) diet to suppress endogenous PTH; or (b) 24-h continuous infusion of 0.2 ng/h 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). The 1 alpha-hydroxylase activity of normal and Hyp-mice was significantly reduced to similar absolute levels following maintenance on the calcium-loaded diet. Further, infusion of 1,25(OH)2D3 caused a comparable reduction of 1 alpha-hydroxylase activity in normal, Hyp-, and phosphate-depleted normal mice. These observations indicate that the inhibitory control of 1 alpha-hydroxylase by reduced levels of PTH or increased 1,25(OH)2D3 concentrations is intact in the mutants. However, the inability of PTH and hypophosphatemia to stimulate enzyme activity in a manner analogous to that in normal and phosphate-depleted mice indicates

  4. Glutathione system in young spontaneously hypertensive rats.

    PubMed

    Lee, S K; Arunkumar, Sundaram; Sirajudeen, K N S; Singh, H J

    2010-12-01

    Glutathione (GSH) forms a part of the antioxidant system that plays a vital role in preventing oxidative stress, and an imbalance in the oxidant/antioxidant system has been linked to the pathogenesis of hypertension. The aim of this study was to investigate the status of the GSH system in the kidney of spontaneously hypertensive rats (SHR). Components of the GSH system, including glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), and total GSH content, were measured in the kidneys of 4, 6, 8, 12, and 16 weeks old SHR and Wistar-Kyoto (WKY) rats. Systolic blood pressure of SHR was significantly higher from the age of 6 weeks onwards compared with age-matched WKY rats. GPx activity in the SHR was significantly lower from the age of 8 weeks onwards when compared to that in age-matched WKY rats. No significant differences were evident in the GPx-1 protein abundance, and its relative mRNA levels, GR, GST activity, and total GSH content between SHR and age-matched WKY rats. The lower GPx activity suggests of an impairment of the GSH system in the SHR, which might be due to an