Sample records for interneurons reveals robust

  1. Stuttering interneurons generate fast and robust inhibition onto projection neurons with low capacity of short term modulation in mouse lateral amygdala.

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    Chen Song

    Full Text Available The stuttering interneurons (STi represent one minor subset of interneuron population and exhibit characteristic stuttering firing upon depolarization current injection. While it has been long held that the GABAergic inhibitory transmission largely varies with the subtype identity of presynaptic interneurons, whether such a rule also applies to STi is largely unknown. Here, by paired recording of interneuron and their neighboring projection neuron in lateral amygdala, we found that relative to the fast spiking and late spiking interneurons, the STi-evoked unitary postsynaptic currents onto the projection neurons had markedly larger amplitude, shorter onset latency and faster rising and decay kinetics. The quantal content and the number of vesicles in the readily releasable pool were also larger in synapses made by STi versus other interneurons. Moreover, the short-term plasticity, as reflected by the paired pulse depression and depolarization-induced suppression of inhibition, was the least prominent in the output synapses of STi. Thus, the fast and robust inhibition together with its low capacity of short term modulation may suggest an important role for STi in preventing the overexcitation of the projection neurons and thus gating the information traffic in amygdala.

  2. Pauses in Striatal Cholinergic Interneurons: What is Revealed by Their Common Themes and Variations?

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    Yan-Feng Zhang


    Full Text Available Striatal cholinergic interneurons, the so-called tonically active neurons (TANs, pause their firing in response to sensory cues and rewards during classical conditioning and instrumental tasks. The respective pause responses observed can demonstrate many commonalities, such as constant latency and duration, synchronous occurrence in a population of cells, and coincidence with phasic activities of midbrain dopamine neurons (DANs that signal reward predictions and errors. Pauses can however also show divergent properties. Pause latencies and durations can differ in a given TAN between appetitive vs. aversive outcomes in classical conditioning, initial excitation can be present or absent, and a second pause can variably follow a rebound. Despite more than 20 years of study, the functions of these pause responses are still elusive. Our understanding of pause function is hindered by an incomplete understanding of how pauses are generated. In this mini-review article, we compare pause types, as well as current key hypotheses for inputs underlying pauses that include dopamine-induced inhibition through D2-receptors, a GABA input from ventral tegmental area, and a prolonged afterhyperpolarization induced by excitatory input from the cortex or from the thalamus. We review how each of these mechanisms alone explains some but not all aspects of pause responses. These mechanisms might need to operate in specific but variable sets of sequences to generate a full range of pause responses. Alternatively, these mechanisms might operate in conjunction with an underlying control mechanism within cholinergic interneurons which could potentially provide a framework to generate the common themes and variations seen amongst pause responses.

  3. Quantitative Imaging of Cholinergic Interneurons Reveals a Distinctive Spatial Organization and a Functional Gradient across the Mouse Striatum.

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    Miriam Matamales

    Full Text Available Information processing in the striatum requires the postsynaptic integration of glutamatergic and dopaminergic signals, which are then relayed to the output nuclei of the basal ganglia to influence behavior. Although cellularly homogeneous in appearance, the striatum contains several rare interneuron populations which tightly modulate striatal function. Of these, cholinergic interneurons (CINs have been recently shown to play a critical role in the control of reward-related learning; however how the striatal cholinergic network is functionally organized at the mesoscopic level and the way this organization influences striatal function remains poorly understood. Here, we systematically mapped and digitally reconstructed the entire ensemble of CINs in the mouse striatum and quantitatively assessed differences in densities, spatial arrangement and neuropil content across striatal functional territories. This approach demonstrated that the rostral portion of the striatum contained a higher concentration of CINs than the caudal striatum and that the cholinergic content in the core of the ventral striatum was significantly lower than in the rest of the regions. Additionally, statistical comparison of spatial point patterns in the striatal cholinergic ensemble revealed that only a minor portion of CINs (17% aggregated into cluster and that they were predominantly organized in a random fashion. Furthermore, we used a fluorescence reporter to estimate the activity of over two thousand CINs in naïve mice and found that there was a decreasing gradient of CIN overall function along the dorsomedial-to-ventrolateral axis, which appeared to be independent of their propensity to aggregate within the striatum. Altogether this work suggests that the regulation of striatal function by acetylcholine across the striatum is highly heterogeneous, and that signals originating in external afferent systems may be principally determining the function of CINs in the

  4. Extended Interneuronal Network of the Dentate Gyrus

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    Gergely G. Szabo


    Full Text Available Local interneurons control principal cells within individual brain areas, but anecdotal observations indicate that interneuronal axons sometimes extend beyond strict anatomical boundaries. Here, we use the case of the dentate gyrus (DG to show that boundary-crossing interneurons with cell bodies in CA3 and CA1 constitute a numerically significant and diverse population that relays patterns of activity generated within the CA regions back to granule cells. These results reveal the existence of a sophisticated retrograde GABAergic circuit that fundamentally extends the canonical interneuronal network.

  5. Cholinergic interneurons are differentially distributed in the human striatum. (United States)

    Bernácer, Javier; Prensa, Lucía; Giménez-Amaya, José Manuel


    The striatum (caudate nucleus, CN, and putamen, Put) is a group of subcortical nuclei involved in planning and executing voluntary movements as well as in cognitive processes. Its neuronal composition includes projection neurons, which connect the striatum with other structures, and interneurons, whose main roles are maintaining the striatal organization and the regulation of the projection neurons. The unique electrophysiological and functional properties of the cholinergic interneurons give them a crucial modulating function on the overall striatal response. This study was carried out using stereological methods to examine the volume and density (cells/mm(3)) of these interneurons, as visualized by choline acetyltransferase (ChAT) immunoreactivity, in the following territories of the CN and Put of nine normal human brains: 1) precommissural head; 2) postcommissural head; 3) body; 4) gyrus and 5) tail of the CN; 6) precommissural and 7) postcommissural Put. The distribution of ChAT interneurons was analyzed with respect to the topographical, functional and chemical territories of the dorsal striatum. The CN was more densely populated by cholinergic neurons than the Put, and their density increased along the anteroposterior axis of the striatum with the CN body having the highest neuronal density. The associative territory of the dorsal striatum was by far the most densely populated. The striosomes of the CN precommissural head and the postcommissural Put contained the greatest number of ChAT-ir interneurons. The intrastriosomal ChAT-ir neurons were abundant on the periphery of the striosomes throughout the striatum. All these data reveal that cholinergic interneurons are differentially distributed in the distinct topographical and functional territories of the human dorsal striatum, as well as in its chemical compartments. This heterogeneity may indicate that the posterior aspects of the CN require a special integration of information by interneurons

  6. Classification of neocortical interneurons using affinity propagation

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    Roberto eSantana


    Full Text Available In spite of over a century of research on cortical circuits, it is still unknown how many classes of cortical neurons exist. Neuronal classification has been a difficult problem because it is unclear what a neuronal cell class actually is and what are the best characteristics are to define them. Recently, unsupervised classifications using cluster analysis based on morphological, physiological or molecular characteristics, when applied to selected datasets, have provided quantitative and unbiased identification of distinct neuronal subtypes. However, better and more robust classification methods are needed for increasingly complex and larger datasets. We explored the use of affinity propagation, a recently developed unsupervised classification algorithm imported from machine learning, which gives a representative example or exemplar for each cluster. As a case study, we applied affinity propagation to a test dataset of 337 interneurons belonging to four subtypes, previously identified based on morphological and physiological characteristics. We found that affinity propagation correctly classified most of the neurons in a blind, non-supervised manner. In fact, using a combined anatomical/physiological dataset, our algorithm differentiated parvalbumin from somatostatin interneurons in 49 out of 50 cases. Affinity propagation could therefore be used in future studies to validly classify neurons, as a first step to help reverse engineer neural circuits.

  7. Developmental programming of cortial interneurons

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    Welagen, J.


    AIM OF THE STUDY: The majority of interneurons originate from the MGE, including PV, SST and NPY expressing subgroups. Although the MGE has been defined as the region of origin for these subgroups, three important questions are still open. First, it was unclear if a spatial or temporal distribution

  8. Neuregulin 3 Mediates Cortical Plate Invasion and Laminar Allocation of GABAergic Interneurons

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    Giorgia Bartolini


    Full Text Available Neural circuits in the cerebral cortex consist of excitatory pyramidal cells and inhibitory interneurons. These two main classes of cortical neurons follow largely different genetic programs, yet they assemble into highly specialized circuits during development following a very precise choreography. Previous studies have shown that signals produced by pyramidal cells influence the migration of cortical interneurons, but the molecular nature of these factors has remained elusive. Here, we identified Neuregulin 3 (Nrg3 as a chemoattractive factor expressed by developing pyramidal cells that guides the allocation of cortical interneurons in the developing cortical plate. Gain- and loss-of-function approaches reveal that Nrg3 modulates the migration of interneurons into the cortical plate in a process that is dependent on the tyrosine kinase receptor ErbB4. Perturbation of Nrg3 signaling in conditional mutants leads to abnormal lamination of cortical interneurons. Nrg3 is therefore a critical mediator in the assembly of cortical inhibitory circuits.

  9. Modelling of Yeast Mating Reveals Robustness Strategies for Cell-Cell Interactions.

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    Weitao Chen


    Full Text Available Mating of budding yeast cells is a model system for studying cell-cell interactions. Haploid yeast cells secrete mating pheromones that are sensed by the partner which responds by growing a mating projection toward the source. The two projections meet and fuse to form the diploid. Successful mating relies on precise coordination of dynamic extracellular signals, signaling pathways, and cell shape changes in a noisy background. It remains elusive how cells mate accurately and efficiently in a natural multi-cell environment. Here we present the first stochastic model of multiple mating cells whose morphologies are driven by pheromone gradients and intracellular signals. Our novel computational framework encompassed a moving boundary method for modeling both a-cells and α-cells and their cell shape changes, the extracellular diffusion of mating pheromones dynamically coupled with cell polarization, and both external and internal noise. Quantification of mating efficiency was developed and tested for different model parameters. Computer simulations revealed important robustness strategies for mating in the presence of noise. These strategies included the polarized secretion of pheromone, the presence of the α-factor protease Bar1, and the regulation of sensing sensitivity; all were consistent with data in the literature. In addition, we investigated mating discrimination, the ability of an a-cell to distinguish between α-cells either making or not making α-factor, and mating competition, in which multiple a-cells compete to mate with one α-cell. Our simulations were consistent with previous experimental results. Moreover, we performed a combination of simulations and experiments to estimate the diffusion rate of the pheromone a-factor. In summary, we constructed a framework for simulating yeast mating with multiple cells in a noisy environment, and used this framework to reproduce mating behaviors and to identify strategies for robust cell

  10. Robust hierarchical state-space models reveal diel variation in travel rates of migrating leatherback turtles. (United States)

    Jonsen, Ian D; Myers, Ransom A; James, Michael C


    1. Biological and statistical complexity are features common to most ecological data that hinder our ability to extract meaningful patterns using conventional tools. Recent work on implementing modern statistical methods for analysis of such ecological data has focused primarily on population dynamics but other types of data, such as animal movement pathways obtained from satellite telemetry, can also benefit from the application of modern statistical tools. 2. We develop a robust hierarchical state-space approach for analysis of multiple satellite telemetry pathways obtained via the Argos system. State-space models are time-series methods that allow unobserved states and biological parameters to be estimated from data observed with error. We show that the approach can reveal important patterns in complex, noisy data where conventional methods cannot. 3. Using the largest Atlantic satellite telemetry data set for critically endangered leatherback turtles, we show that the diel pattern in travel rates of these turtles changes over different phases of their migratory cycle. While foraging in northern waters the turtles show similar travel rates during day and night, but on their southward migration to tropical waters travel rates are markedly faster during the day. These patterns are generally consistent with diving data, and may be related to changes in foraging behaviour. Interestingly, individuals that migrate southward to breed generally show higher daytime travel rates than individuals that migrate southward in a non-breeding year. 4. Our approach is extremely flexible and can be applied to many ecological analyses that use complex, sequential data.

  11. Classification of neocortical interneurons using affinity propagation (United States)

    Santana, Roberto; McGarry, Laura M.; Bielza, Concha; Larrañaga, Pedro; Yuste, Rafael


    In spite of over a century of research on cortical circuits, it is still unknown how many classes of cortical neurons exist. In fact, neuronal classification is a difficult problem because it is unclear how to designate a neuronal cell class and what are the best characteristics to define them. Recently, unsupervised classifications using cluster analysis based on morphological, physiological, or molecular characteristics, have provided quantitative and unbiased identification of distinct neuronal subtypes, when applied to selected datasets. However, better and more robust classification methods are needed for increasingly complex and larger datasets. Here, we explored the use of affinity propagation, a recently developed unsupervised classification algorithm imported from machine learning, which gives a representative example or exemplar for each cluster. As a case study, we applied affinity propagation to a test dataset of 337 interneurons belonging to four subtypes, previously identified based on morphological and physiological characteristics. We found that affinity propagation correctly classified most of the neurons in a blind, non-supervised manner. Affinity propagation outperformed Ward's method, a current standard clustering approach, in classifying the neurons into 4 subtypes. Affinity propagation could therefore be used in future studies to validly classify neurons, as a first step to help reverse engineer neural circuits. PMID:24348339

  12. A defined network of fast-spiking interneurons in orbitofrontal cortex: responses to behavioral contingencies and ketamine administration

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    Michael C Quirk


    Full Text Available Orbitofrontal cortex (OFC is a region of prefrontal cortex implicated in the motivational control of behavior and in related abnormalities seen in psychosis and depression. It has been hypothesized that a critical mechanism in these disorders is the dysfunction of GABAergic interneurons that normally regulate prefrontal information processing. Here, we studied a subclass of interneurons isolated in rat OFC using extracellular waveform and spike train analysis. During performance of a goal-directed behavioral task, the firing of this class of putative fast-spiking (FS interneurons showed robust temporal correlations indicative of a functionally coherent network. FS cell activity also co-varied with behavioral response latency, a key indicator of motivational state. Systemic administration of ketamine, a drug that can mimic psychosis, preferentially inhibited this cell class. Together, these results support the idea that OFC-FS interneurons form a critical link in the regulation of motivation by prefrontal circuits during normal and abnormal brain and behavioral states.

  13. Activity-dependent myelination of parvalbumin interneurons mediated by axonal morphological plasticity. (United States)

    Stedehouder, J; Brizee, D; Shpak, G; Kushner, S A


    Axonal myelination of neocortical pyramidal neurons is dynamically modulated by neuronal activity. Recent studies have shown that a substantial proportion of neocortical myelin content is contributed by fast-spiking, parvalbumin (PV)-positive interneurons. However, it remains unknown whether the myelination of PV + interneurons is also modulated by intrinsic activity. Here, we utilized cell-type specific Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in adult male and female mice to activate a sparse population of medial prefrontal cortex PV + interneurons. Using single-cell axonal reconstructions, we find that DREADD-stimulated PV + interneurons exhibit a nearly two-fold increase in total length of myelination, predominantly mediated by a parallel increase of axonal arborization and number of internodes. In contrast, the distribution of axonal inter-branch segment distance and myelin internode length were not significantly altered. Topographical analysis revealed that myelination of DREADD-stimulated cells extended to higher axonal branch orders, while retaining a similar inter-branch distance threshold for myelination. Together, our results demonstrate that chemogenetically-induced neuronal activity increases the myelination of neocortical PV + interneurons mediated at least in part by an elaboration of their axonal morphology. SIGNIFICANCE STATEMENT Myelination is the wrapping of an axon in order to optimize conduction velocity in an energy-efficient manner. Previous studies have shown that myelination of neocortical pyramidal neurons is experience and activity-dependent. We now show that activity-dependent myelin plasticity in the adult neocortex extends to parvalbumin-expressing fast-spiking interneurons. Specifically, chemogenetic stimulation of parvalbumin interneurons in the medial prefrontal cortex significantly enhanced axonal myelination, which was paralleled by an increase in axonal arborization. This suggests that activity

  14. Design process robustness: A bi-partite network analysis reveals the central importance of people

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    Piccolo, Sebastiano; Jørgensen, Sune Lehmann; Maier, Anja


    and activities. We find that our process is more vulnerable to attacks to people rather than activities. These findings show how the allocation of people to activities can obscure an inherent fragility, making the process highly sensitive and dependent on specific people. More generally, we show......Design processes require the joint effort of many people to collaborate and work on multiple activities. Effective techniques to analyse and model design processes are important for understanding organisational dynamics, for improving collaboration, and for planning robust design processes......, reducing the risk of rework and delays. Although there has been much progress in modelling and understanding design processes, little is known about the interplay between people and the activities they perform and its influence on design process robustness. To analyse this interplay, we model a large...

  15. Essential gene disruptions reveal complex relationships between phenotypic robustness, pleiotropy, and fitness (United States)

    Bauer, Christopher R; Li, Shuang; Siegal, Mark L


    The concept of robustness in biology has gained much attention recently, but a mechanistic understanding of how genetic networks regulate phenotypic variation has remained elusive. One approach to understand the genetic architecture of variability has been to analyze dispensable gene deletions in model organisms; however, the most important genes cannot be deleted. Here, we have utilized two systems in yeast whereby essential genes have been altered to reduce expression. Using high-throughput microscopy and image analysis, we have characterized a large number of morphological phenotypes, and their associated variation, for the majority of essential genes in yeast. Our results indicate that phenotypic robustness is more highly dependent upon the expression of essential genes than on the presence of dispensable genes. Morphological robustness appears to be a general property of a genotype that is closely related to pleiotropy. While the fitness profile across a range of expression levels is idiosyncratic to each gene, the global pattern indicates that there is a window in which phenotypic variation can be released before fitness effects are observable. PMID:25609648

  16. Fermentation-induced variation in heat and oxidative stress phenotypes of Lactococcus lactis MG1363 reveals transcriptome signatures for robustness. (United States)

    Dijkstra, Annereinou R; Alkema, Wynand; Starrenburg, Marjo J C; Hugenholtz, Jeroen; van Hijum, Sacha A F T; Bron, Peter A


    Lactococcus lactis is industrially employed to manufacture various fermented dairy products. The most cost-effective method for the preservation of L. lactis starter cultures is spray drying, but during this process cultures encounter heat and oxidative stress, typically resulting in low survival rates. However, viability of starter cultures is essential for their adequate contribution to milk fermentation, supporting the ambition to better understand and improve their robustness phenotypes. This study describes a transcriptome-phenotype matching approach in which the starter L. lactis MG1363 was fermented under a variety of conditions that differed in the levels of oxygen and/or salt, as well as the fermentation pH and temperature. Samples derived from these fermentations in the exponential phase of bacterial growth were analyzed by full-genome transcriptomics and the assessment of heat and oxidative stress phenotypes. Variations in the fermentation conditions resulted in up to 1000-fold differences in survival during heat and oxidative stress. More specifically, aeration during fermentation induced protection against heat stress, whereas a relatively high fermentation temperature resulted in enhanced robustness towards oxidative stress. Concomitantly, oxygen levels and fermentation temperature induced differential expression of markedly more genes when compared with the other fermentation parameters. Correlation analysis of robustness phenotypes and gene expression levels revealed transcriptome signatures for oxidative and/or heat stress survival, including the metC-cysK operon involved in methionine and cysteine metabolism. To validate this transcriptome-phenotype association we grew L. lactis MG1363 in the absence of cysteine which led to enhanced robustness towards oxidative stress. Overall, we demonstrated the importance of careful selection of fermentation parameters prior to industrial processing of starter cultures. Furthermore, established stress genes as

  17. Interneuron progenitor transplantation to treat CNS dysfunction

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    Muhammad O Chohan


    Full Text Available Due to the inadequacy of endogenous repair mechanisms diseases of the nervous system remain a major challenge to scientists and clinicians. Stem cell based therapy is an exciting and viable strategy that has been shown to ameliorate or even reverse symptoms of CNS dysfunction in preclinical animal models. Of particular importance has been the use of GABAergic interneuron progenitors as a therapeutic strategy. Born in the neurogenic niches of the ventral telencephalon, interneuron progenitors retain their unique capacity to disperse, integrate and induce plasticity in adult host circuitries following transplantation. Here we discuss the potential of interneuron based transplantation strategies as it relates to CNS disease therapeutics. We also discuss mechanisms underlying their therapeutic efficacy and some of the challenges that face the field.

  18. Time-series metagenomic analysis reveals robustness of soil microbiome against chemical disturbance (United States)

    Kato, Hiromi; Mori, Hiroshi; Maruyama, Fumito; Toyoda, Atsushi; Oshima, Kenshiro; Endo, Ryo; Fuchu, Genki; Miyakoshi, Masatoshi; Dozono, Ayumi; Ohtsubo, Yoshiyuki; Nagata, Yuji; Hattori, Masahira; Fujiyama, Asao; Kurokawa, Ken; Tsuda, Masataka


    Soil microbial communities have great potential for bioremediation of recalcitrant aromatic compounds. However, it is unclear which taxa and genes in the communities, and how they contribute to the bioremediation in the polluted soils. To get clues about this fundamental question here, time-course (up to 24 weeks) metagenomic analysis of microbial community in a closed soil microcosm artificially polluted with four aromatic compounds, including phenanthrene, was conducted to investigate the changes in the community structures and gene pools. The pollution led to drastic changes in the community structures and the gene sets for pollutant degradation. Complete degradation of phenanthrene was strongly suggested to occur by the syntrophic metabolism by Mycobacterium and the most proliferating genus, Burkholderia. The community structure at Week 24 (∼12 weeks after disappearance of the pollutants) returned to the structure similar to that before pollution. Our time-course metagenomic analysis of phage genes strongly suggested the involvement of the ‘kill-the-winner’ phenomenon (i.e. phage predation of Burkholderia cells) for the returning of the microbial community structure. The pollution resulted in a decrease in taxonomic diversity and a drastic increase in diversity of gene pools in the communities, showing the functional redundancy and robustness of the communities against chemical disturbance. PMID:26428854

  19. Metabolic Flux Analysis of Shewanella spp. Reveals Evolutionary Robustness in Central Carbon Metabolism

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    Tang, Yinjie J.; Martin, Hector Garcia; Dehal, Paramvir S.; Deutschbauer, Adam; Llora, Xavier; Meadows, Adam; Arkin, Adam; Keasling, Jay D.


    Shewanella spp. are a group of facultative anaerobic bacteria widely distributed in marine and fresh-water environments. In this study, we profiled the central metabolic fluxes of eight recently sequenced Shewanella species grown under the same condition in minimal med-ium with [3-13C] lactate. Although the tested Shewanella species had slightly different growth rates (0.23-0.29 h31) and produced different amounts of acetate and pyruvate during early exponential growth (pseudo-steady state), the relative intracellular metabolic flux distributions were remarkably similar. This result indicates that Shewanella species share similar regulation in regard to central carbon metabolic fluxes under steady growth conditions: the maintenance of metabolic robustness is not only evident in a single species under genetic perturbations (Fischer and Sauer, 2005; Nat Genet 37(6):636-640), but also observed through evolutionary related microbial species. This remarkable conservation of relative flux profiles through phylogenetic differences prompts us to introduce the concept of metabotype as an alternative scheme to classify microbial fluxomics. On the other hand, Shewanella spp. display flexibility in the relative flux profiles when switching their metabolism from consuming lactate to consuming pyruvate and acetate.

  20. Striatal fast-spiking interneurons selectively modulate circuit output and are required for habitual behavior. (United States)

    O'Hare, Justin K; Li, Haofang; Kim, Namsoo; Gaidis, Erin; Ade, Kristen; Beck, Jeff; Yin, Henry; Calakos, Nicole


    Habit formation is a behavioral adaptation that automates routine actions. Habitual behavior correlates with broad reconfigurations of dorsolateral striatal (DLS) circuit properties that increase gain and shift pathway timing. The mechanism(s) for these circuit adaptations are unknown and could be responsible for habitual behavior. Here we find that a single class of interneuron, fast-spiking interneurons (FSIs), modulates all of these habit-predictive properties. Consistent with a role in habits, FSIs are more excitable in habitual mice compared to goal-directed and acute chemogenetic inhibition of FSIs in DLS prevents the expression of habitual lever pressing. In vivo recordings further reveal a previously unappreciated selective modulation of SPNs based on their firing patterns; FSIs inhibit most SPNs but paradoxically promote the activity of a subset displaying high fractions of gamma-frequency spiking. These results establish a microcircuit mechanism for habits and provide a new example of how interneurons mediate experience-dependent behavior.

  1. The behavioral economics of social anxiety disorder reveal a robust effect for interpersonal traits. (United States)

    Rodebaugh, Thomas L; Tonge, Natasha A; Weisman, Jaclyn S; Lim, Michelle H; Fernandez, Katya C; Bogdan, Ryan


    Recent evidence suggests that reduced generosity among individuals with social anxiety disorder (SAD) in behavioral economic tasks may result from constraint in changing behavior according to interpersonal contingencies. That is, people with SAD may be slower to be more generous when the situation warrants. Conversely, more global effects on generosity may be related to interpersonal vindictiveness, a dimension only somewhat related to SAD. A total of 133 participants, 73 with the generalized form of SAD, completed self-report instruments and a behavioral economic task with simulated interpersonal (friend, romantic partner, stranger) interactions. In a separate visit, friends (n = 88) also came to the lab and rated participants on vindictiveness. Interpersonal vindictiveness was associated with reduced initial and overall giving to simulated friends. SAD predicted a lack of increased giving to a simulated friend, and attenuated an increase in giving to simulated known versus unknown players compared to participants without SAD. Friend-reported vindictiveness predicted in the same direction as diagnosis. However, the findings for SAD were less robust than those for vindictiveness. SAD is perhaps weakly related to behavioral constraint in economic tasks that simulate interpersonal interactions, whereas vindictiveness is strongly related to lower overall generosity as well as (via friend report) behavioral constraint. Further study is needed to better characterize the construct of vindictiveness. Our findings dovetail with the suggestion that SAD is related to impairment in the proposed affiliation and attachment system, but further suggest that direct study of that system may be more fruitful than focusing on disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Evidence of a robust resident bacteriophage population revealed through analysis of the human salivary virome (United States)

    Pride, David T; Salzman, Julia; Haynes, Matthew; Rohwer, Forest; Davis-Long, Clara; White, Richard A; Loomer, Peter; Armitage, Gary C; Relman, David A


    Viruses are the most abundant known infectious agents on the planet and are significant drivers of diversity in a variety of ecosystems. Although there have been numerous studies of viral communities, few have focused on viruses within the indigenous human microbiota. We analyzed 2 267 695 virome reads from viral particles and compared them with 263 516 bacterial 16S rRNA gene sequences from the saliva of five healthy human subjects over a 2- to 3-month period, in order to improve our understanding of the role viruses have in the complex oral ecosystem. Our data reveal viral communities in human saliva dominated by bacteriophages whose constituents are temporally distinct. The preponderance of shared homologs between the salivary viral communities in two unrelated subjects in the same household suggests that environmental factors are determinants of community membership. When comparing salivary viromes to those from human stool and the respiratory tract, each group was distinct, further indicating that habitat is of substantial importance in shaping human viromes. Compared with coexisting bacteria, there was concordance among certain predicted host–virus pairings such as Veillonella and Streptococcus, whereas there was discordance among others such as Actinomyces. We identified 122 728 virulence factor homologs, suggesting that salivary viruses may serve as reservoirs for pathogenic gene function in the oral environment. That the vast majority of human oral viruses are bacteriophages whose putative gene function signifies some have a prominent role in lysogeny, suggests these viruses may have an important role in helping shape the microbial diversity in the human oral cavity. PMID:22158393

  3. Robust Regression Analysis of GCMS Data Reveals Differential Rewiring of Metabolic Networks in Hepatitis B and C Patients

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    Cedric Simillion


    Full Text Available About one in 15 of the world’s population is chronically infected with either hepatitis virus B (HBV or C (HCV, with enormous public health consequences. The metabolic alterations caused by these infections have never been directly compared and contrasted. We investigated groups of HBV-positive, HCV-positive, and uninfected healthy controls using gas chromatography-mass spectrometry analyses of their plasma and urine. A robust regression analysis of the metabolite data was conducted to reveal correlations between metabolite pairs. Ten metabolite correlations appeared for HBV plasma and urine, with 18 for HCV plasma and urine, none of which were present in the controls. Metabolic perturbation networks were constructed, which permitted a differential view of the HBV- and HCV-infected liver. HBV hepatitis was consistent with enhanced glucose uptake, glycolysis, and pentose phosphate pathway metabolism, the latter using xylitol and producing threonic acid, which may also be imported by glucose transporters. HCV hepatitis was consistent with impaired glucose uptake, glycolysis, and pentose phosphate pathway metabolism, with the tricarboxylic acid pathway fueled by branched-chain amino acids feeding gluconeogenesis and the hepatocellular loss of glucose, which most probably contributed to hyperglycemia. It is concluded that robust regression analyses can uncover metabolic rewiring in disease states.

  4. Accumbens nNOS Interneurons Regulate Cocaine Relapse. (United States)

    Smith, Alexander C W; Scofield, Michael D; Heinsbroek, Jasper A; Gipson, Cassandra D; Neuhofer, Daniela; Roberts-Wolfe, Doug J; Spencer, Sade; Garcia-Keller, Constanza; Stankeviciute, Neringa M; Smith, Rachel J; Allen, Nicholas P; Lorang, Melissa R; Griffin, William C; Boger, Heather A; Kalivas, Peter W


    Relapse to drug use can be initiated by drug-associated cues. The intensity of cue-induced relapse is correlated with the induction of transient synaptic potentiation (t-SP) at glutamatergic synapses on medium spiny neurons (MSNs) in the nucleus accumbens core (NAcore) and requires spillover of glutamate from prefrontal cortical afferents. We used a rodent self-administration/reinstatement model of relapse to show that cue-induced t-SP and reinstated cocaine seeking result from glutamate spillover, initiating a metabotropic glutamate receptor 5 (mGluR5)-dependent increase in nitric oxide (NO) production. Pharmacological stimulation of mGluR5 in NAcore recapitulated cue-induced reinstatement in the absence of drug-associated cues. Using NO-sensitive electrodes, mGluR5 activation by glutamate was shown to stimulate NO production that depended on activation of neuronal nitric oxide synthase (nNOS). nNOS is expressed in ∼1% of NAcore neurons. Using a transgene strategy to express and stimulate designer receptors that mimicked mGluR5 signaling through Gq in nNOS interneurons, we recapitulated cue-induced reinstatement in the absence of cues. Conversely, using a transgenic caspase strategy, the intensity of cue-induced reinstatement was correlated with the extent of selective elimination of nNOS interneurons. The induction of t-SP during cued reinstatement depends on activating matrix metalloproteinases (MMPs) and selective chemogenetic stimulation of nNOS interneurons recapitulated MMP activation and t-SP induction (increase in AMPA currents in MSNs). These data demonstrate critical involvement of a sparse population of nNOS-expressing interneurons in cue-induced cocaine seeking, revealing a bottleneck in brain processing of drug-associated cues where therapeutic interventions could be effective in treating drug addiction. Relapse to cocaine use in a rat model is associated with transient increases in synaptic strength at prefrontal cortex synapses in the nucleus

  5. Immunohistochemical visualization of mouse interneuron subtypes

    DEFF Research Database (Denmark)

    Jensen, Simon Mølgaard; Ulrichsen, Maj; Boggild, Simon


    of the hippocampus where they have previously been described. Additionally, the antibodies were also tested on sections from mouse spinal cord with similar criteria for specificity of the antibodies. Using the antibodies with a high rating on pAbmAbs, stainings with high signal-to-noise ratios and location......The activity of excitatory neurons is controlled by a small, but highly diverse population of inhibitory interneurons. These cells show a high level of physiological, morphological and neurochemical heterogeneity, and play highly specific roles in neuronal circuits. In the mammalian hippocampus...

  6. Cannabidiol exerts antiepileptic effects by restoring hippocampal interneuron functions in a temporal lobe epilepsy model. (United States)

    Khan, Archie A; Shekh-Ahmad, Tawfeeq; Khalil, Ayatakin; Walker, Matthew C; Ali, Afia B


    A non-psychoactive phytocannabinoid, cannabidiol (CBD), shows promising results as an effective potential antiepileptic drug in some forms of refractory epilepsy. In an attempt to understand the mechanisms by which CBD exerts its anti-seizure effects, we investigated the effects of CBD at synaptic connections, and the intrinsic membrane properties of hippocampal CA1 pyramidal cells and two major inhibitory interneurons: fast spiking, parvalbumin -expressing (PV) and adapting, cholecystokinin-expressing (CCK) interneurons. We also investigated whether in vivo treatment with CBD altered the fate of CCK and PV interneurons using immunohistochemistry. Electrophysiological intracellular whole-cell recordings combined with neuroanatomy were performed in acute brain slices of rat temporal lobe epilepsy (in vivo kainic acid-induced) and in vitro (Mg 2+ -free-induced) epileptic seizure models. For immunohistochemistry experiments, CBD was administered in vivo (100 mg kg -1 ) at zero time and 90 minutes post status epilepticus (SE) induced with kainic acid. Bath-application of CBD (10 μM), dampened excitability at unitary synapses between pyramidal cells, but enhanced inhibitory synaptic potentials elicited by fast spiking and adapting interneurons at postsynaptic pyramidal cells. Furthermore, CBD restored impaired membrane excitability of PV, CCK, and pyramidal cells in a cell type-specific manner. These neuroprotective effects of CBD were corroborated by immunohistochemistry experiments that revealed a significant reduction of atrophy and death of PV- and CCK-expressing interneurons after CBD treatment. In conclusion, our data suggest CBD restores excitability and morphological impairment in epileptic models to pre-epilepsy control levels through multiple mechanisms to restore normal network function. This article is protected by copyright. All rights reserved.

  7. Cortical Interneuron Subtypes Vary in Their Axonal Action Potential Properties. (United States)

    Casale, Amanda E; Foust, Amanda J; Bal, Thierry; McCormick, David A


    The role of interneurons in cortical microcircuits is strongly influenced by their passive and active electrical properties. Although different types of interneurons exhibit unique electrophysiological properties recorded at the soma, it is not yet clear whether these differences are also manifested in other neuronal compartments. To address this question, we have used voltage-sensitive dye to image the propagation of action potentials into the fine collaterals of axons and dendrites in two of the largest cortical interneuron subtypes in the mouse: fast-spiking interneurons, which are typically basket or chandelier neurons; and somatostatin containing interneurons, which are typically regular spiking Martinotti cells. We found that fast-spiking and somatostatin-expressing interneurons differed in their electrophysiological characteristics along their entire dendrosomatoaxonal extent. The action potentials generated in the somata and axons, including axon collaterals, of somatostatin-expressing interneurons are significantly broader than those generated in the same compartments of fast-spiking inhibitory interneurons. In addition, action potentials back-propagated into the dendrites of somatostatin-expressing interneurons much more readily than fast-spiking interneurons. Pharmacological investigations suggested that axonal action potential repolarization in both cell types depends critically upon Kv1 channels, whereas the axonal and somatic action potentials of somatostatin-expressing interneurons also depend on BK Ca(2+)-activated K(+) channels. These results indicate that the two broad classes of interneurons studied here have expressly different subcellular physiological properties, allowing them to perform unique computational roles in cortical circuit operations. Neurons in the cerebral cortex are of two major types: excitatory and inhibitory. The proper balance of excitation and inhibition in the brain is critical for its operation. Neurons contain three main


    Adorjan, Istvan; Sun, Bin; Feher, Virginia; Tyler, Teadora; Damo-Csorba, Bori; Pour, Benedek; Veres, Daniel; Ansorge, Olaf; Chance, Steven Andrew; Szele, Francis


    Abstract Background The excitatory/inhibitory imbalance theory is widely accepted in the pathology of autism spectrum disorder. Recent results suggest its relevance in the aetiology of schizophrenia as well (Jardri 2016, Yang 2017, Gao and Penzes 2015). In order to discover the possibly altered neuronal composition in schizophrenia numerous studies have been focussing mainly on different cortical regions such as the ventromedial prefrontal cortex and dorsolateral prefrontal cortex. In particular, various interneuronal populations have been found altered.2 However, relatively little is known about the neuroanatomical changes of subcortical structures, such as the caudate nucleus, in the pathology of schizophrenia. Methods Therefore, we examined the immunohistochemical distribution of calretinin (CR) and NPY-immunopositive neurons in the caudate nucleus and the dorsolateral prefrontal cortex. The state of microglial activation was controlled by the detection of Iba1 and TMEM119. In order to corroborate our results obtained by immunohistochemistry (IHC) qPCR analyses were also conducted. Results The present study provides evidence for the altered interneuronal composition of caudate nucleus in schizophrenia without signs of microglial activation. There were small, medium and large CR-immunopositive (CR-ip) interneurons detected in the caudate nucleus. There was a 32% decrease in the density of all CR-ip interneurons (p=0.020, statistical power=0.747) that was driven by the loss of the small CR-ip interneurons (p=0.017, statistical power=0.777) while the densities of the medium and large CR-ip and NPY-ip interneurons were not significantly altered (p=0.078, p=0.436, p=0.125, respectively). Our experiments were also extended to the dorsolateral prefrontal cortex (medial frontal gyrus and superior frontal gyrus) where no significant changes were seen by IHC. However, qPCR analyses revealed a trend of decreased CR mRNA levels in schizophrenia (p=0.061, statistical power=0

  9. Cortical interneuron dysfunction in epilepsy associated with autism spectrum disorders. (United States)

    Jacob, John


    Autism and epilepsy are two associated disorders that are highly prevalent, share common developmental origins, and demonstrate substantial heritability. In this review, cross-disciplinary data in a rapidly evolving field that bridges neurology and psychiatry are synthesized to identify shared biologic mechanisms. The relationship between these debilitating, lifelong conditions is examined at the clinical, genetic, and neurophysiologic levels in humans and in animal models. Scopus and PubMed searches were used to identify relevant literature. Clinical observations have prompted speculation about the interdependence of autism and epilepsy, but causal relationships have proved difficult to determine. Despite their heritability, the genetic basis of autism spectrum disorder (ASD) and epilepsy has remained largely elusive until the advent of next-generation sequencing. This approach has revealed that mutations that are either causal or confer an increased disease risk are found in numerous different genes, any one of which accounts for only a small percentage of cases. Conversely, even cases with identical clinical phenotypes can be genetically heterogeneous. Candidate gene identification has facilitated the development of mouse genetic models, which in parallel with human studies have implicated shared brain regions and circuits that mediate disease expression. Diverse genetic causes of ASD and epilepsy converge on cortical interneuron circuits as one important mediator of both disorders. Cortical interneurons are among the most diverse cell types in the brain and their unique chemical and electrical coupling exert a powerful inhibitory influence on excitatory neurons via the release of the neurotransmitter, γ-aminobutyric acid (GABA). These multifaceted approaches have validated theories derived from the field of developmental neurobiology, which propose that the neurologic and neuropsychiatric manifestations are caused by an altered ratio of excitation to

  10. Hilar GABAergic interneuron activity controls spatial learning and memory retrieval.

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    Yaisa Andrews-Zwilling

    Full Text Available Although extensive research has demonstrated the importance of excitatory granule neurons in the dentate gyrus of the hippocampus in normal learning and memory and in the pathogenesis of amnesia in Alzheimer's disease (AD, the role of hilar GABAergic inhibitory interneurons, which control the granule neuron activity, remains unclear.We explored the function of hilar GABAergic interneurons in spatial learning and memory by inhibiting their activity through Cre-dependent viral expression of enhanced halorhodopsin (eNpHR3.0--a light-driven chloride pump. Hilar GABAergic interneuron-specific expression of eNpHR3.0 was achieved by bilaterally injecting adeno-associated virus containing a double-floxed inverted open-reading frame encoding eNpHR3.0 into the hilus of the dentate gyrus of mice expressing Cre recombinase under the control of an enhancer specific for GABAergic interneurons. In vitro and in vivo illumination with a yellow laser elicited inhibition of hilar GABAergic interneurons and consequent activation of dentate granule neurons, without affecting pyramidal neurons in the CA3 and CA1 regions of the hippocampus. We found that optogenetic inhibition of hilar GABAergic interneuron activity impaired spatial learning and memory retrieval, without affecting memory retention, as determined in the Morris water maze test. Importantly, optogenetic inhibition of hilar GABAergic interneuron activity did not alter short-term working memory, motor coordination, or exploratory activity.Our findings establish a critical role for hilar GABAergic interneuron activity in controlling spatial learning and memory retrieval and provide evidence for the potential contribution of GABAergic interneuron impairment to the pathogenesis of amnesia in AD.

  11. Genetics and Function of Neocortical GABAergic Interneurons in Neurodevelopmental Disorders

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    E. Rossignol


    Full Text Available A dysfunction of cortical and limbic GABAergic circuits has been postulated to contribute to multiple neurodevelopmental disorders in humans, including schizophrenia, autism, and epilepsy. In the current paper, I summarize the characteristics that underlie the great diversity of cortical GABAergic interneurons and explore how the multiple roles of these cells in developing and mature circuits might contribute to the aforementioned disorders. Furthermore, I review the tightly controlled genetic cascades that determine the fate of cortical interneurons and summarize how the dysfunction of genes important for the generation, specification, maturation, and function of cortical interneurons might contribute to these disorders.

  12. Apical versus Basal Neurogenesis Directs Cortical Interneuron Subclass Fate

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    Timothy J. Petros


    Full Text Available Fate determination in the mammalian telencephalon, with its diversity of neuronal subtypes and relevance to neuropsychiatric disease, remains a critical area of study in neuroscience. Most studies investigating this topic focus on the diversity of neural progenitors within spatial and temporal domains along the lateral ventricles. Often overlooked is whether the location of neurogenesis within a fate-restricted domain is associated with, or instructive for, distinct neuronal fates. Here, we use in vivo fate mapping and the manipulation of neurogenic location to demonstrate that apical versus basal neurogenesis influences the fate determination of major subgroups of cortical interneurons derived from the subcortical telencephalon. Somatostatin-expressing interneurons arise mainly from apical divisions along the ventricular surface, whereas parvalbumin-expressing interneurons originate predominantly from basal divisions in the subventricular zone. As manipulations that shift neurogenic location alter interneuron subclass fate, these results add an additional dimension to the spatial-temporal determinants of neuronal fate determination.

  13. COUP-TFI controls activity-dependent tyrosine hydroxylase expression in adult dopaminergic olfactory bulb interneurons. (United States)

    Bovetti, Serena; Bonzano, Sara; Garzotto, Donatella; Giannelli, Serena Gea; Iannielli, Angelo; Armentano, Maria; Studer, Michèle; De Marchis, Silvia


    COUP-TFI is an orphan nuclear receptor acting as a strong transcriptional regulator in different aspects of forebrain embryonic development. In this study, we investigated COUP-TFI expression and function in the mouse olfactory bulb (OB), a highly plastic telencephalic region in which continuous integration of newly generated inhibitory interneurons occurs throughout life. OB interneurons belong to different populations that originate from distinct progenitor lineages. Here, we show that COUP-TFI is highly expressed in tyrosine hydroxylase (TH)-positive dopaminergic interneurons in the adult OB glomerular layer (GL). We found that odour deprivation, which is known to downregulate TH expression in the OB, also downregulates COUP-TFI in dopaminergic cells, indicating a possible correlation between TH- and COUP-TFI-activity-dependent action. Moreover, we demonstrate that conditional inactivation of COUP-TFI in the EMX1 lineage results in a significant reduction of both TH and ZIF268 expression in the GL. Finally, lentiviral vector-mediated COUP-TFI deletion in adult-generated interneurons confirmed that COUP-TFI acts cell-autonomously in the control of TH and ZIF268 expression. These data indicate that COUP-TFI regulates TH expression in OB cells through an activity-dependent mechanism involving ZIF268 induction and strongly argue for a maintenance rather than establishment function of COUP-TFI in dopaminergic commitment. Our study reveals a previously unknown role for COUP-TFI in the adult brain as a key regulator in the control of sensory-dependent plasticity in olfactory dopaminergic neurons.

  14. Spike timing of distinct types of GABAergic interneuron during hippocampal gamma oscillations in vitro. (United States)

    Hájos, Norbert; Pálhalmi, János; Mann, Edward O; Németh, Beáta; Paulsen, Ole; Freund, Tamas F


    Gamma frequency (30-100 Hz) network oscillations occur in the intact hippocampus during awake, attentive behavior. Here, we explored the underlying cellular mechanisms in an in vitro model of persistent gamma-frequency oscillations, induced by bath application of 20 microm carbachol in submerged hippocampal slices at 30 +/- 1 degrees C. Current-source density analysis of the field oscillation revealed a prominent alternating sink-source pair in the perisomatic and apical dendritic regions of CA3. To elucidate the active events generating these extracellular dipoles, we examined the firing properties of distinct neuron types. Visually guided unit recordings were obtained from individual CA3 neurons followed by intracellular labeling for anatomical identification. Pyramidal cells fired at 2.82 +/- 0.7 Hz, close to the negative peak of the oscillation (0.03 +/- 0.65 msec), and often in conjunction with a negative spike-like component of the field potential. In contrast, all phase-coupled interneurons fired after this negative peak. Perisomatic inhibitory interneurons fired at high frequency (18.1 +/- 2.7 Hz), shortly after the negative peak (1.97 +/- 0.95 msec) and were strongly phase-coupled. Dendritic inhibitory interneurons fired at lower frequency (8.4 +/- 2.4 Hz) and with less fidelity and a longer delay after the negative peak (4.3 +/- 1.1 msec), whereas interneurons with cell body in the stratum radiatum often showed no phase relationship with the field oscillation. The phase and spike time data of individual neurons, together with the current-source density analysis, support a synaptic feedback model of gamma oscillations primarily involving pyramidal cells and inhibitory cells targeting their perisomatic region.

  15. Striatal cholinergic interneuron regulation and circuit effects

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    Sean Austin Lim


    Full Text Available The striatum plays a central role in motor control and motor learning. Appropriate responses to environmental stimuli, including pursuit of reward or avoidance of aversive experience all require functional striatal circuits. These pathways integrate synaptic inputs from limbic and cortical regions including sensory, motor and motivational information to ultimately connect intention to action. Although many neurotransmitters participate in striatal circuitry, one critically important player is acetylcholine (ACh. Relative to other brain areas, the striatum contains exceptionally high levels of ACh, the enzymes that catalyze its synthesis and breakdown, as well as both nicotinic and muscarinic receptor types that mediate its postsynaptic effects. The principal source of striatal ACh is the cholinergic interneuron (ChI, which comprises only about 1-2% of all striatal cells yet sends dense arbors of projections throughout the striatum. This review summarizes recent advances in our understanding of the factors affecting the excitability of these neurons through acute effects and long term changes in their synaptic inputs. In addition, we discuss the physiological effects of ACh in the striatum, and how changes in ACh levels may contribute to disease states during striatal dysfunction.

  16. Revisiting the enigmatic cortical calretinin-expressing interneurons

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    Bruno eCauli


    Full Text Available Cortical calretinin (CR-expressing interneurons represent a heterogeneous subpopulation of about 10-30% of GABAergic interneurons, which altogether total ca. 12-20% of all cortical neurons. In the rodent neocortex, CR cells display different somatodendritic morphologies ranging from bipolar to multipolar but the bipolar cells and their variations dominate. They are also diverse at the molecular level as they were shown to express numerous neuropeptides in different combinations including vasoactive intestinal polypeptide (VIP, cholecystokinin (CCK, neurokinin B (NKB corticotrophin releasing factor (CRF, enkephalin (Enk but also neuropeptide Y (NPY and somatostatin (SOM to a lesser extent. CR-expressing interneurons exhibit different firing behaviors such as adapting, bursting or irregular. They mainly originate from the caudal ganglionic eminence (CGE but a subpopulation also derives from the dorsal part of the medial ganglionic eminence (MGE. Cortical GABAergic CR-expressing interneurons can be divided in two main populations: VIP-bipolar interneurons deriving from the CGE and SOM-Martinotti-like interneurons originating in the dorsal MGE. Although bipolar cells account for the majority of CR-expressing interneurons, the roles they play in cortical neuronal circuits and in the more general metabolic physiology of the brain remain elusive and enigmatic. The aim of this review is, firstly, to provide a comprehensive view of the morphological, molecular and electrophysiological features defining this cell type. We will, secondly, also summarize what is known about their place in the cortical circuit, their modulation by subcortical afferents and the functional roles they might play in neuronal processing and energy metabolism.

  17. HCN Channel Modulation of Synaptic Integration in GABAergic Interneurons in Malformed Rat Neocortex

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    John J. Hablitz


    Full Text Available Cortical malformations are often associated with pharmaco-resistant epilepsy. Alterations in hyperpolarization-activated, cyclic nucleotide-gated, non-specific cation (HCN channels have been shown to contribute to malformation associated hyperexcitability. We have recently demonstrated that expression of HCN channels and Ih current amplitudes are reduced in layer (L 5 pyramidal neurons of rats with freeze lesion induced malformations. These changes were associated with an increased EPSP temporal summation. Here, we examine the effects of HCN channel inhibition on synaptic responses in fast spiking, presumptive basket cells and accommodating, presumptive Martinotti, GABAergic interneurons in slices from freeze lesioned animals. In control animals, fast spiking cells showed small sag responses which were reduced by the HCN channel antagonist ZD7288. Fast spiking cells in lesioned animals showed absent or reduced sag responses. The amplitude of single evoked EPSPs in fast spiking cells in the control group was not affected by HCN channel inhibition with ZD7288. EPSP ratios during short stimulus trains at 25 Hz were not significantly different between control and lesion groups. ZD7288 produced an increase in EPSP ratios in the control but not lesion groups. Under voltage clamp conditions, ZD7288 did not affect EPSC ratios. In the control group, accommodating interneurons showed robust sag responses which were significantly reduced by ZD7288. HCN channel inhibition increased EPSP ratios and area in controls but not the lesioned group. The results indicate that HCN channels differentially modulate EPSPs in different classes of GABAergic interneurons and that this control is reduced in malformed rat neocortex.

  18. Pan-Antarctic analysis aggregating spatial estimates of Adélie penguin abundance reveals robust dynamics despite stochastic noise. (United States)

    Che-Castaldo, Christian; Jenouvrier, Stephanie; Youngflesh, Casey; Shoemaker, Kevin T; Humphries, Grant; McDowall, Philip; Landrum, Laura; Holland, Marika M; Li, Yun; Ji, Rubao; Lynch, Heather J


    Colonially-breeding seabirds have long served as indicator species for the health of the oceans on which they depend. Abundance and breeding data are repeatedly collected at fixed study sites in the hopes that changes in abundance and productivity may be useful for adaptive management of marine resources, but their suitability for this purpose is often unknown. To address this, we fit a Bayesian population dynamics model that includes process and observation error to all known Adélie penguin abundance data (1982-2015) in the Antarctic, covering >95% of their population globally. We find that process error exceeds observation error in this system, and that continent-wide "year effects" strongly influence population growth rates. Our findings have important implications for the use of Adélie penguins in Southern Ocean feedback management, and suggest that aggregating abundance across space provides the fastest reliable signal of true population change for species whose dynamics are driven by stochastic processes.Adélie penguins are a key Antarctic indicator species, but data patchiness has challenged efforts to link population dynamics to key drivers. Che-Castaldo et al. resolve this issue using a pan-Antarctic Bayesian model to infer missing data, and show that spatial aggregation leads to more robust inference regarding dynamics.

  19. Co-expression of VAL- and TMT-opsins uncovers ancient photosensory interneurons and motorneurons in the vertebrate brain.

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    Ruth M Fischer

    Full Text Available The functional principle of the vertebrate brain is often paralleled to a computer: information collected by dedicated devices is processed and integrated by interneuron circuits and leads to output. However, inter- and motorneurons present in today's vertebrate brains are thought to derive from neurons that combined sensory, integration, and motor function. Consistently, sensory inter-motorneurons have been found in the simple nerve nets of cnidarians, animals at the base of the evolutionary lineage. We show that light-sensory motorneurons and light-sensory interneurons are also present in the brains of vertebrates, challenging the paradigm that information processing and output circuitry in the central brain is shielded from direct environmental influences. We investigated two groups of nonvisual photopigments, VAL- and TMT-Opsins, in zebrafish and medaka fish; two teleost species from distinct habitats separated by over 300 million years of evolution. TMT-Opsin subclasses are specifically expressed not only in hypothalamic and thalamic deep brain photoreceptors, but also in interneurons and motorneurons with no known photoreceptive function, such as the typeXIV interneurons of the fish optic tectum. We further show that TMT-Opsins and Encephalopsin render neuronal cells light-sensitive. TMT-Opsins preferentially respond to blue light relative to rhodopsin, with subclass-specific response kinetics. We discovered that tmt-opsins co-express with val-opsins, known green light receptors, in distinct inter- and motorneurons. Finally, we show by electrophysiological recordings on isolated adult tectal slices that interneurons in the position of typeXIV neurons respond to light. Our work supports "sensory-inter-motorneurons" as ancient units for brain evolution. It also reveals that vertebrate inter- and motorneurons are endowed with an evolutionarily ancient, complex light-sensory ability that could be used to detect changes in ambient light spectra

  20. Glycine Receptor α2 Subunit Activation Promotes Cortical Interneuron Migration

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    Ariel Avila


    Full Text Available Glycine receptors (GlyRs are detected in the developing CNS before synaptogenesis, but their function remains elusive. This study demonstrates that functional GlyRs are expressed by embryonic cortical interneurons in vivo. Furthermore, genetic disruption of these receptors leads to interneuron migration defects. We discovered that extrasynaptic activation of GlyRs containing the α2 subunit in cortical interneurons by endogenous glycine activates voltage-gated calcium channels and promotes calcium influx, which further modulates actomyosin contractility to fine-tune nuclear translocation during migration. Taken together, our data highlight the molecular events triggered by GlyR α2 activation that control cortical tangential migration during embryogenesis.

  1. Apical versus Basal Neurogenesis Directs Cortical Interneuron Subclass Fate. (United States)

    Petros, Timothy J; Bultje, Ronald S; Ross, M Elizabeth; Fishell, Gord; Anderson, Stewart A


    Fate determination in the mammalian telencephalon, with its diversity of neuronal subtypes and relevance to neuropsychiatric disease, remains a critical area of study in neuroscience. Most studies investigating this topic focus on the diversity of neural progenitors within spatial and temporal domains along the lateral ventricles. Often overlooked is whether the location of neurogenesis within a fate-restricted domain is associated with, or instructive for, distinct neuronal fates. Here, we use in vivo fate mapping and the manipulation of neurogenic location to demonstrate that apical versus basal neurogenesis influences the fate determination of major subgroups of cortical interneurons derived from the subcortical telencephalon. Somatostatin-expressing interneurons arise mainly from apical divisions along the ventricular surface, whereas parvalbumin-expressing interneurons originate predominantly from basal divisions in the subventricular zone. As manipulations that shift neurogenic location alter interneuron subclass fate, these results add an additional dimension to the spatial-temporal determinants of neuronal fate determination. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Inhibitory Interneurons of The Human Neocortex after Clinical Death

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    V. A. Akulinin


    Full Text Available Objective: to analyze the human neocortex interneurons (areas 4, 10, 17 and 21 by Brodmann after cardiac arrest (clinical death.Materials and methods. The main group included patients (n=7, men who survived 7—10 days and 70—90 days after cardiac arrest and later died due to heart failure. The control group (n=4, men included individuals after sudden fatal accidents. The morphometric and histological analysis of 420 neocortical fields (Nissl#staining,calbindin D28k, neuropeptide Y was performed using light and confocal microscopy.Results. We verified all main types of interneurons (Basket, Martinotti, and neurogliaform interneurons in neocortex based on the morphology of their bodies and dendritic processes in both groups. The number of calbindin- and NPY-positive neurons in the neocortex was similar in the control and in the postoperative period.However, calbindin- and NPY-immunopositive structure fields including neuronal cell bodies and their dendrites were significantly more represented in neocortex of patients from the main group. Maximum increase in common square in the relative areas of calbindin-immunopositive structures was observed 90 days after ischemia. The squares of NPY#immunopositive fields became larger seven days after resuscitation and remained increased on 90th day post-resuscitation.Conclusion. Our findings demonstrate an increase of calbindin and NPY expression in human neocortex after clinical death, which can be explained by a compensatory  eaction of undamaged inhibitory cortical interneurons directed to protectbrain from ischemia.

  3. A subset of interneurons required for Drosophila larval locomotion. (United States)

    Yoshikawa, Shingo; Long, Hong; Thomas, John B


    Efforts to define the neural circuits generating locomotor behavior have produced an initial understanding of some of the components within the spinal cord, as well as a basic understanding of several invertebrate motor pattern generators. However, how these circuits are assembled during development is poorly understood. We are defining the neural circuit that generates larval locomotion in the genetically tractable fruit fly Drosophila melanogaster to study locomotor circuit development. Forward larval locomotion involves a stereotyped posterior-to-anterior segmental translocation of body wall muscle contraction and is generated by a relatively small number of identified muscles, motor and sensory neurons, plus an unknown number of the ~270 bilaterally-paired interneurons per segment of the 1st instar larva. To begin identifying the relevant interneurons, we have conditionally inactivated synaptic transmission of interneuron subsets and assayed for the effects on locomotion. From this screen we have identified a subset of 25 interneurons per hemisegment, called the lateral locomotor neurons (LLNs), that are required for locomotion. Both inactivation and constitutive activation of the LLNs disrupt locomotion, indicating that patterned output of the LLNs is required. By expressing a calcium indicator in the LLNs, we found that they display a posterior-to-anterior wave of activity within the CNS corresponding to the segmental translocation of the muscle contraction wave. Identification of the LLNs represents the first step toward elucidating the circuit generating larval locomotion. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Subtype-specific reduction of olfactory bulb interneurons in Pax6 heterozygous mutant mice. (United States)

    Haba, Hasumi; Nomura, Tadashi; Suto, Fumikazu; Osumi, Noriko


    Interneurons in the olfactory bulb (OB) play essential roles in the processing of olfactory information. They are classified into several subpopulations by the expression of different neurochemical markers. Here we focused on a transcription factor Pax6, and examined its expression and function in distinct subtypes of OB interneurons. We identified Pax6 expression in specific subtypes of interneurons in the external plexiform layer (EPL). The number of these interneuron subtypes was dramatically decreased in Pax6 heterozygous mutant mice. These results indicate that Pax6 is required for differentiation and/or maintenance of EPL interneurons in the adult mouse OB.

  5. Pyrosequencing the Bemisia tabaci transcriptome reveals a highly diverse bacterial community and a robust system for insecticide resistance.

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    Wen Xie

    Full Text Available BACKGROUND: Bemisia tabaci (Gennadius is a phloem-feeding insect poised to become one of the major insect pests in open field and greenhouse production systems throughout the world. The high level of resistance to insecticides is a main factor that hinders continued use of insecticides for suppression of B. tabaci. Despite its prevalence, little is known about B. tabaci at the genome level. To fill this gap, an invasive B. tabaci B biotype was subjected to pyrosequencing-based transcriptome analysis to identify genes and gene networks putatively involved in various physiological and toxicological processes. METHODOLOGY AND PRINCIPAL FINDINGS: Using Roche 454 pyrosequencing, 857,205 reads containing approximately 340 megabases were obtained from the B. tabaci transcriptome. De novo assembly generated 178,669 unigenes including 30,980 from insects, 17,881 from bacteria, and 129,808 from the nohit. A total of 50,835 (28.45% unigenes showed similarity to the non-redundant database in GenBank with a cut-off E-value of 10-5. Among them, 40,611 unigenes were assigned to one or more GO terms and 6,917 unigenes were assigned to 288 known pathways. De novo metatranscriptome analysis revealed highly diverse bacterial symbionts in B. tabaci, and demonstrated the host-symbiont cooperation in amino acid production. In-depth transcriptome analysis indentified putative molecular markers, and genes potentially involved in insecticide resistance and nutrient digestion. The utility of this transcriptome was validated by a thiamethoxam resistance study, in which annotated cytochrome P450 genes were significantly overexpressed in the resistant B. tabaci in comparison to its susceptible counterparts. CONCLUSIONS: This transcriptome/metatranscriptome analysis sheds light on the molecular understanding of symbiosis and insecticide resistance in an agriculturally important phloem-feeding insect pest, and lays the foundation for future functional genomics research of the

  6. Functional Genetic Screen to Identify Interneurons Governing Behaviorally Distinct Aspects of Drosophila Larval Motor Programs

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    Matt Q. Clark


    Full Text Available Drosophila larval crawling is an attractive system to study rhythmic motor output at the level of animal behavior. Larval crawling consists of waves of muscle contractions generating forward or reverse locomotion. In addition, larvae undergo additional behaviors, including head casts, turning, and feeding. It is likely that some neurons (e.g., motor neurons are used in all these behaviors, but the identity (or even existence of neurons dedicated to specific aspects of behavior is unclear. To identify neurons that regulate specific aspects of larval locomotion, we performed a genetic screen to identify neurons that, when activated, could elicit distinct motor programs. We used 165 Janelia CRM-Gal4 lines—chosen for sparse neuronal expression—to ectopically express the warmth-inducible neuronal activator TrpA1, and screened for locomotor defects. The primary screen measured forward locomotion velocity, and we identified 63 lines that had locomotion velocities significantly slower than controls following TrpA1 activation (28°. A secondary screen was performed on these lines, revealing multiple discrete behavioral phenotypes, including slow forward locomotion, excessive reverse locomotion, excessive turning, excessive feeding, immobile, rigid paralysis, and delayed paralysis. While many of the Gal4 lines had motor, sensory, or muscle expression that may account for some or all of the phenotype, some lines showed specific expression in a sparse pattern of interneurons. Our results show that distinct motor programs utilize distinct subsets of interneurons, and provide an entry point for characterizing interneurons governing different elements of the larval motor program.

  7. Hilar somatostatin interneuron loss reduces dentate gyrus inhibition in a mouse model of temporal lobe epilepsy. (United States)

    Hofmann, Gabrielle; Balgooyen, Laura; Mattis, Joanna; Deisseroth, Karl; Buckmaster, Paul S


    In patients with temporal lobe epilepsy, seizures usually start in the hippocampus, and dentate granule cells are hyperexcitable. Somatostatin interneurons are a major subpopulation of inhibitory neurons in the dentate gyrus, and many are lost in patients and animal models. However, surviving somatostatin interneurons sprout axon collaterals and form new synapses, so the net effect on granule cell inhibition remains unclear. The present study uses optogenetics to activate hilar somatostatin interneurons and measure the inhibitory effect on dentate gyrus perforant path-evoked local field potential responses in a mouse model of temporal lobe epilepsy. In controls, light activation of hilar somatostatin interneurons inhibited evoked responses up to 40%. Epileptic pilocarpine-treated mice exhibited loss of hilar somatostatin interneurons and less light-induced inhibition of evoked responses. These findings suggest that severe epilepsy-related loss of hilar somatostatin interneurons can overwhelm the surviving interneurons' capacity to compensate by sprouting axon collaterals. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

  8. Analysis of the robustness of network-based disease-gene prioritization methods reveals redundancy in the human interactome and functional diversity of disease-genes.

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    Emre Guney

    Full Text Available Complex biological systems usually pose a trade-off between robustness and fragility where a small number of perturbations can substantially disrupt the system. Although biological systems are robust against changes in many external and internal conditions, even a single mutation can perturb the system substantially, giving rise to a pathophenotype. Recent advances in identifying and analyzing the sequential variations beneath human disorders help to comprehend a systemic view of the mechanisms underlying various disease phenotypes. Network-based disease-gene prioritization methods rank the relevance of genes in a disease under the hypothesis that genes whose proteins interact with each other tend to exhibit similar phenotypes. In this study, we have tested the robustness of several network-based disease-gene prioritization methods with respect to the perturbations of the system using various disease phenotypes from the Online Mendelian Inheritance in Man database. These perturbations have been introduced either in the protein-protein interaction network or in the set of known disease-gene associations. As the network-based disease-gene prioritization methods are based on the connectivity between known disease-gene associations, we have further used these methods to categorize the pathophenotypes with respect to the recoverability of hidden disease-genes. Our results have suggested that, in general, disease-genes are connected through multiple paths in the human interactome. Moreover, even when these paths are disturbed, network-based prioritization can reveal hidden disease-gene associations in some pathophenotypes such as breast cancer, cardiomyopathy, diabetes, leukemia, parkinson disease and obesity to a greater extend compared to the rest of the pathophenotypes tested in this study. Gene Ontology (GO analysis highlighted the role of functional diversity for such diseases.

  9. Roles for multifunctional and specialized spinal interneurons during motor pattern generation in tadpoles, zebrafish larvae, and turtles

    Directory of Open Access Journals (Sweden)

    Ari Berkowitz


    Full Text Available The hindbrain and spinal cord can produce multiple forms of locomotion, escape, and withdrawal behaviors and (in limbed vertebrates site-specific scratching. Until recently, the prevailing view was that the same classes of CNS neurons generate multiple kinds of movements, either through reconfiguration of a single, shared network or through an increase in the number of neurons recruited within each class. The mechanisms involved in selecting and generating different motor patterns have recently been explored in detail in some non-mammalian, vertebrate model systems. Work on the hatchling Xenopus tadpole, the larval zebrafish, and the adult turtle has now revealed that distinct kinds of motor patterns are actually selected and generated by combinations of multifunctional and specialized spinal interneurons. Multifunctional interneurons may form a core, multipurpose circuit that generates elements of coordinated motor output utilized in multiple behaviors, such as left-right alternation. But, in addition, specialized spinal interneurons including separate glutamatergic and glycinergic classes are selectively activated during specific patterns: escape-withdrawal, swimming and struggling in tadpoles and zebrafish, and limb withdrawal and scratching in turtles. These specialized neurons can contribute by changing the way central pattern generator (CPG activity is initiated and by altering CPG composition and operation. The combined use of multifunctional and specialized neurons is now established as a principle of organization across a range of vertebrates. Future research may reveal common patterns of multifunctionality and specialization among interneurons controlling diverse movements and whether similar mechanisms exist in higher-order brain circuits that select among a wider array of complex movements.

  10. A Subtype of Inhibitory Interneuron with Intrinsic Persistent Activity in Human and Monkey Neocortex

    Directory of Open Access Journals (Sweden)

    Bo Wang


    Full Text Available A critical step in understanding the neural basis of human cognitive functions is to identify neuronal types in the neocortex. In this study, we performed whole-cell recording from human cortical slices and found a distinct subpopulation of neurons with intrinsic persistent activity that could be triggered by single action potentials (APs but terminated by bursts of APs. This persistent activity was associated with a depolarizing plateau potential induced by the activation of a persistent Na+ current. Single-cell RT-PCR revealed that these neurons were inhibitory interneurons. This type of neuron was found in different cortical regions, including temporal, frontal, occipital, and parietal cortices in human and also in frontal and temporal lobes of nonhuman primate but not in rat cortical tissues, suggesting that it could be unique to primates. The characteristic persistent activity in these inhibitory interneurons may contribute to the regulation of pyramidal cell activity and participate in cortical processing.

  11. Action of tachykinins in the hippocampus: facilitation of inhibitory drive to GABAergic interneurons. (United States)

    Ogier, R; Wrobel, L J; Raggenbass, M


    By acting on neurokinin 1 (NK1) receptors, neuropeptides of the tachykinin family can powerfully excite rat hippocampal GABAergic interneurons located in the CA1 region and by this way indirectly inhibit CA1 pyramidal neurons. In addition to contact pyramidal neurons, however, GABAergic hippocampal interneurons can also innervate other interneurons. We thus asked whether activation of tachykinin-sensitive interneurons could indirectly inhibit other interneurons. The study was performed in hippocampal slices of young adult rats. Synaptic events were recorded using the whole-cell patch clamp technique. We found that substance P enhanced GABAergic inhibitory postsynaptic currents in a majority of the interneurons tested. Miniature, action potential-independent inhibitory postsynaptic currents were unaffected by substance P, as were evoked inhibitory synaptic currents. This suggests that the peptide acted at the somatodendritic membrane of interneurons, rather than at their axon terminals. The effect of substance P was mimicked by a selective NK1 receptor agonist, but not by neurokinin 2 (NK2) or neurokinin 3 (NK3) receptor agonists, and was suppressed by a NK1 selective receptor antagonist. In contrast to substance P, oxytocin, another peptide capable of activating hippocampal interneurons, had no effect on the inhibitory synaptic drive onto interneurons. We conclude that tachykinins, by acting on NK1 receptors, can influence the hippocampal activity by indirectly inhibiting both pyramidal neurons and GABAergic interneurons. Depending on the precise balance between these effects, tachykinins may either activate or depress hippocampal network activity.

  12. Modulation of Apoptosis Controls Inhibitory Interneuron Number in the Cortex

    Directory of Open Access Journals (Sweden)

    Myrto Denaxa


    Full Text Available Cortical networks are composed of excitatory projection neurons and inhibitory interneurons. Finding the right balance between the two is important for controlling overall cortical excitation and network dynamics. However, it is unclear how the correct number of cortical interneurons (CIs is established in the mammalian forebrain. CIs are generated in excess from basal forebrain progenitors, and their final numbers are adjusted via an intrinsically determined program of apoptosis that takes place during an early postnatal window. Here, we provide evidence that the extent of CI apoptosis during this critical period is plastic and cell-type specific and can be reduced in a cell-autonomous manner by acute increases in neuronal activity. We propose that the physiological state of the emerging neural network controls the activity levels of local CIs to modulate their numbers in a homeostatic manner.

  13. Re-emergence of striatal cholinergic interneurons in movement disorders. (United States)

    Pisani, Antonio; Bernardi, Giorgio; Ding, Jun; Surmeier, D James


    Twenty years ago, striatal cholinergic neurons were central figures in models of basal ganglia function. But since then, they have receded in importance. Recent studies are likely to lead to their re-emergence in our thinking. Cholinergic interneurons have been implicated as key players in the induction of synaptic plasticity and motor learning, as well as in motor dysfunction. In Parkinson's disease and dystonia, diminished striatal dopaminergic signalling leads to increased release of acetylcholine by interneurons, distorting network function and inducing structural changes that undoubtedly contribute to the symptoms. By contrast, in Huntington's disease and progressive supranuclear palsy, there is a fall in striatal cholinergic markers. This review gives an overview of these recent experimental and clinical studies, placing them within the context of the pathogenesis of movement disorders.

  14. Distinct Translaminar Glutamatergic Circuits to GABAergic Interneurons in the Neonatal Auditory Cortex

    Directory of Open Access Journals (Sweden)

    Rongkang Deng


    Full Text Available GABAergic activity is important in neocortical development and plasticity. Because the maturation of GABAergic interneurons is regulated by neural activity, the source of excitatory inputs to GABAergic interneurons plays a key role in development. We show, by laser-scanning photostimulation, that layer 4 and layer 5 GABAergic interneurons in the auditory cortex in neonatal mice (interneurons showed two spatial patterns of translaminar connection: inputs originating predominantly from supragranular or from supragranular and infragranular layers, including the subplate, which relays early thalamocortical activity. Sensory deprivation altered the development of translaminar inputs. Thus, distinct translaminar circuits to GABAergic interneurons exist throughout development, and the maturation of excitatory synapses is input-specific. Glutamatergic signaling from subplate and intracortical sources likely plays a role in the maturation of GABAergic interneurons.

  15. Locomotor Rhythm Generation Linked to the Output of Spinal Shox2 Excitatory Interneurons

    DEFF Research Database (Denmark)

    Dougherty, Kimberly J.; Zagoraiou, Laskaro; Satoh, Daisuke


    Locomotion is controlled by spinal networks that generate rhythm and coordinate left-right and flexor-extensor patterning. Defined populations of spinal interneurons have been linked to patterning circuits; however, neurons comprising the rhythm-generating kernel have remained elusive. Here, we...... identify an ipsilaterally projecting excitatory interneuron population, marked by the expression of Shox2 that overlaps partially with V2a interneurons. Optogenetic silencing or blocking synaptic output of Shox2 interneurons (INs) in transgenic mice perturbed rhythm without an effect on pattern generation...

  16. Impaired action potential initiation in GABAergic interneurons causes hyperexcitable networks in an epileptic mouse model carrying a human Na(V)1.1 mutation. (United States)

    Hedrich, Ulrike B S; Liautard, Camille; Kirschenbaum, Daniel; Pofahl, Martin; Lavigne, Jennifer; Liu, Yuanyuan; Theiss, Stephan; Slotta, Johannes; Escayg, Andrew; Dihné, Marcel; Beck, Heinz; Mantegazza, Massimo; Lerche, Holger


    Mutations in SCN1A and other ion channel genes can cause different epileptic phenotypes, but the precise mechanisms underlying the development of hyperexcitable networks are largely unknown. Here, we present a multisystem analysis of an SCN1A mouse model carrying the NaV1.1-R1648H mutation, which causes febrile seizures and epilepsy in humans. We found a ubiquitous hypoexcitability of interneurons in thalamus, cortex, and hippocampus, without detectable changes in excitatory neurons. Interestingly, somatic Na(+) channels in interneurons and persistent Na(+) currents were not significantly changed. Instead, the key mechanism of interneuron dysfunction was a deficit of action potential initiation at the axon initial segment that was identified by analyzing action potential firing. This deficit increased with the duration of firing periods, suggesting that increased slow inactivation, as recorded for recombinant mutated channels, could play an important role. The deficit in interneuron firing caused reduced action potential-driven inhibition of excitatory neurons as revealed by less frequent spontaneous but not miniature IPSCs. Multiple approaches indicated increased spontaneous thalamocortical and hippocampal network activity in mutant mice, as follows: (1) more synchronous and higher-frequency firing was recorded in primary neuronal cultures plated on multielectrode arrays; (2) thalamocortical slices examined by field potential recordings revealed spontaneous activities and pathological high-frequency oscillations; and (3) multineuron Ca(2+) imaging in hippocampal slices showed increased spontaneous neuronal activity. Thus, an interneuron-specific generalized defect in action potential initiation causes multisystem disinhibition and network hyperexcitability, which can well explain the occurrence of seizures in the studied mouse model and in patients carrying this mutation. Copyright © 2014 the authors 0270-6474/14/3414874-16$15.00/0.

  17. Oxytocin modulates female sociosexual behavior through a specific class of prefrontal cortical interneurons (United States)

    Nakajima, Miho; Görlich, Andreas; Heintz, Nathaniel


    SUMMARY Human imaging studies have revealed that intranasal administration of the “prosocial” hormone oxytocin (OT) activates the frontal cortex, and that this action of OT correlates with enhanced brain function in autism. Here we report the discovery of a population of somatostatin (Sst) positive, regular spiking interneurons that express the oxytocin receptor (OxtrINs). Silencing of OxtrINs in the medial prefrontal cortex (mPFC) of female mice resulted in loss of social interest in male mice specifically during the sexually receptive phase of the estrous cycle. This sociosexual deficit was also present in mice in which the Oxtr gene was conditionally deleted from the mPFC, and in control mice infused with an Oxtr antagonist. Our data demonstrate a gender, cell type and state specific role for OT/Oxtr signaling in the mPFC, and identify a latent cortical circuit element that may modulate other complex social behaviors in response to OT. PMID:25303526

  18. Distribution of GABAergic interneurons and dopaminergic cells in the functional territories of the human striatum. (United States)

    Bernácer, Javier; Prensa, Lucía; Giménez-Amaya, José Manuel


    The afferent projections of the striatum (caudate nucleus and putamen) are segregated in three territories: associative, sensorimotor and limbic. Striatal interneurons are in part responsible for the integration of these different types of information. Among them, GABAergic interneurons are the most abundant, and can be sorted in three populations according to their content in the calcium binding proteins calretinin (CR), parvalbumin (PV) and calbindin (CB). Conversely, striatal dopaminergic cells (whose role as interneurons is still unclear) are scarce. This study aims to analyze the interneuron distribution in the striatal functional territories, as well as their organization regarding to the striosomal compartment. We used immunohistochemical methods to visualize CR, PV, CB and tyrosine hydroxylase (TH) positive striatal neurons. The interneuronal distribution was assessed by stereological methods applied to every striatal functional territory. Considering the four cell groups altogether, their density was higher in the associative (2120±91 cells/mm(3)) than in the sensorimotor (959±47 cells/mm(3)) or limbic (633±119 cells/mm(3)) territories. CB- and TH-immunoreactive(-ir) cells were distributed rather homogeneously in the three striatal territories. However, the density of CR and PV interneurons were more abundant in the associative and sensorimotor striatum, respectively. Regarding to their compartmental organization, CR-ir interneurons were frequently found in the border between compartments in the associative and sensorimotor territories, and CB-ir interneurons abounded at the striosome/matrix border in the sensorimotor domain. The present study demonstrates that the architecture of the human striatum in terms of its interneuron composition varies in its three functional territories. Furthermore, our data highlight the importance of CR-ir striatal interneurons in the integration of associative information, and the selective role of PV-ir interneurons in

  19. Electrophysiological and morphological characterization of propriospinal interneurons in the thoracic spinal cord

    DEFF Research Database (Denmark)

    Saywell, S A; Ford, T W; Meehan, Claire Francesca


    Propriospinal interneurons in the thoracic spinal cord have vital roles not only in controlling respiratory and trunk muscles, but also in providing possible substrates for recovery from spinal cord injury. Intracellular recordings were made from such interneurons in anesthetized cats under neuro...

  20. Linking Cholinergic Interneurons, Synaptic Plasticity, and Behavior during the Extinction of a Cocaine-Context Association. (United States)

    Lee, Junuk; Finkelstein, Joel; Choi, Jung Yoon; Witten, Ilana B


    Despite the fact that cholinergic interneurons are a key cell type within the nucleus accumbens, a relationship between synaptic plasticity and the in vivo activity of cholinergic interneurons remains to be established. Here, we identify a three-way link between the activity of cholinergic interneurons, synaptic plasticity, and learning in mice undergoing the extinction of a cocaine-context association. We found that activity of cholinergic interneurons regulates extinction learning for a cocaine-context association and generates a sustained reduction in glutamatergic presynaptic strength onto medium spiny neurons. Interestingly, activation of cholinergic interneurons does not support reinforcement learning or plasticity by itself, suggesting that these neurons have a modulatory rather than a reinforcing function. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Dendritic and Axonal Wiring Optimization of Cortical GABAergic Interneurons. (United States)

    Anton-Sanchez, Laura; Bielza, Concha; Benavides-Piccione, Ruth; DeFelipe, Javier; Larrañaga, Pedro


    The way in which a neuronal tree expands plays an important role in its functional and computational characteristics. We aimed to study the existence of an optimal neuronal design for different types of cortical GABAergic neurons. To do this, we hypothesized that both the axonal and dendritic trees of individual neurons optimize brain connectivity in terms of wiring length. We took the branching points of real three-dimensional neuronal reconstructions of the axonal and dendritic trees of different types of cortical interneurons and searched for the minimal wiring arborization structure that respects the branching points. We compared the minimal wiring arborization with real axonal and dendritic trees. We tested this optimization problem using a new approach based on graph theory and evolutionary computation techniques. We concluded that neuronal wiring is near-optimal in most of the tested neurons, although the wiring length of dendritic trees is generally nearer to the optimum. Therefore, wiring economy is related to the way in which neuronal arborizations grow irrespective of the marked differences in the morphology of the examined interneurons.

  2. Serotonin inhibits low-threshold spike interneurons in the striatum (United States)

    Cains, Sarah; Blomeley, Craig P; Bracci, Enrico


    Low-threshold spike interneurons (LTSIs) are important elements of the striatal architecture and the only known source of nitric oxide in this nucleus, but their rarity has so far prevented systematic studies. Here, we used transgenic mice in which green fluorescent protein is expressed under control of the neuropeptide Y (NPY) promoter and striatal NPY-expressing LTSIs can be easily identified, to investigate the effects of serotonin on these neurons. In sharp contrast with its excitatory action on other striatal interneurons, serotonin (30 μm) strongly inhibited LTSIs, reducing or abolishing their spontaneous firing activity and causing membrane hyperpolarisations. These hyperpolarisations persisted in the presence of tetrodotoxin, were mimicked by 5-HT2C receptor agonists and reversed by 5-HT2C antagonists. Voltage-clamp slow-ramp experiments showed that serotonin caused a strong increase in an outward current activated by depolarisations that was blocked by the specific M current blocker XE 991. In current-clamp experiments, XE 991 per se caused membrane depolarisations in LTSIs and subsequent application of serotonin (in the presence of XE 991) failed to affect these neurons. We concluded that serotonin strongly inhibits striatal LTSIs acting through postsynaptic 5-HT2C receptors and increasing an M type current. PMID:22495583

  3. Somatostatin-expressing inhibitory interneurons in cortical circuits

    Directory of Open Access Journals (Sweden)

    Iryna Yavorska


    Full Text Available Cortical inhibitory neurons exhibit remarkable diversity in their morphology, connectivity, and synaptic properties. Here, we review the function of somatostatin-expressing (SOM inhibitory interneurons, focusing largely on sensory cortex. SOM neurons also comprise a number of subpopulations that can be distinguished by their morphology, input and output connectivity, laminar location, firing properties, and expression of molecular markers. Several of these classes of SOM neurons show unique dynamics and characteristics, such as facilitating synapses, specific axonal projections, intralaminar input, and top-down modulation, which suggest possible computational roles. SOM cells can be differentially modulated by behavioral state depending on their class, sensory system, and behavioral paradigm. The functional effects of such modulation have been studied with optogenetic manipulation of SOM cells, which produces effects on learning and memory, task performance, and the integration of cortical activity. Different classes of SOM cells participate in distinct disinhibitory circuits with different inhibitory partners and in different cortical layers. Through these disinhibitory circuits, SOM cells help encode the behavioral relevance of sensory stimuli by regulating the activity of cortical neurons based on subcortical and intracortical modulatory input. Associative learning leads to long-term changes in the strength of connectivity of SOM cells with other neurons, often influencing the strength of inhibitory input they receive. Thus despite their heterogeneity and variability across cortical areas, current evidence shows that SOM neurons perform unique neural computations, forming not only distinct molecular but also functional subclasses of cortical inhibitory interneurons.

  4. Retinal interneuron survival requires non-cell-autonomous Atrx activity. (United States)

    Lagali, Pamela S; Medina, Chantal F; Zhao, Brandon Y H; Yan, Keqin; Baker, Adam N; Coupland, Stuart G; Tsilfidis, Catherine; Wallace, Valerie A; Picketts, David J


    ATRX is a chromatin remodeling protein that is mutated in several intellectual disability disorders including alpha-thalassemia/mental retardation, X-linked (ATR-X) syndrome. We previously reported the prevalence of ophthalmological defects in ATR-X syndrome patients, and accordingly we find morphological and functional visual abnormalities in a mouse model harboring a mutation occurring in ATR-X patients. The visual system abnormalities observed in these mice parallels the Atrx-null retinal phenotype characterized by interneuron defects and selective loss of amacrine and horizontal cells. The mechanisms that underlie selective neuronal vulnerability and neurodegeneration in the central nervous system upon Atrx mutation or deletion are unknown. To interrogate the cellular specificity of Atrx for its retinal neuroprotective functions, we employed a combination of temporal and lineage-restricted conditional ablation strategies to generate five different conditional knockout mouse models, and subsequently identified a non-cell-autonomous requirement for Atrx in bipolar cells for inhibitory interneuron survival in the retina. Atrx-deficient retinal bipolar cells exhibit functional, structural and molecular alterations consistent with impairments in neuronal activity and connectivity. Gene expression changes in the Atrx-null retina indicate defective synaptic structure and neuronal circuitry, suggest excitotoxic mechanisms of neurodegeneration, and demonstrate that common targets of ATRX in the forebrain and retina may contribute to similar neuropathological processes underlying cognitive impairment and visual dysfunction in ATR-X syndrome.

  5. Identification of Arx targets unveils new candidates for controlling cortical interneuron migration and differentiation

    Directory of Open Access Journals (Sweden)

    Gaelle M Friocourt


    Full Text Available Mutations in the homeobox transcription factor ARX have been found to be responsible for a wide spectrum of disorders extending from phenotypes with severe neuronal migration defects, such as lissencephaly, to mild forms of intellectual disabilities without apparent brain abnormalities, but with associated features of dystonia and epilepsy. Arx expression is mainly restricted to populations of GABA-containing neurons. Studies of the effects of ARX loss of function, either in humans or mutant mice, revealed varying defects, suggesting multiple roles of this gene in brain patterning, neuronal proliferation and migration, cell maturation and differentiation, as well as axonal outgrowth and connectivity. However, to date, little is known about how Arx functions as a transcription factor or which genes it binds and regulates. Recently, we combined chromatin immunoprecipitation and mRNA expression with microarray analysis and identified approximately 1000 gene promoters bound by Arx in transfected neuroblastoma N2a cells and mouse embryonic brain. To narrow the analysis of Arx targets to those most likely to control cortical interneuron migration and/or differentiation, we compare here our data to previously published studies searching for genes enriched or down-regulated in cortical interneurons between E13.5 and E15.5. We thus identified 14 Arx-target genes enriched (Cxcr7, Meis1, Ppap2a, Slc12a5, Ets2, Phlda1, Zif268, Igf1, Lmo3, Sema6, Lgi1, Alk, Tgfb3, Napb and 5 genes specifically down-regulated (Hmgn3, Lmo1, Ebf3, Rasgef1b and Slit2 in cortical migrating neurons. In this review, we present these genes and discuss how their possible regulation by Arx may lead to the dysfunction of GABAergic neurons, resulting in mental retardation and epilepsy.

  6. MDMA-induced loss of parvalbumin interneurons within the dentate gyrus is mediated by 5HT2A and NMDA receptors. (United States)

    Collins, Stuart A; Gudelsky, Gary A; Yamamoto, Bryan K


    MDMA is a widely abused psychostimulant which causes a rapid and robust release of the monoaminergic neurotransmitters dopamine and serotonin. Recently, it was shown that MDMA increases extracellular glutamate concentrations in the dorsal hippocampus, which is dependent on serotonin release and 5HT2A/2C receptor activation. The increased extracellular glutamate concentration coincides with a loss of parvalbumin-immunoreactive (PV-IR) interneurons of the dentate gyrus region. Given the known susceptibility of PV interneurons to excitotoxicity, we examined whether MDMA-induced increases in extracellular glutamate in the dentate gyrus are necessary for the loss of PV cells in rats. Extracellular glutamate concentrations increased in the dentate gyrus during systemic and local administration of MDMA. Administration of the NMDA receptor antagonist, MK-801, during systemic injections of MDMA, prevented the loss of PV-IR interneurons seen 10 days after MDMA exposure. Local administration of MDL100907, a selective 5HT2A receptor antagonist, prevented the increases in glutamate caused by reverse dialysis of MDMA directly into the dentate gyrus and prevented the reduction of PV-IR. These findings provide evidence that MDMA causes decreases in PV within the dentate gyrus through a 5HT2A receptor-mediated increase in glutamate and subsequent NMDA receptor activation. Copyright © 2015 Elsevier B.V. All rights reserved.


    Alvarez, Francisco J.; Jonas, Philip C.; Sapir, Tamar; Hartley, Robert; Berrocal, Maria C.; Geiman, Eric J.; Todd, Andrew J.; Goulding, Martyn


    Developmental studies identified four classes (V0, V1, V2, V3) of embryonic interneurons in the ventral spinal cord. Very little however is known about their adult phenotypes. In order to further characterize interneuron cell types in the adult, the location, neurotransmitter phenotype, calcium-buffering protein expression and axon distributions of V1-derived neurons in the mouse spinal cord was determined. In the mature (P20 and older) spinal cord, most V1-derived neurons are located in lateral LVII and in LIX, few in medial LVII and none in LVIII. Approximately 40% express calbindin and/or parvalbumin, while few express calretinin. Of seven groups of ventral interneurons identified according to calcium-buffering protein expression, two groups (1 and 4) correspond with V1-derived neurons. Group 1 are Renshaw cells and intensely express calbindin and coexpress parvalbumin and calretinin. They represent 9% of the V1 population. Group 4 express only parvalbumin and represent 27% of V1-derived neurons. V1-derived group 4 neurons receive contacts from primary sensory afferents and are therefore proprioceptive interneurons and the most ventral neurons in this group receive convergent calbindin-IR Renshaw cell inputs. This subgroup resembles Ia inhibitory interneurons (IaINs) and represents 13% of V1-derived neurons. Adult V1-interneuron axons target LIX and LVII and some enter the deep dorsal horn. V1-axons do not cross the midline. V1 derived axonal varicosities were mostly (>80%) glycinergic and a third were GABAergic. None were glutamatergic or cholinergic. In summary, V1 interneurons develop into ipsilaterally projecting, inhibitory interneurons that include Renshaw cells, Ia inhibitory interneurons and other unidentified proprioceptive interneurons. PMID:16255029

  8. Neto Auxiliary Subunits Regulate Interneuron Somatodendritic and Presynaptic Kainate Receptors to Control Network Inhibition

    Directory of Open Access Journals (Sweden)

    Megan S. Wyeth


    Full Text Available Although Netos are considered auxiliary subunits critical for kainate receptor (KAR function, direct evidence for their regulation of native KARs is limited. Because Neto KAR regulation is GluK subunit/Neto isoform specific, such regulation must be determined in cell-type-specific contexts. We demonstrate Neto1/2 expression in somatostatin (SOM-, cholecystokinin/cannabinoid receptor 1 (CCK/CB1-, and parvalbumin (PV-containing interneurons. KAR-mediated excitation of these interneurons is contingent upon Neto1 because kainate yields comparable effects in Neto2 knockouts and wild-types but fails to excite interneurons or recruit inhibition in Neto1 knockouts. In contrast, presynaptic KARs in CCK/CB1 interneurons are dually regulated by both Neto1 and Neto2. Neto association promotes tonic presynaptic KAR activation, dampening CCK/CB1 interneuron output, and loss of this brake in Neto mutants profoundly increases CCK/CB1 interneuron-mediated inhibition. Our results confirm that Neto1 regulates endogenous somatodendritic KARs in diverse interneurons and demonstrate Neto regulation of presynaptic KARs in mature inhibitory presynaptic terminals.

  9. Different correlation patterns of cholinergic and GABAergic interneurons with striatal projection neurons

    Directory of Open Access Journals (Sweden)

    Avital eAdler


    Full Text Available The striatum is populated by a single projection neuron group, the medium spiny neurons (MSNs, and several groups of interneurons. Two of the electrophysiologically well-characterized striatal interneuron groups are the tonically active neurons (TANs, which are presumably cholinergic interneurons, and the fast spiking interneurons (FSIs, presumably parvalbumin (PV expressing GABAergic interneurons. To better understand striatal processing it is thus crucial to define the functional relationship between MSNs and these interneurons in the awake and behaving animal. We used multiple electrodes and standard physiological methods to simultaneously record MSN spiking activity and the activity of TANs or FSIs from monkeys engaged in a classical conditioning paradigm. All three cell populations were highly responsive to the behavioral task. However, they displayed different average response profiles and a different degree of response synchronization (signal correlation. TANs displayed the most transient and synchronized response, MSNs the most diverse and sustained response and FSIs were in between on both parameters. We did not find evidence for direct monosynaptic connectivity between the MSNs and either the TANs or the FSIs. However, while the cross correlation histograms of TAN to MSN pairs were flat, those of FSI to MSN displayed positive asymmetrical broad peaks. The FSI-MSN correlogram profile implies that the spikes of MSNs follow those of FSIs and both are driven by a common, most likely cortical, input. Thus, the two populations of striatal interneurons are probably driven by different afferents and play complementary functional roles in the physiology of the striatal microcircuit.

  10. Environmental enrichment as a therapeutic avenue for anxiety in aged Wistar rats: Effect on cat odor exposition and GABAergic interneurons. (United States)

    Sampedro-Piquero, P; Castilla-Ortega, E; Zancada-Menendez, C; Santín, L J; Begega, A


    The use of more ethological animal models to study the neurobiology of anxiety has increased in recent years. We assessed the effect of an environmental enrichment (EE) protocol (24h/day over a period of two months) on anxiety-related behaviors when aged Wistar rats (21months old) were confronted with cat odor stimuli. Owing to the relationship between GABAergic interneurons and the anxiety-related neuronal network, we examined changes in the expression of Parvalbumin (PV) and 67kDa form of glutamic acid decarboxylase (GAD-67) immunoreactive cells in different brain regions involved in stress response. Behavioral results revealed that enriched rats traveled further and made more grooming behaviors during the habituation session. In the cat odor session, they traveled longer distances and they showed more active interaction with the odor stimuli and less time in freezing behavior. Zone analysis revealed that the enriched group spent more time in the intermediate zone according to the proximity of the predator odor. Regarding the neurobiological data, the EE increased the expression of PV-positive cells in some medial prefrontal regions (cingulate (Cg) and prelimbic (PL) cortices), whereas the GAD-67 expression in the basolateral amygdala was reduced in the enriched group. Our results suggest that EE is able to reduce anxiety-like behaviors in aged animals even when ethologically relevant stimuli are used. Moreover, GABAergic interneurons could be involved in mediating this resilient behavior. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Differential expression of parvalbumin interneurons in neonatal phencyclidine treated rats and socially isolated rats

    DEFF Research Database (Denmark)

    Kaalund, Sanne Simone; Riise, Jesper; Broberg, Brian


    fractionator, we counted neurons, PV(+) interneurons, and glial cells in the medial prefrontal cortex (mPFC) and hippocampus (HPC). In addition, we quantified the mRNA level of parvalbumin in the mPFC. There was a statistically significant reduction in the number of PV(+) interneurons (p = 0.021) and glial...... cells (p = 0.024) in the mPFC of neonatal phencyclidine rats. We observed no alterations in the total number of neurons, hippocampal PV(+) interneurons, parvalbumin mRNA expression or volume of the mPFC or HPC in the two models. Thus, as the total number of neurons remains unchanged following...

  12. A comparative perspective on minicolumns and inhibitory GABAergic interneurons in the neocortex

    Directory of Open Access Journals (Sweden)

    Mary Ann Raghanti


    Full Text Available Neocortical columns are functional and morphological units whose architecture may have been under selective evolutionary pressure in different mammalian lineages in response to encephalization and specializations of cognitive abilities. Inhibitory interneurons make a substantial contribution to the morphology and distribution of minicolumns within the cortex. In this context, we review differences in minicolumns and GABAergic interneurons among species and discuss possible implications for signaling among and within minicolumns. Furthermore, we discuss how abnormalities of both minicolumn disposition and inhibitory interneurons might be associated with neuropathological processes, such as Alzheimer’s disease, autism, and schizophrenia. Specifically, we will explore the possibility that phylogenetic variability in calcium-binding protein-expressing interneuron subtypes is directly related to differences in minicolumn morphology among species and might contribute to neuropathological susceptibility in humans.

  13. Myelination of parvalbumin interneurons: a parsimonious locus of pathophysiological convergence in schizophrenia

    NARCIS (Netherlands)

    Stedehouder, J.; S.A. Kushner (Steven)


    textabstractSchizophrenia is a debilitating psychiatric disorder characterized by positive, negative and cognitive symptoms. Despite more than a century of research, the neurobiological mechanism underlying schizophrenia remains elusive. White matter abnormalities and interneuron dysfunction are the

  14. Functional identification of interneurons responsible for left-right coordination of hindlimbs in mammals

    DEFF Research Database (Denmark)

    Butt, Simon J.B.; Kiehn, Ole


    Local neuronal networks that are responsible for walking are poorly characterized in mammals. Using an innovative approach to identify interneuron inputs onto motorneuron populations in a neonatal rodent spinal cord preparation, we have investigated the network responsible for left......-right coordination of the hindlimbs. We demonstrate how commissural interneurons (CINs), whose axons traverse the midline to innervate contralateral neurons, are organized such that distinct flexor and extensor centers in the rostral lumbar spinal cord define activity in both flexor and extensor caudal motor pools....... In addition, the nature of some connections are reconfigured on switching from rest to locomotion via a mechanism that might be associated with synaptic plasticity in the spinal cord. These results from identified pattern-generating interneurons demonstrate how interneuron populations create an effective...

  15. Diversity in the neuronal machine: order and variability in interneuronal microcircuits

    National Research Council Canada - National Science Library

    Soltesz, Ivan


    ... Disorders 42 3: Order in Diversity: From Phenomenology to Function 45 Diversity at Multiple Levels of Neuronal Organization 45 Linnean Order in Diversity: A Modern Compendium of Interneuronal Spe...

  16. Random walk behavior of migrating cortical interneurons in the marginal zone: time-lapse analysis in flat-mount cortex. (United States)

    Tanaka, Daisuke H; Yanagida, Mitsutoshi; Zhu, Yan; Mikami, Sakae; Nagasawa, Takashi; Miyazaki, Jun-ichi; Yanagawa, Yuchio; Obata, Kunihiko; Murakami, Fujio


    Migrating neurons are thought to travel from their origin near the ventricle to distant territories along stereotypical pathways by detecting environmental cues in the extracellular milieu. Here, we report a novel mode of neuronal migration that challenges this view. We performed long-term, time-lapse imaging of medial ganglionic eminence (MGE)-derived cortical interneurons tangentially migrating in the marginal zone (MZ) in flat-mount cortices. We find that they exhibit a diverse range of behaviors in terms of the rate and direction of migration. Curiously, a predominant population of these neurons repeatedly changes its direction of migration in an unpredictable manner. Trajectories of migration vary from one neuron to another. The migration of individual cells lasts for long periods, sometimes up to 2 d. Theoretical analyses reveal that these behaviors can be modeled by a random walk. Furthermore, MZ cells migrate from the cortical subventricular zone to the cortical plate, transiently accumulating in the MZ. These results suggest that MGE-derived cortical interneurons, once arriving at the MZ, are released from regulation by guidance cues and initiate random walk movement, which potentially contributes to their dispersion throughout the cortex.

  17. Developmental profile of the aberrant dopamine D2 receptor response in striatal cholinergic interneurons in DYT1 dystonia.

    Directory of Open Access Journals (Sweden)

    Giuseppe Sciamanna

    Full Text Available DYT1 dystonia, a severe form of genetically determined human dystonia, exhibits reduced penetrance among carriers and begins usually during adolescence. The reasons for such age dependence and variability remain unclear.We characterized the alterations in D2 dopamine receptor (D2R signalling in striatal cholinergic interneurons at different ages in mice overexpressing human mutant torsinA (hMT. An abnormal excitatory response to the D2R agonist quinpirole was recorded at postnatal day 14, consisting of a membrane depolarization coupled to an increase in spiking frequency, and persisted unchanged at 3 and 9 months in hMT mice, compared to mice expressing wild-type human torsinA and non-transgenic mice. This response was blocked by the D2R antagonist sulpiride and depended upon G-proteins, as it was prevented by intrapipette GDP-β-S. Patch-clamp recordings from dissociated interneurons revealed a significant increase in the Cav2.2-mediated current fraction at all ages examined. Consistently, chelation of intracellular calcium abolished the paradoxical response to quinpirole. Finally, no gross morphological changes were observed during development.These results suggest that an imbalanced striatal dopaminergic/cholinergic signaling occurs early in DYT1 dystonia and persists along development, representing a susceptibility factor for symptom generation.

  18. Myelination of parvalbumin interneurons: a parsimonious locus of pathophysiological convergence in schizophrenia (United States)

    Stedehouder, J; Kushner, S A


    Schizophrenia is a debilitating psychiatric disorder characterized by positive, negative and cognitive symptoms. Despite more than a century of research, the neurobiological mechanism underlying schizophrenia remains elusive. White matter abnormalities and interneuron dysfunction are the most widely replicated cellular neuropathological alterations in patients with schizophrenia. However, a unifying model incorporating these findings has not yet been established. Here, we propose that myelination of fast-spiking parvalbumin (PV) interneurons could be an important locus of pathophysiological convergence in schizophrenia. Myelination of interneurons has been demonstrated across a wide diversity of brain regions and appears highly specific for the PV interneuron subclass. Given the critical influence of fast-spiking PV interneurons for mediating oscillations in the gamma frequency range (~30–120 Hz), PV myelination is well positioned to optimize action potential fidelity and metabolic homeostasis. We discuss this hypothesis with consideration of data from human postmortem studies, in vivo brain imaging and electrophysiology, and molecular genetics, as well as fundamental and translational studies in rodent models. Together, the parvalbumin interneuron myelination hypothesis provides a falsifiable model for guiding future studies of schizophrenia pathophysiology. PMID:27646261

  19. Distinct roles of SOM and VIP interneurons during cortical Up states

    Directory of Open Access Journals (Sweden)

    Garrett T. Neske


    Full Text Available During cortical network activity, recurrent synaptic excitation among pyramidal neurons is approximately balanced by synaptic inhibition, which is provided by a vast diversity of inhibitory interneurons. The relative contributions of different interneuron subtypes to inhibitory tone during cortical network activity is not well understood. We previously showed that many of the major interneuron subtypes in mouse barrel cortex are highly active during Up states (Neske et al., 2015; while fast-spiking (FS, parvalbumin (PV-positive cells were the most active interneuron subtype, many non-fast-spiking (NFS, PV-negative interneurons were as active or more active than neighboring pyramidal cells. This suggests that the NFS cells could play a role in maintaining or modulating Up states. Here, using optogenetic techniques, we further dissected the functional roles during Up states of two major NFS, PV-negative interneuron subtypes: somatostatin (SOM-positive cells and vasoactive intestinal peptide (VIP-positive cells. We found that while pyramidal cell excitability during Up states significantly increased when SOM cells were optogenetically silenced, VIP cells did not influence pyramidal cell excitability either upon optogenetic silencing or activation. VIP cells failed to contribute to Up states despite their ability to inhibit SOM cells strongly. We suggest that the contribution of VIP cells to the excitability of pyramidal cells may vary with cortical state.

  20. Robust Scientists

    DEFF Research Database (Denmark)

    Gorm Hansen, Birgitte

    their core i nterests, 2) developing a selfsupply of industry interests by becoming entrepreneurs and thus creating their own compliant industry partner and 3) balancing resources within a larger collective of researchers, thus countering changes in the influx of funding caused by shifts in political...... knowledge", Danish research policy seems to have helped develop politically and economically "robust scientists". Scientific robustness is acquired by way of three strategies: 1) tasting and discriminating between resources so as to avoid funding that erodes academic profiles and push scientists away from...

  1. Modeling of inter-neuronal coupling medium and its impact on neuronal synchronization.

    Directory of Open Access Journals (Sweden)

    Muhammad Iqbal

    Full Text Available In this paper, modeling of the coupling medium between two neurons, the effects of the model parameters on the synchronization of those neurons, and compensation of coupling strength deficiency in synchronization are studied. Our study exploits the inter-neuronal coupling medium and investigates its intrinsic properties in order to get insight into neuronal-information transmittance and, there from, brain-information processing. A novel electrical model of the coupling medium that represents a well-known RLC circuit attributable to the coupling medium's intrinsic resistive, inductive, and capacitive properties is derived. Surprisingly, the integration of such properties reveals the existence of a natural three-term control strategy, referred to in the literature as the proportional integral derivative (PID controller, which can be responsible for synchronization between two neurons. Consequently, brain-information processing can rely on a large number of PID controllers based on the coupling medium properties responsible for the coherent behavior of neurons in a neural network. Herein, the effects of the coupling model (or natural PID controller parameters are studied and, further, a supervisory mechanism is proposed that follows a learning and adaptation policy based on the particle swarm optimization algorithm for compensation of the coupling strength deficiency.

  2. P1 interneurons promote a persistent internal state that enhances inter-male aggression in Drosophila (United States)

    Hoopfer, Eric D; Jung, Yonil; Inagaki, Hidehiko K; Rubin, Gerald M; Anderson, David J


    How brains are hardwired to produce aggressive behavior, and how aggression circuits are related to those that mediate courtship, is not well understood. A large-scale screen for aggression-promoting neurons in Drosophila identified several independent hits that enhanced both inter-male aggression and courtship. Genetic intersections revealed that 8-10 P1 interneurons, previously thought to exclusively control male courtship, were sufficient to promote fighting. Optogenetic experiments indicated that P1 activation could promote aggression at a threshold below that required for wing extension. P1 activation in the absence of wing extension triggered persistent aggression via an internal state that could endure for minutes. High-frequency P1 activation promoted wing extension and suppressed aggression during photostimulation, whereas aggression resumed and wing extension was inhibited following photostimulation offset. Thus, P1 neuron activation promotes a latent, internal state that facilitates aggression and courtship, and controls the overt expression of these social behaviors in a threshold-dependent, inverse manner. DOI: PMID:26714106

  3. Parvalbumin fast-spiking interneurons are selectively altered by paediatric traumatic brain injury. (United States)

    Nichols, Joshua; Bjorklund, George Reed; Newbern, Jason; Anderson, Trent


    Traumatic brain injury (TBI) in children remains a leading cause of death and disability and it remains poorly understood why children have worse outcomes and longer recover times. TBI has shown to alter cortical excitability and inhibitory drive onto excitatory neurons, yet few studies have directly examined changes to cortical interneurons. This is addressed in the present study using a clinically relevant model of severe TBI (controlled cortical impact) in interneuron cell type specific Cre-dependent mice. Mice subjected to controlled cortical impact exhibit specific loss of parvalbumin (PV) but not somatostatin immunoreactivity and cell density in the peri-injury zone. PV interneurons are primarily of a fast-spiking (FS) phenotype that persisted in the peri-injury zone but received less frequent inhibitory and stronger excitatory post-synaptic currents. The targeted loss of PV-FS interneurons appears to be distinct from previous reports in adult mice suggesting that TBI-induced pathophysiology is dependent on the age at time of impact. Paediatric traumatic brain injury (TBI) is a leading cause of death and disability in children. Traditionally, ongoing neurodevelopment and neuroplasticity have been considered to confer children with an advantage following TBI. However, recent findings indicate that the paediatric brain may be more sensitive to brain injury. Inhibitory interneurons are essential for proper cortical function and are implicated in the pathophysiology of TBI, yet few studies have directly investigated TBI-induced changes to interneurons themselves. Accordingly, in the present study, we examine how inhibitory neurons are altered following controlled cortical impact (CCI) in juvenile mice with targeted Cre-dependent fluorescence labelling of interneurons (Vgat:Cre/Ai9 and PV:Cre/Ai6). Although CCI failed to alter the number of excitatory neurons or somatostatin-expressing interneurons in the peri-injury zone, it significantly decreased the density of

  4. A Method to Culture GABAergic Interneurons Derived from the Medial Ganglionic Eminence (United States)

    Franchi, Sira A.; Macco, Romina; Astro, Veronica; Tonoli, Diletta; Savino, Elisa; Valtorta, Flavia; Sala, Kristyna; Botta, Martina; de Curtis, Ivan


    Understanding the mechanisms guiding interneuron development is a central aspect of the current research on cortical/hippocampal interneurons, which is highly relevant to brain function and pathology. In this methodological study we have addressed the setup of protocols for the reproducible culture of dissociated cells from murine medial ganglionic eminences (MGEs), to provide a culture system for the analysis of interneurons in vitro. This study includes the detailed protocols for the preparation of the dissociated cells, and for their culture on optimal substrates for cell migration or differentiation. These cultures enriched in interneurons may allow the investigation of the migratory behavior of interneuron precursors and their differentiation in vitro, up to the formation of morphologically identifiable GABAergic synapses. Live imaging of MGE–derived cells plated on proper substrates shows that they are useful to study the migratory behavior of the precursors, as well as the behavior of growth cones during the development of neurites. Most MGE-derived precursors develop into polarized GABAergic interneurons as determined by axonal, dendritic, and GABAergic markers. We present also a comparison of cells from WT and mutant mice as a proof of principle for the use of these cultures for the analysis of the migration and differentiation of GABAergic cells with different genetic backgrounds. The culture enriched in interneurons described here represents a useful experimental system to examine in a relatively easy and fast way the morpho-functional properties of these cells under physiological or pathological conditions, providing a powerful tool to complement the studies in vivo. PMID:29358905

  5. NMDA Receptors Regulate the Structural Plasticity of Spines and Axonal Boutons in Hippocampal Interneurons

    Directory of Open Access Journals (Sweden)

    Marta Perez-Rando


    Full Text Available N-methyl-D-aspartate receptors (NMDARs are present in both pyramidal neurons and interneurons of the hippocampus. These receptors play an important role in the adult structural plasticity of excitatory neurons, but their impact on the remodeling of interneurons is unknown. Among hippocampal interneurons, somatostatin-expressing cells located in the stratum oriens are of special interest because of their functional importance and structural characteristics: they display dendritic spines, which change density in response to different stimuli. In order to understand the role of NMDARs on the structural plasticity of these interneurons, we have injected acutely MK-801, an NMDAR antagonist, to adult mice which constitutively express enhanced green fluorescent protein (EGFP in these cells. We have behaviorally tested the animals, confirming effects of the drug on locomotion and anxiety-related behaviors. NMDARs were expressed in the somata and dendritic spines of somatostatin-expressing interneurons. Twenty-four hours after the injection, the density of spines did not vary, but we found a significant increase in the density of their en passant boutons (EPB. We have also used entorhino-hippocampal organotypic cultures to study these interneurons in real-time. There was a rapid decrease in the apparition rate of spines after MK-801 administration, which persisted for 24 h and returned to basal levels afterwards. A similar reversible decrease was detected in spine density. Our results show that both spines and axons of interneurons can undergo remodeling and highlight NMDARs as regulators of this plasticity. These results are specially relevant given the importance of all these players on hippocampal physiology and the etiopathology of certain psychiatric disorders.

  6. Robust 8-color flow cytometry panel reveals enhanced effector function of NKG2C+ CD57+ FcεRγ- NK cells in CMV seropositive human blood donors. (United States)

    Nerreter, Thomas; Zeiß, Stephan; Herrmann, Thomas; Einsele, Hermann; Seggewiss-Bernhardt, Ruth


    Increasing evidence suggests that human NK cells may develop memory-like features. Here, we report the establishment of a robust 8-color flow cytometry panel that allows quantification and functional analysis of different memory-like NK cell subsets (NKG2C + /CD57 + , FcεRγ - ) from relatively small blood samples. We could confirm previous publications reporting an enhanced prevalence of the mentioned memory-like NK cell subsets in CMV seropositive human donors and were able to show a clear congruence between enhanced expression of NKG2C and CD57, the absence of FcεRγ and CMV seropositivity supporting the hypothesis of memory-like NK cell development following viral infections. While we could not detect significant differences in effector functions (i.e. degranulation and production of IFNγ) in regard to age or CMV seropositivity when looking at the overall NK cell population, a significantly enhanced expression of CD107a and IFNγ could be observed in NKG2C + /CD57 + as well as FcεRγ - NK cell subpopulations in CMV + donors. This enhancement of effector functions was even more pronounced in NKG2C + /CD57 + NK cells that were also negative for FcεRγ; CMV seropositive donors showed a dramatically increased expression of CD107a as well as IFNγ. With only small-sized volumes of blood needed, our proposed 8-color panel and experimental protocol offers easy handling and a reliable and reproducible option for implementation in accompanying clinical research, e.g. for evaluation of immunosuppressed patients suffering from autoimmune diseases or in allograft recipients. Copyright © 2017 Elsevier GmbH. All rights reserved.

  7. Compromised Survival of Cerebellar Molecular Layer Interneurons Lacking GDNF Receptors GFRα1 or RET Impairs Normal Cerebellar Motor Learning

    Directory of Open Access Journals (Sweden)

    Maria Christina Sergaki


    Full Text Available The role of neurotrophic factors as endogenous survival proteins for brain neurons remains contentious. In the cerebellum, the signals controlling survival of molecular layer interneurons (MLIs are unknown, and direct evidence for the requirement of a full complement of MLIs for normal cerebellar function and motor learning has been lacking. Here, we show that Purkinje cells (PCs, the target of MLIs, express the neurotrophic factor GDNF during MLI development and survival of MLIs depends on GDNF receptors GFRα1 and RET. Conditional mutant mice lacking either receptor lose a quarter of their MLIs, resulting in compromised synaptic inhibition of PCs, increased PC firing frequency, and abnormal acquisition of eyeblink conditioning and vestibulo-ocular reflex performance, but not overall motor activity or coordination. These results identify an endogenous survival mechanism for MLIs and reveal the unexpected vulnerability and selective requirement of MLIs in the control of cerebellar-dependent motor learning.

  8. Identification of DVA interneuron regulatory sequences in Caenorhabditis elegans. (United States)

    Puckett Robinson, Carmie; Schwarz, Erich M; Sternberg, Paul W


    The identity of each neuron is determined by the expression of a distinct group of genes comprising its terminal gene battery. The regulatory sequences that control the expression of such terminal gene batteries in individual neurons is largely unknown. The existence of a complete genome sequence for C. elegans and draft genomes of other nematodes let us use comparative genomics to identify regulatory sequences directing expression in the DVA interneuron. Using phylogenetic comparisons of multiple Caenorhabditis species, we identified conserved non-coding sequences in 3 of 10 genes (fax-1, nmr-1, and twk-16) that direct expression of reporter transgenes in DVA and other neurons. The conserved region and flanking sequences in an 85-bp intronic region of the twk-16 gene directs highly restricted expression in DVA. Mutagenesis of this 85 bp region shows that it has at least four regions. The central 53 bp region contains a 29 bp region that represses expression and a 24 bp region that drives broad neuronal expression. Two short flanking regions restrict expression of the twk-16 gene to DVA. A shared GA-rich motif was identified in three of these genes but had opposite effects on expression when mutated in the nmr-1 and twk-16 DVA regulatory elements. We identified by multi-species conservation regulatory regions within three genes that direct expression in the DVA neuron. We identified four contiguous regions of sequence of the twk-16 gene enhancer with positive and negative effects on expression, which combined to restrict expression to the DVA neuron. For this neuron a single binding site may thus not achieve sufficient specificity for cell specific expression. One of the positive elements, an 8-bp sequence required for expression was identified in silico by sequence comparisons of seven nematode species, demonstrating the potential resolution of expanded multi-species phylogenetic comparisons.

  9. TTX-Resistant NMDA Receptor-Mediated Membrane Potential Oscillations in Neonatal Mouse Hb9 Interneurons (United States)

    Masino, Mark A.; Abbinanti, Matthew D.; Eian, John; Harris-Warrick, Ronald M.


    Conditional neuronal membrane potential oscillations have been identified as a potential mechanism to help support or generate rhythmogenesis in neural circuits. A genetically identified population of ventromedial interneurons, called Hb9, in the mouse spinal cord has been shown to generate TTX-resistant membrane potential oscillations in the presence of NMDA, serotonin and dopamine, but these oscillatory properties are not well characterized. Hb9 interneurons are rhythmically active during fictive locomotor-like behavior. In this study, we report that exogenous N-Methyl-D-Aspartic acid (NMDA) application is sufficient to produce membrane potential oscillations in Hb9 interneurons. In contrast, exogenous serotonin and dopamine application, alone or in combination, are not sufficient. The properties of NMDA-induced oscillations vary among the Hb9 interneuron population; their frequency and amplitude increase with increasing NMDA concentration. NMDA does not modulate the T-type calcium current (ICa(T)), which is thought to be important in generating locomotor-like activity, in Hb9 neurons. These results suggest that NMDA receptor activation is sufficient for the generation of TTX-resistant NMDA-induced membrane potential oscillations in Hb9 interneurons. PMID:23094101

  10. New insights into the classification and nomenclature of cortical GABAergic interneurons (United States)

    DeFelipe, Javier; López-Cruz, Pedro L.; Benavides-Piccione, Ruth; Bielza, Concha; Larrañaga, Pedro; Anderson, Stewart; Burkhalter, Andreas; Cauli, Bruno; Fairén, Alfonso; Feldmeyer, Dirk; Fishell, Gord; Fitzpatrick, David; Freund, Tamás F.; González-Burgos, Guillermo; Hestrin, Shaul; Hill, Sean; Hof, Patrick R.; Huang, Josh; Jones, Edward G.; Kawaguchi, Yasuo; Kisvárday, Zoltán; Kubota, Yoshiyuki; Lewis, David A.; Marín, Oscar; Markram, Henry; McBain, Chris J.; Meyer, Hanno S.; Monyer, Hannah; Nelson, Sacha B.; Rockland, Kathleen; Rossier, Jean; Rubenstein, John L. R.; Rudy, Bernardo; Scanziani, Massimo; Shepherd, Gordon M.; Sherwood, Chet C.; Staiger, Jochen F.; Tamás, Gábor; Thomson, Alex; Wang, Yun; Yuste, Rafael; Ascoli, Giorgio A.


    A systematic classification and accepted nomenclature of neuron types is much needed but is currently lacking. This article describes a possible taxonomical solution for classifying GABAergic interneurons of the cerebral cortex based on a novel, web-based interactive system that allows experts to classify neurons with pre-determined criteria. Using Bayesian analysis and clustering algorithms on the resulting data, we investigated the suitability of several anatomical terms and neuron names for cortical GABAergic interneurons. Moreover, we show that supervised classification models could automatically categorize interneurons in agreement with experts’ assignments. These results demonstrate a practical and objective approach to the naming, characterization and classification of neurons based on community consensus. PMID:23385869

  11. Interneuron Deficit Associates Attenuated Network Synchronization to Mismatch of Energy Supply and Demand in Aging Mouse Brains

    DEFF Research Database (Denmark)

    Jessen, Sanne Barsballe; Mathiesen, Claus; Lind, Barbara Lykke


    Higher cognitive functions depend critically on synchronized network activity in the gamma range (30-100 Hz), which results from activity of fast-spiking parvalbumin-positive (PV) interneurons. Here, we examined synaptic activity in the gamma band in relation to PV interneuron activity, stimulati...... and CMRO2 responses may contribute to increased frailty and risk of cognitive decline in aged brains....

  12. Age-Related Uptake of Heavy Metals in Human Spinal Interneurons. (United States)

    Pamphlett, Roger; Kum Jew, Stephen


    Toxic heavy metals have been implicated in the loss of spinal motoneurons in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). Motoneuron loss in the spinal anterior horn is severe in ALS/MND at the time of death, making this tissue unsuitable for examination. We therefore examined spinal cords of people without muscle weakness to look for any presence of heavy metals that could make these neurons susceptible to damage. Spinal cord samples from 50 individuals aged 1-95 y who had no clinical or histopathological evidence of spinal motoneuron loss were studied. Seven μm formalin-fixed paraffin-embedded sections were stained for heavy metals with silver nitrate autometallography (AMGHM) which detects intracellular mercury, silver or bismuth. Neurons in the spinal cord were classified as interneurons or α-motoneurons based on their site and cell body diameter. Spinal interneurons containing heavy metals were present in 8 of 24 people (33%) aged 61-95 y, but not at younger ages. These AMGHM interneurons were most numerous in the lumbar spinal cord, with moderate numbers in the caudal cervical cord, few in the rostral cervical cord, and almost none in the thoracic cord. All people with AMGHM interneurons had occasional AMGHM staining in α-motoneurons as well. In one man AMGHM staining was present in addition in dorsomedial nucleus and sensory neurons. In conclusion, heavy metals are present in many spinal interneurons, and in a few α-motoneurons, in a large proportion of older people. Damage to inhibitory interneurons from toxic metals in later life could result in excitotoxic injury to motoneurons and may underlie motoneuron injury or loss in conditions such as ALS/MND, multiple sclerosis, sarcopenia and calf fasciculations.

  13. MGE-derived nNOS+ interneurons promote fear acquisition in nNOS-/- mice. (United States)

    Zhang, Lin; Yuan, Hong-Jin; Cao, Bo; Kong, Cheng-Cheng; Yuan, Fang; Li, Jun; Ni, Huan-Yu; Wu, Hai-Yin; Chang, Lei; Liu, Yan; Luo, Chun-Xia


    Neuronal nitric oxide synthase (nNOS) 1 , mainly responsible for NO release in central nervous system (CNS) 2 , plays a significant role in multiple physiological functions. However, the function of nNOS + interneurons in fear learning has not been much explored. Here we focused on the medial ganglionic eminences (MGE) 3 -derived nNOS + interneurons in fear learning. To determine the origin of nNOS + interneurons, we cultured neurons in vitro from MGE, cortex, lateral ganglionic eminence (LGE) 4 , caudal ganglionic eminences (CGE) 5 and preoptic area (POA) 6 . The results showed that MGE contained the most abundant precursors of nNOS + interneurons. Moreover, donor cells from E12.5 embryos demonstrated the highest positive rate of nNOS + interneurons compared with other embryonic periods (E11.5, E12, E13, E13.5 and E14). Additionally, these cells from E12.5 embryos showed long axonal and abundant dendritic arbors after 10 days culture, indicating the capability to disperse and integrate in host neural circuits after transplantation. To investigate the role of MGE-derived nNOS + interneurons in fear learning, donor MGE cells were transplanted into dentate gyrus (DG) 7 of nNOS knock-out (nNOS -/- ) or wild-type mice. Results showed that the transplantation of MGE cells promoted the acquisition of nNOS -/- but not the wild-type mice, suggesting the importance of nNOS + neurons in fear acquisition. Moreover, we transplanted MGE cells from nNOS -/- mice or wild-type mice into DG of the nNOS -/- mice and found that only MGE cells from wild-type mice but not the nNOS -/- mice rescued the deficit in acquisition of the nNOS -/- mice, further confirming the positive role of nNOS + neurons in fear learning. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Age-Related Uptake of Heavy Metals in Human Spinal Interneurons.

    Directory of Open Access Journals (Sweden)

    Roger Pamphlett

    Full Text Available Toxic heavy metals have been implicated in the loss of spinal motoneurons in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND. Motoneuron loss in the spinal anterior horn is severe in ALS/MND at the time of death, making this tissue unsuitable for examination. We therefore examined spinal cords of people without muscle weakness to look for any presence of heavy metals that could make these neurons susceptible to damage. Spinal cord samples from 50 individuals aged 1-95 y who had no clinical or histopathological evidence of spinal motoneuron loss were studied. Seven μm formalin-fixed paraffin-embedded sections were stained for heavy metals with silver nitrate autometallography (AMGHM which detects intracellular mercury, silver or bismuth. Neurons in the spinal cord were classified as interneurons or α-motoneurons based on their site and cell body diameter. Spinal interneurons containing heavy metals were present in 8 of 24 people (33% aged 61-95 y, but not at younger ages. These AMGHM interneurons were most numerous in the lumbar spinal cord, with moderate numbers in the caudal cervical cord, few in the rostral cervical cord, and almost none in the thoracic cord. All people with AMGHM interneurons had occasional AMGHM staining in α-motoneurons as well. In one man AMGHM staining was present in addition in dorsomedial nucleus and sensory neurons. In conclusion, heavy metals are present in many spinal interneurons, and in a few α-motoneurons, in a large proportion of older people. Damage to inhibitory interneurons from toxic metals in later life could result in excitotoxic injury to motoneurons and may underlie motoneuron injury or loss in conditions such as ALS/MND, multiple sclerosis, sarcopenia and calf fasciculations.

  15. Evidence That the Laminar Fate of LGE/CGE-Derived Neocortical Interneurons Is Dependent on Their Progenitor Domains. (United States)

    Torigoe, Makio; Yamauchi, Kenta; Kimura, Toshiya; Uemura, Yo; Murakami, Fujio


    Neocortical interneurons show tremendous diversity in terms of their neurochemical marker expressions, morphology, electrophysiological properties, and laminar fate. Allocation of interneurons to their appropriate regions and layers in the neocortex is thought to play important roles for the emergence of higher functions of the neocortex. Neocortical interneurons mainly originate from the medial ganglionic eminence (MGE) and the caudal ganglionic eminence (CGE). The diversity and the laminar fate of MGE-derived interneurons depend on the location of their birth and birthdate, respectively. However, this relationship does not hold for CGE-derived interneurons. Here, using the method of in utero electroporation, which causes arbitrary occurrence of labeled progenitor domains, we tracked all descendants of the lateral ganglionic eminence (LGE)/CGE progenitors in mice. We provide evidence that neocortical interneurons with distinct laminar fate originate from distinct progenitor domains within the LGE/CGE. We find layer I interneurons are predominantly labeled in a set of animals, whereas other upper layer neurons are predominantly labeled in another set. We also find distinct subcortical structures labeled between the two sets. Further, interneurons labeled in layer I show distinct neurochemical properties from those in other layers. Together, these results suggest that the laminar fate of LGE/CGE-derived interneurons depends on their spatial origin. Diverse types of neocortical interneurons have distinct laminar fate, neurochemical marker expression, morphology, and electrophysiological properties. Although the specifications and laminar fate of medial ganglionic eminence-derived neocortical interneurons depend on their location of embryonic origin and birthdate, no similar causality of lateral/caudal ganglionic eminence (LGE/CGE)-derived neocortical interneurons is known. Here, we performed in utero electroporation on mouse LGE/CGE and found two groups of animals

  16. A New Approach of Modified Submerged Patch Clamp Recording Reveals Interneuronal Dynamics during Epileptiform Oscillations

    Czech Academy of Sciences Publication Activity Database

    Morris, G.; Jiruška, Přemysl; Jefferys, J. G. R.; Powell, A. D.


    Roč. 10, Nov 9 (2016), č. článku 519. ISSN 1662-453X R&D Projects: GA ČR(CZ) GA14-02634S; GA MZd(CZ) NV15-29835A Institutional support: RVO:67985823 Keywords : in vitro * membrane chamber * LFP * patch clamp * epilepsy * high frequency activity Subject RIV: FH - Neurology Impact factor: 3.566, year: 2016

  17. Effects of active conductance distribution over dendrites on the synaptic integration in an identified nonspiking interneuron.

    Directory of Open Access Journals (Sweden)

    Akira Takashima

    Full Text Available The synaptic integration in individual central neuron is critically affected by how active conductances are distributed over dendrites. It has been well known that the dendrites of central neurons are richly endowed with voltage- and ligand-regulated ion conductances. Nonspiking interneurons (NSIs, almost exclusively characteristic to arthropod central nervous systems, do not generate action potentials and hence lack voltage-regulated sodium channels, yet having a variety of voltage-regulated potassium conductances on their dendritic membrane including the one similar to the delayed-rectifier type potassium conductance. It remains unknown, however, how the active conductances are distributed over dendrites and how the synaptic integration is affected by those conductances in NSIs and other invertebrate neurons where the cell body is not included in the signal pathway from input synapses to output sites. In the present study, we quantitatively investigated the functional significance of active conductance distribution pattern in the spatio-temporal spread of synaptic potentials over dendrites of an identified NSI in the crayfish central nervous system by computer simulation. We systematically changed the distribution pattern of active conductances in the neuron's multicompartment model and examined how the synaptic potential waveform was affected by each distribution pattern. It was revealed that specific patterns of nonuniform distribution of potassium conductances were consistent, while other patterns were not, with the waveform of compound synaptic potentials recorded physiologically in the major input-output pathway of the cell, suggesting that the possibility of nonuniform distribution of potassium conductances over the dendrite cannot be excluded as well as the possibility of uniform distribution. Local synaptic circuits involving input and output synapses on the same branch or on the same side were found to be potentially affected under

  18. A convergent and essential interneuron pathway for Mauthner-cell-mediated escapes. (United States)

    Lacoste, Alix M B; Schoppik, David; Robson, Drew N; Haesemeyer, Martin; Portugues, Ruben; Li, Jennifer M; Randlett, Owen; Wee, Caroline L; Engert, Florian; Schier, Alexander F


    The Mauthner cell (M-cell) is a command-like neuron in teleost fish whose firing in response to aversive stimuli is correlated with short-latency escapes [1-3]. M-cells have been proposed as evolutionary ancestors of startle response neurons of the mammalian reticular formation [4], and studies of this circuit have uncovered important principles in neurobiology that generalize to more complex vertebrate models [3]. The main excitatory input was thought to originate from multisensory afferents synapsing directly onto the M-cell dendrites [3]. Here, we describe an additional, convergent pathway that is essential for the M-cell-mediated startle behavior in larval zebrafish. It is composed of excitatory interneurons called spiral fiber neurons, which project to the M-cell axon hillock. By in vivo calcium imaging, we found that spiral fiber neurons are active in response to aversive stimuli capable of eliciting escapes. Like M-cell ablations, bilateral ablations of spiral fiber neurons largely eliminate short-latency escapes. Unilateral spiral fiber neuron ablations shift the directionality of escapes and indicate that spiral fiber neurons excite the M-cell in a lateralized manner. Their optogenetic activation increases the probability of short-latency escapes, supporting the notion that spiral fiber neurons help activate M-cell-mediated startle behavior. These results reveal that spiral fiber neurons are essential for the function of the M-cell in response to sensory cues and suggest that convergent excitatory inputs that differ in their input location and timing ensure reliable activation of the M-cell, a feedforward excitatory motif that may extend to other neural circuits. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Closed-loop response properties of a visual interneuron involved in fly optomotor control

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    Naveed eEjaz


    Full Text Available Due to methodological limitations neural function is mostly studied under open-loop conditions. Normally, however, nervous systems operate in closed-loop where sensory input is processed to generate behavioural outputs, which again change the sensory input. Here, we investigate the closed-loop responses of an identified visual interneuron, the blowfly H1-cell, that is part of a neural circuit involved in optomotor flight and gaze control. Those behaviours may be triggered by attitude changes during flight in turbulent air. The fly analyses the resulting retinal image shifts and performs compensatory body and head rotations to regain its default attitude. We developed a fly-robot interface to study H1-cell responses in a 1 degree-of-freedom image stabilization task. Image shifts, induced by externally forced rotations, modulate the cell’s spike rate that controls counter rotations of a mobile robot to minimize relative motion between the robot and its visual surroundings. A feedback controller closed the loop between neural activity and the rotation of the robot. Under these conditions we found the following H1-cell response properties: (i the peak spike rate decreases when the mean image velocity is increased, (ii the relationship between spike rate and image velocity depends on the standard deviation of the image velocities suggesting adaptive scaling of the cell’s signalling range, and (iii the cell’s gain decreases linearly with increasing image accelerations.Our results reveal a remarkable qualitative similarity between the response dynamics of the H1-cell under closed-loop conditions with those obtained in previous open-loop experiments. Finally, we show that the adaptive scaling of the H1-cell’s responses, while maximizing information on image velocity, decreases the cell’s sensitivity to image accelerations. Understanding such trade-offs in biological vision systems may advance the design of smart vision sensors for autonomous

  20. Synapsin function in GABA-ergic interneurons is required for short-term olfactory habituation. (United States)

    Sadanandappa, Madhumala K; Blanco Redondo, Beatriz; Michels, Birgit; Rodrigues, Veronica; Gerber, Bertram; VijayRaghavan, K; Buchner, Erich; Ramaswami, Mani


    In Drosophila, short-term (STH) and long-term habituation (LTH) of olfactory avoidance behavior are believed to arise from the selective potentiation of GABAergic synapses between multiglomerular local circuit interneurons (LNs) and projection neurons in the antennal lobe. However, the underlying mechanisms remain poorly understood. Here, we show that synapsin (syn) function is necessary for STH and that syn(97)-null mutant defects in STH can be rescued by syn(+) cDNA expression solely in the LN1 subset of GABAergic local interneurons. As synapsin is a synaptic vesicle-clustering phosphoprotein, these observations identify a presynaptic mechanism for STH as well as the inhibitory interneurons in which this mechanism is deployed. Serine residues 6 and/or 533, potential kinase target sites of synapsin, are necessary for synapsin function suggesting that synapsin phosphorylation is essential for STH. Consistently, biochemical analyses using a phospho-synapsin-specific antiserum show that synapsin is a target of Ca(2+) calmodulin-dependent kinase II (CaMKII) phosphorylation in vivo. Additional behavioral and genetic observations demonstrate that CaMKII function is necessary in LNs for STH. Together, these data support a model in which CaMKII-mediated synapsin phosphorylation in LNs induces synaptic vesicle mobilization and thereby presynaptic facilitation of GABA release that underlies olfactory STH. Finally, the striking observation that LTH occurs normally in syn(97) mutants indicates that signaling pathways for STH and LTH diverge upstream of synapsin function in GABAergic interneurons.

  1. Parvalbumin-expressing interneurons coordinate hippocampal network dynamics required for memory consolidation (United States)

    Ognjanovski, Nicolette; Schaeffer, Samantha; Wu, Jiaxing; Mofakham, Sima; Maruyama, Daniel; Zochowski, Michal; Aton, Sara J.


    Activity in hippocampal area CA1 is essential for consolidating episodic memories, but it is unclear how CA1 activity patterns drive memory formation. We find that in the hours following single-trial contextual fear conditioning (CFC), fast-spiking interneurons (which typically express parvalbumin (PV)) show greater firing coherence with CA1 network oscillations. Post-CFC inhibition of PV+ interneurons blocks fear memory consolidation. This effect is associated with loss of two network changes associated with normal consolidation: (1) augmented sleep-associated delta (0.5-4 Hz), theta (4-12 Hz) and ripple (150-250 Hz) oscillations; and (2) stabilization of CA1 neurons' functional connectivity patterns. Rhythmic activation of PV+ interneurons increases CA1 network coherence and leads to a sustained increase in the strength and stability of functional connections between neurons. Our results suggest that immediately following learning, PV+ interneurons drive CA1 oscillations and reactivation of CA1 ensembles, which directly promotes network plasticity and long-term memory formation.

  2. The Onecut Transcription Factors Regulate Differentiation and Distribution of Dorsal Interneurons during Spinal Cord Development

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    Karolina U. Kabayiza


    Full Text Available During embryonic development, the dorsal spinal cord generates numerous interneuron populations eventually involved in motor circuits or in sensory networks that integrate and transmit sensory inputs from the periphery. The molecular mechanisms that regulate the specification of these multiple dorsal neuronal populations have been extensively characterized. In contrast, the factors that contribute to their diversification into smaller specialized subsets and those that control the specific distribution of each population in the developing spinal cord remain unknown. Here, we demonstrate that the Onecut transcription factors, namely Hepatocyte Nuclear Factor-6 (HNF-6 (or OC-1, OC-2 and OC-3, regulate the diversification and the distribution of spinal dorsal interneuron (dINs. Onecut proteins are dynamically and differentially distributed in spinal dINs during differentiation and migration. Analyzes of mutant embryos devoid of Onecut factors in the developing spinal cord evidenced a requirement in Onecut proteins for proper production of a specific subset of dI5 interneurons. In addition, the distribution of dI3, dI5 and dI6 interneuron populations was altered. Hence, Onecut transcription factors control genetic programs that contribute to the regulation of spinal dIN diversification and distribution during embryonic development.


    NARCIS (Netherlands)


    Striatal cholinergic interneurons have been shown to receive input from striatal gamma-aminobutyric acid (GABA)-containing cell elements. GABA is known to act on two different types of receptors, the GABA(A) and the GABA(B) receptor. Using in vivo microdialysis, we have studied the effect of

  4. Functional organization of locomotor interneurons in the ventral lumbar spinal cord of the newborn rat.

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    Myriam Antri

    Full Text Available Although the mammalian locomotor CPG has been localized to the lumbar spinal cord, the functional-anatomical organization of flexor and extensor interneurons has not been characterized. Here, we tested the hypothesis that flexor and extensor interneuronal networks for walking are physically segregated in the lumbar spinal cord. For this purpose, we performed optical recordings and lesion experiments from a horizontally sectioned lumbar spinal cord isolated from neonate rats. This ventral hemi spinal cord preparation produces well-organized fictive locomotion when superfused with 5-HT/NMDA. The dorsal surface of the preparation was visualized using the Ca(2+ indicator fluo-4 AM, while simultaneously monitoring motor output at ventral roots L2 and L5. Using calcium imaging, we provided a general mapping view of the interneurons that maintained a stable phase relationship with motor output. We showed that the dorsal surface of L1 segment contains a higher density of locomotor rhythmic cells than the other segments. Moreover, L1 segment lesioning induced the most important changes in the locomotor activity in comparison with lesions at the T13 or L2 segments. However, no lesions led to selective disruption of either flexor or extensor output. In addition, this study found no evidence of functional parcellation of locomotor interneurons into flexor and extensor pools at the dorsal-ventral midline of the lumbar spinal cord of the rat.

  5. MHC-I promotes apoptosis of GABAergic interneurons in the spinal dorsal horn and contributes to cancer induced bone pain. (United States)

    Fu, Qiaochu; Shi, Dai; Zhou, Yaqun; Zheng, Hua; Xiang, Hongbing; Tian, Xuebi; Gao, Feng; Manyande, Anne; Cao, Fei; Tian, Yuke; Ye, Dawei


    Cancer induced bone pain (CIBP) remains one of the most intractable clinical problems due to poor understanding of its underlying mechanisms. Recent studies demonstrate the decline of inhibitory interneurons, especially GABAergic interneurons in the spinal cord, can evoke generation of chronic pain. It has also been reported that neuronal MHC-I expression renders neurons vulnerable to cytotoxic CD8 + T cells and finally lead to neurons apoptosis in a variety neurological disorders. However, whether MHC-I could induce the apoptosis of GABAergic interneurons in spinal cord and contribute to the development of CIBP remains unknown. In this study, we investigated roles of MHC-I and underlying mechanisms in CIBP on a rat model. Our results showed that increased MHC-I expression on GABAergic interneurons could deplete GABAergic interneurons by inducing their apoptosis in the spinal dorsal horn of tumor-bearing rats. Pretreatment of MHC-I RNAi-lentivirus could prevent the apoptosis of GABAergic interneurons and therefore alleviated mechanical allodynia induced by tumor cells intratibial injection. Additionally, we also found that CD8 + T cells were colocalized with MHC-I and GABAergic neurons and presented a significant and persistent increase in the spinal cord of tumor-bearing rats. Taken together, these findings indicated that MHC-I could evoke CIBP by promoting apoptosis of GABAergic interneurons in the dorsal horn, and this apoptosis was closely related to local CD8 + T cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Dendritic orientation and branching distinguish a class of multifunctional turtle spinal interneurons

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    Jonathan R. Holmes


    Full Text Available Spinal interneurons can integrate diverse propriospinal and supraspinal inputs that trigger or modulate locomotion and other limb movements. These synaptic inputs can occur on distal dendrites and yet must remain effective at the soma. Active dendritic conductances may amplify distal dendritic inputs, but appear to play a minimal role during scratching, at least. Another possibility is that spinal interneurons that integrate inputs on distal dendrites have unusually simple dendritic trees that effectively funnel current to the soma. We previously described a class of spinal interneurons, called transverse interneurons (or T neurons, in adult turtles. T neurons were defined as having dendrites that extend further in the transverse plane than rostrocaudally and a soma that extends further mediolaterally than rostrocaudally. T neurons are multifunctional, as they were activated during both swimming and scratching motor patterns. T neurons had higher peak firing rates and larger membrane potential oscillations during scratching than scratch-activated interneurons with different dendritic morphologies (non-T neurons. These characteristics make T neurons good candidates to play an important role in integrating diverse inputs and generating or relaying rhythmic motor patterns.Here, we quantitatively investigated additional dendritic morphological characteristics of T neurons as compared to non-T neurons. We found that T neurons have less total dendritic length, a greater proportion of dendritic length in primary dendrites, and dendrites that are oriented more mediolaterally. Thus, T neuron dendritic trees extend far mediolaterally, yet are unusually simple, which may help channel synaptic current from distal dendrites in the lateral and ventral funiculi to the soma. In combination with T neuron physiological properties, these dendritic properties may help integrate supraspinal and propriospinal inputs and generate and/or modulate rhythmic limb

  7. Meningeal defects alter the tangential migration of cortical interneurons in Foxc1hith/hith mice

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    Zarbalis Konstantinos


    Full Text Available Abstract Background Tangential migration presents the primary mode of migration of cortical interneurons translocating into the cerebral cortex from subpallial domains. This migration takes place in multiple streams with the most superficial one located in the cortical marginal zone. While a number of forebrain-expressed molecules regulating this process have emerged, it remains unclear to what extent structures outside the brain, like the forebrain meninges, are involved. Results We studied a unique Foxc1 hypomorph mouse model (Foxc1hith/hith with meningeal defects and impaired tangential migration of cortical interneurons. We identified a territorial correlation between meningeal defects and disruption of interneuron migration along the adjacent marginal zone in these animals, suggesting that impaired meningeal integrity might be the primary cause for the observed migration defects. Moreover, we postulate that the meningeal factor regulating tangential migration that is affected in homozygote mutants is the chemokine Cxcl12. In addition, by using chromatin immunoprecipitation analysis, we provide evidence that the Cxcl12 gene is a direct transcriptional target of Foxc1 in the meninges. Further, we observe migration defects of a lesser degree in Cajal-Retzius cells migrating within the cortical marginal zone, indicating a less important role for Cxcl12 in their migration. Finally, the developmental migration defects observed in Foxc1hith/hith mutants do not lead to obvious differences in interneuron distribution in the adult if compared to control animals. Conclusions Our results suggest a critical role for the forebrain meninges to promote during development the tangential migration of cortical interneurons along the cortical marginal zone and Cxcl12 as the factor responsible for this property.

  8. GABA regulates the multidirectional tangential migration of GABAergic interneurons in living neonatal mice.

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    Hiroyuki Inada

    Full Text Available Cortical GABAergic interneurons originate from ganglionic eminences and tangentially migrate into the cortical plate at early developmental stages. To elucidate the characteristics of this migration of GABAergic interneurons in living animals, we established an experimental design specialized for in vivo time-lapse imaging of the neocortex of neonate mice with two-photon laser-scanning microscopy. In vesicular GABA/glycine transporter (VGAT-Venus transgenic mice from birth (P0 through P3, we observed multidirectional tangential migration of genetically-defined GABAergic interneurons in the neocortical marginal zone. The properties of this migration, such as the motility rate (distance/hr, the direction moved, and the proportion of migrating neurons to stationary neurons, did not change through P0 to P3, although the density of GABAergic neurons at the marginal zone decreased with age. Thus, the characteristics of the tangential motility of individual GABAergic neurons remained constant in development. Pharmacological block of GABA(A receptors and of the Na⁺-K⁺-Cl⁻ cotransporters, and chelating intracellular Ca²⁺, all significantly reduced the motility rate in vivo. The motility rate and GABA content within the cortex of neonatal VGAT-Venus transgenic mice were significantly greater than those of GAD67-GFP knock-in mice, suggesting that extracellular GABA concentration could facilitate the multidirectional tangential migration. Indeed, diazepam applied to GAD67-GFP mice increased the motility rate substantially. In an in vitro neocortical slice preparation, we confirmed that GABA induced a NKCC sensitive depolarization of GABAergic interneurons in VGAT-Venus mice at P0-P3. Thus, activation of GABA(AR by ambient GABA depolarizes GABAergic interneurons, leading to an acceleration of their multidirectional motility in vivo.

  9. Chemical anatomy of striatal interneurons in normal individuals and in patients with Huntington's disease. (United States)

    Cicchetti, F; Prensa, L; Wu, Y; Parent, A


    This paper reviews the major anatomical and chemical features of the various types of interneurons in the human striatum, as detected by immunostaining procedures applied to postmortem tissue from normal individuals and patients with Huntington's disease (HD). The human striatum harbors a highly pleomorphic population of aspiny interneurons that stain for either a calcium-binding protein (calretinin, parvalbumin or calbindin D-28k), choline acetyltransferase (ChAT) or NADPH-diaphorase, or various combinations thereof. Neurons that express calretinin (CR), including multitudinous medium and a smaller number of large neurons, are by far the most abundant interneurons in the human striatum. The medium CR+ neurons do not colocalize with any of the known chemical markers of striatal neurons, except perhaps GABA, and are selectively spared in HD. Most large CR+ interneurons display ChAT immunoreactivity and also express substance P receptors. The medium and large CR+ neurons are enriched with glutamate receptor subunit GluR2 and GluR4, respectively. This difference in AMPA GluR subunit expression may account for the relative resistance of medium CR+ neurons to glutamate-mediated excitotoxicity that may be involved in HD. The various striatal chemical markers display a highly heterogeneous distribution pattern in human. In addition to the classic striosomes/matrix compartmentalization, the striosomal compartment itself is composed of a core and a peripheral region, each subdivided by distinct subsets of striatal interneurons. A proper knowledge of all these features that appear unique to humans should greatly help our understanding of the organization of the human striatum in both health and disease states.

  10. Acetylcholine release in mouse hippocampal CA1 preferentially activates inhibitory-selective interneurons via alpha4 beta2* nicotinic receptor activation

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    L. Andrew Bell


    Full Text Available Acetylcholine (ACh release onto nicotinic receptors directly activates subsets of inhibitory interneurons in hippocampal CA1. However, the specific interneurons activated and their effect on the hippocampal network is not completely understood. Therefore, we investigated subsets of hippocampal CA1 interneurons that respond to ACh release through the activation of nicotinic receptors and the potential downstream effects this may have on hippocampal CA1 network function. ACh was optogenetically released in mouse hippocampal slices by expressing the excitatory optogenetic protein oChIEF-tdTomato in medial septum/diagonal band of Broca cholinergic neurons using Cre recombinase-dependent adeno-associated viral mediated transfection. The actions of optogenetically released ACh were assessed on both pyramidal neurons and different interneuron subtypes via whole cell patch clamp methods. Vasoactive intestinal peptide (VIP-expressing interneurons that selectively innervate other interneurons (VIP/IS were excited by ACh through the activation of nicotinic receptors containing alpah4 and beta2 subunits (alpha4 beta2*. ACh release onto VIP/IS was presynaptically inhibited by M2 muscarinic autoreceptors. ACh release produced spontaneous inhibitory postsynaptic current (sIPSC barrages blocked by dihydro-beta-erythroidine in interneurons but not pyramidal neurons. Optogenetic suppression of VIP interneurons did not inhibit these sIPSC barrages suggesting other interneuron-selective interneurons were also excited by 42* nicotinic receptor activation. In contrast, interneurons that innervate pyramidal neuron perisomatic regions were not activated by ACh release onto nicotinic receptors. Therefore, we propose ACh release in CA1 facilitates disinhibition through activation of 42* nicotinic receptors on interneuron-selective interneurons whereas interneurons that innervate pyramidal neurons are less affected by nicotinic receptor activation.

  11. Caudal Ganglionic Eminence Precursor Transplants Disperse and Integrate as Lineage-Specific Interneurons but Do Not Induce Cortical Plasticity

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    Phillip Larimer


    Full Text Available The maturation of inhibitory GABAergic cortical circuits regulates experience-dependent plasticity. We recently showed that the heterochronic transplantation of parvalbumin (PV or somatostatin (SST interneurons from the medial ganglionic eminence (MGE reactivates ocular dominance plasticity (ODP in the postnatal mouse visual cortex. Might other types of interneurons similarly induce cortical plasticity? Here, we establish that caudal ganglionic eminence (CGE-derived interneurons, when transplanted into the visual cortex of neonatal mice, migrate extensively in the host brain and acquire laminar distribution, marker expression, electrophysiological properties, and visual response properties like those of host CGE interneurons. Although transplants from the anatomical CGE do induce ODP, we found that this plasticity reactivation is mediated by a small fraction of MGE-derived cells contained in the transplant. These findings demonstrate that transplanted CGE cells can successfully engraft into the postnatal mouse brain and confirm the unique role of MGE lineage neurons in the induction of ODP.

  12. Acute phencyclidine administration induces c-Fos-immunoreactivity in interneurons in cortical and subcortical regions

    DEFF Research Database (Denmark)

    Hervig, Mona E; Thomsen, Morten S; Kalló, Imre


    and subcortical areas, but whether such induction occurs in specific populations of GABAergic interneuron subtypes still remains to be established. We performed an immunohistochemical analysis of the PCP-induced c-Fos-immunoreactivity (IR) in parvalbumin (PV) and calbindin (CB) interneuron subtypes in the cortex...... and thalamus of rats. A single dose of PCP (10mg/kg, s.c.) significantly increased total number of c-Fos-IR in: (1) the prelimbic, infralimbic, anterior cingulate, ventrolateral orbital, motor, somatosensory and retrosplenial cortices as well as the nucleus accumbens (NAc), field CA1 of the hippocampus (CA1......) field of hippocampus and mediodorsal thalamus (MD); (2) PV-IR cells in the ventrolateral orbitofrontal and retrosplenial cortices and CA1 field of hippocampus; and (3) CB-IR cells in the motor cortex. Overall, our data indicate that PCP activates a wide range of cortical and subcortical brain regions...

  13. skn-1 is required for interneuron sensory integration and foraging behavior in Caenorhabditis elegans. (United States)

    Wilson, Mark A; Iser, Wendy B; Son, Tae Gen; Logie, Anne; Cabral-Costa, Joao V; Mattson, Mark P; Camandola, Simonetta


    Nrf2/skn-1, a transcription factor known to mediate adaptive responses of cells to stress, also regulates energy metabolism in response to changes in nutrient availability. The ability to locate food sources depends upon chemosensation. Here we show that Nrf2/skn-1 is expressed in olfactory interneurons, and is required for proper integration of multiple food-related sensory cues in Caenorhabditis elegans. Compared to wild type worms, skn-1 mutants fail to perceive that food density is limiting, and display altered chemo- and thermotactic responses. These behavioral deficits are associated with aberrant AIY interneuron morphology and migration in skn-1 mutants. Both skn-1-dependent AIY autonomous and non-autonomous mechanisms regulate the neural circuitry underlying multisensory integration of environmental cues related to energy acquisition.

  14. Quantitative assessment of CA1 local circuits: knowledge base for interneuron-pyramidal cell connectivity. (United States)

    Bezaire, Marianne J; Soltesz, Ivan


    In this work, through a detailed literature review, data-mining, and extensive calculations, we provide a current, quantitative estimate of the cellular and synaptic constituents of the CA1 region of the rat hippocampus. Beyond estimating the cell numbers of GABAergic interneuron types, we calculate their convergence onto CA1 pyramidal cells and compare it with the known input synapses on CA1 pyramidal cells. The convergence calculation and comparison are also made for excitatory inputs to CA1 pyramidal cells. In addition, we provide a summary of the excitatory and inhibitory convergence onto interneurons. The quantitative knowledge base assembled and synthesized here forms the basis for data-driven, large-scale computational modeling efforts. Additionally, this work highlights specific instances where the available data are incomplete, which should inspire targeted experimental projects toward a more complete quantification of the CA1 neurons and their connectivity. Copyright © 2013 Wiley Periodicals, Inc.

  15. Spinal Hb9::Cre-derived excitatory interneurons contribute to rhythm generation in the mouse

    DEFF Research Database (Denmark)

    Caldeira, Vanessa; Dougherty, Kimberly J.; Borgius, Lotta


    Rhythm generating neurons are thought to be ipsilaterally-projecting excitatory neurons in the thoracolumbar mammalian spinal cord. Recently, a subset of Shox2 interneurons (Shox2 non-V2a INs) was found to fulfill these criteria and make up a fraction of the rhythm-generating population. Here we...... than in cords from controls. Collectively, our findings indicate that excitatory Hb9::Cre-derived INs constitute a distinct population of neurons that participates in the rhythm generating kernel for spinal locomotion....... use Hb9::Cre mice to genetically manipulate Hb9::Cre-derived excitatory interneurons (INs) in order to determine the role of these INs in rhythm generation. We demonstrate that this line captures a consistent population of spinal INs which is mixed with respect to neurotransmitter phenotype...

  16. Activity-dependent brain-derived neurotrophic factor expression regulates cortistatin-interneurons and sleep behavior

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    Martinowich Keri


    Full Text Available Abstract Background Sleep homeostasis is characterized by a positive correlation between sleep length and intensity with the duration of the prior waking period. A causal role for brain-derived neurotrophic factor (BDNF in sleep homeostasis has been suggested, but the underlying mechanisms remain unclear. Cortistatin, a neuropeptide expressed primarily in a subset of cortical GABAergic interneurons, is another molecule implicated in sleep homeostasis. Results We confirmed that sleep deprivation leads to an increase in cortical cortistatin mRNA expression. Disruption of activity-dependent BDNF expression in a genetically modified mouse line impairs both baseline levels of cortistatin mRNA as well as its levels following sleep deprivation. Disruption of activity-dependent BDNF also leads to a decrease in sleep time during the active (dark phase. Conclusion Our studies suggest that regulation of cortistatin-expressing interneurons by activity-dependent BDNF expression may contribute to regulation of sleep behavior.

  17. The many tunes of perisomatic targeting interneurons in the hippocampal network

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    Tommas J Ellender


    Full Text Available The axonal targets of perisomatic targeting interneurons make them ideally suited to synchronise excitatory neurons. As such they have been implicated in rhythm generation of network activity in many brain regions including the hippocampus. However, several recent publications indicate that their roles extend beyond that of rhythm generation. Firstly, it has been shown that, in addition to rhythm generation, GABAergic perisomatic inhibition also serves as a current generator contributing significantly to hippocampal oscillatory EEG signals. Furthermore, GABAergic interneurons have a hitherto unexpected role in the initiation of hippocampal population bursts, both in the developing and adult hippocampus. In this review, we describe these new observations in detail and discuss the implications they have for our understanding of the mechanisms underlying physiological and pathological hippocampal network activities. This review is part of the Frontiers in Cellular Neuroscience's special topic entitled GABA signalling in health and disease based on the meeting at the CNCR Amsterdam.

  18. Patterned sensory nerve stimulation enhances the reactivity of spinal Ia inhibitory interneurons. (United States)

    Kubota, Shinji; Hirano, Masato; Morishita, Takuya; Uehara, Kazumasa; Funase, Kozo


    Patterned sensory nerve stimulation has been shown to induce plastic changes in the reciprocal Ia inhibitory circuit. However, the mechanisms underlying these changes have not yet been elucidated in detail. The aim of the present study was to determine whether the reactivity of Ia inhibitory interneurons could be altered by patterned sensory nerve stimulation. The degree of reciprocal Ia inhibition, the conditioning effects of transcranial magnetic stimulation (TMS) on the soleus (SOL) muscle H-reflex, and the ratio of the maximum H-reflex amplitude versus maximum M-wave (H(max)/M(max)) were examined in 10 healthy individuals. Patterned electrical nerve stimulation was applied to the common peroneal nerve every 1 s (100 Hz-5 train) at the motor threshold intensity of tibialis anterior muscle to induce activity changes in the reciprocal Ia inhibitory circuit. Reciprocal Ia inhibition, the TMS-conditioned H-reflex amplitude, and H(max)/M(max) were recorded before, immediately after, and 15 min after the electrical stimulation. The patterned electrical nerve stimulation significantly increased the degree of reciprocal Ia inhibition and decreased the amplitude of the TMS-conditioned H-reflex in the short-latency inhibition phase, which was presumably mediated by Ia inhibitory interneurons. However, it had no effect on H(max)/M(max). Our results indicated that patterned sensory nerve stimulation could modulate the activity of Ia inhibitory interneurons, and this change may have been caused by the synaptic modification of Ia inhibitory interneuron terminals. These results may lead to a clearer understanding of the spinal cord synaptic plasticity produced by repetitive sensory inputs. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

  19. Striatal fast-spiking interneurons: from firing patterns to postsynaptic impact

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    Andreas eKlaus


    Full Text Available In the striatal microcircuit, fast-spiking (FS interneurons have an important role in mediating inhibition onto neighboring medium spiny (MS projection neurons. In this study, we combined computational modeling with in vitro and in vivo electrophysiological measurements to investigate FS cells in terms of their discharge properties and their synaptic efficacies onto MS neurons. In vivo firing of striatal FS interneurons is characterized by a high firing variability. It is not known, however, if this variability results from the input that FS cells receive, or if it is promoted by the stuttering spike behavior of these neurons. Both our model and measurements in vitro show that FS neurons that exhibit random stuttering discharge in response to steady depolarization, do not show the typical stuttering behavior when they receive fluctuating input. Importantly, our model predicts that electrically coupled FS cells show substantial spike synchronization only when they are in the stuttering regime. Therefore, together with the lack of synchronized firing of striatal FS interneurons that has been reported in vivo, these results suggest that neighboring FS neurons are not in the stuttering regime simultaneously and that in vivo FS firing variability is more likely determined by the input fluctuations. Furthermore, the variability in FS firing is translated to variability in the postsynaptic amplitudes in MS neurons due to the strong synaptic depression of the FS-to-MS synapse. Our results support the idea that these synapses operate over a wide range from strongly depressed to almost fully recovered. The strong inhibitory effects that FS cells can impose on their postsynaptic targets, and the fact that the FS-to-MS synapse model showed substantial depression over extended periods of time might indicate the importance of cooperative effects of multiple presynaptic FS interneurons and the precise orchestration of their activity.

  20. Response characteristics of vibration-sensitive interneurons related to Johnston's organ in the honeybee, Apis mellifera. (United States)

    Ai, Hiroyuki; Rybak, Jürgen; Menzel, Randolf; Itoh, Tsunao


    Honeybees detect airborne vibration by means of Johnston's organ (JO), located in the pedicel of each antenna. In this study we identified two types of vibration-sensitive interneurons with arborizations in the primary sensory area of the JO, namely, the dorsal lobe-interneuron 1 (DL-Int-1) and dorsal lobe-interneuron 2 (DL-Int-2) using intracellular recordings combined with intracellular staining. For visualizing overlapping areas between the JO sensory terminals and the branches of these identified interneurons, the three-dimensional images of the individual neurons were registered into the standard atlas of the honeybee brain (Brandt et al. [2005] J Comp Neurol 492:1-19). Both DL-Int-1 and DL-Int-2 overlapped with the central terminal area of receptor neurons of the JO in the DL. For DL-Int-1 an on-off phasic excitation was elicited by vibrational stimuli applied to the JO when the spontaneous spike frequency was low, whereas tonic inhibition was induced when it was high. Moreover, current injection into a DL-Int-1 led to changes of the response pattern from on-off phasic excitation to tonic inhibition, in response to the vibratory stimulation. Although the vibration usually induced on-off phasic excitation in DL-Int-1, vibration applied immediately after odor stimulation induced tonic inhibition in it. DL-Int-2 responded to vibration stimuli applied to the JO by a tonic burst and were most sensitive to 265 Hz vibration, which is coincident with the strongest frequency of airborne vibrations arising during the waggle dance. These results suggest that DL-Int-1 and DL-Int-2 are related to coding of the duration of the vibration as sensed by the JO. Copyright 2009 Wiley-Liss, Inc.

  1. Short-Term Synaptic Plasticity at Interneuronal Synapses Could Sculpt Rhythmic Motor Patterns. (United States)

    Jia, Yan; Parker, David


    The output of a neuronal network depends on the organization and functional properties of its component cells and synapses. While the characterization of synaptic properties has lagged cellular analyses, a potentially important aspect in rhythmically active networks is how network synapses affect, and are in turn affected by, network activity. This could lead to a potential circular interaction where short-term activity-dependent synaptic plasticity is both influenced by and influences the network output. The analysis of synaptic plasticity in the lamprey locomotor network was extended here to characterize the short-term plasticity of connections between network interneurons and to try and address its potential network role. Paired recordings from identified interneurons in quiescent networks showed synapse-specific synaptic properties and plasticity that supported the presence of two hemisegmental groups that could influence bursting: depression in an excitatory interneuron group, and facilitation in an inhibitory feedback circuit. The influence of activity-dependent synaptic plasticity on network activity was investigated experimentally by changing Ringer Ca(2+) levels, and in a simple computer model. A potential caveat of the experimental analyses was that changes in Ringer Ca(2+) (and compensatory adjustments in Mg(2+) in some cases) could alter several other cellular and synaptic properties. Several of these properties were tested, and while there was some variability, these were not usually significantly affected by the Ringer changes. The experimental analyses suggested that depression of excitatory inputs had the strongest influence on the patterning of network activity. The simulation supported a role for this effect, and also suggested that the inhibitory facilitating group could modulate the influence of the excitatory synaptic depression. Short-term activity-dependent synaptic plasticity has not generally been considered in spinal cord models. These

  2. Graphene Oxide Dysregulates Neuroligin/NLG-1-Mediated Molecular Signaling in Interneurons in Caenorhabditis elegans (United States)

    Chen, He; Li, Huirong; Wang, Dayong


    Graphene oxide (GO) can be potentially used in many medical and industrial fields. Using assay system of Caenorhabditis elegans, we identified the NLG-1/Neuroligin-mediated neuronal signaling dysregulated by GO exposure. In nematodes, GO exposure significantly decreased the expression of NLG-1, a postsynaptic cell adhesion protein. Loss-of-function mutation of nlg-1 gene resulted in a susceptible property of nematodes to GO toxicity. Rescue experiments suggested that NLG-1 could act in AIY interneurons to regulate the response to GO exposure. In the AIY interneurons, PKC-1, a serine/threonine protein kinase C (PKC) protein, was identified as the downstream target for NLG-1 in the regulation of response to GO exposure. LIN-45, a Raf protein in ERK signaling pathway, was further identified as the downstream target for PKC-1 in the regulation of response to GO exposure. Therefore, GO may dysregulate NLG-1-mediated molecular signaling in the interneurons, and a neuronal signaling cascade of NLG-1-PKC-1-LIN-45 was raised to be required for the control of response to GO exposure. More importantly, intestinal RNAi knockdown of daf-16 gene encoding a FOXO transcriptional factor in insulin signaling pathway suppressed the resistant property of nematodes overexpressing NLG-1 to GO toxicity, suggesting the possible link between neuronal NLG-1 signaling and intestinal insulin signaling in the regulation of response to GO exposure.

  3. Enhanced flexibility of place discrimination learning by targeting striatal cholinergic interneurons. (United States)

    Okada, Kana; Nishizawa, Kayo; Fukabori, Ryoji; Kai, Nobuyuki; Shiota, Akira; Ueda, Masatsugu; Tsutsui, Yuji; Sakata, Shogo; Matsushita, Natsuki; Kobayashi, Kazuto


    Behavioural flexibility is mediated through the neural circuitry linking the prefrontal cortex and basal ganglia. Here we conduct selective elimination of striatal cholinergic interneurons in transgenic rats by immunotoxin-mediated cell targeting. Elimination of cholinergic interneurons from the dorsomedial striatum (DMS), but not from the dorsolateral striatum, results in enhanced reversal and extinction learning, sparing the acquisition of place discrimination. This enhancement is prevented by infusion of a non-selective muscarinic acetylcholine receptor agonist into the DMS either in the acquisition, reversal or extinction phase. In addition, gene-specific silencing of M4 muscarinic receptor by lentiviral expression of short hairpin RNA (shRNA) mimics the place reversal learning promoted by cholinergic elimination, whereas shRNA-mediated gene silencing of M1 muscarinic receptor shows the normal performance of reversal learning. Our data indicate that DMS cholinergic interneurons inhibit behavioural flexibility, mainly through the M4 muscarinic receptor, suggesting that this role is engaged to the stabilization of acquired reward contingency and the suppression of response switch to changed contingency.

  4. Arid1b haploinsufficiency disrupts cortical interneuron development and mouse behavior. (United States)

    Jung, Eui-Man; Moffat, Jeffrey Jay; Liu, Jinxu; Dravid, Shashank Manohar; Gurumurthy, Channabasavaiah Basavaraju; Kim, Woo-Yang


    Haploinsufficiency of the AT-rich interactive domain 1B (ARID1B) gene causes autism spectrum disorder and intellectual disability; however, the neurobiological basis for this is unknown. Here we generated Arid1b-knockout mice and examined heterozygotes to model human patients. Arid1b-heterozygous mice showed a decreased number of cortical GABAergic interneurons and reduced proliferation of interneuron progenitors in the ganglionic eminence. Arid1b haploinsufficiency also led to an imbalance between excitatory and inhibitory synapses in the cerebral cortex. Furthermore, we found that Arid1b haploinsufficiency suppressed histone H3 lysine 9 acetylation (H3K9ac) overall and particularly reduced H3K9ac of the Pvalb promoter, resulting in decreased transcription. Arid1b-heterozygous mice exhibited abnormal cognitive and social behaviors, which were rescued by treatment with a positive allosteric GABA A receptor modulator. Our results demonstrate a critical role for Arid1b in interneuron development and behavior and provide insight into the pathogenesis of autism spectrum disorder and intellectual disability.

  5. Cortical GABAergic Interneurons in Cross-Modal Plasticity following Early Blindness

    Directory of Open Access Journals (Sweden)

    Sébastien Desgent


    Full Text Available Early loss of a given sensory input in mammals causes anatomical and functional modifications in the brain via a process called cross-modal plasticity. In the past four decades, several animal models have illuminated our understanding of the biological substrates involved in cross-modal plasticity. Progressively, studies are now starting to emphasise on cell-specific mechanisms that may be responsible for this intermodal sensory plasticity. Inhibitory interneurons expressing γ-aminobutyric acid (GABA play an important role in maintaining the appropriate dynamic range of cortical excitation, in critical periods of developmental plasticity, in receptive field refinement, and in treatment of sensory information reaching the cerebral cortex. The diverse interneuron population is very sensitive to sensory experience during development. GABAergic neurons are therefore well suited to act as a gate for mediating cross-modal plasticity. This paper attempts to highlight the links between early sensory deprivation, cortical GABAergic interneuron alterations, and cross-modal plasticity, discuss its implications, and further provide insights for future research in the field.

  6. GABAergic interneuron to astrocyte signalling: a neglected form of cell communication in the brain. (United States)

    Losi, Gabriele; Mariotti, Letizia; Carmignoto, Giorgio


    GABAergic interneurons represent a minority of all cortical neurons and yet they efficiently control neural network activities in all brain areas. In parallel, glial cell astrocytes exert a broad control of brain tissue homeostasis and metabolism, modulate synaptic transmission and contribute to brain information processing in a dynamic interaction with neurons that is finely regulated in time and space. As most studies have focused on glutamatergic neurons and excitatory transmission, our knowledge of functional interactions between GABAergic interneurons and astrocytes is largely defective. Here, we critically discuss the currently available literature that hints at a potential relevance of this specific signalling in brain function. Astrocytes can respond to GABA through different mechanisms that include GABA receptors and transporters. GABA-activated astrocytes can, in turn, modulate local neuronal activity by releasing gliotransmitters including glutamate and ATP. In addition, astrocyte activation by different signals can modulate GABAergic neurotransmission. Full clarification of the reciprocal signalling between different GABAergic interneurons and astrocytes will improve our understanding of brain network complexity and has the potential to unveil novel therapeutic strategies for brain disorders. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  7. Prolonged response to calling songs by the L3 auditory interneuron in female crickets (Acheta domesticus): intracellular evaluation. (United States)

    Navia, Benjamin; Stout, John; Atkins, Gordon


    The L3 auditory interneuron in female Acheta domesticus, produces two different responses to the male calling song: an immediate response and a prolonged response. The prolonged response exhibited spiking activity and a correlated prolonged depolarization, both of which are clearly seen in intracellular recordings. The morphology revealed by intracellular staining was clearly the L3 neuron. The amplitude of the prolonged depolarization associated with the prolonged response increased with increases in sound intensity, resulting in increased spiking rates. Both depolarization and sound presentation increased the spiking rate and the slope of pre-potentials (thus leading to spiking threshold more quickly). Injecting hyperpolarizing current had the expected opposite effect. The effects of positive current injection and sound presentation were additive, resulting in spiking rates that were approximately double the rates in response to sound alone. Short postsynaptic potentials (PSPs), whose duration ranged from 15-60 ms, which may lead to action potentials were also observed in all recordings and summated with the prolonged depolarization, increasing the probability of spiking. Copyright 2003 Wiley-Liss, Inc.

  8. NR2 subunits and NMDA receptors on lamina II inhibitory and excitatory interneurons of the mouse dorsal horn

    Directory of Open Access Journals (Sweden)

    MacDermott Amy B


    Full Text Available Abstract Background NMDA receptors expressed by spinal cord neurons in the superficial dorsal horn are involved in the development of chronic pain associated with inflammation and nerve injury. The superficial dorsal horn has a complex and still poorly understood circuitry that is mainly populated by inhibitory and excitatory interneurons. Little is known about how NMDA receptor subunit composition, and therefore pharmacology and voltage dependence, varies with neuronal cell type. NMDA receptors are typically composed of two NR1 subunits and two of four NR2 subunits, NR2A-2D. We took advantage of the differences in Mg2+ sensitivity of the NMDA receptor subtypes together with subtype preferring antagonists to identify the NR2 subunit composition of NMDA receptors expressed on lamina II inhibitory and excitatory interneurons. To distinguish between excitatory and inhibitory interneurons, we used transgenic mice expressing enhanced green fluorescent protein driven by the GAD67 promoter. Results Analysis of conductance ratio and selective antagonists showed that lamina II GABAergic interneurons express both the NR2A/B containing Mg2+ sensitive receptors and the NR2C/D containing NMDA receptors with less Mg2+ sensitivity. In contrast, excitatory lamina II interneurons express primarily NR2A/B containing receptors. Despite this clear difference in NMDA receptor subunit expression in the two neuronal populations, focally stimulated synaptic input is mediated exclusively by NR2A and 2B containing receptors in both neuronal populations. Conclusions Stronger expression of NMDA receptors with NR2C/D subunits by inhibitory interneurons compared to excitatory interneurons may provide a mechanism to selectively increase activity of inhibitory neurons during intense excitatory drive that can provide inhibitory feedback.

  9. Trajectory of the main GABAergic interneuron populations from early development to old age in the rat primary auditory cortex

    Directory of Open Access Journals (Sweden)

    Lydia eOuellet


    Full Text Available In both humans and rodents, decline in cognitive function is a hallmark of the aging process, the basis for this decrease has yet to be fully characterized. However, using aged rodent models, deficits in auditory processing have been associated with significant decreases in inhibitory signaling attributed to a loss of GABAergic interneurons. Not only are these interneurons crucial for pattern detection and other large-scale population dynamics, but they have also been linked to mechanisms mediating plasticity and learning, making them a prime candidate for study and modelling of modifications to cortical communication pathways in neurodegenerative diseases. Using the rat primary auditory cortex (A1 as a model, we probed the known markers of GABAergic interneurons with immunohistological methods, using antibodies against gamma aminobutyric acid (GABA, parvalbumin (PV, somatostatin (SOM, calretinin (CR, vasoactive intestinal peptide (VIP, choline acetyltransferase (ChAT, neuropeptide Y (NPY and cholecystokinin (CCK to document the changes observed in interneuron populations across the rat’s lifespan. This analysis provided strong evidence that several but not all GABAergic neurons were affected by the aging process, showing most dramatic changes in expression of parvalbumin (PV and somatostatin (SOM expression. With this evidence, we show how understanding these trajectories of cell counts may be factored into a simple model to quantify changes in inhibitory signalling across the course of life, which may be applied as a framework for creating more advanced simulations of interneuronal implication in normal cerebral processing, normal aging, or pathological processes.

  10. Active action potential propagation but not initiation in thalamic interneuron dendrites (United States)

    Casale, Amanda E.; McCormick, David A.


    Inhibitory interneurons of the dorsal lateral geniculate nucleus of the thalamus modulate the activity of thalamocortical cells in response to excitatory input through the release of inhibitory neurotransmitter from both axons and dendrites. The exact mechanisms by which release can occur from dendrites are, however, not well understood. Recent experiments using calcium imaging have suggested that Na/K based action potentials can evoke calcium transients in dendrites via local active conductances, making the back-propagating action potential a candidate for dendritic neurotransmitter release. In this study, we employed high temporal and spatial resolution voltage-sensitive dye imaging to assess the characteristics of dendritic voltage deflections in response to Na/K action potentials in interneurons of the mouse dorsal lateral geniculate nucleus. We found that trains or single action potentials elicited by somatic current injection or local synaptic stimulation led to action potentials that rapidly and actively back-propagated throughout the entire dendritic arbor and into the fine filiform dendritic appendages known to release GABAergic vesicles. Action potentials always appeared first in the soma or proximal dendrite in response to somatic current injection or local synaptic stimulation, and the rapid back-propagation into the dendritic arbor depended upon voltage-gated sodium and TEA-sensitive potassium channels. Our results indicate that thalamic interneuron dendrites integrate synaptic inputs that initiate action potentials, most likely in the axon initial segment, that then back-propagate with high-fidelity into the dendrites, resulting in a nearly synchronous release of GABA from both axonal and dendritic compartments. PMID:22171033

  11. Interneuronal systems of the cervical spinal cord assessed with BOLD imaging at 1.5 T

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    Stracke, C.P.; Schoth, F.; Moeller-Hartmann, W.; Krings, T. [University Hospital of the University of Technology, Departments of Neuroradiology and Diagnostic Radiology, Aachen (Germany); Pettersson, L.G. [University of Goeteborg, Department of Physiology, Goeteborg (Sweden)


    The purpose of this study was to investigate if functional activity with spinal cord somatosensory stimulation can be visualized using BOLD fMRI. We investigated nine healthy volunteers using a somatosensory stimulus generator. The stimuli were applied in three different runs at the first, third, and fifth finger tip of the right hand, respectively, corresponding to dermatomes c6, c7, and c8. The stimuli gave an increase of BOLD signal (activation) in three different locations of the spinal cord and brain stem. First, activations could be seen in the spinal segment corresponding to the stimulated dermatome in seven out of nine volunteers for c6 stimulation, two out of eight for c7, and three out of eight for c8. These activations were located close to the posterior margin of the spinal cord, presumably reflecting synaptic transmission to dorsal horn interneurons. Second, activation in the medulla oblongata was evident in four subjects, most likely corresponding to the location of the nucleus cuneatus. The third location of activation, which was the strongest and most reliable observed was inside the spinal cord in the c3 and c4 segments. Activation at these spinal levels was almost invariably observed independently of the dermatome stimulated (9/9 for c6, 8/8 for c7, and 7/8 for c8 stimulation). These activations may pertain to an interneuronal system at this spinal level. The results are discussed in relation to neurophysiological studies on cervical spinal interneuronal pathways in animals and humans. (orig.)

  12. Interneurons in the Honeybee Primary Auditory Center Responding to Waggle Dance-Like Vibration Pulses. (United States)

    Ai, Hiroyuki; Kai, Kazuki; Kumaraswamy, Ajayrama; Ikeno, Hidetoshi; Wachtler, Thomas


    Female honeybees use the "waggle dance" to communicate the location of nectar sources to their hive mates. Distance information is encoded in the duration of the waggle phase (von Frisch, 1967). During the waggle phase, the dancer produces trains of vibration pulses, which are detected by the follower bees via Johnston's organ located on the antennae. To uncover the neural mechanisms underlying the encoding of distance information in the waggle dance follower, we investigated morphology, physiology, and immunohistochemistry of interneurons arborizing in the primary auditory center of the honeybee ( Apis mellifera ). We identified major interneuron types, named DL-Int-1, DL-Int-2, and bilateral DL-dSEG-LP, that responded with different spiking patterns to vibration pulses applied to the antennae. Experimental and computational analyses suggest that inhibitory connection plays a role in encoding and processing the duration of vibration pulse trains in the primary auditory center of the honeybee. SIGNIFICANCE STATEMENT The waggle dance represents a form of symbolic communication used by honeybees to convey the location of food sources via species-specific sound. The brain mechanisms used to decipher this symbolic information are unknown. We examined interneurons in the honeybee primary auditory center and identified different neuron types with specific properties. The results of our computational analyses suggest that inhibitory connection plays a role in encoding waggle dance signals. Our results are critical for understanding how the honeybee deciphers information from the sound produced by the waggle dance and provide new insights regarding how common neural mechanisms are used by different species to achieve communication. Copyright © 2017 the authors 0270-6474/17/3710624-12$15.00/0.

  13. Interneuronal systems of the cervical spinal cord assessed with BOLD imaging at 1.5 T

    International Nuclear Information System (INIS)

    Stracke, C.P.; Schoth, F.; Moeller-Hartmann, W.; Krings, T.; Pettersson, L.G.


    The purpose of this study was to investigate if functional activity with spinal cord somatosensory stimulation can be visualized using BOLD fMRI. We investigated nine healthy volunteers using a somatosensory stimulus generator. The stimuli were applied in three different runs at the first, third, and fifth finger tip of the right hand, respectively, corresponding to dermatomes c6, c7, and c8. The stimuli gave an increase of BOLD signal (activation) in three different locations of the spinal cord and brain stem. First, activations could be seen in the spinal segment corresponding to the stimulated dermatome in seven out of nine volunteers for c6 stimulation, two out of eight for c7, and three out of eight for c8. These activations were located close to the posterior margin of the spinal cord, presumably reflecting synaptic transmission to dorsal horn interneurons. Second, activation in the medulla oblongata was evident in four subjects, most likely corresponding to the location of the nucleus cuneatus. The third location of activation, which was the strongest and most reliable observed was inside the spinal cord in the c3 and c4 segments. Activation at these spinal levels was almost invariably observed independently of the dermatome stimulated (9/9 for c6, 8/8 for c7, and 7/8 for c8 stimulation). These activations may pertain to an interneuronal system at this spinal level. The results are discussed in relation to neurophysiological studies on cervical spinal interneuronal pathways in animals and humans. (orig.)

  14. Synaptic polarity of the command interneurons for Caenorhabditis Elegans directional motion

    Directory of Open Access Journals (Sweden)

    Franciszek Maria Rakowski


    Full Text Available The command interneuron circuit for Caenorhabditis Elegans locomotion has been known for a long time [1,2]. However, synaptic polarities of these interneurons, and thus, the circuit functioning is largely unknown. Additionally, nematode command neurons express both glutamate-gated chloride channels and glutamate-gated cation channels, which causes that each synapse, even when belonging to the same neuron, might be either inhibitory or excitatory. We use an experimental behavioral data set: eighteen different neural ablations were performed and times spent in the forward and reverse motions were registered. Therefore one can consider eighteen different command neuron network structures where each one as a whole, controls the behavior of the nematode, and results with one of the eighteen different behavioral patterns. In order to decipher the particular polarities of each neuron we have constructed a theoretical (interneuron network model, in which neural activities are represented by a set of differential equations and searched all possible synaptic polarity combinations in the circuit to find the best match to the timing data [3,4]. Here, we present the extension of this model, where we explicitly incorporate calcium concentration dynamics as the regulatory factor and detailed connectivity diagram based on the transmission type of each synapse. Since the parameter space spanned by the morphological and regulatory factors is huge, we have applied an evolutionary strategy for finding the parameters of the mathematical model, for which the theoretical results and the experimental data fit the best. The overall model output consists of the averaged values: neuron activities, calcium concentration levels, input signal (the upstream neurons activity pattern and of the resolved detailed connectivity diagram. The deciphered list of the types of synapses states that most of the synapses, including strongest connections, e.g. ASH ->

  15. Organization of projection-specific interneurons in the spinal cord of the red-eared turtle

    DEFF Research Database (Denmark)

    Nissen, Ulla Vig; Moldovan, Mihai; Hounsgaard, Jørn


    Using differential retrograde axonal tracing, we identified motoneurons (MNs) and projection-specific interneuron (IN) classes in lumbar segment D9 of the adult red-eared turtle spinal cord. We characterized the distribution of these neurons in the transverse plane, and estimated their numbers...... zone. Within the IIN and CIN populations, aINs and dINs overlap extensively. The adIINs and adCINs make up only a small fraction of the total number of INs and are scattered throughout much of the respective IIN and CIN domains. The proportions of IINs and CINs are about equal, as are the proportions...

  16. Synaptic targets of commissural interneurons in the lumbar spinal cord of neonatal rats

    DEFF Research Database (Denmark)

    Birinyi, András; Viszokay, Kornél; Wéber, Ildikó


    dextran amine (BDA) into the lateral motor column to retrogradely label commissural interneurons that may have direct projections to motor neurons. Stained neurons were recovered in the ventromedial areas of the contralateral gray matter in substantial numbers. In the second experiment BDA was injected...... into the ventromedial gray matter on one side of the lumbar spinal cord, whereas motor neurons were simultaneously labeled on the opposite side by applying biocytin onto the ventral roots. BDA injections into the ventromedial gray matter labeled a strong axon bundle that arose from the site of injection, crossed...

  17. Representation of the body in the lateral striatum of the freely moving rat: Fast Spiking Interneurons respond to stimulation of individual body parts. (United States)

    Kulik, Julianna M; Pawlak, Anthony P; Kalkat, Manraj; Coffey, Kevin R; West, Mark O


    Numerous studies have shown that certain types of striatal interneurons play a crucial role in selection and regulation of striatal output. Striatal Fast-Spiking Interneurons (FSIs) are parvalbumin positive, GABAergic interneurons that constitute less than 1% of the total striatal population. It is becoming increasingly evident that these sparsely distributed neurons exert a strong inhibitory effect on Medium Spiny projection Neurons (MSNs). MSNs in lateral striatum receive direct synaptic input from regions of cortex representing discrete body parts, and show phasic increases in activity during touch or movement of specific body parts. In the present study, we sought to determine whether lateral striatal FSIs identified by their electrophysiological properties, i.e., short-duration spike and fast firing rate (FR), display body part sensitivity similar to that exhibited by MSNs. During video recorded somatosensorimotor exams, each individual body part was stimulated and responses of single neurons were observed and quantified. Individual FSIs displayed patterns of activity related selectively to stimulation of a discrete body part. Most patterns of activity were similar to those exhibited by typical MSNs, but some phasic decreases were observed. These results serve as evidence that some striatal FSIs process information related to discrete body parts and participate in sensorimotor processing by striatal networks that contribute to motor output. Parvalbumin positive, striatal FSIs are hypothesized to play an important role in behavior by inhibiting MSNs. We asked a fundamental question regarding information processed during behavior by FSIs: whether FSIs, which preferentially occupy the sensorimotor portion of the striatum, process activity of discrete body parts. Our finding that they do, in a selective manner similar to MSNs, begins to reveal the types of phasic signals that FSI feed forward to projection neurons during striatal processing of cortical input

  18. Robustness of Structural Systems

    DEFF Research Database (Denmark)

    Canisius, T.D.G.; Sørensen, John Dalsgaard; Baker, J.W.


    The importance of robustness as a property of structural systems has been recognised following several structural failures, such as that at Ronan Point in 1968,where the consequenceswere deemed unacceptable relative to the initiating damage. A variety of research efforts in the past decades have ...... will be proposed. The document adopts a probabilistic risk assessment framework and includes guidance for decision-making related to robustness....... attempted to quantify aspects of robustness such as redundancy and identify design principles that can improve robustness. This paper outlines the progress of recent work by the Joint Committee on Structural Safety (JCSS) to develop comprehensive guidance on assessing and providing robustness in structural...... systems. Guidance is provided regarding the assessment of robustness in a framework that considers potential hazards to the system, vulnerability of system components, and failure consequences. Several proposed methods for quantifying robustness are reviewed, and guidelines for robust design...

  19. Robustness and Eurocodes

    NARCIS (Netherlands)

    Gulvanessian, H.; Vrouwenvelder, A.C.W.M.


    The topic of robustness is essentially covered by two Eurocodes, EN 1990: Euro-code: Basis of Structural Design [5] which provides the high level principles for achieving robustness and EN 1991-1-7 Eurocode 1: Part 1-7 Accidental Actions [6] which provides strategies and methods to obtain robustness

  20. Drosophila Ovipositor Extension in Mating Behavior and Egg Deposition Involves Distinct Sets of Brain Interneurons (United States)

    Kimura, Ken-ichi; Sato, Chiaki; Koganezawa, Masayuki; Yamamoto, Daisuke


    Oviposition is a female-specific behavior that directly affects fecundity, and therefore fitness. If a fertilized female encounters another male that she has evaluated to be of better quality than her previous mate, it would be beneficial for her to remate with this male rather than depositing her eggs. Females who decided not to remate exhibited rejection behavior toward a courting male and engaged in oviposition. Although recent studies of Drosophila melanogaster identified sensory neurons and putative second-order ascending interneurons that mediate uterine afferents affecting female reproductive behavior, little is known about the brain circuitry that selectively activates rejection versus oviposition behaviors. We identified the sexually dimorphic pC2l and female-specific pMN2 neurons, two distinct classes of doublesex (dsx)-expressing neurons that can initiate ovipositor extension associated with rejection and oviposition behavior, respectively. pC2l interneurons, which induce ovipositor extrusion for rejection in females, have homologues that control courtship behavior in males. Activation of these two classes of neurons appears to be mutually exclusive and each governs hierarchical control of the motor program in the VNC either for rejection or oviposition, contributing centrally to the switching on or off of the alternative motor programs. PMID:25955600

  1. Spinal Hb9::Cre-derived excitatory interneurons contribute to rhythm generation in the mouse. (United States)

    Caldeira, Vanessa; Dougherty, Kimberly J; Borgius, Lotta; Kiehn, Ole


    Rhythm generating neurons are thought to be ipsilaterally-projecting excitatory neurons in the thoracolumbar mammalian spinal cord. Recently, a subset of Shox2 interneurons (Shox2 non-V2a INs) was found to fulfill these criteria and make up a fraction of the rhythm-generating population. Here we use Hb9::Cre mice to genetically manipulate Hb9::Cre-derived excitatory interneurons (INs) in order to determine the role of these INs in rhythm generation. We demonstrate that this line captures a consistent population of spinal INs which is mixed with respect to neurotransmitter phenotype and progenitor domain, but does not overlap with the Shox2 non-V2a population. We also show that Hb9::Cre-derived INs include the comparatively small medial population of INs which continues to express Hb9 postnatally. When excitatory neurotransmission is selectively blocked by deleting Vglut2 from Hb9::Cre-derived INs, there is no difference in left-right and/or flexor-extensor phasing between these cords and controls, suggesting that excitatory Hb9::Cre-derived INs do not affect pattern generation. In contrast, the frequencies of locomotor activity are significantly lower in cords from Hb9::Cre-Vglut2 Δ/Δ mice than in cords from controls. Collectively, our findings indicate that excitatory Hb9::Cre-derived INs constitute a distinct population of neurons that participates in the rhythm generating kernel for spinal locomotion.

  2. Robustness of Structures

    DEFF Research Database (Denmark)

    Faber, Michael Havbro; Vrouwenvelder, A.C.W.M.; Sørensen, John Dalsgaard


    the development of a joint European project on structural robustness under the COST (European Cooperation in Science and Technology) programme and the decision to develop a more elaborate document on structural robustness in collaboration between experts from the JCSS and the IABSE. Accordingly, a project titled...... ‘COST TU0601: Robustness of Structures’ was initiated in February 2007, aiming to provide a platform for exchanging and promoting research in the area of structural robustness and to provide a basic framework, together with methods, strategies and guidelines enhancing robustness of structures...

  3. Robust multivariate analysis

    CERN Document Server

    J Olive, David


    This text presents methods that are robust to the assumption of a multivariate normal distribution or methods that are robust to certain types of outliers. Instead of using exact theory based on the multivariate normal distribution, the simpler and more applicable large sample theory is given.  The text develops among the first practical robust regression and robust multivariate location and dispersion estimators backed by theory.   The robust techniques  are illustrated for methods such as principal component analysis, canonical correlation analysis, and factor analysis.  A simple way to bootstrap confidence regions is also provided. Much of the research on robust multivariate analysis in this book is being published for the first time. The text is suitable for a first course in Multivariate Statistical Analysis or a first course in Robust Statistics. This graduate text is also useful for people who are familiar with the traditional multivariate topics, but want to know more about handling data sets with...

  4. Organization of the Mammalian Locomotor CPG: Review of Computational Model and Circuit Architectures Based on Genetically Identified Spinal Interneurons (United States)

    Dougherty, Kimberly J.; Shevtsova, Natalia A.


    Abstract The organization of neural circuits that form the locomotor central pattern generator (CPG) and provide flexor–extensor and left–right coordination of neuronal activity remains largely unknown. However, significant progress has been made in the molecular/genetic identification of several types of spinal interneurons, including V0 (V0D and V0V subtypes), V1, V2a, V2b, V3, and Shox2, among others. The possible functional roles of these interneurons can be suggested from changes in the locomotor pattern generated in mutant mice lacking particular neuron types. Computational modeling of spinal circuits may complement these studies by bringing together data from different experimental studies and proposing the possible connectivity of these interneurons that may define rhythm generation, flexor–extensor interactions on each side of the cord, and commissural interactions between left and right circuits. This review focuses on the analysis of potential architectures of spinal circuits that can reproduce recent results and suggest common explanations for a series of experimental data on genetically identified spinal interneurons, including the consequences of their genetic ablation, and provides important insights into the organization of the spinal CPG and neural control of locomotion. PMID:26478909

  5. Antipsychotics promote GABAergic interneuron genesis in the adult rat brain: Role of heat-shock protein production. (United States)

    Kaneta, Hiroo; Ukai, Wataru; Tsujino, Hanako; Furuse, Kengo; Kigawa, Yoshiyasu; Tayama, Masaya; Ishii, Takao; Hashimoto, Eri; Kawanishi, Chiaki


    Current antipsychotics reduce positive symptoms and reverse negative symptoms in conjunction with cognitive behavioral issues with the goal of restoring impaired occupational and social functioning. However, limited information is available on their influence on gliogenesis or their neurogenic properties in adult schizophrenia brains, particularly on GABAergic interneuron production. In the present study, we used young adult subventricular zone (SVZ)-derived progenitor cells expressing proteoglycan NG2 cultures to examine the oligodendrocyte and GABAergic interneuron genesis effects of several kinds of antipsychotics on changes in differentiation function induced by exposure to the NMDA receptor antagonist MK-801. We herein demonstrated that antipsychotics promoted or restored changes in the oligodendrocyte/GABAergic interneuron differentiation functions of NG2(+) cells induced by the exposure to MK-801, which was considered to be one of the drug-induced schizophrenia model. We also demonstrated that antipsychotics restored heat-shock protein (HSP) production in NG2(+) cells with differentiation impairment. The antipsychotics olanzapine, aripiprazole, and blonanserin, but not haloperidol increased HSP90 levels, which were reduced by the exposure to MK-801. Our results showed that antipsychotics, particularly those recently synthesized, exerted similar GABAergic interneuron genesis effects on NG2(+) neuronal/glial progenitor cells in the adult rat brain by increasing cellular HSP production, and also suggest that HSP90 may play a crucial role in the pathophysiology of schizophrenia and is a key target for next drug development. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Calretinin and parvalbumin immunoreactive interneurons in the retrosplenial cortex of the rat brain: Qualitative and quantitative analyses

    Czech Academy of Sciences Publication Activity Database

    Salaj, M.; Druga, Rastislav; Cerman, J.; Kubová, Hana; Barinka, F.


    Roč. 1627, Nov 19 (2015), s. 201-215 ISSN 0006-8993 R&D Projects: GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : retrosplenial cortex * calretinin * parvalbumin * interneurons * calcium-binding proteins * perirhinal cortex Subject RIV: FH - Neurology Impact factor: 2.561, year: 2015

  7. In Vivo Study of Dynamics and Stability of Dendritic Spines on Olfactory Bulb Interneurons in Xenopus laevis Tadpoles.

    Directory of Open Access Journals (Sweden)

    Yu-Bin Huang

    Full Text Available Dendritic spines undergo continuous remodeling during development of the nervous system. Their stability is essential for maintaining a functional neuronal circuit. Spine dynamics and stability of cortical excitatory pyramidal neurons have been explored extensively in mammalian animal models. However, little is known about spiny interneurons in non-mammalian vertebrate models. In the present study, neuronal morphology was visualized by single-cell electroporation. Spiny neurons were surveyed in the Xenopus tadpole brain and observed to be widely distributed in the olfactory bulb and telencephalon. DsRed- or PSD95-GFP-expressing spiny interneurons in the olfactory bulb were selected for in vivo time-lapse imaging. Dendritic protrusions were classified as filopodia, thin, stubby, or mushroom spines based on morphology. Dendritic spines on the interneurons were highly dynamic, especially the filopodia and thin spines. The stubby and mushroom spines were relatively more stable, although their stability significantly decreased with longer observation intervals. The 4 spine types exhibited diverse preferences during morphological transitions from one spine type to others. Sensory deprivation induced by severing the olfactory nerve to block the input of mitral/tufted cells had no significant effects on interneuron spine stability. Hence, a new model was established in Xenopus laevis tadpoles to explore dendritic spine dynamics in vivo.

  8. Axonal regeneration and development of de novo axons from distal dendrites of adult feline commissural interneurons after a proximal axotomy

    DEFF Research Database (Denmark)

    Fenrich, Keith K; Skelton, Nicole; MacDermid, Victoria E


    Following proximal axotomy, several types of neurons sprout de novo axons from distal dendrites. These processes may represent a means of forming new circuits following spinal cord injury. However, it is not know whether mammalian spinal interneurons, axotomized as a result of a spinal cord injur...

  9. Representation of behaviourally relevant information by blowfly motion-sensitive visual interneurons requires precise compensatory head movements

    NARCIS (Netherlands)

    Kern, R.; Hateren, J.H. van; Egelhaaf, M.


    Flying blowflies shift their gaze by saccadic turns of body and head, keeping their gaze basically fixed between saccades. For the head, this results in almost pure translational optic flow between saccades, enabling visual interneurons in the fly motion pathway to extract information about

  10. Synaptic Changes in AMPA Receptor Subunit Expression in Cortical Parvalbumin Interneurons in the Stargazer Model of Absence Epilepsy

    Directory of Open Access Journals (Sweden)

    Nadia K. Adotevi


    Full Text Available Feedforward inhibition is essential to prevent run away excitation within the brain. Recent evidence suggests that a loss of feed-forward inhibition in the corticothalamocortical circuitry may underlie some absence seizures. However, it is unclear if this aberration is specifically linked to loss of synaptic excitation onto local fast-spiking parvalbumin-containing (PV+ inhibitory interneurons, which are responsible for mediating feedforward inhibition within cortical networks. We recently reported a global tissue loss of AMPA receptors (AMPARs, and a specific mistrafficking of these AMPARs in PV+ interneurons in the stargazer somatosensory cortex. The current study was aimed at investigating if cellular changes in AMPAR expression were translated into deficits in receptors at specific synapses in the feedforward inhibitory microcircuit. Using western blot immunolabeling on biochemically isolated synaptic fractions, we demonstrate a loss of AMPAR GluA1–4 subunits in the somatosensory cortex of stargazers compared to non-epileptic control mice. Furthermore, using double post-embedding immunogold-cytochemistry, we show a loss of GluA1–4-AMPARs at excitatory synapses onto cortical PV+ interneurons. Altogether, these data indicate a loss of synaptic AMPAR-mediated excitation of cortical PV+ inhibitory neurons. As the cortex is considered the site of initiation of spike wave discharges (SWDs within the corticothalamocortical circuitry, loss of AMPARs at cortical PV+ interneurons likely impairs feed-forward inhibitory output, and contributes to the generation of SWDs and absence seizures in stargazers.

  11. Encoding of tactile stimuli by mechanoreceptors and interneurons of the medicinal leech

    Directory of Open Access Journals (Sweden)

    Jutta Kretzberg


    Full Text Available For many animals processing of tactile information is a crucial task in behavioral contexts like exploration, foraging and stimulus avoidance. The leech, having infrequent access to food, developed an energy efficient reaction to tactile stimuli, avoiding unnecessary muscle movements: The local bend behavior moves only a small part of the body wall away from an object touching the skin, while the rest of the animal remains stationary. Amazingly, the precision of this localized behavioral response is similar to the spatial discrimination threshold of the human fingertip, although the leech skin is innervated by an order of magnitude fewer mechanoreceptors and each midbody ganglion contains only 400 individually identified neurons in total. Prior studies suggested that this behavior is controlled by a three-layered feed-forward network, consisting of four mechanoreceptors (P cells, approximately 20 interneurons and 10 individually characterized motor neurons, all of which encode tactile stimulus location by overlapping, symmetrical tuning curves. Additionally, encoding of mechanical force was attributed to three types of mechanoreceptors reacting to distinct intensity ranges: T cells for touch, P cells for pressure and N cells for strong, noxious skin stimulation. In this study, we provide evidences that tactile stimulus encoding in the leech is more complex than previously thought. Combined electrophysiological, anatomical and voltage sensitive dye approaches indicate that P and T cells both play a major role in tactile information processing resulting in local bending. Our results indicate that tactile encoding neither relies on distinct force intensity ranges of different cell types, nor location encoding is restricted to spike count tuning. Instead, we propose that P and T cells form a mixed type population, which simultaneously employs temporal response features and spike counts for multiplexed encoding of touch location and force intensity

  12. Galanin-immunoreactivity identifies a distinct population of inhibitory interneurons in laminae I-III of the rat spinal cord

    Directory of Open Access Journals (Sweden)

    Watanabe Masahiko


    Full Text Available Abstract Background Inhibitory interneurons constitute 30-40% of neurons in laminae I-III and have an important anti-nociceptive role. However, because of the difficulty in classifying them we know little about their organisation. Previous studies have identified 3 non-overlapping groups of inhibitory interneuron, which contain neuropeptide Y (NPY, neuronal nitric oxide synthase (nNOS or parvalbumin, and have shown that these differ in postsynaptic targets. Some inhibitory interneurons contain galanin and the first aim of this study was to determine whether these form a different population from those containing NPY, nNOS or parvalbumin. We also estimated the proportion of neurons and GABAergic axons that contain galanin in laminae I-III. Results Galanin cells were concentrated in laminae I-IIo, with few in laminae IIi-III. Galanin showed minimal co-localisation with NPY, nNOS or parvalbumin in laminae I-II, but most galanin-containing cells in lamina III were nNOS-positive. Galanin cells constituted ~7%, 3% and 2% of all neurons in laminae I, II and III, and we estimate that this corresponds to 26%, 10% and 5% of the GABAergic neurons in these laminae. However, galanin was only found in ~6% of GABAergic boutons in laminae I-IIo, and ~1% of those in laminae IIi-III. Conclusions These results show that galanin, NPY, nNOS and parvalbumin can be used to define four distinct neurochemical populations of inhibitory interneurons. Together with results of a recent study, they suggest that the galanin and NPY populations account for around half of the inhibitory interneurons in lamina I and a quarter of those in lamina II.

  13. Responses of Withdrawal Interneurons to Serotonin Applications in Naïve and Learned Snails Are Different

    Directory of Open Access Journals (Sweden)

    Tatiana K. Bogodvid


    Full Text Available Long-term changes in membrane potential after associative training were described previously in identified premotor interneurons for withdrawal of the terrestrial snail Helix. Serotonin was shown to be a major transmitter involved in triggering the long-term changes in mollusks. In the present study we compared the changes in electrophysiological characteristics of identifiable premotor interneurons for withdrawal in response to bath applications of serotonin (5-HT or serotonin precursor 5-hydroxytryptophan (5-HTP in preparations from naïve, neurotoxin-injected or associatively trained snails. It was found that 5-HT or 5-HTP applications caused a significant decrease of membrane potential in premotor interneurons of naïve snails, associatively trained snails and snails with impaired serotonergic system by injection of a selective neurotoxin 5,7-dihydroxytryptamine (5,7-DHT 1 week before the experiments. Applications of 5-HT or 5-HTP did not cause significant changes in the action potential (AP threshold potential of these neurons in naïve snails. Conversely, applications of 5-HT or 5-HTP to the premotor interneurons of previously trained or 5,7-DHT-injected snails caused a significant increase in the firing threshold potential in spite of a depolarizing shift of the resting membrane potential. Results demonstrate that responsiveness of premotor interneurons to extracellularly applied 5-HT or 5-HTP changes for days after the associative training or serotonin depletion. Similarity of the effects in trained and 5,7-DHT-injected animals may be due to massive release of serotonin elicited by 5,7-DHT injection. Our results suggest that serotonin release due to aversive conditionining or elicited by the neurotoxin administration triggers similar changes in resting membrane potential and AP threshold in response to bath applications of 5-HT or its precursor 5-HTP.

  14. Colocalization of allatotropin and tachykinin-related peptides with classical transmitters in physiologically distinct subtypes of olfactory local interneurons in the cockroach (Periplaneta americana). (United States)

    Fusca, Debora; Schachtner, Joachim; Kloppenburg, Peter


    In the insect antennal lobe different types of local interneurons mediate complex excitatory and inhibitory interactions between the glomerular pathways to structure the spatiotemporal representation of odors. Mass spectrometric and immunohistochemical studies have shown that in local interneurons classical neurotransmitters are likely to colocalize with a variety of substances that can potentially act as cotransmitters or neuromodulators. In the antennal lobe of the cockroach Periplaneta americana, gamma-aminobutyric acid (GABA) has been identified as the potential inhibitory transmitter of spiking type I local interneurons, whereas acetylcholine is most likely the excitatory transmitter of nonspiking type IIa1 local interneurons. This study used whole-cell patch clamp recordings combined with single-cell labeling and immunohistochemistry to test if the GABAergic type I local interneurons and the cholinergic type IIa1 local interneurons express allatotropin and tachykinin-related neuropeptides (TKRPs). These are two of the most abundant types of peptides in the insect antennal lobe. GABA-like and choline acetyltransferase (ChAT)-like immunoreactivity were used as markers for GABAergic and cholinergic neurons, respectively. About 50% of the GABA-like immunoreactive (-lir) spiking type I local interneurons were allatotropin-lir, and ∼ 40% of these neurons were TKRP-lir. About 20% of nonspiking ChAT-lir type IIa1 local interneurons were TKRP-lir. Our results suggest that in subpopulations of GABAergic and cholinergic local interneurons, allatotropin and TKRPs might act as cotransmitters or neuromodulators. To unequivocally assign neurotransmitters, cotransmitters, and neuromodulators to identified classes of antennal lobe neurons is an important step to deepen our understanding of information processing in the insect olfactory system. © 2015 Wiley Periodicals, Inc.

  15. Selective Activation of Cholinergic Interneurons Enhances Accumbal Phasic Dopamine Release: Setting the Tone for Reward Processing

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    Roger Cachope


    Full Text Available Dopamine plays a critical role in motor control, addiction, and reward-seeking behaviors, and its release dynamics have traditionally been linked to changes in midbrain dopamine neuron activity. Here, we report that selective endogenous cholinergic activation achieved via in vitro optogenetic stimulation of nucleus accumbens, a terminal field of dopaminergic neurons, elicits real-time dopamine release. This mechanism occurs via direct actions on dopamine terminals, does not require changes in neuron firing within the midbrain, and is dependent on glutamatergic receptor activity. More importantly, we demonstrate that in vivo selective activation of cholinergic interneurons is sufficient to elicit dopamine release in the nucleus accumbens. Therefore, the control of accumbal extracellular dopamine levels by endogenous cholinergic activity results from a complex convergence of neurotransmitter/neuromodulator systems that may ultimately synergize to drive motivated behavior.

  16. Projection patterns of commissural interneurons in the lumbar spinal cord of the neonatal rat

    DEFF Research Database (Denmark)

    Stokke, Mathis Frøshaug; Nissen, Ulla Vig; Glover, Joel C.


    We have studied the axonal projection patterns of commissural interneurons (CINs) in the neonatal rat spinal cord. Some CINs are integral components of the neuronal networks in the vertebrate spinal cord that generate locomotor activity. By using differential retrograde labeling protocols...... with fluorescent dextran amines, we show that CINs with ascending axons (ascending CINs, or aCINs) and CINs with descending axons (descending CINs, or dCINs) constitute largely different populations. We show that aCINs and dCINs occupy partially overlapping domains in the transverse plane. The aCINs are located...... and a half segment rostrally or caudally and are present in roughly equal numbers. We also demonstrate the presence of a third, smaller population of CINs whose axons bifurcate to project for at least one and a half segment both rostrally and caudally (adCINs). The adCINs are located predominantly among...

  17. Septal innervation regulates the function of alpha7 nicotinic receptors in CA1 hippocampal interneurons. (United States)

    Thinschmidt, Jeffrey S; Frazier, Charles J; King, Michael A; Meyer, Edwin M; Papke, Roger L


    The hippocampus receives substantial input from the medial septum/diagonal band of broca (MS/DB) via the fibria-fornix (FF). Projections from the MS/DB innervate hippocampal interneurons that express alpha7 nicotinic receptors and regulate excitation in principal cell populations. In the present report we used stereotaxic surgery, whole-cell patch clamping, and immunohistochemical techniques to evaluate the effects of FF and MS/DB lesions on alpha7 nicotinic receptors in stratum radiatum interneurons. Focal somatic application of ACh (1 mM) evoked methyllycaconitine (MLA)-sensitive currents that were markedly reduced following aspirative lesions of the FF. Reductions in current amplitudes were prevented or restored to levels not significantly different from controls following in vivo treatment with the alpha7-selective agonist GTS-21, and GTS-21 treatment did not change current amplitudes measured in tissue from unlesioned animals. MS/DB injections of the selective cholinergic neurotoxin 192 IgG-saporin did not affect alpha7 receptor currents, although MS/DB ChAT and hippocampal AChE immunolabeling were significantly reduced. In contrast, kainic acid lesions of the MS/DB, potentially more selective for GABAergic projection neurons, produced significant reductions in current amplitudes. These findings are the first to show functional changes in alpha7 receptors following hippocampal denervation and suggest that MS/DB hippocampal innervation regulates functional aspects of hippocampal alpha7 receptors. The results confirm hippocampal alpha7 nicotinic receptors as viable therapeutic targets in diseases that involve degradation of the septohippocampal pathway and may indicate that GABAergic MS/DB hippocampal input plays a more substantial role in the regulation of alpha7 nicotinic receptor function than MS/DB hippocampal cholinergic input.

  18. A cholinergic modulatory interneuron in the feeding system of the snail, Lymnaea. (United States)

    Yeoman, M S; Parish, D C; Benjamin, P R


    1. Pharmacological and physiological methods were used to examine the role of acetylcholine (ACh) in modulation of the Lymnaea feeding central pattern generator (CPG) by the slow oscillator (SO) interneuron. 2. Extracts of dissected SO cell bodies inhibited spontaneous ventricular contractions of the clam Mya arenaria, indicating the presence of ACh. These effects were blocked by the specific antagonist benzoquinonium chloride (10(-7) M). 3. Isolated SO cells grown in culture synthesized ACh from tritiated choline. 4. High [K+] saline induced release of synthesized ACh from cultured SO cells into the medium. 5. The specific ACh antagonist phenyltrimethylammonium (10(-4) M) blocked both excitatory, biphasic (inhibitory-excitatory) and inhibitory monosynaptic connections from the SO to feeding CPG interneurons and motor neurons. Less specific cholinergic antagonists blocked either excitatory (hexamethonium, 10(-4) M) or both excitatory and inhibitory connections (d-tubo-curarine, 10(-4) M). 6. The synaptic responses of the SO could be mimicked by brief (20 ms) pressure-pulsed application of ACh onto the cell bodies of the postsynaptic cells in high-Mg2+ saline. In normal saline, ACh elicited bursts of spikes in the N1 cells, indicating that a fictive feeding pattern had been induced in the CPG. This mimics the main mechanism by which the SO activates the CPG, which is by exciting the N1s. 7. The frequency of SO-induced fictive feeding rhythm was reduced by bath application of hexamethonium chloride to the buccal ganglia. This reduced the amplitude of the SO-->N1 excitatory synaptic response (30% of controls) and is probably the main mechanism for the reduction in the frequency of the rhythm. 8. The evidence suggests that ACh is the main neurochemical involved in allowing the SO to initiate and control the frequency of the Lymnaea feeding CPG.

  19. Iterative robust multiprocessor scheduling

    NARCIS (Netherlands)

    Adyanthaya, S.; Geilen, M.; Basten, T.; Voeten, J.; Schiffelers, R.


    General purpose platforms are characterized by unpredictable timing behavior. Real-time schedules of tasks on general purpose platforms need to be robust against variations in task execution times. We define robustness in terms of the expected number of tasks that miss deadlines. We present an

  20. Robustness to strategic uncertainty

    NARCIS (Netherlands)

    Andersson, O.; Argenton, C.; Weibull, J.W.

    We introduce a criterion for robustness to strategic uncertainty in games with continuum strategy sets. We model a player's uncertainty about another player's strategy as an atomless probability distribution over that player's strategy set. We call a strategy profile robust to strategic uncertainty

  1. Robustness - theoretical framework

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Rizzuto, Enrico; Faber, Michael H.


    not be disproportional to the causes of the damages'. However, despite the importance of robustness for structural design such requirements are not substantiated in more detail, nor have the engineering profession been able to agree on an interpretation of robustness which facilitates for its quantification. The ain...

  2. Mechanisms for Robust Cognition (United States)

    Walsh, Matthew M.; Gluck, Kevin A.


    To function well in an unpredictable environment using unreliable components, a system must have a high degree of robustness. Robustness is fundamental to biological systems and is an objective in the design of engineered systems such as airplane engines and buildings. Cognitive systems, like biological and engineered systems, exist within…

  3. TRPC1 Channels Are Expressed in Pyramidal Neurons and in a Subset of Somatostatin Interneurons in the Rat Neocortex

    Directory of Open Access Journals (Sweden)

    Juan R. Martinez-Galan


    Full Text Available Disturbances in calcium homeostasis due to canonical transient receptor potential (TRPC and/or store-operated calcium (SOC channels can play a key role in a large number of brain disorders. TRPC channels are plasma membrane cation channels included in the transient receptor potential (TRP superfamily. The most widely distributed member of the TRPC subfamily in the brain is TRPC1, which is frequently linked to group I metabotropic glutamate receptors (mGluRs and to the components of SOC channels. Proposing TRPC/SOC channels as a therapeutic target in neurological diseases previously requires a detailed knowledge of the distribution of such molecules in the brain. The aim of our study was to analyze the neuroanatomical distribution of TRPC1 in the rat neocortex. By double- and triple-labeling and confocal microscopy, we tested the presence of TRPC1 by using a series of specific neurochemical markers. TRPC1 was abundant in SMI 32-positive pyramidal neurons, and in some glutamic acid decarboxylase 67 (GAD67 interneurons, but was lacking in glial fibrillary acidic protein (GFAP-positive glial cells. In neurons it colocalized with postsynaptic marker MAP2 in cell bodies and apical dendritic trunks and it was virtually absent in synaptophysin-immunoreactive terminals. By using a panel of antibodies to classify interneurons, we identified the GABAergic interneurons that contained TRPC1. TRPC1 was lacking in basket and chandelier parvalbumin (PVALB cells, and a very low percentage of calretinin (CALR or calbindin (CALB interneurons expressed TRPC1. Moreover, 63% of somatostatin (SST expressing-cells and 37% of reelin-positive cells expressed TRPC1. All the SST/TRPC1 double-labeled cells, many of which were presumptive Martinotti cells (MC, were positive for reelin. The presence of TRPC1 in the somata and apical dendritic trunks of neocortical pyramidal cells suggests a role for this channel in sensory processing and synaptic plasticity. Conversely in SST

  4. How Robust is Your System Resilience? (United States)

    Homayounfar, M.; Muneepeerakul, R.


    Robustness and resilience are concepts in system thinking that have grown in importance and popularity. For many complex social-ecological systems, however, robustness and resilience are difficult to quantify and the connections and trade-offs between them difficult to study. Most studies have either focused on qualitative approaches to discuss their connections or considered only one of them under particular classes of disturbances. In this study, we present an analytical framework to address the linkage between robustness and resilience more systematically. Our analysis is based on a stylized dynamical model that operationalizes a widely used concept framework for social-ecological systems. The model enables us to rigorously define robustness and resilience and consequently investigate their connections. The results reveal the tradeoffs among performance, robustness, and resilience. They also show how the nature of the such tradeoffs varies with the choices of certain policies (e.g., taxation and investment in public infrastructure), internal stresses and external disturbances.

  5. Robustness Beamforming Algorithms

    Directory of Open Access Journals (Sweden)

    Sajad Dehghani


    Full Text Available Adaptive beamforming methods are known to degrade in the presence of steering vector and covariance matrix uncertinity. In this paper, a new approach is presented to robust adaptive minimum variance distortionless response beamforming make robust against both uncertainties in steering vector and covariance matrix. This method minimize a optimization problem that contains a quadratic objective function and a quadratic constraint. The optimization problem is nonconvex but is converted to a convex optimization problem in this paper. It is solved by the interior-point method and optimum weight vector to robust beamforming is achieved.

  6. Perceptual Robust Design

    DEFF Research Database (Denmark)

    Pedersen, Søren Nygaard

    are just a few examples of cost drivers. In general, the earlier quality issues are addressed the less costs they impose. Robust design methodology seeks to anticipate many of these quality issues by making product designs less sensitive to variation. The approach was first introduced by Genichi Taguchi......The research presented in this PhD thesis has focused on a perceptual approach to robust design. The results of the research and the original contribution to knowledge is a preliminary framework for understanding, positioning, and applying perceptual robust design. Product quality is a topic...... in the 1980s and has since been expanded and refined. In more recent contributions, the notion of visual robustness has been introduced to the field of design research. However, contributions have only addressed the visual domain and no underlying theory on which to position or understand these studies have...

  7. Activation of two forms of locomotion by a previously identified trigger interneuron for swimming in the medicinal leech. (United States)

    Brodfuehrer, Peter D; McCormick, Kathryn; Tapyrik, Lauren; Albano, Alfonso M; Graybeal, Carolyn


    Higher-order projection interneurons that function in more than one behavior have been identified in a number of preparations. In this study, we document that stimulation of cell Tr1, a previously identified trigger interneuron for swimming in the medicinal leech, can also elicit the motor program for crawling in isolated nerve cords. We also show that motor choice is independent of the firing frequency of Tr1 and amount of spiking activity recorded extracellularly at three locations along the ventral nerve cord prior to Tr1 stimulation. On the other hand, during Tr1 stimulation there is a significant difference in the amount of activity elicited in the ventral nerve cord that correlates with the motor program activated. On average, Tr1 stimulation trials that lead to crawling elicit greater amounts of activity than in trials that lead to swimming.

  8. Robust Microarray Image Processing


    Novikov, Eugene; Barillot, Emmanuel


    In this work we have presented a complete solution for robust, high-throughput, two-color microarray image processing comprising procedures for automatic spot localization, spot quantification and spot quality control. The spot localization algorithm is fully automatic and robust with respect to deviations from perfect spot alignment and contamination. As an input, it requires only the common array design parameters: number of blocks and number of spots in the x and y directions of the array....

  9. Robust Crane Control


    Marek Hičár; Juraj Ritók


    The paper presents robust crane design by asynchronnous motor with frequencyconvertor at ensuring system robustness against load weight and rope length variation.Exact position control and elimination of swinging in the final position are required too.Firstly were assemblied mathematical models of main crane components: crab, bridge anduplift by real model of double beamed bridge experimental crane. Was designed robustcontrol for defined interval variation of weight and rope length for real c...

  10. Inhibitory interneuron progenitor transplantation restores normal learning and memory in ApoE4 knock-in mice without or with Aβ accumulation. (United States)

    Tong, Leslie M; Djukic, Biljana; Arnold, Christine; Gillespie, Anna K; Yoon, Seo Yeon; Wang, Max M; Zhang, Olivia; Knoferle, Johanna; Rubenstein, John L R; Alvarez-Buylla, Arturo; Huang, Yadong


    Excitatory and inhibitory balance of neuronal network activity is essential for normal brain function and may be of particular importance to memory. Apolipoprotein (apo) E4 and amyloid-β (Aβ) peptides, two major players in Alzheimer's disease (AD), cause inhibitory interneuron impairments and aberrant neuronal activity in the hippocampal dentate gyrus in AD-related mouse models and humans, leading to learning and memory deficits. To determine whether replacing the lost or impaired interneurons rescues neuronal signaling and behavioral deficits, we transplanted embryonic interneuron progenitors into the hippocampal hilus of aged apoE4 knock-in mice without or with Aβ accumulation. In both conditions, the transplanted cells developed into mature interneurons, functionally integrated into the hippocampal circuitry, and restored normal learning and memory. Thus, restricted hilar transplantation of inhibitory interneurons restores normal cognitive function in two widely used AD-related mouse models, highlighting the importance of interneuron impairments in AD pathogenesis and the potential of cell replacement therapy for AD. More broadly, it demonstrates that excitatory and inhibitory balance are crucial for learning and memory, and suggests an avenue for investigating the processes of learning and memory and their alterations in healthy aging and diseases. Copyright © 2014 the authors 0270-6474/14/349506-10$15.00/0.

  11. Unaltered Network Activity and Interneuronal Firing During Spontaneous Cortical Dynamics In Vivo in a Mouse Model of Severe Myoclonic Epilepsy of Infancy. (United States)

    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


    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. © The Author 2016. Published by Oxford University Press.

  12. ZC4H2, an XLID gene, is required for the generation of a specific subset of CNS interneurons. (United States)

    May, Melanie; Hwang, Kyu-Seok; Miles, Judith; Williams, Charlie; Niranjan, Tejasvi; Kahler, Stephen G; Chiurazzi, Pietro; Steindl, Katharina; Van Der Spek, Peter J; Swagemakers, Sigrid; Mueller, Jennifer; Stefl, Shannon; Alexov, Emil; Ryu, Jeong-Im; Choi, Jung-Hwa; Kim, Hyun-Taek; Tarpey, Patrick; Neri, Giovanni; Holloway, Lynda; Skinner, Cindy; Stevenson, Roger E; Dorsky, Richard I; Wang, Tao; Schwartz, Charles E; Kim, Cheol-Hee


    Miles-Carpenter syndrome (MCS) was described in 1991 as an XLID syndrome with fingertip arches and contractures and mapped to proximal Xq. Patients had microcephaly, short stature, mild spasticity, thoracic scoliosis, hyperextendable MCP joints, rocker-bottom feet, hyperextended elbows and knees. A mutation, p.L66H, in ZC4H2, was identified in a XLID re-sequencing project. Additional screening of linked families and next generation sequencing of XLID families identified three ZC4H2 mutations: p.R18K, p.R213W and p.V75in15aa. The families shared some relevant clinical features. In silico modeling of the mutant proteins indicated all alterations would destabilize the protein. Knockout mutations in zc4h2 were created in zebrafish and homozygous mutant larvae exhibited abnormal swimming, increased twitching, defective eye movement and pectoral fin contractures. Because several of the behavioral defects were consistent with hyperactivity, we examined the underlying neuronal defects and found that sensory neurons and motoneurons appeared normal. However, we observed a striking reduction in GABAergic interneurons. Analysis of cell-type-specific markers showed a specific loss of V2 interneurons in the brain and spinal cord, likely arising from mis-specification of neural progenitors. Injected human wt ZC4H2 rescued the mutant phenotype. Mutant zebrafish injected with human p.L66H or p.R213W mRNA failed to be rescued, while the p.R18K mRNA was able to rescue the interneuron defect. Our findings clearly support ZC4H2 as a novel XLID gene with a required function in interneuron development. Loss of function of ZC4H2 thus likely results in altered connectivity of many brain and spinal circuits. © The Author 2015. Published by Oxford University Press.

  13. Immunohistochemical visualization of mouse interneuron subtypes [v1; ref status: indexed,

    Directory of Open Access Journals (Sweden)

    Simon Molgaard


    Full Text Available The activity of excitatory neurons is controlled by a small, but highly diverse population of inhibitory interneurons. These cells show a high level of physiological, morphological and neurochemical heterogeneity, and play highly specific roles in neuronal circuits. In the mammalian hippocampus, these are divided into 21 different subtypes of GABAergic interneurons based on their expression of different markers, morphology and their electrophysiological properties. Ideally, all can be marked using an antibody directed against the inhibitory neurotransmitter GABA, but parvalbumin, calbindin, somatostatin, and calretinin are also commonly used as markers to narrow down the specific interneuron subtype. Here, we describe a journey to find the necessary immunological reagents for studying GABAergic interneurons of the mouse hippocampus. Based on web searches there are several hundreds of different antibodies on the market directed against these four markers. Searches in the literature databases allowed us to narrow it down to a subset of antibodies most commonly used in publications. However, in our hands the most cited ones did not work for immunofluorescence stainings of formaldehyde fixed tissue sections and cultured hippocampal neurons, and we had to immunostain our way through thirteen different commercial antibodies before finally finding a suitable antibody for each of the four markers. The antibodies were evaluated based on signal-to-noise ratios as well as if positive cells were found in layers of the hippocampus where they have previously been described. Additionally, the antibodies were also tested on sections from mouse spinal cord with similar criteria for specificity of the antibodies. Using the antibodies with a high rating on pAbmAbs, stainings with high signal-to-noise ratios and location of the immunostained cells in accordance with the literature could be obtained, making these antibodies suitable choices for studying the

  14. Compulsive Social Behavior Emerges after Selective Ablation of Striatal Cholinergic Interneurons. (United States)

    Martos, Yanina V; Braz, Barbara Y; Beccaria, Juan P; Murer, M Gustavo; Belforte, Juan E


    The mechanisms underlying social dysfunction in neuropsychiatric conditions such as obsessive-compulsive disorder and Tourette syndrome remain uncertain. However, it is known that dysfunctions in basal ganglia, including a reduced number of striatal cholinergic interneurons (SCIN), are involved in their pathophysiology. To explore the role of SCIN in relation to perseverative behaviors, we characterized a new transgenic mouse model in which inducible ablation of SCIN is achieved with high efficiency in a cell-type- and region-specific manner. Mice were subjected to extensive behavioral testing, including assessment of social behaviors, and corticostriatal functional connectivity was evaluated in vivo Selective SCIN ablation leads to altered social interactions together with exacerbated spontaneously emitted repetitive behaviors. Lesioned mice showed normal motor coordination, balance, and general locomotion. Interestingly, only environmentally driven, but not self-directed, repetitive behaviors were exacerbated in lesioned mice. Remarkably, in mice with SCIN ablation, the normal pattern of social exploration was replayed continuously. The emerging pattern of social interactions is highly predictable and invariant across time. In vivo electrophysiological recordings indicate that SCIN ablation results in an increase of the functional connectivity between different cortical areas and the motor, but not associative, region of the striatum. Our results identify a role of SCIN in suppressing perseverative behaviors, including socially related ones. In sum, SCIN ablation in mice leads to exacerbated ritualistic-like behaviors that affect social performance, providing a link between SCIN dysfunction and the social impairments present in psychiatric disorders. SIGNIFICANCE STATEMENT We sought to uncover the impact of striatal cholinergic interneuron (SCIN) degeneration on perseverative behaviors related to obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). We

  15. Role of Somatostatin-Positive Cortical Interneurons in the Generation of Sleep Slow Waves. (United States)

    Funk, Chadd M; Peelman, Kayla; Bellesi, Michele; Marshall, William; Cirelli, Chiara; Tononi, Giulio


    During non-rapid eye-movement (NREM) sleep, cortical and thalamic neurons oscillate every second or so between ON periods, characterized by membrane depolarization and wake-like tonic firing, and OFF periods, characterized by membrane hyperpolarization and neuronal silence. Cortical slow waves, the hallmark of NREM sleep, reflect near-synchronous OFF periods in cortical neurons. However, the mechanisms triggering such OFF periods are unclear, as there is little evidence for somatic inhibition. We studied cortical inhibitory interneurons that express somatostatin (SOM), because ∼70% of them are Martinotti cells that target diffusely layer I and can block excitatory transmission presynaptically, at glutamatergic terminals, and postsynaptically, at apical dendrites, without inhibiting the soma. In freely moving male mice, we show that SOM+ cells can fire immediately before slow waves and their optogenetic stimulation during ON periods of NREM sleep triggers long OFF periods. Next, we show that chemogenetic activation of SOM+ cells increases slow-wave activity (SWA), slope of individual slow waves, and NREM sleep duration; whereas their chemogenetic inhibition decreases SWA and slow-wave incidence without changing time spent in NREM sleep. By contrast, activation of parvalbumin+ (PV+) cells, the most numerous population of cortical inhibitory neurons, greatly decreases SWA and cortical firing, triggers short OFF periods in NREM sleep, and increases NREM sleep duration. Thus SOM+ cells, but not PV+ cells, are involved in the generation of sleep slow waves. Whether Martinotti cells are solely responsible for this effect, or are complemented by other classes of inhibitory neurons, remains to be investigated. SIGNIFICANCE STATEMENT Cortical slow waves are a defining feature of non-rapid eye-movement (NREM) sleep and are thought to be important for many of its restorative benefits. Yet, the mechanism by which cortical neurons abruptly and synchronously cease firing, the

  16. Genetic and Environmental Control of Neurodevelopmental Robustness in Drosophila.

    Directory of Open Access Journals (Sweden)

    David J Mellert

    Full Text Available Interindividual differences in neuronal wiring may contribute to behavioral individuality and affect susceptibility to neurological disorders. To investigate the causes and potential consequences of wiring variation in Drosophila melanogaster, we focused on a hemilineage of ventral nerve cord interneurons that exhibits morphological variability. We find that late-born subclasses of the 12A hemilineage are highly sensitive to genetic and environmental variation. Neurons in the second thoracic segment are particularly variable with regard to two developmental decisions, whereas its segmental homologs are more robust. This variability "hotspot" depends on Ultrabithorax expression in the 12A neurons, indicating variability is cell-intrinsic and under genetic control. 12A development is more variable and sensitive to temperature in long-established laboratory strains than in strains recently derived from the wild. Strains with a high frequency of one of the 12A variants also showed a high frequency of animals with delayed spontaneous flight initiation, whereas other wing-related behaviors did not show such a correlation and were thus not overtly affected by 12A variation. These results show that neurodevelopmental robustness is variable and under genetic control in Drosophila and suggest that the fly may serve as a model for identifying conserved gene pathways that stabilize wiring in stressful developmental environments. Moreover, some neuronal lineages are variation hotspots and thus may be more amenable to evolutionary change.

  17. Adenosine A2A Receptors Control Glutamatergic Synaptic Plasticity in Fast Spiking Interneurons of the Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Amber Kerkhofs


    Full Text Available Adenosine A2A receptors (A2AR are activated upon increased synaptic activity to assist in the implementation of long-term plastic changes at synapses. While it is reported that A2AR are involved in the control of prefrontal cortex (PFC-dependent behavior such as working memory, reversal learning and effort-based decision making, it is not known whether A2AR control glutamatergic synapse plasticity within the medial PFC (mPFC. To elucidate that, we tested whether A2AR blockade affects long-term plasticity (LTP of excitatory post-synaptic potentials in pyramidal neurons and fast spiking (FS interneurons in layer 5 of the mPFC and of population spikes. Our results show that A2AR are enriched at mPFC synapses, where their blockade reversed the direction of plasticity at excitatory synapses onto layer 5 FS interneurons from LTP to long-term depression, while their blockade had no effect on the induction of LTP at excitatory synapses onto layer 5 pyramidal neurons. At the network level, extracellularly induced LTP of population spikes was reduced by A2AR blockade. The interneuron-specificity of A2AR in controlling glutamatergic synapse LTP may ensure that during periods of high synaptic activity, a proper excitation/inhibition balance is maintained within the mPFC.

  18. Postsynaptic GABABRs Inhibit L-Type Calcium Channels and Abolish Long-Term Potentiation in Hippocampal Somatostatin Interneurons

    Directory of Open Access Journals (Sweden)

    Sam A. Booker


    Full Text Available Summary: Inhibition provided by local GABAergic interneurons (INs activates ionotropic GABAA and metabotropic GABAB receptors (GABABRs. Despite GABABRs representing a major source of inhibition, little is known of their function in distinct IN subtypes. Here, we show that, while the archetypal dendritic-inhibitory somatostatin-expressing INs (SOM-INs possess high levels of GABABR on their somato-dendritic surface, they fail to produce significant postsynaptic inhibitory currents. Instead, GABABRs selectively inhibit dendritic CaV1.2 (L-type Ca2+ channels on SOM-IN dendrites, leading to reduced calcium influx and loss of long-term potentiation at excitatory input synapses onto these INs. These data provide a mechanism by which GABABRs can contribute to disinhibition and control the efficacy of extrinsic inputs to hippocampal networks. : Booker et al. show that GABAB receptors are highly expressed on somatostatin interneuron dendrites. Rather than activating Kir3 channels, they preferentially co-cluster with, and negatively couple to, L-type calcium channels inhibiting long-term potentiation at excitatory inputs. Keywords: GABAergic interneurons, feedback inhibition, GABAB receptors, dendrites, Cav1.2 channels, synaptic plasticity, hippocampus, electron microscopy, whole-cell recording, multi-photon imaging

  19. Identification of Early RET+ Deep Dorsal Spinal Cord Interneurons in Gating Pain (United States)

    Cui, Lian; Miao, Xuerong; Liang, Lingli; Abdus-Saboor, Ishmail; Olson, William; Fleming, Michael S; Ma, Minghong; Tao, Yuan-Xiang; Luo, Wenqin


    The gate control theory (GCT) of pain proposes that pain- and touch-sensing neurons antagonize each other through spinal cord dorsal horn (DH) gating neurons. However, the exact neural circuits underlying the GCT remain largely elusive. Here, we identified a new population of deep layer DH (dDH) inhibitory interneurons that express the receptor tyrosine kinase Ret neonatally. These early RET+ dDH neurons receive excitatory as well as polysynaptic inhibitory inputs from touch- and/or pain-sensing afferents. In addition, they negatively regulate DH pain and touch pathways through both pre- and postsynaptic inhibition. Finally, specific ablation of early RET+ dDH neurons increases basal and chronic pain, whereas their acute activation reduces basal pain perception and relieves inflammatory and neuropathic pain. Taken together, our findings uncover a novel spinal circuit that mediates crosstalk between touch and pain pathways and suggest that some early RET+ dDH neurons could function as pain “gating” neurons. PMID:27545714

  20. Anatomical Correlates of Local, Translaminar, and Transcolumnar Inhibition by Layer 6 GABAergic Interneurons in Somatosensory Cortex. (United States)

    Arzt, Marlene; Sakmann, Bert; Meyer, Hanno S


    In the vibrissal area of rodent somatosensory cortex, information on whisker stimulation is processed by neuronal networks in a corresponding cortical column. To understand how sensory stimuli are represented in a column, it is essential to identify cell types constituting these networks. Layer 6 (L6) comprises 25% of all neurons in a column. In rats, 430 of these are inhibitory interneurons (INs). Little is known about the axon projection of L6 INs with reference to columnar and laminar organization. We quantified axonal projections of L6 INs (n = 68) with reference to columns and layers in somatosensory cortex of rats. We found distinct projection types differentially targeting layers of a cortical column. The majority of L6 INs did not show a column-specific innervation, densely projecting to neighboring columns as well as the home column. However, a small fraction targeted granular and supragranular layers, where axon projections were confined to the home column. We also quantified putative innervation of pyramidal cells as a functional correlate of axonal distribution. Electrophysiological properties were not correlated to axon projection. The quantitative data on axonal projections and electrophysiological properties of L6 INs can guide future studies investigating cortical processing of sensory information at the single cell level. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:

  1. The complex contribution of NOS interneurons in the physiology of cerebrovascular regulation

    Directory of Open Access Journals (Sweden)

    Sonia eDuchemin


    Full Text Available Following the discovery of the vasorelaxant properties of nitric oxide (NO by Furchgott and Ignarro, the finding by Bredt and coll. of a constitutively expressed NO synthase in neurons (nNOS led to the presumption that neuronal NO may control cerebrovascular functions. Consequently, numerous studies have sought to determine whether neuraly-derived NO is involved in the regulation of cerebral blood flow. Anatomically, axons, dendrites or somata of NO neurons have been found to contact the basement membrane of blood vessels or perivascular astrocytes in all segments of the cortical microcirculation. Functionally, various experimental approaches support a role of neuronal NO in the maintenance of resting cerebral blood flow as well as in the vascular response to neuronal activity. Since decades, it has been assumed that neuronal NO simply diffuses to the local blood vessels and produce vasodilation through a cGMP-PKG dependent mechanism. However, NO is not the sole mediator of vasodilation in the cerebral microcirculation and is known to interact with a myriad of signaling pathways also involved in vascular control. In addition, cerebrovascular regulation is the result of a complex orchestration between all components of the neurovascular unit (i.e. neuronal, glial and vascular cells also known to produce NO. In this review article, the role of NO interneuron in the regulation of cortical microcirculation will be discussed in the context of the neurovascular unit.

  2. Cholinergic Interneurons Amplify Corticostriatal Synaptic Responses in the Q175 Model of Huntington’s Disease

    Directory of Open Access Journals (Sweden)

    Asami Tanimura


    Full Text Available Huntington’s disease (HD is a neurodegenerative disorder characterized by deficits in movement control that are widely viewed as stemming from pathophysiological changes in the striatum. Giant, aspiny cholinergic interneurons (ChIs are key elements in the striatal circuitry controlling movement, but whether their physiological properties are intact in the HD brain is unclear. To address this issue, the synaptic properties of ChIs were examined using optogenetic approaches in the Q175 mouse model of HD. In ex vivo brain slices, synaptic facilitation at thalamostriatal synapses onto ChIs was reduced in Q175 mice. The alteration in thalamostriatal transmission was paralleled by an increased response to optogenetic stimulation of cortical axons, enabling these inputs to more readily induce burst-pause patterns of activity in ChIs. This adaptation was dependent upon amplification of cortically evoked responses by a post-synaptic upregulation of voltage-dependent Na+ channels. This upregulation also led to an increased ability of somatic spikes to invade ChI dendrites. However, there was not an alteration in the basal pacemaking rate of ChIs, possibly due to increased availability of Kv4 channels. Thus, there is a functional ‘re-wiring’ of the striatal networks in Q175 mice, which results in greater cortical control of phasic ChI activity, which is widely thought to shape the impact of salient stimuli on striatal action selection.

  3. A spiking network model of cerebellar Purkinje cells and molecular layer interneurons exhibiting irregular firing

    Directory of Open Access Journals (Sweden)

    William eLennon


    Full Text Available While the anatomy of the cerebellar microcircuit is well studied, how it implements cerebellar function is not understood. A number of models have been proposed to describe this mechanism but few emphasize the role of the vast network Purkinje cells (PKJs form with the molecular layer interneurons (MLIs – the stellate and basket cells. We propose a model of the MLI-PKJ network composed of simple spiking neurons incorporating the major anatomical and physiological features. In computer simulations, the model reproduces the irregular firing patterns observed in PKJs and MLIs in vitro and a shift toward faster, more regular firing patterns when inhibitory synaptic currents are blocked. In the model, the time between PKJ spikes is shown to be proportional to the amount of feedforward inhibition from an MLI on average. The two key elements of the model are: (1 spontaneously active PKJs and MLIs due to an endogenous depolarizing current, and (2 adherence to known anatomical connectivity along a parasagittal strip of cerebellar cortex. We propose this model to extend previous spiking network models of the cerebellum and for further computational investigation into the role of irregular firing and MLIs in cerebellar learning and function.

  4. Serotonin enhances excitability and gamma frequency temporal integration in mouse prefrontal fast-spiking interneurons. (United States)

    Athilingam, Jegath C; Ben-Shalom, Roy; Keeshen, Caroline M; Sohal, Vikaas S; Bender, Kevin J


    The medial prefrontal cortex plays a key role in higher order cognitive functions like decision making and social cognition. These complex behaviors emerge from the coordinated firing of prefrontal neurons. Fast-spiking interneurons (FSIs) control the timing of excitatory neuron firing via somatic inhibition and generate gamma (30-100 Hz) oscillations. Therefore, factors that regulate how FSIs respond to gamma-frequency input could affect both prefrontal circuit activity and behavior. Here, we show that serotonin (5HT), which is known to regulate gamma power, acts via 5HT2A receptors to suppress an inward-rectifying potassium conductance in FSIs. This leads to depolarization, increased input resistance, enhanced spiking, and slowed decay of excitatory post-synaptic potentials (EPSPs). Notably, we found that slowed EPSP decay preferentially enhanced temporal summation and firing elicited by gamma frequency inputs. These findings show how changes in passive membrane properties can affect not only neuronal excitability but also the temporal filtering of synaptic inputs.

  5. Robustness in econometrics

    CERN Document Server

    Sriboonchitta, Songsak; Huynh, Van-Nam


    This book presents recent research on robustness in econometrics. Robust data processing techniques – i.e., techniques that yield results minimally affected by outliers – and their applications to real-life economic and financial situations are the main focus of this book. The book also discusses applications of more traditional statistical techniques to econometric problems. Econometrics is a branch of economics that uses mathematical (especially statistical) methods to analyze economic systems, to forecast economic and financial dynamics, and to develop strategies for achieving desirable economic performance. In day-by-day data, we often encounter outliers that do not reflect the long-term economic trends, e.g., unexpected and abrupt fluctuations. As such, it is important to develop robust data processing techniques that can accommodate these fluctuations.

  6. Robust Manufacturing Control

    CERN Document Server


    This contributed volume collects research papers, presented at the CIRP Sponsored Conference Robust Manufacturing Control: Innovative and Interdisciplinary Approaches for Global Networks (RoMaC 2012, Jacobs University, Bremen, Germany, June 18th-20th 2012). These research papers present the latest developments and new ideas focusing on robust manufacturing control for global networks. Today, Global Production Networks (i.e. the nexus of interconnected material and information flows through which products and services are manufactured, assembled and distributed) are confronted with and expected to adapt to: sudden and unpredictable large-scale changes of important parameters which are occurring more and more frequently, event propagation in networks with high degree of interconnectivity which leads to unforeseen fluctuations, and non-equilibrium states which increasingly characterize daily business. These multi-scale changes deeply influence logistic target achievement and call for robust planning and control ...

  7. Information theoretic analysis of dynamical encoding by four identified primary sensory interneurons in the cricket cercal system. (United States)

    Theunissen, F; Roddey, J C; Stufflebeam, S; Clague, H; Miller, J P


    1. The stimulus/response properties of four identified primary sensory interneurons in the cricket cercal sensory system were studied using electrophysiological techniques. These four cells are thought to represent a functionally discrete subunit of the cercal system: they are the only cells that encode information about stimulus direction to higher centers for low intensity stimuli. Previous studies characterized the quantity of information encoded by these cells about the direction of air currents in the horizontal plane. In the experiments reported here, we characterized the quantity and quality of information encoded in the cells' elicited responses about the dynamics of air current waveforms presented at their optimal stimulus directions. The total sample set included 22 cells. 2. This characterization was achieved by determining the cells' frequency sensitivities and encoding accuracy using the methods of stochastic systems analysis and information theory. The specific approach used for the analysis was the "stimulus reconstruction" technique in which a functional expansion was derived to transform the observed spike train responses into the optimal estimate (i.e., "reconstruction") of the actual stimulus. A novel derivation of the crucial equations is presented. The reverse approach is compared with the more traditional forward analysis, in which an expansion is derived that transforms the stimulus to a prediction of the spike train response. Important aspects of the application of these analytical approaches are considered. 3. All four interneurons were found to have identical frequency tuning, as assessed by the accuracy with which different frequency components of stimulus waveforms could be reconstructed with a linear expansion. The interneurons encoded significant information about stimulus frequencies between 5 and 80 Hz, which peak sensitivities at approximately 15 Hz. 4. All four interneurons were found to have identical stimulus/response latencies

  8. Robust plasmonic substrates

    DEFF Research Database (Denmark)

    Kostiučenko, Oksana; Fiutowski, Jacek; Tamulevicius, Tomas


    Robustness is a key issue for the applications of plasmonic substrates such as tip-enhanced Raman spectroscopy, surface-enhanced spectroscopies, enhanced optical biosensing, optical and optoelectronic plasmonic nanosensors and others. A novel approach for the fabrication of robust plasmonic...... substrates is presented, which relies on the coverage of gold nanostructures with diamond-like carbon (DLC) thin films of thicknesses 25, 55 and 105 nm. DLC thin films were grown by direct hydrocarbon ion beam deposition. In order to find the optimum balance between optical and mechanical properties...

  9. Robust Self Tuning Controllers

    DEFF Research Database (Denmark)

    Poulsen, Niels Kjølstad


    The present thesis concerns robustness properties of adaptive controllers. It is addressed to methods for robustifying self tuning controllers with respect to abrupt changes in the plant parameters. In the thesis an algorithm for estimating abruptly changing parameters is presented. The estimator...... has several operation modes and a detector for controlling the mode. A special self tuning controller has been developed to regulate plant with changing time delay.......The present thesis concerns robustness properties of adaptive controllers. It is addressed to methods for robustifying self tuning controllers with respect to abrupt changes in the plant parameters. In the thesis an algorithm for estimating abruptly changing parameters is presented. The estimator...

  10. Robust Multiobjective Controllability of Complex Neuronal Networks. (United States)

    Tang, Yang; Gao, Huijun; Du, Wei; Lu, Jianquan; Vasilakos, Athanasios V; Kurths, Jurgen


    This paper addresses robust multiobjective identification of driver nodes in the neuronal network of a cat's brain, in which uncertainties in determination of driver nodes and control gains are considered. A framework for robust multiobjective controllability is proposed by introducing interval uncertainties and optimization algorithms. By appropriate definitions of robust multiobjective controllability, a robust nondominated sorting adaptive differential evolution (NSJaDE) is presented by means of the nondominated sorting mechanism and the adaptive differential evolution (JaDE). The simulation experimental results illustrate the satisfactory performance of NSJaDE for robust multiobjective controllability, in comparison with six statistical methods and two multiobjective evolutionary algorithms (MOEAs): nondominated sorting genetic algorithms II (NSGA-II) and nondominated sorting composite differential evolution. It is revealed that the existence of uncertainties in choosing driver nodes and designing control gains heavily affects the controllability of neuronal networks. We also unveil that driver nodes play a more drastic role than control gains in robust controllability. The developed NSJaDE and obtained results will shed light on the understanding of robustness in controlling realistic complex networks such as transportation networks, power grid networks, biological networks, etc.

  11. Robust surgery loading

    NARCIS (Netherlands)

    Hans, Elias W.; Wullink, Gerhard; van Houdenhoven, Mark; Kazemier, Geert


    We consider the robust surgery loading problem for a hospital’s operating theatre department, which concerns assigning surgeries and sufficient planned slack to operating room days. The objective is to maximize capacity utilization and minimize the risk of overtime, and thus cancelled patients. This

  12. Robustness of structures

    DEFF Research Database (Denmark)

    Vrouwenvelder, T.; Sørensen, John Dalsgaard


    robustness is still an issue of controversy and poses difficulties in regard to interpretation as well as regulation. Typically modern structural design codes require that ‘the consequence of damages to structures should not be disproportional to the causes of the damages'. However, despite the importance...

  13. Robustness of Structures

    DEFF Research Database (Denmark)

    Faber, Michael Havbro; Vrouwenvelder, A.C.W.M.; Sørensen, John Dalsgaard


    In 2005, the Joint Committee on Structural Safety (JCSS) together with Working Commission (WC) 1 of the International Association of Bridge and Structural Engineering (IABSE) organized a workshop on robustness of structures. Two important decisions resulted from this workshop, namely the developm...

  14. Robustness of spatial micronetworks (United States)

    McAndrew, Thomas C.; Danforth, Christopher M.; Bagrow, James P.


    Power lines, roadways, pipelines, and other physical infrastructure are critical to modern society. These structures may be viewed as spatial networks where geographic distances play a role in the functionality and construction cost of links. Traditionally, studies of network robustness have primarily considered the connectedness of large, random networks. Yet for spatial infrastructure, physical distances must also play a role in network robustness. Understanding the robustness of small spatial networks is particularly important with the increasing interest in microgrids, i.e., small-area distributed power grids that are well suited to using renewable energy resources. We study the random failures of links in small networks where functionality depends on both spatial distance and topological connectedness. By introducing a percolation model where the failure of each link is proportional to its spatial length, we find that when failures depend on spatial distances, networks are more fragile than expected. Accounting for spatial effects in both construction and robustness is important for designing efficient microgrids and other network infrastructure.

  15. Toward robust phase-locking in Melibe swim central pattern generator models (United States)

    Jalil, Sajiya; Allen, Dane; Youker, Joseph; Shilnikov, Andrey


    Small groups of interneurons, abbreviated by CPG for central pattern generators, are arranged into neural networks to generate a variety of core bursting rhythms with specific phase-locked states, on distinct time scales, which govern vital motor behaviors in invertebrates such as chewing and swimming. These movements in lower level animals mimic motions of organs in higher animals due to evolutionarily conserved mechanisms. Hence, various neurological diseases can be linked to abnormal movement of body parts that are regulated by a malfunctioning CPG. In this paper, we, being inspired by recent experimental studies of neuronal activity patterns recorded from a swimming motion CPG of the sea slug Melibe leonina, examine a mathematical model of a 4-cell network that can plausibly and stably underlie the observed bursting rhythm. We develop a dynamical systems framework for explaining the existence and robustness of phase-locked states in activity patterns produced by the modeled CPGs. The proposed tools can be used for identifying core components for other CPG networks with reliable bursting outcomes and specific phase relationships between the interneurons. Our findings can be employed for identifying or implementing the conditions for normal and pathological functioning of basic CPGs of animals and artificially intelligent prosthetics that can regulate various movements.

  16. A multi-compartment model for interneurons in the dorsal lateral geniculate nucleus.

    Directory of Open Access Journals (Sweden)

    Geir Halnes


    Full Text Available GABAergic interneurons (INs in the dorsal lateral geniculate nucleus (dLGN shape the information flow from retina to cortex, presumably by controlling the number of visually evoked spikes in geniculate thalamocortical (TC neurons, and refining their receptive field. The INs exhibit a rich variety of firing patterns: Depolarizing current injections to the soma may induce tonic firing, periodic bursting or an initial burst followed by tonic spiking, sometimes with prominent spike-time adaptation. When released from hyperpolarization, some INs elicit rebound bursts, while others return more passively to the resting potential. A full mechanistic understanding that explains the function of the dLGN on the basis of neuronal morphology, physiology and circuitry is currently lacking. One way to approach such an understanding is by developing a detailed mathematical model of the involved cells and their interactions. Limitations of the previous models for the INs of the dLGN region prevent an accurate representation of the conceptual framework needed to understand the computational properties of this region. We here present a detailed compartmental model of INs using, for the first time, a morphological reconstruction and a set of active dendritic conductances constrained by experimental somatic recordings from INs under several different current-clamp conditions. The model makes a number of experimentally testable predictions about the role of specific mechanisms for the firing properties observed in these neurons. In addition to accounting for the significant features of all experimental traces, it quantitatively reproduces the experimental recordings of the action-potential- firing frequency as a function of injected current. We show how and why relative differences in conductance values, rather than differences in ion channel composition, could account for the distinct differences between the responses observed in two different neurons, suggesting

  17. Dichotomous Effects of Mu Opioid Receptor Activation on Striatal Low-Threshold Spike Interneurons

    Directory of Open Access Journals (Sweden)

    Rasha Elghaba


    Full Text Available Striatal low-threshold spike interneurons (LTSIs are tonically active neurons that express GABA and nitric oxide synthase and are involved in information processing as well as neurovascular coupling. While mu opioid receptors (MORs and their ligand encephalin are prominent in the striatum, their action on LTSIs has not been investigated. We addressed this issue carrying out whole-cell recordings in transgenic mice in which the NPY-expressing neurons are marked with green fluorescent protein (GFP. The MOR agonist (D-Ala(2, N-MePhe(4, Gly-ol-enkephalin (DAMGO produced dual effects on subpopulations of LTSIs. DAMGO caused inhibitory effects, accompanied by decreases of spontaneous firing, in 62% of LTSIs, while depolarizing effects (accompanied by an increase in spontaneous firing were observed in 23% of LTSIs tested. The dual effects of DAMGO persisted in the presence of tetrodotoxin (TTX, a sodium channel blocker or in the presence of the nicotinic acetylcholine receptor antagonist mecamylamine. However, in the presence of either the GABAA receptor antagonist picrotoxin or the muscarinic cholinergic receptor antagonist atropine, DAMGO only elicited inhibitory effects on LTSIs. Furthermore, we found that DAMGO decreased the amplitude and frequency of spontaneous GABAergic events. Unexpectedly, these effects of DAMGO on spontaneous GABAergic events disappeared after blocking of the muscarinic and nicotinic cholinergic blockers, showing that GABA inputs to LTSIs are not directly modulated by presynaptic MORs. These finding suggest that activation of MORs affect LTSIs both directly and indirectly, through modulation of GABAergic and cholinergic tones. The complex balance between direct and indirect effects determines the net effect of DAMGO on LTSIs.

  18. Memory-guided sensory comparisons in the prefrontal cortex: contribution of putative pyramidal cells and interneurons. (United States)

    Hussar, Cory R; Pasternak, Tatiana


    Comparing two stimuli that occur at different times demands the coordination of bottom-up and top-down processes. It has been hypothesized that the dorsolateral prefrontal (PFC) cortex, the likely source of top-down cortical influences, plays a key role in such tasks, contributing to both maintenance and sensory comparisons. We examined this hypothesis by recording from the PFC of monkeys comparing directions of two moving stimuli, S1 and S2, separated by a memory delay. We determined the contribution of the two principal cell types to these processes by classifying neurons into broad-spiking (BS) putative pyramidal cells and narrow-spiking (NS) putative local interneurons. During the delay, BS cells were more likely to exhibit anticipatory modulation and represent the remembered direction. While this representation was transient, appearing at different times in different neurons, it weakened when direction was not task relevant, suggesting its utility. During S2, both putative cell types showed comparison-related activity modulations. These modulations were of two types, each carried by different neurons, which either preferred trials with stimuli moving in the same direction or trials with stimuli of different directions. These comparison effects were strongly correlated with choice, suggesting their role in circuitry underlying decision making. These results provide the first demonstration of distinct contributions made by principal cell types to memory-guided perceptual decisions. During sensory stimulation both cell types represent behaviorally relevant stimulus features contributing to comparison and decision-related activity. However in the absence of sensory stimulation, putative pyramidal cells dominated, carrying information about the elapsed time and the preceding direction.

  19. Synaptic and functional linkages between spinal premotor interneurons and hand-muscle activity during precision grip

    Directory of Open Access Journals (Sweden)

    Tomohiko eTakei


    Full Text Available Grasping is a highly complex movement that requires the coordination of a number of hand joints and muscles. Previous studies showed that spinal premotor interneurons (PreM-INs in the primate cervical spinal cord have divergent synaptic effects on hand motoneurons and that they might contribute to hand-muscle synergies. However, the extent to which these PreM-IN synaptic connections functionally contribute to modulating hand-muscle activity is not clear. In this paper, we explored the contribution of spinal PreM-INs to hand-muscle activation by quantifying the synaptic linkage (SL and functional linkage (FL of the PreM-INs with hand-muscle activities. The activity of 23 PreM-INs was recorded from the cervical spinal cord (C6–T1, with EMG signals measured simultaneously from hand and arm muscles in two macaque monkeys performing a precision grip task. Spike-triggered averages (STAs of rectified EMGs were compiled for 456 neuron–muscle pairs; 63 pairs showed significant post-spike effects (i.e., SL. Conversely, 231 of 456 pairs showed significant cross-correlations between the IN firing rate and rectified EMG (i.e., FL. Importantly, a greater proportion of the neuron–muscle pairs with SL showed FL (43/63 pairs, 68% compared with the pairs without SL (203/393, 52%, and the presence of SL was significantly associated with that of FL. However, a significant number of pairs had SL without FL (SL∩!FL, n = 20 or FL without SL (!SL∩FL, n = 203, and the proportions of these incongruities exceeded the number expected by chance. These results suggested that spinal PreM-INs function to significantly modulate hand-muscle activity during precision grip, but the contribution of other neural structures is also needed to recruit an adequate combination of hand-muscle motoneurons.

  20. Propensity for Bistability of Bursting and Silence in the Leech Heart Interneuron

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    Tatiana Dashevskiy


    Full Text Available The coexistence of neuronal activity regimes has been reported under normal and pathological conditions. Such multistability could enhance the flexibility of the nervous system and has many implications for motor control, memory, and decision making. Multistability is commonly promoted by neuromodulation targeting specific membrane ionic currents. Here, we investigated how modulation of different ionic currents could affect the neuronal propensity for bistability. We considered a leech heart interneuron model. It exhibits bistability of bursting and silence in a narrow range of the leak current parameters, conductance (gleak and reversal potential (Eleak. We assessed the propensity for bistability of the model by using bifurcation diagrams. On the diagram (gleak, Eleak, we mapped bursting and silent regimes. For the canonical value of Eleak we determined the range of gleak which supported the bistability. We use this range as an index of propensity for bistability. We investigated how this index was affected by alterations of ionic currents. We systematically changed their conductances, one at a time, and built corresponding bifurcation diagrams in parameter planes of the maximal conductance of a given current and the leak conductance. We found that conductance of only one current substantially affected the index of propensity; the increase of the maximal conductance of the hyperpolarization-activated cationic current increased the propensity index. The second conductance with the strongest effect was the conductance of the low-threshold fast Ca2+ current; its reduction increased the propensity index although the effect was about two times smaller in magnitude. Analyzing the model with both changes applied simultaneously, we found that the diagram (gleak, Eleak showed a progressively expanded area of bistability of bursting and silence.

  1. Fluctuating inhibitory inputs promote reliable spiking at theta frequencies in hippocampal interneurons

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    Duluxan eSritharan


    Full Text Available Theta frequency (4-12 Hz rhythms in the hippocampus play important roles in learning and memory. CA1 interneurons located at the stratum lacunosum-moleculare and radiatum junction (LM/RAD are thought to contribute to hippocampal theta population activities by rhythmically pacing pyramidal cells with inhibitory postsynaptic potentials. This implies that LM/RAD cells need to fire reliably at theta frequencies in vivo. To determine whether this could occur, we use biophysically-based LM/RAD model cells and apply different cholinergic and synaptic inputs to simulate in vivo-like network environments. We assess spike reliabilities and spiking frequencies, identifying biophysical properties and network conditions that best promote reliable theta spiking. We find that synaptic background activities that feature large inhibitory, but not excitatory, fluctuations are essential. This suggests that strong inhibitory input to these cells is vital for them to be able to contribute to population theta activities. Furthermore, we find that Type I-like oscillator models produced by augmented persistent sodium currents (INap or diminished A type potassium currents (IA enhance reliable spiking at lower theta frequencies. These Type I-like models are also the most responsive to large inhibitory fluctuations and can fire more reliably under such conditions. In previous work, we showed that INap and IA are largely responsible for establishing LM/RAD cells’ subthreshold activities. Taken together with this study, we see that while both these currents are important for subthreshold theta fluctuations and reliable theta spiking, they contribute in different ways – INap to reliable theta spiking and subthreshold activity generation, and IA to subthreshold activities at theta frequencies. This suggests that linking subthreshold and suprathreshold activities should be done with consideration of both in vivo contexts and biophysical specifics.

  2. Octopaminergic modulation of temporal frequency coding in an identified optic flow-processing interneuron

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    Kit D. Longden


    Full Text Available Flying generates predictably different patterns of optic flow compared with other locomotor states. A sensorimotor system tuned to rapid responses and a high bandwidth of optic flow would help the animal to avoid wasting energy through imprecise motor action. However, neural processing that covers a higher input bandwidth itself comes at higher energetic costs which would be a poor investment when the animal was not flying. How does the blowfly adjust the dynamic range of its optic flow-processing neurons to the locomotor state? Octopamine (OA is a biogenic amine central to the initiation and maintenance of flight in insects. We used an OA agonist chlordimeform (CDM to simulate the widespread OA release during flight and recorded the effects on the temporal frequency coding of the H2 cell. This cell is a visual interneuron known to be involved in flight stabilization reflexes. The application of CDM resulted in i an increase in the cell's spontaneous activity, expanding the inhibitory signalling range ii an initial response gain to moving gratings (20 – 60 ms post-stimulus that depended on the temporal frequency of the grating and iii a reduction in the rate and magnitude of motion adaptation that was also temporal frequency-dependent. To our knowledge, this is the first demonstration that the application of a neuromodulator can induce velocity-dependent alterations in the gain of a wide-field optic flow-processing neuron. The observed changes in the cell’s response properties resulted in a 33% increase of the cell’s information rate when encoding random changes in temporal frequency of the stimulus. The increased signalling range and more rapid, longer lasting responses employed more spikes to encode each bit, and so consumed a greater amount of energy. It appears that for the fly investing more energy in sensory processing during flight is more efficient than wasting energy on under-performing motor control.

  3. Robust Affine Invariant Descriptors

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    Jianwei Yang


    Full Text Available An approach is developed for the extraction of affine invariant descriptors by cutting object into slices. Gray values associated with every pixel in each slice are summed up to construct affine invariant descriptors. As a result, these descriptors are very robust to additive noise. In order to establish slices of correspondence between an object and its affine transformed version, general contour (GC of the object is constructed by performing projection along lines with different polar angles. Consequently, affine in-variant division curves are derived. A slice is formed by points fall in the region enclosed by two adjacent division curves. To test and evaluate the proposed method, several experiments have been conducted. Experimental results show that the proposed method is very robust to noise.

  4. Robustness in Feedback Systems. (United States)


    Horowitz [1%3]). A central focus of robust control theory over the years has been an attempt to generalize these results to multiinput. multioutput ... multioutput systems. These include uniformly (or li.-) optimal control (see Zames [1981]. Zames and Francis [19831. Francis and Zames [1984], and...describes a computable upper bound for multiinput multioutput two-disk problems which requires only the solution of several one-disk prob!ems. To begin

  5. Robust Airline Schedules


    Eggenberg, Niklaus; Salani, Matteo; Bierlaire, Michel


    Due to economic pressure industries, when planning, tend to focus on optimizing the expected profit or the yield. The consequence of highly optimized solutions is an increased sensitivity to uncertainty. This generates additional "operational" costs, incurred by possible modifications of the original plan to be performed when reality does not reflect what was expected in the planning phase. The modern research trend focuses on "robustness" of solutions instead of yield or profit. Although ro...

  6. Robustness for Dummies


    Vincenzo Verardi; Marjorie Gassner; Darwin Ugarte Ontiveros


    In the robust statistics literature, a wide variety of models have been devel- oped to cope with outliers in a rather large number of scenarios. Nevertheless, a recurrent problem for the empirical implementation of these estimators is that optimization algorithms generally do not perform well when dummy vari- ables are present. What we propose in this paper is a simple solution to this involving the replacement of the sub-sampling step of the maximization procedures by a projection-based meth...

  7. Anatomical and electrophysiological characterization of a population of dI6 interneurons in the neonatal mouse spinal cord. (United States)

    Griener, Anna; Zhang, Wei; Kao, Henry; Haque, Farhia; Gosgnach, Simon


    The locomotor central pattern generator is a neural network located in the ventral aspect of the caudal spinal cord that underlies stepping in mammals. While many genetically defined interneurons that are thought to comprise this neural network have been identified and characterized, the dI6 cells- which express the transcription factors WT1 and/or DMRT3- are one population that settle in this region, are active during locomotion, whose function is poorly understood. These cells were originally hypothesized to be commissural premotor interneurons, however evidence in support of this is sparse. Here we characterize this population of cells using the TgDbx1 Cre ;R26 EFP ;Dbx1 LacZ transgenic mouse line, which has been shown to be an effective marker of dI6 interneurons. We show dI6 cells to be abundant in laminae VII and VIII along the entire spinal cord and provide evidence that subtypes outside the WT1/DMRT3 expressing dI6 cells may exist. Retrograde tracing experiments indicate that the majority of dI6 cells project descending axons, and some make monosynaptic or disynaptic contacts onto motoneurons on either side of the spinal cord. Analysis of their activity during non-resetting deletions, which occur during bouts of fictive locomotion, suggests that these cells are involved in both locomotor rhythm generation and pattern formation. This study provides a thorough characterization of the dI6 cells labeled in the TgDbx1 Cre ;R26 EFP ;Dbx1 LacZ transgenic mouse, and supports previous work suggesting that these cells play multiple roles during locomotor activity. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Morphological features, distribution and compartmental organization of the nicotinamide adenine dinucleotide phosphate reduced-diaphorase interneurons in the human striatum. (United States)

    Bernácer, Javier; Prensa, Lucía; Giménez-Amaya, José Manuel


    Striatal nicotinamide adenine dinucleotide phosphate reduced-diaphorase (NADPH-d)-positive (+) cells are one of the major classes of striatal interneurons. The present study analyzes their somatodendritic morphology, distribution pattern, and compartmental organization in the caudate nucleus (CN) and putamen (Put) of nine normal human brains. The following striatal territories are examined: 1) the precommissural head of the CN; 2) the postcommissural head of the CN; 3) the body of the CN; 4) the gyrus of the CN; 5) the tail of the CN; 6) the precommissural Put; and 7) the postcommissural Put. Three morphologically distinct types of NADPH-d+ neurons were found in each of these territories. The two most common NADPH-d+ neurons displayed an ovoid or triangular perikaryon from which several thick primary dendrites emerged, although much less numerous, bipolar-shaped NADPH-d+ cells were also observed. The highest density of NADPH-d+ neurons was found in the gyrus of the CN, followed by the body of the CN, tail of the CN, postcommissural head of the CN, postcommissural Put, precommissural head of the CN, and precommissural Put. The matrix was the striatal compartment with the densest NADPH-d+ neuronal population. Some of these cells also occurred in the center and peripheral regions of the striosomes located in the head of the CN and in the Put. In the body and gyrus of the CN, the striosomes were largely devoid of these striatal interneurons. Knowledge of the density and distribution of these interneurons should advance our understanding of the organization of the normal human striatum and help to evaluate the effects of neurodegenerative processes on cell density. (c) 2005 Wiley-Liss, Inc.

  9. Decreased number of interneurons and increased seizures in neuropilin 2 deficient mice: implications for autism and epilepsy. (United States)

    Gant, John C; Thibault, Oliver; Blalock, Eric M; Yang, Jun; Bachstetter, Adam; Kotick, James; Schauwecker, Paula E; Hauser, Kurt F; Smith, George M; Mervis, Ron; Li, YanFang; Barnes, Gregory N


    Clinically, perturbations in the semaphorin signaling system have been associated with autism and epilepsy. The semaphorins have been implicated in guidance, migration, differentiation, and synaptic plasticity of neurons. The semaphorin 3F (Sema3F) ligand and its receptor, neuropilin 2 (NPN2) are highly expressed within limbic areas. NPN2 signaling may intimately direct the apposition of presynaptic and postsynaptic locations, facilitating the development and maturity of hippocampal synaptic function. To further understand the role of NPN2 signaling in central nevous system (CNS) plasticity, structural and functional alterations were assessed in NPN2 deficient mice. In NPN2 deficient mice, we measured seizure susceptibility after kainic acid or pentylenetetrazol, neuronal excitability and synaptic throughput in slice preparations, principal and interneuron cell counts with immunocytochemical protocols, synaptosomal protein levels with immunoblots, and dendritic morphology with Golgi-staining. NPN2 deficient mice had shorter seizure latencies, increased vulnerability to seizure-related death, were more likely to develop spontaneous recurrent seizure activity after chemical challenge, and had an increased slope on input/output curves. Principal cell counts were unchanged, but GABA, parvalbumin, and neuropeptide Y interneuron cell counts were significantly reduced. Synaptosomal NPN2 protein levels and total number of GABAergic synapses were decreased in a gene dose-dependent fashion. CA1 pyramidal cells showed reduced dendritic length and complexity, as well as an increased number of dendritic spines. These data suggest the novel hypothesis that the Sema 3F signaling system's role in appropriate placement of subsets of hippocampal interneurons has critical downstream consequences for hippocampal function, resulting in a more seizure susceptible phenotype.

  10. Robustness of metabolic networks (United States)

    Jeong, Hawoong


    We investigated the robustness of cellular metabolism by simulating the system-level computational models, and also performed the corresponding experiments to validate our predictions. We address the cellular robustness from the ``metabolite''-framework by using the novel concept of ``flux-sum,'' which is the sum of all incoming or outgoing fluxes (they are the same under the pseudo-steady state assumption). By estimating the changes of the flux-sum under various genetic and environmental perturbations, we were able to clearly decipher the metabolic robustness; the flux-sum around an essential metabolite does not change much under various perturbations. We also identified the list of the metabolites essential to cell survival, and then ``acclimator'' metabolites that can control the cell growth were discovered. Furthermore, this concept of ``metabolite essentiality'' should be useful in developing new metabolic engineering strategies for improved production of various bioproducts and designing new drugs that can fight against multi-antibiotic resistant superbacteria by knocking-down the enzyme activities around an essential metabolite. Finally, we combined a regulatory network with the metabolic network to investigate its effect on dynamic properties of cellular metabolism.

  11. The Crane Robust Control

    Directory of Open Access Journals (Sweden)

    Marek Hicar


    Full Text Available The article is about a control design for complete structure of the crane: crab, bridge and crane uplift.The most important unknown parameters for simulations are burden weight and length of hanging rope. We will use robustcontrol for crab and bridge control to ensure adaptivity for burden weight and rope length. Robust control will be designed for current control of the crab and bridge, necessary is to know the range of unknown parameters. Whole robust will be splitto subintervals and after correct identification of unknown parameters the most suitable robust controllers will be chosen.The most important condition at the crab and bridge motion is avoiding from burden swinging in the final position. Crab and bridge drive is designed by asynchronous motor fed from frequency converter. We will use crane uplift with burden weightobserver in combination for uplift, crab and bridge drive with cooperation of their parameters: burden weight, rope length and crab and bridge position. Controllers are designed by state control method. We will use preferably a disturbance observerwhich will identify burden weight as a disturbance. The system will be working in both modes at empty hook as well asat maximum load: burden uplifting and dropping down.

  12. Dopamine D4 receptor activation increases hippocampal gamma oscillations by enhancing synchronization of fast-spiking interneurons.

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    Richard Andersson

    Full Text Available BACKGROUND: Gamma oscillations are electric activity patterns of the mammalian brain hypothesized to serve attention, sensory perception, working memory and memory encoding. They are disrupted or altered in schizophrenic patients with associated cognitive deficits, which persist in spite of treatment with antipsychotics. Because cognitive symptoms are a core feature of schizophrenia it is relevant to explore signaling pathways that potentially regulate gamma oscillations. Dopamine has been reported to decrease gamma oscillation power via D1-like receptors. Based on the expression pattern of D4 receptors (D4R in hippocampus, and pharmacological effects of D4R ligands in animals, we hypothesize that they are in a position to regulate gamma oscillations as well. METHODOLOGY/PRINCIPAL FINDINGS: To address this hypothesis we use rat hippocampal slices and kainate-induced gamma oscillations. Local field potential recordings as well as intracellular recordings of pyramidal cells, fast-spiking and non-fast-spiking interneurons were carried out. We show that D4R activation with the selective ligand PD168077 increases gamma oscillation power, which can be blocked by the D4R-specific antagonist L745,870 as well as by the antipsychotic drug Clozapine. Pyramidal cells did not exhibit changes in excitatory or inhibitory synaptic current amplitudes, but inhibitory currents became more coherent with the oscillations after application of PD168077. Fast-spiking, but not non-fast spiking, interneurons, increase their action potential phase-coupling and coherence with regard to ongoing gamma oscillations in response to D4R activation. Among several possible mechanisms we found that the NMDA receptor antagonist AP5 also blocks the D4R mediated increase in gamma oscillation power. CONCLUSIONS/SIGNIFICANCE: We conclude that D4R activation affects fast-spiking interneuron synchronization and thereby increases gamma power by an NMDA receptor-dependent mechanism. This

  13. Ca2+ -Mediated Plateau Potentials in a Subpopulation of Interneurons in the Ventral Horn of the Turtle Spinal Cord

    DEFF Research Database (Denmark)

    Hounsgaard, J.; Kjaerulff, O.


    The response properties of interneurons in the ventral horn were studied in transverse slices of segments D8 to S2 from the turtle spinal cord, using the current clamp technique. In about half of the neurons the response properties were dominated by their ability to generate plateau potentials...... root and occasionally from the contralateral root. The plateau potential was insensitive to tetrodotoxin but blocked by nifedipine and by replacing Ca2+ with Co2+ in the medium. It is concluded that the response properties of neurons in the ventral horn outside the motor nucleus have differentiated...

  14. [Structural and functional reorganization of the interneuronal contacts of the cerebral cortex after a single convulsive paroxysm]. (United States)

    Savchenko, Iu N; Ereniev, S I; Semchenko, V V; Stepanov, S S


    Using the technique of contrasting the cerebral tissue with phosphotungstic acid, the authors studied the structural and functional status of interneuronal contacts of the molecular layer of the sensomotor cortex in the brain of Krushinsky-Molodkina rats following convulsive sound stimulation and the subsequent audiogenic convulsive paroxysm. Marked reduction in the general number of synapses 4 h after the attack was attended by transformation of some flat functionally mature contacts into concave ones, which reflects the activation of the synaptic pool. The relative levels of concave and flat mature contacts returned to the initial level 8 to 24 h later.

  15. Oscillation-Driven Spike-Timing Dependent Plasticity Allows Multiple Overlapping Pattern Recognition in Inhibitory Interneuron Networks

    DEFF Research Database (Denmark)

    Garrido, Jesús A.; Luque, Niceto R.; Tolu, Silvia


    The majority of operations carried out by the brain require learning complex signal patterns for future recognition, retrieval and reuse. Although learning is thought to depend on multiple forms of long-term synaptic plasticity, the way this latter contributes to pattern recognition is still poorly...... understood. Here, we have used a simple model of afferent excitatory neurons and interneurons with lateral inhibition, reproducing a network topology found in many brain areas from the cerebellum to cortical columns. When endowed with spike-timing dependent plasticity (STDP) at the excitatory input synapses...... representations of information in excitatory neuron populations falling under their control....

  16. The sodium channel activator Lu AE98134 normalizes the altered firing properties of fast spiking interneurons in Dlx5/6+/- mice

    DEFF Research Database (Denmark)

    von Schoubye, Nadia Lybøl; Frederiksen, Kristen; Kristiansen, Uffe


    Mental disorders such as schizophrenia are associated with impaired firing properties of fast spiking inhibitory interneurons (FSINs) causing reduced task-evoked gamma-oscillation in prefrontal cortex. The voltage-gated sodium channel NaV1.1 is highly expressed in PV-positive interneurons, but only...... facilitated the sodium current mediated by NaV1.1 expressed in HEK cells by shifting its activation to more negative values, decreasing its inactivation kinetics and promoting a persistent inward current. In a slice preparation from the brain of adult mice, Lu AE98134 promoted the excitability of fast spiking...... interneurons by decreasing the threshold for action potentials. We then tested if Lu AE98134 could normalize the altered firing properties of FSINs in Dlx5/6+/- mutant mice. FSINs of this model for schizophrenia are characterized by broader action potentials and higher spike threshold. We found...

  17. Combined Pharmacological and Genetic Manipulations Unlock Unprecedented Temporal Elasticity and Reveal Phase-Specific Modulation of the Molecular Circadian Clock of the Mouse Suprachiasmatic Nucleus


    Patton, Andrew P.; Chesham, Johanna E.; Hastings, Michael H.


    The suprachiasmatic nucleus (SCN) is the master circadian oscillator encoding time-of-day information. SCN timekeeping is sustained by a cell-autonomous transcriptional–translational feedback loop, whereby expression of the Period and Cryptochrome genes is negatively regulated by their protein products. This loop in turn drives circadian oscillations in gene expression that direct SCN electrical activity and thence behavior. The robustness of SCN timekeeping is further enhanced by interneuron...

  18. Impairments in Motor Neurons, Interneurons and Astrocytes Contribute to Hyperexcitability in ALS: Underlying Mechanisms and Paths to Therapy. (United States)

    Do-Ha, Dzung; Buskila, Yossi; Ooi, Lezanne


    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by the loss of motor neurons leading to progressive paralysis and death. Using transcranial magnetic stimulation (TMS) and nerve excitability tests, several clinical studies have identified that cortical and peripheral hyperexcitability are among the earliest pathologies observed in ALS patients. The changes in the electrophysiological properties of motor neurons have been identified in both sporadic and familial ALS patients, despite the diverse etiology of the disease. The mechanisms behind the change in neuronal signalling are not well understood, though current findings implicate intrinsic changes in motor neurons and dysfunction of cells critical in regulating motor neuronal excitability, such as astrocytes and interneurons. Alterations in ion channel expression and/or function in motor neurons has been associated with changes in cortical and peripheral nerve excitability. In addition to these intrinsic changes in motor neurons, inhibitory signalling through GABAergic interneurons is also impaired in ALS, likely contributing to increased neuronal excitability. Astrocytes have also recently been implicated in increasing neuronal excitability in ALS by failing to adequately regulate glutamate levels and extracellular K + concentration at the synaptic cleft. As hyperexcitability is a common and early feature of ALS, it offers a therapeutic and diagnostic target. Thus, understanding the underlying pathways and mechanisms leading to hyperexcitability in ALS offers crucial insight for future development of ALS treatments.

  19. The PKA-C3 catalytic subunit is required in two pairs of interneurons for successful mating of Drosophila. (United States)

    Cassar, Marlène; Sunderhaus, Elizabeth; Wentzell, Jill S; Kuntz, Sara; Strauss, Roland; Kretzschmar, Doris


    Protein kinase A (PKA) has been shown to play a role in a plethora of cellular processes ranging from development to memory formation. Its activity is mediated by the catalytic subunits whereby many species express several paralogs. Drosophila encodes three catalytic subunits (PKA-C1-3) and whereas PKA-C1 has been well studied, the functions of the other two subunits were unknown. PKA-C3 is the orthologue of mammalian PRKX/Pkare and they are structurally more closely related to each other than to other catalytic subunits within their species. PRKX is expressed in the nervous system in mice but its function is also unknown. We now show that the loss of PKA-C3 in Drosophila causes copulation defects, though the flies are active and show no defects in other courtship behaviours. This phenotype is specifically due to the loss of PKA-C3 because PKA-C1 cannot replace PKA-C3. PKA-C3 is expressed in two pairs of interneurons that send projections to the ventro-lateral protocerebrum and the mushroom bodies and that synapse onto motor neurons in the ventral nerve cord. Rescue experiments show that expression of PKA-C3 in these interneurons is sufficient for copulation, suggesting a role in relaying information from the sensory system to motor neurons to initiate copulation.

  20. NMDAR hypofunction and somatostatin-expressing GABAergic interneurons and receptors: A newly identified correlation and its effects in schizophrenia

    Directory of Open Access Journals (Sweden)

    Fatemah Alherz


    Full Text Available This review investigates the association between N-methyl-d-Aspartate receptor (NMDAR hypofunction and somatostatin-expressing GABAergic interneurons (SST+ and how it contributes to the cognitive deficits observed in schizophrenia (SZ. This is based on evidence that NMDAR antagonists caused symptoms resembling SZ in healthy individuals. NMDAR hypofunction in GABAergic interneurons results in the modulation of the cortical network oscillation, particularly in the gamma range (30–80 Hz. These gamma-band oscillation (GBO abnormalities were found to lead to the cognitive deficits observed in the disorder. Postmortem mRNA studies have shown that SST decreased more significantly than any other biomarker in schizophrenic subjects. The functional role of Somatostatin (SST in the aetiology of SZ can be studied through its receptors. Genetic knockout studies in animal models in Huntington's disease (HD have shown that a specific SST receptor, SSTR2, is increased along with the increased NMDAR activity, with opposing patterns observed in SZ. A direct correlation between SSTR and NMDAR is hence inferred in this review with the hope of finding a potential new therapeutic target for the treatment of SZ and related neurological conditions.

  1. TRPV1 in GABAergic interneurons mediates neuropathic mechanical allodynia and disinhibition of the nociceptive circuitry in the spinal cord. (United States)

    Kim, Yong Ho; Back, Seung Keun; Davies, Alexander J; Jeong, Heejin; Jo, Hyun Jung; Chung, Geehoon; Na, Heung Sik; Bae, Yong Chul; Kim, Sang Jeong; Kim, Joong Soo; Jung, Sung Jun; Oh, Seog Bae


    Neuropathic pain and allodynia may arise from sensitization of central circuits. We report a mechanism of disinhibition-based central sensitization resulting from long-term depression (LTD) of GABAergic interneurons as a consequence of TRPV1 activation in the spinal cord. Intrathecal administration of TRPV1 agonists led to mechanical allodynia that was not dependent on peripheral TRPV1 neurons. TRPV1 was functionally expressed in GABAergic spinal interneurons and activation of spinal TRPV1 resulted in LTD of excitatory inputs and a reduction of inhibitory signaling to spinothalamic tract (STT) projection neurons. Mechanical hypersensitivity after peripheral nerve injury was attenuated in TRPV1(-/-) mice but not in mice lacking TRPV1-expressing peripheral neurons. Mechanical pain was reversed by a spinally applied TRPV1 antagonist while avoiding the hyperthermic side effect of systemic treatment. Our results demonstrate that spinal TRPV1 plays a critical role as a synaptic regulator and suggest the utility of central nervous system-specific TRPV1 antagonists for treating neuropathic pain. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Local Optogenetic Induction of Fast (20-40 Hz Pyramidal-Interneuron Network Oscillations in the In Vitro and In Vivo CA1 Hippocampus: Modulation by CRF and Enforcement of Perirhinal Theta Activity

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    Julien eDine


    Full Text Available The neurophysiological processes that can cause theta-to-gamma frequency range (4-80 Hz network oscillations in the rhinal cortical-hippocampal system and the potential connectivity-based interactions of such forebrain rhythms are a topic of intensive investigation. Here, using selective Channelrhodopsin-2 (ChR2 expression in mouse forebrain glutamatergic cells, we were able to locally, temporally precisely, and reliably induce fast (20-40 Hz field potential oscillations in hippocampal area CA1 in vitro (at 25°C and in vivo (i.e., slightly anaesthetized NEX-Cre-ChR2 mice. As revealed by pharmacological analyses and patch-clamp recordings from pyramidal cells and GABAergic interneurons in vitro, these light-triggered oscillations can exclusively arise from sustained suprathreshold depolarization (~200 ms or longer and feedback inhibition of CA1 pyramidal neurons, as being mandatory for prototypic pyramidal-interneuron network (P-I oscillations. Consistently, the oscillations comprised rhythmically occurring population spikes (generated by pyramidal cells and their frequency increased with increasing spectral power. We further demonstrate that the optogenetically driven CA1 oscillations, which remain stable over repeated evocations, are impaired by the stress hormone corticotropin-releasing factor (CRF, 125 nM in vitro and, even more remarkably, found that they are accompanied by concurrent states of enforced theta activity in the memory-associated perirhinal cortex (PrC in vivo. The latter phenomenon most likely derives from neurotransmission via a known, but poorly studied excitatory CA1PrC pathway. Collectively, our data provide evidence for the existence of a prototypic (CRF-sensitive P-I gamma rhythm generator in area CA1 and suggest that CA1 P-I oscillations can rapidly up-regulate theta activity strength in hippocampus-innervated rhinal networks, at least in the PrC.

  3. Robust efficient video fingerprinting (United States)

    Puri, Manika; Lubin, Jeffrey


    We have developed a video fingerprinting system with robustness and efficiency as the primary and secondary design criteria. In extensive testing, the system has shown robustness to cropping, letter-boxing, sub-titling, blur, drastic compression, frame rate changes, size changes and color changes, as well as to the geometric distortions often associated with camcorder capture in cinema settings. Efficiency is afforded by a novel two-stage detection process in which a fast matching process first computes a number of likely candidates, which are then passed to a second slower process that computes the overall best match with minimal false alarm probability. One key component of the algorithm is a maximally stable volume computation - a three-dimensional generalization of maximally stable extremal regions - that provides a content-centric coordinate system for subsequent hash function computation, independent of any affine transformation or extensive cropping. Other key features include an efficient bin-based polling strategy for initial candidate selection, and a final SIFT feature-based computation for final verification. We describe the algorithm and its performance, and then discuss additional modifications that can provide further improvement to efficiency and accuracy.

  4. Robust Cultural Pluralism

    Directory of Open Access Journals (Sweden)

    Richard A. Shweder


    Full Text Available In this wide ranging interview, Professor Richard A. Shweder from the Department of Comparative Human Development at the University of Chicago, discusses whether it is or is not possible to be a robust cultural pluralist and a dedicated political liberal at the same time. In this discussion, Professor Shweder offers his insights - based on over 40 years of research - on issues related to the history and re-emergence of cultural psychology; moral anthropology and psychology; the experimental method in psychological investigation and its philosophical basis; contemporary and historical cultural collisions – most notably conflicting representations of female genital surgeries; cultural diversity and inequality; and the dissemination of ideas through open access publishing and Twitter. Professor Shweder ends by offering valuable advice to young researchers in the field of cultural psychology as well as a glimpse into the larger themes of his forthcoming book, which seeks to provide answers to the question of what forms of political liberalism are most compatible with robust cultural pluralism and which are not.

  5. Robustness Metrics: Consolidating the multiple approaches to quantify Robustness

    DEFF Research Database (Denmark)

    Göhler, Simon Moritz; Eifler, Tobias; Howard, Thomas J.


    determined to be conceptually different from one another. The metrics were classified by their meaning and interpretation based on the types of information necessary to calculate the metrics. Four different classes were identified: 1) Sensitivity robustness metrics; 2) Size of feasible design space......, this ambiguity can have significant influence on the strategies used to combat variability, the way it is quantified and ultimately, the quality of the final design. In this contribution the literature for robustness metrics was systematically reviewed. From the 108 relevant publications found, 38 metrics were...... robustness metrics; 3) Functional expectancy and dispersion robustness metrics; and 4) Probability of conformance robustness metrics. The goal was to give a comprehensive overview of robustness metrics and guidance to scholars and practitioners to understand the different types of robustness metrics...

  6. NPR-9, a Galanin-Like G-Protein Coupled Receptor, and GLR-1 Regulate Interneuronal Circuitry Underlying Multisensory Integration of Environmental Cues in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Jason C Campbell


    Full Text Available C. elegans inhabit environments that require detection of diverse stimuli to modulate locomotion in order to avoid unfavourable conditions. In a mammalian context, a failure to appropriately integrate environmental signals can lead to Parkinson's, Alzheimer's, and epilepsy. Provided that the circuitry underlying mammalian sensory integration can be prohibitively complex, we analyzed nematode behavioral responses in differing environmental contexts to evaluate the regulation of context dependent circuit reconfiguration and sensorimotor control. Our work has added to the complexity of a known parallel circuit, mediated by interneurons AVA and AIB, that integrates sensory cues and is responsible for the initiation of backwards locomotion. Our analysis of the galanin-like G-protein coupled receptor NPR-9 in C. elegans revealed that upregulation of galanin signaling impedes the integration of sensory evoked neuronal signals. Although the expression pattern of npr-9 is limited to AIB, upregulation of the receptor appears to impede AIB and AVA circuits to broadly prevent backwards locomotion, i.e. reversals, suggesting that these two pathways functionally interact. Galanin signaling similarly plays a broadly inhibitory role in mammalian models. Moreover, our identification of a mutant, which rarely initiates backwards movement, allowed us to interrogate locomotory mechanisms underlying chemotaxis. In support of the pirouette model of chemotaxis, organisms that did not exhibit reversal behavior were unable to navigate towards an attractant peak. We also assessed ionotropic glutamate receptor GLR-1 cell-specifically within AIB and determined that GLR-1 fine-tunes AIB activity to modify locomotion following reversal events. Our research highlights that signal integration underlying the initiation and fine-tuning of backwards locomotion is AIB and NPR-9 dependent, and has demonstrated the suitability of C. elegans for analysis of multisensory integration

  7. International Conference on Robust Statistics

    CERN Document Server

    Filzmoser, Peter; Gather, Ursula; Rousseeuw, Peter


    Aspects of Robust Statistics are important in many areas. Based on the International Conference on Robust Statistics 2001 (ICORS 2001) in Vorau, Austria, this volume discusses future directions of the discipline, bringing together leading scientists, experienced researchers and practitioners, as well as younger researchers. The papers cover a multitude of different aspects of Robust Statistics. For instance, the fundamental problem of data summary (weights of evidence) is considered and its robustness properties are studied. Further theoretical subjects include e.g.: robust methods for skewness, time series, longitudinal data, multivariate methods, and tests. Some papers deal with computational aspects and algorithms. Finally, the aspects of application and programming tools complete the volume.

  8. Robust procedures in chemometrics

    DEFF Research Database (Denmark)

    Kotwa, Ewelina

    -way chemometrical methods, such as PCA and PARAFAC models for analysing spatial and depth profiles of sea water samples, defined by three data modes: depth, variables and geographical location. Emphasis was also put on predicting fluorescence values, as being a natural measure of biological activity, by applying...... if contamination in the data is present. For this becoming a standard procedure, further work is required, aiming at implementing reliable robust algorithms into standard statistical programs.......The general aim of the thesis was to contribute to the improvement of data analytical techniques within the chemometric field. Regardless the multivariate structure of the data, it is still common in some fields to perform uni-variate data analysis using only simple statistics such as sample mean...

  9. Robust automated knowledge capture.

    Energy Technology Data Exchange (ETDEWEB)

    Stevens-Adams, Susan Marie; Abbott, Robert G.; Forsythe, James Chris; Trumbo, Michael Christopher Stefan; Haass, Michael Joseph; Hendrickson, Stacey M. Langfitt


    This report summarizes research conducted through the Sandia National Laboratories Robust Automated Knowledge Capture Laboratory Directed Research and Development project. The objective of this project was to advance scientific understanding of the influence of individual cognitive attributes on decision making. The project has developed a quantitative model known as RumRunner that has proven effective in predicting the propensity of an individual to shift strategies on the basis of task and experience related parameters. Three separate studies are described which have validated the basic RumRunner model. This work provides a basis for better understanding human decision making in high consequent national security applications, and in particular, the individual characteristics that underlie adaptive thinking.

  10. Robust Optical Flow Estimation

    Directory of Open Access Journals (Sweden)

    Javier Sánchez Pérez


    Full Text Available n this work, we describe an implementation of the variational method proposed by Brox etal. in 2004, which yields accurate optical flows with low running times. It has several benefitswith respect to the method of Horn and Schunck: it is more robust to the presence of outliers,produces piecewise-smooth flow fields and can cope with constant brightness changes. Thismethod relies on the brightness and gradient constancy assumptions, using the information ofthe image intensities and the image gradients to find correspondences. It also generalizes theuse of continuous L1 functionals, which help mitigate the effect of outliers and create a TotalVariation (TV regularization. Additionally, it introduces a simple temporal regularizationscheme that enforces a continuous temporal coherence of the flow fields.

  11. Robust snapshot interferometric spectropolarimetry. (United States)

    Kim, Daesuk; Seo, Yoonho; Yoon, Yonghee; Dembele, Vamara; Yoon, Jae Woong; Lee, Kyu Jin; Magnusson, Robert


    This Letter describes a Stokes vector measurement method based on a snapshot interferometric common-path spectropolarimeter. The proposed scheme, which employs an interferometric polarization-modulation module, can extract the spectral polarimetric parameters Ψ(k) and Δ(k) of a transmissive anisotropic object by which an accurate Stokes vector can be calculated in the spectral domain. It is inherently strongly robust to the object 3D pose variation, since it is designed distinctly so that the measured object can be placed outside of the interferometric module. Experiments are conducted to verify the feasibility of the proposed system. The proposed snapshot scheme enables us to extract the spectral Stokes vector of a transmissive anisotropic object within tens of msec with high accuracy.

  12. Robust Schur Stability and Robust H^2 Performance

    DEFF Research Database (Denmark)

    Stoustrup, Jakob; Zhao, K.-Y.


    In this paper we address the problems of robust stability androbust QTR H^2 performance for uncertain discrete time systemswith nonlinear parametric uncertainties. We consider two families ofsystems with parametric uncertainties described by state space modelswhich offer a fairly general...... providea line search algorithm for the these two problems in case of two parameters.Both for the robust stability and the robust performance probelm, explicitnecessary and sufficient conditions are derived. An illustrative exampledemonstrates the algorithms....

  13. Functional α7β2 nicotinic acetylcholine receptors expressed in hippocampal interneurons exhibit high sensitivity to pathological level of amyloid β peptides

    Directory of Open Access Journals (Sweden)

    Liu Qiang


    Full Text Available Abstract Background β-amyloid (Aβ accumulation is described as a hallmark of Alzheimer’s disease (AD. Aβ perturbs a number of synaptic components including nicotinic acetylcholine receptors containing α7 subunits (α7-nAChRs, which are abundantly expressed in the hippocampus and found on GABAergic interneurons. We have previously demonstrated the existence of a novel, heteromeric α7β2-nAChR in basal forebrain cholinergic neurons that exhibits high sensitivity to acute Aβ exposure. To extend our previous work, we evaluated the expression and pharmacology of α7β2-nAChRs in hippocampal interneurons and their sensitivity to Aβ. Results GABAergic interneurons in the CA1 subregion of the hippocampus expressed functional α7β2-nAChRs, which were characterized by relatively slow whole-cell current kinetics, pharmacological sensitivity to dihydro-β-erythroidine (DHβE, a nAChR β2* subunit selective blocker, and α7 and β2 subunit interaction using immunoprecipitation assay. In addition, α7β2-nAChRs were sensitive to 1 nM oligomeric Aβ. Similar effects were observed in identified hippocampal interneurons prepared from GFP-GAD mice. Conclusion These findings suggest that Aβ modulation of cholinergic signaling in hippocampal GABAergic interneurons via α7β2-nAChRs could be an early and critical event in Aβ-induced functional abnormalities of hippocampal function, which may be relevant to learning and memory deficits in AD.

  14. Robust cognitive change. (United States)

    Salthouse, Timothy A


    Two major challenges facing researchers interested in cognitive change are that measures of change are often not very reliable, and they may reflect effects of prior test experience in addition to the factors of primary interest. One approach to dealing with these problems is to obtain multiple measures of change on parallel versions of the same tests in a measurement burst design. A total of 783 adults performed three parallel versions of cognitive tests on two occasions separated by an average of 2.6 years. Performance increased substantially across the three sessions within each occasion, and for all but vocabulary ability these within-occasion improvements were considerably larger than the between-occasion changes. Reliabilities of the changes in composite scores were low, but averages of the three changes had larger, albeit still quite modest, reliabilities. In some cognitive abilities individual differences were evident in the relation of prior test experience and the magnitude of longitudinal change. Although multiple assessments are more time consuming than traditional measurement procedures, the resulting estimates of change are more robust than those from conventional methods, and also allow the influence of practice on change to be systematically investigated.

  15. Robust continuous clustering. (United States)

    Shah, Sohil Atul; Koltun, Vladlen


    Clustering is a fundamental procedure in the analysis of scientific data. It is used ubiquitously across the sciences. Despite decades of research, existing clustering algorithms have limited effectiveness in high dimensions and often require tuning parameters for different domains and datasets. We present a clustering algorithm that achieves high accuracy across multiple domains and scales efficiently to high dimensions and large datasets. The presented algorithm optimizes a smooth continuous objective, which is based on robust statistics and allows heavily mixed clusters to be untangled. The continuous nature of the objective also allows clustering to be integrated as a module in end-to-end feature learning pipelines. We demonstrate this by extending the algorithm to perform joint clustering and dimensionality reduction by efficiently optimizing a continuous global objective. The presented approach is evaluated on large datasets of faces, hand-written digits, objects, newswire articles, sensor readings from the Space Shuttle, and protein expression levels. Our method achieves high accuracy across all datasets, outperforming the best prior algorithm by a factor of 3 in average rank.

  16. Temporal processing of vibratory communication signals at the level of ascending interneurons in Nezara viridula (Hemiptera: Pentatomidae). (United States)

    Zorović, Maja


    During mating, males and females of N. viridula (Heteroptera: Pentatomidae) produce sex- and species-specific calling and courtship substrate-borne vibratory signals, grouped into songs. Recognition and localization of these signals are fundamental for successful mating. The recognition is mainly based on the temporal pattern, i.e. the amplitude modulation, while the frequency spectrum of the signals usually only plays a minor role. We examined the temporal selectivity for vibratory signals in four types of ascending vibratory interneurons in N. viridula. Using intracellular recording and labelling technique, we analyzed the neurons' responses to 30 pulse duration/interval duration (PD/ID) combinations. Two response arrays were created for each neuron type, showing the intensity of the responses either as time-averaged spike counts or as peak instantaneous spike rates. The mean spike rate response arrays showed preference of the neurons for short PDs (below 600 ms) and no selectivity towards interval duration; while the peak spike rate response arrays exhibited either short PD/long ID selectivity or no selectivity at all. The long PD/short ID combinations elicited the weakest responses in all neurons tested. No response arrays showed the receiver preference for either constant period or duty cycle. The vibratory song pattern selectivity matched the PD of N. viridula male vibratory signals, thus pointing to temporal filtering for the conspecific vibratory signals already at level of the ascending interneurons. In some neurons the responses elicited by the vibratory stimuli were followed by distinct, regular oscillations of the membrane potential. The distance between the oscillation peaks matched the temporal structure of the male calling song, indicating a possible resonance based mechanism for signal recognition.

  17. Differential alterations of kainate receptor subunits in inhibitory interneurons in the anterior cingulate cortex in schizophrenia and bipolar disorder. (United States)

    Woo, Tsung-Ung W; Shrestha, Kevin; Amstrong, Christopher; Minns, Martin M; Walsh, John P; Benes, Francine M


    The aim of this study was to examine whether glutamatergic inputs onto GABA interneurons via the kainate receptor in the anterior cingulate cortex may be altered in schizophrenia and bipolar disorder. Hence, in a cohort of 60 post-mortem human brains from schizophrenia, bipolar disorder, and normal control subjects, we simultaneously labeled the mRNA for the GluR5 or GluR6 subunit of the kainate receptor with [(35)S] and the mRNA for the 67 kD isoform of the GABA synthesizing enzyme glutamic acid decarboxylase (GAD)(67) with digoxigenin using an immunoperoxidase method. The density of the GAD(67) mRNA-containing neurons that co-expressed GluR5 mRNA was decreased by 43% and 40% in layer 2 of the anterior cingulate cortex in schizophrenia and bipolar disorder, respectively. In contrast, the density of the GAD(67) mRNA-containing cells that expressed GluR6 mRNA was unaltered in either condition. Furthermore, the amount of GluR5 or GluR6 mRNA in the GAD(67) mRNA-expressing cells that contained a detectable level of these transcripts was also unchanged. Finally, the density of cells that did not contain GAD(67) mRNA, which presumably included all pyramidal neurons, but expressed the mRNA for the GluR5 or GluR6 subunit was not altered. Thus, glutamatergic modulation of inhibitory interneurons, but not pyramidal neurons, via kainate receptors containing the GluR5 subunit appears to be selectively altered in the anterior cingulate cortex in schizophrenia and bipolar disorder.

  18. Population-specific regulation of Chmp2b by Lbx1 during onset of synaptogenesis in lateral association interneurons.

    Directory of Open Access Journals (Sweden)

    Jun Xu

    Full Text Available Chmp2b is closely related to Vps2, a key component of the yeast protein complex that creates the intralumenal vesicles of multivesicular bodies. Dominant negative mutations in Chmp2b cause autophagosome accumulation and neurodegenerative disease. Loss of Chmp2b causes failure of dendritic spine maturation in cultured neurons. The homeobox gene Lbx1 plays an essential role in specifying postmitotic dorsal interneuron populations during late pattern formation in the neural tube. We have discovered that Chmp2b is one of the most highly regulated cell-autonomous targets of Lbx1 in the embryonic mouse neural tube. Chmp2b was expressed and depended on Lbx1 in only two of the five nascent, Lbx1-expressing, postmitotic, dorsal interneuron populations. It was also expressed in neural tube cell populations that lacked Lbx1 protein. The observed population-specific expression of Chmp2b indicated that only certain population-specific combinations of sequence specific transcription factors allow Chmp2b expression. The cell populations that expressed Chmp2b corresponded, in time and location, to neurons that make the first synapses of the spinal cord. Chmp2b protein was transported into neurites within the motor- and association-neuropils, where the first synapses are known to form between E11.5 and E12.5 in mouse neural tubes. Selective, developmentally-specified gene expression of Chmp2b may therefore be used to endow particular neuronal populations with the ability to mature dendritic spines. Such a mechanism could explain how mammalian embryos reproducibly establish the disynaptic cutaneous reflex only between particular cell populations.

  19. Sparing of descending axons rescues interneuron plasticity in the lumbar cord to allow adaptive learning after thoracic spinal cord injury

    Directory of Open Access Journals (Sweden)

    Christopher Nelson Hansen


    Full Text Available This study evaluated the role of spared axons on structural and behavioral neuroplasticity in the lumbar enlargement after a thoracic spinal cord injury (SCI. Previous work has demonstrated that recovery in the presence of spared axons after an incomplete lesion increases behavioral output after a subsequent complete spinal cord transection (TX. This suggests that spared axons direct adaptive changes in below-level neuronal networks of the lumbar cord. In response to spared fibers, we postulate that lumbar neuron networks support behavioral gains by preventing aberrant plasticity. As such, the present study measured histological and functional changes in the isolated lumbar cord after complete TX or incomplete contusion (SCI. To measure functional plasticity in the lumbar cord, we used an established instrumental learning paradigm. In this paradigm, neural circuits within isolated lumbar segments demonstrate learning by an increase in flexion duration that reduces exposure to a noxious leg shock. We employed this model using a proof-of-principle design to evaluate the role of sparing on lumbar learning and plasticity early (7 days or late (42 days after midthoracic SCI in a rodent model. Early after SCI or TX at 7d, spinal learning was unattainable regardless of whether the animal recovered with or without axonal substrate. Failed learning occurred alongside measures of cell soma atrophy and aberrant dendritic spine expression within interneuron populations responsible for sensorimotor integration and learning. Alternatively, exposure of the lumbar cord to a small amount of spared axons for 6 weeks produced near-normal learning late after SCI. This coincided with greater cell soma volume and fewer aberrant dendritic spines on interneurons. Thus, an opportunity to influence activity-based learning in locomotor networks depends on spared axons limiting maladaptive plasticity. Together, this work identifies a time dependent interaction between

  20. Temporal processing of vibratory communication signals at the level of ascending interneurons in Nezara viridula (Hemiptera: Pentatomidae.

    Directory of Open Access Journals (Sweden)

    Maja Zorović

    Full Text Available During mating, males and females of N. viridula (Heteroptera: Pentatomidae produce sex- and species-specific calling and courtship substrate-borne vibratory signals, grouped into songs. Recognition and localization of these signals are fundamental for successful mating. The recognition is mainly based on the temporal pattern, i.e. the amplitude modulation, while the frequency spectrum of the signals usually only plays a minor role. We examined the temporal selectivity for vibratory signals in four types of ascending vibratory interneurons in N. viridula. Using intracellular recording and labelling technique, we analyzed the neurons' responses to 30 pulse duration/interval duration (PD/ID combinations. Two response arrays were created for each neuron type, showing the intensity of the responses either as time-averaged spike counts or as peak instantaneous spike rates. The mean spike rate response arrays showed preference of the neurons for short PDs (below 600 ms and no selectivity towards interval duration; while the peak spike rate response arrays exhibited either short PD/long ID selectivity or no selectivity at all. The long PD/short ID combinations elicited the weakest responses in all neurons tested. No response arrays showed the receiver preference for either constant period or duty cycle. The vibratory song pattern selectivity matched the PD of N. viridula male vibratory signals, thus pointing to temporal filtering for the conspecific vibratory signals already at level of the ascending interneurons. In some neurons the responses elicited by the vibratory stimuli were followed by distinct, regular oscillations of the membrane potential. The distance between the oscillation peaks matched the temporal structure of the male calling song, indicating a possible resonance based mechanism for signal recognition.

  1. Robustness Evaluation of Timber Structures

    DEFF Research Database (Denmark)

    Kirkegaard, Poul Henning; Sørensen, John Dalsgaard


    The present paper considers robustness evaluation of a Norwegian sports arena with a structural system of glulam frames. The robustness evaluation is based on the framework for robustness analysis introduced in the Danish Code of Practice for the Safety of Structures and a probabilistic modelling...... of the timber material proposed in the Probabilistic Model Code (PMC) of the Joint Committee on Structural Safety (JCSS). The results show that the requirements for robustness of the structure are highly related to the modelling of the snow load used on the structures when ‘removal of a limited part...

  2. Robust and distributed hypothesis testing

    CERN Document Server

    Gül, Gökhan


    This book generalizes and extends the available theory in robust and decentralized hypothesis testing. In particular, it presents a robust test for modeling errors which is independent from the assumptions that a sufficiently large number of samples is available, and that the distance is the KL-divergence. Here, the distance can be chosen from a much general model, which includes the KL-divergence as a very special case. This is then extended by various means. A minimax robust test that is robust against both outliers as well as modeling errors is presented. Minimax robustness properties of the given tests are also explicitly proven for fixed sample size and sequential probability ratio tests. The theory of robust detection is extended to robust estimation and the theory of robust distributed detection is extended to classes of distributions, which are not necessarily stochastically bounded. It is shown that the quantization functions for the decision rules can also be chosen as non-monotone. Finally, the boo...

  3. Robustness Evaluation of Timber Structures

    DEFF Research Database (Denmark)

    Kirkegaard, Poul Henning; Sørensen, John Dalsgaard


    Robustness of structural systems has obtained a renewed interest due to a much more frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure.......Robustness of structural systems has obtained a renewed interest due to a much more frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure....

  4. Robustness of IPTV business models

    NARCIS (Netherlands)

    Bouwman, H.; Zhengjia, M.; Duin, P. van der; Limonard, S.


    The final stage in the STOF method is an evaluation of the robustness of the design, for which the method provides some guidelines. For many innovative services, the future holds numerous uncertainties, which makes evaluating the robustness of a business model a difficult task. In this chapter, we

  5. An Intercompany Perspective on Biopharmaceutical Drug Product Robustness Studies. (United States)

    Morar-Mitrica, Sorina; Adams, Monica L; Crotts, George; Wurth, Christine; Ihnat, Peter M; Tabish, Tanvir; Antochshuk, Valentyn; DiLuzio, Willow; Dix, Daniel B; Fernandez, Jason E; Gupta, Kapil; Fleming, Michael S; He, Bing; Kranz, James K; Liu, Dingjiang; Narasimhan, Chakravarthy; Routhier, Eric; Taylor, Katherine D; Truong, Nobel; Stokes, Elaine S E


    The Biophorum Development Group (BPDG) is an industry-wide consortium enabling networking and sharing of best practices for the development of biopharmaceuticals. To gain a better understanding of current industry approaches for establishing biopharmaceutical drug product (DP) robustness, the BPDG-Formulation Point Share group conducted an intercompany collaboration exercise, which included a bench-marking survey and extensive group discussions around the scope, design, and execution of robustness studies. The results of this industry collaboration revealed several key common themes: (1) overall DP robustness is defined by both the formulation and the manufacturing process robustness; (2) robustness integrates the principles of quality by design (QbD); (3) DP robustness is an important factor in setting critical quality attribute control strategies and commercial specifications; (4) most companies employ robustness studies, along with prior knowledge, risk assessments, and statistics, to develop the DP design space; (5) studies are tailored to commercial development needs and the practices of each company. Three case studies further illustrate how a robustness study design for a biopharmaceutical DP balances experimental complexity, statistical power, scientific understanding, and risk assessment to provide the desired product and process knowledge. The BPDG-Formulation Point Share discusses identified industry challenges with regard to biopharmaceutical DP robustness and presents some recommendations for best practices. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  6. Robustness Analysis of Kinetic Structures

    DEFF Research Database (Denmark)

    Kirkegaard, Poul Henning; Sørensen, John Dalsgaard


    The present paper considers robustness of kinetic structures. Robustness of structures has obtained a renewed interest due to a much more frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure. Especially for these types of structural syst...... systems, it is of interest to investigate how robust the structures are, or what happens if a structural element is added to or removed from the original structure. The present paper discusses this issue for kinetic structures in architecture.......The present paper considers robustness of kinetic structures. Robustness of structures has obtained a renewed interest due to a much more frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure. Especially for these types of structural...

  7. Comparison of robust input shapers (United States)

    Vaughan, Joshua; Yano, Aika; Singhose, William


    The rapid movement of machines is a challenging control problem because it often results in high levels of vibration. As a result, flexible machines are typically moved relatively slowly. Input shaping is a control method that allows much higher speeds of motion by limiting vibration induced by the reference command. To design an input-shaping controller, estimates of the system natural frequency and damping ratio are required. However, real world systems cannot be modeled exactly, making the robustness to modeling errors an important consideration. Many robust input shapers have been developed, but robust shapers typically have longer durations that slow the system response. This creates a compromise between shaper robustness and rise time. This paper analyzes the compromise between rapidity of motion and shaper robustness for several input-shaping methods. Experimental results from a portable bridge crane verify the theoretical predictions.

  8. Theoretical Framework for Robustness Evaluation

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard


    This paper presents a theoretical framework for evaluation of robustness of structural systems, incl. bridges and buildings. Typically modern structural design codes require that ‘the consequence of damages to structures should not be disproportional to the causes of the damages’. However, although...... the importance of robustness for structural design is widely recognized the code requirements are not specified in detail, which makes the practical use difficult. This paper describes a theoretical and risk based framework to form the basis for quantification of robustness and for pre-normative guidelines...

  9. Robustness of airline route networks (United States)

    Lordan, Oriol; Sallan, Jose M.; Escorihuela, Nuria; Gonzalez-Prieto, David


    Airlines shape their route network by defining their routes through supply and demand considerations, paying little attention to network performance indicators, such as network robustness. However, the collapse of an airline network can produce high financial costs for the airline and all its geographical area of influence. The aim of this study is to analyze the topology and robustness of the network route of airlines following Low Cost Carriers (LCCs) and Full Service Carriers (FSCs) business models. Results show that FSC hubs are more central than LCC bases in their route network. As a result, LCC route networks are more robust than FSC networks.

  10. Aberrant Epigenetic Gene Regulation in GABAergic Interneuron Subpopulations in the Hippocampal Dentate Gyrus of Mouse Offspring Following Developmental Exposure to Hexachlorophene. (United States)

    Watanabe, Yousuke; Abe, Hajime; Nakajima, Kota; Ideta-Otsuka, Maky; Igarashi, Katsuhide; Woo, Gye-Hyeong; Yoshida, Toshinori; Shibutani, Makoto


    Maternal hexachlorophene (HCP) exposure causes transient disruption of hippocampal neurogenesis in mouse offspring. We examined epigenetically hypermethylated and downregulated genes related to this HCP-induced disrupted neurogenesis. Mated female mice were dietary exposed to 0 or 100 ppm HCP from gestational day 6 to postnatal day (PND) 21 on weaning. The hippocampal dentate gyrus of male offspring was subjected to methyl-capture sequencing and real-time reverse transcription-polymerase chain reaction analyses on PND 21. Validation analyses on methylation identified three genes, Dlx4, Dmrt1, and Plcb4, showing promoter-region hypermethylation. Immunohistochemically, DLX4+, DMRT1+, and PLCB4+ cells in the dentate hilus co-expressed GAD67, a γ-aminobutyric acid (GABA)ergic neuron marker. HCP decreased all of three subpopulations as well as GAD67+ cells on PND 21. PLCB4+ cells also co-expressed the metabotropic glutamate receptor, GRM1. HCP also decreased transcript level of synaptic plasticity-related genes in the dentate gyrus and immunoreactive granule cells for synaptic plasticity-related ARC. On PND 77, all immunohistochemical cellular density changes were reversed, whereas the transcript expression of the synaptic plasticity-related genes fluctuated. Thus, HCP-exposed offspring transiently reduced the number of GABAergic interneurons. Among them, subpopulations expressing DLX4, DMRT1, or PLCB4 were transiently reduced in number through an epigenetic mechanism. Considering the role of the Dlx gene family in GABAergic interneuron migration and differentiation, the decreased number of DLX4+ cells may be responsible for reducing those GABAergic interneurons regulating neurogenesis. The effect on granule cell synaptic plasticity was sustained until the adult stage, and reduced GABAergic interneurons active in GRM1-PLCB4 signaling may be responsible for the suppression on weaning.

  11. Differentiation and functional incorporation of embryonic stem cell-derived GABAergic interneurons in the dentate gyrus of mice with temporal lobe epilepsy. (United States)

    Maisano, Xu; Litvina, Elizabeth; Tagliatela, Stephanie; Aaron, Gloster B; Grabel, Laura B; Naegele, Janice R


    Cell therapies for neurological disorders require an extensive knowledge of disease-associated neuropathology and procedures for generating neurons for transplantation. In many patients with severe acquired temporal lobe epilepsy (TLE), the dentate gyrus exhibits sclerosis and GABAergic interneuron degeneration. Mounting evidence suggests that therapeutic benefits can be obtained by transplanting fetal GABAergic progenitors into the dentate gyrus in rodents with TLE, but the scarcity of human fetal cells limits applicability in patient populations. In contrast, virtually limitless quantities of neural progenitors can be obtained from embryonic stem (ES) cells. ES cell-based therapies for neurological repair in TLE require evidence that the transplanted neurons integrate functionally and replace cell types that degenerate. To address these issues, we transplanted mouse ES cell-derived neural progenitors (ESNPs) with ventral forebrain identities into the hilus of the dentate gyrus of mice with TLE and evaluated graft differentiation, mossy fiber sprouting, cellular morphology, and electrophysiological properties of the transplanted neurons. In addition, we compared electrophysiological properties of the transplanted neurons with endogenous hilar interneurons in mice without TLE. The majority of transplanted ESNPs differentiated into GABAergic interneuron subtypes expressing calcium-binding proteins parvalbumin, calbindin, or calretinin. Global suppression of mossy fiber sprouting was not observed; however, ESNP-derived neurons formed dense axonal arborizations in the inner molecular layer and throughout the hilus. Whole-cell hippocampal slice electrophysiological recordings and morphological analyses of the transplanted neurons identified five basic types; most with strong after-hyperpolarizations and smooth or sparsely spiny dendritic morphologies resembling endogenous hippocampal interneurons. Moreover, intracellular recordings of spontaneous EPSCs indicated that

  12. Robust methods for data reduction

    CERN Document Server

    Farcomeni, Alessio


    Robust Methods for Data Reduction gives a non-technical overview of robust data reduction techniques, encouraging the use of these important and useful methods in practical applications. The main areas covered include principal components analysis, sparse principal component analysis, canonical correlation analysis, factor analysis, clustering, double clustering, and discriminant analysis.The first part of the book illustrates how dimension reduction techniques synthesize available information by reducing the dimensionality of the data. The second part focuses on cluster and discriminant analy

  13. Inter-individual variation in reciprocal Ia inhibition is dependent on the descending volleys delivered from corticospinal neurons to Ia interneurons. (United States)

    Kubota, Shinji; Uehara, Kazumasa; Morishita, Takuya; Hirano, Masato; Funase, Kozo


    We investigated the extent to which the corticospinal inputs delivered to Ia inhibitory interneurons influence the strength of disynaptic reciprocal Ia inhibition. Seventeen healthy subjects participated in this study. The degree of reciprocal Ia inhibition was determined via short-latency (condition-test interval: 1-3ms) suppression of Sol H-reflex by conditioning stimulation of common peroneal nerve. The effect of corticospinal descending inputs on Ia inhibitory interneurons was assessed by evaluating the conditioning effect of transcranial magnetic stimulation (TMS) on the Sol H-reflex. Then, we determined the relationship between the degree of reciprocal Ia inhibition and the conditioning effect of TMS on the Sol H-reflex. We found that the degree of reciprocal Ia inhibition and the extent of change in the amplitude of the TMS-conditioned H-reflex, which was measured from short latency facilitation to inhibition, displayed a strong correlation (r=0.76, pIa inhibition is affected by the corticospinal descending inputs delivered to Ia inhibitory interneurons, which might explain the inter-individual variations in reciprocal Ia inhibition. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Ablation of fast-spiking interneurons in the dorsal striatum, recapitulating abnormalities seen post-mortem in Tourette syndrome, produces anxiety and elevated grooming. (United States)

    Xu, M; Li, L; Pittenger, C


    Tic disorders, including Tourette syndrome (TS), are thought to involve pathology of cortico-basal ganglia loops, but their pathology is not well understood. Post-mortem studies have shown a reduced number of several populations of striatal interneurons, including the parvalbumin-expressing fast-spiking interneurons (FSIs), in individuals with severe, refractory TS. We tested the causal role of this interneuronal deficit by recapitulating it in an otherwise normal adult mouse using a combination transgenic-viral cell ablation approach. FSIs were reduced bilaterally by ∼40%, paralleling the deficit found post-mortem. This did not produce spontaneous stereotypies or tic-like movements, but there was increased stereotypic grooming after acute stress in two validated paradigms. Stereotypy after amphetamine, in contrast, was not elevated. FSI ablation also led to increased anxiety-like behavior in the elevated plus maze, but not to alterations in motor learning on the rotorod or to alterations in prepulse inhibition, a measure of sensorimotor gating. These findings indicate that a striatal FSI deficit can produce stress-triggered repetitive movements and anxiety. These repetitive movements may recapitulate aspects of the pathophysiology of tic disorders. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Robustness of the Blandford-Znajek mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Palenzuela, Carlos [Canadian Institute for Theoretical Astrophysics, Toronto, Ontario M5S 3H8 (Canada); Bona, Carles [Institute for Applied Computing with Community Code (IAC3), Universitat de les Illes Balears, Palma de Mallorca 07122 (Spain); Lehner, Luis; Reula, Oscar, E-mail: [Department of Physics and Astronomy, Louisiana State University, Baton Rouge, LA 70802 (United States)


    The Blandford-Znajek (BZ) mechanism has long been regarded as a key ingredient in models attempting to explain powerful jets in AGNs, quasars, blazzars, etc. In such a mechanism, energy is extracted from a rotating black hole and dissipated at a load at far distances. In this work we examine the behavior of the BZ mechanism with respect to different boundary conditions, revealing the robustness of the mechanism upon variation of these conditions. Consequently, this work closes a gap in our understanding of this important scenario.

  16. Transplanted Human Stem Cell-Derived Interneuron Precursors Mitigate Mouse Bladder Dysfunction and Central Neuropathic Pain after Spinal Cord Injury. (United States)

    Fandel, Thomas M; Trivedi, Alpa; Nicholas, Cory R; Zhang, Haoqian; Chen, Jiadong; Martinez, Aida F; Noble-Haeusslein, Linda J; Kriegstein, Arnold R


    Neuropathic pain and bladder dysfunction represent significant quality-of-life issues for many spinal cord injury patients. Loss of GABAergic tone in the injured spinal cord may contribute to the emergence of these symptoms. Previous studies have shown that transplantation of rodent inhibitory interneuron precursors from the medial ganglionic eminence (MGE) enhances GABAergic signaling in the brain and spinal cord. Here we look at whether transplanted MGE-like cells derived from human embryonic stem cells (hESC-MGEs) can mitigate the pathological effects of spinal cord injury. We find that 6 months after transplantation into injured mouse spinal cords, hESC-MGEs differentiate into GABAergic neuron subtypes and receive synaptic inputs, suggesting functional integration into host spinal cord. Moreover, the transplanted animals show improved bladder function and mitigation of pain-related symptoms. Our results therefore suggest that this approach may be a valuable strategy for ameliorating the adverse effects of spinal cord injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Loss of Interneuron-Derived Collagen XIX Leads to a Reduction in Perineuronal Nets in the Mammalian Telencephalon. (United States)

    Su, Jianmin; Cole, James; Fox, Michael A


    Perineuronal nets (PNNs) are lattice-like supramolecular assemblies of extracellular glycoproteins that surround subsets of neuronal cell bodies in the mammalian telencephalon. PNNs emerge at the end of the critical period of brain development, limit neuronal plasticity in the adult brain, and are lost in a variety of complex brain disorders diseases, including schizophrenia. The link between PNNs and schizophrenia led us to question whether neuronally expressed extracellular matrix (ECM) molecules associated with schizophrenia contribute to the assembly of these specialized supramolecular ECM assemblies. We focused on collagen XIX-a minor, nonfibrillar collagen expressed by subsets of telencephalic interneurons. Genetic alterations in the region encoding collagen XIX have been associated with familial schizophrenia, and loss of this collagen in mice results in altered inhibitory synapses, seizures, and the acquisition of schizophrenia-related behaviors. Here, we demonstrate that loss of collagen XIX also results in a reduction of telencephalic PNNs. Loss of PNNs was accompanied with reduced levels of aggrecan (Acan), a major component of PNNs. Despite reduced levels of PNN constituents in collagen XIX-deficient mice ( col19a1 - / - ), we failed to detect reduced expression of genes encoding these ECM molecules. Instead, we discovered a widespread upregulation of extracellular proteases capable of cleaving Acan and other PNN constituents in col19a1 - / - brains. Taken together, these results suggest a mechanism by which the loss of collagen XIX speeds PNN degradation and they identify a novel mechanism by which the loss of collagen XIX may contribute to complex brain disorders.

  18. Activity blockade and GABAA receptor blockade produce synaptic scaling through chloride accumulation in embryonic spinal motoneurons and interneurons.

    Directory of Open Access Journals (Sweden)

    Casie Lindsly

    Full Text Available Synaptic scaling represents a process whereby the distribution of a cell's synaptic strengths are altered by a multiplicative scaling factor. Scaling is thought to be a compensatory response that homeostatically controls spiking activity levels in the cell or network. Previously, we observed GABAergic synaptic scaling in embryonic spinal motoneurons following in vivo blockade of either spiking activity or GABAA receptors (GABAARs. We had determined that activity blockade triggered upward GABAergic scaling through chloride accumulation, thus increasing the driving force for these currents. To determine whether chloride accumulation also underlies GABAergic scaling following GABAAR blockade we have developed a new technique. We expressed a genetically encoded chloride-indicator, Clomeleon, in the embryonic chick spinal cord, which provides a non-invasive fast measure of intracellular chloride. Using this technique we now show that chloride accumulation underlies GABAergic scaling following blockade of either spiking activity or the GABAAR. The finding that GABAAR blockade and activity blockade trigger scaling via a common mechanism supports our hypothesis that activity blockade reduces GABAAR activation, which triggers synaptic scaling. In addition, Clomeleon imaging demonstrated the time course and widespread nature of GABAergic scaling through chloride accumulation, as it was also observed in spinal interneurons. This suggests that homeostatic scaling via chloride accumulation is a common feature in many neuronal classes within the embryonic spinal cord and opens the possibility that this process may occur throughout the nervous system at early stages of development.

  19. Following Spinal Cord Injury Transected Reticulospinal Tract Axons Develop New Collateral Inputs to Spinal Interneurons in Parallel with Locomotor Recovery

    Directory of Open Access Journals (Sweden)

    Zacnicte May


    Full Text Available The reticulospinal tract (RtST descends from the reticular formation and terminates in the spinal cord. The RtST drives the initiation of locomotion and postural control. RtST axons form new contacts with propriospinal interneurons (PrINs after incomplete spinal cord injury (SCI; however, it is unclear if injured or uninjured axons make these connections. We completely transected all traced RtST axons in rats using a staggered model, where a hemisection SCI at vertebra T10 is followed by a contralateral hemisection at vertebra T7. In one group of the animals, the T7 SCI was performed 2 weeks after the T10 SCI (delayed; dSTAG, and in another group, the T10 and T7 SCIs were concomitant (cSTAG. dSTAG animals had significantly more RtST-PrIN contacts in the grey matter compared to cSTAG animals (p<0.05. These results were accompanied by enhanced locomotor recovery with dSTAG animals significantly outperforming cSTAG animals (BBB test; p<0.05. This difference suggests that activity in neuronal networks below the first SCI may contribute to enhanced recovery, because dSTAG rats recovered locomotor ability before the second hemisection. In conclusion, our findings support the hypothesis that the injured RtST forms new connections and is a key player in the recovery of locomotion post-SCI.

  20. Npas4 Regulates Mdm2 and thus Dcx in Experience-Dependent Dendritic Spine Development of Newborn Olfactory Bulb Interneurons

    Directory of Open Access Journals (Sweden)

    Sei-ichi Yoshihara


    Full Text Available Sensory experience regulates the development of various brain structures, including the cortex, hippocampus, and olfactory bulb (OB. Little is known about how sensory experience regulates the dendritic spine development of OB interneurons, such as granule cells (GCs, although it is well studied in mitral/tufted cells. Here, we identify a transcription factor, Npas4, which is expressed in OB GCs immediately after sensory input and is required for dendritic spine formation. Npas4 overexpression in OB GCs increases dendritic spine density, even under sensory deprivation, and rescues reduction of dendrite spine density in the Npas4 knockout OB. Furthermore, loss of Npas4 upregulates expression of the E3-ubiquitin ligase Mdm2, which ubiquitinates a microtubule-associated protein Dcx. This leads to reduction in the dendritic spine density of OB GCs. Together, these findings suggest that Npas4 regulates Mdm2 expression to ubiquitinate and degrade Dcx during dendritic spine development in newborn OB GCs after sensory experience.

  1. [Interneuronal relationships in the basolateral amygdala of cats trained for choice in the quality of food reinforcement]. (United States)

    Merzhanova, G Kh; Dolbakian, E E; Partev, A Z


    The alimentary instrumental conditioned bar-pressing reflex was elaborated in cats by the method of "active choice" of either short-delayed reinforcement with bread-meat mixture of delayed more valuable reinforcement with meat. The animals differed in behavior strategy: some animals preferred bar-pressing with the long delay (the so-called "self-control" group), other animals pressed the bar with short delay (the so-called "impulsive" group). The multiunit activity in the basolateral amygdala was recorded with chronically implanted nichrome microelectrodes. The interactions between the spike trains of the neighbouring neurons selected from the multiunit activity were evaluated by means of statistical crosscorrelation analysis. It was shown that the number of correlations between the discharges of neurons was significantly higher in the "impulsive" cats. In both groups the number of cross-correlations was maximal in cases of a difficult choice, i.e., during the omission of the conditioned bar-pressing response. In "impulsive" cats the number of interneuronal correlations was highest with the latencies in the range of 0-30 msec. We suggest that the basolateral amygdala is involved in the system of structures which determine the individual-typological characteristics of animals.

  2. Repeated Blockade of NMDA Receptors during Adolescence Impairs Reversal Learning and Disrupts GABAergic Interneurons in Rat Medial Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Jitao eLi


    Full Text Available Adolescence is of particular significance to schizophrenia, since psychosis onset typically occurs in this critical period. Based on the N-methyl-D-aspartate (NMDA receptor hypofunction hypothesis of schizophrenia, in this study, we investigated whether and how repeated NMDA receptor blockade during adolescence would affect GABAergic interneurons in rat medial prefrontal cortex (mPFC and mPFC-mediated cognitive functions. Specifically, adolescent rats were subjected to intraperitoneal administration of MK-801 (0.1, 0.2, 0.4 mg/kg, a non-competitive NMDA receptor antagonist, for 14 days and then tested for reference memory and reversal learning in the water maze. The density of parvabumin (PV-, calbindin (CB- and calretinin (CR-positive neurons in mPFC were analyzed at either 24 hours or 7 days after drug cessation. We found that MK-801 treatment delayed reversal learning in the water maze without affecting initial acquisition. Strikingly, MK-801 treatment also significantly reduced the density of PV+ and CB+ neurons, and this effect persisted for 7 days after drug cessation at the dose of 0.2 mg/kg. We further demonstrated that the reduction in PV+ and CB+ neuron densities was ascribed to a downregulation of the expression levels of PV and CB, but not to neuronal death. These results parallel the behavioral and neuropathological changes of schizophrenia and provide evidence that adolescent NMDA receptors antagonism offers a useful tool for unraveling the etiology of the disease.

  3. Delayed Maturation of Fast-Spiking Interneurons Is Rectified by Activation of the TrkB Receptor in the Mouse Model of Fragile X Syndrome. (United States)

    Nomura, Toshihiro; Musial, Timothy F; Marshall, John J; Zhu, Yiwen; Remmers, Christine L; Xu, Jian; Nicholson, Daniel A; Contractor, Anis


    Fragile X syndrome (FXS) is a neurodevelopmental disorder that is a leading cause of inherited intellectual disability, and the most common known cause of autism spectrum disorder. FXS is broadly characterized by sensory hypersensitivity and several developmental alterations in synaptic and circuit function have been uncovered in the sensory cortex of the mouse model of FXS ( Fmr1 KO). GABA-mediated neurotransmission and fast-spiking (FS) GABAergic interneurons are central to cortical circuit development in the neonate. Here we demonstrate that there is a delay in the maturation of the intrinsic properties of FS interneurons in the sensory cortex, and a deficit in the formation of excitatory synaptic inputs on to these neurons in neonatal Fmr1 KO mice. Both these delays in neuronal and synaptic maturation were rectified by chronic administration of a TrkB receptor agonist. These results demonstrate that the maturation of the GABAergic circuit in the sensory cortex is altered during a critical developmental period due in part to a perturbation in BDNF-TrkB signaling, and could contribute to the alterations in cortical development underlying the sensory pathophysiology of FXS. SIGNIFICANCE STATEMENT Fragile X (FXS) individuals have a range of sensory related phenotypes, and there is growing evidence of alterations in neuronal circuits in the sensory cortex of the mouse model of FXS ( Fmr1 KO). GABAergic interneurons are central to the correct formation of circuits during cortical critical periods. Here we demonstrate a delay in the maturation of the properties and synaptic connectivity of interneurons in Fmr1 KO mice during a critical period of cortical development. The delays both in cellular and synaptic maturation were rectified by administration of a TrkB receptor agonist, suggesting reduced BDNF-TrkB signaling as a contributing factor. These results provide evidence that the function of fast-spiking interneurons is disrupted due to a deficiency in neurotrophin

  4. Robust Watermarking of Cartographic Images

    Directory of Open Access Journals (Sweden)

    Mauro Barni


    Full Text Available We present a method (Text-Based Geometric Normalization—TBGN which, by exploiting the particular content of cartographic images, namely text content, permits to cope with global geometric transformations. First, text is extracted from the to-be-marked map, then text orientation and size are exploited to normalize the image geometry prior to watermark insertion. Watermarking is performed by means of any of the existing algorithms ensuring good robustness against image processing tools. At the decoder side, text is extracted again from the map and used to normalize image geometry. Owing to the robustness of text features with respect to common image manipulations, and to the likely spreading of text all across the digital map, the proposed system exhibits an excellent robustness.

  5. Robust estimation and hypothesis testing

    CERN Document Server

    Tiku, Moti L


    In statistical theory and practice, a certain distribution is usually assumed and then optimal solutions sought. Since deviations from an assumed distribution are very common, one cannot feel comfortable with assuming a particular distribution and believing it to be exactly correct. That brings the robustness issue in focus. In this book, we have given statistical procedures which are robust to plausible deviations from an assumed mode. The method of modified maximum likelihood estimation is used in formulating these procedures. The modified maximum likelihood estimators are explicit functions of sample observations and are easy to compute. They are asymptotically fully efficient and are as efficient as the maximum likelihood estimators for small sample sizes. The maximum likelihood estimators have computational problems and are, therefore, elusive. A broad range of topics are covered in this book. Solutions are given which are easy to implement and are efficient. The solutions are also robust to data anomali...

  6. Attractive ellipsoids in robust control

    CERN Document Server

    Poznyak, Alexander; Azhmyakov, Vadim


    This monograph introduces a newly developed robust-control design technique for a wide class of continuous-time dynamical systems called the “attractive ellipsoid method.” Along with a coherent introduction to the proposed control design and related topics, the monograph studies nonlinear affine control systems in the presence of uncertainty and presents a constructive and easily implementable control strategy that guarantees certain stability properties. The authors discuss linear-style feedback control synthesis in the context of the above-mentioned systems. The development and physical implementation of high-performance robust-feedback controllers that work in the absence of complete information is addressed, with numerous examples to illustrate how to apply the attractive ellipsoid method to mechanical and electromechanical systems. While theorems are proved systematically, the emphasis is on understanding and applying the theory to real-world situations. Attractive Ellipsoids in Robust Control will a...

  7. Advances in robust fractional control

    CERN Document Server

    Padula, Fabrizio


    This monograph presents design methodologies for (robust) fractional control systems. It shows the reader how to take advantage of the superior flexibility of fractional control systems compared with integer-order systems in achieving more challenging control requirements. There is a high degree of current interest in fractional systems and fractional control arising from both academia and industry and readers from both milieux are catered to in the text. Different design approaches having in common a trade-off between robustness and performance of the control system are considered explicitly. The text generalizes methodologies, techniques and theoretical results that have been successfully applied in classical (integer) control to the fractional case. The first part of Advances in Robust Fractional Control is the more industrially-oriented. It focuses on the design of fractional controllers for integer processes. In particular, it considers fractional-order proportional-integral-derivative controllers, becau...

  8. Robustness of digital artist authentication

    DEFF Research Database (Denmark)

    Jacobsen, Robert; Nielsen, Morten

    is in focus, while the robustness has not been considered, i.e. the degree to which the data collection process influences the decision of the method. However, in order for an authentication method to be successful in practice, it needs to be robust to plausible error sources from the data collection....... In this paper we investigate the robustness of the newly proposed authenticity method introduced by the authors based on second generation multiresolution analysis. This is done by modelling a number of realistic factors that can occur in the data collection.......In many cases it is possible to determine the authenticity of a painting from digital reproductions of the paintings; this has been demonstrated for a variety of artists and with different approaches. Common to all these methods in digital artist authentication is that the potential of the method...

  9. A Robust Enough Virtue Epistemology

    DEFF Research Database (Denmark)

    Broncano-Berrocal, Fernando


    What is the nature of knowledge? A popular answer to that long-standing question comes from robust virtue epistemology, whose key idea is that knowing is just a matter of succeeding cognitively—i.e., coming to believe a proposition truly—due to an exercise of cognitive ability. Versions of robust...... virtue epistemology further developing and systematizing this idea offer different accounts of the relation that must hold between an agent’s cognitive success and the exercise of her cognitive abilities as well as of the very nature of those abilities. This paper aims to give a new robust virtue...... epistemological account of knowledge based on a different understanding of the nature and structure of the kind of abilities that give rise to knowledge....

  10. Robust Portfolio Optimization Using Pseudodistances (United States)


    The presence of outliers in financial asset returns is a frequently occurring phenomenon which may lead to unreliable mean-variance optimized portfolios. This fact is due to the unbounded influence that outliers can have on the mean returns and covariance estimators that are inputs in the optimization procedure. In this paper we present robust estimators of mean and covariance matrix obtained by minimizing an empirical version of a pseudodistance between the assumed model and the true model underlying the data. We prove and discuss theoretical properties of these estimators, such as affine equivariance, B-robustness, asymptotic normality and asymptotic relative efficiency. These estimators can be easily used in place of the classical estimators, thereby providing robust optimized portfolios. A Monte Carlo simulation study and applications to real data show the advantages of the proposed approach. We study both in-sample and out-of-sample performance of the proposed robust portfolios comparing them with some other portfolios known in literature. PMID:26468948

  11. On Robustness of Power Grids

    NARCIS (Netherlands)

    Koç, Y.


    Current and future trends in environmental, economical, and human-caused factors (such as power demand growth, over-ageing of assets in power grids, and extreme weather conditions) challenge power grid robustness in the near future, necessitating research to better analyse and understand the notion

  12. Network Robustness: the whole story (United States)

    Longjas, A.; Tejedor, A.; Zaliapin, I. V.; Ambroj, S.; Foufoula-Georgiou, E.


    A multitude of actual processes operating on hydrological networks may exhibit binary outcomes such as clean streams in a river network that may become contaminated. These binary outcomes can be modeled by node removal processes (attacks) acting in a network. Network robustness against attacks has been widely studied in fields as diverse as the Internet, power grids and human societies. However, the current definition of robustness is only accounting for the connectivity of the nodes unaffected by the attack. Here, we put forward the idea that the connectivity of the affected nodes can play a crucial role in proper evaluation of the overall network robustness and its future recovery from the attack. Specifically, we propose a dual perspective approach wherein at any instant in the network evolution under attack, two distinct networks are defined: (i) the Active Network (AN) composed of the unaffected nodes and (ii) the Idle Network (IN) composed of the affected nodes. The proposed robustness metric considers both the efficiency of destroying the AN and the efficiency of building-up the IN. This approach is motivated by concrete applied problems, since, for example, if we study the dynamics of contamination in river systems, it is necessary to know both the connectivity of the healthy and contaminated parts of the river to assess its ecological functionality. We show that trade-offs between the efficiency of the Active and Idle network dynamics give rise to surprising crossovers and re-ranking of different attack strategies, pointing to significant implications for decision making.

  13. Approximability of Robust Network Design

    NARCIS (Netherlands)

    Olver, N.K.; Shepherd, F.B.


    We consider robust (undirected) network design (RND) problems where the set of feasible demands may be given by an arbitrary convex body. This model, introduced by Ben-Ameur and Kerivin [Ben-Ameur W, Kerivin H (2003) New economical virtual private networks. Comm. ACM 46(6):69-73], generalizes the

  14. Mental Models: A Robust Definition (United States)

    Rook, Laura


    Purpose: The concept of a mental model has been described by theorists from diverse disciplines. The purpose of this paper is to offer a robust definition of an individual mental model for use in organisational management. Design/methodology/approach: The approach adopted involves an interdisciplinary literature review of disciplines, including…

  15. Robust Optimization of Database Queries

    Indian Academy of Sciences (India)



    Jul 6, 2011 ... join order [ ((S R) C) or ((R C) S) ? ] join techniques [ Nested-Loops or Sort-Merge or Hash ? ] ○ DBMS query optimizer identifies the optimal. ○ DBMS query optimizer identifies the optimal evaluation strategy: “query execution plan”. July 2011. Robust Query Optimization (IASc Mid-year Meeting). 6 ...

  16. Robust control design with MATLAB

    CERN Document Server

    Gu, Da-Wei; Konstantinov, Mihail M


    Robust Control Design with MATLAB® (second edition) helps the student to learn how to use well-developed advanced robust control design methods in practical cases. To this end, several realistic control design examples from teaching-laboratory experiments, such as a two-wheeled, self-balancing robot, to complex systems like a flexible-link manipulator are given detailed presentation. All of these exercises are conducted using MATLAB® Robust Control Toolbox 3, Control System Toolbox and Simulink®. By sharing their experiences in industrial cases with minimum recourse to complicated theories and formulae, the authors convey essential ideas and useful insights into robust industrial control systems design using major H-infinity optimization and related methods allowing readers quickly to move on with their own challenges. The hands-on tutorial style of this text rests on an abundance of examples and features for the second edition: ·        rewritten and simplified presentation of theoretical and meth...

  17. A robust adaptive robot controller

    NARCIS (Netherlands)

    Berghuis, Harry; Berghuis, Harry; Ortega, Romeo; Nijmeijer, Henk


    A globally convergent adaptive control scheme for robot motion control with the following features is proposed. First, the adaptation law possesses enhanced robustness with respect to noisy velocity measurements. Second, the controller does not require the inclusion of high gain loops that may

  18. Facial Symmetry in Robust Anthropometrics

    Czech Academy of Sciences Publication Activity Database

    Kalina, Jan


    Roč. 57, č. 3 (2012), s. 691-698 ISSN 0022-1198 R&D Projects: GA MŠk(CZ) 1M06014 Institutional research plan: CEZ:AV0Z10300504 Keywords : forensic science * anthropology * robust image analysis * correlation analysis * multivariate data * classification Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 1.244, year: 2012

  19. Robust multiplatform RF emitter localization (United States)

    Al Issa, Huthaifa; Ordóñez, Raúl


    In recent years, position based services has increase. Thus, recent developments in communications and RF technology have enabled system concept formulations and designs for low-cost radar systems using state-of-the-art software radio modules. This research is done to investigate a novel multi-platform RF emitter localization technique denoted as Position-Adaptive RF Direction Finding (PADF). The formulation is based on the investigation of iterative path-loss (i.e., Path Loss Exponent, or PLE) metrics estimates that are measured across multiple platforms in order to autonomously adapt (i.e. self-adjust) of the location of each distributed/cooperative platform. Experiments conducted at the Air-Force Research laboratory (AFRL) indicate that this position-adaptive approach exhibits potential for accurate emitter localization in challenging embedded multipath environments such as in urban environments. The focus of this paper is on the robustness of the distributed approach to RF-based location tracking. In order to localize the transmitter, we use the Received Signal Strength Indicator (RSSI) data to approximate distance from the transmitter to the revolving receivers. We provide an algorithm for on-line estimation of the Path Loss Exponent (PLE) that is used in modeling the distance based on Received Signal Strength (RSS) measurements. The emitter position estimation is calculated based on surrounding sensors RSS values using Least-Square Estimation (LSE). The PADF has been tested on a number of different configurations in the laboratory via the design and implementation of four IRIS wireless sensor nodes as receivers and one hidden sensor as a transmitter during the localization phase. The robustness of detecting the transmitters position is initiated by getting the RSSI data through experiments and then data manipulation in MATLAB will determine the robustness of each node and ultimately that of each configuration. The parameters that are used in the functions are

  20. The subcellular distribution of T-type Ca2+ channels in interneurons of the lateral geniculate nucleus. (United States)

    Allken, Vaneeda; Chepkoech, Joy-Loi; Einevoll, Gaute T; Halnes, Geir


    Inhibitory interneurons (INs) in the lateral geniculate nucleus (LGN) provide both axonal and dendritic GABA output to thalamocortical relay cells (TCs). Distal parts of the IN dendrites often enter into complex arrangements known as triadic synapses, where the IN dendrite plays a dual role as postsynaptic to retinal input and presynaptic to TC dendrites. Dendritic GABA release can be triggered by retinal input, in a highly localized process that is functionally isolated from the soma, but can also be triggered by somatically elicited Ca(2+)-spikes and possibly by backpropagating action potentials. Ca(2+)-spikes in INs are predominantly mediated by T-type Ca(2+)-channels (T-channels). Due to the complex nature of the dendritic signalling, the function of the IN is likely to depend critically on how T-channels are distributed over the somatodendritic membrane (T-distribution). To study the relationship between the T-distribution and several IN response properties, we here run a series of simulations where we vary the T-distribution in a multicompartmental IN model with a realistic morphology. We find that the somatic response to somatic current injection is facilitated by a high T-channel density in the soma-region. Conversely, a high T-channel density in the distal dendritic region is found to facilitate dendritic signalling in both the outward direction (increases the response in distal dendrites to somatic input) and the inward direction (the soma responds stronger to distal synaptic input). The real T-distribution is likely to reflect a compromise between several neural functions, involving somatic response patterns and dendritic signalling.

  1. Ovarian cycle-linked plasticity of δ-GABAA receptor subunits in hippocampal interneurons affects γ oscillations in vivo

    Directory of Open Access Journals (Sweden)

    Albert Miklos Barth


    Full Text Available GABAA receptors containing δ subunits (δ-GABAARs are GABA-gated ion channels with extra- and perisynaptic localization, strong sensitivity to neurosteroids (NS, and a high degree of plasticity. In selective brain regions they are expressed on specific principal cells and interneurons (INs, and generate a tonic conductance that controls neuronal excitability and oscillations. Plasticity of δ-GABAARs in principal cells has been described during states of altered NS synthesis including acute stress, puberty, ovarian cycle, pregnancy and the postpartum period, with direct consequences on neuronal excitability and network dynamics. The defining network events implicated in cognitive function, memory formation and encoding are γ oscillations (30-120 Hz, a well-timed loop of excitation and inhibition between principal cells and PV-expressing INs (PV+INs. The δ-GABAARs of INs can modify γ oscillations, and a lower expression of δ-GABAARs on INs during pregnancy alters γ frequency recorded in vitro. The ovarian cycle is another physiological event with large fluctuations in NS levels and δ-GABAARs. Stages of the cycle are paralleled by swings in memory performance, cognitive function, and mood in both humans and rodents. Here we show δ-GABAARs changes during the mouse ovarian cycle in hippocampal cell types, with enhanced expression during diestrus in principal cells and specific INs. The plasticity of δ-GABAARs on PV-INs decreases the magnitude of γ oscillations continuously recorded in area CA1 throughout several days in vivo during diestrus and increases it during estrus. Such recurring changes in γ magnitude were not observed in non-cycling wild-type (WT females, cycling females lacking δ-GABAARs only on PV-INs (PV-Gabrd-/-, and in male mice during a time course equivalent to the ovarian cycle. Our findings may explain the impaired memory and cognitive performance experienced by women with premenstrual syndrome (PMS or premenstrual

  2. Balanced plasticity and stability of the electrical properties of a molluscan modulatory interneuron after classical conditioning: a computational study

    Directory of Open Access Journals (Sweden)

    Dimitris Vavoulis


    Full Text Available The Cerebral Giant Cells (CGCs are a pair of identified modulatory interneurons in the Central Nervous System of the pond snail Lymnaea stagnalis with an important role in the expression of both unconditioned and conditioned feeding behavior. Following single-trial food-reward classical conditioning, the membrane potential of the CGCs becomes persistently depolarized. This depolarization contributes to the conditioned response by facilitating sensory cell to command neuron synapses, which results in the activation of the feeding network by the conditioned stimulus. Despite the depolarization of the membrane potential, which enables the CGGs to play a key role in learning-induced network plasticity, there is no persistent change in the tonic firing rate or shape of the action potentials, allowing these neurons to retain their normal network function in feeding. In order to understand the ionic mechanisms of this novel combination of plasticity and stability of intrinsic electrical properties, we first constructed and validated a Hodgkin-Huxley-type model of the CGCs. We then used this model to elucidate how learning-induced changes in a somal persistent sodium and a delayed rectifier potassium current lead to a persistent depolarization of the CGCs whilst maintaining their firing rate. Including in the model an additional increase in the conductance of a high-voltage-activated calcium current allowed the spike amplitude and spike duration also to be maintained after conditioning. We conclude therefore that a balanced increase in three identified conductances is sufficient to explain the electrophysiological changes found in the CGCs after classical conditioning.

  3. Robust Reliability or reliable robustness? - Integrated consideration of robustness and reliability aspects

    DEFF Research Database (Denmark)

    Kemmler, S.; Eifler, Tobias; Bertsche, B.


    products are and vice versa. For a comprehensive understanding and to use existing synergies between both domains, this paper discusses the basic principles of Reliability- and Robust Design theory. The development of a comprehensive model will enable an integrated consideration of both domains...

  4. Afferent drive of medial prefrontal cortex by hippocampus and amygdala is altered in MAM-treated rats: evidence for interneuron dysfunction. (United States)

    Esmaeili, Behnaz; Grace, Anthony A


    Evidence indicates that the prefrontal cortex and its regulation by afferent inputs are disrupted in schizophrenia. Using a validated rat model of schizophrenia based on prenatal administration of the mitotoxin methyl azoxymethanol acetate (MAM), we examined the convergent projections from the ventral hippocampus (vHipp) and the basolateral amygdala (BLA) in the medial prefrontal cortex (mPFC). In vivo extracellular recordings were done in anesthetized rats to assess how prior stimulation of the BLA or vHipp input to the mPFC affected mPFC responses to subsequent stimulation of these regions. The interstimulus interval (ISI) of the BLA and vHipp pulse stimulation was varied randomly between 0 and 130 ms, and the probability of evoked spike response in the mPFC measured. We found that BLA input increased vHipp-evoked spike probability at ISIs 40-130 ms, but decreased spike probability at ISIs 10-20 ms. This would be consistent with activation of inhibitory interneurons at shorter ISIs by BLA stimulation. In contrast, in MAM-treated rats BLA stimulation increased vHipp-evoked spike probability in mPFC at all ISIs tested. Given that interneurons are driven primarily by N-methyl-D-aspartate (NMDA) channel activation, the effects of the NMDA channel blocker, phencyclidine (PCP), were tested. PCP was found to completely attenuate the inhibitory effect of BLA input on vHipp-evoked responses in mPFC at shorter ISIs, causing the response in control rats treated with PCP to resemble that observed in the MAM rat. In contrast to the effects of BLA stimulation on vHipp-mPFC-evoked responses, there was no inhibitory period when examining the effects of vHipp stimulation on BLA-mPFC-evoked responses in control rats, but in MAM-treated rats there was a significant inhibition at short intervals. Thus, both affective input arising from the BLA and context-dependent input from the vHipp exert a modulatory effect on mPFC neural activity in response to these inputs. Whereas the

  5. Time organization of frontal-motor cortex interneuron interactions in the cat neocortex in conditions of different levels of food motivation. (United States)

    Merzhanova, G Kh; Dolbakyan, E E


    Studies were carried out in conscious cats with recording of multicellular activity in moderate hunger and after 24-h food deprivation. Cross-correlation analysis was used to assess statistical interneuron interactions between closely-located neurons in the frontal and sensorimotor regions of the neocortex (local networks), and between the cells of these regions (distributed networks). One-day food deprivation increased the number of interactions formed within both local and distributed neuron networks. Increases in intercortical connections between the frontal and motor regions was seen at all time intervals studied (0-100 msec), though the most significant changes occurred at time intervals of up to 30 msec.

  6. cAMP-dependent protein kinase inhibits α7 nicotinic receptor activity in layer 1 cortical interneurons through activation of D1/D5 dopamine receptors. (United States)

    Komal, Pragya; Estakhr, Jasem; Kamran, Melad; Renda, Anthony; Nashmi, Raad


    Protein kinases can modify the function of many proteins including ion channels. However, the role of protein kinase A in modifying nicotinic receptors in the CNS has never been investigated. We showed through whole-cell recordings of layer 1 prefrontal cortical interneurons that α7 nicotinic responses are negatively modulated by protein kinase A. Furthermore, we show that stimulation of dopamine receptors can similarly attenuate α7 nicotinic responses through the activation of protein kinase A. These results suggest how the interaction of the cholinergic and dopaminergic systems may influence neuronal excitability in the brain. Phosphorylation of ion channels, including nicotinic acetylcholine receptors (nAChRs), by protein kinases plays a key role in the modification of synaptic transmission and neuronal excitability. α7 nAChRs are the second most prevalent nAChR subtype in the CNS following α4β2. Serine 365 in the M3-M4 cytoplasmic loop of the α7 nAChR is a phosphorylation site for protein kinase A (PKA). D1/D5 dopamine receptors signal through the adenylate cyclase-PKA pathway and play a key role in working memory and attention in the prefrontal cortex. Thus, we examined whether the dopaminergic system, mediated through PKA, functionally interacts with the α7-dependent cholinergic neurotransmission. In layer 1 interneurons of mouse prefrontal cortex, α7 nicotinic currents were decreased upon stimulation with 8-Br-cAMP, a PKA activator. In HEK 293T cells, dominant negative PKA abolished 8-Br-cAMP's effect of diminishing α7 nicotinic currents, while a constitutively active PKA catalytic subunit decreased α7 currents. In brain slices, the PKA inhibitor KT-5720 nullified 8-Br-cAMP's effect of attenuating α7 nicotinic responses, while applying a PKA catalytic subunit in the pipette solution decreased α7 currents. 8-Br-cAMP stimulation reduced surface expression of α7 nAChRs, but there was no change in single-channel conductance. The D1/D5 dopamine

  7. A Robust Design Applicability Model

    DEFF Research Database (Denmark)

    Ebro, Martin; Lars, Krogstie; Howard, Thomas J.


    This paper introduces a model for assessing the applicability of Robust Design (RD) in a project or organisation. The intention of the Robust Design Applicability Model (RDAM) is to provide support for decisions by engineering management considering the relevant level of RD activities...... to be applicable in organisations assigning a high importance to one or more factors that are known to be impacted by RD, while also experiencing a high level of occurrence of this factor. The RDAM supplements existing maturity models and metrics to provide a comprehensive set of data to support management....... The applicability assessment is based on two considerations: 1) Whether there is a correlation between the factors that are important to the project or organisation and the factors that impact from the use of RD and 2) What is the occurrence level of the given factor in the organisation. The RDAM defines RD...

  8. Robust Decentralized Formation Flight Control

    Directory of Open Access Journals (Sweden)

    Zhao Weihua


    Full Text Available Motivated by the idea of multiplexed model predictive control (MMPC, this paper introduces a new framework for unmanned aerial vehicles (UAVs formation flight and coordination. Formulated using MMPC approach, the whole centralized formation flight system is considered as a linear periodic system with control inputs of each UAV subsystem as its periodic inputs. Divided into decentralized subsystems, the whole formation flight system is guaranteed stable if proper terminal cost and terminal constraints are added to each decentralized MPC formulation of the UAV subsystem. The decentralized robust MPC formulation for each UAV subsystem with bounded input disturbances and model uncertainties is also presented. Furthermore, an obstacle avoidance control scheme for any shape and size of obstacles, including the nonapriorily known ones, is integrated under the unified MPC framework. The results from simulations demonstrate that the proposed framework can successfully achieve robust collision-free formation flights.

  9. Robust statistics for image deconvolution (United States)

    Lee, M. A.; Budavári, T.; White, R. L.; Gulian, C.


    We present a blind multiframe image-deconvolution method based on robust statistics. The usual shortcomings of iterative optimization of the likelihood function are alleviated by minimizing the M-scale of the residuals, which achieves more uniform convergence across the image. We focus on the deconvolution of astronomical images, which are among the most challenging due to their huge dynamic ranges and the frequent presence of large noise-dominated regions in the images. We show that high-quality image reconstruction is possible even in super-resolution and without the use of traditional regularization terms. Using a robust ρ-function is straightforward to implement in a streaming setting and, hence our method is applicable to the large volumes of astronomy images. The power of our method is demonstrated on observations from the Sloan Digital Sky Survey (Stripe 82) and we briefly discuss the feasibility of a pipeline based on Graphical Processing Units for the next generation of telescope surveys.

  10. Testing Heteroscedasticity in Robust Regression

    Czech Academy of Sciences Publication Activity Database

    Kalina, Jan


    Roč. 1, č. 4 (2011), s. 25-28 ISSN 2045-3345 Grant - others:GA ČR(CZ) GA402/09/0557 Institutional research plan: CEZ:AV0Z10300504 Keywords : robust regression * heteroscedasticity * regression quantiles * diagnostics Subject RIV: BB - Applied Statistics , Operational Research

  11. Robust power system frequency control

    CERN Document Server

    Bevrani, Hassan


    This updated edition of the industry standard reference on power system frequency control provides practical, systematic and flexible algorithms for regulating load frequency, offering new solutions to the technical challenges introduced by the escalating role of distributed generation and renewable energy sources in smart electric grids. The author emphasizes the physical constraints and practical engineering issues related to frequency in a deregulated environment, while fostering a conceptual understanding of frequency regulation and robust control techniques. The resulting control strategi

  12. Robust flight control of rotorcraft (United States)

    Pechner, Adam Daniel

    With recent design improvement in fixed wing aircraft, there has been a considerable interest in the design of robust flight control systems to compensate for the inherent instability necessary to achieve desired performance. Such systems are designed for maximum available retention of stability and performance in the presence of significant vehicle damage or system failure. The rotorcraft industry has shown similar interest in adopting these reconfigurable flight control schemes specifically because of their ability to reject disturbance inputs and provide a significant amount of robustness for all but the most catastrophic of situations. The research summarized herein focuses on the extension of the pseudo-sliding mode control design procedure interpreted in the frequency domain. Application of the technique is employed and simulated on two well known helicopters, a simplified model of a hovering Sikorsky S-61 and the military's Black Hawk UH-60A also produced by Sikorsky. The Sikorsky helicopter model details are readily available and was chosen because it can be limited to pitch and roll motion reducing the number of degrees of freedom and yet contains two degrees of freedom, which is the minimum requirement in proving the validity of the pseudo-sliding control technique. The full order model of a hovering Black Hawk system was included both as a comparison to the S-61 helicopter design system and as a means to demonstrate the scaleability and effectiveness of the control technique on sophisticated systems where design robustness is of critical concern.

  13. Mathematics revealed

    CERN Document Server

    Berman, Elizabeth


    Mathematics Revealed focuses on the principles, processes, operations, and exercises in mathematics.The book first offers information on whole numbers, fractions, and decimals and percents. Discussions focus on measuring length, percent, decimals, numbers as products, addition and subtraction of fractions, mixed numbers and ratios, division of fractions, addition, subtraction, multiplication, and division. The text then examines positive and negative numbers and powers and computation. Topics include division and averages, multiplication, ratios, and measurements, scientific notation and estim

  14. Neuregulin repellent signaling via ErbB4 restricts GABAergic interneurons to migratory paths from ganglionic eminence to cortical destinations

    Directory of Open Access Journals (Sweden)

    Li Hao


    Full Text Available Abstract Background Cortical GABAergic interneurons (INs are generated in the medial ganglionic eminence (MGE and migrate tangentially into cortex. Because most, if not all, migrating MGE-derived INs express the neuregulin (NRG receptor, ErbB4, we investigated influences of Nrg1 isoforms and Nrg3 on IN migration through ventral telencephalon (vTel and within cortex. Results During IN migration, NRG expression domains and distributions of ErbB4-expressing, MGE-derived INs are complementary with minimal overlap, both in vTel and cortex. In wild-type mice, within fields of NRG expression, these INs are focused at positions of low or absent NRG expression. However, in ErbB4-/- HER4heart mutant mice in which INs lack ErbB4, these complementary patterns are degraded with considerable overlap evident between IN distribution and NRG expression domains. These findings suggest that NRGs are repellents for migrating ErbB4-expressing INs, a function supported by in vitro and in vivo experiments. First, in collagen co-cultures, MGE-derived cells preferentially migrate away from a source of secreted NRGs. Second, cells migrating from wild-type MGE explants on living forebrain slices from wild-type embryonic mice tend to avoid endogenous NRG expression domains, whereas this avoidance behavior is not exhibited by ErbB4-deficient cells migrating from MGE explants and instead they have a radial pattern with a more uniform distribution. Third, ectopic NRG expression in the IN migration pathway produced by in utero electroporation blocks IN migration and results in cortex distal to the blockade being largely devoid of INs. Finally, fewer INs reach cortex in ErbB4 mutants, indicating that NRG-ErbB4 signaling is required for directing IN migration from the MGE to cortex. Conclusions Our results show that NRGs act as repellents for migrating ErbB4-expressing, MGE-derived GABAergic INs and that the patterned expression of NRGs funnels INs as they migrate from the MGE

  15. Robustness Analysis of Timber Truss Structure

    DEFF Research Database (Denmark)

    Rajčić, Vlatka; Čizmar, Dean; Kirkegaard, Poul Henning


    The present paper discusses robustness of structures in general and the robustness requirements given in the codes. Robustness of timber structures is also an issues as this is closely related to Working group 3 (Robustness of systems) of the COST E55 project. Finally, an example of a robustness...... evaluation of a widespan timber truss structure is presented. This structure was built few years ago near Zagreb and has a span of 45m. Reliability analysis of the main members and the system is conducted and based on this a robustness analysis is preformed....

  16. Computational modeling of distinct neocortical oscillations driven by cell-type selective optogenetic drive: Separable resonant circuits controlled by low-threshold spiking and fast-spiking interneurons

    Directory of Open Access Journals (Sweden)

    Dorea Vierling-Claassen


    Full Text Available Selective optogenetic drive of fast spiking interneurons (FS leads to enhanced local field potential (LFP power across the traditional gamma frequency band (20-80Hz; Cardin et al., 2009. In contrast, drive to regular-spiking pyramidal cells (RS enhances power at lower frequencies, with a peak at 8 Hz. The first result is consistent with previous computational studies emphasizing the role of FS and the time constant of GABAA synaptic inhibition in gamma rhythmicity. However, the same theoretical models do not typically predict low-frequency LFP enhancement with RS drive. To develop hypotheses as to how the same network can support these contrasting behaviors, we constructed a biophysically principled network model of primary somatosensory neocortex containing FS, RS and low-threshold-spiking (LTS interneurons. Cells were modeled with detailed cell anatomy and physiology, multiple dendritic compartments, and included active somatic and dendritic ionic currents. Consistent with prior studies, the model demonstrated gamma resonance during FS drive, dependent on the time-constant of GABAA inhibition induced by synchronous FS activity. Lower frequency enhancement during RS drive was replicated only on inclusion of an inhibitory LTS population, whose activation was critically dependent on RS synchrony and evoked longer-lasting inhibition. Our results predict that differential recruitment of FS and LTS inhibitory populations is essential to the observed cortical dynamics and may provide a means for amplifying the natural expression of distinct oscillations in normal cortical processing.

  17. Prolonged response to calling songs by the L3 auditory interneuron in female crickets (Acheta domesticus): possible roles in regulating phonotactic threshold and selectiveness for call carrier frequency. (United States)

    Bronsert, Michael; Bingol, Hilary; Atkins, Gordon; Stout, John


    L3, an auditory interneuron in the prothoracic ganglion of female crickets (Acheta domesticus) exhibited two kinds of responses to models of the male's calling song (CS): a previously described, phasically encoded immediate response; a more tonically encoded prolonged response. The onset of the prolonged response required 3-8 sec of stimulation to reach its maximum spiking rate and 6-20 sec to decay once the calling song ceased. It did not encode the syllables of the chirp. The prolonged response was sharply selective for the 4-5 kHz carrier frequency of the male's calling songs and its threshold tuning matched the threshold tuning of phonotaxis, while the immediate response of the same neuron was broadly tuned to a wide range of carrier frequencies. The thresholds for the prolonged response covaried with the changing phonotactic thresholds of 2- and 5-day-old females. Treatment of females with juvenile hormone reduced the thresholds for both phonotaxis and the prolonged response by equivalent amounts. Of the 3 types of responses to CSs provided by the ascending L1 and L3 auditory interneurons, the threshold for L3's prolonged response, on average, best matched the same females phonotactic threshold. The prolonged response was stimulated by inputs from both ears while L3's immediate response was driven only from its axon-ipsilateral ear. The prolonged response was not selective for either the CS's syllable period or chirp rate. Copyright 2003 Wiley-Liss, Inc.

  18. NOX2 Mediated-Parvalbumin Interneuron Loss Might Contribute to Anxiety-Like and Enhanced Fear Learning Behavior in a Rat Model of Post-Traumatic Stress Disorder. (United States)

    Liu, Fang-Fang; Yang, Lin-Dong; Sun, Xiao-Ru; Zhang, Hui; Pan, Wei; Wang, Xing-Ming; Yang, Jian-Jun; Ji, Mu-Huo; Yuan, Hong-Mei


    Post-traumatic stress disorder (PTSD) is a common psychiatric disease following exposure to a severe traumatic event or physiological stress, yet the precise mechanisms underlying PTSD remains largely to be determined. Using an animal model of PTSD induced by a single prolonged stress (SPS), we assessed the role of hippocampal nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and parvalbumin (PV) interneurons in the development of PTSD symptoms. In the present study, behavioral tests were performed by the open field (day 13 after SPS) and fear conditioning tests (days 13 and 14 after SPS). For the interventional study, rats were chronically treated with a NADPH oxidase inhibitor apocynin either by early or delayed administration. The levels of tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, IL-10, malondialdehyde, superoxide dismutase, NOX2, 4-hydroxynonenal, and PV in the hippocampus were measured at the indicated time points. In the present study, we showed that SPS rats displayed anxiety-like and enhanced fear learning behavior, which was accompanied by the increased expressions of malondialdehyde, IL-6, NOX2, 4-hydroxynonenal, and decreased PV expression. Notably, early but not delayed treatment with apocynin reversed all these abnormalities after SPS. In conclusion, our results provided evidence that NOX2 activation in the hippocampus, at least in part, contributes to oxidative stress and neuroinflammation, which further results in PV interneuron loss and consequent PTSD symptoms in a rat model of PTSD induced by SPS.

  19. Sustainable Resilient, Robust & Resplendent Enterprises

    DEFF Research Database (Denmark)

    Edgeman, Rick

    to their impact. Resplendent enterprises are introduced with resplendence referring not to some sort of public or private façade, but instead refers to organizations marked by dual brilliance and nobility of strategy, governance and comportment that yields superior and sustainable triple bottom line performance....... Herein resilience, robustness, and resplendence (R3) are integrated with sustainable enterprise excellence (Edgeman and Eskildsen, 2013) or SEE and social-ecological innovation (Eskildsen and Edgeman, 2012) to aid progress of a firm toward producing continuously relevant performance that proceed from...

  20. Robustness Evaluation of Timber Structures

    DEFF Research Database (Denmark)

    Kirkegaard, Poul Henning; Sørensen, John Dalsgaard; Cizmar, D.


    The present paper outlines results from working group 3 (WG3) in the EU COST Action E55 – ‘Modelling of the performance of timber structures’. The objectives of the project are related to the three main research activities: the identification and modelling of relevant load and environmental expos...... exposure scenarios, the improvement of knowledge concerning the behaviour of timber structural elements and the development of a generic framework for the assessment of the life-cycle vulnerability and robustness of timber structures....

  1. Robust Software Architecture for Robots (United States)

    Aghazanian, Hrand; Baumgartner, Eric; Garrett, Michael


    Robust Real-Time Reconfigurable Robotics Software Architecture (R4SA) is the name of both a software architecture and software that embodies the architecture. The architecture was conceived in the spirit of current practice in designing modular, hard, realtime aerospace systems. The architecture facilitates the integration of new sensory, motor, and control software modules into the software of a given robotic system. R4SA was developed for initial application aboard exploratory mobile robots on Mars, but is adaptable to terrestrial robotic systems, real-time embedded computing systems in general, and robotic toys.

  2. Robust Instrumentation[Water treatment for power plant]; Robust Instrumentering

    Energy Technology Data Exchange (ETDEWEB)

    Wik, Anders [Vattenfall Utveckling AB, Stockholm (Sweden)


    Cementa Slite Power Station is a heat recovery steam generator (HRSG) with moderate steam data; 3.0 MPa and 420 deg C. The heat is recovered from Cementa, a cement industry, without any usage of auxiliary fuel. The Power station commenced operation in 2001. The layout of the plant is unusual, there are no similar in Sweden and very few world-wide, so the operational experiences are limited. In connection with the commissioning of the power plant a R and D project was identified with the objective to minimise the manpower needed for chemistry management of the plant. The lean chemistry management is based on robust instrumentation and chemical-free water treatment plant. The concept with robust instrumentation consists of the following components; choice of on-line instrumentation with a minimum of O and M and a chemical-free water treatment. The parameters are specific conductivity, cation conductivity, oxygen and pH. In addition to that, two fairly new on-line instruments were included; corrosion monitors and differential pH calculated from specific and cation conductivity. The chemical-free water treatment plant consists of softening, reverse osmosis and electro-deionisation. The operational experience shows that the cycle chemistry is not within the guidelines due to major problems with the operation of the power plant. These problems have made it impossible to reach steady state and thereby not viable to fully verify and validate the concept with robust instrumentation. From readings on the panel of the online analysers some conclusions may be drawn, e.g. the differential pH measurements have fulfilled the expectations. The other on-line analysers have been working satisfactorily apart from contamination with turbine oil, which has been noticed at least twice. The corrosion monitors seem to be working but the lack of trend curves from the mainframe computer system makes it hard to draw any clear conclusions. The chemical-free water treatment has met all

  3. Perspective: Evolution and detection of genetic robustness

    NARCIS (Netherlands)

    Visser, de J.A.G.M.; Hermisson, J.; Wagner, G.P.; Ancel Meyers, L.; Bagheri-Chaichian, H.; Blanchard, J.L.; Chao, L.; Cheverud, J.M.; Elena, S.F.; Fontana, W.; Gibson, G.; Hansen, T.F.; Krakauer, D.; Lewontin, R.C.; Ofria, C.; Rice, S.H.; Dassow, von G.; Wagner, A.; Whitlock, M.C.


    Robustness is the invariance of phenotypes in the face of perturbation. The robustness of phenotypes appears at various levels of biological organization, including gene expression, protein folding, metabolic flux, physiological homeostasis, development, and even organismal fitness. The mechanisms

  4. Robust distributed cognitive relay beamforming

    KAUST Repository

    Pandarakkottilil, Ubaidulla


    In this paper, we present a distributed relay beamformer design for a cognitive radio network in which a cognitive (or secondary) transmit node communicates with a secondary receive node assisted by a set of cognitive non-regenerative relays. The secondary nodes share the spectrum with a licensed primary user (PU) node, and each node is assumed to be equipped with a single transmit/receive antenna. The interference to the PU resulting from the transmission from the cognitive nodes is kept below a specified limit. The proposed robust cognitive relay beamformer design seeks to minimize the total relay transmit power while ensuring that the transceiver signal-to-interference- plus-noise ratio and PU interference constraints are satisfied. The proposed design takes into account a parameter of the error in the channel state information (CSI) to render the performance of the beamformer robust in the presence of imperfect CSI. Though the original problem is non-convex, we show that the proposed design can be reformulated as a tractable convex optimization problem that can be solved efficiently. Numerical results are provided and illustrate the performance of the proposed designs for different network operating conditions and parameters. © 2012 IEEE.

  5. Robust excitation power spectrum design for broadband impedance spectroscopy

    International Nuclear Information System (INIS)

    Sanchez, B; Rojas, C R


    This paper focuses on the robust design of broadband impedance spectroscopy (IS) experiments. This contribution extends the optimal IS experiment design presented in previous work (Sanchez et al 2012 Meas. Sci. Technol. 23 085702) in order to design a robust broadband excitation which gives relatively good estimation performance over a large number of possible impedance models. To this end, we assume as prior knowledge that the parameters of the impedance model lie in a compact set. Then, we pose the experiment design problem as a convex optimization program, which gives the excitation signal of bounded power that minimizes the worst value of a given scalar function of the Fisher information matrix, as the parameters range over the given compact set. Supported by numerical simulations, our results reveal the robust excitation for impedance experiments has a discrete power spectrum, e.g. (periodic) multisine signals. (paper)

  6. Methodology in robust and nonparametric statistics

    CERN Document Server

    Jurecková, Jana; Picek, Jan


    Introduction and SynopsisIntroductionSynopsisPreliminariesIntroductionInference in Linear ModelsRobustness ConceptsRobust and Minimax Estimation of LocationClippings from Probability and Asymptotic TheoryProblemsRobust Estimation of Location and RegressionIntroductionM-EstimatorsL-EstimatorsR-EstimatorsMinimum Distance and Pitman EstimatorsDifferentiable Statistical FunctionsProblemsAsymptotic Representations for L-Estimators

  7. Robust Adaptive Synchronization of Ring Configured Uncertain Chaotic FitzHugh–Nagumo Neurons under Direction-Dependent Coupling

    Directory of Open Access Journals (Sweden)

    Muhammad Iqbal


    Full Text Available This paper exploits the dynamical modeling, behavior analysis, and synchronization of a network of four different FitzHugh–Nagumo (FHN neurons with unknown parameters linked in a ring configuration under direction-dependent coupling. The main purpose is to investigate a robust adaptive control law for the synchronization of uncertain and perturbed neurons, communicating in a medium of bidirectional coupling. The neurons are assumed to be different and interconnected in a ring structure. The strength of the gap junctions is taken to be different for each link in the network, owing to the inter-neuronal coupling medium properties. Robust adaptive control mechanism based on Lyapunov stability analysis is employed and theoretical criteria are derived to realize the synchronization of the network of four FHN neurons in a ring form with unknown parameters under direction-dependent coupling and disturbances. The proposed scheme for synchronization of dissimilar neurons, under external electrical stimuli, coupled in a ring communication topology, having all parameters unknown, and subject to directional coupling medium and perturbations, is addressed for the first time as per our knowledge. To demonstrate the efficacy of the proposed strategy, simulation results are provided.

  8. Robust Adaptive Synchronization of Ring Configured Uncertain Chaotic FitzHugh–Nagumo Neurons under Direction-Dependent Coupling (United States)

    Iqbal, Muhammad; Rehan, Muhammad; Hong, Keum-Shik


    This paper exploits the dynamical modeling, behavior analysis, and synchronization of a network of four different FitzHugh–Nagumo (FHN) neurons with unknown parameters linked in a ring configuration under direction-dependent coupling. The main purpose is to investigate a robust adaptive control law for the synchronization of uncertain and perturbed neurons, communicating in a medium of bidirectional coupling. The neurons are assumed to be different and interconnected in a ring structure. The strength of the gap junctions is taken to be different for each link in the network, owing to the inter-neuronal coupling medium properties. Robust adaptive control mechanism based on Lyapunov stability analysis is employed and theoretical criteria are derived to realize the synchronization of the network of four FHN neurons in a ring form with unknown parameters under direction-dependent coupling and disturbances. The proposed scheme for synchronization of dissimilar neurons, under external electrical stimuli, coupled in a ring communication topology, having all parameters unknown, and subject to directional coupling medium and perturbations, is addressed for the first time as per our knowledge. To demonstrate the efficacy of the proposed strategy, simulation results are provided. PMID:29535622

  9. Robust network topologies for generating switch-like cellular responses.

    Directory of Open Access Journals (Sweden)

    Najaf A Shah


    Full Text Available Signaling networks that convert graded stimuli into binary, all-or-none cellular responses are critical in processes ranging from cell-cycle control to lineage commitment. To exhaustively enumerate topologies that exhibit this switch-like behavior, we simulated all possible two- and three-component networks on random parameter sets, and assessed the resulting response profiles for both steepness (ultrasensitivity and extent of memory (bistability. Simulations were used to study purely enzymatic networks, purely transcriptional networks, and hybrid enzymatic/transcriptional networks, and the topologies in each class were rank ordered by parametric robustness (i.e., the percentage of applied parameter sets exhibiting ultrasensitivity or bistability. Results reveal that the distribution of network robustness is highly skewed, with the most robust topologies clustering into a small number of motifs. Hybrid networks are the most robust in generating ultrasensitivity (up to 28% and bistability (up to 18%; strikingly, a purely transcriptional framework is the most fragile in generating either ultrasensitive (up to 3% or bistable (up to 1% responses. The disparity in robustness among the network classes is due in part to zero-order ultrasensitivity, an enzyme-specific phenomenon, which repeatedly emerges as a particularly robust mechanism for generating nonlinearity and can act as a building block for switch-like responses. We also highlight experimentally studied examples of topologies enabling switching behavior, in both native and synthetic systems, that rank highly in our simulations. This unbiased approach for identifying topologies capable of a given response may be useful in discovering new natural motifs and in designing robust synthetic gene networks.

  10. Robustness of muscle synergies during visuomotor adaptation

    Directory of Open Access Journals (Sweden)

    Reinhard eGentner


    Full Text Available During visuomotor adaptation a novel mapping between visual targets and motor commands is gradually acquired. How muscle activation patterns are affected by this process is an open question. We tested whether the structure of muscle synergies is preserved during adaptation to a visuomotor rotation. Eight subjects applied targeted isometric forces on a handle instrumented with a force transducer while electromyographic (EMG activity was recorded from 13 shoulder and elbow muscles. The recorded forces were mapped into horizontal displacements of a virtual sphere with simulated mass, elasticity, and damping. The task consisted of moving the sphere to a target at one of eight equally spaced directions. Subjects performed three baseline blocks of 32 trials, followed by six blocks with a 45° CW rotation applied to the planar force, and finally three wash-out blocks without the perturbation. The sphere position at 100 ms after movement onset revealed significant directional error at the beginning of the rotation, a gradual learning in subsequent blocks, and aftereffects at the beginning of the wash-out. The change in initial force direction was closely related to the change in directional tuning of the initial EMG activity of most muscles. Throughout the experiment muscle synergies extracted using a non-negative matrix factorization algorithm from the muscle patterns recorded during the baseline blocks could reconstruct the muscle patterns of all other blocks with an accuracy significantly higher than chance indicating structural robustness. In addition, the synergies extracted from individual blocks remained similar to the baseline synergies throughout the experiment. Thus synergy structure is robust during visuomotor adaptation suggesting that changes in muscle patterns are obtained by rotating the directional tuning of the synergy recruitment.

  11. A Bicriteria Approach for Robust Timetabling (United States)

    Schöbel, Anita; Kratz, Albrecht

    Finding robust solutions of an optimization problem is an important issue in practice. Various concepts on how to define the robustness of an algorithm or of a solution have been suggested. However, there is always a trade-off between the best possible solution and a robust solution, called the price of robustness. In this paper, we analyze this trade-off using the following bicriteria approach. We treat an optimization problem as a bicriteria problem adding the robustness of its solution as an additional objective function. We demonstrate this approach at the aperiodic timetabling problem in which a timetable which is robust under delays is sought. We are able to derive necessary conditions for the resulting Pareto-optimal timetables. For the case in which the robustness is defined as the largest delay for which all connections are maintained we show the bicriteria problem can be solved with the same time complexity as the original single-criteria problem.

  12. A robust multivariate long run analysis of European electricity prices


    Bruno Bosco; Lucia Parisio; Matteo Pelagatti; Fabio Baldi


    This paper analyses the interdependencies existing in wholesale electricity prices in six major European countries. The results of our robust multivariate long run dynamic analysis reveal the presence of four highly integrated central European markets (France, Germany, the Netherlands and Austria). The trend shared by these four electricity markets appears to be common also to gas prices, but not to oil prices. The existence of long term dynamics among electricity prices and between electrici...

  13. Building Robust Systems with Fallible Construction (Elaboration de systemes informatiques robustes a l’architecutre faillible) (United States)


    IST-047 Building Robust Systems with Fallible Construction (Elaboration de systèmes informatiques robustes à l’architecture faillible) Final...IST-047 Building Robust Systems with Fallible Construction (Elaboration de systèmes informatiques robustes à l’architecture faillible...and cost investments. ES - 2 RTO-TR-IST-047 Elaboration de systèmes informatiques robustes à l’architecture faillible (RTO-TR-IST-047

  14. The opposite effects of nandrolone decanoate and exercise on anxiety levels in rats may involve alterations in hippocampal parvalbumin-positive interneurons.

    Directory of Open Access Journals (Sweden)

    Dragica Selakovic

    Full Text Available The aim of this study was to evaluate the behavioral effects of chronic (six weeks nandrolone decanoate (ND, 20 mg/kg, s.c., weekly in single dose administration (in order to mimic heavy human abuse, and exercise (swimming protocol of 60 minutes a day, five days in a row/two days break, applied alone and simultaneously with ND, in male rats (n = 40. Also, we evaluated the effects of those protocols on hippocampal parvalbumin (PV content and the possible connection between the alterations in certain parts of hippocampal GABAergic system and behavioral patterns. Both ND and exercise protocols induced increase in testosterone, dihydrotestosterone and estradiol blood levels. Our results confirmed anxiogenic effects of ND observed in open field (OF test (decrease in the locomotor activity, as well as in frequency and cumulative duration in the centre zone and in elevated plus maze (EPM test (decrease in frequency and cumulative duration in open arms, and total exploratory activity, that were accompanied with a mild decrease in the number of PV interneurons in hippocampus. Chronic exercise protocol induced significant increase in hippocampal PV neurons (dentate gyrus and CA1 region, followed by anxiolytic-like behavioral changes, observed in both OF and EPM (increase in all estimated parameters, and in evoked beam-walking test (increase in time to cross the beam, compared to ND treated animals. The applied dose of ND was sufficient to attenuate beneficial effects of exercise in rats by means of decreased exercise-induced anxiolytic effect, as well as to reverse exercise-induced augmentation in number of PV immunoreactive neurons in hippocampus. Our results implicate the possibility that alterations in hippocampal PV interneurons (i.e. GABAergic system may be involved in modulation of anxiety level induced by ND abuse and/or extended exercise protocols.

  15. Synaptic Conductance Estimates of the Connection Between Local Inhibitor Interneurons and Pyramidal Neurons in Layer 2/3 of a Cortical Column (United States)

    Hoffmann, Jochen H.O.; Meyer, H. S.; Schmitt, Arno C.; Straehle, Jakob; Weitbrecht, Trinh; Sakmann, Bert; Helmstaedter, Moritz


    Stimulation of a principal whisker yields sparse action potential (AP) spiking in layer 2/3 (L2/3) pyramidal neurons in a cortical column of rat barrel cortex. The low AP rates in pyramidal neurons could be explained by activation of interneurons in L2/3 providing inhibition onto L2/3 pyramidal neurons. L2/3 interneurons classified as local inhibitors based on their axonal projection in the same column were reported to receive strong excitatory input from spiny neurons in L4, which are also the main source of the excitatory input to L2/3 pyramidal neurons. Here, we investigated the remaining synaptic connection in this intracolumnar microcircuit. We found strong and reliable inhibitory synaptic transmission between intracolumnar L2/3 local-inhibitor-to-L2/3 pyramidal neuron pairs [inhibitory postsynaptic potential (IPSP) amplitude −0.88 ± 0.67 mV]. On average, 6.2 ± 2 synaptic contacts were made by L2/3 local inhibitors onto L2/3 pyramidal neurons at 107 ± 64 µm path distance from the pyramidal neuron soma, thus overlapping with the distribution of synaptic contacts from L4 spiny neurons onto L2/3 pyramidal neurons (67 ± 34 µm). Finally, using compartmental simulations, we determined the synaptic conductance per synaptic contact to be 0.77 ± 0.4 nS. We conclude that the synaptic circuit from L4 to L2/3 can provide efficient shunting inhibition that is temporally and spatially aligned with the excitatory input from L4 to L2/3. PMID:25761638

  16. Efficient robust conditional random fields. (United States)

    Song, Dongjin; Liu, Wei; Zhou, Tianyi; Tao, Dacheng; Meyer, David A


    Conditional random fields (CRFs) are a flexible yet powerful probabilistic approach and have shown advantages for popular applications in various areas, including text analysis, bioinformatics, and computer vision. Traditional CRF models, however, are incapable of selecting relevant features as well as suppressing noise from noisy original features. Moreover, conventional optimization methods often converge slowly in solving the training procedure of CRFs, and will degrade significantly for tasks with a large number of samples and features. In this paper, we propose robust CRFs (RCRFs) to simultaneously select relevant features. An optimal gradient method (OGM) is further designed to train RCRFs efficiently. Specifically, the proposed RCRFs employ the l1 norm of the model parameters to regularize the objective used by traditional CRFs, therefore enabling discovery of the relevant unary features and pairwise features of CRFs. In each iteration of OGM, the gradient direction is determined jointly by the current gradient together with the historical gradients, and the Lipschitz constant is leveraged to specify the proper step size. We show that an OGM can tackle the RCRF model training very efficiently, achieving the optimal convergence rate [Formula: see text] (where k is the number of iterations). This convergence rate is theoretically superior to the convergence rate O(1/k) of previous first-order optimization methods. Extensive experiments performed on three practical image segmentation tasks demonstrate the efficacy of OGM in training our proposed RCRFs.

  17. Robustness Validation in Service-Oriented Architectures (United States)

    Laranjeiro, Nuno; Vieira, Marco; Madeira, Henrique

    The use of Service Oriented Architecture (SOA) in enterprise applications development is increasing very quickly. In a SOA environment providers supply a set of services that must be robust. Although SOA is being used in business-critical environments, there is no practical means to measure or compare the robustness of services. Robustness failures in such environments are dangerous, as they can be maliciously exploited with severe consequences for the attacked systems. This chapter addresses the problem of robustness validation in SOA environments. The approach proposed is based on a set of robustness tests that is used to discover both programming and design errors. Two concrete examples are presented: one focusing on web services and the other targeting Java Message Service (JMS) middleware. The proposed approach is useful for both providers (to validate the robustness of deployed services) and consumers (to select the services that best fit architectural requirements).

  18. Robustness of Long Span Reciprocal Timber Structures

    DEFF Research Database (Denmark)

    Balfroid, Nathalie; Kirkegaard, Poul Henning; Sassone, Mario SASSONE


    engineer may take necessary steps to design robust structures that are insensitive to accidental circumstances. The present paper makes a discussion of such robustness issues related to the future development of reciprocal timber structures. The paper concludes that these kind of structures can have...... a potential as long span timber structures in real projects if they are carefully designed with respect to the overall robustness strategies....

  19. Molecular mechanisms of robustness in plants. (United States)

    Lempe, Janne; Lachowiec, Jennifer; Sullivan, Alessandra M; Queitsch, Christine


    Robustness, the ability of organisms to buffer phenotypes against perturbations, has drawn renewed interest among developmental biologists and geneticists. A growing body of research supports an important role of robustness in the genotype to phenotype translation, with far-reaching implications for evolutionary processes and disease susceptibility. Similar to animals and fungi, plant robustness is a function of genetic network architecture. Most perturbations are buffered; however, perturbation of network hubs destabilizes many traits. Here, we review recent advances in identifying molecular robustness mechanisms in plants that have been enabled by a combination of classical genetics and population genetics with genome-scale data. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. A Survey on Robustness in Railway Planning

    DEFF Research Database (Denmark)

    Lusby, Richard Martin; Larsen, Jesper; Bull, Simon Henry


    in the quality of solutions to individual planning problems, and of operations in general. Robustness in general is the capacity for some system to absorb or resist changes. In the context of railway robustness it is often taken to be the capacity for operations to continue at some level when faced...... with a disruption such as delay or failure. This has resulted in more attention given to the inclusion of robustness measures and objectives in individual planning problems, and to the providing of tools to ensure operations continue under disrupted situations. In this paper we survey the literature on robustness...

  1. Robustness: confronting lessons from physics and biology. (United States)

    Lesne, Annick


    The term robustness is encountered in very different scientific fields, from engineering and control theory to dynamical systems to biology. The main question addressed herein is whether the notion of robustness and its correlates (stability, resilience, self-organisation) developed in physics are relevant to biology, or whether specific extensions and novel frameworks are required to account for the robustness properties of living systems. To clarify this issue, the different meanings covered by this unique term are discussed; it is argued that they crucially depend on the kind of perturbations that a robust system should by definition withstand. Possible mechanisms underlying robust behaviours are examined, either encountered in all natural systems (symmetries, conservation laws, dynamic stability) or specific to biological systems (feedbacks and regulatory networks). Special attention is devoted to the (sometimes counterintuitive) interrelations between robustness and noise. A distinction between dynamic selection and natural selection in the establishment of a robust behaviour is underlined. It is finally argued that nested notions of robustness, relevant to different time scales and different levels of organisation, allow one to reconcile the seemingly contradictory requirements for robustness and adaptability in living systems.

  2. Robust and efficient walking with spring-like legs

    International Nuclear Information System (INIS)

    Rummel, J; Blum, Y; Seyfarth, A


    The development of bipedal walking robots is inspired by human walking. A way of implementing walking could be performed by mimicking human leg dynamics. A fundamental model, representing human leg dynamics during walking and running, is the bipedal spring-mass model which is the basis for this paper. The aim of this study is the identification of leg parameters leading to a compromise between robustness and energy efficiency in walking. It is found that, compared to asymmetric walking, symmetric walking with flatter angles of attack reveals such a compromise. With increasing leg stiffness, energy efficiency increases continuously. However, robustness is the maximum at moderate leg stiffness and decreases slightly with increasing stiffness. Hence, an adjustable leg compliance would be preferred, which is adaptable to the environment. If the ground is even, a high leg stiffness leads to energy efficient walking. However, if external perturbations are expected, e.g. when the robot walks on uneven terrain, the leg should be softer and the angle of attack flatter. In the case of underactuated robots with constant physical springs, the leg stiffness should be larger than k-tilde = 14 in order to use the most robust gait. Soft legs, however, lack in both robustness and efficiency.

  3. In Silico Design of Robust Bolalipid Membranes

    NARCIS (Netherlands)

    Bulacu, Monica; Periole, Xavier; Marrink, Siewert J.; Périole, Xavier

    The robustness of microorganisms used in industrial fermentations is essential for the efficiency and yield of the production process. A viable tool to increase the robustness is through engineering of the cell membrane and especially by incorporating lipids from species that survive under harsh

  4. Robust bayesian inference of generalized Pareto distribution ...

    African Journals Online (AJOL)

    Abstract. In this work, robust Bayesian estimation of the generalized Pareto distribution is proposed. The methodology is presented in terms of oscillation of posterior risks of the Bayesian estimators. By using a Monte Carlo simulation study, we show that, under a suitable generalized loss function, we can obtain a robust ...

  5. Globalized robust optimization for nonlinear uncertain inequalities

    NARCIS (Netherlands)

    Ben-Tal, A.; Brekelmans, Ruud; den Hertog, Dick; Vial, J.P.

    Robust optimization is a methodology that can be applied to problems that are affected by uncertainty in their parameters. The classical robust counterpart of a problem requires the solution to be feasible for all uncertain parameter values in a so-called uncertainty set and offers no guarantees for

  6. Implicitly Weighted Methods in Robust Image Analysis

    Czech Academy of Sciences Publication Activity Database

    Kalina, Jan


    Roč. 44, č. 3 (2012), s. 449-462 ISSN 0924-9907 R&D Projects: GA MŠk(CZ) 1M06014 Institutional research plan: CEZ:AV0Z10300504 Keywords : robustness * high breakdown point * outlier detection * robust correlation analysis * template matching * face recognition Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 1.767, year: 2012

  7. Extending the Scope of Robust Quadratic Optimization

    NARCIS (Netherlands)

    Marandi, Ahmadreza; Ben-Tal, A.; den Hertog, Dick; Melenberg, Bertrand

    In this paper, we derive tractable reformulations of the robust counterparts of convex quadratic and conic quadratic constraints with concave uncertainties for a broad range of uncertainty sets. For quadratic constraints with convex uncertainty, it is well-known that the robust counterpart is, in

  8. A practical guide to robust optimization

    NARCIS (Netherlands)

    Gorissen, Bram; Yanikoglu, Ihsan; den Hertog, Dick

    Robust optimization is a young and active research field that has been mainly developed in the last 15 years. Robust optimization is very useful for practice, since it is tailored to the information at hand, and it leads to computationally tractable formulations. It is therefore remarkable that

  9. Robust dissipativity for uncertain impulsive dynamical systems

    Directory of Open Access Journals (Sweden)

    Liu Bin


    Full Text Available We discuss the robust dissipativity with respect to the quadratic supply rate for uncertain impulsive dynamical systems. By employing the Hamilton-Jacobi inequality approach, some sufficient conditions of robust dissipativity for this kind of system are established. Finally, we specialize the obtained results to the case of uncertain linear impulsive dynamical systems.

  10. What is it to be sturdy (robust)?

    DEFF Research Database (Denmark)

    Nielsen, Niss Skov; Zwisler, Lars Pagter; Bojsen, Ann Kristina Mikkelsen

    Purpose: This paper intends to give a first insight into the concept of being "sturdy/robust"; To develop and test a Danish model of how to measure sturdi-ness/robustness; To test the scale's ability to identify people in emergency situa-tions who have high risk of developing psychological illness....

  11. Applying Robust Design in an Industrial Context

    DEFF Research Database (Denmark)

    Christensen, Martin Ebro

    mechanical architectures. Furthermore a set of 15 robust design principles for reducing the variation in functional performance is compiled in a format directly supporting the work of the design engineer. With these foundational methods in place, the existing tools, methods and KPIs of Robust Design...

  12. Recoverable Robustness in Shunting and Timetabling (United States)

    Cicerone, Serafino; D'Angelo, Gianlorenzo; di Stefano, Gabriele; Frigioni, Daniele; Navarra, Alfredo; Schachtebeck, Michael; Schöbel, Anita

    In practical optimization problems, disturbances to a given instance are unavoidable due to unpredictable events which can occur when the system is running. In order to face these situations, many approaches have been proposed during the last years in the area of robust optimization. The basic idea of robustness is to provide a solution which is able to keep feasibility even if the input instance is disturbed, at the cost of optimality. However, the notion of robustness in every day life is much broader than that pursued in the area of robust optimization so far. In fact, robustness is not always suitable unless some recovery strategies are introduced. Recovery strategies are some capabilities that can be used when disturbing events occur, in order to keep the feasibility of the pre-computed solution. This suggests to study robustness and recoverability in a unified framework. Recently, a first tentative of unifying the notions of robustness and recoverability into a new integrated notion of recoverable robustness has been done in the context of railway optimization.

  13. Boolean networks with robust and reliable trajectories

    International Nuclear Information System (INIS)

    Schmal, Christoph; Peixoto, Tiago P; Drossel, Barbara


    We construct and investigate Boolean networks that follow a given reliable trajectory in state space, which is insensitive to fluctuations in the updating schedule and which is also robust against noise. Robustness is quantified as the probability that the dynamics return to the reliable trajectory after a perturbation of the state of a single node. In order to achieve high robustness, we navigate through the space of possible update functions by using an evolutionary algorithm. We constrain the networks to those having the minimum number of connections required to obtain the reliable trajectory. Surprisingly, we find that robustness always reaches values close to 100% during the evolutionary optimization process. The set of update functions can be evolved such that it differs only slightly from that of networks that were not optimized with respect to robustness. The state space of the optimized networks is dominated by the basin of attraction of the reliable trajectory.

  14. International Conference on Robust Statistics 2015

    CERN Document Server

    Basu, Ayanendranath; Filzmoser, Peter; Mukherjee, Diganta


    This book offers a collection of recent contributions and emerging ideas in the areas of robust statistics presented at the International Conference on Robust Statistics 2015 (ICORS 2015) held in Kolkata during 12–16 January, 2015. The book explores the applicability of robust methods in other non-traditional areas which includes the use of new techniques such as skew and mixture of skew distributions, scaled Bregman divergences, and multilevel functional data methods; application areas being circular data models and prediction of mortality and life expectancy. The contributions are of both theoretical as well as applied in nature. Robust statistics is a relatively young branch of statistical sciences that is rapidly emerging as the bedrock of statistical analysis in the 21st century due to its flexible nature and wide scope. Robust statistics supports the application of parametric and other inference techniques over a broader domain than the strictly interpreted model scenarios employed in classical statis...

  15. Histone variant HTZ1 shows extensive epistasis with, but does not increase robustness to, new mutations.

    Directory of Open Access Journals (Sweden)

    Joshua B Richardson

    Full Text Available Biological systems produce phenotypes that appear to be robust to perturbation by mutations and environmental variation. Prior studies identified genes that, when impaired, reveal previously cryptic genetic variation. This result is typically interpreted as evidence that the disrupted gene normally increases robustness to mutations, as such robustness would allow cryptic variants to accumulate. However, revelation of cryptic genetic variation is not necessarily evidence that a mutationally robust state has been made less robust. Demonstrating a difference in robustness requires comparing the ability of each state (with the gene perturbed or intact to suppress the effects of new mutations. Previous studies used strains in which the existing genetic variation had been filtered by selection. Here, we use mutation accumulation (MA lines that have experienced minimal selection, to test the ability of histone H2A.Z (HTZ1 to increase robustness to mutations in the yeast Saccharomyces cerevisiae. HTZ1, a regulator of chromatin structure and gene expression, represents a class of genes implicated in mutational robustness. It had previously been shown to increase robustness of yeast cell morphology to fluctuations in the external or internal microenvironment. We measured morphological variation within and among 79 MA lines with and without HTZ1. Analysis of within-line variation confirms that HTZ1 increases microenvironmental robustness. Analysis of between-line variation shows the morphological effects of eliminating HTZ1 to be highly dependent on the line, which implies that HTZ1 interacts with mutations that have accumulated in the lines. However, lines without HTZ1 are, as a group, not more phenotypically diverse than lines with HTZ1 present. The presence of HTZ1, therefore, does not confer greater robustness to mutations than its absence. Our results provide experimental evidence that revelation of cryptic genetic variation cannot be assumed to be

  16. Histone Variant HTZ1 Shows Extensive Epistasis with, but Does Not Increase Robustness to, New Mutations (United States)

    Richardson, Joshua B.; Uppendahl, Locke D.; Traficante, Maria K.; Levy, Sasha F.; Siegal, Mark L.


    Biological systems produce phenotypes that appear to be robust to perturbation by mutations and environmental variation. Prior studies identified genes that, when impaired, reveal previously cryptic genetic variation. This result is typically interpreted as evidence that the disrupted gene normally increases robustness to mutations, as such robustness would allow cryptic variants to accumulate. However, revelation of cryptic genetic variation is not necessarily evidence that a mutationally robust state has been made less robust. Demonstrating a difference in robustness requires comparing the ability of each state (with the gene perturbed or intact) to suppress the effects of new mutations. Previous studies used strains in which the existing genetic variation had been filtered by selection. Here, we use mutation accumulation (MA) lines that have experienced minimal selection, to test the ability of histone H2A.Z (HTZ1) to increase robustness to mutations in the yeast Saccharomyces cerevisiae. HTZ1, a regulator of chromatin structure and gene expression, represents a class of genes implicated in mutational robustness. It had previously been shown to increase robustness of yeast cell morphology to fluctuations in the external or internal microenvironment. We measured morphological variation within and among 79 MA lines with and without HTZ1. Analysis of within-line variation confirms that HTZ1 increases microenvironmental robustness. Analysis of between-line variation shows the morphological effects of eliminating HTZ1 to be highly dependent on the line, which implies that HTZ1 interacts with mutations that have accumulated in the lines. However, lines without HTZ1 are, as a group, not more phenotypically diverse than lines with HTZ1 present. The presence of HTZ1, therefore, does not confer greater robustness to mutations than its absence. Our results provide experimental evidence that revelation of cryptic genetic variation cannot be assumed to be caused by loss of

  17. Deriving robust and globalized robust solutions of uncertain linear programs having general convex uncertainty sets

    NARCIS (Netherlands)

    Gorissen, B.L.; Blanc, J.P.C.; den Hertog, D.; Ben-Tal, A.

    We propose a new way to derive tractable robust counterparts of a linear program based on the duality between the robust (“pessimistic”) primal problem and its “optimistic” dual. First we obtain a new convex reformulation of the dual problem of a robust linear program, and then show how to construct

  18. Robustness of steel joints with stainless steel bolts in fire (United States)

    Satheeskumar, N.; Davison, J. B.


    The robustness of steel joints in fire is important for steel building structures because of the need to prevent progressive collapse. Stainless steel is widely used in building construction mainly because of its corrosion resistance, but it also possesses improved fire resistance compared with conventional non-alloy, fine grain structural steels. Extensive research performed on the robustness of steel joints in fire has revealed that failure at elevated temperature may be controlled by bolt shear for fin plate and web cleat connections. Hence, this study focussed on the use of stainless steel in experimental tests conducted on fin plate and web cleat connections at high temperatures. In addition, this study investigated the use of a component-based model to predict connection performance at elevated temperature.

  19. Robustness Analysis of Dynamic Watermarks

    Directory of Open Access Journals (Sweden)

    Ivan V. Nechta


    Full Text Available In this paper we consider previously known scheme of dynamic watermarks embedding (Ra- dix-n that is used for preventing illegal use of software. According to the scheme a watermark is dynamic linked data structure (graph, which is created in memory during program execution. Hidden data, such as information about author, can be represented in a different type of graph structure. This data can be extracted and demonstrated in judicial proceedings. This paper declared that the above mentioned scheme was previously one of the most reliable, has a number of features that allows an attacker to detect a stage of watermark construction in the program, and therefore it can be corrupted or deleted. The author of this article shows the weakness of Radix-N scheme, which consists in the fact that we can reveal dynamic data structures of a program by using information received from some API-functions hooker which catches function calls of dynamic memory allocation. One of these data structures is the watermark. Pointers on dynamically created objects (arrays, variables, class items, etc. of a program can be detected by content analysis of computer's RAM. Different dynamic objects in memory interconnected by pointers form dynamic data structures of a program such as lists, stacks, trees and other graphs (including the watermark. Our experiment shows that in the vast majority of cases the amount of data structure in programs is small, which increases probability of a successful attack. Also we present an algorithm for finding connected components of a graph with linear time-consuming in cases where the number of nodes is about 106. On the basis of the experimental findings the new watermarking scheme has been presented, which is resistant to the proposed attack. It is offered to use different graph structure representation of a watermark, where edges are implemented using unique signatures. Our scheme uses content encrypting of graph nodes (except signature

  20. Similar distribution changes of GABAergic interneuron subpopulations in contrast to the different impact on neurogenesis between developmental and adult-stage hypothyroidism in the hippocampal dentate gyrus in rats. (United States)

    Shiraki, Ayako; Akane, Hirotoshi; Ohishi, Takumi; Wang, Liyun; Morita, Reiko; Suzuki, Kazuhiko; Mitsumori, Kunitoshi; Shibutani, Makoto


    Hypothyroidism affects neurogenesis. The present study was performed to clarify the sensitivity of neurogenesis-related cellular responses in the hippocampal dentate gyrus between developmental and adult-stage hypothyroidism. An exposure study of methimazole (MMI) as an anti-thyroid agent at 0, 50, 200 ppm in the drinking water was performed using pregnant rats from gestation day 10 to postnatal day (PND) 21 (developmental hypothyroidism) and adult male rats by setting an identical exposure period from PND 46 through to PND 77 (adult-stage hypothyroidism). Offspring with developmental hypothyroidism were killed at PND 21 or PND 77, and animals with adult-stage hypothyroidism were killed at PND 77. Proliferation and apoptosis were unchanged in the dentate subgranular zone by either developmental or adult-stage hypothyroidism. With regard to precursor granule cells, a sustained reduction of paired box 6-positive stem or early progenitor cells and a transient reduction of doublecortin-positive late-stage progenitor cells were observed after developmental hypothyroidism with MMI at 50 and 200 ppm. These cells were unchanged by adult-stage hypothyroidism. With regard to γ-aminobutyric acid (GABA) ergic interneuron subpopulations in the dentate hilus, the number of parvalbumin-positive cells was decreased and the number of calretinin-positive cells was increased after both developmental and adult-stage hypothyroidism with MMI at 50 and 200 ppm. Fluctuations in GABAergic interneuron numbers with developmental hypothyroidism continued through to PND 77 with 200 ppm MMI. Considering the roles of GABAergic interneuron subpopulations in neurogenesis and neuronal differentiation, subpopulation changes in GABAergic interneurons by hypothyroidism may be the signature of aberrant neurogenesis even at the adult stage.

  1. Amelioration of oxidative stress-induced phenotype loss of parvalbumin interneurons might contribute to the beneficial effects of environmental enrichment in a rat model of post-traumatic stress disorder. (United States)

    Sun, Xiao R; Zhang, Hui; Zhao, Hong T; Ji, Mu H; Li, Hui H; Wu, Jing; Li, Kuan Y; Yang, Jian J


    Post-traumatic stress disorder (PTSD) is a common psychiatric disease following exposure to a severe traumatic event or physiological stress, which is characterized by anxiety- and depression-like behaviors and cognitive impairment. However, the underlying mechanisms remain elusive. Parvalbumin (PV) interneurons that are susceptible to oxidative stress are a subset of inhibitory GABAergic neurons regulating the excitability of pyramidal neurons, while dysfunction of PV interneurons is casually linked to many mental disorders including PTSD. We therefore hypothesized that environmental enrichment (EE), a method of enhanced cognitive, sensory and motor stimulation, can reverse the behavioral impairments by normalizing PV interneurons in a rat model of PTSD induced by inescapable foot shocks (IFS). Behavioral changes were determined by the open field, elevated plus maze, fear conditioning, and Morris water maze tests. The levels of nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase 2 (NOX2), NOX4, PV, glutamic acid decarboxylase 67 (GAD-67), and 8-hydroxy-2-deoxyguanosine (8-OH-dG) in the hippocampus and prefrontal cortex were determined. Our results showed that in this PTSD model, rats displayed the anxiety-like behavior, enhanced fear learning behavior, and hippocampus- dependent spatial memory deficit, which were accompanied by the up-regulation of NOX2, 8-OH-dG, and down-regulation of PV and GAD-67. Notably, EE reversed all these abnormalities. These results suggest that restoration of PV interneurons by inhibiting oxidative stress in the hippocampus and prefrontal cortex might represent a mechanism through which EE reverses the behavioral impairments in a rat model of PTSD induced by IFS. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Towards distortion-free robust image authentication

    International Nuclear Information System (INIS)

    Coltuc, D


    This paper investigates a general framework for distortion-free robust image authentication by multiple marking. First, by robust watermarking a subsampled version of image edges is embedded. Then, by reversible watermarking the information needed to recover the original image is inserted, too. The hiding capacity of the reversible watermarking is the essential requirement for this approach. Thus in case of no attacks not only image is authenticated but also the original is exactly recovered. In case of attacks, reversibility is lost, but image can still be authenticated. Preliminary results providing very good robustness against JPEG compression are presented

  3. Robust statistics and geochemical data analysis

    International Nuclear Information System (INIS)

    Di, Z.


    Advantages of robust procedures over ordinary least-squares procedures in geochemical data analysis is demonstrated using NURE data from the Hot Springs Quadrangle, South Dakota, USA. Robust principal components analysis with 5% multivariate trimming successfully guarded the analysis against perturbations by outliers and increased the number of interpretable factors. Regression with SINE estimates significantly increased the goodness-of-fit of the regression and improved the correspondence of delineated anomalies with known uranium prospects. Because of the ubiquitous existence of outliers in geochemical data, robust statistical procedures are suggested as routine procedures to replace ordinary least-squares procedures

  4. Danish Requirements for Robustness of Structures

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Christensen, H. H.


    Increased use of advanced types of structures with limited redundancy and serious failure consequences combined with strengthened requirements to efficiency in design and execution as well as increased risk of human errors necessitates requirements for the robustness of new structures, essential....... This paper describes the background of the revised robustness requirements implemented in the Danish Code of Practice for Safety of Structures in 2003 [1, 2, 3]. According to the Danish design rules robustness shall be documented for all structures where consequences of failure are serious. This paper...

  5. Robust Structured Control Design via LMI Optimization

    DEFF Research Database (Denmark)

    Adegas, Fabiano Daher; Stoustrup, Jakob


    This paper presents a new procedure for discrete-time robust structured control design. Parameter-dependent nonconvex conditions for stabilizable and induced L2-norm performance controllers are solved by an iterative linear matrix inequalities (LMI) optimization. A wide class of controller...... structures including decentralized of any order, fixed-order dynamic output feedback, static output feedback can be designed robust to polytopic uncertainties. Stability is proven by a parameter-dependent Lyapunov function. Numerical examples on robust stability margins shows that the proposed procedure can...

  6. Evolution of robust and efficient system topologies. (United States)

    Netotea, Sergiu; Pongor, Sándor


    Mutation/selection algorithms were applied to increase the efficiency and the robustness of sparse random networks. Selection for better efficiency leads to the well-known star topology, while selection for robustness only results in a relatively dense core and a small periphery. Concomitant selection for both efficiency and robustness leads to networks with intermittent center/periphery values. Networks evolving under multiple attack regimes develop distinct topologies with larger cores, and are characterized by parameter distributions different from those developing under single-attack regimes.

  7. Robustness-related issues in speaker recognition

    CERN Document Server

    Zheng, Thomas Fang


    This book presents an overview of speaker recognition technologies with an emphasis on dealing with robustness issues. Firstly, the book gives an overview of speaker recognition, such as the basic system framework, categories under different criteria, performance evaluation and its development history. Secondly, with regard to robustness issues, the book presents three categories, including environment-related issues, speaker-related issues and application-oriented issues. For each category, the book describes the current hot topics, existing technologies, and potential research focuses in the future. The book is a useful reference book and self-learning guide for early researchers working in the field of robust speech recognition.

  8. A Survey on Robustness in Railway Planning

    DEFF Research Database (Denmark)

    Lusby, Richard Martin; Larsen, Jesper; Bull, Simon Henry


    Planning problems in passenger railway range from long term strategic decision making to the detailed planning of operations.Operations research methods have played an increasing role in this planning process. However, recently more attention has been given to considerations of robustness...... with a disruption such as delay or failure. This has resulted in more attention given to the inclusion of robustness measures and objectives in individual planning problems, and to the providing of tools to ensure operations continue under disrupted situations. In this paper we survey the literature on robustness...

  9. Robust recognition via information theoretic learning

    CERN Document Server

    He, Ran; Yuan, Xiaotong; Wang, Liang


    This Springer Brief represents a comprehensive review of information theoretic methods for robust recognition. A variety of information theoretic methods have been proffered in the past decade, in a large variety of computer vision applications; this work brings them together, attempts to impart the theory, optimization and usage of information entropy.The?authors?resort to a new information theoretic concept, correntropy, as a robust measure and apply it to solve robust face recognition and object recognition problems. For computational efficiency,?the brief?introduces the additive and multip

  10. Design Robust Controller for Rotary Kiln

    Directory of Open Access Journals (Sweden)

    Omar D. Hernández-Arboleda


    Full Text Available This paper presents the design of a robust controller for a rotary kiln. The designed controller is a combination of a fractional PID and linear quadratic regulator (LQR, these are not used to control the kiln until now, in addition robustness criteria are evaluated (gain margin, phase margin, strength gain, rejecting high frequency noise and sensitivity applied to the entire model (controller-plant, obtaining good results with a frequency range of 0.020 to 90 rad/s, which contributes to the robustness of the system.

  11. Assessment of Process Robustness for Mass Customization

    DEFF Research Database (Denmark)

    Nielsen, Kjeld; Brunø, Thomas Ditlev


    robustness and their capability to develop it. Through literature study and analysis of robust process design characteristics a number of metrics are described which can be used for assessment. The metrics are evaluated and analyzed to be applied as KPI’s to help MC companies prioritize efforts in business......In mass customization, the capability Robust Process Design defined as the ability to reuse or recombine existing organizational and value-chain resources is essential to deliver a high variety cost effectively. We argue that there is a need for methods which can assess a company’s process...

  12. Hippocampal cholinergic interneurons visualized with the choline acetyltransferase promoter: anatomical distribution, intrinsic membrane properties, neurochemical characteristics, and capacity for cholinergic modulation

    Directory of Open Access Journals (Sweden)

    Feng eYi


    Full Text Available Release of acetylcholine (ACh in the hippocampus (HC occurs during exploration, arousal, and learning. Although the medial septum-diagonal band of Broca (MS-DBB is the major extrinsic source of cholinergic input to the HC, cholinergic neurons intrinsic to the HC also exist but remain poorly understood. Here, ChAT-tauGFP and ChAT-CRE/Rosa26YFP (ChAT-Rosa mice were examined in HC. The HC of ChAT-tauGFP mice was densely innervated with GFP-positive axons, often accompanied by large GFP-positive structures, some of which were Neurotrace/DAPI-negative and likely represent large axon terminals. In the HC of ChAT-Rosa mice, ChAT-YFP cells were Neurotrace-positive and more abundant in CA3 and dentate gyrus than CA1 with partial overlapping with calretinin/VIP. Moreover, an anti-ChAT antibody consistently showed ChAT immunoreactivity in ChAT-YFP cells from MS-DBB but rarely from HC. Furthermore, ChAT-YFP cells from CA1 stratum radiatum/stratum lacunosum moleculare (SR/SLM exhibited a stuttering firing phenotype but a delayed firing phenotype in stratum pyramidale (SP of CA3. Input resistance and capacitance were also different between CA1 SR/LM and CA3 SP ChAT-YFP cells. Bath application of ACh increased firing frequency in all ChAT-YFP cells; however, cholinergic modulation was larger in CA1 SR/SLM than CA3 SP ChAT-YFP cells. Finally, CA3 SP ChAT-YFP cells exhibited a wider AP half-width and weaker cholinergic modulation than YFP-negative CA3 pyramidal cells. Consistent with CRE expression in a subpopulation of principal cells, optogenetic stimulation evoked glutamatergic postsynaptic currents in CA1 SR/SLM interneurons. In conclusion, the presence of fluorescently labeled hippocampal cells common to both ChAT-Rosa and ChAT-tauGFP mice are in good agreement with previous reports on the existence of cholinergic interneurons, but both transgenic mouse lines exhibited unexpected anatomical features that departed considerably from earlier observations.

  13. Efficient reanalysis techniques for robust topology optimization

    DEFF Research Database (Denmark)

    Amir, Oded; Sigmund, Ole; Lazarov, Boyan Stefanov


    The article focuses on the reduction of the computational effort involved in robust topology optimization procedures. The performance of structures designed by means of topology optimization may be seriously degraded due to fabrication errors. Robust formulations of the optimization problem were...... shown to yield optimized designs that are tolerant with respect to such manufacturing uncertainties. The main drawback of such procedures is the added computational cost associated with the need to evaluate a set of designs by performing multiple finite element analyses. In this article, we propose...... efficient robust topology optimization procedures based on reanalysis techniques. The approach is demonstrated on two compliant mechanism design problems where robust design is achieved by employing either a worst case formulation or a stochastic formulation. It is shown that the time spent on finite...

  14. Robust Tracking Control for a Piezoelectric Actuator

    National Research Council Canada - National Science Library

    Salah, M; McIntyre, M; Dawson, D; Wagner, J


    In this paper, a hysteresis model-based nonlinear robust controller is developed for a piezoelectric actuator, utilizing a Lyapunov-based stability analysis, which ensures that a desired displacement...

  15. Robust nonlinear control of vectored thrust aircraft (United States)

    Doyle, John C.; Murray, Richard; Morris, John


    An interdisciplinary program in robust control for nonlinear systems with applications to a variety of engineering problems is outlined. Major emphasis will be placed on flight control, with both experimental and analytical studies. This program builds on recent new results in control theory for stability, stabilization, robust stability, robust performance, synthesis, and model reduction in a unified framework using Linear Fractional Transformations (LFT's), Linear Matrix Inequalities (LMI's), and the structured singular value micron. Most of these new advances have been accomplished by the Caltech controls group independently or in collaboration with researchers in other institutions. These recent results offer a new and remarkably unified framework for all aspects of robust control, but what is particularly important for this program is that they also have important implications for system identification and control of nonlinear systems. This combines well with Caltech's expertise in nonlinear control theory, both in geometric methods and methods for systems with constraints and saturations.

  16. Multifidelity Robust Aeroelastic Design, Phase I (United States)

    National Aeronautics and Space Administration — Nielsen Engineering & Research (NEAR) proposes a new method to generate mathematical models of wind-tunnel models and flight vehicles for robust aeroelastic...

  17. Robust entangled qutrit states in atmospheric turbulence

    CSIR Research Space (South Africa)

    Brunner, T


    Full Text Available The entangled quantum state of a photon pair propagating through atmospheric turbulence suffers decay of entanglement due to the scintillation it experiences. Here we investigate the robustness against this decay for different qutrit states. We use...

  18. Design principles for robust oscillatory behavior. (United States)

    Castillo-Hair, Sebastian M; Villota, Elizabeth R; Coronado, Alberto M


    Oscillatory responses are ubiquitous in regulatory networks of living organisms, a fact that has led to extensive efforts to study and replicate the circuits involved. However, to date, design principles that underlie the robustness of natural oscillators are not completely known. Here we study a three-component enzymatic network model in order to determine the topological requirements for robust oscillation. First, by simulating every possible topological arrangement and varying their parameter values, we demonstrate that robust oscillators can be obtained by augmenting the number of both negative feedback loops and positive autoregulations while maintaining an appropriate balance of positive and negative interactions. We then identify network motifs, whose presence in more complex topologies is a necessary condition for obtaining oscillatory responses. Finally, we pinpoint a series of simple architectural patterns that progressively render more robust oscillators. Together, these findings can help in the design of more reliable synthetic biomolecular networks and may also have implications in the understanding of other oscillatory systems.

  19. Robust resource allocation in future wireless networks

    CERN Document Server

    Parsaeefard, Saeedeh; Mokari, Nader


    This book presents state-of-the-art research on robust resource allocation in current and future wireless networks. The authors describe the nominal resource allocation problems in wireless networks and explain why introducing robustness in such networks is desirable. Then, depending on the objectives of the problem, namely maximizing the social utility or the per-user utility, cooperative or competitive approaches are explained and their corresponding robust problems are considered in detail. For each approach, the costs and benefits of robust schemes are discussed and the algorithms for reducing their costs and improving their benefits are presented. Considering the fact that such problems are inherently non-convex and intractable, a taxonomy of different relaxation techniques is presented, and applications of such techniques are shown via several examples throughout the book. Finally, the authors argue that resource allocation continues to be an important issue in future wireless networks, and propose spec...

  20. Robust logic gates and realistic quantum computation

    International Nuclear Information System (INIS)

    Xiao Li; Jones, Jonathan A.


    The composite rotation approach has been used to develop a range of robust quantum logic gates, including single qubit gates and two qubit gates, which are resistant to systematic errors in their implementation. Single qubit gates based on the BB1 family of composite rotations have been experimentally demonstrated in a variety of systems, but little study has been made of their application in extended computations, and there has been no experimental study of the corresponding robust two qubit gates to date. Here we describe an application of robust gates to nuclear magnetic resonance studies of approximate quantum counting. We find that the BB1 family of robust gates is indeed useful, but that the related NB1, PB1, B4, and P4 families of tailored logic gates are less useful than initially expected

  1. Robust control of robots fault tolerant approaches

    CERN Document Server

    Siqueira, Adriano A G; Bergerman, Marcel


    Bridging the divide between robust control theory and its application, this volume focuses on robotic manipulators and illustrates the mathematical concepts through experimental results in reproducible detail, obtained with a two-manipulator system.

  2. Robust Satellite Communications Under Hostile Interference (United States)


    or elimination of required feedback signals, jammer herding, multi-source signalling, and interference alignment . In the case of the replace with...AFRL-RV-PS- AFRL-RV-PS- TR-2016-0079 TR-2016-0079 ROBUST SATELLITE COMMUNICATIONS UNDER HOSTILE INTERFERENCE Marc Lichtman and Jeffrey Reed...FA9453-14-1-0222 Robust Satellite Communications Under Hostile Interference 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 62601F 6. AUTHOR(S) 5d

  3. Three Contributions to Robust Regression Diagnostics

    Czech Academy of Sciences Publication Activity Database

    Kalina, Jan


    Roč. 11, č. 2 (2015), s. 69-78 ISSN 1336-9180 Grant - others:GA ČR(CZ) GA13-01930S; Nadační fond na podporu vědy(CZ) Neuron Institutional support: RVO:67985807 Keywords : robust regression * robust econometrics * hypothesis testing Subject RIV: BA - General Mathematics xml ?format=INT

  4. Framework for Robustness Assessment of Timber Structures

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard


    This paper presents a theoretical framework for the design and analysis of robustness of timber structures. This is actualized by a more4 frequent use of advanced types of timber structures with limited redundancy and serious consequences in the case of failure. Combined with increased requirements...... are not specified in detail, which makes the practical use difficult. This paper describes a theoretical and risk based framework to form the basis for quantification of robustness and for pre-normative guidelines....

  5. Robust Planning for Effects-Based Operations (United States)


    hypothesis or options [56]. Recency tends to trump primacy in complex problems. "* Elimination by aspect: When trying to choose among several options...THESIS 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS ROBUST PLANNING FOR EFFECTS BASED OPERATIONS 6. AUTHOR(S) 2D LT BRYANT CORBAN H 7. PERFORMING ORGANIZATION...EG) escribed by ANSI Std. 239.18 DesgJned using Perform Pro, WHS/DIOR, Oct 94 Robust Planning for Effects -Based Operations by Corban Harrell Bryant

  6. Antecedents and Dimensions of Supply Chain Robustness


    Durach, Christian F.; Wieland, Andreas; Machuca, Jose A.D.


    Purpose – The purpose of this paper is to provide groundwork for an emerging theory of supply chain robustness – which has been conceptualized as a dimension of supply chain resilience – through reviewing and synthesizing related yet disconnected studies. The paper develops a formal definition of supply chain robustness to build a framework that captures the dimensions, antecedents and moderators of the construct as discussed in the literature. Design/methodology/approach – The...

  7. Adaptive Critic Nonlinear Robust Control: A Survey. (United States)

    Wang, Ding; He, Haibo; Liu, Derong


    Adaptive dynamic programming (ADP) and reinforcement learning are quite relevant to each other when performing intelligent optimization. They are both regarded as promising methods involving important components of evaluation and improvement, at the background of information technology, such as artificial intelligence, big data, and deep learning. Although great progresses have been achieved and surveyed when addressing nonlinear optimal control problems, the research on robustness of ADP-based control strategies under uncertain environment has not been fully summarized. Hence, this survey reviews the recent main results of adaptive-critic-based robust control design of continuous-time nonlinear systems. The ADP-based nonlinear optimal regulation is reviewed, followed by robust stabilization of nonlinear systems with matched uncertainties, guaranteed cost control design of unmatched plants, and decentralized stabilization of interconnected systems. Additionally, further comprehensive discussions are presented, including event-based robust control design, improvement of the critic learning rule, nonlinear H ∞ control design, and several notes on future perspectives. By applying the ADP-based optimal and robust control methods to a practical power system and an overhead crane plant, two typical examples are provided to verify the effectiveness of theoretical results. Overall, this survey is beneficial to promote the development of adaptive critic control methods with robustness guarantee and the construction of higher level intelligent systems.


    Directory of Open Access Journals (Sweden)

    Jan Kalina


    Full Text Available This paper is devoted to highly robust methods for information extraction from data, with a special attention paid to methods suitable for management applications. The sensitivity of availabledata mining methods to the presence of outlying measurements in the observed data is discussed as a major drawback of available data mining methods. The paper proposes several newhighly robustmethods for data mining, which are based on the idea of implicit weighting of individual data values.Particularly it propose a novel robust method of hierarchical cluster analysis, which is a popular data mining method of unsupervised learning. Further, a robust method for estimating parameters in thelogistic regression was proposed. This idea is extended to a robust multinomial logistic classification analysis. Finally, the sensitivity of neural networks to the presence of noise and outlying measurements in the data was discussed. The method for robust training of neural networks for the task of function approximation, which has the form of a robust estimator in nonlinear regression, was proposed.

  9. Robust reflective ghost imaging against different partially polarized thermal light (United States)

    Li, Hong-Guo; Wang, Yan; Zhang, Rui-Xue; Zhang, De-Jian; Liu, Hong-Chao; Li, Zong-Guo; Xiong, Jun


    We theoretically study the influence of degree of polarization (DOP) of thermal light on the contrast-to-noise ratio (CNR) of the reflective ghost imaging (RGI), which is a novel and indirect imaging modality. An expression for the CNR of RGI with partially polarized thermal light is carefully derived, which suggests a weak dependence of CNR on the DOP, especially when the ratio of the object size to the speckle size of thermal light has a large value. Different from conventional imaging approaches, our work reveals that RGI is much more robust against the DOP of the light source, which thereby has advantages in practical applications, such as remote sensing.

  10. The Rationality of Four Metrics of Network Robustness: A Viewpoint of Robust Growth of Generalized Meshes.

    Directory of Open Access Journals (Sweden)

    Xiaofan Yang

    Full Text Available There are quite a number of different metrics of network robustness. This paper addresses the rationality of four metrics of network robustness (the algebraic connectivity, the effective resistance, the average edge betweenness, and the efficiency by investigating the robust growth of generalized meshes (GMs. First, a heuristic growth algorithm (the Proximity-Growth algorithm is proposed. The resulting proximity-optimal GMs are intuitively robust and hence are adopted as the benchmark. Then, a generalized mesh (GM is grown up by stepwise optimizing a given measure of network robustness. The following findings are presented: (1 The algebraic connectivity-optimal GMs deviate quickly from the proximity-optimal GMs, yielding a number of less robust GMs. This hints that the rationality of the algebraic connectivity as a measure of network robustness is still in doubt. (2 The effective resistace-optimal GMs and the average edge betweenness-optimal GMs are in line with the proximity-optimal GMs. This partly justifies the two quantities as metrics of network robustness. (3 The efficiency-optimal GMs deviate gradually from the proximity-optimal GMs, yielding some less robust GMs. This suggests the limited utility of the efficiency as a measure of network robustness.

  11. Hypocretin (orexin) regulates glutamate input to fast-spiking interneurons in layer V of the Fr2 region of the murine prefrontal cortex. (United States)

    Aracri, Patrizia; Banfi, Daniele; Pasini, Maria Enrica; Amadeo, Alida; Becchetti, Andrea


    We studied the effect of hypocretin 1 (orexin A) in the frontal area 2 (Fr2) of the murine neocortex, implicated in the motivation-dependent goal-directed tasks. In layer V, hypocretin stimulated the spontaneous excitatory postsynaptic currents (EPSCs) on fast-spiking (FS) interneurons. The effect was accompanied by increased frequency of miniature EPSCs, indicating that hypocretin can target the glutamatergic terminals. Moreover, hypocretin stimulated the spontaneous inhibitory postsynaptic currents (IPSCs) on pyramidal neurons, with no effect on miniature IPSCs. This action was prevented by blocking 1) the ionotropic glutamatergic receptors; 2) the hypocretin receptor type 1 (HCRTR-1), with SB-334867. Finally, hypocretin increased the firing frequency in FS cells, and the effect was blocked when the ionotropic glutamate transmission was inhibited. Immunolocalization confirmed that HCRTR-1 is highly expressed in Fr2, particularly in layer V-VI. Conspicuous labeling was observed in pyramidal neuron somata and in VGLUT1+ glutamatergic terminals, but not in VGLUT2+ fibers (mainly thalamocortical afferents). The expression of HCRTR-1 in GABAergic structures was scarce. We conclude that 1) hypocretin regulates glutamate release in Fr2; 2) the effect presents a presynaptic component; 3) the peptide control of FS cells is indirect, and probably mediated by the regulation of glutamatergic input onto these cells. © The Author 2013. Published by Oxford University Press.

  12. Neonatal NMDA receptor blockade disrupts spike timing and glutamatergic synapses in fast spiking interneurons in a NMDA receptor hypofunction model of schizophrenia.

    Directory of Open Access Journals (Sweden)

    Kevin S Jones

    Full Text Available The dysfunction of parvalbumin-positive, fast-spiking interneurons (FSI is considered a primary contributor to the pathophysiology of schizophrenia (SZ, but deficits in FSI physiology have not been explicitly characterized. We show for the first time, that a widely-employed model of schizophrenia minimizes first spike latency and increases GluN2B-mediated current in neocortical FSIs. The reduction in FSI first-spike latency coincides with reduced expression of the Kv1.1 potassium channel subunit which provides a biophysical explanation for the abnormal spiking behavior. Similarly, the increase in NMDA current coincides with enhanced expression of the GluN2B NMDA receptor subunit, specifically in FSIs. In this study mice were treated with the NMDA receptor antagonist, MK-801, during the first week of life. During adolescence, we detected reduced spike latency and increased GluN2B-mediated NMDA current in FSIs, which suggests transient disruption of NMDA signaling during neonatal development exerts lasting changes in the cellular and synaptic physiology of neocortical FSIs. Overall, we propose these physiological disturbances represent a general impairment to the physiological maturation of FSIs which may contribute to schizophrenia-like behaviors produced by this model.

  13. Robust Evaluation for Transportation Network Capacity under Demand Uncertainty

    Directory of Open Access Journals (Sweden)

    Muqing Du


    Full Text Available As more and more cities in worldwide are facing the problems of traffic jam, governments have been concerned about how to design transportation networks with adequate capacity to accommodate travel demands. To evaluate the capacity of a transportation system, the prescribed origin and destination (O-D matrix for existing travel demand has been noticed to have a significant effect on the results of network capacity models. However, the exact data of the existing O-D demand are usually hard to be obtained in practice. Considering the fluctuation of the real travel demand in transportation networks, the existing travel demand is represented as uncertain parameters which are defined within a bounded set. Thus, a robust reserve network capacity (RRNC model using min–max optimization is formulated based on the demand uncertainty. An effective heuristic approach utilizing cutting plane method and sensitivity analysis is proposed for the solution of the RRNC problem. Computational experiments and simulations are implemented to demonstrate the validity and performance of the proposed robust model. According to simulation experiments, it is showed that the link flow pattern from the robust solutions to network capacity problems can reveal the probability of high congestion for each link.

  14. Robust Visual Tracking Using the Bidirectional Scale Estimation

    Directory of Open Access Journals (Sweden)

    An Zhiyong


    Full Text Available Object tracking with robust scale estimation is a challenging task in computer vision. This paper presents a novel tracking algorithm that learns the translation and scale filters with a complementary scheme. The translation filter is constructed using the ridge regression and multidimensional features. A robust scale filter is constructed by the bidirectional scale estimation, including the forward scale and backward scale. Firstly, we learn the scale filter using the forward tracking information. Then the forward scale and backward scale can be estimated using the respective scale filter. Secondly, a conservative strategy is adopted to compromise the forward and backward scales. Finally, the scale filter is updated based on the final scale estimation. It is effective to update scale filter since the stable scale estimation can improve the performance of scale filter. To reveal the effectiveness of our tracker, experiments are performed on 32 sequences with significant scale variation and on the benchmark dataset with 50 challenging videos. Our results show that the proposed tracker outperforms several state-of-the-art trackers in terms of robustness and accuracy.

  15. The comparison of robust partial least squares regression with robust principal component regression on a real (United States)

    Polat, Esra; Gunay, Suleyman


    One of the problems encountered in Multiple Linear Regression (MLR) is multicollinearity, which causes the overestimation of the regression parameters and increase of the variance of these parameters. Hence, in case of multicollinearity presents, biased estimation procedures such as classical Principal Component Regression (CPCR) and Partial Least Squares Regression (PLSR) are then performed. SIMPLS algorithm is the leading PLSR algorithm because of its speed, efficiency and results are easier to interpret. However, both of the CPCR and SIMPLS yield very unreliable results when the data set contains outlying observations. Therefore, Hubert and Vanden Branden (2003) have been presented a robust PCR (RPCR) method and a robust PLSR (RPLSR) method called RSIMPLS. In RPCR, firstly, a robust Principal Component Analysis (PCA) method for high-dimensional data on the independent variables is applied, then, the dependent variables are regressed on the scores using a robust regression method. RSIMPLS has been constructed from a robust covariance matrix for high-dimensional data and robust linear regression. The purpose of this study is to show the usage of RPCR and RSIMPLS methods on an econometric data set, hence, making a comparison of two methods on an inflation model of Turkey. The considered methods have been compared in terms of predictive ability and goodness of fit by using a robust Root Mean Squared Error of Cross-validation (R-RMSECV), a robust R2 value and Robust Component Selection (RCS) statistic.

  16. Network properties of robust immunity in plants.

    Directory of Open Access Journals (Sweden)

    Kenichi Tsuda


    Full Text Available Two modes of plant immunity against biotrophic pathogens, Effector Triggered Immunity (ETI and Pattern-Triggered Immunity (PTI, are triggered by recognition of pathogen effectors and Microbe-Associated Molecular Patterns (MAMPs, respectively. Although the jasmonic acid (JA/ethylene (ET and salicylic acid (SA signaling sectors are generally antagonistic and important for immunity against necrotrophic and biotrophic pathogens, respectively, their precise roles and interactions in ETI and PTI have not been clear. We constructed an Arabidopsis dde2/ein2/pad4/sid2-quadruple mutant. DDE2, EIN2, and SID2 are essential components of the JA, ET, and SA sectors, respectively. The pad4 mutation affects the SA sector and a poorly characterized sector. Although the ETI triggered by the bacterial effector AvrRpt2 (AvrRpt2-ETI and the PTI triggered by the bacterial MAMP flg22 (flg22-PTI were largely intact in plants with mutations in any one of these genes, they were mostly abolished in the quadruple mutant. For the purposes of this study, AvrRpt2-ETI and flg22-PTI were measured as relative growth of Pseudomonas syringae bacteria within leaves. Immunity to the necrotrophic fungal pathogen Alternaria brassicicola was also severely compromised in the quadruple mutant. Quantitative measurements of the immunity levels in all combinatorial mutants and wild type allowed us to estimate the effects of the wild-type genes and their interactions on the immunity by fitting a mixed general linear model. This signaling allocation analysis showed that, contrary to current ideas, each of the JA, ET, and SA signaling sectors can positively contribute to immunity against both biotrophic and necrotrophic pathogens. The analysis also revealed that while flg22-PTI and AvrRpt2-ETI use a highly overlapping signaling network, the way they use the common network is very different: synergistic relationships among the signaling sectors are evident in PTI, which may amplify the signal

  17. Robust adaptive control for Unmanned Aerial Vehicles (United States)

    Kahveci, Nazli E.

    anti-windup compensation. Our analysis on the indirect adaptive scheme reveals that the perturbation terms due to parameter errors do not cause any unbounded signals in the closed-loop. The stability of the adaptive system is established, and the properties of the proposed control scheme are demonstrated through simulations on a UAV model with input magnitude saturation constraints. The robust adaptive control design is further developed to extend our results to rate-saturated systems.

  18. A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-off on Phenotype Robustness in Biological Networks Part I: Gene Regulatory Networks in Systems and Evolutionary Biology. (United States)

    Chen, Bor-Sen; Lin, Ying-Po


    Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties observed in biological systems at different levels. The underlying principles for robust stabilization and environmental disturbance attenuation are universal to both complex biological systems and sophisticated engineering systems. In many biological networks, network robustness should be enough to confer intrinsic robustness in order to tolerate intrinsic parameter fluctuations, genetic robustness for buffering genetic variations, and environmental robustness for resisting environmental disturbances. With this, the phenotypic stability of biological network can be maintained, thus guaranteeing phenotype robustness. This paper presents a survey on biological systems and then develops a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation in systems and evolutionary biology. Further, from the unifying mathematical framework, it was discovered that the phenotype robustness criterion for biological networks at different levels relies upon intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness. When this is true, the phenotype robustness can be maintained in spite of intrinsic parameter fluctuations, genetic variations, and environmental disturbances. Therefore, the trade-offs between intrinsic robustness, genetic robustness, environmental robustness, and network robustness in systems and evolutionary biology can also be investigated through their corresponding phenotype robustness criterion from the systematic point of view.

  19. Information theory perspective on network robustness

    Energy Technology Data Exchange (ETDEWEB)

    Schieber, Tiago A. [Departmento de Engenharia de Produção, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Industrial and Systems Engineering, University of Florida, Gainesville, FL (United States); Carpi, Laura [Departament de Física i Enginyeria Nuclear, Universitat Politècnica de Catalunya, Colom 11, Terrassa, 08222, Barcelona (Spain); Frery, Alejandro C. [Laboratório de Computação Científica e Análise Numérica (LaCCAN), Universidade Federal de Alagoas, Maceió, Alagoas (Brazil); Rosso, Osvaldo A. [Instituto de Física, Universidade Federal de Alagoas, Maceió, Alagoas (Brazil); Instituto Tecnológico de Buenos Aires (ITBA), Ciudad Autónoma de Buenos Aires (Argentina); Pardalos, Panos M. [Industrial and Systems Engineering, University of Florida, Gainesville, FL (United States); Ravetti, Martín G., E-mail: [Departmento de Engenharia de Produção, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Departament de Física Fonamental, Universitat de Barcelona, Barcelona (Spain)


    A crucial challenge in network theory is the study of the robustness of a network when facing a sequence of failures. In this work, we propose a dynamical definition of network robustness based on Information Theory, that considers measurements of the structural changes caused by failures of the network's components. Failures are defined here as a temporal process defined in a sequence. Robustness is then evaluated by measuring dissimilarities between topologies after each time step of the sequence, providing a dynamical information about the topological damage. We thoroughly analyze the efficiency of the method in capturing small perturbations by considering different probability distributions on networks. In particular, we find that distributions based on distances are more consistent in capturing network structural deviations, as better reflect the consequences of the failures. Theoretical examples and real networks are used to study the performance of this methodology. - Highlights: • A novel methodology to measure the robustness of a network to component failure or targeted attacks is proposed. • The use of the network's distance PDF allows a precise analysis. • The method provides a dynamic robustness profile showing the response of the topology to each failure event. • The measure is capable to detect network's critical elements.

  20. Non-Hermitian bidirectional robust transport (United States)

    Longhi, Stefano


    Transport of quantum or classical waves in open systems is known to be strongly affected by non-Hermitian terms that arise from an effective description of system-environment interaction. A simple and paradigmatic example of non-Hermitian transport, originally introduced by Hatano and Nelson two decades ago [N. Hatano and D. R. Nelson, Phys. Rev. Lett. 77, 570 (1996), 10.1103/PhysRevLett.77.570], is the hopping dynamics of a quantum particle on a one-dimensional tight-binding lattice in the presence of an imaginary vectorial potential. The imaginary gauge field can prevent Anderson localization via non-Hermitian delocalization, opening up a mobility region and realizing robust transport immune to disorder and backscattering. Like for robust transport of topologically protected edge states in quantum Hall and topological insulator systems, non-Hermitian robust transport in the Hatano-Nelson model is unidirectional. However, there is not any physical impediment to observe robust bidirectional non-Hermitian transport. Here it is shown that in a quasi-one-dimensional zigzag lattice, with non-Hermitian (imaginary) hopping amplitudes and a synthetic gauge field, robust transport immune to backscattering can occur bidirectionally along the lattice.

  1. Information theory perspective on network robustness

    International Nuclear Information System (INIS)

    Schieber, Tiago A.; Carpi, Laura; Frery, Alejandro C.; Rosso, Osvaldo A.; Pardalos, Panos M.; Ravetti, Martín G.


    A crucial challenge in network theory is the study of the robustness of a network when facing a sequence of failures. In this work, we propose a dynamical definition of network robustness based on Information Theory, that considers measurements of the structural changes caused by failures of the network's components. Failures are defined here as a temporal process defined in a sequence. Robustness is then evaluated by measuring dissimilarities between topologies after each time step of the sequence, providing a dynamical information about the topological damage. We thoroughly analyze the efficiency of the method in capturing small perturbations by considering different probability distributions on networks. In particular, we find that distributions based on distances are more consistent in capturing network structural deviations, as better reflect the consequences of the failures. Theoretical examples and real networks are used to study the performance of this methodology. - Highlights: • A novel methodology to measure the robustness of a network to component failure or targeted attacks is proposed. • The use of the network's distance PDF allows a precise analysis. • The method provides a dynamic robustness profile showing the response of the topology to each failure event. • The measure is capable to detect network's critical elements.

  2. Emergence of robustness in networks of networks (United States)

    Roth, Kevin; Morone, Flaviano; Min, Byungjoon; Makse, Hernán A.


    A model of interdependent networks of networks (NONs) was introduced recently [Proc. Natl. Acad. Sci. (USA) 114, 3849 (2017), 10.1073/pnas.1620808114] in the context of brain activation to identify the neural collective influencers in the brain NON. Here we investigate the emergence of robustness in such a model, and we develop an approach to derive an exact expression for the random percolation transition in Erdös-Rényi NONs of this kind. Analytical calculations are in agreement with numerical simulations, and highlight the robustness of the NON against random node failures, which thus presents a new robust universality class of NONs. The key aspect of this robust NON model is that a node can be activated even if it does not belong to the giant mutually connected component, thus allowing the NON to be built from below the percolation threshold, which is not possible in previous models of interdependent networks. Interestingly, the phase diagram of the model unveils particular patterns of interconnectivity for which the NON is most vulnerable, thereby marking the boundary above which the robustness of the system improves with increasing dependency connections.

  3. Robustness analysis of chiller sequencing control

    International Nuclear Information System (INIS)

    Liao, Yundan; Sun, Yongjun; Huang, Gongsheng


    Highlights: • Uncertainties with chiller sequencing control were systematically quantified. • Robustness of chiller sequencing control was systematically analyzed. • Different sequencing control strategies were sensitive to different uncertainties. • A numerical method was developed for easy selection of chiller sequencing control. - Abstract: Multiple-chiller plant is commonly employed in the heating, ventilating and air-conditioning system to increase operational feasibility and energy-efficiency under part load condition. In a multiple-chiller plant, chiller sequencing control plays a key role in achieving overall energy efficiency while not sacrifices the cooling sufficiency for indoor thermal comfort. Various sequencing control strategies have been developed and implemented in practice. Based on the observation that (i) uncertainty, which cannot be avoided in chiller sequencing control, has a significant impact on the control performance and may cause the control fail to achieve the expected control and/or energy performance; and (ii) in current literature few studies have systematically addressed this issue, this paper therefore presents a study on robustness analysis of chiller sequencing control in order to understand the robustness of various chiller sequencing control strategies under different types of uncertainty. Based on the robustness analysis, a simple and applicable method is developed to select the most robust control strategy for a given chiller plant in the presence of uncertainties, which will be verified using case studies

  4. Primal and dual approaches to adjustable robust optimization

    NARCIS (Netherlands)

    de Ruiter, Frans


    Robust optimization has become an important paradigm to deal with optimization under uncertainty. Adjustable robust optimization is an extension that deals with multistage problems. This thesis starts with a short but comprehensive introduction to adjustable robust optimization. Then the two

  5. Calcium Imaging Reveals Coordinated Simple Spike Pauses in Populations of Cerebellar Purkinje Cells

    Directory of Open Access Journals (Sweden)

    Jorge E. Ramirez


    Full Text Available The brain’s control of movement is thought to involve coordinated activity between cerebellar Purkinje cells. The results reported here demonstrate that somatic Ca2+ imaging is a faithful reporter of Na+-dependent “simple spike” pauses and enables us to optically record changes in firing rates in populations of Purkinje cells in brain slices and in vivo. This simultaneous calcium imaging of populations of Purkinje cells reveals a striking spatial organization of pauses in Purkinje cell activity between neighboring cells. The source of this organization is shown to be the presynaptic gamma-Aminobutyric acid producing (GABAergic network, and blocking ionotropic gamma-Aminobutyric acid receptor (GABAARs abolishes the synchrony. These data suggest that presynaptic interneurons synchronize (inactivity between neighboring Purkinje cells, and thereby maximize their effect on downstream targets in the deep cerebellar nuclei.

  6. Robust control systems theory and case studies

    CERN Document Server

    Mackenroth, Uwe


    "Robust Control Systems" gives a self-contained introduction to modern Control Theory. It thus adds a textbook to the existing research-oriented literature on Robust Control. The author lays emphasis on the modern aspects of the design of controllers with prescribed performance and robustness properties. Different to the classical engineering approach, a rigorous mathematical treatment is essential for the full understanding and applicability of the modern methods such as H2 or H8 control or methods based on the structured singular value µ. Nevertheless, no prior knowledge of Control Theory is required as the classical fundamentals are introduced within the first few chapters. Subsequently a large part of the text provides elementary examples and industrial case studies, which are developed in full detail to show how modern methods can be applied to advanced problems. They make intensive use of MATLAB, especially the Control Systems Toolbox and the µ-Analysis and Synthesis Toolbox.

  7. Robust Portfolio Optimization using CAPM Approach

    Directory of Open Access Journals (Sweden)

    mohsen gharakhani


    Full Text Available In this paper, a new robust model of multi-period portfolio problem has been developed. One of the key concerns in any asset allocation problem is how to cope with uncertainty about future returns. There are some approaches in the literature for this purpose including stochastic programming and robust optimization. Applying these techniques to multi-period portfolio problem may increase the problem size in a way that the resulting model is intractable. In this paper, a novel approach has been proposed to formulate multi-period portfolio problem as an uncertain linear program assuming that asset return follows the single-index factor model. Robust optimization technique has been also used to solve the problem. In order to evaluate the performance of the proposed model, a numerical example has been applied using simulated data.

  8. Occupant behaviour and robustness of building design

    DEFF Research Database (Denmark)

    Buso, Tiziana; Fabi, Valentina; Andersen, Rune Korsholm


    in a dynamic building energy simulation tool (IDA ICE). The analysis was carried out by simulating 15 building envelope designs in different thermal zones of an Office Reference Building in 3 climates: Stockholm, Frankfurt and Athens.In general, robustness towards changes in occupants' behaviour increased...... with increasing thermal mass and with decreasing transparent area of the envelope. The importance of the robustness' evaluation is highlighted in this paper, in order to obtain optimized buildings' designs for more accurate and realistic energy predictions.......Occupant behaviour can cause major discrepancies between the designed and the real total energy use in buildings. A possible solution to reduce the differences between predictions and actual performances is designing robust buildings, i.e. buildings whose performances show little variations...

  9. Clustering Incomplete Spectral Data with Robust Methods (United States)

    Äyrämö, S.; Pölönen, I.; Eskelinen, M. A.


    Missing value imputation is a common approach for preprocessing incomplete data sets. In case of data clustering, imputation methods may cause unexpected bias because they may change the underlying structure of the data. In order to avoid prior imputation of missing values the computational operations must be projected on the available data values. In this paper, we apply a robust nan-K-spatmed algorithm to the clustering problem on hyperspectral image data. Robust statistics, such as multivariate medians, are more insensitive to outliers than classical statistics relying on the Gaussian assumptions. They are, however, computationally more intractable due to the lack of closed-form solutions. We will compare robust clustering methods on the bands incomplete data cubes to standard K-means with full data cubes.

  10. Robust Object Tracking Using Valid Fragments Selection. (United States)

    Zheng, Jin; Li, Bo; Tian, Peng; Luo, Gang

    Local features are widely used in visual tracking to improve robustness in cases of partial occlusion, deformation and rotation. This paper proposes a local fragment-based object tracking algorithm. Unlike many existing fragment-based algorithms that allocate the weights to each fragment, this method firstly defines discrimination and uniqueness for local fragment, and builds an automatic pre-selection of useful fragments for tracking. Then, a Harris-SIFT filter is used to choose the current valid fragments, excluding occluded or highly deformed fragments. Based on those valid fragments, fragment-based color histogram provides a structured and effective description for the object. Finally, the object is tracked using a valid fragment template combining the displacement constraint and similarity of each valid fragment. The object template is updated by fusing feature similarity and valid fragments, which is scale-adaptive and robust to partial occlusion. The experimental results show that the proposed algorithm is accurate and robust in challenging scenarios.

  11. Blebbishields and mitotic cells exhibit robust macropinocytosis. (United States)

    Jinesh, Goodwin G; Kamat, Ashish M


    Cancer stem cells can survive and undergo transformation after apoptosis by initiating robust endocytosis. Endocytosis in-turn drives formation of serpentine filopodia, which promote construction of blebbishields from apoptotic bodies. However, the status and role of macropinocytosis in blebbishields is not known. Here, we show by scanning electron microscopy and by macropinocytosis assays that blebbishields exhibit robust macropinocytosis. Inhibiting dynamin-mediated endocytosis does not affect macropinocytosis in blebbishields or in mitotic cells. In addition, inhibiting macropinocytosis did not inhibit construction of blebbishields from apoptotic bodies. Thus, although apoptotic cancer stem cells exhibit robust macropinocytosis, macropinocytosis is not essential to generate blebbishields, although it may play other roles in blebbishield biology. © 2016 BioFactors, 43(2):181-186, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

  12. Robust optimization in electromagnetic scattering problems (United States)

    Bertsimas, Dimitris; Nohadani, Omid; Teo, Kwong Meng


    In engineering design, the physical properties of a system can often only be described by numerical simulation. Optimization of such systems is usually accomplished heuristically without taking into account that there are implementation errors that lead to very suboptimal, and often, infeasible solutions. We present a robust optimization method for electromagnetic scattering problems with large degrees of freedom and report on results when this technique is applied to optimization of aperiodic dielectric structures. The spatial configuration of 50 dielectric scattering cylinders is optimized to match a desired target function such that the optimal arrangement is robust against placement and prototype errors. Our optimization method inherently improves the robustness of the optimized solution with respect to relevant errors and is suitable for real-world design of materials with unconventional electromagnetic functionalities, as relevant to nanophotonics.

  13. Robust Optimization of Aperiodic Photonic Structures (United States)

    Nohadani, Omid; Meng Teo, Kwong; Bertsimas, Dimitris


    In engineering design, the physical properties of a system can often only be described by numerical simulation. Optimization of such systems is usually accomplished heuristically without taking into account that there are implementation errors that lead to very suboptimal, and often, infeasible solutions. We present a novel robust optimization method for electromagnetic scattering problems with large degrees of freedom, and report on results when this technique is applied to optimization of aperiodic dielectric structures. The spatial configuration of 50 dielectric scattering cylinders is optimized to match a desired target function such that the optimal arrangement is robust against placement and prototype errors. Our optimization method inherently improves the robustness of the optimized solution with respect to relevant errors and is suitable for real-world design of materials with novel electromagnetic functionalities.

  14. Robust fuzzy logic stabilization with disturbance elimination. (United States)

    Danapalasingam, Kumeresan A


    A robust fuzzy logic controller is proposed for stabilization and disturbance rejection in nonlinear control systems of a particular type. The dynamic feedback controller is designed as a combination of a control law that compensates for nonlinear terms in a control system and a dynamic fuzzy logic controller that addresses unknown model uncertainties and an unmeasured disturbance. Since it is challenging to derive a highly accurate mathematical model, the proposed controller requires only nominal functions of a control system. In this paper, a mathematical derivation is carried out to prove that the controller is able to achieve asymptotic stability by processing state measurements. Robustness here refers to the ability of the controller to asymptotically steer the state vector towards the origin in the presence of model uncertainties and a disturbance input. Simulation results of the robust fuzzy logic controller application in a magnetic levitation system demonstrate the feasibility of the control design.

  15. Robust estimation procedure in panel data model

    Energy Technology Data Exchange (ETDEWEB)

    Shariff, Nurul Sima Mohamad [Faculty of Science of Technology, Universiti Sains Islam Malaysia (USIM), 71800, Nilai, Negeri Sembilan (Malaysia); Hamzah, Nor Aishah [Institute of Mathematical Sciences, Universiti Malaya, 50630, Kuala Lumpur (Malaysia)


    The panel data modeling has received a great attention in econometric research recently. This is due to the availability of data sources and the interest to study cross sections of individuals observed over time. However, the problems may arise in modeling the panel in the presence of cross sectional dependence and outliers. Even though there are few methods that take into consideration the presence of cross sectional dependence in the panel, the methods may provide inconsistent parameter estimates and inferences when outliers occur in the panel. As such, an alternative method that is robust to outliers and cross sectional dependence is introduced in this paper. The properties and construction of the confidence interval for the parameter estimates are also considered in this paper. The robustness of the procedure is investigated and comparisons are made to the existing method via simulation studies. Our results have shown that robust approach is able to produce an accurate and reliable parameter estimates under the condition considered.

  16. Robust Mediation Analysis Based on Median Regression (United States)

    Yuan, Ying; MacKinnon, David P.


    Mediation analysis has many applications in psychology and the social sciences. The most prevalent methods typically assume that the error distribution is normal and homoscedastic. However, this assumption may rarely be met in practice, which can affect the validity of the mediation analysis. To address this problem, we propose robust mediation analysis based on median regression. Our approach is robust to various departures from the assumption of homoscedasticity and normality, including heavy-tailed, skewed, contaminated, and heteroscedastic distributions. Simulation studies show that under these circumstances, the proposed method is more efficient and powerful than standard mediation analysis. We further extend the proposed robust method to multilevel mediation analysis, and demonstrate through simulation studies that the new approach outperforms the standard multilevel mediation analysis. We illustrate the proposed method using data from a program designed to increase reemployment and enhance mental health of job seekers. PMID:24079925

  17. Handling Occlusions for Robust Augmented Reality Systems

    Directory of Open Access Journals (Sweden)

    Maidi Madjid


    Full Text Available Abstract In Augmented Reality applications, the human perception is enhanced with computer-generated graphics. These graphics must be exactly registered to real objects in the scene and this requires an effective Augmented Reality system to track the user's viewpoint. In this paper, a robust tracking algorithm based on coded fiducials is presented. Square targets are identified and pose parameters are computed using a hybrid approach based on a direct method combined with the Kalman filter. An important factor for providing a robust Augmented Reality system is the correct handling of targets occlusions by real scene elements. To overcome tracking failure due to occlusions, we extend our method using an optical flow approach to track visible points and maintain virtual graphics overlaying when targets are not identified. Our proposed real-time algorithm is tested with different camera viewpoints under various image conditions and shows to be accurate and robust.

  18. Robust C-Loss Kernel Classifiers. (United States)

    Xu, Guibiao; Hu, Bao-Gang; Principe, Jose C


    The correntropy-induced loss (C-loss) function has the nice property of being robust to outliers. In this paper, we study the C-loss kernel classifier with the Tikhonov regularization term, which is used to avoid overfitting. After using the half-quadratic optimization algorithm, which converges much faster than the gradient optimization algorithm, we find out that the resulting C-loss kernel classifier is equivalent to an iterative weighted least square support vector machine (LS-SVM). This relationship helps explain the robustness of iterative weighted LS-SVM from the correntropy and density estimation perspectives. On the large-scale data sets which have low-rank Gram matrices, we suggest to use incomplete Cholesky decomposition to speed up the training process. Moreover, we use the representer theorem to improve the sparseness of the resulting C-loss kernel classifier. Experimental results confirm that our methods are more robust to outliers than the existing common classifiers.

  19. Robustness of Distance-to-Default

    DEFF Research Database (Denmark)

    Jessen, Cathrine; Lando, David


    . A notable exception is a model with stochastic volatility of assets. In this case both the ranking of firms and the estimated default probabilities using distance-to-default perform significantly worse. We therefore propose a volatility adjustment of the distance-to-default measure, that significantly...... simulations to investigate the robustness of the distance-to-default measure to different model specifications. Overall we find distance-to-default to be robust to a number of deviations from the simple Merton model that involve different asset value dynamics and different default triggering mechanisms...

  20. Design of Robust Neural Network Classifiers

    DEFF Research Database (Denmark)

    Larsen, Jan; Andersen, Lars Nonboe; Hintz-Madsen, Mads


    This paper addresses a new framework for designing robust neural network classifiers. The network is optimized using the maximum a posteriori technique, i.e., the cost function is the sum of the log-likelihood and a regularization term (prior). In order to perform robust classification, we present...... a modified likelihood function which incorporates the potential risk of outliers in the data. This leads to the introduction of a new parameter, the outlier probability. Designing the neural classifier involves optimization of network weights as well as outlier probability and regularization parameters. We...

  1. Robust Inference with Multi-way Clustering


    A. Colin Cameron; Jonah B. Gelbach; Douglas L. Miller; Doug Miller


    In this paper we propose a variance estimator for the OLS estimator as well as for nonlinear estimators such as logit, probit and GMM. This variance estimator enables cluster-robust inference when there is two-way or multi-way clustering that is non-nested. The variance estimator extends the standard cluster-robust variance estimator or sandwich estimator for one-way clustering (e.g. Liang and Zeger (1986), Arellano (1987)) and relies on similar relatively weak distributional assumptions. Our...

  2. Robustness and modular structure in networks

    DEFF Research Database (Denmark)

    Bagrow, James P.; Lehmann, Sune; Ahn, Yong-Yeol


    -12]. Many complex systems, from power grids and the Internet to the brain and society [13-15], can be modeled using modular networks comprised of small, densely connected groups of nodes [16, 17]. These modules often overlap, with network elements belonging to multiple modules [18, 19]. Yet existing work...... on robustness has not considered the role of overlapping, modular structure. Here we study the robustness of these systems to the failure of elements. We show analytically and empirically that it is possible for the modules themselves to become uncoupled or non-overlapping well before the network disintegrates...

  3. Introduction to Robust Estimation and Hypothesis Testing

    CERN Document Server

    Wilcox, Rand R


    This revised book provides a thorough explanation of the foundation of robust methods, incorporating the latest updates on R and S-Plus, robust ANOVA (Analysis of Variance) and regression. It guides advanced students and other professionals through the basic strategies used for developing practical solutions to problems, and provides a brief background on the foundations of modern methods, placing the new methods in historical context. Author Rand Wilcox includes chapter exercises and many real-world examples that illustrate how various methods perform in different situations.Introduction to R

  4. Robust median estimator in logisitc regression

    Czech Academy of Sciences Publication Activity Database

    Hobza, T.; Pardo, L.; Vajda, Igor


    Roč. 138, č. 12 (2008), s. 3822-3840 ISSN 0378-3758 R&D Projects: GA MŠk 1M0572 Grant - others:Instituto Nacional de Estadistica(ES) MPO FI - IM3/136; GA MŠk(CZ) MTM 2006-06872 Institutional research plan: CEZ:AV0Z10750506 Keywords : Logistic regression * Median * Robustness * Consistency and asymptotic normality * Morgenthaler * Bianco and Yohai * Croux and Hasellbroeck Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 0.679, year: 2008

  5. Robust-mode analysis of hydrodynamic flows (United States)

    Roy, Sukesh; Gord, James R.; Hua, Jia-Chen; Gunaratne, Gemunu H.


    The emergence of techniques to extract high-frequency high-resolution data introduces a new avenue for modal decomposition to assess the underlying dynamics, especially of complex flows. However, this task requires the differentiation of robust, repeatable flow constituents from noise and other irregular features of a flow. Traditional approaches involving low-pass filtering and principle components analysis have shortcomings. The approach outlined here, referred to as robust-mode analysis, is based on Koopman decomposition. Three applications to (a) a counter-rotating cellular flame state, (b) variations in financial markets, and (c) turbulent injector flows are provided.

  6. The Robustness of High Danish National Happiness

    DEFF Research Database (Denmark)

    Hussain, M. Azhar


    Denmark’s top position in various rankings of country happiness is well-documented. This study goes beyond the national average comparisons and investigates whether Denmark’s top position is also found when we disaggregate data in line with social categories often used within the social sciences...... of the five rounds are included in this study. The results show that Denmark’s position at the top of the happiness scale is also robust when we look at population subgroups, but not in the sense that Denmark dominates all countries for all years. Instead, a modified version of robustness is necessary...

  7. Return Predictability, Model Uncertainty, and Robust Investment

    DEFF Research Database (Denmark)

    Lukas, Manuel

    Stock return predictability is subject to great uncertainty. In this paper we use the model confidence set approach to quantify uncertainty about expected utility from investment, accounting for potential return predictability. For monthly US data and six representative return prediction models, we...... find that confidence sets are very wide, change significantly with the predictor variables, and frequently include expected utilities for which the investor prefers not to invest. The latter motivates a robust investment strategy maximizing the minimal element of the confidence set. The robust investor...... allocates a much lower share of wealth to stocks compared to a standard investor....

  8. Learning and robustness to catch-and-release fishing in a shark social network. (United States)

    Mourier, Johann; Brown, Culum; Planes, Serge


    Individuals can play different roles in maintaining connectivity and social cohesion in animal populations and thereby influence population robustness to perturbations. We performed a social network analysis in a reef shark population to assess the vulnerability of the global network to node removal under different scenarios. We found that the network was generally robust to the removal of nodes with high centrality. The network appeared also highly robust to experimental fishing. Individual shark catchability decreased as a function of experience, as revealed by comparing capture frequency and site presence. Altogether, these features suggest that individuals learnt to avoid capture, which ultimately increased network robustness to experimental catch-and-release. Our results also suggest that some caution must be taken when using capture-recapture models often used to assess population size as assumptions (such as equal probabilities of capture and recapture) may be violated by individual learning to escape recapture. © 2017 The Author(s).

  9. Intermittent Theta-Burst Transcranial Magnetic Stimulation Alters Electrical Properties of Fast-Spiking Neocortical Interneurons in an Age-Dependent Fashion

    Directory of Open Access Journals (Sweden)

    Kathrin eHoppenrath


    Full Text Available Modulation of human cortical excitability by repetitive transcranial magnetic stimulation (rTMS appears to be in part related to changed activity of inhibitory systems. Our own studies showed that intermittent theta-burst stimulation (iTBS applied via rTMS to rat cortex primarily affects the parvalbumin-expressing (PV fast-spiking interneurons (FSIs, evident via a strongly reduced PV expression. We further found the iTBS effect on PV to be age-dependent since no reduction in PV could be induced before the perineuronal nets (PNNs of FSIs start to grow around postnatal day 30. To elucidate possible iTBS-induced changes in the electrical properties of FSIs and cortical network activity during cortical critical period, we performed ex vivo – in vitro whole-cell patch clamp recordings from pre-labelled FSIs in the current study. FSIs of verum iTBS-treated rats displayed a higher excitability than sham-treated controls at PD29-38, evident as higher rates of induced action potential firing at low current injections (100-200 pA and a more depolarized resting membrane potential. This effect was absent in younger (PD26-28 and older animals (PD40-62. Slices of verum iTBS-treated rats further showed higher rates of spontaneous EPSCs. Based on these and previous findings we conclude that FSIs are particularly sensitive to theta-burst stimulation during early cortical development, when FSIs show an activity-driven step of maturation which is paralleled by intense growth of the PNNs and subsequent closure of the cortical critical period. Although to be proven further, rTMS may be a possible early intervention to compensate for hypo-activity related mal-development of cortical neuronal circuits.

  10. Intermittent Theta-Burst Transcranial Magnetic Stimulation Alters Electrical Properties of Fast-Spiking Neocortical Interneurons in an Age-Dependent Fashion. (United States)

    Hoppenrath, Kathrin; Härtig, Wolfgang; Funke, Klaus


    Modulation of human cortical excitability by repetitive transcranial magnetic stimulation (rTMS) appears to be in part related to changed activity of inhibitory systems. Our own studies showed that intermittent theta-burst stimulation (iTBS) applied via rTMS to rat cortex primarily affects the parvalbumin-expressing (PV) fast-spiking interneurons (FSIs), evident via a strongly reduced PV expression. We further found the iTBS effect on PV to be age-dependent since no reduction in PV could be induced before the perineuronal nets (PNNs) of FSIs start to grow around postnatal day (PD) 30. To elucidate possible iTBS-induced changes in the electrical properties of FSIs and cortical network activity during cortical critical period, we performed ex vivo-in vitro whole-cell patch clamp recordings from pre-labeled FSIs in the current study. FSIs of verum iTBS-treated rats displayed a higher excitability than sham-treated controls at PD29-38, evident as higher rates of induced action potential firing at low current injections (100-200 pA) and a more depolarized resting membrane potential. This effect was absent in younger (PD26-28) and older animals (PD40-62). Slices of verum iTBS-treated rats further showed higher rates of spontaneous excitatory postsynaptic currents (sEPSCs). Based on these and previous findings we conclude that FSIs are particularly sensitive to TBS during early cortical development, when FSIs show an activity-driven step of maturation which is paralleled by intense growth of the PNNs and subsequent closure of the cortical critical period. Although to be proven further, rTMS may be a possible early intervention to compensate for hypo-activity related mal-development of cortical neuronal circuits.

  11. Long-lasting memory deficits in mice withdrawn from cocaine are concomitant with neuroadaptations in hippocampal basal activity, GABAergic interneurons and adult neurogenesis

    Directory of Open Access Journals (Sweden)

    David Ladrón de Guevara-Miranda


    Full Text Available Cocaine addiction disorder is notably aggravated by concomitant cognitive and emotional pathology that impedes recovery. We studied whether a persistent cognitive/emotional dysregulation in mice withdrawn from cocaine holds a neurobiological correlate within the hippocampus, a limbic region with a key role in anxiety and memory but that has been scarcely investigated in cocaine addiction research. Mice were submitted to a chronic cocaine (20 mg/kg/day for 12 days or vehicle treatment followed by 44 drug-free days. Some mice were then assessed on a battery of emotional (elevated plus-maze, light/dark box, open field, forced swimming and cognitive (object and place recognition memory, cocaine-induced conditioned place preference, continuous spontaneous alternation behavioral tests, while other mice remained in their home cage. Relevant hippocampal features [basal c-Fos activity, GABA+, parvalbumin (PV+ and neuropeptide Y (NPY+ interneurons and adult neurogenesis (cell proliferation and immature neurons] were immunohistochemically assessed 73 days after the chronic cocaine or vehicle protocol. The cocaine-withdrawn mice showed no remarkable exploratory or emotional alterations but were consistently impaired in all the cognitive tasks. All the cocaine-withdrawn groups, independent of whether they were submitted to behavioral assessment or not, showed enhanced basal c-Fos expression and an increased number of GABA+ cells in the dentate gyrus. Moreover, the cocaine-withdrawn mice previously submitted to behavioral training displayed a blunted experience-dependent regulation of PV+ and NPY+ neurons in the dentate gyrus, and neurogenesis in the hippocampus. Results highlight the importance of hippocampal neuroplasticity for the ingrained cognitive deficits present during chronic cocaine withdrawal.

  12. TOR signaling pathway and autophagy are involved in the regulation of circadian rhythms in behavior and plasticity of L2 interneurons in the brain of Drosophila melanogaster. (United States)

    Kijak, Ewelina; Pyza, Elżbieta


    Drosophila melanogaster is a common model used to study circadian rhythms in behavior and circadian clocks. However, numerous circadian rhythms have also been detected in non-clock neurons, especially in the first optic neuropil (lamina) of the fly's visual system. Such rhythms have been observed in the number of synapses and in the structure of interneurons, which exhibit changes in size and shape in a circadian manner. Although the patterns of these changes are known, the mechanism remains unclear. In the present study, we investigated the role of the TOR signaling pathway and autophagy in regulating circadian rhythms based on the behavior and structural plasticity of the lamina L2 monopolar cell dendritic trees. In addition, we examined the cyclic expression of the TOR signaling pathway (Tor, Pi3K class 1, Akt1) and autophagy (Atg5 and Atg7) genes in the fly's brain. We observed that Tor, Atg5 and Atg7 exhibit rhythmic expressions in the brain of wild-type flies in day/night conditions (LD 12:12) that are abolished in per01 clock mutants. The silencing of Tor in per expressing cells shortens a period of the locomotor activity rhythm of flies. In addition, silencing of the Tor and Atg5 genes in L2 cells disrupts the circadian plasticity of the L2 cell dendritic trees measured in the distal lamina. In turn, silencing of the Atg7 gene in L2 cells changes the pattern of this rhythm. Our results indicate that the TOR signaling pathway and autophagy are involved in the regulation of circadian rhythms in the behavior and plasticity of neurons in the brain of adult flies.

  13. Robust fitting of diurnal brightness temperature cycle

    CSIR Research Space (South Africa)

    Udahemuka, G


    Full Text Available . In this paper, diurnal brightness temperatures received from the METEOSAT Second Generation (MSG) satellite were interpolated for missing data based on a model, and a performance test was performed by comparing a new approach based on robust modelling...

  14. Robust and Adaptive Control With Aerospace Applications

    CERN Document Server

    Lavretsky, Eugene


    Robust and Adaptive Control shows the reader how to produce consistent and accurate controllers that operate in the presence of uncertainties and unforeseen events. Driven by aerospace applications the focus of the book is primarily on continuous-dynamical systems.  The text is a three-part treatment, beginning with robust and optimal linear control methods and moving on to a self-contained presentation of the design and analysis of model reference adaptive control (MRAC) for nonlinear uncertain dynamical systems. Recent extensions and modifications to MRAC design are included, as are guidelines for combining robust optimal and MRAC controllers. Features of the text include: ·         case studies that demonstrate the benefits of robust and adaptive control for piloted, autonomous and experimental aerial platforms; ·         detailed background material for each chapter to motivate theoretical developments; ·         realistic examples and simulation data illustrating key features ...

  15. Robust control charts in statistical process control

    NARCIS (Netherlands)

    Nazir, H.Z.


    The presence of outliers and contaminations in the output of the process highly affects the performance of the design structures of commonly used control charts and hence makes them of less practical use. One of the solutions to deal with this problem is to use control charts which are robust

  16. Robust Utility Maximization Under Convex Portfolio Constraints

    International Nuclear Information System (INIS)

    Matoussi, Anis; Mezghani, Hanen; Mnif, Mohamed


    We study a robust maximization problem from terminal wealth and consumption under a convex constraints on the portfolio. We state the existence and the uniqueness of the consumption–investment strategy by studying the associated quadratic backward stochastic differential equation. We characterize the optimal control by using the duality method and deriving a dynamic maximum principle

  17. Robust Utility Maximization Under Convex Portfolio Constraints

    Energy Technology Data Exchange (ETDEWEB)

    Matoussi, Anis, E-mail: [Université du Maine, Risk and Insurance institut of Le Mans Laboratoire Manceau de Mathématiques (France); Mezghani, Hanen, E-mail:; Mnif, Mohamed, E-mail: [University of Tunis El Manar, Laboratoire de Modélisation Mathématique et Numérique dans les Sciences de l’Ingénieur, ENIT (Tunisia)


    We study a robust maximization problem from terminal wealth and consumption under a convex constraints on the portfolio. We state the existence and the uniqueness of the consumption–investment strategy by studying the associated quadratic backward stochastic differential equation. We characterize the optimal control by using the duality method and deriving a dynamic maximum principle.

  18. Finite Algorithms for Robust Linear Regression

    DEFF Research Database (Denmark)

    Madsen, Kaj; Nielsen, Hans Bruun


    The Huber M-estimator for robust linear regression is analyzed. Newton type methods for solution of the problem are defined and analyzed, and finite convergence is proved. Numerical experiments with a large number of test problems demonstrate efficiency and indicate that this kind of approach may...

  19. Robust topology optimization accounting for geometric imperfections

    DEFF Research Database (Denmark)

    Schevenels, M.; Jansen, M.; Lombaert, Geert


    performance. As a consequence, the actual structure may be far from optimal. In this paper, a robust approach to topology optimization is presented, taking into account two types of geometric imperfections: variations of (1) the crosssections and (2) the locations of structural elements. The first type...

  20. Regularized robust coding for face recognition. (United States)

    Yang, Meng; Zhang, Lei; Yang, Jian; Zhang, David


    Recently the sparse representation based classification (SRC) has been proposed for robust face recognition (FR). In SRC, the testing image is coded as a sparse linear combination of the training samples, and the representation fidelity is measured by the l2-norm or l1 -norm of the coding residual. Such a sparse coding model assumes that the coding residual follows Gaussian or Laplacian distribution, which may not be effective enough to describe the coding residual in practical FR systems. Meanwhile, the sparsity constraint on the coding coefficients makes the computational cost of SRC very high. In this paper, we propose a new face coding model, namely regularized robust coding (RRC), which could robustly regress a given signal with regularized regression coefficients. By assuming that the coding residual and the coding coefficient are respectively independent and identically distributed, the RRC seeks for a maximum a posterior solution of the coding problem. An iteratively reweighted regularized robust coding (IR(3)C) algorithm is proposed to solve the RRC model efficiently. Extensive experiments on representative face databases demonstrate that the RRC is much more effective and efficient than state-of-the-art sparse representation based methods in dealing with face occlusion, corruption, lighting, and expression changes, etc.

  1. Robustness of Long Span Reciprocal Timber Structures

    DEFF Research Database (Denmark)

    Balfroid, Nathalie; Kirkegaard, Poul Henning


    Robustness of structural systems has obtained a renewed interest due to a much more frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure. The interest has also been facilitated due to recently severe structural failures such as that at R...

  2. Robust classification using mixtures of dependency networks

    DEFF Research Database (Denmark)

    Gámez, José A.; Mateo, Juan L.; Nielsen, Thomas Dyhre


    -ups are often obtained at the expense of accuracy. In this paper we try to address this issue through the use of mixtures of dependency networks. To reduce learning time and improve robustness when dealing with data sparse classes, we outline methods for reusing calculations across mixture components. Finally...

  3. Robustness of dynamic systems with parameter uncertainties

    CERN Document Server

    Balemi, S; Truöl, W


    Robust Control is one of the fastest growing and promising areas of research today. In many practical systems there exist uncertainties which have to be considered in the analysis and design of control systems. In the last decade methods were developed for dealing with dynamic systems with unstructured uncertainties such as HOO_ and £I-optimal control. For systems with parameter uncertainties, the seminal paper of V. L. Kharitonov has triggered a large amount of very promising research. An international workshop dealing with all aspects of robust control was successfully organized by S. P. Bhattacharyya and L. H. Keel in San Antonio, Texas, USA in March 1991. We organized the second international workshop in this area in Ascona, Switzer­ land in April 1992. However, this second workshop was restricted to robust control of dynamic systems with parameter uncertainties with the objective to concentrate on some aspects of robust control. This book contains a collection of papers presented at the International W...

  4. Robust tensor estimation in diffusion tensor imaging (United States)

    Maximov, Ivan I.; Grinberg, Farida; Jon Shah, N.


    The signal response measured in diffusion tensor imaging is subject to detrimental influences caused by noise. Noise fields arise due to various contributions such as thermal and physiological noise and sources related to the hardware imperfection. As a result, diffusion tensors estimated by different linear and non-linear least squares methods in absence of a proper noise correction tend to be substantially corrupted. In this work, we propose an advanced tensor estimation approach based on the least median squares method of the robust statistics. Both constrained and non-constrained versions of the method are considered. The performance of the developed algorithm is compared to that of the conventional least squares method and of the alternative robust methods proposed in the literature. Two examples of simulated diffusion attenuations and experimental in vivo diffusion data sets were used as a basis for comparison. The robust algorithms were shown to be advantageous compared to the least squares method in the cases where elimination of the outliers is desirable. Additionally, the constraints were applied in order to prevent generation of the non-positive definite tensors and reduce related artefacts in the maps of fractional anisotropy. The developed method can potentially be exploited also by other MR techniques where a robust regression or outlier localisation is required.

  5. Grassmann Averages for Scalable Robust PCA

    DEFF Research Database (Denmark)

    Hauberg, Søren; Feragen, Aasa; Black, Michael J.


    to vectors (subspaces) or elements of vectors; we focus on the latter and use a trimmed average. The resulting Trimmed Grassmann Average (TGA) is particularly appropriate for computer vision because it is robust to pixel outliers. The algorithm has low computational complexity and minimal memory requirements...

  6. Robust control investigations for equipment loaded panels

    DEFF Research Database (Denmark)

    Aglietti, G.S.; Langley, R.S.; Rogers, E.


    This paper develops a modelling technique for equipment load panels which directly produces (adequate) models of the underlying dynamics on which to base robust controller design/evaluations. This technique is based on the use of the Lagrange's equations of motion and the resulting models are ver...... are verified against those produced by a finite Element Method Model...

  7. Robust balance shift control with posture optimization

    NARCIS (Netherlands)

    Kavafoglu, Z.; Kavafoglu, Ersan; Egges, J.


    In this paper we present a control framework which creates robust and natural balance shifting behaviours during standing. Given high-level features such as the position of the center of mass projection and the foot configurations, a kinematic posture satisfying these features is synthesized using

  8. Stability and robustness analysis of acyclic timetable

    NARCIS (Netherlands)

    Goverde, R.M.P.; Yan, F.


    o satisfy the growing passenger transportation demands and improve the service quality n railway system, a more stable and robust timetable needs to be designed while considering highly utilized capacity. Acyclic timetable is extensively applied in large ailway networks. In order to acquire the

  9. Robust giant magnetoresistive effect type multilayer sensor

    NARCIS (Netherlands)

    Lenssen, K.M.H.; Kuiper, A.E.T.; Roozeboom, F.


    A robust Giant Magneto Resistive effect type multilayer sensor comprising a free and a pinned ferromagnetic layer, which can withstand high temperatures and strong magnetic fields as required in automotive applications. The GMR multi-layer has an asymmetric magneto-resistive curve and enables

  10. Robustness of river basin water quality models

    NARCIS (Netherlands)

    de Blois, Chris; Wind, H.G.; de Kok, Jean-Luc; Koppeschaar, K.


    In this paper the concept of robustness is introduced and applied to a model for the analysis of the impacts of spatially distributed policy measures on the surface water quality on a river basin scale. In this model the influence of precipitation on emissions and resuspension of pollutants in the

  11. Chromatin regulators, phenotypic robustness and autism risk

    Directory of Open Access Journals (Sweden)

    Reut eSuliman


    Full Text Available Though extensively characterized clinically, the causes of autism spectrum disorder (ASD remain a mystery. ASD is known to have a strong genetic basis, but it is genetically very heterogeneous. Recent studies have estimated that de novo disruptive mutations in hundreds of genes may contribute to ASD. However, it is unclear how it is possible for mutations in so many different genes to contribute to ASD. Recent findings suggest that many of the mutations disrupt genes involved in transcription regulation that are expressed prenatally in the developing brain. De novo disruptive mutations are also more frequent in girls with ASD, despite the fact that ASD is more prevalent in boys. In this paper, we hypothesize that loss of robustness may contribute to ASD. Loss of phenotypic robustness may be caused by mutations that disrupt capacitors that operate in the developing brain. This may lead to the release of cryptic genetic variation that contributes to ASD. Reduced robustness is consistent with the observed variability in expressivity and incomplete penetrance. It is also consistent with the hypothesis that the development of the female brain is more robust, and it may explain the higher rate and severity of disruptive de novo mutations in girls with ASD.

  12. Robust Satisfiability of Systems of Equations

    Czech Academy of Sciences Publication Activity Database

    Franek, Peter; Krčál, M.


    Roč. 62, č. 4 (2015), Article 26 ISSN 0004-5411 R&D Projects: GA ČR GBP202/12/G061 Grant - others:GA MŠk(CZ) LL1201 Institutional support: RVO:67985807 Keywords : nonlinear equations * satisfability * undecibility * topological extensions * uncertainty * robustness Subject RIV: IN - Informatics, Computer Science Impact factor: 1.803, year: 2015

  13. Neuromorphic Configurable Architecture for Robust Motion Estimation

    Directory of Open Access Journals (Sweden)

    Guillermo Botella


    Full Text Available The robustness of the human visual system recovering motion estimation in almost any visual situation is enviable, performing enormous calculation tasks continuously, robustly, efficiently, and effortlessly. There is obviously a great deal we can learn from our own visual system. Currently, there are several optical flow algorithms, although none of them deals efficiently with noise, illumination changes, second-order motion, occlusions, and so on. The main contribution of this work is the efficient implementation of a biologically inspired motion algorithm that borrows nature templates as inspiration in the design of architectures and makes use of a specific model of human visual motion perception: Multichannel Gradient Model (McGM. This novel customizable architecture of a neuromorphic robust optical flow can be constructed with FPGA or ASIC device using properties of the cortical motion pathway, constituting a useful framework for building future complex bioinspired systems running in real time with high computational complexity. This work includes the resource usage and performance data, and the comparison with actual systems. This hardware has many application fields like object recognition, navigation, or tracking in difficult environments due to its bioinspired and robustness properties.

  14. New solutions for NPP robustness improvement

    International Nuclear Information System (INIS)

    Wolski, Alexander


    Fukushima accident has triggered a major re-assessment of robustness of nuclear stations. First round of evaluations has been Finished. Improvement areas and strategies have been identified. Implementation of upgrades has started world-wide. New solutions can provide substantial benefits

  15. Robust unit commitment with dispatchable wind power

    NARCIS (Netherlands)

    Morales Espana, G.; Lorca, Álvaro; de Weerdt, M.M.

    The increasing penetration of uncertain generation such as wind and solar in power systems imposes new challenges to the unit commitment (UC) problem, one of the most critical tasks in power systems operations. The two most common approaches to address these challenges — stochastic and robust

  16. Quantifying the robustness of metro networks

    NARCIS (Netherlands)

    Wang, X.; Koç, Y.; Derrible, S.; Nasir Ahmad, Sk.; Kooij, R.E.


    Metros (heavy rail transit systems) are integral parts of urban transportation systems. Failures in their operations can have serious impacts on urban mobility, and measuring their robustness is therefore critical. Moreover, as physical networks, metros can be viewed as network topological entities,

  17. Robustness of Distance-to-Default

    DEFF Research Database (Denmark)

    Jessen, Cathrine; Lando, David


    Distance-to-default is a remarkably robust measure for ranking firms according to their risk of default. The ranking seems to work despite the fact that the Merton model from which the measure is derived produces default probabilities that are far too small when applied to real data. We use simul...

  18. Robust Geometric Control of a Distillation Column

    DEFF Research Database (Denmark)

    Kymmel, Mogens; Andersen, Henrik Weisberg


    A frequency domain method, which makes it possible to adjust multivariable controllers with respect to both nominal performance and robustness, is presented. The basic idea in the approach is that the designer assigns objectives such as steady-state tracking, maximum resonance peaks, bandwidth, m...... is used to examine and improve geometric control of a binary distillation column....

  19. Structurally robust control of complex networks (United States)

    Nacher, Jose C.; Akutsu, Tatsuya


    Robust control theory has been successfully applied to numerous real-world problems using a small set of devices called controllers. However, the real systems represented by networks contain unreliable components and modern robust control engineering has not addressed the problem of structural changes on complex networks including scale-free topologies. Here, we introduce the concept of structurally robust control of complex networks and provide a concrete example using an algorithmic framework that is widely applied in engineering. The developed analytical tools, computer simulations, and real network analyses lead herein to the discovery that robust control can be achieved in scale-free networks with exactly the same order of controllers required in a standard nonrobust configuration by adjusting only the minimum degree. The presented methodology also addresses the probabilistic failure of links in real systems, such as neural synaptic unreliability in Caenorhabditis elegans, and suggests a new direction to pursue in studies of complex networks in which control theory has a role.

  20. Highly Robust Methods in Data Mining

    Czech Academy of Sciences Publication Activity Database

    Kalina, Jan


    Roč. 8, č. 1 (2013), s. 9-24 ISSN 1452-4864 Institutional support: RVO:67985807 Keywords : data mining * robust statistics * high-dimensional data * cluster analysis * logistic regression * neural networks Subject RIV: BB - Applied Statistics, Operational Research

  1. Automatic Synthesis of Robust and Optimal Controllers

    DEFF Research Database (Denmark)

    Cassez, Franck; Jessen, Jan Jacob; Larsen, Kim Guldstrand


    In this paper, we show how to apply recent tools for the automatic synthesis of robust and near-optimal controllers for a real industrial case study. We show how to use three different classes of models and their supporting existing tools, Uppaal-TiGA for synthesis, phaver for verification...

  2. A robust adaptive controller for robot manipulators

    NARCIS (Netherlands)

    Berghuis, Harry; Berghuis, Harry; Ortega, Romeo; Nijmeijer, Henk


    The authors propose a globally convergent adaptive control scheme for robot motion control with the following features: first, the adaptation law processes enhanced robustness with respect to noisy velocity measurements; secondly, the controller does not require the inclusion of high-gain loops that

  3. Robust weighted scan matching with quadtrees

    NARCIS (Netherlands)

    Visser, A.; Slamet, B.A.; Pfingsthorn, M.


    This paper presents the improvement of the robustness and accuracy of the weighted scan matching algorithm matching against the union of earlier acquired scans. The approach allows to reduce the correspondence error, which is explicitly modeled in the weighted scan matching algorithm, by providing a

  4. Robust Pedestrian Navigation for Challenging Applications


    Gilliéron, PY; Renaudin, V


    Presentation of a concept for robust indoor navigation. The concept is based on three key elements: - the use of an absolute geographical reference - the hybridisation of complementary technologies - specific motion models. This concept is illustrated by the means of two applications: the urban displacement of blind people and the indoor guidance of fire-fighters

  5. Robust inference in sample selection models

    KAUST Repository

    Zhelonkin, Mikhail


    The problem of non-random sample selectivity often occurs in practice in many fields. The classical estimators introduced by Heckman are the backbone of the standard statistical analysis of these models. However, these estimators are very sensitive to small deviations from the distributional assumptions which are often not satisfied in practice. We develop a general framework to study the robustness properties of estimators and tests in sample selection models. We derive the influence function and the change-of-variance function of Heckman\\'s two-stage estimator, and we demonstrate the non-robustness of this estimator and its estimated variance to small deviations from the model assumed. We propose a procedure for robustifying the estimator, prove its asymptotic normality and give its asymptotic variance. Both cases with and without an exclusion restriction are covered. This allows us to construct a simple robust alternative to the sample selection bias test. We illustrate the use of our new methodology in an analysis of ambulatory expenditures and we compare the performance of the classical and robust methods in a Monte Carlo simulation study.

  6. Robust network design for multispecies conservation (United States)

    Ronan Le Bras; Bistra Dilkina; Yexiang Xue; Carla P. Gomes; Kevin S. McKelvey; Michael K. Schwartz; Claire A. Montgomery


    Our work is motivated by an important network design application in computational sustainability concerning wildlife conservation. In the face of human development and climate change, it is important that conservation plans for protecting landscape connectivity exhibit certain level of robustness. While previous work has focused on conservation strategies that result...

  7. Parametric uncertainty modeling for robust control

    DEFF Research Database (Denmark)

    Rasmussen, K.H.; Jørgensen, Sten Bay


    to perform robustness analysis on a control system using the structured singular value. The idea behind the proposed method is to fit a rational function to the parameter variation. The parameter variation can then be expressed as a linear fractional transformation (LFT), It is discussed how the proposed....... (C) 1999 Elsevier Science Ltd. All rights reserved....

  8. Robust online face tracking-by-detection

    NARCIS (Netherlands)

    Comaschi, F.; Stuijk, S.; Basten, T.; Corporaal, H.


    The problem of online face tracking from unconstrained videos is still unresolved. Challenges range from coping with severe online appearance variations to coping with occlusion. We propose RFTD (Robust Face Tracking-by-Detection), a system which combines tracking and detection into a single

  9. A robust interpretation of duration calculus

    DEFF Research Database (Denmark)

    Franzle, M.; Hansen, Michael Reichhardt


    Calculus (DC), our findings are that the robust interpretation of DC is equivalent to a multi-valued interpretation that uses the real numbers as semantic domain and assigns Lipschitz-continuous interpretations to all operators of DC. Furthermore, this continuity permits approximation between discrete...

  10. Some Diagnostic Tools in Robust Econometrics

    Czech Academy of Sciences Publication Activity Database

    Kalina, Jan


    Roč. 50, č. 2 (2011), s. 55-67 ISSN 0231-9721 Grant - others:GA ČR(CZ) GA402/09/0557 Institutional research plan: CEZ:AV0Z10300504 Keywords : robust regression * autocorrelated errors * heteroscedastic regression * instrumental variables * least weighted squares Subject RIV: BB - Applied Statistics, Operational Research

  11. Quantitative Robust Control Engineering: Theory and Applications (United States)


    the twentieth century, there has been a tremendous advance in the state-of-the- art of robust frequency domain methods. One of the main techniques...Templates [28]. Bartlett, A.C., Tesi , A., Vicino, A. (1993). Frequency response of uncertain systems with interval plants. IEEE Trans. On Automatic

  12. Replication and Robustness in Developmental Research (United States)

    Duncan, Greg J.; Engel, Mimi; Claessens, Amy; Dowsett, Chantelle J.


    Replications and robustness checks are key elements of the scientific method and a staple in many disciplines. However, leading journals in developmental psychology rarely include explicit replications of prior research conducted by different investigators, and few require authors to establish in their articles or online appendices that their key…

  13. Robust Refinement as Implemented in TOPAS

    Energy Technology Data Exchange (ETDEWEB)

    Stone, K.; Stephens, P


    A robust refinement procedure is implemented in the program TOPAS through an iterative reweighting of the data. Examples are given of the procedure as applied to fitting partially overlapped peaks by full and partial models and also of the structures of ibuprofen and acetaminophen in the presence of unmodeled impurity contributions

  14. Changepoint detection in base-resolution methylome data reveals a robust signature of methylated domain landscape. (United States)

    Yokoyama, Takao; Miura, Fumihito; Araki, Hiromitsu; Okamura, Kohji; Ito, Takashi


    Base-resolution methylome data generated by whole-genome bisulfite sequencing (WGBS) is often used to segment the genome into domains with distinct methylation levels. However, most segmentation methods include many parameters to be carefully tuned and/or fail to exploit the unsurpassed resolution of the data. Furthermore, there is no simple method that displays the composition of the domains to grasp global trends in each methylome. We propose to use changepoint detection for domain demarcation based on base-resolution methylome data. While the proposed method segments the methylome in a largely comparable manner to conventional approaches, it has only a single parameter to be tuned. Furthermore, it fully exploits the base-resolution of the data to enable simultaneous detection of methylation changes in even contrasting size ranges, such as focal hypermethylation and global hypomethylation in cancer methylomes. We also propose a simple plot termed methylated domain landscape (MDL) that globally displays the size, the methylation level and the number of the domains thus defined, thereby enabling one to intuitively grasp trends in each methylome. Since the pattern of MDL often reflects cell lineages and is largely unaffected by data size, it can serve as a novel signature of methylome. Changepoint detection in base-resolution methylome data followed by MDL plotting provides a novel method for methylome characterization and will facilitate global comparison among various WGBS data differing in size and even species origin.

  15. Evidence of a robust resident bacteriophage population revealed through analysis of the human salivary virome


    Pride, David T; Salzman, Julia; Haynes, Matthew; Rohwer, Forest; Davis-Long, Clara; White, Richard A; Loomer, Peter; Armitage, Gary C; Relman, David A


    Viruses are the most abundant known infectious agents on the planet and are significant drivers of diversity in a variety of ecosystems. Although there have been numerous studies of viral communities, few have focused on viruses within the indigenous human microbiota. We analyzed 2 267 695 virome reads from viral particles and compared them with 263 516 bacterial 16S rRNA gene sequences from the saliva of five healthy human subjects over a 2- to 3-month period, in order to improve our underst...

  16. Robust dynamic classes revealed by measuring the response function of a social system. (United States)

    Crane, Riley; Sornette, Didier


    We study the relaxation response of a social system after endogenous and exogenous bursts of activity using the time series of daily views for nearly 5 million videos on YouTube. We find that most activity can be described accurately as a Poisson process. However, we also find hundreds of thousands of examples in which a burst of activity is followed by an ubiquitous power-law relaxation governing the timing of views. We find that these relaxation exponents cluster into three distinct classes and allow for the classification of collective human dynamics. This is consistent with an epidemic model on a social network containing two ingredients: a power-law distribution of waiting times between cause and action and an epidemic cascade of actions becoming the cause of future actions. This model is a conceptual extension of the fluctuation-dissipation theorem to social systems [Ruelle, D (2004) Phys Today 57:48-53] and [Roehner BM, et al., (2004) Int J Mod Phys C 15:809-834], and provides a unique framework for the investigation of timing in complex systems.

  17. Robust FIR Beamforming Applied TO Medical Ultrasound (United States)

    Guenther, Drake A.; Walker, William F.


    We previously described a beamformer architecture that replaces the single apodization weights on each receive channel with channel-unique finite impulse response (FIR) filters. The filter weights are designed to optimize the contrast resolution performance of the imaging system. While the FIR beamformer offers significant gains in contrast resolution, the beamformer suffers from low sensitivity and its performance rapidly degrades in the presence of noise. In this paper a new method is presented to improve the robustness of the FIR beamformer to electronic noise as well as variation or uncertainty in the array response. A method is also described, which controls the sidelobe levels of the FIR beamformer’s spatial response by applying an arbitrary weighting function in the filter design algorithm. The robust FIR beamformer is analyzed using a generalized cystic resolution metric that quantifies a beamformer’s clinical imaging performance as a function of cyst size and channel input signal-to-noise ratio (SNR). Fundamental performance limits are compared between two robust FIR beamformers (the dynamic focus FIR (DF-FIR) beamformer and the group focus FIR (GF-FIR) beamformer), the conventional delay-and-sum (DAS) beamformer, and the spatial matched filter (SMF) beamformer. Results from this study show that the new DF- and GF-FIR beamformers are more robust to electronic noise compared to the optimal contrast resolution FIR beamformer. Furthermore, the added robustness only comes with a slight loss in cystic resolution. Results from the generalized cystic resolution metric show that a 9-tap robust FIR beamformer outperforms the SMF and DAS beamformer until receive channel input SNR drops below −5 dB; whereas, the 9-tap optimal contrast resolution beamformer’s performance deteriorates around 50 dB SNR. The effects of moderate phase aberrations, characterized by an a priori root-mean-square strength of 28 ns and an a priori full-width at half-maximum correlation

  18. Robust Nonnegative Patch Alignment for Dimensionality Reduction. (United States)

    You, Xinge; Ou, Weihua; Chen, Chun Lung Philip; Li, Qiang; Zhu, Ziqi; Tang, Yuanyan


    Dimensionality reduction is an important method to analyze high-dimensional data and has many applications in pattern recognition and computer vision. In this paper, we propose a robust nonnegative patch alignment for dimensionality reduction, which includes a reconstruction error term and a whole alignment term. We use correntropy-induced metric to measure the reconstruction error, in which the weight is learned adaptively for each entry. For the whole alignment, we propose locality-preserving robust nonnegative patch alignment (LP-RNA) and sparsity-preserviing robust nonnegative patch alignment (SP-RNA), which are unsupervised and supervised, respectively. In the LP-RNA, we propose a locally sparse graph to encode the local geometric structure of the manifold embedded in high-dimensional space. In particular, we select large p -nearest neighbors for each sample, then obtain the sparse representation with respect to these neighbors. The sparse representation is used to build a graph, which simultaneously enjoys locality, sparseness, and robustness. In the SP-RNA, we simultaneously use local geometric structure and discriminative information, in which the sparse reconstruction coefficient is used to characterize the local geometric structure and weighted distance is used to measure the separability of different classes. For the induced nonconvex objective function, we formulate it into a weighted nonnegative matrix factorization based on half-quadratic optimization. We propose a multiplicative update rule to solve this function and show that the objective function converges to a local optimum. Several experimental results on synthetic and real data sets demonstrate that the learned representation is more discriminative and robust than most existing dimensionality reduction methods.

  19. Effects of methodology and analysis strategy on robustness of pestivirus phylogeny. (United States)

    Liu, Lihong; Xia, Hongyan; Baule, Claudia; Belák, Sándor; Wahlberg, Niklas


    Phylogenetic analysis of pestiviruses is a useful tool for classifying novel pestiviruses and for revealing their phylogenetic relationships. In this study, robustness of pestivirus phylogenies has been compared by analyses of the 5'UTR, and complete N(pro) and E2 gene regions separately and combined, performed by four methods: neighbour-joining (NJ), maximum parsimony (MP), maximum likelihood (ML), and Bayesian inference (BI). The strategy of analysing the combined sequence dataset by BI, ML, and MP methods resulted in a single, well-supported tree topology, indicating a reliable and robust pestivirus phylogeny. By contrast, the single-gene analysis strategy resulted in 12 trees of different topologies, revealing different relationships among pestiviruses. These results indicate that the strategies and methodologies are two vital aspects affecting the robustness of the pestivirus phylogeny. The strategy and methodologies outlined in this paper may have a broader application in inferring phylogeny of other RNA viruses.

  20. Robust mutant strain design by pessimistic optimization. (United States)

    Apaydin, Meltem; Xu, Liang; Zeng, Bo; Qian, Xiaoning


    Flux Balance Analysis (FBA) based mathematical modeling enables in silico prediction of systems behavior for genome-scale metabolic networks. Computational methods have been derived in the FBA framework to solve bi-level optimization for deriving "optimal" mutant microbial strains with targeted biochemical overproduction. The common inherent assumption of these methods is that the surviving mutants will always cooperate with the engineering objective by overproducing the maximum desired biochemicals. However, it has been shown that this optimistic assumption may not be valid in practice. We study the validity and robustness of existing bi-level methods for strain optimization under uncertainty and non-cooperative environment. More importantly, we propose new pessimistic optimization formulations: P-ROOM and P-OptKnock, aiming to derive robust mutants with the desired overproduction under two different mutant cell survival models: (1) ROOM assuming mutants have the minimum changes in reaction fluxes from wild-type flux values, and (2) the one considered by OptKnock maximizing the biomass production yield. When optimizing for desired overproduction, our pessimistic formulations derive more robust mutant strains by considering the uncertainty of the cell survival models at the inner level and the cooperation between the outer- and inner-level decision makers. For both P-ROOM and P-OptKnock, by converting multi-level formulations into single-level Mixed Integer Programming (MIP) problems based on the strong duality theorem, we can derive exact optimal solutions that are highly scalable with large networks. Our robust formulations P-ROOM and P-OptKnock are tested with a small E. coli core metabolic network and a large-scale E. coli iAF1260 network. We demonstrate that the original bi-level formulations (ROOM and OptKnock) derive mutants that may not achieve the predicted overproduction under uncertainty and non-cooperative environment. The knockouts obtained by the

  1. Reliability-Based Robustness Analysis for a Croatian Sports Hall

    DEFF Research Database (Denmark)

    Čizmar, Dean; Kirkegaard, Poul Henning; Sørensen, John Dalsgaard


    This paper presents a probabilistic approach for structural robustness assessment for a timber structure built a few years ago. The robustness analysis is based on a structural reliability based framework for robustness and a simplified mechanical system modelling of a timber truss system...... is expressed and evaluated by a robustness index. Next, the robustness is assessed using system reliability indices where the probabilistic failure model is modelled by a series system of parallel systems....

  2. Robustness of Linear Systems towards Multi-Dissipative Pertubations

    DEFF Research Database (Denmark)

    Thygesen, Uffe Høgsbro; Poulsen, Niels Kjølstad


    We consider the question of robust stability of a linear time invariant plant subject to dynamic perturbations, which are dissipative in the sense of Willems with respect to several quadratic supply rates. For instance, parasitic dynamics are often both small gain and passive. We reduce several...... robustness analysis questions to linear matrix inequalities: robust stability, robust H2 performance and robust performance in presence of disturbances with finite signal-to-noise ratios...

  3. Combined Pharmacological and Genetic Manipulations Unlock Unprecedented Temporal Elasticity and Reveal Phase-Specific Modulation of the Molecular Circadian Clock of the Mouse Suprachiasmatic Nucleus. (United States)

    Patton, Andrew P; Chesham, Johanna E; Hastings, Michael H


    The suprachiasmatic nucleus (SCN) is the master circadian oscillator encoding time-of-day information. SCN timekeeping is sustained by a cell-autonomous transcriptional-translational feedback loop, whereby expression of the Period and Cryptochrome genes is negatively regulated by their protein products. This loop in turn drives circadian oscillations in gene expression that direct SCN electrical activity and thence behavior. The robustness of SCN timekeeping is further enhanced by interneuronal, circuit-level coupling. The aim of this study was to combine pharmacological and genetic manipulations to push the SCN clockwork toward its limits and, by doing so, probe cell-autonomous and emergent, circuit-level properties. Circadian oscillation of mouse SCN organotypic slice cultures was monitored as PER2::LUC bioluminescence. SCN of three genetic backgrounds-wild-type, short-period CK1ε(Tau/Tau) mutant, and long-period Fbxl3(Afh/Afh) mutant-all responded reversibly to pharmacological manipulation with period-altering compounds: picrotoxin, PF-670462 (4-[1-Cyclohexyl-4-(4-fluorophenyl)-1H-imidazol-5-yl]-2-pyrimidinamine dihydrochloride), and KNK437 (N-Formyl-3,4-methylenedioxy-benzylidine-gamma-butyrolactam). This revealed a remarkably wide operating range of sustained periods extending across 25 h, from ≤17 h to >42 h. Moreover, this range was maintained at network and single-cell levels. Development of a new technique for formal analysis of circadian waveform, first derivative analysis (FDA), revealed internal phase patterning to the circadian oscillation at these extreme periods and differential phase sensitivity of the SCN to genetic and pharmacological manipulations. For example, FDA of the CK1ε(Tau/Tau) mutant SCN treated with the CK1ε-specific inhibitor PF-4800567 (3-[(3-Chlorophenoxy)methyl]-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine hydrochloride) revealed that period acceleration in the mutant is due to inappropriately phased

  4. Robust Reed Solomon Coded MPSK Modulation

    Directory of Open Access Journals (Sweden)

    Emir M. Husni


    Full Text Available In this paper, construction of partitioned Reed Solomon coded modulation (RSCM, which is robust for the additive white Gaussian noise channel and a Rayleigh fading channel, is investigated. By matching configuration of component codes with the channel characteristics, it is shown that this system is robust for the Gaussian and a Rayleigh fading channel. This approach is compared with non-partitioned RSCM, a Reed Solomon code combined with an MPSK signal set using Gray mapping; and block coded MPSK modulation using binary codes, Reed Muller codes. All codes use hard decision decoding algorithm. Simulation results for these schemes show that RSCM based on set partitioning performs better than those that are not based on set partitioning and Reed Muller Coded Modulation across a wide range of conditions. The novel idea here is that in the receiver, we use a rotated 2^(m+1-PSK detector if the transmitter uses a 2^m-PSK modulator.

  5. Robust Multiparty Computation with Linear Communication Complexity

    DEFF Research Database (Denmark)

    Hirt, Martin; Nielsen, Jesper Buus


    We present a robust multiparty computation protocol. The protocol is for the cryptographic model with open channels and a poly-time adversary, and allows n parties to actively securely evaluate any poly-sized circuit with resilience t communication complexity in bits over the point......-to-point channels is (Sn+n), where S is the size of the circuit being securely evaluated, κ is the security parameter and is the communication complexity of one broadcast of a κ-bit value. This means the average number of bits sent and received by a single party is (S+), which is almost independent of the number...... of participating parties. This is the first robust multiparty computation protocol with this property....

  6. Robust lyapunov controller for uncertain systems

    KAUST Repository

    Laleg-Kirati, Taous-Meriem


    Various examples of systems and methods are provided for Lyapunov control for uncertain systems. In one example, a system includes a process plant and a robust Lyapunov controller configured to control an input of the process plant. The robust Lyapunov controller includes an inner closed loop Lyapunov controller and an outer closed loop error stabilizer. In another example, a method includes monitoring a system output of a process plant; generating an estimated system control input based upon a defined output reference; generating a system control input using the estimated system control input and a compensation term; and adjusting the process plant based upon the system control input to force the system output to track the defined output reference. An inner closed loop Lyapunov controller can generate the estimated system control input and an outer closed loop error stabilizer can generate the system control input.

  7. Communicating via robust synchronization of chaotic lasers

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Gutierrez, R.M. [Engineering Faculty, Baja California Autonomous University (UABC), Km. 103 Carret. Tij-Ens., 22860 Ensenada, B.C. (Mexico); Posadas-Castillo, C. [Engineering Faculty, Baja California Autonomous University (UABC), Km. 103 Carret. Tij-Ens., 22860 Ensenada, B.C. (Mexico); FIME, Autonomous University of Nuevo Leon (UANL), Pedro de Alba, S.N., Cd. Universitaria, San Nicolas de los Garza, NL (Mexico); Lopez-Mancilla, D. [Departamento de Ciencias Exactas y Tecnologicas, Centro Universitario de los Lagos, Universidad de Guadalajara (CULagos-UdeG), Enrique Diaz de Leon s/n, 47460 Lagos de Moreno, Jal. (Mexico); Cruz-Hernandez, C. [Electronics and Telecommunications Department, Scientific Research and Advanced Studies of Ensenada (CICESE), Km. 107 Carret. Tij-Ens., 22860 Ensenada, B.C. (Mexico)], E-mail:


    In this paper, the robust synchronization problem for coupled chaotic Nd:YAG lasers is addressed. We resort to complex systems theory to achieve chaos synchronization. Based on stability theory, it is shown that the state trajectories of the perturbed error synchronization are ultimately bounded, provided the unperturbed synchronization error system is exponentially stable, and some conditions on the bounds of the perturbation terms are satisfied. So that, encoding, transmission, and decoding in chaotic optical communications are presented. We analyze the transmission and recovery of encrypted information when parameter mismatches are considered. Computer simulations are provided to show the effectiveness of this robustness synchronization property, we present the encrypted transmission of image messages, and we show that, the transmitted image is faithfully recovered.

  8. Adding query privacy to robust DHTs

    DEFF Research Database (Denmark)

    Backes, Michael; Goldberg, Ian; Kate, Aniket


    Interest in anonymous communication over distributed hash tables (DHTs) has increased in recent years. However, almost all known solutions solely aim at achieving sender or requestor anonymity in DHT queries. In many application scenarios, it is crucial that the queried key remains secret from...... intermediate peers that (help to) route the queries towards their destinations. In this paper, we satisfy this requirement by presenting an approach for providing privacy for the keys in DHT queries. We use the concept of oblivious transfer (OT) in communication over DHTs to preserve query privacy without...... compromising spam resistance. Although our OT-based approach can work over any DHT, we concentrate on robust DHTs that can tolerate Byzantine faults and resist spam. We choose the best-known robust DHT construction, and employ an efficient OT protocol well-suited for achieving our goal of obtaining query...

  9. Adding Query Privacy to Robust DHTs

    DEFF Research Database (Denmark)

    Backes, Michael; Goldberg, Ian; Kate, Aniket


    Interest in anonymous communication over distributed hash tables (DHTs) has increased in recent years. However, almost all known solutions solely aim at achieving sender or requestor anonymity in DHT queries. In many application scenarios, it is crucial that the queried key remains secret from...... intermediate peers that (help to) route the queries towards their destinations. In this paper, we satisfy this requirement by presenting an approach for providing privacy for the keys in DHT queries. We use the concept of oblivious transfer (OT) in communication over DHTs to preserve query privacy without...... compromising spam resistance. Although our OT-based approach can work over any DHT, we concentrate on communication over robust DHTs that can tolerate Byzantine faults and resist spam. We choose the best-known robust DHT construction, and employ an efficient OT protocol well-suited for achieving our goal...

  10. Model predictive control classical, robust and stochastic

    CERN Document Server

    Kouvaritakis, Basil


    For the first time, a textbook that brings together classical predictive control with treatment of up-to-date robust and stochastic techniques. Model Predictive Control describes the development of tractable algorithms for uncertain, stochastic, constrained systems. The starting point is classical predictive control and the appropriate formulation of performance objectives and constraints to provide guarantees of closed-loop stability and performance. Moving on to robust predictive control, the text explains how similar guarantees may be obtained for cases in which the model describing the system dynamics is subject to additive disturbances and parametric uncertainties. Open- and closed-loop optimization are considered and the state of the art in computationally tractable methods based on uncertainty tubes presented for systems with additive model uncertainty. Finally, the tube framework is also applied to model predictive control problems involving hard or probabilistic constraints for the cases of multiplic...

  11. Robust control of the activated sludge process. (United States)

    David, R; Vande Wouwer, A; Vasel, J-L; Queinnec, I


    In this work, a robust control strategy is proposed for maintaining the oxygen concentration in the aerobic tank and the pollutant, i.e., ammonium, nitrate, nitrite, concentrations at acceptable levels in the effluent water at the outlet of the activated sludge process. To this end, the Activated Sludge Model no. 1 (ASM1) is first reduced using biological arguments and a singular perturbation method, and a simplified model of the secondary settler is included. In contrast with previous studies that make use of piecewise linear models, an average operating point is evaluated using available data (here data from the COST Action 624) and the reduced-order model is linearized around it using standard techniques. Finally, a H(2) robust control strategy acting on the oxygen injection and the recirculated flow rate is designed and tested in simulation. 2009 American Institute of Chemical Engineers

  12. Communicating via robust synchronization of chaotic lasers

    International Nuclear Information System (INIS)

    Lopez-Gutierrez, R.M.; Posadas-Castillo, C.; Lopez-Mancilla, D.; Cruz-Hernandez, C.


    In this paper, the robust synchronization problem for coupled chaotic Nd:YAG lasers is addressed. We resort to complex systems theory to achieve chaos synchronization. Based on stability theory, it is shown that the state trajectories of the perturbed error synchronization are ultimately bounded, provided the unperturbed synchronization error system is exponentially stable, and some conditions on the bounds of the perturbation terms are satisfied. So that, encoding, transmission, and decoding in chaotic optical communications are presented. We analyze the transmission and recovery of encrypted information when parameter mismatches are considered. Computer simulations are provided to show the effectiveness of this robustness synchronization property, we present the encrypted transmission of image messages, and we show that, the transmitted image is faithfully recovered.

  13. The importance of robust design methodology

    DEFF Research Database (Denmark)

    Eifler, Tobias; Howard, Thomas J.


    of unanticipated variation effects remain largely underestimated and thus unaccounted for in design practice, sometimes with disastrous consequences. To foster the awareness of this variation and to illustrate the benefits of its early consideration in product development, this paper reviews one of the most...... to illustrate how already simple analyses and early stage design methods can help to better understand one of the potential reasons for these failures, namely the variation inherent in manufacturing, assembly, and use processes. Usually thoroughly controlled in production, it seems as if particularly the risk...... infamous recalls in automotive history, that of the GM ignition switch, from the perspective of Robust Design. It is investigated if available Robust Design methods such as sensitivity analysis, tolerance stack-ups, design clarity, etc. would have been suitable to account for the performance variation...

  14. Reliability and Robustness Evaluation of Timber Structures

    DEFF Research Database (Denmark)

    Cizmar, Dean; Sørensen, John Dalsgaard; Kirkegaard, Poul Henning

    In the last few decades there have been intensely research concerning reliability of timber structures. This is primarily because there is an increased focus on society on sustainability and environmental aspects. Modern timber as a building material is also being competitive compared to concrete...... and steel. However, reliability models applied to timber were always related to individual components but not the systems. as any real structure is a complex system, system behaviour must be of a particular interest. In the chapter 1 of this document an overview of stochastic models for strength and loads...... (deterministic, probabilistic and risk based approaches) of the robustness are given. Chapter 3 deals more detailed with the robustness of timber structures....

  15. Robust photometric stereo using structural light sources (United States)

    Han, Tian-Qi; Cheng, Yue; Shen, Hui-Liang; Du, Xin


    We propose a robust photometric stereo method by using structural arrangement of light sources. In the arrangement, light sources are positioned on a planar grid and form a set of collinear combinations. The shadow pixels are detected by adaptive thresholding. The specular highlight and diffuse pixels are distinguished according to their intensity deviations of the collinear combinations, thanks to the special arrangement of light sources. The highlight detection problem is cast as a pattern classification problem and is solved using support vector machine classifiers. Considering the possible misclassification of highlight pixels, the ℓ1 regularization is further employed in normal map estimation. Experimental results on both synthetic and real-world scenes verify that the proposed method can robustly recover the surface normal maps in the case of heavy specular reflection and outperforms the state-of-the-art techniques.

  16. Doubly Constrained Robust Blind Beamforming Algorithm

    Directory of Open Access Journals (Sweden)

    Xin Song


    Full Text Available We propose doubly constrained robust least-squares constant modulus algorithm (LSCMA to solve the problem of signal steering vector mismatches via the Bayesian method and worst-case performance optimization, which is based on the mismatches between the actual and presumed steering vectors. The weight vector is iteratively updated with penalty for the worst-case signal steering vector by the partial Taylor-series expansion and Lagrange multiplier method, in which the Lagrange multipliers can be optimally derived and incorporated at each step. A theoretical analysis for our proposed algorithm in terms of complexity cost, convergence performance, and SINR performance is presented in this paper. In contrast to the linearly constrained LSCMA, the proposed algorithm provides better robustness against the signal steering vector mismatches, yields higher signal captive performance, improves greater array output SINR, and has a lower computational cost. The simulation results confirm the superiority of the proposed algorithm on beampattern control and output SINR enhancement.

  17. Robust facility location: Hedging against failures

    International Nuclear Information System (INIS)

    Hernandez, Ivan; Emmanuel Ramirez-Marquez, Jose; Rainwater, Chase; Pohl, Edward; Medal, Hugh


    While few companies would be willing to sacrifice day-to-day operations to hedge against disruptions, designing for robustness can yield solutions that perform well before and after failures have occurred. Through a multi-objective optimization approach this paper provides decision makers the option to trade-off total weighted distance before and after disruptions in the Facility Location Problem. Additionally, this approach allows decision makers to understand the impact on the opening of facilities on total distance and on system robustness (considering the system as the set of located facilities). This approach differs from previous studies in that hedging against failures is done without having to elicit facility failure probabilities concurrently without requiring the allocation of additional hardening/protections resources. The approach is applied to two datasets from the literature

  18. Robust Reconfiguration of A Distribution System

    Energy Technology Data Exchange (ETDEWEB)

    Moradzadeh, Benyamin [University of Tennessee, Knoxville (UTK); Tomsovic, Kevin [University of Tennessee, Knoxville (UTK)


    In this paper, a robust reconfiguration approach based on Mixed Integer Programming (MIP) is proposed to minimize loss in distribution systems. A Depth-First Search (DFS) algorithm to enumerate possible loops provides radiality constraint. This provides a general solution to the radiality constraint for distribution system reconfiguration/expansion problems. Still, imprecision and ambiguity in net loads, i.e. load minus renewable generation, due to lack of sufficient measurements and high utilization of demand response programs and renewable resources, creates challenges for effective reconfiguration. Deterministic optimization of reconfiguration may no lead to optimal/feasible results. Two methods to address these uncertainties are introduced in this paper: one, based on a stochastic MIP (SMIP) formulation and two, based on a fuzzy MIP (FMIP) formulation. Case studies demonstrate the robustness and efficiency of the proposed reconfiguration methods.

  19. Generalized Correntropy for RobustAdaptive Filtering (United States)

    Chen, Badong; Xing, Lei; Zhao, Haiquan; Zheng, Nanning; Principe, Jose C.


    As a robust nonlinear similarity measure in kernel space, correntropy has received increasing attention in domains of machine learning and signal processing. In particular, the maximum correntropy criterion (MCC) has recently been successfully applied in robust regression and filtering. The default kernel function in correntropy is the Gaussian kernel, which is, of course, not always the best choice. In this work, we propose a generalized correntropy that adopts the generalized Gaussian density (GGD) function as the kernel (not necessarily a Mercer kernel), and present some important properties. We further propose the generalized maximum correntropy criterion (GMCC), and apply it to adaptive filtering. An adaptive algorithm, called the GMCC algorithm, is derived, and the mean square convergence performance is studied. We show that the proposed algorithm is very stable and can achieve zero probability of divergence (POD). Simulation results confirm the theoretical expectations and demonstrate the desirable performance of the new algorithm.

  20. 2D Vector Field Simplification Based on Robustness

    KAUST Repository

    Skraba, Primoz


    Vector field simplification aims to reduce the complexity of the flow by removing features in order of their relevance and importance, to reveal prominent behavior and obtain a compact representation for interpretation. Most existing simplification techniques based on the topological skeleton successively remove pairs of critical points connected by separatrices, using distance or area-based relevance measures. These methods rely on the stable extraction of the topological skeleton, which can be difficult due to instability in numerical integration, especially when processing highly rotational flows. These geometric metrics do not consider the flow magnitude, an important physical property of the flow. In this paper, we propose a novel simplification scheme derived from the recently introduced topological notion of robustness, which provides a complementary view on flow structure compared to the traditional topological-skeleton-based approaches. Robustness enables the pruning of sets of critical points according to a quantitative measure of their stability, that is, the minimum amount of vector field perturbation required to remove them. This leads to a hierarchical simplification scheme that encodes flow magnitude in its perturbation metric. Our novel simplification algorithm is based on degree theory, has fewer boundary restrictions, and so can handle more general cases. Finally, we provide an implementation under the piecewise-linear setting and apply it to both synthetic and real-world datasets. © 2014 IEEE.

  1. Robust web image/video super-resolution. (United States)

    Xiong, Zhiwei; Sun, Xiaoyan; Wu, Feng


    This paper proposes a robust single-image super-resolution method for enlarging low quality web image/video degraded by downsampling and compression. To simultaneously improve the resolution and perceptual quality of such web image/video, we bring forward a practical solution which combines adaptive regularization and learning-based super-resolution. The contribution of this work is twofold. First, we propose to analyze the image energy change characteristics during the iterative regularization process, i.e., the energy change ratio between primitive (e.g., edges, ridges and corners) and nonprimitive fields. Based on the revealed convergence property of the energy change ratio, appropriate regularization strength can then be determined to well balance compression artifacts removal and primitive components preservation. Second, we verify that this adaptive regularization can steadily and greatly improve the pair matching accuracy in learning-based super-resolution. Consequently, their combination effectively eliminates the quantization noise and meanwhile faithfully compensates the missing high-frequency details, yielding robust super-resolution performance in the compression scenario. Experimental results demonstrate that our solution produces visually pleasing enlargements for various web images/videos.

  2. A secure and robust information hiding technique for covert communication (United States)

    Parah, S. A.; Sheikh, J. A.; Hafiz, A. M.; Bhat, G. M.


    The unprecedented advancement of multimedia and growth of the internet has made it possible to reproduce and distribute digital media easier and faster. This has given birth to information security issues, especially when the information pertains to national security, e-banking transactions, etc. The disguised form of encrypted data makes an adversary suspicious and increases the chance of attack. Information hiding overcomes this inherent problem of cryptographic systems and is emerging as an effective means of securing sensitive data being transmitted over insecure channels. In this paper, a secure and robust information hiding technique referred to as Intermediate Significant Bit Plane Embedding (ISBPE) is presented. The data to be embedded is scrambled and embedding is carried out using the concept of Pseudorandom Address Vector (PAV) and Complementary Address Vector (CAV) to enhance the security of the embedded data. The proposed ISBPE technique is fully immune to Least Significant Bit (LSB) removal/replacement attack. Experimental investigations reveal that the proposed technique is more robust to various image processing attacks like JPEG compression, Additive White Gaussian Noise (AWGN), low pass filtering, etc. compared to conventional LSB techniques. The various advantages offered by ISBPE technique make it a good candidate for covert communication.

  3. Robust Sequential Analysis for Special Capacities


    高橋, 一


    Huber type robustness will be considered for some extensions of Wald's Sequential Probability Ratio Test, including Wald's three decision problem and the Kiefer-Weiss formulation. The results of Huber (1965, 1968), Huber and Strassen (1973), Rieder (1977) and Osterreicher (1978) will be extended to derive a least favorable tuple in the multiple decision problem. And then the asymptotically least favorable KieferWeiss procedure together with its asymptotic relative efficiency for the s-contami...

  4. Muscle Synergy-Driven Robust Motion Control. (United States)

    Min, Kyuengbo; Iwamoto, Masami; Kakei, Shinji; Kimpara, Hideyuki


    Humans are able to robustly maintain desired motion and posture under dynamically changing circumstances, including novel conditions. To accomplish this, the brain needs to optimize the synergistic control between muscles against external dynamic factors. However, previous related studies have usually simplified the control of multiple muscles using two opposing muscles, which are minimum actuators to simulate linear feedback control. As a result, they have been unable to analyze how muscle synergy contributes to motion control robustness in a biological system. To address this issue, we considered a new muscle synergy concept used to optimize the synergy between muscle units against external dynamic conditions, including novel conditions. We propose that two main muscle control policies synergistically control muscle units to maintain the desired motion against external dynamic conditions. Our assumption is based on biological evidence regarding the control of multiple muscles via the corticospinal tract. One of the policies is the group control policy (GCP), which is used to control muscle group units classified based on functional similarities in joint control. This policy is used to effectively resist external dynamic circumstances, such as disturbances. The individual control policy (ICP) assists the GCP in precisely controlling motion by controlling individual muscle units. To validate this hypothesis, we simulated the reinforcement of the synergistic actions of the two control policies during the reinforcement learning of feedback motion control. Using this learning paradigm, the two control policies were synergistically combined to result in robust feedback control under novel transient and sustained disturbances that did not involve learning. Further, by comparing our data to experimental data generated by human subjects under the same conditions as those of the simulation, we showed that the proposed synergy concept may be used to analyze muscle synergy

  5. Automatic Mode Transition Enabled Robust Triboelectric Nanogenerators. (United States)

    Chen, Jun; Yang, Jin; Guo, Hengyu; Li, Zhaoling; Zheng, Li; Su, Yuanjie; Wen, Zhen; Fan, Xing; Wang, Zhong Lin


    Although the triboelectric nanogenerator (TENG) has been proven to be a renewable and effective route for ambient energy harvesting, its robustness remains a great challenge due to the requirement of surface friction for a decent output, especially for the in-plane sliding mode TENG. Here, we present a rationally designed TENG for achieving a high output performance without compromising the device robustness by, first, converting the in-plane sliding electrification into a contact separation working mode and, second, creating an automatic transition between a contact working state and a noncontact working state. The magnet-assisted automatic transition triboelectric nanogenerator (AT-TENG) was demonstrated to effectively harness various ambient rotational motions to generate electricity with greatly improved device robustness. At a wind speed of 6.5 m/s or a water flow rate of 5.5 L/min, the harvested energy was capable of lighting up 24 spot lights (0.6 W each) simultaneously and charging a capacitor to greater than 120 V in 60 s. Furthermore, due to the rational structural design and unique output characteristics, the AT-TENG was not only capable of harvesting energy from natural bicycling and car motion but also acting as a self-powered speedometer with ultrahigh accuracy. Given such features as structural simplicity, easy fabrication, low cost, wide applicability even in a harsh environment, and high output performance with superior device robustness, the AT-TENG renders an effective and practical approach for ambient mechanical energy harvesting as well as self-powered active sensing.

  6. Is CBA ranking of transport investments robust?


    Börjesson, Maria; Eliasson, Jonas; Lundberg, Mattias


    Cost-benefit analysis (CBA) is often used when many transport investments need to be ranked against each other, for example in national investment planning. However, results are often questioned on claims that the ranking depends crucially on uncertain assumptions about the future, and on methodologically or ethically contestable trade-offs of different types of benefits relative to each other. This paper explores the robustness of CBA rankings of transport investments with respect to two typ...

  7. Frozen robust multiarray analysis (fRMA)


    McCall, Matthew N.; Bolstad, Benjamin M.; Irizarry, Rafael A.


    Robust multiarray analysis (RMA) is the most widely used preprocessing algorithm for Affymetrix and Nimblegen gene expression microarrays. RMA performs background correction, normalization, and summarization in a modular way. The last 2 steps require multiple arrays to be analyzed simultaneously. The ability to borrow information across samples provides RMA various advantages. For example, the summarization step fits a parametric model that accounts for probe effects, assumed to be fixed acro...

  8. Robust inversion via semistochastic dimensionality reduction


    Aravkin, Aleksandr; Friedlander, Michael P.; van Leeuwen, Tristan


    We consider a class of inverse problems where it is possible to aggregate the results of multiple experiments. This class includes problems where the forward model is the solution operator to linear ODEs or PDEs. The tremendous size of such problems motivates dimensionality reduction techniques based on randomly mixing experiments. These techniques break down, however, when robust data-fitting formulations are used, which are essential in cases of missing data, unusually large errors, and sys...

  9. Heteroscedasticity resistant robust covariance matrix estimator

    Czech Academy of Sciences Publication Activity Database

    Víšek, Jan Ámos


    Roč. 17, č. 27 (2010), s. 33-49 ISSN 1212-074X Grant - others:GA UK(CZ) GA402/09/0557 Institutional research plan: CEZ:AV0Z10750506 Keywords : Regression * Covariance matrix * Heteroscedasticity * Resistant Subject RIV: BB - Applied Statistics, Operational Research resistant robust covariance matrix estimator.pdf

  10. Robust topology design of periodic grating surfaces

    DEFF Research Database (Denmark)

    Friis, Kasper Storgaard; Sigmund, Ole


    Modern nanoscale manufacturing techniques allow for a high degree of flexibility in designing surface microstructures and nanostructures. Injection molding of nanosized features allows for mass production of plastic components with a tailored nanostructure producing specific optical effects...... depending on the purpose. This work details the use of topology optimization for designing periodic polymer grating surfaces with complex optical properties. A method based on robust topology optimization is formulated for designing the nanostructure of plastic surfaces with extreme reflection...

  11. A Robust Control Framework for Malware Filtering


    Bloem, Michael; Alpcan, Tansu; Basar, Tamer


    We study and develop a robust control framework for malware filtering and network security. We investigate the malware filtering problem by capturing the tradeoff between increased security on one hand and continued usability of the network on the other. We analyze the problem using a linear control system model with a quadratic cost structure and develop algorithms based on H infinity-optimal control theory. A dynamic feedback filter is derived and shown via numerical analysis to be an impro...

  12. Efficient CEPSTRAL Normalization for Robust Speech Recognition (United States)


    CMN curve depends on the duration of the utterance, and is plotted in Figure 2 for the average duration in the DARPA Wall Street Journal task, 7...task consisting of dictation of sentences from the Wall Street Journal . A component of that evaluation involved utterances from a set of unknown... Wall Street Journal domain. 73 The version of SPHINX-II used for this evaluation was con- figured to maximize the robustness of the recognition pro

  13. Matlab as a robust control design tool (United States)

    Gregory, Irene M.


    This presentation introduces Matlab as a tool used in flight control research. The example used to illustrate some of the capabilities of this software is a robust controller designed for a single stage to orbit air breathing vehicles's ascent to orbit. The global requirements of the controller are to stabilize the vehicle and follow a trajectory in the presence of atmospheric disturbances and strong dynamic coupling between airframe and propulsion.

  14. Robust Decision Making for Improved Mission Assurance (United States)


    Computer Science, Computer Engineering, and Applied Computing ( GEM 󈧑 & ICAI󈧑). A detailed description of a RML model/agent capable of employing...Democratic Republic of Congo. A D-optimal design of experiments enables identification of a robust national policy. Employment of a multi-attribute utility...ed) Handbook of Computational Approaches to Counterterrorism. Springer, New York, pages 363-399. [24] Schvaneveldt, R.W. (1990). Pathfinder

  15. TAO-robust backpropagation learning algorithm. (United States)

    Pernía-Espinoza, Alpha V; Ordieres-Meré, Joaquín B; Martínez-de-Pisón, Francisco J; González-Marcos, Ana


    In several fields, as industrial modelling, multilayer feedforward neural networks are often used as universal function approximations. These supervised neural networks are commonly trained by a traditional backpropagation learning format, which minimises the mean squared error (mse) of the training data. However, in the presence of corrupted data (outliers) this training scheme may produce wrong models. We combine the benefits of the non-linear regression model tau-estimates [introduced by Tabatabai, M. A. Argyros, I. K. Robust Estimation and testing for general nonlinear regression models. Applied Mathematics and Computation. 58 (1993) 85-101] with the backpropagation algorithm to produce the TAO-robust learning algorithm, in order to deal with the problems of modelling with outliers. The cost function of this approach has a bounded influence function given by the weighted average of two psi functions, one corresponding to a very robust estimate and the other to a highly efficient estimate. The advantages of the proposed algorithm are studied with an example.

  16. Distributed redundancy and robustness in complex systems

    KAUST Repository

    Randles, Martin


    The uptake and increasing prevalence of Web 2.0 applications, promoting new large-scale and complex systems such as Cloud computing and the emerging Internet of Services/Things, requires tools and techniques to analyse and model methods to ensure the robustness of these new systems. This paper reports on assessing and improving complex system resilience using distributed redundancy, termed degeneracy in biological systems, to endow large-scale complicated computer systems with the same robustness that emerges in complex biological and natural systems. However, in order to promote an evolutionary approach, through emergent self-organisation, it is necessary to specify the systems in an \\'open-ended\\' manner where not all states of the system are prescribed at design-time. In particular an observer system is used to select robust topologies, within system components, based on a measurement of the first non-zero Eigen value in the Laplacian spectrum of the components\\' network graphs; also known as the algebraic connectivity. It is shown, through experimentation on a simulation, that increasing the average algebraic connectivity across the components, in a network, leads to an increase in the variety of individual components termed distributed redundancy; the capacity for structurally distinct components to perform an identical function in a particular context. The results are applied to a specific application where active clustering of like services is used to aid load balancing in a highly distributed network. Using the described procedure is shown to improve performance and distribute redundancy. © 2010 Elsevier Inc.

  17. Sparse alignment for robust tensor learning. (United States)

    Lai, Zhihui; Wong, Wai Keung; Xu, Yong; Zhao, Cairong; Sun, Mingming


    Multilinear/tensor extensions of manifold learning based algorithms have been widely used in computer vision and pattern recognition. This paper first provides a systematic analysis of the multilinear extensions for the most popular methods by using alignment techniques, thereby obtaining a general tensor alignment framework. From this framework, it is easy to show that the manifold learning based tensor learning methods are intrinsically different from the alignment techniques. Based on the alignment framework, a robust tensor learning method called sparse tensor alignment (STA) is then proposed for unsupervised tensor feature extraction. Different from the existing tensor learning methods, L1- and L2-norms are introduced to enhance the robustness in the alignment step of the STA. The advantage of the proposed technique is that the difficulty in selecting the size of the local neighborhood can be avoided in the manifold learning based tensor feature extraction algorithms. Although STA is an unsupervised learning method, the sparsity encodes the discriminative information in the alignment step and provides the robustness of STA. Extensive experiments on the well-known image databases as well as action and hand gesture databases by encoding object images as tensors demonstrate that the proposed STA algorithm gives the most competitive performance when compared with the tensor-based unsupervised learning methods.

  18. Interlinked bistable mechanisms generate robust mitotic transitions. (United States)

    Hutter, Lukas H; Rata, Scott; Hochegger, Helfrid; Novák, Béla


    The transitions between phases of the cell cycle have evolved to be robust and switch-like, which ensures temporal separation of DNA replication, sister chromatid separation, and cell division. Mathematical models describing the biochemical interaction networks of cell cycle regulators attribute these properties to underlying bistable switches, which inherently generate robust, switch-like, and irreversible transitions between states. We have recently presented new mathematical models for two control systems that regulate crucial transitions in the cell cycle: mitotic entry and exit, 1 and the mitotic checkpoint. 2 Each of the two control systems is characterized by two interlinked bistable switches. In the case of mitotic checkpoint control, these switches are mutually activating, whereas in the case of the mitotic entry/exit network, the switches are mutually inhibiting. In this Perspective we describe the qualitative features of these regulatory motifs and show that having two interlinked bistable mechanisms further enhances robustness and irreversibility. We speculate that these network motifs also underlie other cell cycle transitions and cellular transitions between distinct biochemical states.

  19. A robust nonlinear filter for image restoration. (United States)

    Koivunen, V


    A class of nonlinear regression filters based on robust estimation theory is introduced. The goal of the filtering is to recover a high-quality image from degraded observations. Models for desired image structures and contaminating processes are employed, but deviations from strict assumptions are allowed since the assumptions on signal and noise are typically only approximately true. The robustness of filters is usually addressed only in a distributional sense, i.e., the actual error distribution deviates from the nominal one. In this paper, the robustness is considered in a broad sense since the outliers may also be due to inappropriate signal model, or there may be more than one statistical population present in the processing window, causing biased estimates. Two filtering algorithms minimizing a least trimmed squares criterion are provided. The design of the filters is simple since no scale parameters or context-dependent threshold values are required. Experimental results using both real and simulated data are presented. The filters effectively attenuate both impulsive and nonimpulsive noise while recovering the signal structure and preserving interesting details.

  20. Mutational robustness of gene regulatory networks.

    Directory of Open Access Journals (Sweden)

    Aalt D J van Dijk

    Full Text Available Mutational robustness of gene regulatory networks refers to their ability to generate constant biological output upon mutations that change network structure. Such networks contain regulatory interactions (transcription factor-target gene interactions but often also protein-protein interactions between transcription factors. Using computational modeling, we study factors that influence robustness and we infer several network properties governing it. These include the type of mutation, i.e. whether a regulatory interaction or a protein-protein interaction is mutated, and in the case of mutation of a regulatory interaction, the sign of the interaction (activating vs. repressive. In addition, we analyze the effect of combinations of mutations and we compare networks containing monomeric with those containing dimeric transcription factors. Our results are consistent with available data on biological networks, for example based on evolutionary conservation of network features. As a novel and remarkable property, we predict that networks are more robust against mutations in monomer than in dimer transcription factors, a prediction for which analysis of conservation of DNA binding residues in monomeric vs. dimeric transcription factors provides indirect evidence.