WorldWideScience

Sample records for total neuronal population

  1. Genetic variation in total number and locations of GnRH neurons identified using in situ hybridization in a wild-source population.

    Science.gov (United States)

    Kaugars, Katherine E; Rivers, Charlotte I; Saha, Margaret S; Heideman, Paul D

    2016-02-01

    The evolution of brain function in the regulation of physiology may depend in part upon the numbers and locations of neurons. Wild populations of rodents contain natural genetic variation in the inhibition of reproduction by winter-like short photoperiod, and it has been hypothesized that this functional variation might be due in part to heritable variation in the numbers or location of gonadotropin releasing hormone (GnRH) neurons. A naturally variable wild-source population of white-footed mice was used to develop lines artificially selected for or against mature gonads in short, winter-like photoperiods. We compared a selection line that is reproductively inhibited in short photoperiod (Responsive) to a line that is weakly inhibited by short photoperiod (Nonresponsive) for differences in counts of neurons identified using in situ hybridization for GnRH mRNA. There was no effect of photoperiod, but there were 60% more GnRH neurons in total in the Nonresponsive selection line than the Responsive selection line. The lines differed specifically in numbers of GnRH neurons in more anterior regions, whereas numbers of GnRH neurons in posterior areas were not statistically different between lines. We compare these results to those of an earlier study that used immunohistochemical labeling for GnRH neurons. The results are consistent with the hypothesis that the selection lines and natural source population contain significant genetic variation in the number and location of GnRH neurons. The variation in GnRH neurons may contribute to functional variation in fertility that occurs in short photoperiods in the laboratory and in the wild source population in winter. © 2015 Wiley Periodicals, Inc.

  2. Kappe neurons, a novel population of olfactory sensory neurons

    OpenAIRE

    Ahuja, Gaurav; Nia, Shahrzad Bozorg; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I.

    2014-01-01

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons ar...

  3. Information processing by neuronal populations

    National Research Council Canada - National Science Library

    Hölscher, Christian; Munk, Matthias

    2009-01-01

    ... simultaneously recorded spike trains 120 Mark Laubach, Nandakumar S. Narayanan, and Eyal Y. Kimchi Part III Neuronal population information coding and plasticity in specific brain areas 149 7 F...

  4. Kappe neurons, a novel population of olfactory sensory neurons.

    Science.gov (United States)

    Ahuja, Gaurav; Bozorg Nia, Shahrzad; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I

    2014-02-10

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons are identified by their Go-like immunoreactivity, and show a distinct spatial distribution within the olfactory epithelium, similar to, but significantly different from that of crypt neurons. Furthermore, kappe neurons project to a single identified target glomerulus within the olfactory bulb, mdg5 of the mediodorsal cluster, whereas crypt neurons are known to project exclusively to the mdg2 glomerulus. Kappe neurons are negative for established markers of ciliated, microvillous and crypt neurons, but appear to have microvilli. Kappe neurons constitute the fourth type of olfactory sensory neurons reported in teleost fishes and their existence suggests that encoding of olfactory stimuli may require a higher complexity than hitherto assumed already in the peripheral olfactory system.

  5. Bayesian population decoding of spiking neurons.

    Science.gov (United States)

    Gerwinn, Sebastian; Macke, Jakob; Bethge, Matthias

    2009-01-01

    The timing of action potentials in spiking neurons depends on the temporal dynamics of their inputs and contains information about temporal fluctuations in the stimulus. Leaky integrate-and-fire neurons constitute a popular class of encoding models, in which spike times depend directly on the temporal structure of the inputs. However, optimal decoding rules for these models have only been studied explicitly in the noiseless case. Here, we study decoding rules for probabilistic inference of a continuous stimulus from the spike times of a population of leaky integrate-and-fire neurons with threshold noise. We derive three algorithms for approximating the posterior distribution over stimuli as a function of the observed spike trains. In addition to a reconstruction of the stimulus we thus obtain an estimate of the uncertainty as well. Furthermore, we derive a 'spike-by-spike' online decoding scheme that recursively updates the posterior with the arrival of each new spike. We use these decoding rules to reconstruct time-varying stimuli represented by a Gaussian process from spike trains of single neurons as well as neural populations.

  6. Bayesian population decoding of spiking neurons

    Directory of Open Access Journals (Sweden)

    Sebastian Gerwinn

    2009-10-01

    Full Text Available The timing of action potentials in spiking neurons depends on the temporal dynamics of their inputs and contains information about temporal fluctuations in the stimulus. Leaky integrate-and-fire neurons constitute a popular class of encoding models, in which spike times depend directly on the temporal structure of the inputs. However, optimal decoding rules for these models have only been studied explicitly in the noiseless case. Here, we study decoding rules for probabilistic inference of a continuous stimulus from the spike times of a population of leaky integrate-and-fire neurons with threshold noise. We derive three algorithms for approximating the posterior distribution over stimuli as a function of the observed spike trains. In addition to a reconstruction of the stimulus we thus obtain an estimate of the uncertainty as well. Furthermore, we derive a `spike-by-spike' online decoding scheme that recursively updates the posterior with the arrival of each new spike. We use these decoding rules to reconstruct time-varying stimuli represented by a Gaussian process from spike trains of single neurons as well as neural populations.

  7. Population coding in sparsely connected networks of noisy neurons

    OpenAIRE

    Tripp, Bryan P.; Orchard, Jeff

    2012-01-01

    This study examines the relationship between population coding and spatial connection statistics in networks of noisy neurons. Encoding of sensory information in the neocortex is thought to require coordinated neural populations, because individual cortical neurons respond to a wide range of stimuli, and exhibit highly variable spiking in response to repeated stimuli. Population coding is rooted in network structure, because cortical neurons receive information only from other neurons, and be...

  8. Diverse coupling of neurons to populations in sensory cortex.

    Science.gov (United States)

    Okun, Michael; Steinmetz, Nicholas; Cossell, Lee; Iacaruso, M Florencia; Ko, Ho; Barthó, Péter; Moore, Tirin; Hofer, Sonja B; Mrsic-Flogel, Thomas D; Carandini, Matteo; Harris, Kenneth D

    2015-05-28

    A large population of neurons can, in principle, produce an astronomical number of distinct firing patterns. In cortex, however, these patterns lie in a space of lower dimension, as if individual neurons were "obedient members of a huge orchestra". Here we use recordings from the visual cortex of mouse (Mus musculus) and monkey (Macaca mulatta) to investigate the relationship between individual neurons and the population, and to establish the underlying circuit mechanisms. We show that neighbouring neurons can differ in their coupling to the overall firing of the population, ranging from strongly coupled 'choristers' to weakly coupled 'soloists'. Population coupling is largely independent of sensory preferences, and it is a fixed cellular attribute, invariant to stimulus conditions. Neurons with high population coupling are more strongly affected by non-sensory behavioural variables such as motor intention. Population coupling reflects a causal relationship, predicting the response of a neuron to optogenetically driven increases in local activity. Moreover, population coupling indicates synaptic connectivity; the population coupling of a neuron, measured in vivo, predicted subsequent in vitro estimates of the number of synapses received from its neighbours. Finally, population coupling provides a compact summary of population activity; knowledge of the population couplings of n neurons predicts a substantial portion of their n(2) pairwise correlations. Population coupling therefore represents a novel, simple measure that characterizes the relationship of each neuron to a larger population, explaining seemingly complex network firing patterns in terms of basic circuit variables.

  9. Linking macroscopic with microscopic neuroanatomy using synthetic neuronal populations.

    Science.gov (United States)

    Schneider, Calvin J; Cuntz, Hermann; Soltesz, Ivan

    2014-10-01

    Dendritic morphology has been shown to have a dramatic impact on neuronal function. However, population features such as the inherent variability in dendritic morphology between cells belonging to the same neuronal type are often overlooked when studying computation in neural networks. While detailed models for morphology and electrophysiology exist for many types of single neurons, the role of detailed single cell morphology in the population has not been studied quantitatively or computationally. Here we use the structural context of the neural tissue in which dendritic trees exist to drive their generation in silico. We synthesize the entire population of dentate gyrus granule cells, the most numerous cell type in the hippocampus, by growing their dendritic trees within their characteristic dendritic fields bounded by the realistic structural context of (1) the granule cell layer that contains all somata and (2) the molecular layer that contains the dendritic forest. This process enables branching statistics to be linked to larger scale neuroanatomical features. We find large differences in dendritic total length and individual path length measures as a function of location in the dentate gyrus and of somatic depth in the granule cell layer. We also predict the number of unique granule cell dendrites invading a given volume in the molecular layer. This work enables the complete population-level study of morphological properties and provides a framework to develop complex and realistic neural network models.

  10. Population activity structure of excitatory and inhibitory neurons.

    Directory of Open Access Journals (Sweden)

    Sean R Bittner

    Full Text Available Many studies use population analysis approaches, such as dimensionality reduction, to characterize the activity of large groups of neurons. To date, these methods have treated each neuron equally, without taking into account whether neurons are excitatory or inhibitory. We studied population activity structure as a function of neuron type by applying factor analysis to spontaneous activity from spiking networks with balanced excitation and inhibition. Throughout the study, we characterized population activity structure by measuring its dimensionality and the percentage of overall activity variance that is shared among neurons. First, by sampling only excitatory or only inhibitory neurons, we found that the activity structures of these two populations in balanced networks are measurably different. We also found that the population activity structure is dependent on the ratio of excitatory to inhibitory neurons sampled. Finally we classified neurons from extracellular recordings in the primary visual cortex of anesthetized macaques as putative excitatory or inhibitory using waveform classification, and found similarities with the neuron type-specific population activity structure of a balanced network with excitatory clustering. These results imply that knowledge of neuron type is important, and allows for stronger statistical tests, when interpreting population activity structure.

  11. Population activity structure of excitatory and inhibitory neurons.

    Science.gov (United States)

    Bittner, Sean R; Williamson, Ryan C; Snyder, Adam C; Litwin-Kumar, Ashok; Doiron, Brent; Chase, Steven M; Smith, Matthew A; Yu, Byron M

    2017-01-01

    Many studies use population analysis approaches, such as dimensionality reduction, to characterize the activity of large groups of neurons. To date, these methods have treated each neuron equally, without taking into account whether neurons are excitatory or inhibitory. We studied population activity structure as a function of neuron type by applying factor analysis to spontaneous activity from spiking networks with balanced excitation and inhibition. Throughout the study, we characterized population activity structure by measuring its dimensionality and the percentage of overall activity variance that is shared among neurons. First, by sampling only excitatory or only inhibitory neurons, we found that the activity structures of these two populations in balanced networks are measurably different. We also found that the population activity structure is dependent on the ratio of excitatory to inhibitory neurons sampled. Finally we classified neurons from extracellular recordings in the primary visual cortex of anesthetized macaques as putative excitatory or inhibitory using waveform classification, and found similarities with the neuron type-specific population activity structure of a balanced network with excitatory clustering. These results imply that knowledge of neuron type is important, and allows for stronger statistical tests, when interpreting population activity structure.

  12. Population activity structure of excitatory and inhibitory neurons

    Science.gov (United States)

    Doiron, Brent

    2017-01-01

    Many studies use population analysis approaches, such as dimensionality reduction, to characterize the activity of large groups of neurons. To date, these methods have treated each neuron equally, without taking into account whether neurons are excitatory or inhibitory. We studied population activity structure as a function of neuron type by applying factor analysis to spontaneous activity from spiking networks with balanced excitation and inhibition. Throughout the study, we characterized population activity structure by measuring its dimensionality and the percentage of overall activity variance that is shared among neurons. First, by sampling only excitatory or only inhibitory neurons, we found that the activity structures of these two populations in balanced networks are measurably different. We also found that the population activity structure is dependent on the ratio of excitatory to inhibitory neurons sampled. Finally we classified neurons from extracellular recordings in the primary visual cortex of anesthetized macaques as putative excitatory or inhibitory using waveform classification, and found similarities with the neuron type-specific population activity structure of a balanced network with excitatory clustering. These results imply that knowledge of neuron type is important, and allows for stronger statistical tests, when interpreting population activity structure. PMID:28817581

  13. The Isolation of Pure Populations of Neurons by Laser Capture Microdissection: Methods and Application in Neuroscience.

    Science.gov (United States)

    Morris, Renée; Mehta, Prachi

    2018-01-01

    In mammals, the central nervous system (CNS) is constituted of various cellular elements, posing a challenge to isolating specific cell types to investigate their expression profile. As a result, tissue homogenization is not amenable to analyses of motor neurons profiling as these represent less than 10% of the total spinal cord cell population. One way to tackle the problem of tissue heterogeneity and obtain meaningful genomic, proteomic, and transcriptomic profiling is to use laser capture microdissection technology (LCM). In this chapter, we describe protocols for the capture of isolated populations of motor neurons from spinal cord tissue sections and for downstream transcriptomic analysis of motor neurons with RT-PCR. We have also included a protocol for the immunological confirmation that the captured neurons are indeed motor neurons. Although focused on spinal cord motor neurons, these protocols can be easily optimized for the isolation of any CNS neurons.

  14. Discontinuous Galerkin finite element method for solving population density functions of cortical pyramidal and thalamic neuronal populations.

    Science.gov (United States)

    Huang, Chih-Hsu; Lin, Chou-Ching K; Ju, Ming-Shaung

    2015-02-01

    Compared with the Monte Carlo method, the population density method is efficient for modeling collective dynamics of neuronal populations in human brain. In this method, a population density function describes the probabilistic distribution of states of all neurons in the population and it is governed by a hyperbolic partial differential equation. In the past, the problem was mainly solved by using the finite difference method. In a previous study, a continuous Galerkin finite element method was found better than the finite difference method for solving the hyperbolic partial differential equation; however, the population density function often has discontinuity and both methods suffer from a numerical stability problem. The goal of this study is to improve the numerical stability of the solution using discontinuous Galerkin finite element method. To test the performance of the new approach, interaction of a population of cortical pyramidal neurons and a population of thalamic neurons was simulated. The numerical results showed good agreement between results of discontinuous Galerkin finite element and Monte Carlo methods. The convergence and accuracy of the solutions are excellent. The numerical stability problem could be resolved using the discontinuous Galerkin finite element method which has total-variation-diminishing property. The efficient approach will be employed to simulate the electroencephalogram or dynamics of thalamocortical network which involves three populations, namely, thalamic reticular neurons, thalamocortical neurons and cortical pyramidal neurons. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. A New Population of Parvocellular Oxytocin Neurons Controlling Magnocellular Neuron Activity and Inflammatory Pain Processing.

    Science.gov (United States)

    Eliava, Marina; Melchior, Meggane; Knobloch-Bollmann, H Sophie; Wahis, Jérôme; da Silva Gouveia, Miriam; Tang, Yan; Ciobanu, Alexandru Cristian; Triana Del Rio, Rodrigo; Roth, Lena C; Althammer, Ferdinand; Chavant, Virginie; Goumon, Yannick; Gruber, Tim; Petit-Demoulière, Nathalie; Busnelli, Marta; Chini, Bice; Tan, Linette L; Mitre, Mariela; Froemke, Robert C; Chao, Moses V; Giese, Günter; Sprengel, Rolf; Kuner, Rohini; Poisbeau, Pierrick; Seeburg, Peter H; Stoop, Ron; Charlet, Alexandre; Grinevich, Valery

    2016-03-16

    Oxytocin (OT) is a neuropeptide elaborated by the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Magnocellular OT neurons of these nuclei innervate numerous forebrain regions and release OT into the blood from the posterior pituitary. The PVN also harbors parvocellular OT cells that project to the brainstem and spinal cord, but their function has not been directly assessed. Here, we identified a subset of approximately 30 parvocellular OT neurons, with collateral projections onto magnocellular OT neurons and neurons of deep layers of the spinal cord. Evoked OT release from these OT neurons suppresses nociception and promotes analgesia in an animal model of inflammatory pain. Our findings identify a new population of OT neurons that modulates nociception in a two tier process: (1) directly by release of OT from axons onto sensory spinal cord neurons and inhibiting their activity and (2) indirectly by stimulating OT release from SON neurons into the periphery. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Noise and neuronal populations conspire to encode simple waveforms reliably

    Science.gov (United States)

    Parnas, B. R.

    1996-01-01

    Sensory systems rely on populations of neurons to encode information transduced at the periphery into meaningful patterns of neuronal population activity. This transduction occurs in the presence of intrinsic neuronal noise. This is fortunate. The presence of noise allows more reliable encoding of the temporal structure present in the stimulus than would be possible in a noise-free environment. Simulations with a parallel model of signal processing at the auditory periphery have been used to explore the effects of noise and a neuronal population on the encoding of signal information. The results show that, for a given set of neuronal modeling parameters and stimulus amplitude, there is an optimal amount of noise for stimulus encoding with maximum fidelity.

  17. Population coding in sparsely connected networks of noisy neurons.

    Science.gov (United States)

    Tripp, Bryan P; Orchard, Jeff

    2012-01-01

    This study examines the relationship between population coding and spatial connection statistics in networks of noisy neurons. Encoding of sensory information in the neocortex is thought to require coordinated neural populations, because individual cortical neurons respond to a wide range of stimuli, and exhibit highly variable spiking in response to repeated stimuli. Population coding is rooted in network structure, because cortical neurons receive information only from other neurons, and because the information they encode must be decoded by other neurons, if it is to affect behavior. However, population coding theory has often ignored network structure, or assumed discrete, fully connected populations (in contrast with the sparsely connected, continuous sheet of the cortex). In this study, we modeled a sheet of cortical neurons with sparse, primarily local connections, and found that a network with this structure could encode multiple internal state variables with high signal-to-noise ratio. However, we were unable to create high-fidelity networks by instantiating connections at random according to spatial connection probabilities. In our models, high-fidelity networks required additional structure, with higher cluster factors and correlations between the inputs to nearby neurons.

  18. Population Coding in Sparsely Connected Networks of Noisy Neurons

    Directory of Open Access Journals (Sweden)

    Bryan Patrick Tripp

    2012-05-01

    Full Text Available This study examines the relationship between population coding and spatial connection statistics in networks of noisy neurons. Encoding of sensory information in the neocortex is thought to require coordinated neural populations, because individual cortical neurons respond to a wide range of stimuli, and exhibit highly variable spiking in response to repeated stimuli. Population coding is rooted in network structure, because cortical neurons receive information only from other neurons, and because the information they encode must be decoded by other neurons, if it is to affect behaviour. However, population coding theory has often ignored network structure, or assumed discrete, fully-connected populations (in contrast with the sparsely connected, continuous sheet of the cortex. In this study, we model a sheet of cortical neurons with sparse, primarily local connections, and find that a network with this structure can encode multiple internal state variables with high signal-to-noise ratio. However, in our model, although connection probability varies with the distance between neurons, we find that the connections cannot be instantiated at random according to these probabilities, but must have additional structure if information is to be encoded with high fidelity.

  19. Dynamics of a structured neuron population

    International Nuclear Information System (INIS)

    Pakdaman, Khashayar; Salort, Delphine; Perthame, Benoît

    2010-01-01

    We study the dynamics of assemblies of interacting neurons. For large fully connected networks, the dynamics of the system can be described by a partial differential equation reminiscent of age-structure models used in mathematical ecology, where the 'age' of a neuron represents the time elapsed since its last discharge. The nonlinearity arises from the connectivity J of the network. We prove some mathematical properties of the model that are directly related to qualitative properties. On the one hand, we prove that it is well-posed and that it admits stationary states which, depending upon the connectivity, can be unique or not. On the other hand, we study the long time behaviour of solutions; both for small and large J, we prove the relaxation to the steady state describing asynchronous firing of the neurons. In the middle range, numerical experiments show that periodic solutions appear expressing re-synchronization of the network and asynchronous firing

  20. Temporal structure of neuronal population oscillations with empirical model decomposition

    International Nuclear Information System (INIS)

    Li Xiaoli

    2006-01-01

    Frequency analysis of neuronal oscillation is very important for understanding the neural information processing and mechanism of disorder in the brain. This Letter addresses a new method to analyze the neuronal population oscillations with empirical mode decomposition (EMD). Following EMD of neuronal oscillation, a series of intrinsic mode functions (IMFs) are obtained, then Hilbert transform of IMFs can be used to extract the instantaneous time frequency structure of neuronal oscillation. The method is applied to analyze the neuronal oscillation in the hippocampus of epileptic rats in vivo, the results show the neuronal oscillations have different descriptions during the pre-ictal, seizure onset and ictal periods of the epileptic EEG at the different frequency band. This new method is very helpful to provide a view for the temporal structure of neural oscillation

  1. Stochastic synchronization of neuronal populations with intrinsic and extrinsic noise.

    KAUST Repository

    Bressloff, Paul C; Lai, Yi Ming

    2011-01-01

    We extend the theory of noise-induced phase synchronization to the case of a neural master equation describing the stochastic dynamics of an ensemble of uncoupled neuronal population oscillators with intrinsic and extrinsic noise. The master

  2. Relating normalization to neuronal populations across cortical areas.

    Science.gov (United States)

    Ruff, Douglas A; Alberts, Joshua J; Cohen, Marlene R

    2016-09-01

    Normalization, which divisively scales neuronal responses to multiple stimuli, is thought to underlie many sensory, motor, and cognitive processes. In every study where it has been investigated, neurons measured in the same brain area under identical conditions exhibit a range of normalization, ranging from suppression by nonpreferred stimuli (strong normalization) to additive responses to combinations of stimuli (no normalization). Normalization has been hypothesized to arise from interactions between neuronal populations, either in the same or different brain areas, but current models of normalization are not mechanistic and focus on trial-averaged responses. To gain insight into the mechanisms underlying normalization, we examined interactions between neurons that exhibit different degrees of normalization. We recorded from multiple neurons in three cortical areas while rhesus monkeys viewed superimposed drifting gratings. We found that neurons showing strong normalization shared less trial-to-trial variability with other neurons in the same cortical area and more variability with neurons in other cortical areas than did units with weak normalization. Furthermore, the cortical organization of normalization was not random: neurons recorded on nearby electrodes tended to exhibit similar amounts of normalization. Together, our results suggest that normalization reflects a neuron's role in its local network and that modulatory factors like normalization share the topographic organization typical of sensory tuning properties. Copyright © 2016 the American Physiological Society.

  3. Predicting oculomotor behaviour from correlated populations of posterior parietal neurons.

    Science.gov (United States)

    Graf, Arnulf B A; Andersen, Richard A

    2015-01-23

    Oculomotor function critically depends on how signals representing saccade direction and eye position are combined across neurons in the lateral intraparietal (LIP) area of the posterior parietal cortex. Here we show that populations of parietal neurons exhibit correlated variability, and that using these interneuronal correlations yields oculomotor predictions that are more accurate and also less uncertain. The structure of LIP population responses is therefore essential for reliable read-out of oculomotor behaviour.

  4. Engineering connectivity by multiscale micropatterning of individual populations of neurons.

    Science.gov (United States)

    Albers, Jonas; Toma, Koji; Offenhäusser, Andreas

    2015-02-01

    Functional networks are the basis of information processing in the central nervous system. Essential for their formation are guided neuronal growth as well as controlled connectivity and information flow. The basis of neuronal development is generated by guiding cues and geometric constraints. To investigate the neuronal growth and connectivity of adjacent neuronal networks, two-dimensional protein patterns were created. A mixture of poly-L-lysine and laminin was transferred onto a silanized glass surface by microcontact printing. The structures were populated with dissociated primary cortical embryonic rat neurons. Triangular structures with diverse opening angles, height, and design were chosen as two-dimensional structures to allow network formation with constricted gateways. Neuronal development was observed by immunohistochemistry to pursue the influence of the chosen structures on the neuronal outgrowth. Neurons were stained for MAP2, while poly-L-lysine was FITC labeled. With this study we present an easy-to-use technique to engineer two-dimensional networks in vitro with defined gateways. The presented micropatterning method is used to generate daisy-chained neuronal networks with predefined connectivity. Signal propagation among geometrically constrained networks can easily be monitored by calcium-sensitive dyes, providing insights into network communication in vitro. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Intrinsically active and pacemaker neurons in pluripotent stem cell-derived neuronal populations.

    Science.gov (United States)

    Illes, Sebastian; Jakab, Martin; Beyer, Felix; Gelfert, Renate; Couillard-Despres, Sébastien; Schnitzler, Alfons; Ritter, Markus; Aigner, Ludwig

    2014-03-11

    Neurons generated from pluripotent stem cells (PSCs) self-organize into functional neuronal assemblies in vitro, generating synchronous network activities. Intriguingly, PSC-derived neuronal assemblies develop spontaneous activities that are independent of external stimulation, suggesting the presence of thus far undetected intrinsically active neurons (IANs). Here, by using mouse embryonic stem cells, we provide evidence for the existence of IANs in PSC-neuronal networks based on extracellular multielectrode array and intracellular patch-clamp recordings. IANs remain active after pharmacological inhibition of fast synaptic communication and possess intrinsic mechanisms required for autonomous neuronal activity. PSC-derived IANs are functionally integrated in PSC-neuronal populations, contribute to synchronous network bursting, and exhibit pacemaker properties. The intrinsic activity and pacemaker properties of the neuronal subpopulation identified herein may be particularly relevant for interventions involving transplantation of neural tissues. IANs may be a key element in the regulation of the functional activity of grafted as well as preexisting host neuronal networks.

  6. Inflammatory mediator bradykinin increases population of sensory neurons expressing functional T-type Ca(2+) channels.

    Science.gov (United States)

    Huang, Dongyang; Liang, Ce; Zhang, Fan; Men, Hongchao; Du, Xiaona; Gamper, Nikita; Zhang, Hailin

    2016-04-29

    T-type Ca(2+) channels are important regulators of peripheral sensory neuron excitability. Accordingly, T-type Ca(2+) currents are often increased in various pathological pain conditions, such as inflammation or nerve injury. Here we investigated effects of inflammation on functional expression of T-type Ca(2+) channels in small-diameter cultured dorsal root ganglion (DRG) neurons. We found that overnight treatment of DRG cultures with a cocktail of inflammatory mediators bradykinin (BK), adenosine triphosphate (ATP), norepinephrine (NE) and prostaglandin E2 (PGE2) strongly increased the population size of the small-diameter neurons displaying low-voltage activated (LVA, T-type) Ca(2+) currents while having no effect on the peak LVA current amplitude. When applied individually, BK and ATP also increased the population size of LVA-positive neurons while NE and PGE2 had no effect. The PLC inhibitor U-73122 and B2 receptor antagonist, Hoe-140, both abolished the increase of the population of LVA-positive DRG neurons. Inflammatory treatment did not affect CaV3.2 mRNA or protein levels in DRG cultures. Furthermore, an ubiquitination inhibitor, MG132, did not increase the population of LVA-positive neurons. Our data suggest that inflammatory mediators BK and ATP increase the abundance of LVA-positive DRG neurons in total neuronal population by stimulating the recruitment of a 'reserve pool' of CaV3.2 channels, particularly in neurons that do not display measurable LVA currents under control conditions. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Emergent properties of interacting populations of spiking neurons.

    Science.gov (United States)

    Cardanobile, Stefano; Rotter, Stefan

    2011-01-01

    Dynamic neuronal networks are a key paradigm of increasing importance in brain research, concerned with the functional analysis of biological neuronal networks and, at the same time, with the synthesis of artificial brain-like systems. In this context, neuronal network models serve as mathematical tools to understand the function of brains, but they might as well develop into future tools for enhancing certain functions of our nervous system. Here, we present and discuss our recent achievements in developing multiplicative point processes into a viable mathematical framework for spiking network modeling. The perspective is that the dynamic behavior of these neuronal networks is faithfully reflected by a set of non-linear rate equations, describing all interactions on the population level. These equations are similar in structure to Lotka-Volterra equations, well known by their use in modeling predator-prey relations in population biology, but abundant applications to economic theory have also been described. We present a number of biologically relevant examples for spiking network function, which can be studied with the help of the aforementioned correspondence between spike trains and specific systems of non-linear coupled ordinary differential equations. We claim that, enabled by the use of multiplicative point processes, we can make essential contributions to a more thorough understanding of the dynamical properties of interacting neuronal populations.

  8. Emergent properties of interacting populations of spiking neurons

    Directory of Open Access Journals (Sweden)

    Stefano eCardanobile

    2011-12-01

    Full Text Available Dynamic neuronal networks are a key paradigm of increasing importance in brain research, concerned with the functional analysis of biological neuronal networks and, at the same time, with the synthesis of artificial brain-like systems. In this context, neuronal network models serve as mathematical tools to understand the function of brains, but they might as well develop into future tools for enhancing certain functions of our nervous system.Here, we discuss our recent achievements in developing multiplicative point processes into a viable mathematical framework for spiking network modeling. The perspective is that the dynamic behavior of these neuronal networks on the population level is faithfully reflected by a set of non-linear rate equations, describing all interactions on this level. These equations, in turn, are similar in structure to the Lotka-Volterra equations, well known by their use in modeling predator-prey relationships in population biology, but abundant applications to economic theory have also been described.We present a number of biologically relevant examples for spiking network function, which can be studied with the help of the aforementioned correspondence between spike trains and specific systems of non-linear coupled ordinary differential equations. We claim that, enabled by the use of multiplicative point processes, we can make essential contributions to a more thorough understanding of the dynamical properties of neural populations.

  9. Two-population model for medial temporal lobe neurons: The vast majority are almost silent.

    Science.gov (United States)

    Magyar, Andrew; Collins, John

    2015-07-01

    Recordings in the human medial temporal lobe have found many neurons that respond to pictures (and related stimuli) of just one particular person of those presented. It has been proposed that these are concept cells, responding to just a single concept. However, a direct experimental test of the concept cell idea appears impossible, because it would need the measurement of the response of each cell to enormous numbers of other stimuli. Here we propose a new statistical method for analysis of the data that gives a more powerful way to analyze how close data are to the concept-cell idea. Central to the model is the neuronal sparsity, defined as the total fraction of stimuli that elicit an above-threshold response in the neuron. The model exploits the large number of sampled neurons to give sensitivity to situations where the average response sparsity is much less than one response for the number of presented stimuli. We show that a conventional model where a single sparsity is postulated for all neurons gives an extremely poor fit to the data. In contrast, a model with two dramatically different populations gives an excellent fit to data from the hippocampus and entorhinal cortex. In the hippocampus, one population has 7% of the cells with a 2.6% sparsity. But a much larger fraction (93%) respond to only 0.1% of the stimuli. This can result in an extreme bias in the responsiveness of reported neurons compared with a typical neuron. Finally, we show how to allow for the fact that some identified units correspond to multiple neurons and find that our conclusions at the neural level are quantitatively changed but strengthened, with an even stronger difference between the two populations.

  10. Population: Census Bureau Total Estimates (2010-2012)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — Total population estimates are estimates of the total number of residents living in an area on July 1 of each year. The Census Bureau’s Population Division produces...

  11. Stochastic synchronization of neuronal populations with intrinsic and extrinsic noise.

    KAUST Repository

    Bressloff, Paul C

    2011-05-03

    We extend the theory of noise-induced phase synchronization to the case of a neural master equation describing the stochastic dynamics of an ensemble of uncoupled neuronal population oscillators with intrinsic and extrinsic noise. The master equation formulation of stochastic neurodynamics represents the state of each population by the number of currently active neurons, and the state transitions are chosen so that deterministic Wilson-Cowan rate equations are recovered in the mean-field limit. We apply phase reduction and averaging methods to a corresponding Langevin approximation of the master equation in order to determine how intrinsic noise disrupts synchronization of the population oscillators driven by a common extrinsic noise source. We illustrate our analysis by considering one of the simplest networks known to generate limit cycle oscillations at the population level, namely, a pair of mutually coupled excitatory (E) and inhibitory (I) subpopulations. We show how the combination of intrinsic independent noise and extrinsic common noise can lead to clustering of the population oscillators due to the multiplicative nature of both noise sources under the Langevin approximation. Finally, we show how a similar analysis can be carried out for another simple population model that exhibits limit cycle oscillations in the deterministic limit, namely, a recurrent excitatory network with synaptic depression; inclusion of synaptic depression into the neural master equation now generates a stochastic hybrid system.

  12. Inferring eye position from populations of lateral intraparietal neurons.

    Science.gov (United States)

    Graf, Arnulf Ba; Andersen, Richard A

    2014-05-20

    Understanding how the brain computes eye position is essential to unraveling high-level visual functions such as eye movement planning, coordinate transformations and stability of spatial awareness. The lateral intraparietal area (LIP) is essential for this process. However, despite decades of research, its contribution to the eye position signal remains controversial. LIP neurons have recently been reported to inaccurately represent eye position during a saccadic eye movement, and to be too slow to support a role in high-level visual functions. We addressed this issue by predicting eye position and saccade direction from the responses of populations of LIP neurons. We found that both signals were accurately predicted before, during and after a saccade. Also, the dynamics of these signals support their contribution to visual functions. These findings provide a principled understanding of the coding of information in populations of neurons within an important node of the cortical network for visual-motor behaviors.DOI: http://dx.doi.org/10.7554/eLife.02813.001. Copyright © 2014, Graf and Andersen.

  13. A Discrete Population of Neurons in the Lateral Amygdala Is Specifically Activated by Contextual Fear Conditioning

    Science.gov (United States)

    Wilson, Yvette M.; Murphy, Mark

    2009-01-01

    There is no clear identification of the neurons involved in fear conditioning in the amygdala. To search for these neurons, we have used a genetic approach, the "fos-tau-lacZ" (FTL) mouse, to map functionally activated expression in neurons following contextual fear conditioning. We have identified a discrete population of neurons in the lateral…

  14. The effect of correlated neuronal firing and neuronal heterogeneity on population coding accuracy in guinea pig inferior colliculus.

    Directory of Open Access Journals (Sweden)

    Oran Zohar

    Full Text Available It has been suggested that the considerable noise in single-cell responses to a stimulus can be overcome by pooling information from a large population. Theoretical studies indicated that correlations in trial-to-trial fluctuations in the responses of different neurons may limit the improvement due to pooling. Subsequent theoretical studies have suggested that inherent neuronal diversity, i.e., the heterogeneity of tuning curves and other response properties of neurons preferentially tuned to the same stimulus, can provide a means to overcome this limit. Here we study the effect of spike-count correlations and the inherent neuronal heterogeneity on the ability to extract information from large neural populations. We use electrophysiological data from the guinea pig Inferior-Colliculus to capture inherent neuronal heterogeneity and single cell statistics, and introduce response correlations artificially. To this end, we generate pseudo-population responses, based on single-cell recording of neurons responding to auditory stimuli with varying binaural correlations. Typically, when pseudo-populations are generated from single cell data, the responses within the population are statistically independent. As a result, the information content of the population will increase indefinitely with its size. In contrast, here we apply a simple algorithm that enables us to generate pseudo-population responses with variable spike-count correlations. This enables us to study the effect of neuronal correlations on the accuracy of conventional rate codes. We show that in a homogenous population, in the presence of even low-level correlations, information content is bounded. In contrast, utilizing a simple linear readout, that takes into account the natural heterogeneity, even of neurons preferentially tuned to the same stimulus, within the neural population, one can overcome the correlated noise and obtain a readout whose accuracy grows linearly with the size of

  15. Deciphering neuronal population codes for acute thermal pain

    Science.gov (United States)

    Chen, Zhe; Zhang, Qiaosheng; Phuong Sieu Tong, Ai; Manders, Toby R.; Wang, Jing

    2017-06-01

    Objective. Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Current pain research mostly focuses on molecular and synaptic changes at the spinal and peripheral levels. However, a complete understanding of pain mechanisms requires the physiological study of the neocortex. Our goal is to apply a neural decoding approach to read out the onset of acute thermal pain signals, which can be used for brain-machine interface. Approach. We used micro wire arrays to record ensemble neuronal activities from the primary somatosensory cortex (S1) and anterior cingulate cortex (ACC) in freely behaving rats. We further investigated neural codes for acute thermal pain at both single-cell and population levels. To detect the onset of acute thermal pain signals, we developed a novel latent state-space framework to decipher the sorted or unsorted S1 and ACC ensemble spike activities, which reveal information about the onset of pain signals. Main results. The state space analysis allows us to uncover a latent state process that drives the observed ensemble spike activity, and to further detect the ‘neuronal threshold’ for acute thermal pain on a single-trial basis. Our method achieved good detection performance in sensitivity and specificity. In addition, our results suggested that an optimal strategy for detecting the onset of acute thermal pain signals may be based on combined evidence from S1 and ACC population codes. Significance. Our study is the first to detect the onset of acute pain signals based on neuronal ensemble spike activity. It is important from a mechanistic viewpoint as it relates to the significance of S1 and ACC activities in the regulation of the acute pain onset.

  16. Defining POMC neurons using transgenic reagents: impact of transient Pomc expression in diverse immature neuronal populations.

    Science.gov (United States)

    Padilla, Stephanie L; Reef, Daniel; Zeltser, Lori M

    2012-03-01

    Melanocortin signaling plays a central role in the regulation of phenotypes related to body weight and energy homeostasis. To specifically target and study the function of proopiomelanocortin (POMC) neurons, Pomc promoter elements have been utilized to generate reporter and Cre recombinase transgenic reagents. Across gestation, we find that Pomc is dynamically expressed in many sites in the developing mouse forebrain, midbrain, hindbrain, spinal cord, and retina. Although Pomc expression in most embryonic brain regions is transient, it is sufficient to direct Cre-mediated recombination of floxed alleles. We visualize the populations affected by this transgene by crossing Pomc-Cre mice to ROSA reporter strains and identify 62 sites of recombination throughout the adult brain, including several nuclei implicated in energy homeostasis regulation. To compare the relationship between acute Pomc promoter activity and Pomc-Cre-mediated recombination at the single cell level, we crossed Pomc-enhanced green fluorescent protein (eGFP) and Pomc-Cre;ROSA-tdTomato lines. We detect the highest concentration of Pomc-eGFP+ cells in the arcuate nucleus of the hypothalamus and dentate gyrus but also observe smaller populations of labeled cells in the nucleus of the solitary tract, periventricular zone of the third ventricle, and cerebellum. Consistent with the dynamic nature of Pomc expression in the embryo, the vast majority of neurons marked with the tdTomato reporter do not express eGFP in the adult. Thus, recombination in off-target sites could contribute to physiological phenotypes using Pomc-Cre transgenics. For example, we find that approximately 83% of the cells in the arcuate nucleus of the hypothalamus immunoreactive for leptin-induced phosphorylated signal transducer and activator of transcription 3 are marked with Pomc-Cre;ROSA-tdTomato; only 13% of these are eGFP+ POMC neurons.

  17. Representation of dynamical stimuli in populations of threshold neurons.

    Directory of Open Access Journals (Sweden)

    Tatjana Tchumatchenko

    2011-10-01

    Full Text Available Many sensory or cognitive events are associated with dynamic current modulations in cortical neurons. This raises an urgent demand for tractable model approaches addressing the merits and limits of potential encoding strategies. Yet, current theoretical approaches addressing the response to mean- and variance-encoded stimuli rarely provide complete response functions for both modes of encoding in the presence of correlated noise. Here, we investigate the neuronal population response to dynamical modifications of the mean or variance of the synaptic bombardment using an alternative threshold model framework. In the variance and mean channel, we provide explicit expressions for the linear and non-linear frequency response functions in the presence of correlated noise and use them to derive population rate response to step-like stimuli. For mean-encoded signals, we find that the complete response function depends only on the temporal width of the input correlation function, but not on other functional specifics. Furthermore, we show that both mean- and variance-encoded signals can relay high-frequency inputs, and in both schemes step-like changes can be detected instantaneously. Finally, we obtain the pairwise spike correlation function and the spike triggered average from the linear mean-evoked response function. These results provide a maximally tractable limiting case that complements and extends previous results obtained in the integrate and fire framework.

  18. Using neuronal populations to study the mechanisms underlying spatial and feature attention

    Science.gov (United States)

    Cohen, Marlene R.; Maunsell, John H.R.

    2012-01-01

    Summary Visual attention affects both perception and neuronal responses. Whether the same neuronal mechanisms mediate spatial attention, which improves perception of attended locations, and non-spatial forms of attention has been a subject of considerable debate. Spatial and feature attention have similar effects on individual neurons. Because visual cortex is retinotopically organized, however, spatial attention can co-modulate local neuronal populations, while feature attention generally requires more selective modulation. We compared the effects of feature and spatial attention on local and spatially separated populations by recording simultaneously from dozens of neurons in both hemispheres of V4. Feature and spatial attention affect the activity of local populations similarly, modulating both firing rates and correlations between pairs of nearby neurons. However, while spatial attention appears to act on local populations, feature attention is coordinated across hemispheres. Our results are consistent with a unified attentional mechanism that can modulate the responses of arbitrary subgroups of neurons. PMID:21689604

  19. PINP: a new method of tagging neuronal populations for identification during in vivo electrophysiological recording.

    Directory of Open Access Journals (Sweden)

    Susana Q Lima

    Full Text Available Neural circuits are exquisitely organized, consisting of many different neuronal subpopulations. However, it is difficult to assess the functional roles of these subpopulations using conventional extracellular recording techniques because these techniques do not easily distinguish spikes from different neuronal populations. To overcome this limitation, we have developed PINP (Photostimulation-assisted Identification of Neuronal Populations, a method of tagging neuronal populations for identification during in vivo electrophysiological recording. The method is based on expressing the light-activated channel channelrhodopsin-2 (ChR2 to restricted neuronal subpopulations. ChR2-tagged neurons can be detected electrophysiologically in vivo since illumination of these neurons with a brief flash of blue light triggers a short latency reliable action potential. We demonstrate the feasibility of this technique by expressing ChR2 in distinct populations of cortical neurons using two different strategies. First, we labeled a subpopulation of cortical neurons-mainly fast-spiking interneurons-by using adeno-associated virus (AAV to deliver ChR2 in a transgenic mouse line in which the expression of Cre recombinase was driven by the parvalbumin promoter. Second, we labeled subpopulations of excitatory neurons in the rat auditory cortex with ChR2 based on projection target by using herpes simplex virus 1 (HSV1, which is efficiently taken up by axons and transported retrogradely; we find that this latter population responds to acoustic stimulation differently from unlabeled neurons. Tagging neurons is a novel application of ChR2, used in this case to monitor activity instead of manipulating it. PINP can be readily extended to other populations of genetically identifiable neurons, and will provide a useful method for probing the functional role of different neuronal populations in vivo.

  20. Dense reconstruction of brain-wide neuronal population close to the ground truth

    OpenAIRE

    Li, Yun; Zhou, Hang; Li, Shiwei; Li, Jing; Su, Lei; Li, Anan; Feng, Xiong; Li, Ning; Han, Jiacheng; Kang, Hongtao; Chen, Yijun; Fang, Wenqian; Liu, Yidong; Lin, Huimin; Jin, Sen

    2017-01-01

    Neuron is the basic structure and functional unit of the brain, its projection and connections with other neurons provide a basic physical infrastructure for neural signal storage, allocation, processing, and integration. Recent technique progresses allow for labeling and imaging specific neuronal populations at single axonal level across a whole mouse brain. However, digital reconstruction of these neuron individuals needs months of human labor or sometimes is even an impossible task. Here w...

  1. The Limited Utility of Multiunit Data in Differentiating Neuronal Population Activity.

    Directory of Open Access Journals (Sweden)

    Corey J Keller

    Full Text Available To date, single neuron recordings remain the gold standard for monitoring the activity of neuronal populations. Since obtaining single neuron recordings is not always possible, high frequency or 'multiunit activity' (MUA is often used as a surrogate. Although MUA recordings allow one to monitor the activity of a large number of neurons, they do not allow identification of specific neuronal subtypes, the knowledge of which is often critical for understanding electrophysiological processes. Here, we explored whether prior knowledge of the single unit waveform of specific neuron types is sufficient to permit the use of MUA to monitor and distinguish differential activity of individual neuron types. We used an experimental and modeling approach to determine if components of the MUA can monitor medium spiny neurons (MSNs and fast-spiking interneurons (FSIs in the mouse dorsal striatum. We demonstrate that when well-isolated spikes are recorded, the MUA at frequencies greater than 100Hz is correlated with single unit spiking, highly dependent on the waveform of each neuron type, and accurately reflects the timing and spectral signature of each neuron. However, in the absence of well-isolated spikes (the norm in most MUA recordings, the MUA did not typically contain sufficient information to permit accurate prediction of the respective population activity of MSNs and FSIs. Thus, even under ideal conditions for the MUA to reliably predict the moment-to-moment activity of specific local neuronal ensembles, knowledge of the spike waveform of the underlying neuronal populations is necessary, but not sufficient.

  2. The impact of maternal separation on adult mouse behaviour and on the total neuron number in the mouse hippocampus

    DEFF Research Database (Denmark)

    Fabricius, K.; Wörtwein, Gitta; Pakkenberg, B.

    2008-01-01

    , the number of errors made by the MS24 mice compared to controls and in total distance moved. The mice were subsequently sacrificed and the total number of neurons estimated in the hippocampus using the optical fractionator. We found a significant loss of neurons in the dentate gyrus in MS mice compared...... to controls. Apparently a single maternal separation can impact the number of neurons in mouse hippocampus either by a decrease of neurogenesis or as an increase in neuron apoptosis. This study is the first to assess the result of maternal separation combining behaviour and stereology Udgivelsesdato: 2008/2...

  3. Encoding of Naturalistic Optic Flow by a Population of Blowfly Motion-Sensitive Neurons

    NARCIS (Netherlands)

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

    In sensory systems information is encoded by the activity of populations of neurons. To analyze the coding properties of neuronal populations sensory stimuli have usually been used that were much simpler than those encountered in real life. It has been possible only recently to stimulate visual

  4. Inhibitory coherence in a heterogeneous population of subthreshold and suprathreshold type-I neurons

    International Nuclear Information System (INIS)

    Kim, Sang-Yoon; Hong, Duk-Geun; Kim, Jean; Lim, Woochang

    2012-01-01

    We study inhibitory coherence (i.e. collective coherence by synaptic inhibition) in a population of globally coupled type-I neurons, which can fire at arbitrarily low frequency. No inhibitory coherence is observed in a homogeneous population composed of only subthreshold neurons, which exhibit noise-induced firings. In addition to subthreshold neurons, there exist spontaneously firing suprathreshold neurons in a noisy environment of a real brain. To take into consideration the effect of suprathreshold neurons on inhibitory coherence, we consider a heterogeneous population of subthreshold and suprathreshold neurons and investigate the inhibitory coherence by increasing the fraction of suprathreshold neurons P supra . As P supra passes a threshold P* supra , suprathreshold neurons begin to synchronize and play the role of coherent inhibitors for the emergence of inhibitory coherence. Thus, regularly oscillating population-averaged global potential appears for P supra > P* supra . For this coherent case, suprathreshold neurons exhibit sparse spike synchronization (i.e. individual potentials of suprathreshold neurons consist of coherent sparse spikings and coherent subthreshold small-amplitude hoppings). By virtue of their coherent inhibition, sparsely synchronized suprathreshold neurons suppress the noisy activity of subthreshold neurons. Thus, subthreshold neurons exhibit hopping synchronization (i.e. only coherent subthreshold hopping oscillations without spikings appear in the individual potentials of subthreshold neurons). We also characterize the inhibitory coherence in terms of the ‘statistical-mechanical’ spike-based and correlation-based measures, which quantify the average contributions of the microscopic individual spikes and individual potentials to the macroscopic global potential. Finally, the effect of sparse randomness of synaptic connectivity on the inhibitory coherence is briefly discussed. (paper)

  5. [Protective effect of Uncaria rhynchophylla total alkaloids pretreatment on hippocampal neurons after acute hypoxia].

    Science.gov (United States)

    Liu, Wei; Zhang, Zhao-qin; Zhao, Xiao-min; Gao, Yun-sheng

    2006-05-01

    To investigate the effect of Uncaria rhynchophylla total alkaloids (RTA) pretreatment on the voltage-gated sodium currents of the rat hippocampal neurons after acute hypoxia. Primary cultured hippocampal neurons were divided into RTA pre-treated and non-pretreated groups. Patch clamp whole-cell recording was used to compare the voltage-gated sodium current amplitude and threshold with those before hypoxia. After acute hypoxia, sodium current amplitude was significantly decreased and its threshold was upside. RTA pretreatment could inhibit the reduction of sodium current amplitude. RTA pretreatment alleviates the acute hypoxia-induced change of sodium currents, which may be one of the mechanisms for protective effect of RTA on cells.

  6. Long-term memory in Aplysia modulates the total number of varicosities of single identified sensory neurons.

    OpenAIRE

    Bailey, C H; Chen, M

    1988-01-01

    The morphological consequences of long-term habituation and sensitization of the gill withdrawal reflex in Aplysia california were explored by examining the total number of presynaptic varicosities of single identified sensory neurons (a critical site of plasticity for the biochemical and biophysical changes that underlie both types of learning) in control and behaviorally trained animals. Sensory neurons from habituated animals had 35% fewer synaptic varicosities than did sensory neurons fro...

  7. Towards a theory of cortical columns: From spiking neurons to interacting neural populations of finite size

    Science.gov (United States)

    Gerstner, Wulfram

    2017-01-01

    Neural population equations such as neural mass or field models are widely used to study brain activity on a large scale. However, the relation of these models to the properties of single neurons is unclear. Here we derive an equation for several interacting populations at the mesoscopic scale starting from a microscopic model of randomly connected generalized integrate-and-fire neuron models. Each population consists of 50–2000 neurons of the same type but different populations account for different neuron types. The stochastic population equations that we find reveal how spike-history effects in single-neuron dynamics such as refractoriness and adaptation interact with finite-size fluctuations on the population level. Efficient integration of the stochastic mesoscopic equations reproduces the statistical behavior of the population activities obtained from microscopic simulations of a full spiking neural network model. The theory describes nonlinear emergent dynamics such as finite-size-induced stochastic transitions in multistable networks and synchronization in balanced networks of excitatory and inhibitory neurons. The mesoscopic equations are employed to rapidly integrate a model of a cortical microcircuit consisting of eight neuron types, which allows us to predict spontaneous population activities as well as evoked responses to thalamic input. Our theory establishes a general framework for modeling finite-size neural population dynamics based on single cell and synapse parameters and offers an efficient approach to analyzing cortical circuits and computations. PMID:28422957

  8. Towards a theory of cortical columns: From spiking neurons to interacting neural populations of finite size.

    Science.gov (United States)

    Schwalger, Tilo; Deger, Moritz; Gerstner, Wulfram

    2017-04-01

    Neural population equations such as neural mass or field models are widely used to study brain activity on a large scale. However, the relation of these models to the properties of single neurons is unclear. Here we derive an equation for several interacting populations at the mesoscopic scale starting from a microscopic model of randomly connected generalized integrate-and-fire neuron models. Each population consists of 50-2000 neurons of the same type but different populations account for different neuron types. The stochastic population equations that we find reveal how spike-history effects in single-neuron dynamics such as refractoriness and adaptation interact with finite-size fluctuations on the population level. Efficient integration of the stochastic mesoscopic equations reproduces the statistical behavior of the population activities obtained from microscopic simulations of a full spiking neural network model. The theory describes nonlinear emergent dynamics such as finite-size-induced stochastic transitions in multistable networks and synchronization in balanced networks of excitatory and inhibitory neurons. The mesoscopic equations are employed to rapidly integrate a model of a cortical microcircuit consisting of eight neuron types, which allows us to predict spontaneous population activities as well as evoked responses to thalamic input. Our theory establishes a general framework for modeling finite-size neural population dynamics based on single cell and synapse parameters and offers an efficient approach to analyzing cortical circuits and computations.

  9. Transgenic tools to characterize neuronal properties of discrete populations of zebrafish neurons.

    Science.gov (United States)

    Satou, Chie; Kimura, Yukiko; Hirata, Hiromi; Suster, Maximiliano L; Kawakami, Koichi; Higashijima, Shin-ichi

    2013-09-01

    The developing nervous system consists of a variety of cell types. Transgenic animals expressing reporter genes in specific classes of neuronal cells are powerful tools for the study of neuronal network formation. We generated a wide variety of transgenic zebrafish that expressed reporter genes in specific classes of neurons or neuronal progenitors. These include lines in which neurons of specific neurotransmitter phenotypes expressed fluorescent proteins or Gal4, and lines in which specific subsets of the dorsal progenitor domain in the spinal cord expressed fluorescent proteins. Using these, we examined domain organization in the developing dorsal spinal cord, and found that there are six progenitor domains in zebrafish, which is similar to the domain organization in mice. We also systematically characterized neurotransmitter properties of the neurons that are produced from each domain. Given that reporter gene expressions occurs in a wide area of the nervous system in the lines generated, these transgenic fish should serve as powerful tools for the investigation of not only the neurons in the dorsal spinal cord but also neuronal structures and functions in many other regions of the nervous system.

  10. Laser capture microdissection of enriched populations of neurons or single neurons for gene expression analysis after traumatic brain injury.

    Science.gov (United States)

    Boone, Deborah R; Sell, Stacy L; Hellmich, Helen Lee

    2013-04-10

    Long-term cognitive disability after TBI is associated with injury-induced neurodegeneration in the hippocampus-a region in the medial temporal lobe that is critical for learning, memory and executive function. Hence our studies focus on gene expression analysis of specific neuronal populations in distinct subregions of the hippocampus. The technique of laser capture microdissection (LCM), introduced in 1996 by Emmert-Buck, et al., has allowed for significant advances in gene expression analysis of single cells and enriched populations of cells from heterogeneous tissues such as the mammalian brain that contains thousands of functional cell types. We use LCM and a well established rat model of traumatic brain injury (TBI) to investigate the molecular mechanisms that underlie the pathogenesis of TBI. Following fluid-percussion TBI, brains are removed at pre-determined times post-injury, immediately frozen on dry ice, and prepared for sectioning in a cryostat. The rat brains can be embedded in OCT and sectioned immediately, or stored several months at -80 °C before sectioning for laser capture microdissection. Additionally, we use LCM to study the effects of TBI on circadian rhythms. For this, we capture neurons from the suprachiasmatic nuclei that contain the master clock of the mammalian brain. Here, we demonstrate the use of LCM to obtain single identified neurons (injured and degenerating, Fluoro-Jade-positive, or uninjured, Fluoro-Jade-negative) and enriched populations of hippocampal neurons for subsequent gene expression analysis by real time PCR and/or whole-genome microarrays. These LCM-enabled studies have revealed that the selective vulnerability of anatomically distinct regions of the rat hippocampus are reflected in the different gene expression profiles of different populations of neurons obtained by LCM from these distinct regions. The results from our single-cell studies, where we compare the transcriptional profiles of dying and adjacent surviving

  11. Extracting functionally feedforward networks from a population of spiking neurons.

    Science.gov (United States)

    Vincent, Kathleen; Tauskela, Joseph S; Thivierge, Jean-Philippe

    2012-01-01

    Neuronal avalanches are a ubiquitous form of activity characterized by spontaneous bursts whose size distribution follows a power-law. Recent theoretical models have replicated power-law avalanches by assuming the presence of functionally feedforward connections (FFCs) in the underlying dynamics of the system. Accordingly, avalanches are generated by a feedforward chain of activation that persists despite being embedded in a larger, massively recurrent circuit. However, it is unclear to what extent networks of living neurons that exhibit power-law avalanches rely on FFCs. Here, we employed a computational approach to reconstruct the functional connectivity of cultured cortical neurons plated on multielectrode arrays (MEAs) and investigated whether pharmacologically induced alterations in avalanche dynamics are accompanied by changes in FFCs. This approach begins by extracting a functional network of directed links between pairs of neurons, and then evaluates the strength of FFCs using Schur decomposition. In a first step, we examined the ability of this approach to extract FFCs from simulated spiking neurons. The strength of FFCs obtained in strictly feedforward networks diminished monotonically as links were gradually rewired at random. Next, we estimated the FFCs of spontaneously active cortical neuron cultures in the presence of either a control medium, a GABA(A) receptor antagonist (PTX), or an AMPA receptor antagonist combined with an NMDA receptor antagonist (APV/DNQX). The distribution of avalanche sizes in these cultures was modulated by this pharmacology, with a shallower power-law under PTX (due to the prominence of larger avalanches) and a steeper power-law under APV/DNQX (due to avalanches recruiting fewer neurons) relative to control cultures. The strength of FFCs increased in networks after application of PTX, consistent with an amplification of feedforward activity during avalanches. Conversely, FFCs decreased after application of APV

  12. Membrane potential and response properties of populations of cortical neurons in the high conductance state

    International Nuclear Information System (INIS)

    Moreno-Bote, Ruben; Parga, Nestor

    2005-01-01

    Because of intense synaptic activity, cortical neurons are in a high conductance state. We show that this state has important consequences on the properties of a population of independent model neurons with conductance-based synapses. Using an adiabaticlike approximation we study both the membrane potential and the firing probability distributions across the population. We find that the latter is bimodal in such a way that at any particular moment some neurons are inactive while others are active. The population rate and the response variability are also characterized

  13. Not a single but multiple populations of GABAergic neurons control sleep.

    Science.gov (United States)

    Luppi, Pierre-Hervé; Peyron, Christelle; Fort, Patrice

    2017-04-01

    The role of gamma-amino butyric acid (GABA) in sleep induction and maintenance is well accepted since most insomnia treatments target GABAa receptors. However, the population(s) of GABAergic neurons involved in the beneficial effect of GABA on sleep remains to be identified. This is not an easy task since GABAergic neurons are widely distributed in all brain structures. A recently growing number of populations of GABAergic neurons have been involved in sleep control. We first review here possible candidates for inducing non-rapid eye movement (NREM) sleep including the GABAergic neurons of the ventrolateral preoptic area, the parafacial zone in the brainstem, the nucleus accumbens and the cortex. We also discuss the role of several populations of GABAergic neurons in rapid eye movement (REM) sleep control. Indeed, it is well accepted that muscle atonia occurring during REM sleep is due to a GABA/glycinergic hyperpolarization of motoneurons. Recent evidence strongly suggests that these neurons are located in the ventral medullary reticular formation. It has also recently been shown that neurons containing the neuropeptide melanin concentrating hormone and GABA located in the lateral hypothalamic area control REM sleep expression. Finally, a population of REM-off GABAergic neurons located in the ventrolateral periaqueductal gray has been shown to gate REM sleep by inhibiting glutamatergic neurons located in the sublaterodorsal tegmental nucleus. In summary, recent data clearly indicate that multiple populations of GABAergic neurons located throughout the brain from the cortex to the medulla oblongata control NREM and REM sleep. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Context Fear Learning Specifically Activates Distinct Populations of Neurons in Amygdala and Hypothalamus

    Science.gov (United States)

    Trogrlic, Lidia; Wilson, Yvette M.; Newman, Andrew G.; Murphy, Mark

    2011-01-01

    The identity and distribution of neurons that are involved in any learning or memory event is not known. In previous studies, we identified a discrete population of neurons in the lateral amygdala that show learning-specific activation of a c-"fos"-regulated transgene following context fear conditioning. Here, we have extended these studies to…

  15. Niche-dependent development of functional neuronal networks from embryonic stem cell-derived neural populations

    Directory of Open Access Journals (Sweden)

    Siebler Mario

    2009-08-01

    Full Text Available Abstract Background The present work was performed to investigate the ability of two different embryonic stem (ES cell-derived neural precursor populations to generate functional neuronal networks in vitro. The first ES cell-derived neural precursor population was cultivated as free-floating neural aggregates which are known to form a developmental niche comprising different types of neural cells, including neural precursor cells (NPCs, progenitor cells and even further matured cells. This niche provides by itself a variety of different growth factors and extracellular matrix proteins that influence the proliferation and differentiation of neural precursor and progenitor cells. The second population was cultivated adherently in monolayer cultures to control most stringently the extracellular environment. This population comprises highly homogeneous NPCs which are supposed to represent an attractive way to provide well-defined neuronal progeny. However, the ability of these different ES cell-derived immature neural cell populations to generate functional neuronal networks has not been assessed so far. Results While both precursor populations were shown to differentiate into sufficient quantities of mature NeuN+ neurons that also express GABA or vesicular-glutamate-transporter-2 (vGlut2, only aggregate-derived neuronal populations exhibited a synchronously oscillating network activity 2–4 weeks after initiating the differentiation as detected by the microelectrode array technology. Neurons derived from homogeneous NPCs within monolayer cultures did merely show uncorrelated spiking activity even when differentiated for up to 12 weeks. We demonstrated that these neurons exhibited sparsely ramified neurites and an embryonic vGlut2 distribution suggesting an inhibited terminal neuronal maturation. In comparison, neurons derived from heterogeneous populations within neural aggregates appeared as fully mature with a dense neurite network and punctuated

  16. Convergent processing of both positive and negative motivational signals by the VTA dopamine neuronal populations.

    Directory of Open Access Journals (Sweden)

    Dong V Wang

    2011-02-01

    Full Text Available Dopamine neurons in the ventral tegmental area (VTA have been traditionally studied for their roles in reward-related motivation or drug addiction. Here we study how the VTA dopamine neuron population may process fearful and negative experiences as well as reward information in freely behaving mice. Using multi-tetrode recording, we find that up to 89% of the putative dopamine neurons in the VTA exhibit significant activation in response to the conditioned tone that predict food reward, while the same dopamine neuron population also respond to the fearful experiences such as free fall and shake events. The majority of these VTA putative dopamine neurons exhibit suppression and offset-rebound excitation, whereas ∼25% of the recorded putative dopamine neurons show excitation by the fearful events. Importantly, VTA putative dopamine neurons exhibit parametric encoding properties: their firing change durations are proportional to the fearful event durations. In addition, we demonstrate that the contextual information is crucial for these neurons to respectively elicit positive or negative motivational responses by the same conditioned tone. Taken together, our findings suggest that VTA dopamine neurons may employ the convergent encoding strategy for processing both positive and negative experiences, intimately integrating with cues and environmental context.

  17. Symmetry breaking in two interacting populations of quadratic integrate-and-fire neurons

    Science.gov (United States)

    Ratas, Irmantas; Pyragas, Kestutis

    2017-10-01

    We analyze the dynamics of two coupled identical populations of quadratic integrate-and-fire neurons, which represent the canonical model for class I neurons near the spiking threshold. The populations are heterogeneous; they include both inherently spiking and excitable neurons. The coupling within and between the populations is global via synapses that take into account the finite width of synaptic pulses. Using a recently developed reduction method based on the Lorentzian ansatz, we derive a closed system of equations for the neuron's firing rates and the mean membrane potentials in both populations. The reduced equations are exact in the infinite-size limit. The bifurcation analysis of the equations reveals a rich variety of nonsymmetric patterns, including a splay state, antiphase periodic oscillations, chimera-like states, and chaotic oscillations as well as bistabilities between various states. The validity of the reduced equations is confirmed by direct numerical simulations of the finite-size networks.

  18. Different requirements for GFRα2-signaling in three populations of cutaneous sensory neurons.

    Science.gov (United States)

    Kupari, Jussi; Airaksinen, Matti S

    2014-01-01

    Many primary sensory neurons in mouse dorsal root ganglia (DRG) express one or several GFRα's, the ligand-binding receptors of the GDNF family, and their common signaling receptor Ret. GFRα2, the principal receptor for neurturin, is expressed in most of the small nonpeptidergic DRG neurons, but also in some large DRG neurons that start to express Ret earlier. Previously, GFRα2 has been shown to be crucial for the soma size of small nonpeptidergic nociceptors and for their target innervation of glabrous epidermis. However, little is known about this receptor in other Ret-expressing DRG neuron populations. Here we have investigated two populations of Ret-positive low-threshold mechanoreceptors that innervate different types of hair follicles on mouse back skin: the small C-LTMRs and the large Aβ-LTMRs. Using GFRα2-KO mice and immunohistochemistry we found that, similar to the nonpeptidergic nociceptors, GFRα2 controls the cell size but not the survival of both C-LTMRs and Aβ-LTMRs. In contrast to the nonpeptidergic neurons, GFRα2 is not required for the target innervation of C-LTMRs and Aβ-LTMRs in the back skin. These results suggest that different factors drive target innervation in these three populations of neurons. In addition, the observation that the large Ret-positive DRG neurons lack GFRα2 immunoreactivity in mature animals suggests that these neurons switch their GFRα signaling pathways during postnatal development.

  19. From Quasiperiodic Partial Synchronization to Collective Chaos in Populations of Inhibitory Neurons with Delay.

    Science.gov (United States)

    Pazó, Diego; Montbrió, Ernest

    2016-06-10

    Collective chaos is shown to emerge, via a period-doubling cascade, from quasiperiodic partial synchronization in a population of identical inhibitory neurons with delayed global coupling. This system is thoroughly investigated by means of an exact model of the macroscopic dynamics, valid in the thermodynamic limit. The collective chaotic state is reproduced numerically with a finite population, and persists in the presence of weak heterogeneities. Finally, the relationship of the model's dynamics with fast neuronal oscillations is discussed.

  20. The total satellite population of the Milky Way

    Science.gov (United States)

    Newton, Oliver; Cautun, Marius; Jenkins, Adrian; Frenk, Carlos S.; Helly, John C.

    2018-05-01

    The total number and luminosity function of the population of dwarf galaxies of the Milky Way (MW) provide important constraints on the nature of the dark matter and on the astrophysics of galaxy formation at low masses. However, only a partial census of this population exists because of the flux limits and restricted sky coverage of existing Galactic surveys. We combine the sample of satellites recently discovered by the Dark Energy Survey (DES) survey with the satellites found in Sloan Digital Sky Survey (SDSS) Data Release 9 (together these surveys cover nearly half the sky) to estimate the total luminosity function of satellites down to MV = 0. We apply a new Bayesian inference method in which we assume that the radial distribution of satellites independently of absolute magnitude follows that of subhaloes selected according to their peak maximum circular velocity. We find that there should be at least 124^{+40}_{-27}(68% CL, statistical error) satellites brighter than MV = 0 within 300kpc of the Sun. As a result of our use of new data and better simulations, and a more robust statistical method, we infer a much smaller population of satellites than reported in previous studies using earlier SDSS data only; we also address an underestimation of the uncertainties in earlier work by accounting for stochastic effects. We find that the inferred number of faint satellites depends only weakly on the assumed mass of the MW halo and we provide scaling relations to extend our results to different assumed halo masses and outer radii. We predict that half of our estimated total satellite population of the MW should be detected by the Large Synoptic Survey Telescope (LSST). The code implementing our estimation method is available online.†

  1. A Tractable Method for Describing Complex Couplings between Neurons and Population Rate.

    Science.gov (United States)

    Gardella, Christophe; Marre, Olivier; Mora, Thierry

    2016-01-01

    Neurons within a population are strongly correlated, but how to simply capture these correlations is still a matter of debate. Recent studies have shown that the activity of each cell is influenced by the population rate, defined as the summed activity of all neurons in the population. However, an explicit, tractable model for these interactions is still lacking. Here we build a probabilistic model of population activity that reproduces the firing rate of each cell, the distribution of the population rate, and the linear coupling between them. This model is tractable, meaning that its parameters can be learned in a few seconds on a standard computer even for large population recordings. We inferred our model for a population of 160 neurons in the salamander retina. In this population, single-cell firing rates depended in unexpected ways on the population rate. In particular, some cells had a preferred population rate at which they were most likely to fire. These complex dependencies could not be explained by a linear coupling between the cell and the population rate. We designed a more general, still tractable model that could fully account for these nonlinear dependencies. We thus provide a simple and computationally tractable way to learn models that reproduce the dependence of each neuron on the population rate.

  2. Long-term estradiol-17β administration changes the population of paracervical ganglion neurons supplying the ovary in adult gilts.

    Science.gov (United States)

    Jana, Barbara; Palus, Katarzyna; Czarzasta, Joanna; Całka, Jarosław

    2013-07-01

    The aim of this study was to determine the influence of estradiol-17β (E(2)) overdose on the number and distribution of ovarian parasympathetic neurons in the paracervical ganglion (PCG) in adult pigs. To identify the neurons innervating gonads on day 3 of the estrous cycle, the ovaries of both the control and experimental gilts were injected with retrograde neuronal tracer Fast Blue. From next day to the expected day 20 of the second studied cycle, experimental gilts were injected with E(2), while control gilts received oil. The PCG were then collected and processed for double-labeling immunofluorescence. Injections of E(2) increased the E(2) level in the peripheral blood approximately four- to fivefold and reduced the following in the PCG: the total number of Fast Blue-positive neurons; the number of perikarya in the lateral part of the PCG; the numbers of vesicular acetylcholine transporter (VAChT)(+)/somatostatin(+), VAChT(+)/vasoactive intestinal polypeptide (VIP)(+), VAChT(+)/neuronal isoform of nitric oxide synthase(+), VAChT(+)/VIP(-), VAChT(+)/dopamine β-hydroxylase (DβH)(-), VAChT(-)/VIP(-), and VAChT(-)/DβH(-) perikarya; and the total number of perikarya expressing estrogen receptors (ERs) subtype α and/or β. In summary, long-term E(2) treatment of adult gilts downregulates the population of both cholinergic and ERs expressing the PCG ovary-projecting neurons. Our results suggest that elevated E(2) levels occurring during pathological states may regulate gonadal function(s) by affecting ovary-supplying neurons.

  3. Gene expression profiling of two distinct neuronal populations in the rodent spinal cord.

    Directory of Open Access Journals (Sweden)

    Jesper Ryge

    Full Text Available BACKGROUND: In the field of neuroscience microarray gene expression profiles on anatomically defined brain structures are being used increasingly to study both normal brain functions as well as pathological states. Fluorescent tracing techniques in brain tissue that identifies distinct neuronal populations can in combination with global gene expression profiling potentially increase the resolution and specificity of such studies to shed new light on neuronal functions at the cellular level. METHODOLOGY/PRINCIPAL FINDINGS: We examine the microarray gene expression profiles of two distinct neuronal populations in the spinal cord of the neonatal rat, the principal motor neurons and specific interneurons involved in motor control. The gene expression profiles of the respective cell populations were obtained from amplified mRNA originating from 50-250 fluorescently identified and laser microdissected cells. In the data analysis we combine a new microarray normalization procedure with a conglomerate measure of significant differential gene expression. Using our methodology we find 32 genes to be more expressed in the interneurons compared to the motor neurons that all except one have not previously been associated with this neuronal population. As a validation of our method we find 17 genes to be more expressed in the motor neurons than in the interneurons and of these only one had not previously been described in this population. CONCLUSIONS/SIGNIFICANCE: We provide an optimized experimental protocol that allows isolation of gene transcripts from fluorescent retrogradely labeled cell populations in fresh tissue, which can be used to generate amplified aRNA for microarray hybridization from as few as 50 laser microdissected cells. Using this optimized experimental protocol in combination with our microarray analysis methodology we find 49 differentially expressed genes between the motor neurons and the interneurons that reflect the functional

  4. Populations of subplate and interstitial neurons in fetal and adult human telencephalon.

    Science.gov (United States)

    Judaš, Miloš; Sedmak, Goran; Pletikos, Mihovil; Jovanov-Milošević, Nataša

    2010-10-01

    In the adult human telencephalon, subcortical (gyral) white matter contains a special population of interstitial neurons considered to be surviving descendants of fetal subplate neurons [Kostovic & Rakic (1980) Cytology and the time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. J Neurocytol9, 219]. We designate this population of cells as superficial (gyral) interstitial neurons and describe their morphology and distribution in the postnatal and adult human cerebrum. Human fetal subplate neurons cannot be regarded as interstitial, because the subplate zone is an essential part of the fetal cortex, the major site of synaptogenesis and the 'waiting' compartment for growing cortical afferents, and contains both projection neurons and interneurons with distinct input-output connectivity. However, although the subplate zone is a transient fetal structure, many subplate neurons survive postnatally as superficial (gyral) interstitial neurons. The fetal white matter is represented by the intermediate zone and well-defined deep periventricular tracts of growing axons, such as the corpus callosum, anterior commissure, internal and external capsule, and the fountainhead of the corona radiata. These tracts gradually occupy the territory of transient fetal subventricular and ventricular zones.The human fetal white matter also contains distinct populations of deep fetal interstitial neurons, which, by virtue of their location, morphology, molecular phenotypes and advanced level of dendritic maturation, remain distinct from subplate neurons and neurons in adjacent structures (e.g. basal ganglia, basal forebrain). We describe the morphological, histochemical (nicotinamide-adenine dinucleotide phosphate-diaphorase) and immunocytochemical (neuron-specific nuclear protein, microtubule-associated protein-2, calbindin, calretinin, neuropeptide Y) features of both deep fetal interstitial neurons and deep (periventricular

  5. A Specific Population of Reticulospinal Neurons Controls the Termination of Locomotion.

    Science.gov (United States)

    Juvin, Laurent; Grätsch, Swantje; Trillaud-Doppia, Emilie; Gariépy, Jean-François; Büschges, Ansgar; Dubuc, Réjean

    2016-06-14

    Locomotion requires the proper sequencing of neural activity to start, maintain, and stop it. Recently, brainstem neurons were shown to specifically stop locomotion in mammals. However, the cellular properties of these neurons and their activity during locomotion are still unknown. Here, we took advantage of the lamprey model to characterize the activity of a cell population that we now show to be involved in stopping locomotion. We find that these neurons display a burst of spikes that coincides with the end of swimming activity. Their pharmacological activation ends ongoing swimming, whereas the inactivation of these neurons dramatically impairs the rapid termination of swimming. These neurons are henceforth referred to as stop cells, because they play a crucial role in the termination of locomotion. Our findings contribute to the fundamental understanding of motor control and provide important details about the cellular mechanisms involved in locomotor termination. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. Synchronous spikes are necessary but not sufficient for a synchrony code in populations of spiking neurons.

    Science.gov (United States)

    Grewe, Jan; Kruscha, Alexandra; Lindner, Benjamin; Benda, Jan

    2017-03-07

    Synchronous activity in populations of neurons potentially encodes special stimulus features. Selective readout of either synchronous or asynchronous activity allows formation of two streams of information processing. Theoretical work predicts that such a synchrony code is a fundamental feature of populations of spiking neurons if they operate in specific noise and stimulus regimes. Here we experimentally test the theoretical predictions by quantifying and comparing neuronal response properties in tuberous and ampullary electroreceptor afferents of the weakly electric fish Apteronotus leptorhynchus These related systems show similar levels of synchronous activity, but only in the more irregularly firing tuberous afferents a synchrony code is established, whereas in the more regularly firing ampullary afferents it is not. The mere existence of synchronous activity is thus not sufficient for a synchrony code. Single-cell features such as the irregularity of spiking and the frequency dependence of the neuron's transfer function determine whether synchronous spikes possess a distinct meaning for the encoding of time-dependent signals.

  7. Population density models of integrate-and-fire neurons with jumps: well-posedness.

    Science.gov (United States)

    Dumont, Grégory; Henry, Jacques

    2013-09-01

    In this paper we study the well-posedness of different models of population of leaky integrate-and-fire neurons with a population density approach. The synaptic interaction between neurons is modeled by a potential jump at the reception of a spike. We study populations that are self excitatory or self inhibitory. We distinguish the cases where this interaction is instantaneous from the one where there is a repartition of conduction delays. In the case of a bounded density of delays both excitatory and inhibitory population models are shown to be well-posed. But without conduction delay the solution of the model of self excitatory neurons may blow up. We analyze the different behaviours of the model with jumps compared to its diffusion approximation.

  8. Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity

    Science.gov (United States)

    Chiu, Isaac M; Barrett, Lee B; Williams, Erika K; Strochlic, David E; Lee, Seungkyu; Weyer, Andy D; Lou, Shan; Bryman, Gregory S; Roberson, David P; Ghasemlou, Nader; Piccoli, Cara; Ahat, Ezgi; Wang, Victor; Cobos, Enrique J; Stucky, Cheryl L; Ma, Qiufu; Liberles, Stephen D; Woolf, Clifford J

    2014-01-01

    The somatosensory nervous system is critical for the organism's ability to respond to mechanical, thermal, and nociceptive stimuli. Somatosensory neurons are functionally and anatomically diverse but their molecular profiles are not well-defined. Here, we used transcriptional profiling to analyze the detailed molecular signatures of dorsal root ganglion (DRG) sensory neurons. We used two mouse reporter lines and surface IB4 labeling to purify three major non-overlapping classes of neurons: 1) IB4+SNS-Cre/TdTomato+, 2) IB4−SNS-Cre/TdTomato+, and 3) Parv-Cre/TdTomato+ cells, encompassing the majority of nociceptive, pruriceptive, and proprioceptive neurons. These neurons displayed distinct expression patterns of ion channels, transcription factors, and GPCRs. Highly parallel qRT-PCR analysis of 334 single neurons selected by membership of the three populations demonstrated further diversity, with unbiased clustering analysis identifying six distinct subgroups. These data significantly increase our knowledge of the molecular identities of known DRG populations and uncover potentially novel subsets, revealing the complexity and diversity of those neurons underlying somatosensation. DOI: http://dx.doi.org/10.7554/eLife.04660.001 PMID:25525749

  9. The Itch-Producing Agents Histamine and Cowhage Activate Separate Populations of Primate Spinothalamic Tract Neurons

    Science.gov (United States)

    Davidson, Steve; Zhang, Xijing; Yoon, Chul H.; Khasabov, Sergey G.; Simone, Donald A.; Giesler, Glenn J.

    2010-01-01

    Itch is an everyday sensation, but when associated with disease or infection it can be chronic and debilitating. Several forms of itch can be blocked using antihistamines, but others cannot and these constitute an important clinical problem. Little information is available on the mechanisms underlying itch that is produced by nonhistaminergic mechanisms. We examined the responses of spinothalamic tract neurons to histaminergic and, for the first time, nonhistaminergic forms of itch stimuli. Fifty-seven primate spinothalamic tract (STT) neurons were identified using antidromic activation techniques and examined for their responses to histamine and cowhage, the nonhistaminergic itch-producing spicules covering the pod of the legume Mucuna pruriens. Each examined neuron had a receptive field on the hairy skin of the hindlimb and responded to noxious mechanical stimulation. STT neurons were tested with both pruritogens applied in a random order and we found 12 that responded to histamine and seven to cowhage. Each pruritogen-responsive STT neuron was activated by the chemical algogen capsaicin and two-thirds responded to noxious heat stimuli, demonstrating that these neurons convey chemical, thermal, and mechanical nociceptive information as well. Histamine or cowhage responsive STT neurons were found in both the marginal zone and the deep dorsal horn and were classified as high threshold and wide dynamic range. Unexpectedly, histamine and cowhage never activated the same cell. Our results demonstrate that the spinothalamic tract contains mutually exclusive populations of neurons responsive to histamine or the nonhistaminergic itch-producing agent cowhage. PMID:17855615

  10. Stereological estimate of the total number of neurons in spinal segment D9 of the red-eared turtle

    DEFF Research Database (Denmark)

    Walløe, Solveig; Nissen, Ulla Vig; Berg, Rune W

    2011-01-01

    The red-eared turtle is an important animal model for investigating the neural activity in the spinal circuit that generates motor behavior. However, basic anatomical features, including the number of neurons in the spinal segments involved, are unknown. In the present study, we estimate the total...... number of neurons in segment D9 of the spinal cord in the red-eared turtle (Trachemys scripta elegans) using stereological cell counting methods. In transverse spinal cord sections stained with modified Giemsa, motoneurons (MNs), interneurons (INs), and non-neuronal cells were distinguished according...... to location and morphology. Each cell type was then counted separately using an optical disector with the cell nucleus as counting item. The number of cells in segment D9 was as follows (mean ± SE): MNs, 2049 ± 74; INs, 16,135 ± 316; non-neuronal cells, 47,504 ± 478 (n = 6). These results provide the first...

  11. Metastable states and quasicycles in a stochastic Wilson-Cowan model of neuronal population dynamics

    KAUST Repository

    Bressloff, Paul C.

    2010-01-01

    We analyze a stochastic model of neuronal population dynamics with intrinsic noise. In the thermodynamic limit N→∞, where N determines the size of each population, the dynamics is described by deterministic Wilson-Cowan equations. On the other hand

  12. Phase-coherence transitions and communication in the gamma range between delay-coupled neuronal populations.

    Directory of Open Access Journals (Sweden)

    Alessandro Barardi

    2014-07-01

    Full Text Available Synchronization between neuronal populations plays an important role in information transmission between brain areas. In particular, collective oscillations emerging from the synchronized activity of thousands of neurons can increase the functional connectivity between neural assemblies by coherently coordinating their phases. This synchrony of neuronal activity can take place within a cortical patch or between different cortical regions. While short-range interactions between neurons involve just a few milliseconds, communication through long-range projections between different regions could take up to tens of milliseconds. How these heterogeneous transmission delays affect communication between neuronal populations is not well known. To address this question, we have studied the dynamics of two bidirectionally delayed-coupled neuronal populations using conductance-based spiking models, examining how different synaptic delays give rise to in-phase/anti-phase transitions at particular frequencies within the gamma range, and how this behavior is related to the phase coherence between the two populations at different frequencies. We have used spectral analysis and information theory to quantify the information exchanged between the two networks. For different transmission delays between the two coupled populations, we analyze how the local field potential and multi-unit activity calculated from one population convey information in response to a set of external inputs applied to the other population. The results confirm that zero-lag synchronization maximizes information transmission, although out-of-phase synchronization allows for efficient communication provided the coupling delay, the phase lag between the populations, and the frequency of the oscillations are properly matched.

  13. Two distinct populations of projection neurons in the rat lateral parafascicular thalamic nucleus and their cholinergic responsiveness.

    Science.gov (United States)

    Beatty, J A; Sylwestrak, E L; Cox, C L

    2009-08-04

    The lateral parafascicular nucleus (lPf) is a member of the intralaminar thalamic nuclei, a collection of nuclei that characteristically provides widespread projections to the neocortex and basal ganglia and is associated with arousal, sensory, and motor functions. Recently, lPf neurons have been shown to possess different characteristics than other cortical-projecting thalamic relay neurons. We performed whole cell recordings from lPf neurons using an in vitro rat slice preparation and found two distinct neuronal subtypes that were differentiated by distinct morphological and physiological characteristics: diffuse and bushy. Diffuse neurons, which had been previously described, were the predominant neuronal subtype (66%). These neurons had few, poorly-branching, extended dendrites, and rarely displayed burst-like action potential discharge, a ubiquitous feature of thalamocortical relay neurons. Interestingly, we discovered a smaller population of bushy neurons (34%) that shared similar morphological and physiological characteristics with thalamocortical relay neurons of primary sensory thalamic nuclei. In contrast to other thalamocortical relay neurons, activation of muscarinic cholinergic receptors produced a membrane hyperpolarization via activation of M(2) receptors in most lPf neurons (60%). In a minority of lPf neurons (33%), muscarinic agonists produced a membrane depolarization via activation of predominantly M(3) receptors. The muscarinic receptor-mediated actions were independent of lPf neuronal subtype (i.e. diffuse or bushy neurons); however the cholinergic actions were correlated with lPf neurons with different efferent targets. Retrogradely-labeled lPf neurons from frontal cortical fluorescent bead injections primarily consisted of bushy type lPf neurons (78%), but more importantly, all of these neurons were depolarized by muscarinic agonists. On the other hand, lPf neurons labeled by striatal injections were predominantly hyperpolarized by muscarinic

  14. Primary Lateral Sclerosis and Early Upper Motor Neuron Disease: Characteristics of a Cross-Sectional Population.

    Science.gov (United States)

    Fournier, Christina N; Murphy, Alyssa; Loci, Lorena; Mitsumoto, Hiroshi; Lomen-Hoerth, Catherine; Kisanuki, Yasushi; Simmons, Zachary; Maragakis, Nicholas J; McVey, April L; Al-Lahham, Tawfiq; Heiman-Patterson, Terry D; Andrews, Jinsy; McDonnell, Erin; Cudkowicz, Merit; Atassi, Nazem

    2016-03-01

    The goals of this study were to characterize clinical and electrophysiologic findings of subjects with upper motor neuron disease and to explore feasibility of clinical trials in this population. Twenty northeast amyotrophic lateral sclerosis consortium (northeast amyotrophic lateral sclerosis) sites performed chart reviews to identify active clinical pure upper motor neuron disease patients. Patients with hereditary spastic paraplegia or meeting revised El Escorial electrodiagnostic criteria for amyotrophic lateral sclerosis were excluded. Patients were classified into 2 groups according to the presence or absence of minor electromyography (EMG) abnormalities. Two hundred thirty-three subjects with upper motor neuron disease were identified; 217 had available EMG data. Normal EMGs were seen in 140 subjects, and 77 had minor denervation. Mean disease duration was 84 (±80) months for the entire cohort with no difference seen between the 2 groups. No difference was seen in clinical symptoms, disability, or outcome measures between the 2 groups after correcting for multiple comparisons. Minor EMG abnormalities were not associated with phenotypic differences in a clinical upper motor neuron disease population. These findings suggest that subtle EMG abnormalities can not necessarily be used as a prognostic tool in patients with clinical upper motor neuron disease. This study also demonstrates the availability of a large number of patients with upper motor neuron diseases within the northeast amyotrophic lateral sclerosis network and suggests feasibility for conducting clinical trials in this population.

  15. Population dynamics of active and total ciliate populations in arable soil amended with wheat

    DEFF Research Database (Denmark)

    Ekelund, F.; Frederiksen, Helle B.; Ronn, R.

    2002-01-01

    of the population may be encysted. The factors governing the dynamics of active and encysted cells in the soil are not well understood. Our objective was to determine the dynamics of active and encysted populations of ciliates during the decomposition of freshly added organic material. We monitored, in soil...... microcosms, the active and total populations of ciliates, their potential prey (bacteria and small protozoa), their potential competitors (amoebae, flagellates, and nematodes), and their potential predators (nematodes). We sampled with short time intervals (2 to 6 days) and generated a data set, suitable...

  16. Proteolytic Remodeling of Perineuronal Nets: Effects on Synaptic Plasticity and Neuronal Population Dynamics

    Directory of Open Access Journals (Sweden)

    P. Lorenzo Bozzelli

    2018-01-01

    Full Text Available The perineuronal net (PNN represents a lattice-like structure that is prominently expressed along the soma and proximal dendrites of parvalbumin- (PV- positive interneurons in varied brain regions including the cortex and hippocampus. It is thus apposed to sites at which PV neurons receive synaptic input. Emerging evidence suggests that changes in PNN integrity may affect glutamatergic input to PV interneurons, a population that is critical for the expression of synchronous neuronal population discharges that occur with gamma oscillations and sharp-wave ripples. The present review is focused on the composition of PNNs, posttranslation modulation of PNN components by sulfation and proteolysis, PNN alterations in disease, and potential effects of PNN remodeling on neuronal plasticity at the single-cell and population level.

  17. The effect of noise correlations in populations of diversely tuned neurons.

    Science.gov (United States)

    Ecker, Alexander S; Berens, Philipp; Tolias, Andreas S; Bethge, Matthias

    2011-10-05

    The amount of information encoded by networks of neurons critically depends on the correlation structure of their activity. Neurons with similar stimulus preferences tend to have higher noise correlations than others. In homogeneous populations of neurons, this limited range correlation structure is highly detrimental to the accuracy of a population code. Therefore, reduced spike count correlations under attention, after adaptation, or after learning have been interpreted as evidence for a more efficient population code. Here, we analyze the role of limited range correlations in more realistic, heterogeneous population models. We use Fisher information and maximum-likelihood decoding to show that reduced correlations do not necessarily improve encoding accuracy. In fact, in populations with more than a few hundred neurons, increasing the level of limited range correlations can substantially improve encoding accuracy. We found that this improvement results from a decrease in noise entropy that is associated with increasing correlations if the marginal distributions are unchanged. Surprisingly, for constant noise entropy and in the limit of large populations, the encoding accuracy is independent of both structure and magnitude of noise correlations.

  18. Conditional Viral Tract Tracing Delineates the Projections of the Distinct Kisspeptin Neuron Populations to Gonadotropin-Releasing Hormone (GnRH) Neurons in the Mouse.

    Science.gov (United States)

    Yip, Siew Hoong; Boehm, Ulrich; Herbison, Allan E; Campbell, Rebecca E

    2015-07-01

    Kisspeptin neurons play an essential role in the regulation of fertility through direct regulation of the GnRH neurons. However, the relative contributions of the two functionally distinct kisspeptin neuron subpopulations to this critical regulation are not fully understood. Here we analyzed the specific projection patterns of kisspeptin neurons originating from either the rostral periventricular nucleus of the third ventricle (RP3V) or the arcuate nucleus (ARN) using a cell-specific, viral-mediated tract-tracing approach. We stereotaxically injected a Cre-dependent recombinant adenovirus encoding farnesylated enhanced green fluorescent protein into the ARN or RP3V of adult male and female mice expressing Cre recombinase in kisspeptin neurons. Fibers from ARN kisspeptin neurons projected widely; however, we did not find any evidence for direct contact with GnRH neuron somata or proximal dendrites in either sex. In contrast, we identified RP3V kisspeptin fibers in close contact with GnRH neuron somata and dendrites in both sexes. Fibers originating from both the RP3V and ARN were observed in close contact with distal GnRH neuron processes in the ARN and in the lateral and internal aspects of the median eminence. Furthermore, GnRH nerve terminals were found in close contact with the proximal dendrites of ARN kisspeptin neurons in the ARN, and ARN kisspeptin fibers were found contacting RP3V kisspeptin neurons in both sexes. Together these data delineate selective zones of kisspeptin neuron inputs to GnRH neurons and demonstrate complex interconnections between the distinct kisspeptin populations and GnRH neurons.

  19. Populations of auditory cortical neurons can accurately encode acoustic space across stimulus intensity.

    Science.gov (United States)

    Miller, Lee M; Recanzone, Gregg H

    2009-04-07

    The auditory cortex is critical for perceiving a sound's location. However, there is no topographic representation of acoustic space, and individual auditory cortical neurons are often broadly tuned to stimulus location. It thus remains unclear how acoustic space is represented in the mammalian cerebral cortex and how it could contribute to sound localization. This report tests whether the firing rates of populations of neurons in different auditory cortical fields in the macaque monkey carry sufficient information to account for horizontal sound localization ability. We applied an optimal neural decoding technique, based on maximum likelihood estimation, to populations of neurons from 6 different cortical fields encompassing core and belt areas. We found that the firing rate of neurons in the caudolateral area contain enough information to account for sound localization ability, but neurons in other tested core and belt cortical areas do not. These results provide a detailed and plausible population model of how acoustic space could be represented in the primate cerebral cortex and support a dual stream processing model of auditory cortical processing.

  20. Segregated populations of hippocampal principal CA1 neurons mediating conditioning and extinction of contextual fear.

    Science.gov (United States)

    Tronson, Natalie C; Schrick, Christina; Guzman, Yomayra F; Huh, Kyu Hwan; Srivastava, Deepak P; Penzes, Peter; Guedea, Anita L; Gao, Can; Radulovic, Jelena

    2009-03-18

    Learning processes mediating conditioning and extinction of contextual fear require activation of several key signaling pathways in the hippocampus. Principal hippocampal CA1 neurons respond to fear conditioning by a coordinated activation of multiple protein kinases and immediate early genes, such as cFos, enabling rapid and lasting consolidation of contextual fear memory. The extracellular signal-regulated kinase (Erk) additionally acts as a central mediator of fear extinction. It is not known however, whether these molecular events take place in overlapping or nonoverlapping neuronal populations. By using mouse models of conditioning and extinction of fear, we set out to determine the time course of cFos and Erk activity, their cellular overlap, and regulation by afferent cholinergic input from the medial septum. Analyses of cFos(+) and pErk(+) cells by immunofluorescence revealed predominant nuclear activation of either protein during conditioning and extinction of fear, respectively. Transgenic cFos-LacZ mice were further used to label in vivo Fos(+) hippocampal cells during conditioning followed by pErk immunostaining after extinction. The results showed that these signaling molecules were activated in segregated populations of hippocampal principal neurons. Furthermore, immunotoxin-induced lesions of medial septal neurons, providing cholinergic input into the hippocampus, selectively abolished Erk activation and extinction of fear without affecting cFos responses and conditioning. These results demonstrate that extinction mechanisms based on Erk signaling involve a specific population of CA1 principal neurons distinctively regulated by afferent cholinergic input from the medial septum.

  1. Different populations of subthalamic neurons encode cocaine vs. sucrose reward and predict future error.

    Science.gov (United States)

    Lardeux, Sylvie; Paleressompoulle, Dany; Pernaud, Remy; Cador, Martine; Baunez, Christelle

    2013-10-01

    The search for treatment of cocaine addiction raises the challenge to find a way to diminish motivation for the drug without decreasing it for natural rewards. Subthalamic nucleus (STN) inactivation decreases motivation for cocaine while increasing motivation for food, suggesting that STN can dissociate different rewards. Here, we investigated how rat STN neurons respond to cues predicting cocaine or sucrose and to reward delivery while rats are performing a discriminative stimuli task. We show that different neuronal populations of STN neurons encode cocaine and sucrose. In addition, we show that STN activity at the cue onset predicts future error. When changing the reward predicted unexpectedly, STN neurons show capacities of adaptation, suggesting a role in reward-prediction error. Furthermore, some STN neurons show a response to executive error (i.e., "oops neurons") that is specific to the missed reward. These results position the STN as a nexus where natural rewards and drugs of abuse are coded differentially and can influence the performance. Therefore, STN can be viewed as a structure where action could be taken for the treatment of cocaine addiction.

  2. Mouse V1 population correlates of visual detection rely on heterogeneity within neuronal response patterns

    Science.gov (United States)

    Montijn, Jorrit S; Goltstein, Pieter M; Pennartz, Cyriel MA

    2015-01-01

    Previous studies have demonstrated the importance of the primary sensory cortex for the detection, discrimination, and awareness of visual stimuli, but it is unknown how neuronal populations in this area process detected and undetected stimuli differently. Critical differences may reside in the mean strength of responses to visual stimuli, as reflected in bulk signals detectable in functional magnetic resonance imaging, electro-encephalogram, or magnetoencephalography studies, or may be more subtly composed of differentiated activity of individual sensory neurons. Quantifying single-cell Ca2+ responses to visual stimuli recorded with in vivo two-photon imaging, we found that visual detection correlates more strongly with population response heterogeneity rather than overall response strength. Moreover, neuronal populations showed consistencies in activation patterns across temporally spaced trials in association with hit responses, but not during nondetections. Contrary to models relying on temporally stable networks or bulk signaling, these results suggest that detection depends on transient differentiation in neuronal activity within cortical populations. DOI: http://dx.doi.org/10.7554/eLife.10163.001 PMID:26646184

  3. Intraspinal serotonergic neurons consist of two, temporally distinct populations in developing zebrafish.

    Science.gov (United States)

    Montgomery, Jacob E; Wiggin, Timothy D; Rivera-Perez, Luis M; Lillesaar, Christina; Masino, Mark A

    2016-06-01

    Zebrafish intraspinal serotonergic neuron (ISN) morphology and distribution have been examined in detail at different ages; however, some aspects of the development of these cells remain unclear. Although antibodies to serotonin (5-HT) have detected ISNs in the ventral spinal cord of embryos, larvae, and adults, the only tryptophan hydroxylase (tph) transcript that has been described in the spinal cord is tph1a. Paradoxically, spinal tph1a is only expressed transiently in embryos, which brings the source of 5-HT in the ISNs of larvae and adults into question. Because the pet1 and tph2 promoters drive transgene expression in the spinal cord, we hypothesized that tph2 is expressed in spinal cords of zebrafish larvae. We confirmed this hypothesis through in situ hybridization. Next, we used 5-HT antibody labeling and transgenic markers of tph2-expressing neurons to identify a transient population of ISNs in embryos that was distinct from ISNs that appeared later in development. The existence of separate ISN populations may not have been recognized previously due to their shared location in the ventral spinal cord. Finally, we used transgenic markers and immunohistochemical labeling to identify the transient ISN population as GABAergic Kolmer-Agduhr double-prime (KA″) neurons. Altogether, this study revealed a novel developmental paradigm in which KA″ neurons are transiently serotonergic before the appearance of a stable population of tph2-expressing ISNs. © 2015 Wiley Periodicals, Inc.

  4. Understanding how discrete populations of hypothalamic neurons orchestrate complicated behavioral states

    Directory of Open Access Journals (Sweden)

    Allison eGraebner

    2015-08-01

    Full Text Available A major question in systems neuroscience is how a single population of neurons can interact with the rest of the brain to orchestrate complex behavioral states. The hypothalamus contains many such discrete neuronal populations that individually regulate arousal, feeding, and drinking. For example, hypothalamic neurons that express hypocretin (Hcrt neuropeptides can sense homeostatic and metabolic factors affecting wakefulness and orchestrate organismal arousal. Neurons that express agouti-related protein (AgRP can sense the metabolic needs of the body and orchestrate a state of hunger. The organum vasculosum of the lamina terminalis (OVLT can detect the hypertonicity of blood and orchestrate a state of thirst. Each hypothalamic population is sufficient to generate complicated behavioral states through the combined efforts of distinct efferent projections. The principal challenge to understanding these brain systems is therefore to determine the individual roles of each downstream projection for each behavioral state. In recent years, the development and application of temporally precise, genetically encoded tools have greatly improved our understanding of the structure and function of these neural systems. This review will survey recent advances in our understanding of how these individual hypothalamic populations can orchestrate complicated behavioral states due to the combined efforts of individual downstream projections.

  5. Fluctuations and information filtering in coupled populations of spiking neurons with adaptation.

    Science.gov (United States)

    Deger, Moritz; Schwalger, Tilo; Naud, Richard; Gerstner, Wulfram

    2014-12-01

    Finite-sized populations of spiking elements are fundamental to brain function but also are used in many areas of physics. Here we present a theory of the dynamics of finite-sized populations of spiking units, based on a quasirenewal description of neurons with adaptation. We derive an integral equation with colored noise that governs the stochastic dynamics of the population activity in response to time-dependent stimulation and calculate the spectral density in the asynchronous state. We show that systems of coupled populations with adaptation can generate a frequency band in which sensory information is preferentially encoded. The theory is applicable to fully as well as randomly connected networks and to leaky integrate-and-fire as well as to generalized spiking neurons with adaptation on multiple time scales.

  6. Coding and decoding with adapting neurons: a population approach to the peri-stimulus time histogram.

    Science.gov (United States)

    Naud, Richard; Gerstner, Wulfram

    2012-01-01

    The response of a neuron to a time-dependent stimulus, as measured in a Peri-Stimulus-Time-Histogram (PSTH), exhibits an intricate temporal structure that reflects potential temporal coding principles. Here we analyze the encoding and decoding of PSTHs for spiking neurons with arbitrary refractoriness and adaptation. As a modeling framework, we use the spike response model, also known as the generalized linear neuron model. Because of refractoriness, the effect of the most recent spike on the spiking probability a few milliseconds later is very strong. The influence of the last spike needs therefore to be described with high precision, while the rest of the neuronal spiking history merely introduces an average self-inhibition or adaptation that depends on the expected number of past spikes but not on the exact spike timings. Based on these insights, we derive a 'quasi-renewal equation' which is shown to yield an excellent description of the firing rate of adapting neurons. We explore the domain of validity of the quasi-renewal equation and compare it with other rate equations for populations of spiking neurons. The problem of decoding the stimulus from the population response (or PSTH) is addressed analogously. We find that for small levels of activity and weak adaptation, a simple accumulator of the past activity is sufficient to decode the original input, but when refractory effects become large decoding becomes a non-linear function of the past activity. The results presented here can be applied to the mean-field analysis of coupled neuron networks, but also to arbitrary point processes with negative self-interaction.

  7. Differential effects of cocaine on histone posttranslational modifications in identified populations of striatal neurons.

    Science.gov (United States)

    Jordi, Emmanuelle; Heiman, Myriam; Marion-Poll, Lucile; Guermonprez, Pierre; Cheng, Shuk Kei; Nairn, Angus C; Greengard, Paul; Girault, Jean-Antoine

    2013-06-04

    Drugs of abuse, such as cocaine, induce changes in gene expression and epigenetic marks including alterations in histone posttranslational modifications in striatal neurons. These changes are thought to participate in physiological memory mechanisms and to be critical for long-term behavioral alterations. However, the striatum is composed of multiple cell types, including two distinct populations of medium-sized spiny neurons, and little is known concerning the cell-type specificity of epigenetic modifications. To address this question we used bacterial artificial chromosome transgenic mice, which express EGFP fused to the N-terminus of the large subunit ribosomal protein L10a driven by the D1 or D2 dopamine receptor (D1R, D2R) promoter, respectively. Fluorescence in nucleoli was used to sort nuclei from D1R- or D2R-expressing neurons and to quantify by flow cytometry the cocaine-induced changes in histone acetylation and methylation specifically in these two types of nuclei. The two populations of medium-sized spiny neurons displayed different patterns of histone modifications 15 min or 24 h after a single injection of cocaine or 24 h after seven daily injections. In particular, acetylation of histone 3 on Lys 14 and of histone 4 on Lys 5 and 12, and methylation of histone 3 on Lys 9 exhibited distinct and persistent changes in the two cell types. Our data provide insights into the differential epigenetic responses to cocaine in D1R- and D2R-positive neurons and their potential regulation, which may participate in the persistent effects of cocaine in these neurons. The method described should have general utility for studying nuclear modifications in different types of neuronal or nonneuronal cell types.

  8. Permanent Genetic Access to Transiently Active Neurons via TRAP: Targeted Recombination in Active Populations

    OpenAIRE

    Guenthner, Casey J.; Miyamichi, Kazunari; Yang, Helen H.; Heller, H. Craig; Luo, Liqun

    2013-01-01

    Targeting genetically encoded tools for neural circuit dissection to relevant cellular populations is a major challenge in neurobiology. We developed a new approach, Targeted Recombination in Active Populations (TRAP), to obtain genetic access to neurons that were activated by defined stimuli. This method utilizes mice in which the tamoxifen-dependent recombinase CreERT2 is expressed in an activity-dependent manner from the loci of the immediate early genes Arc and Fos. Active cells that expr...

  9. A Unique "Angiotensin-Sensitive" Neuronal Population Coordinates Neuroendocrine, Cardiovascular, and Behavioral Responses to Stress.

    Science.gov (United States)

    de Kloet, Annette D; Wang, Lei; Pitra, Soledad; Hiller, Helmut; Smith, Justin A; Tan, Yalun; Nguyen, Dani; Cahill, Karlena M; Sumners, Colin; Stern, Javier E; Krause, Eric G

    2017-03-29

    Stress elicits neuroendocrine, autonomic, and behavioral responses that mitigate homeostatic imbalance and ensure survival. However, chronic engagement of such responses promotes psychological, cardiovascular, and metabolic impairments. In recent years, the renin-angiotensin system has emerged as a key mediator of stress responding and its related pathologies, but the neuronal circuits that orchestrate these interactions are not known. These studies combine the use of the Cre-recombinase/loxP system in mice with optogenetics to structurally and functionally characterize angiotensin type-1a receptor-containing neurons of the paraventricular nucleus of the hypothalamus, the goal being to determine the extent of their involvement in the regulation of stress responses. Initial studies use neuroanatomical techniques to reveal that angiotensin type-1a receptors are localized predominantly to the parvocellular neurosecretory neurons of the paraventricular nucleus of the hypothalamus. These neurons are almost exclusively glutamatergic and send dense projections to the exterior portion of the median eminence. Furthermore, these neurons largely express corticotrophin-releasing hormone or thyrotropin-releasing hormone and do not express arginine vasopressin or oxytocin. Functionally, optogenetic stimulation of these neurons promotes the activation of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axes, as well as a rise in systolic blood pressure. When these neurons are optogenetically inhibited, the activity of these neuroendocrine axes are suppressed and anxiety-like behavior in the elevated plus maze is dampened. Collectively, these studies implicate this neuronal population in the integration and coordination of the physiological responses to stress and may therefore serve as a potential target for therapeutic intervention for stress-related pathology. SIGNIFICANCE STATEMENT Chronic stress leads to an array of physiological responses that ultimately

  10. An improved ivermectin-activated chloride channel receptor for inhibiting electrical activity in defined neuronal populations

    DEFF Research Database (Denmark)

    Lynagh, Timothy Peter; Lynch, Joseph W

    2010-01-01

    The ability to silence the electrical activity of defined neuronal populations in vivo is dramatically advancing our understanding of brain function. This technology may eventually be useful clinically for treating a variety of neuropathological disorders caused by excessive neuronal activity...... conductance, homomeric expression, and human origin may render the F207A/A288G alpha1 glycine receptor an improved silencing receptor for neuroscientific and clinical purposes. As all known highly ivermectin-sensitive GluClRs contain an endogenous glycine residue at the corresponding location, this residue...

  11. Separate populations of neurons in ventral striatum encode value and motivation.

    Science.gov (United States)

    Bissonette, Gregory B; Burton, Amanda C; Gentry, Ronny N; Goldstein, Brandon L; Hearn, Taylor N; Barnett, Brian R; Kashtelyan, Vadim; Roesch, Matthew R

    2013-01-01

    Neurons in the ventral striatum (VS) fire to cues that predict differently valued rewards. It is unclear whether this activity represents the value associated with the expected reward or the level of motivation induced by reward anticipation. To distinguish between the two, we trained rats on a task in which we varied value independently from motivation by manipulating the size of the reward expected on correct trials and the threat of punishment expected upon errors. We found that separate populations of neurons in VS encode expected value and motivation.

  12. Time related total lactic acid bacteria population diversity and ...

    African Journals Online (AJOL)

    user

    2011-02-07

    Feb 7, 2011 ... the diversity and dynamics of lactic acid bacteria (LAB) population in fresh ..... combining morphological, biochemical and molecular data are important for ..... acid bacteria from fermented maize (Kenkey) and their interactions.

  13. Time related total lactic acid bacteria population diversity and ...

    African Journals Online (AJOL)

    The total lactic acid bacterial community involved in the spontaneous fermentation of malted cowpea fortified cereal weaning food was investigated by phenotypically and cultivation independent method. A total of 74 out of the isolated 178 strains were Lactobacillus plantarum, 32 were Pediococcus acidilactici and over 60% ...

  14. Single bumps in a 2-population homogenized neuronal network model

    Science.gov (United States)

    Kolodina, Karina; Oleynik, Anna; Wyller, John

    2018-05-01

    We investigate existence and stability of single bumps in a homogenized 2-population neural field model, when the firing rate functions are given by the Heaviside function. The model is derived by means of the two-scale convergence technique of Nguetseng in the case of periodic microvariation in the connectivity functions. The connectivity functions are periodically modulated in both the synaptic footprint and in the spatial scale. The bump solutions are constructed by using a pinning function technique for the case where the solutions are independent of the local variable. In the weakly modulated case the generic picture consists of two bumps (one narrow and one broad bump) for each admissible set of threshold values for firing. In addition, a new threshold value regime for existence of bumps is detected. Beyond the weakly modulated regime the number of bumps depends sensitively on the degree of heterogeneity. For the latter case we present a configuration consisting of three coexisting bumps. The linear stability of the bumps is studied by means of the spectral properties of a Fredholm integral operator, block diagonalization of this operator and the Fourier decomposition method. In the weakly modulated regime, one of the bumps is unstable for all relative inhibition times, while the other one is stable for small and moderate values of this parameter. The latter bump becomes unstable as the relative inhibition time exceeds a certain threshold. In the case of the three coexisting bumps detected in the regime of finite degree of heterogeneity, we have at least one stable bump (and maximum two stable bumps) for small and moderate values of the relative inhibition time.

  15. Populations of striatal medium spiny neurons encode vibrotactile frequency in rats: modulation by slow wave oscillations.

    Science.gov (United States)

    Hawking, Thomas G; Gerdjikov, Todor V

    2013-01-01

    Dorsolateral striatum (DLS) is implicated in tactile perception and receives strong projections from somatosensory cortex. However, the sensory representations encoded by striatal projection neurons are not well understood. Here we characterized the contribution of DLS to the encoding of vibrotactile information in rats by assessing striatal responses to precise frequency stimuli delivered to a single vibrissa. We applied stimuli in a frequency range (45-90 Hz) that evokes discriminable percepts and carries most of the power of vibrissa vibration elicited by a range of complex fine textures. Both medium spiny neurons and evoked potentials showed tactile responses that were modulated by slow wave oscillations. Furthermore, medium spiny neuron population responses represented stimulus frequency on par with previously reported behavioral benchmarks. Our results suggest that striatum encodes frequency information of vibrotactile stimuli which is dynamically modulated by ongoing brain state.

  16. Peroxiredoxin distribution in the mouse brain with emphasis on neuronal populations affected in neurodegenerative disorders.

    Science.gov (United States)

    Goemaere, Julie; Knoops, Bernard

    2012-02-01

    Redox changes are observed in neurodegenerative diseases, ranging from increased levels of reactive oxygen/nitrogen species and disturbance of antioxidant systems, to nitro-oxidative damage. By reducing hydrogen peroxide, peroxynitrite, and organic hydroperoxides, peroxiredoxins (Prdxs) represent a major potential protective barrier against nitro-oxidative insults in the brain. While recent works have investigated the putative role of Prdxs in neurodegenerative disorders, less is known about their expression in the healthy brain. Here we used immunohistochemistry to map basal expression of Prdxs throughout C57BL/6 mouse brain. We first confirmed the neuronal localization of Prdx2-5 and the glial expression of Prdx1, Prdx4, and Prdx6. Then we performed an in-depth analysis of neuronal Prdx distribution in the brain. Our results show that Prdx2-5 are widely detected in the different neuronal populations, and especially well expressed in the olfactory bulb, in the cerebral cortex, in pons nuclei, in the red nucleus, in all cranial nerve nuclei, in the cerebellum, and in motor neurons of the spinal cord. In contrast, Prdx expression is very low in the dopaminergic neurons of substantia nigra pars compacta and in the CA1/2 pyramidal cells of hippocampus. This low basal expression may contribute to the vulnerability of these neurons to nitro-oxidative attacks occurring in Parkinson's disease and Alzheimer's disease. In addition, we found that Prdx expression levels are unevenly distributed among neurons of a determined region and that distinct regional patterns of expression are observed between isoforms, reinforcing the hypothesis of the nonredundant function of Prdxs. Copyright © 2011 Wiley-Liss, Inc.

  17. Cutaneous TRPM8-expressing sensory afferents are a small population of neurons with unique firing properties.

    Science.gov (United States)

    Jankowski, Michael P; Rau, Kristofer K; Koerber, H Richard

    2017-04-01

    It has been well documented that the transient receptor potential melastatin 8 (TRPM8) receptor is involved in environmental cold detection. The role that this receptor plays in nociception however, has been somewhat controversial since conflicting reports have shown different neurochemical identities and responsiveness of TRPM8 neurons. In order to functionally characterize cutaneous TRMP8 fibers, we used two ex vivo somatosensory recording preparations to functionally characterize TRPM8 neurons that innervate the hairy skin in mice genetically engineered to express GFP from the TRPM8 locus. We found several types of cold-sensitive neurons that innervate the hairy skin of the mouse but the TRPM8-expressing neurons were found to be of two specific populations that responded with rapid firing to cool temperatures. The first group was mechanically insensitive but the other did respond to high threshold mechanical deformation of the skin. None of these fibers were found to contain calcitonin gene-related peptide, transient receptor potential vanilloid type 1 or bind isolectin B4. These results taken together with other reports suggest that TRPM8 containing sensory neurons are environmental cooling detectors that may be nociceptive or non-nociceptive depending on the sensitivity of individual fibers to different combinations of stimulus modalities. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  18. Large-scale Reconstructions and Independent, Unbiased Clustering Based on Morphological Metrics to Classify Neurons in Selective Populations.

    Science.gov (United States)

    Bragg, Elise M; Briggs, Farran

    2017-02-15

    This protocol outlines large-scale reconstructions of neurons combined with the use of independent and unbiased clustering analyses to create a comprehensive survey of the morphological characteristics observed among a selective neuronal population. Combination of these techniques constitutes a novel approach for the collection and analysis of neuroanatomical data. Together, these techniques enable large-scale, and therefore more comprehensive, sampling of selective neuronal populations and establish unbiased quantitative methods for describing morphologically unique neuronal classes within a population. The protocol outlines the use of modified rabies virus to selectively label neurons. G-deleted rabies virus acts like a retrograde tracer following stereotaxic injection into a target brain structure of interest and serves as a vehicle for the delivery and expression of EGFP in neurons. Large numbers of neurons are infected using this technique and express GFP throughout their dendrites, producing "Golgi-like" complete fills of individual neurons. Accordingly, the virus-mediated retrograde tracing method improves upon traditional dye-based retrograde tracing techniques by producing complete intracellular fills. Individual well-isolated neurons spanning all regions of the brain area under study are selected for reconstruction in order to obtain a representative sample of neurons. The protocol outlines procedures to reconstruct cell bodies and complete dendritic arborization patterns of labeled neurons spanning multiple tissue sections. Morphological data, including positions of each neuron within the brain structure, are extracted for further analysis. Standard programming functions were utilized to perform independent cluster analyses and cluster evaluations based on morphological metrics. To verify the utility of these analyses, statistical evaluation of a cluster analysis performed on 160 neurons reconstructed in the thalamic reticular nucleus of the thalamus

  19. Spiking, Bursting, and Population Dynamics in a Network of Growth Transform Neurons.

    Science.gov (United States)

    Gangopadhyay, Ahana; Chakrabartty, Shantanu

    2017-04-27

    This paper investigates the dynamical properties of a network of neurons, each of which implements an asynchronous mapping based on polynomial growth transforms. In the first part of this paper, we present a geometric approach for visualizing the dynamics of the network where each of the neurons traverses a trajectory in a dual optimization space, whereas the network itself traverses a trajectory in an equivalent primal optimization space. We show that as the network learns to solve basic classification tasks, different choices of primal-dual mapping produce unique but interpretable neural dynamics like noise shaping, spiking, and bursting. While the proposed framework is general enough, in this paper, we demonstrate its use for designing support vector machines (SVMs) that exhibit noise-shaping properties similar to those of ΣΔ modulators, and for designing SVMs that learn to encode information using spikes and bursts. It is demonstrated that the emergent switching, spiking, and burst dynamics produced by each neuron encodes its respective margin of separation from a classification hyperplane whose parameters are encoded by the network population dynamics. We believe that the proposed growth transform neuron model and the underlying geometric framework could serve as an important tool to connect well-established machine learning algorithms like SVMs to neuromorphic principles like spiking, bursting, population encoding, and noise shaping.

  20. Permanent genetic access to transiently active neurons via TRAP: targeted recombination in active populations.

    Science.gov (United States)

    Guenthner, Casey J; Miyamichi, Kazunari; Yang, Helen H; Heller, H Craig; Luo, Liqun

    2013-06-05

    Targeting genetically encoded tools for neural circuit dissection to relevant cellular populations is a major challenge in neurobiology. We developed an approach, targeted recombination in active populations (TRAP), to obtain genetic access to neurons that were activated by defined stimuli. This method utilizes mice in which the tamoxifen-dependent recombinase CreER(T2) is expressed in an activity-dependent manner from the loci of the immediate early genes Arc and Fos. Active cells that express CreER(T2) can only undergo recombination when tamoxifen is present, allowing genetic access to neurons that are active during a time window of less than 12 hr. We show that TRAP can provide selective access to neurons activated by specific somatosensory, visual, and auditory stimuli and by experience in a novel environment. When combined with tools for labeling, tracing, recording, and manipulating neurons, TRAP offers a powerful approach for understanding how the brain processes information and generates behavior. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Complex population response of dorsal putamen neurons predicts the ability to learn.

    Science.gov (United States)

    Laquitaine, Steeve; Piron, Camille; Abellanas, David; Loewenstein, Yonatan; Boraud, Thomas

    2013-01-01

    Day-to-day variability in performance is a common experience. We investigated its neural correlate by studying learning behavior of monkeys in a two-alternative forced choice task, the two-armed bandit task. We found substantial session-to-session variability in the monkeys' learning behavior. Recording the activity of single dorsal putamen neurons we uncovered a dual function of this structure. It has been previously shown that a population of neurons in the DLP exhibits firing activity sensitive to the reward value of chosen actions. Here, we identify putative medium spiny neurons in the dorsal putamen that are cue-selective and whose activity builds up with learning. Remarkably we show that session-to-session changes in the size of this population and in the intensity with which this population encodes cue-selectivity is correlated with session-to-session changes in the ability to learn the task. Moreover, at the population level, dorsal putamen activity in the very beginning of the session is correlated with the performance at the end of the session, thus predicting whether the monkey will have a "good" or "bad" learning day. These results provide important insights on the neural basis of inter-temporal performance variability.

  2. Decoding a Decision Process in the Neuronal Population of Dorsal Premotor Cortex.

    Science.gov (United States)

    Rossi-Pool, Román; Zainos, Antonio; Alvarez, Manuel; Zizumbo, Jerónimo; Vergara, José; Romo, Ranulfo

    2017-12-20

    When trained monkeys discriminate the temporal structure of two sequential vibrotactile stimuli, dorsal premotor cortex (DPC) showed high heterogeneity among its neuronal responses. Notably, DPC neurons coded stimulus patterns as broader categories and signaled them during working memory, comparison, and postponed decision periods. Here, we show that such population activity can be condensed into two major coding components: one that persistently represented in working memory both the first stimulus identity and the postponed informed choice and another that transiently coded the initial sensory information and the result of the comparison between the two stimuli. Additionally, we identified relevant signals that coded the timing of task events. These temporal and task-parameter readouts were shown to be strongly linked to the monkeys' behavior when contrasted to those obtained in a non-demanding cognitive control task and during error trials. These signals, hidden in the heterogeneity, were prominently represented by the DPC population response. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. [Pulse flows of populations of cortical neurons under low-intensity pulsed microwave: interspike intervals].

    Science.gov (United States)

    Chizhenkova, R A

    2014-01-01

    Pulse flows of populations of cortical neurons were investigated on unanesthetized nonimmobilized rabbits prior, during, and after 1-min microwave irradiation (wavelength 37.5 cm, power density 0.5-1.0 mW/cm2) in continuous and pulse-modulated modes with a frequency of 5, 20 and 100 Hz. The changes in the characteristics of interspike intervals resulted from these exposures. The peculiarity of rearrangements of pulse flows and their dynamics was determined by modes of irradiation.

  4. OGJ300 population shrinks, but assets total grows

    International Nuclear Information System (INIS)

    Beck, R.J.; Bell, L.

    1995-01-01

    Publicly traded oil and gas companies in the US are declining in population but growing in financial terms. The Oil and Gas Journal 300, the annual list of publicly traded companies with oil production in the US, includes only 281 companies this year. As of the data compilation deadline, only that number of companies had filed annual financial results with the US Securities and Exchange Commission. The OGJ300 ranks companies by assets without regard to whether the companies use the successful efforts or full cost accounting method. Normally, assets for a given set of properties are higher under full cost than under successful efforts accounting

  5. A sodium afterdepolarization in rat superior colliculus neurons and its contribution to population activity.

    Science.gov (United States)

    Ghitani, Nima; Bayguinov, Peter O; Basso, Michele A; Jackson, Meyer B

    2016-07-01

    The mammalian superior colliculus (SC) is a midbrain structure that integrates multimodal sensory inputs and computes commands to initiate rapid eye movements. SC neurons burst with the sudden onset of a visual stimulus, followed by persistent activity that may underlie shifts of attention and decision making. Experiments in vitro suggest that circuit reverberations play a role in the burst activity in the SC, but the origin of persistent activity is unclear. In the present study we characterized an afterdepolarization (ADP) that follows action potentials in slices of rat SC. Population responses seen with voltage-sensitive dye imaging consisted of rapid spikes followed immediately by a second distinct depolarization of lower amplitude and longer duration. Patch-clamp recordings showed qualitatively similar behavior: in nearly all neurons throughout the SC, rapid spikes were followed by an ADP. Ionic and pharmacological manipulations along with experiments with current and voltage steps indicated that the ADP of SC neurons arises from Na(+) current that either persists or resurges following Na(+) channel inactivation at the end of an action potential. Comparisons of pharmacological properties and frequency dependence revealed a clear parallel between patch-clamp recordings and voltage imaging experiments, indicating a common underlying membrane mechanism for the ADP in both single neurons and populations. The ADP can initiate repetitive spiking at intervals consistent with the frequency of persistent activity in the SC. These results indicate that SC neurons have intrinsic membrane properties that can contribute to electrical activity that underlies shifts of attention and decision making. Copyright © 2016 the American Physiological Society.

  6. Stochastic Nonlinear Evolutional Model of the Large-Scaled Neuronal Population and Dynamic Neural Coding Subject to Stimulation

    International Nuclear Information System (INIS)

    Wang Rubin; Yu Wei

    2005-01-01

    In this paper, we investigate how the population of neuronal oscillators deals with information and the dynamic evolution of neural coding when the external stimulation acts on it. Numerically computing method is used to describe the evolution process of neural coding in three-dimensioned space. The numerical result proves that only the suitable stimulation can change the coupling structure and plasticity of neurons

  7. A small population of hypothalamic neurons govern fertility: the critical role of VAX1 in GnRH neuron development and fertility maintenance.

    Science.gov (United States)

    Hoffmann, Hanne M; Mellon, Pamela L

    2016-01-01

    Fertility depends on the correct maturation and function of approximately 800 gonadotropin-releasing hormone (GnRH) neurons in the brain. GnRH neurons are at the apex of the hypothalamic-pituitary-gonadal axis that regulates fertility. In adulthood, GnRH neurons are scattered throughout the anterior hypothalamic area and project to the median eminence, where GnRH is released into the portal vasculature to stimulate release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary. LH and FSH then regulate gonadal steroidogenesis and gametogenesis. Absence of GnRH neurons or inappropriate GnRH release leads to infertility. Despite the critical role of GnRH neurons in fertility, we still have a limited understanding of the genes responsible for proper GnRH neuron development and function in adulthood. GnRH neurons originate in the olfactory placode then migrate into the brain. Homeodomain transcription factors expressed within GnRH neurons or along their migratory path are candidate genes for inherited infertility. Using a combined in vitro and in vivo approach, we have identified Ventral Anterior Homeobox 1 ( Vax1 ) as a novel homeodomain transcription factor responsible for GnRH neuron maturation and fertility. GnRH neuron counts in Vax1 knock-out embryos revealed Vax1 to be required for the presence of GnRH-expressing cells at embryonic day 17.5 (E17.5), but not at E13.5. To localize the effects of Vax1 on fertility, we generated Vax1 flox mice and crossed them with Gnrh cre mice to specifically delete Vax1 within GnRH neurons. GnRH staining in Vax1 flox/flox :GnRH cre mice show a total absence of GnRH expression in the adult. We performed lineage tracing in Vax1 flox/flox :GnRH cre :RosaLacZ mice which proved GnRH neurons to be alive, but incapable of expressing GnRH. The absence of GnRH leads to delayed puberty, hypogonadism and complete infertility in both sexes. Finally, using the immortalized model GnRH neuron cell lines, GN11 and

  8. Interstitial cells of the adult neocortical white matter are the remnant of the early generated subplate neuron population

    International Nuclear Information System (INIS)

    Chun, J.J.; Shatz, C.J.

    1989-01-01

    The postnatal fate of the first-generated neurons of the cat cerebral cortex was examined. These neurons can be identified uniquely by 3H-thymidine exposure during the week preceding the neurogenesis of cortical layer 6. Previous studies in which 3H-thymidine birthdating at embryonic day 27 (E27) was combined with immunohistochemistry have shown that these neurons are present in large numbers during fetal and early postnatal life within the subplate (future white matter), that they are immunoreactive for the neuron-specific protein MAP2 and for the putative neurotransmitters GABA, NPY, SRIF, and CCK. Here, the same techniques were used to follow the postnatal location and disappearance of the early generated subplate neuron population. At birth (P0), subplate neurons showing immunoreactivity for GABA, NPY, SRIF, or CCK are present in large numbers and at high density within the white matter throughout the neocortex, and the entire population can be observed as a dense MAP2-immunoreactive band situated beneath cortical layer 6. Between P0 and P401 (adulthood), the MAP2-immunostained band disappears so that comparatively few MAP2-immunoreactive neurons remain within the white matter. There is a corresponding decrease in the number and density of neurons stained with antibodies against neurotransmitters. In each instance, these neurons could be double-labeled by the administration of 3H-thymidine at E27, indicating that they are the remnants of the early generated subplate neuron population. The major period of decrease occurs during the first 4 postnatal weeks, and adult values are attained by 5 months. Within the white matter of the lateral gyrus (visual cortex), the density of immunostained neurons decreases dramatically: MAP2, 82%, SRIF, 81%, and NPY, 96%

  9. Code-specific learning rules improve action selection by populations of spiking neurons.

    Science.gov (United States)

    Friedrich, Johannes; Urbanczik, Robert; Senn, Walter

    2014-08-01

    Population coding is widely regarded as a key mechanism for achieving reliable behavioral decisions. We previously introduced reinforcement learning for population-based decision making by spiking neurons. Here we generalize population reinforcement learning to spike-based plasticity rules that take account of the postsynaptic neural code. We consider spike/no-spike, spike count and spike latency codes. The multi-valued and continuous-valued features in the postsynaptic code allow for a generalization of binary decision making to multi-valued decision making and continuous-valued action selection. We show that code-specific learning rules speed up learning both for the discrete classification and the continuous regression tasks. The suggested learning rules also speed up with increasing population size as opposed to standard reinforcement learning rules. Continuous action selection is further shown to explain realistic learning speeds in the Morris water maze. Finally, we introduce the concept of action perturbation as opposed to the classical weight- or node-perturbation as an exploration mechanism underlying reinforcement learning. Exploration in the action space greatly increases the speed of learning as compared to exploration in the neuron or weight space.

  10. A model based approach in observing the activity of neuronal populations for the prediction of epileptic seizures

    International Nuclear Information System (INIS)

    Chong, M.S.; Nesic, D.; Kuhlmann, L.; Postoyan, R.; Varsavsky, A.; Cook, M.

    2010-01-01

    Full text: Epilepsy is a common neurological disease that affects 0.5-1 % of the world's population. In cases where known treatments cannot achieve complete recovery, seizure prediction is essential so that preventive measures can be undertaken to prevent resultant injury. The elcctroencephalogram (EEG) is a widely used diagnostic tool for epilepsy. However, the EEG does not provide a detailed view of the underlying seizure causing neuronal mechanisms. Knowing the dynamics of the neuronal population is useful because tracking the evolution of the neuronal mechanisms will allow us to track the brain's progression from interictal to ictal state. Wendling and colleagues proposed a parameterised mathematical model that represents the activity of interconnected neuronal populations. By modifying the parameters, this model is able to reproduce signals that are very similar to the real EEG depicting commonly observed patterns during interictal and ictal periods. The transition from non-seizure to seizure activity, as seen in the EEG. is hypothesised to be due to the impairment of inhibition. Using Wendling's model, we designed a deterministic nonlinear estimator to recover the average membrane potential of the neuronal populations from a single channel EEG signal. for any fixed and known parameter values. Our nonlinear estimator is analytically proven to asymptotically converge to the true state of the model and illustrated in simulations. We were able to computationally observe the dynamics of the three neuronal populations described in the model: excitatory, fast and slow inhibitory populations. This forms a first step towards the prediction of epileptic seiwres. (author)

  11. Transient optogenetic inactivation of the medial entorhinal cortex biases the active population of hippocampal neurons.

    Science.gov (United States)

    Rueckemann, Jon W; DiMauro, Audrey J; Rangel, Lara M; Han, Xue; Boyden, Edward S; Eichenbaum, Howard

    2016-02-01

    The mechanisms that enable the hippocampal network to express the appropriate spatial representation for a particular circumstance are not well understood. Previous studies suggest that the medial entorhinal cortex (MEC) may have a role in reproducibly selecting the hippocampal representation of an environment. To examine how ongoing MEC activity is continually integrated by the hippocampus, we performed transient unilateral optogenetic inactivations of the MEC while simultaneously recording place cell activity in CA1. Inactivation of the MEC caused a partial remapping in the CA1 population without diminishing the degree of spatial tuning across the active cell assembly. These changes remained stable irrespective of intermittent disruption of MEC input, indicating that while MEC input is integrated over long time scales to bias the active population, there are mechanisms for stabilizing the population of active neurons independent of the MEC. We find that MEC inputs to the hippocampus shape its ongoing activity by biasing the participation of the neurons in the active network, thereby influencing how the hippocampus selectively represents information. © 2015 Wiley Periodicals, Inc.

  12. Imaging auditory representations of song and syllables in populations of sensorimotor neurons essential to vocal communication.

    Science.gov (United States)

    Peh, Wendy Y X; Roberts, Todd F; Mooney, Richard

    2015-04-08

    Vocal communication depends on the coordinated activity of sensorimotor neurons important to vocal perception and production. How vocalizations are represented by spatiotemporal activity patterns in these neuronal populations remains poorly understood. Here we combined intracellular recordings and two-photon calcium imaging in anesthetized adult zebra finches (Taeniopygia guttata) to examine how learned birdsong and its component syllables are represented in identified projection neurons (PNs) within HVC, a sensorimotor region important for song perception and production. These experiments show that neighboring HVC PNs can respond at markedly different times to song playback and that different syllables activate spatially intermingled PNs within a local (~100 μm) region of HVC. Moreover, noise correlations were stronger between PNs that responded most strongly to the same syllable and were spatially graded within and between classes of PNs. These findings support a model in which syllabic and temporal features of song are represented by spatially intermingled PNs functionally organized into cell- and syllable-type networks within local spatial scales in HVC. Copyright © 2015 the authors 0270-6474/15/355589-17$15.00/0.

  13. Ih equalizes membrane input resistance in a heterogeneous population of fusiform neurons in the dorsal cochlear nucleus.

    Directory of Open Access Journals (Sweden)

    Cesar Celis Ceballos

    2016-10-01

    Full Text Available In a neuronal population, several combinations of its ionic conductances are used to attain a specific firing phenotype. Some neurons present heterogeneity in their firing, generally produced by expression of a specific conductance, but how additional conductances vary along in order to homeostatically regulate membrane excitability is less known. Dorsal cochlear nucleus principal neurons, fusiform neurons, display heterogeneous spontaneous action potential activity and thus represent an appropriate model to study the role of different conductances in establishing firing heterogeneity. Particularly, fusiform neurons are divided into quiet, with no spontaneous firing, or active neurons, presenting spontaneous, regular firing. These modes are determined by the expression levels of an intrinsic membrane conductance, an inwardly rectifying potassium current (IKir. In this work, we tested whether other subthreshold conductances vary homeostatically to maintain membrane excitability constant across the two subtypes. We found that Ih expression covaries specifically with IKir in order to maintain membrane resistance constant. The impact of Ih on membrane resistance is dependent on the level of IKir expression, being much smaller in quiet neurons with bigger IKir, but Ih variations are not relevant for creating the quiet and active phenotypes. Finally, we demonstrate that the individual proportion of each conductance, and not their absolute conductance, is relevant for determining the neuronal firing mode. We conclude that in fusiform neurons the variations of their different subthreshold conductances are limited to specific conductances in order to create firing heterogeneity and maintain membrane homeostasis.

  14. Model-based estimation of finite population total in stratified sampling

    African Journals Online (AJOL)

    The work presented in this paper concerns the estimation of finite population total under model – based framework. Nonparametric regression approach as a method of estimating finite population total is explored. The asymptotic properties of the estimators based on nonparametric regression are also developed under ...

  15. Neurons derived from patients with bipolar disorder divide into intrinsically different sub-populations of neurons, predicting the patients' responsiveness to lithium.

    Science.gov (United States)

    Stern, S; Santos, R; Marchetto, M C; Mendes, A P D; Rouleau, G A; Biesmans, S; Wang, Q-W; Yao, J; Charnay, P; Bang, A G; Alda, M; Gage, F H

    2017-02-28

    Bipolar disorder (BD) is a progressive psychiatric disorder with more than 3% prevalence worldwide. Affected individuals experience recurrent episodes of depression and mania, disrupting normal life and increasing the risk of suicide greatly. The complexity and genetic heterogeneity of psychiatric disorders have challenged the development of animal and cellular models. We recently reported that hippocampal dentate gyrus (DG) neurons differentiated from induced pluripotent stem cell (iPSC)-derived fibroblasts of BD patients are electrophysiologically hyperexcitable. Here we used iPSCs derived from Epstein-Barr virus-immortalized B-lymphocytes to verify that the hyperexcitability of DG-like neurons is reproduced in this different cohort of patients and cells. Lymphocytes are readily available for research with a large number of banked lines with associated patient clinical description. We used whole-cell patch-clamp recordings of over 460 neurons to characterize neurons derived from control individuals and BD patients. Extensive functional analysis showed that intrinsic cell parameters are very different between the two groups of BD neurons, those derived from lithium (Li)-responsive (LR) patients and those derived from Li-non-responsive (NR) patients, which led us to partition our BD neurons into two sub-populations of cells and suggested two different subdisorders. Training a Naïve Bayes classifier with the electrophysiological features of patients whose responses to Li are known allows for accurate classification with more than 92% success rate for a new patient whose response to Li is unknown. Despite their very different functional profiles, both populations of neurons share a large, fast after-hyperpolarization (AHP). We therefore suggest that the large, fast AHP is a key feature of BD and a main contributor to the fast, sustained spiking abilities of BD neurons. Confirming our previous report with fibroblast-derived DG neurons, chronic Li treatment reduced

  16. Reconstructing the population activity of olfactory output neurons that innervate identifiable processing units

    Directory of Open Access Journals (Sweden)

    Shigehiro Namiki

    2008-06-01

    Full Text Available We investigated the functional organization of the moth antennal lobe (AL, the primary olfactory network, using in vivo electrophysiological recordings and anatomical identification. The moth AL contains about 60 processing units called glomeruli that are identifiable from one animal to another. We were able to monitor the output information of the AL by recording the activity of a population of output neurons, each of which innervated a single glomerulus. Using compiled intracellular recordings and staining data from different animals, we mapped the odor-evoked dynamics on a digital atlas of the AL and geometrically reconstructed the population activity. We examined the quantitative relationship between the similarity of olfactory responses and the anatomical distance between glomeruli. Globally, the olfactory response profile was independent of the anatomical distance, although some local features were present.

  17. Analyzing dendritic growth in a population of immature neurons in the adult dentate gyrus using laminar quantification of disjointed dendrites

    Directory of Open Access Journals (Sweden)

    Shira eRosenzweig

    2011-03-01

    Full Text Available In the dentate gyrus of the hippocampus, new granule neurons are continuously produced throughout adult life. A prerequisite for the successful synaptic integration of these neurons is the sprouting and extension of dendrites into the molecular layer of the dentate gyrus. Thus, studies aimed at investigating the developmental stages of adult neurogenesis often use dendritic growth as an important indicator of neuronal health and maturity. Based on the known topography of the dentate gyrus, characterized by distinct laminar arrangement of granule neurons and their extensions, we have developed a new method for analysis of dendritic growth in immature adult-born granule neurons. The method is comprised of laminar quantification of cell bodies, primary, secondary and tertiary dendrites separately and independently from each other. In contrast to most existing methods, laminar quantification of dendrites does not require the use of exogenous markers and does not involve arbitrary selection of individual neurons. The new method relies on immonuhistochemical detection of endogenous markers such as doublecortin to perform a comprehensive analysis of a sub-population of immature neurons. Disjointed, orphan dendrites that often appear in the thin histological sections are taken into account. Using several experimental groups of rats and mice, we demonstrate here the suitable techniques for quantifying neurons and dendrites, and explain how the ratios between the quantified values can be used in a comparative analysis to indicate variations in dendritic growth and complexity.

  18. Metastable states and quasicycles in a stochastic Wilson-Cowan model of neuronal population dynamics

    KAUST Repository

    Bressloff, Paul C.

    2010-11-03

    We analyze a stochastic model of neuronal population dynamics with intrinsic noise. In the thermodynamic limit N→∞, where N determines the size of each population, the dynamics is described by deterministic Wilson-Cowan equations. On the other hand, for finite N the dynamics is described by a master equation that determines the probability of spiking activity within each population. We first consider a single excitatory population that exhibits bistability in the deterministic limit. The steady-state probability distribution of the stochastic network has maxima at points corresponding to the stable fixed points of the deterministic network; the relative weighting of the two maxima depends on the system size. For large but finite N, we calculate the exponentially small rate of noise-induced transitions between the resulting metastable states using a Wentzel-Kramers- Brillouin (WKB) approximation and matched asymptotic expansions. We then consider a two-population excitatory or inhibitory network that supports limit cycle oscillations. Using a diffusion approximation, we reduce the dynamics to a neural Langevin equation, and show how the intrinsic noise amplifies subthreshold oscillations (quasicycles). © 2010 The American Physical Society.

  19. Different populations of prostaglandin EP3 receptor-expressing preoptic neurons project to two fever-mediating sympathoexcitatory brain regions.

    Science.gov (United States)

    Nakamura, Y; Nakamura, K; Morrison, S F

    2009-06-30

    The central mechanism of fever induction is triggered by an action of prostaglandin E(2) (PGE(2)) on neurons in the preoptic area (POA) through the EP3 subtype of prostaglandin E receptor. EP3 receptor (EP3R)-expressing POA neurons project directly to the dorsomedial hypothalamus (DMH) and to the rostral raphe pallidus nucleus (rRPa), key sites for the control of thermoregulatory effectors. Based on physiological findings, we hypothesize that the febrile responses in brown adipose tissue (BAT) and those in cutaneous vasoconstrictors are controlled independently by separate neuronal pathways: PGE(2) pyrogenic signaling is transmitted from EP3R-expressing POA neurons via a projection to the DMH to activate BAT thermogenesis and via another projection to the rRPa to increase cutaneous vasoconstriction. In this case, DMH-projecting and rRPa-projecting neurons would constitute segregated populations within the EP3R-expressing neuronal group in the POA. Here, we sought direct anatomical evidence to test this hypothesis with a double-tracing experiment in which two types of the retrograde tracer, cholera toxin b-subunit (CTb), conjugated with different fluorophores were injected into the DMH and the rRPa of rats and the resulting retrogradely labeled populations of EP3R-immunoreactive neurons in the POA were identified with confocal microscopy. We found substantial numbers of EP3R-immunoreactive neurons in both the DMH-projecting and the rRPa-projecting populations. However, very few EP3R-immunoreactive POA neurons were labeled with both the CTb from the DMH and that from the rRPa, although a substantial number of neurons that were not immunoreactive for EP3R were double-labeled with both CTbs. The paucity of the EP3R-expressing neurons that send collaterals to both the DMH and the rRPa suggests that pyrogenic signals are sent independently to these caudal brain regions from the POA and that such pyrogenic outputs from the POA reflect different control mechanisms for BAT

  20. Vertical binocular disparity is encoded implicitly within a model neuronal population tuned to horizontal disparity and orientation.

    Directory of Open Access Journals (Sweden)

    Jenny C A Read

    2010-04-01

    Full Text Available Primary visual cortex is often viewed as a "cyclopean retina", performing the initial encoding of binocular disparities between left and right images. Because the eyes are set apart horizontally in the head, binocular disparities are predominantly horizontal. Yet, especially in the visual periphery, a range of non-zero vertical disparities do occur and can influence perception. It has therefore been assumed that primary visual cortex must contain neurons tuned to a range of vertical disparities. Here, I show that this is not necessarily the case. Many disparity-selective neurons are most sensitive to changes in disparity orthogonal to their preferred orientation. That is, the disparity tuning surfaces, mapping their response to different two-dimensional (2D disparities, are elongated along the cell's preferred orientation. Because of this, even if a neuron's optimal 2D disparity has zero vertical component, the neuron will still respond best to a non-zero vertical disparity when probed with a sub-optimal horizontal disparity. This property can be used to decode 2D disparity, even allowing for realistic levels of neuronal noise. Even if all V1 neurons at a particular retinotopic location are tuned to the expected vertical disparity there (for example, zero at the fovea, the brain could still decode the magnitude and sign of departures from that expected value. This provides an intriguing counter-example to the common wisdom that, in order for a neuronal population to encode a quantity, its members must be tuned to a range of values of that quantity. It demonstrates that populations of disparity-selective neurons encode much richer information than previously appreciated. It suggests a possible strategy for the brain to extract rarely-occurring stimulus values, while concentrating neuronal resources on the most commonly-occurring situations.

  1. A Population of Indirect Pathway Striatal Projection Neurons Is Selectively Entrained to Parkinsonian Beta Oscillations.

    Science.gov (United States)

    Sharott, Andrew; Vinciati, Federica; Nakamura, Kouichi C; Magill, Peter J

    2017-10-11

    Classical schemes of basal ganglia organization posit that parkinsonian movement difficulties presenting after striatal dopamine depletion stem from the disproportionate firing rates of spiny projection neurons (SPNs) therein. There remains, however, a pressing need to elucidate striatal SPN firing in the context of the synchronized network oscillations that are abnormally exaggerated in cortical-basal ganglia circuits in parkinsonism. To address this, we recorded unit activities in the dorsal striatum of dopamine-intact and dopamine-depleted rats during two brain states, respectively defined by cortical slow-wave activity (SWA) and activation. Dopamine depletion escalated striatal net output but had contrasting effects on "direct pathway" SPNs (dSPNs) and "indirect pathway" SPNs (iSPNs); their firing rates became imbalanced, and they disparately engaged in network oscillations. Disturbed striatal activity dynamics relating to the slow (∼1 Hz) oscillations prevalent during SWA partly generalized to the exaggerated beta-frequency (15-30 Hz) oscillations arising during cortical activation. In both cases, SPNs exhibited higher incidences of phase-locked firing to ongoing cortical oscillations, and SPN ensembles showed higher levels of rhythmic correlated firing, after dopamine depletion. Importantly, in dopamine-depleted striatum, a widespread population of iSPNs, which often displayed excessive firing rates and aberrant phase-locked firing to cortical beta oscillations, preferentially and excessively synchronized their firing at beta frequencies. Conversely, dSPNs were neither hyperactive nor synchronized to a large extent during cortical activation. These data collectively demonstrate a cell type-selective entrainment of SPN firing to parkinsonian beta oscillations. We conclude that a population of overactive, excessively synchronized iSPNs could orchestrate these pathological rhythms in basal ganglia circuits. SIGNIFICANCE STATEMENT Chronic depletion of dopamine

  2. Anatomical and molecular consequences of Unilateral Naris Closure on two populations of olfactory sensory neurons expressing defined odorant receptors.

    Science.gov (United States)

    Molinas, Adrien; Aoudé, Imad; Soubeyre, Vanessa; Tazir, Bassim; Cadiou, Hervé; Grosmaitre, Xavier

    2016-07-28

    Mammalian olfactory sensory neurons (OSNs), the primary elements of the olfactory system, are located in the olfactory epithelium lining the nasal cavity. Exposed to the environment, their lifespan is short. Consequently, OSNs are regularly regenerated and several reports show that activity strongly modulates their development and regeneration: the peripheral olfactory system can adjust to the amount of stimulus through compensatory mechanisms. Unilateral naris occlusion (UNO) was frequently used to investigate this mechanism at the entire epithelium level. However, there is little data regarding the effects of UNO at the cellular level, especially on individual neuronal populations expressing a defined odorant receptor. Here, using UNO during the first three postnatal weeks, we analyzed the anatomical and molecular consequences of sensory deprivation in OSNs populations expressing the MOR23 and M71 receptors. The density of MOR23-expressing neurons is decreased in the closed side while UNO does not affect the density of M71-expressing neurons. Using Real Time qPCR on isolated neurons, we observed that UNO modulates the transcript levels for transduction pathway proteins (odorant receptors, CNGA2, PDE1c). The transcripts modulated by UNO will differ between populations depending on the receptor expressed. These results suggest that sensory deprivation will have different effects on different OSNs' populations. As a consequence, early experience will shape the functional properties of OSNs differently depending on the type of odorant receptor they express. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Facial injections of pruritogens and algogens excite partly overlapping populations of primary and second-order trigeminal neurons in mice.

    Science.gov (United States)

    Akiyama, T; Carstens, M Iodi; Carstens, E

    2010-11-01

    Intradermal cheek injection of pruitogens or algogens differentially elicits hindlimb scratching or forelimb wiping, suggesting that these behaviors distinguish between itch and pain. We studied whether pruritogens and algogens excite separate or overlapping populations of primary afferent and second-order trigeminal neurons in mice. Calcium imaging of primary sensory trigeminal ganglion (TG) cells showed that 15.4% responded to histamine, 5.8% to the protease-activated receptor (PAR)-2 agonist, 13.4% to allyl isothiocyanate (AITC), and 36.7% to capsaicin. AITC and/or capsaicin activated the vast majority of histamine- and PAR-2 agonist-sensitive TG cells. A chemical search strategy identified second-order neurons in trigeminal subnucleus caudalis (Vc) responsive to histamine, the PAR-2 agonist, or AITC. A minority of histamine or PAR-2 agonist-responsive Vc neurons responded to the other pruritogen, whereas a large majority of puritogen-responsive Vc neurons responded to capsaicin and/or AITC. A minority of AITC-responsive Vc neurons responded to pruritogens, whereas most responded to capsaicin. These data indicate that most primary and higher-order trigeminal sensory neurons are activated by both pruritic and algesic stimuli, although a minority exhibit selectivity. The results are discussed in terms of population codes for itch and pain that result in distinct behavioral responses of hindlimb scratching and forelimb wiping that are mediated at lumbar and cervical segmental levels, respectively.

  4. Mean-field dynamics of a population of stochastic map neurons

    Science.gov (United States)

    Franović, Igor; Maslennikov, Oleg V.; Bačić, Iva; Nekorkin, Vladimir I.

    2017-07-01

    We analyze the emergent regimes and the stimulus-response relationship of a population of noisy map neurons by means of a mean-field model, derived within the framework of cumulant approach complemented by the Gaussian closure hypothesis. It is demonstrated that the mean-field model can qualitatively account for stability and bifurcations of the exact system, capturing all the generic forms of collective behavior, including macroscopic excitability, subthreshold oscillations, periodic or chaotic spiking, and chaotic bursting dynamics. Apart from qualitative analogies, we find a substantial quantitative agreement between the exact and the approximate system, as reflected in matching of the parameter domains admitting the different dynamical regimes, as well as the characteristic properties of the associated time series. The effective model is further shown to reproduce with sufficient accuracy the phase response curves of the exact system and the assembly's response to external stimulation of finite amplitude and duration.

  5. Elucidating distinct ion channel populations on the surface of hippocampal neurons via single-particle tracking recurrence analysis

    Science.gov (United States)

    Sikora, Grzegorz; Wyłomańska, Agnieszka; Gajda, Janusz; Solé, Laura; Akin, Elizabeth J.; Tamkun, Michael M.; Krapf, Diego

    2017-12-01

    Protein and lipid nanodomains are prevalent on the surface of mammalian cells. In particular, it has been recently recognized that ion channels assemble into surface nanoclusters in the soma of cultured neurons. However, the interactions of these molecules with surface nanodomains display a considerable degree of heterogeneity. Here, we investigate this heterogeneity and develop statistical tools based on the recurrence of individual trajectories to identify subpopulations within ion channels in the neuronal surface. We specifically study the dynamics of the K+ channel Kv1.4 and the Na+ channel Nav1.6 on the surface of cultured hippocampal neurons at the single-molecule level. We find that both these molecules are expressed in two different forms with distinct kinetics with regards to surface interactions, emphasizing the complex proteomic landscape of the neuronal surface. Further, the tools presented in this work provide new methods for the analysis of membrane nanodomains, transient confinement, and identification of populations within single-particle trajectories.

  6. Model-Based Design of Stimulus Trains for Selective Microstimulation of Targeted Neuronal Populations

    National Research Council Canada - National Science Library

    McIntyre, Cameron

    2001-01-01

    ... that accurately reproduced the dynamic firing properties of mammalian neurons, The neuron models were coupled to a three-dimensional finite element model of the spinal cord that solved for the potentials...

  7. Histamine influences body temperature by acting at H1 and H3 receptors on distinct populations of preoptic neurons.

    Science.gov (United States)

    Lundius, Ebba Gregorsson; Sanchez-Alavez, Manuel; Ghochani, Yasmin; Klaus, Joseph; Tabarean, Iustin V

    2010-03-24

    The preoptic area/anterior hypothalamus, a region that contains neurons that control thermoregulation, is the main locus at which histamine affects body temperature. Here we report that histamine reduced the spontaneous firing rate of GABAergic preoptic neurons by activating H3 subtype histamine receptors. This effect involved a decrease in the level of phosphorylation of the extracellular signal-regulated kinase and was not dependent on synaptic activity. Furthermore, a population of non-GABAergic neurons was depolarized, and their firing rate was enhanced by histamine acting at H1 subtype receptors. In our experiments, activation of the H1R receptors was linked to the PLC pathway and Ca(2+) release from intracellular stores. This depolarization persisted in TTX or when fast synaptic potentials were blocked, indicating that it represents a postsynaptic effect. Single-cell reverse transcription-PCR analysis revealed expression of H3 receptors in a population of GABAergic neurons, while H1 receptors were expressed in non-GABAergic cells. Histamine applied in the median preoptic nucleus induced a robust, long-lasting hyperthermia effect that was mimicked by either H1 or H3 histamine receptor subtype-specific agonists. Our data indicate that histamine modulates the core body temperature by acting at two distinct populations of preoptic neurons that express H1 and H3 receptor subtypes, respectively.

  8. Activin A Inhibits MPTP and LPS-Induced Increases in Inflammatory Cell Populations and Loss of Dopamine Neurons in the Mouse Midbrain In Vivo.

    Science.gov (United States)

    Stayte, Sandy; Rentsch, Peggy; Tröscher, Anna R; Bamberger, Maximilian; Li, Kong M; Vissel, Bryce

    2017-01-01

    Parkinson's disease is a chronic neurodegenerative disease characterized by a significant loss of dopaminergic neurons within the substantia nigra pars compacta region and a subsequent loss of dopamine within the striatum. A promising avenue of research has been the administration of growth factors to promote the survival of remaining midbrain neurons, although the mechanism by which they provide neuroprotection is not understood. Activin A, a member of the transforming growth factor β superfamily, has been shown to be a potent anti-inflammatory following acute brain injury and has been demonstrated to play a role in the neuroprotection of midbrain neurons against MPP+-induced degeneration in vitro. We hypothesized that activin A may offer similar anti-inflammatory and neuroprotective effects in in vivo mouse models of Parkinson's disease. We found that activin A significantly attenuated the inflammatory response induced by both MPTP and intranigral administration of lipopolysaccharide in C57BL/6 mice. We found that administration of activin A promoted survival of dopaminergic and total neuron populations in the pars compacta region both 8 days and 8 weeks after MPTP-induced degeneration. Surprisingly, no corresponding protection of striatal dopamine levels was found. Furthermore, activin A failed to protect against loss of striatal dopamine transporter expression in the striatum, suggesting the neuroprotective action of activin A may be localized to the substantia nigra. Together, these results provide the first evidence that activin A exerts potent neuroprotection and anti-inflammatory effects in the MPTP and lipopolysaccharide mouse models of Parkinson's disease.

  9. Differential response of olfactory sensory neuron populations to copper ion exposure in zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Lazzari, Maurizio, E-mail: maurizio.lazzari@unibo.it; Bettini, Simone; Milani, Liliana; Maurizii, Maria Gabriella; Franceschini, Valeria

    2017-02-15

    Highlights: • Copper exposure affects ciliated olfactory receptors more than microvillar cells. • Crypt olfactory sensory neurons are not affected by copper exposure. • Copper exposure induces an increase in the amount of sensory epithelium. - Abstract: The peripheral olfactory system of fish is in direct contact with the external aqueous environment, so dissolved contaminants can easily impair sensory functions and cause neurobehavioral injuries. The olfactory epithelium of fish is arranged in lamellae forming a rosette in the olfactory cavity and contains three main types of olfactory sensory neurons (OSNs): ciliated (cOSNs) and microvillous olfactory sensory neurons (mOSNs), common to all vertebrates, and a third minor group of olfactory neurons, crypt cells, absent in tetrapods. Since copper is a ubiquitously diffusing olfactory toxicant and a spreading contaminant in urban runoff, we investigated the effect of low copper concentration on the three different OSNs in the olfactory epithelium of zebrafish, a model system widely used in biological research. Image analysis was applied for morphometry and quantification of immunohistochemically detected OSNs. Copper exposure resulted in an evident decrease in olfactory epithelium thickness. Moreover, after exposure, the lamellae of the dorsal and ventral halves of the olfactory rosettes showed a different increase in their sensory areas, suggesting a lateral migration of new cells into non-sensory regions. The results of the present study provide clear evidence of a differential response of the three neural cell populations of zebrafish olfactory mucosa after 96 h of exposure to copper ions at the sublethal concentration of 30 μg L{sup −1}. Densitometric values of cONS, immunostained with anti-G {sub αolf}, decreased of about 60% compared to the control. When the fish were transferred to water without copper addition and examined after 3, 10 and 30 days, we observed a partial restoration of anti-G {sub

  10. Differential response of olfactory sensory neuron populations to copper ion exposure in zebrafish

    International Nuclear Information System (INIS)

    Lazzari, Maurizio; Bettini, Simone; Milani, Liliana; Maurizii, Maria Gabriella; Franceschini, Valeria

    2017-01-01

    Highlights: • Copper exposure affects ciliated olfactory receptors more than microvillar cells. • Crypt olfactory sensory neurons are not affected by copper exposure. • Copper exposure induces an increase in the amount of sensory epithelium. - Abstract: The peripheral olfactory system of fish is in direct contact with the external aqueous environment, so dissolved contaminants can easily impair sensory functions and cause neurobehavioral injuries. The olfactory epithelium of fish is arranged in lamellae forming a rosette in the olfactory cavity and contains three main types of olfactory sensory neurons (OSNs): ciliated (cOSNs) and microvillous olfactory sensory neurons (mOSNs), common to all vertebrates, and a third minor group of olfactory neurons, crypt cells, absent in tetrapods. Since copper is a ubiquitously diffusing olfactory toxicant and a spreading contaminant in urban runoff, we investigated the effect of low copper concentration on the three different OSNs in the olfactory epithelium of zebrafish, a model system widely used in biological research. Image analysis was applied for morphometry and quantification of immunohistochemically detected OSNs. Copper exposure resulted in an evident decrease in olfactory epithelium thickness. Moreover, after exposure, the lamellae of the dorsal and ventral halves of the olfactory rosettes showed a different increase in their sensory areas, suggesting a lateral migration of new cells into non-sensory regions. The results of the present study provide clear evidence of a differential response of the three neural cell populations of zebrafish olfactory mucosa after 96 h of exposure to copper ions at the sublethal concentration of 30 μg L"−"1. Densitometric values of cONS, immunostained with anti-G _α_o_l_f, decreased of about 60% compared to the control. When the fish were transferred to water without copper addition and examined after 3, 10 and 30 days, we observed a partial restoration of anti-G _

  11. Tracking the fear memory engram: discrete populations of neurons within amygdala, hypothalamus, and lateral septum are specifically activated by auditory fear conditioning

    Science.gov (United States)

    Wilson, Yvette M.; Gunnersen, Jenny M.; Murphy, Mark

    2015-01-01

    Memory formation is thought to occur via enhanced synaptic connectivity between populations of neurons in the brain. However, it has been difficult to localize and identify the neurons that are directly involved in the formation of any specific memory. We have previously used fos-tau-lacZ (FTL) transgenic mice to identify discrete populations of neurons in amygdala and hypothalamus, which were specifically activated by fear conditioning to a context. Here we have examined neuronal activation due to fear conditioning to a more specific auditory cue. Discrete populations of learning-specific neurons were identified in only a small number of locations in the brain, including those previously found to be activated in amygdala and hypothalamus by context fear conditioning. These populations, each containing only a relatively small number of neurons, may be directly involved in fear learning and memory. PMID:26179231

  12. Genetic epidemiology of motor neuron disease-associated variants in the Scottish population.

    Science.gov (United States)

    Black, Holly A; Leighton, Danielle J; Cleary, Elaine M; Rose, Elaine; Stephenson, Laura; Colville, Shuna; Ross, David; Warner, Jon; Porteous, Mary; Gorrie, George H; Swingler, Robert; Goldstein, David; Harms, Matthew B; Connick, Peter; Pal, Suvankar; Aitman, Timothy J; Chandran, Siddharthan

    2017-03-01

    Genetic understanding of motor neuron disease (MND) has evolved greatly in the past 10 years, including the recent identification of association between MND and variants in TBK1 and NEK1. Our aim was to determine the frequency of pathogenic variants in known MND genes and to assess whether variants in TBK1 and NEK1 contribute to the burden of MND in the Scottish population. SOD1, TARDBP, OPTN, TBK1, and NEK1 were sequenced in 441 cases and 400 controls. In addition to 44 cases known to carry a C9orf72 hexanucleotide repeat expansion, we identified 31 cases and 2 controls that carried a loss-of-function or pathogenic variant. Loss-of-function variants were found in TBK1 in 3 cases and no controls and, separately, in NEK1 in 3 cases and no controls. This study provides an accurate description of the genetic epidemiology of MND in Scotland and provides support for the contribution of both TBK1 and NEK1 to MND susceptibility in the Scottish population. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. A simple approach to ignoring irrelevant variables by population decoding based on multisensory neurons

    Science.gov (United States)

    Kim, HyungGoo R.; Pitkow, Xaq; Angelaki, Dora E.

    2016-01-01

    Sensory input reflects events that occur in the environment, but multiple events may be confounded in sensory signals. For example, under many natural viewing conditions, retinal image motion reflects some combination of self-motion and movement of objects in the world. To estimate one stimulus event and ignore others, the brain can perform marginalization operations, but the neural bases of these operations are poorly understood. Using computational modeling, we examine how multisensory signals may be processed to estimate the direction of self-motion (i.e., heading) and to marginalize out effects of object motion. Multisensory neurons represent heading based on both visual and vestibular inputs and come in two basic types: “congruent” and “opposite” cells. Congruent cells have matched heading tuning for visual and vestibular cues and have been linked to perceptual benefits of cue integration during heading discrimination. Opposite cells have mismatched visual and vestibular heading preferences and are ill-suited for cue integration. We show that decoding a mixed population of congruent and opposite cells substantially reduces errors in heading estimation caused by object motion. In addition, we present a general formulation of an optimal linear decoding scheme that approximates marginalization and can be implemented biologically by simple reinforcement learning mechanisms. We also show that neural response correlations induced by task-irrelevant variables may greatly exceed intrinsic noise correlations. Overall, our findings suggest a general computational strategy by which neurons with mismatched tuning for two different sensory cues may be decoded to perform marginalization operations that dissociate possible causes of sensory inputs. PMID:27334948

  14. Comparison of classifiers for decoding sensory and cognitive information from prefrontal neuronal populations.

    Directory of Open Access Journals (Sweden)

    Elaine Astrand

    Full Text Available Decoding neuronal information is important in neuroscience, both as a basic means to understand how neuronal activity is related to cerebral function and as a processing stage in driving neuroprosthetic effectors. Here, we compare the readout performance of six commonly used classifiers at decoding two different variables encoded by the spiking activity of the non-human primate frontal eye fields (FEF: the spatial position of a visual cue, and the instructed orientation of the animal's attention. While the first variable is exogenously driven by the environment, the second variable corresponds to the interpretation of the instruction conveyed by the cue; it is endogenously driven and corresponds to the output of internal cognitive operations performed on the visual attributes of the cue. These two variables were decoded using either a regularized optimal linear estimator in its explicit formulation, an optimal linear artificial neural network estimator, a non-linear artificial neural network estimator, a non-linear naïve Bayesian estimator, a non-linear Reservoir recurrent network classifier or a non-linear Support Vector Machine classifier. Our results suggest that endogenous information such as the orientation of attention can be decoded from the FEF with the same accuracy as exogenous visual information. All classifiers did not behave equally in the face of population size and heterogeneity, the available training and testing trials, the subject's behavior and the temporal structure of the variable of interest. In most situations, the regularized optimal linear estimator and the non-linear Support Vector Machine classifiers outperformed the other tested decoders.

  15. A SAGE-based screen for genes expressed in sub-populations of neurons in the mouse dorsal root ganglion

    Directory of Open Access Journals (Sweden)

    Garces Alain

    2007-11-01

    Full Text Available Abstract Background The different sensory modalities temperature, pain, touch and muscle proprioception are carried by somatosensory neurons of the dorsal root ganglia. Study of this system is hampered by the lack of molecular markers for many of these neuronal sub-types. In order to detect genes expressed in sub-populations of somatosensory neurons, gene profiling was carried out on wild-type and TrkA mutant neonatal dorsal root ganglia (DRG using SAGE (serial analysis of gene expression methodology. Thermo-nociceptors constitute up to 80 % of the neurons in the DRG. In TrkA mutant DRGs, the nociceptor sub-class of sensory neurons is lost due to absence of nerve growth factor survival signaling through its receptor TrkA. Thus, comparison of wild-type and TrkA mutants allows the identification of transcripts preferentially expressed in the nociceptor or mechano-proprioceptor subclasses, respectively. Results Our comparison revealed 240 genes differentially expressed between the two tissues (P Conclusion We have identified and characterized the detailed expression patterns of three genes in the developing DRG, placing them in the context of the known major neuronal sub-types defined by molecular markers. Further analysis of differentially expressed genes in this tissue promises to extend our knowledge of the molecular diversity of different cell types and forms the basis for understanding their particular functional specificities.

  16. Interleukin-1 beta activates specific populations of enteric neurons and enteric glia in the guinea pig ileum and colon

    NARCIS (Netherlands)

    Tjwa, ETTL; Bradley, JM; Keenan, CM; Kroese, ABA; Sharkey, KA

    2003-01-01

    Fos expression was used to assess whether the proinflammatory cytokine interleukin-1beta (IL-1beta) activated specific, chemically coded neuronal populations in isolated preparations of guinea pig ileum and colon. Whether the effects of IL-1beta were mediated through a prostaglandin pathway and

  17. Distinct populations of GABAergic neurons in mouse rhombomere 1 express but do not require the homeodomain transcription factor PITX2.

    Science.gov (United States)

    Waite, Mindy R; Skaggs, Kaia; Kaviany, Parisa; Skidmore, Jennifer M; Causeret, Frédéric; Martin, James F; Martin, Donna M

    2012-01-01

    Hindbrain rhombomere 1 (r1) is located caudal to the isthmus, a critical organizer region, and rostral to rhombomere 2 in the developing mouse brain. Dorsal r1 gives rise to the cerebellum, locus coeruleus, and several brainstem nuclei, whereas cells from ventral r1 contribute to the trochlear and trigeminal nuclei as well as serotonergic and GABAergic neurons of the dorsal raphe. Recent studies have identified several molecular events controlling dorsal r1 development. In contrast, very little is known about ventral r1 gene expression and the genetic mechanisms regulating its formation. Neurons with distinct neurotransmitter phenotypes have been identified in ventral r1 including GABAergic, serotonergic, and cholinergic neurons. Here we show that PITX2 marks a distinct population of GABAergic neurons in mouse embryonic ventral r1. This population appears to retain its GABAergic identity even in the absence of PITX2. We provide a comprehensive map of markers that places these PITX2-positive GABAergic neurons in a region of r1 that intersects and is potentially in communication with the dorsal raphe. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Gene Expression and the Diversity of Identified Neurons

    OpenAIRE

    Buck, L.; Stein, R.; Palazzolo, M.; Anderson, D. J.; Axel, R.

    1983-01-01

    Nervous systems consist of diverse populations of neurons that are anatomically and functionally distinct. The diversity of neurons and the precision with which they are interconnected suggest that specific genes or sets of genes are activated in some neurons but not expressed in others. Experimentally, this problem may be considered at two levels. First, what is the total number of genes expressed in the brain, and how are they distributed among the different populations of neurons? Second, ...

  19. Rate response of neurons subject to fast or frozen noise: from stochastic and homogeneous to deterministic and heterogeneous populations.

    Science.gov (United States)

    Alijani, Azadeh Khajeh; Richardson, Magnus J E

    2011-07-01

    The response of a neuronal population to afferent drive can be expected to be sensitive to both the distribution and dynamics of membrane voltages within the population. Voltage fluctuations can be driven by synaptic noise, neuromodulators, or cellular inhomogeneities: processes ranging from millisecond autocorrelation times to effectively static or "frozen" noise. Here we extend previous studies of filtered fluctuations to the experimentally verified exponential integrate-and-fire model. How fast or frozen fluctuations affect the steady-state rate and firing-rate response are both examined using perturbative solutions and limits of a 1 + 2 dimensional Fokker-Planck equation. The central finding is that, under conditions of a more-or-less constant population voltage variance, the firing-rate response is only weakly dependent on the fluctuation filter constant: The voltage distribution is the principal determinant of the population response. This result is unexpected given the nature of the systems underlying the extreme limits of fast and frozen fluctuations; the first limit represents a homogeneous population of neurons firing stochastically, whereas the second limit is equivalent to a heterogeneous population of neurons firing deterministically.

  20. A principled dimension-reduction method for the population density approach to modeling networks of neurons with synaptic dynamics.

    Science.gov (United States)

    Ly, Cheng

    2013-10-01

    The population density approach to neural network modeling has been utilized in a variety of contexts. The idea is to group many similar noisy neurons into populations and track the probability density function for each population that encompasses the proportion of neurons with a particular state rather than simulating individual neurons (i.e., Monte Carlo). It is commonly used for both analytic insight and as a time-saving computational tool. The main shortcoming of this method is that when realistic attributes are incorporated in the underlying neuron model, the dimension of the probability density function increases, leading to intractable equations or, at best, computationally intensive simulations. Thus, developing principled dimension-reduction methods is essential for the robustness of these powerful methods. As a more pragmatic tool, it would be of great value for the larger theoretical neuroscience community. For exposition of this method, we consider a single uncoupled population of leaky integrate-and-fire neurons receiving external excitatory synaptic input only. We present a dimension-reduction method that reduces a two-dimensional partial differential-integral equation to a computationally efficient one-dimensional system and gives qualitatively accurate results in both the steady-state and nonequilibrium regimes. The method, termed modified mean-field method, is based entirely on the governing equations and not on any auxiliary variables or parameters, and it does not require fine-tuning. The principles of the modified mean-field method have potential applicability to more realistic (i.e., higher-dimensional) neural networks.

  1. Total numbers of neurons and glial cells in cortex and basal ganglia of aged brains with Down syndrome--a stereological study.

    Science.gov (United States)

    Karlsen, Anna Schou; Pakkenberg, Bente

    2011-11-01

    The total numbers of neurons and glial cells in the neocortex and basal ganglia in adults with Down syndrome (DS) were estimated with design-based stereological methods, providing quantitative data on brains affected by delayed development and accelerated aging. Cell numbers, volume of regions, and densities of neurons and glial cell subtypes were estimated in brains from 4 female DS subjects (mean age 66 years) and 6 female controls (mean age 70 years). The DS subjects were estimated to have about 40% fewer neocortical neurons in total (11.1 × 10(9) vs. 17.8 × 10(9), 2p ≤ 0.001) and almost 30% fewer neocortical glial cells with no overlap to controls (12.8 × 10(9) vs. 18.2 × 10(9), 2p = 0.004). In contrast, the total number of neurons in the basal ganglia was the same in the 2 groups, whereas the number of oligodendrocytes in the basal ganglia was reduced by almost 50% in DS (405 × 10(6) vs. 816 × 10(6), 2p = 0.01). We conclude that trisomy 21 affects cortical structures more than central gray matter emphasizing the differential impairment of brain development. Despite concomitant Alzheimer-like pathology, the neurodegenerative outcome in a DS brain deviates from common Alzheimer disease.

  2. Mapping human temporal and parietal neuronal population activity and functional coupling during mathematical cognition

    Science.gov (United States)

    Daitch, Amy L.; Foster, Brett L.; Schrouff, Jessica; Rangarajan, Vinitha; Kaşikçi, Itır; Gattas, Sandra; Parvizi, Josef

    2016-01-01

    Brain areas within the lateral parietal cortex (LPC) and ventral temporal cortex (VTC) have been shown to code for abstract quantity representations and for symbolic numerical representations, respectively. To explore the fast dynamics of activity within each region and the interaction between them, we used electrocorticography recordings from 16 neurosurgical subjects implanted with grids of electrodes over these two regions and tracked the activity within and between the regions as subjects performed three different numerical tasks. Although our results reconfirm the presence of math-selective hubs within the VTC and LPC, we report here a remarkable heterogeneity of neural responses within each region at both millimeter and millisecond scales. Moreover, we show that the heterogeneity of response profiles within each hub mirrors the distinct patterns of functional coupling between them. Our results support the existence of multiple bidirectional functional loops operating between discrete populations of neurons within the VTC and LPC during the visual processing of numerals and the performance of arithmetic functions. These findings reveal information about the dynamics of numerical processing in the brain and also provide insight into the fine-grained functional architecture and connectivity within the human brain. PMID:27821758

  3. The 50/50 cc Total Artificial Heart Trial: Extending the Benefits of the Total Artificial Heart to Underserved Populations.

    Science.gov (United States)

    Wells, Dennis; Villa, Chet R; Simón Morales, David Luís

    2017-01-01

    While use of the total artificial heart (TAH) is growing, the use of the device is not uniform across the gender and age spectrum because the vast majority of implants are in adult males. SynCardia has recently developed a smaller 50 cc TAH that was designed to accommodate patients with a body surface area as low as 1.2 m 2 (potentially even lower using virtual implantation). Herein, we describe the early use of the 50 cc TAH (10 implants in the US and 18 outside the US). Twenty-eight devices have been implanted worldwide. Nineteen (68%) patients were female, 4 (14%) were 21 years of age or younger, and 2 (7%) had a diagnosis of congenital heart disease (1 Fontan). The smallest patient, by body surface area, was 1.35 m 2 . Six patients (21%) have been placed on the Freedom Driver, all of whom have survived. Fourteen patients (50%) have had a positive outcome to date. The development of the 50 cc TAH has expanded the population of patients who may benefit from TAH support and thus may help improve outcomes for patients who have had limited biventricular support options to date. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Propidium iodide (PI) stains Nissl bodies and may serve as a quick marker for total neuronal cell count.

    Science.gov (United States)

    Niu, Junfei; Li, Chunman; Wu, Haihui; Feng, Xianling; Su, Qingning; Li, Shihe; Zhang, Lihong; Yew, David Tai Wai; Cho, Eric Yu Pang; Sha, Ou

    2015-03-01

    Propidium iodide (PI) reacts with both DNA and RNA and is a commonly used fluorescent reagent for nucleic acid staining. The aim of the study was to compare the cellular staining patterns of PI with that of Nissl staining in rat nervous tissues and to report a modified staining method that selectively labels Nissl bodies in neurons. Cryosections and paraffin sections of different tissues of normal Sprague-Dawley rats, including trigeminal ganglia, dorsal root ganglia, spinal cord, liver, and small intestine, were stained by either PI or the hematoxylin and eosin method. Some sections were treated with RNase or DNase before the above staining, and some were double stained with PI and a Nissl stain. The sections were observed by light, fluorescence or confocal microscopy. Results showed strong PI signals detected as patterns of granules in the neuronal cytoplasm of all nervous tissues, whereas the staining of neuronal nuclei was weaker. In contrast, nuclei of neuroglial cells were strongly stained by PI, while the cytoplasm was not obviously stained. Pretreatment of the neural tissue with RNase abolished the PI signals. Furthermore, the PI positive granules in neuronal cytoplasm co-localized with Nissl bodies stained by the fluorescent Nissl stain. When the tissue was pretreated with DNase, PI only stained the cytoplasmic granules of neurons, but not that of glial cells. Our results show that PI stains Nissl bodies and may serve as an economical and convenient neuron marker for neuronal cell counting when specific neural markers such as antibodies are not readily available. Copyright © 2015. Published by Elsevier GmbH.

  5. Distinct populations of neurons respond to emotional valence and arousal in the human subthalamic nucleus.

    Science.gov (United States)

    Sieger, Tomáš; Serranová, Tereza; Růžička, Filip; Vostatek, Pavel; Wild, Jiří; Štastná, Daniela; Bonnet, Cecilia; Novák, Daniel; Růžička, Evžen; Urgošík, Dušan; Jech, Robert

    2015-03-10

    Both animal studies and studies using deep brain stimulation in humans have demonstrated the involvement of the subthalamic nucleus (STN) in motivational and emotional processes; however, participation of this nucleus in processing human emotion has not been investigated directly at the single-neuron level. We analyzed the relationship between the neuronal firing from intraoperative microrecordings from the STN during affective picture presentation in patients with Parkinson's disease (PD) and the affective ratings of emotional valence and arousal performed subsequently. We observed that 17% of neurons responded to emotional valence and arousal of visual stimuli according to individual ratings. The activity of some neurons was related to emotional valence, whereas different neurons responded to arousal. In addition, 14% of neurons responded to visual stimuli. Our results suggest the existence of neurons involved in processing or transmission of visual and emotional information in the human STN, and provide evidence of separate processing of the affective dimensions of valence and arousal at the level of single neurons as well.

  6. Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus.

    Science.gov (United States)

    Hernández, Vivian M; Hegeman, Daniel J; Cui, Qiaoling; Kelver, Daniel A; Fiske, Michael P; Glajch, Kelly E; Pitt, Jason E; Huang, Tina Y; Justice, Nicholas J; Chan, C Savio

    2015-08-26

    Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping expression of the

  7. Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus

    Science.gov (United States)

    Hernández, Vivian M.; Hegeman, Daniel J.; Cui, Qiaoling; Kelver, Daniel A.; Fiske, Michael P.; Glajch, Kelly E.; Pitt, Jason E.; Huang, Tina Y.; Justice, Nicholas J.

    2015-01-01

    Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. SIGNIFICANCE STATEMENT Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping

  8. Neurochemical differences between target-specific populations of rat dorsal raphe projection neurons.

    Science.gov (United States)

    Prouty, Eric W; Chandler, Daniel J; Waterhouse, Barry D

    2017-11-15

    Serotonin (5-HT)-containing neurons in the dorsal raphe (DR) nucleus project throughout the forebrain and are implicated in many physiological processes and neuropsychiatric disorders. Diversity among these neurons has been characterized in terms of their neurochemistry and anatomical organization, but a clear sense of whether these attributes align with specific brain functions or terminal fields is lacking. DR 5-HT neurons can co-express additional neuroactive substances, increasing the potential for individualized regulation of target circuits. The goal of this study was to link DR neurons to a specific functional role by characterizing cells according to both their neurotransmitter expression and efferent connectivity; specifically, cells projecting to the medial prefrontal cortex (mPFC), a region implicated in cognition, emotion, and responses to stress. Following retrograde tracer injection, brainstem sections from Sprague-Dawley rats were immunohistochemically stained for markers of serotonin, glutamate, GABA, and nitric oxide (NO). 98% of the mPFC-projecting serotonergic neurons co-expressed the marker for glutamate, while the markers for NO and GABA were observed in 60% and less than 1% of those neurons, respectively. To identify potential target-specific differences in co-transmitter expression, we also characterized DR neurons projecting to a visual sensory structure, the lateral geniculate nucleus (LGN). The proportion of serotonergic neurons co-expressing NO was greater amongst cells targeting the mPFC vs LGN (60% vs 22%). The established role of 5-HT in affective disorders and the emerging role of NO in stress signaling suggest that the impact of 5-HT/NO co-localization in DR neurons that regulate mPFC circuit function may be clinically relevant. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Vagal stimulation targets select populations of intrinsic cardiac neurons to control neurally induced atrial fibrillation.

    Science.gov (United States)

    Salavatian, Siamak; Beaumont, Eric; Longpré, Jean-Philippe; Armour, J Andrew; Vinet, Alain; Jacquemet, Vincent; Shivkumar, Kalyanam; Ardell, Jeffrey L

    2016-11-01

    Mediastinal nerve stimulation (MNS) reproducibly evokes atrial fibrillation (AF) by excessive and heterogeneous activation of intrinsic cardiac (IC) neurons. This study evaluated whether preemptive vagus nerve stimulation (VNS) impacts MNS-induced evoked changes in IC neural network activity to thereby alter susceptibility to AF. IC neuronal activity in the right atrial ganglionated plexus was directly recorded in anesthetized canines (n = 8) using a linear microelectrode array concomitant with right atrial electrical activity in response to: 1) epicardial touch or great vessel occlusion vs. 2) stellate or vagal stimulation. From these stressors, post hoc analysis (based on the Skellam distribution) defined IC neurons so recorded as afferent, efferent, or convergent (afferent and efferent inputs) local circuit neurons (LCN). The capacity of right-sided MNS to modify IC activity in the induction of AF was determined before and after preemptive right (RCV)- vs. left (LCV)-sided VNS (15 Hz, 500 μs; 1.2× bradycardia threshold). Neuronal (n = 89) activity at baseline (0.11 ± 0.29 Hz) increased during MNS-induced AF (0.51 ± 1.30 Hz; P neuronal synchrony increased during neurally induced AF, a local neural network response mitigated by preemptive VNS. These antiarrhythmic effects persisted post-VNS for, on average, 26 min. In conclusion, VNS preferentially targets convergent LCNs and their interactive coherence to mitigate the potential for neurally induced AF. The antiarrhythmic properties imposed by VNS exhibit memory. Copyright © 2016 the American Physiological Society.

  10. Variable expression of GFP in different populations of peripheral cholinergic neurons of ChATBAC-eGFP transgenic mice.

    Science.gov (United States)

    Brown, T Christopher; Bond, Cherie E; Hoover, Donald B

    2018-03-01

    Immunohistochemistry is used widely to identify cholinergic neurons, but this approach has some limitations. To address these problems, investigators developed transgenic mice that express enhanced green fluorescent protein (GFP) directed by the promoter for choline acetyltransferase (ChAT), the acetylcholine synthetic enzyme. Although, it was reported that these mice express GFP in all cholinergic neurons and non-neuronal cholinergic cells, we could not detect GFP in cardiac cholinergic nerves in preliminary experiments. Our goals for this study were to confirm our initial observation and perform a qualitative screen of other representative autonomic structures for the presences of GFP in cholinergic innervation of effector tissues. We evaluated GFP fluorescence of intact, unfixed tissues and the cellular localization of GFP and vesicular acetylcholine transporter (VAChT), a specific cholinergic marker, in tissue sections and intestinal whole mounts. Our experiments identified two major tissues where cholinergic neurons and/or nerve fibers lacked GFP: 1) most cholinergic neurons of the intrinsic cardiac ganglia and all cholinergic nerve fibers in the heart and 2) most cholinergic nerve fibers innervating airway smooth muscle. Most cholinergic neurons in airway ganglia stained for GFP. Cholinergic systems in the bladder and intestines were fully delineated by GFP staining. GFP labeling of input to ganglia with long preganglionic projections (vagal) was sparse or weak, while that to ganglia with short preganglionic projections (spinal) was strong. Total absence of GFP might be due to splicing out of the GFP gene. Lack of GFP in nerve projections from GFP-positive cell bodies might reflect a transport deficiency. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Tracking the Fear Memory Engram: Discrete Populations of Neurons within Amygdala, Hypothalamus, and Lateral Septum Are Specifically Activated by Auditory Fear Conditioning

    Science.gov (United States)

    Butler, Christopher W.; Wilson, Yvette M.; Gunnersen, Jenny M.; Murphy, Mark

    2015-01-01

    Memory formation is thought to occur via enhanced synaptic connectivity between populations of neurons in the brain. However, it has been difficult to localize and identify the neurons that are directly involved in the formation of any specific memory. We have previously used "fos-tau-lacZ" ("FTL") transgenic mice to identify…

  12. Activation of different neural precursor populations in the adult hippocampus: does this lead to new neurons with discrete functions?

    Science.gov (United States)

    Jhaveri, Dhanisha J; Taylor, Chanel J; Bartlett, Perry F

    2012-07-01

    Resident populations of stem and precursor cells drive the production of new neurons in the adult hippocampus. Recent discoveries have highlighted that a large proportion of these precursor cells are in fact quiescent and can be activated by distinct neuronal activity under both normal physiological and pathological conditions. As growing evidence indicates that newborn neurons play a critical role in cognitive functions such as learning and memory and in mood regulation, it is paramount that we obtain a better understanding of how the reservoirs of stem and precursor cells are maintained and activated. In this review, we critically examine the roles of key molecular mechanisms that have been shown to regulate hippocampal precursor cells, especially their activation. We believe that understanding the mechanistic details of the activity-driven regulation of precursor cells will equip us with the ability to develop tailored strategies to trigger the generation of new neurons, thereby improving the functional outcomes in various neurological and psychiatric conditions. Copyright © 2012 Wiley Periodicals, Inc.

  13. Midbrain and forebrain patterning delivers immunocytochemically and functionally similar populations of neuropeptide Y containing GABAergic neurons.

    Science.gov (United States)

    Khaira, S K; Nefzger, C M; Beh, S J; Pouton, C W; Haynes, J M

    2011-09-01

    Neurons differentiated in vitro from embryonic stem cells (ESCs) have the potential to serve both as models of disease states and in drug discovery programs. In this study, we use sonic hedgehog (SHH) and fibroblast growth factor 8 (FGF-8) to enrich for forebrain and midbrain phenotypes from mouse ESCs. We then investigate, using Ca(2+) imaging and [(3)H]-GABA release studies, whether the GABAergic neurons produced exhibit distinct functional phenotypes. At day 24 of differentiation, reverse transcriptase-PCR showed the presence of both forebrain (Bf-1, Hesx1, Pgc-1α, Six3) and midbrain (GATA2, GATA3) selective mRNA markers in developing forebrain-enriched cultures. All markers were present in midbrain cultures except for Bf-1 and Pgc-1α. Irrespective of culture conditions all GABA immunoreactive neurons were also immunoreactive to neuropeptide Y (NPY) antibodies. Forebrain and midbrain GABAergic neurons responded to ATP (1 mM), L-glutamate (30 μM), noradrenaline (30 μM), acetylcholine (30 μM) and dopamine (30 μM), with similar elevations of intracellular Ca(2+)([Ca(2+)](i)). The presence of GABA(A) and GABA(B) antagonists, bicuculline (30 μM) and CGP55845 (1 μM), increased the elevation of [Ca(2+)](i) in response to dopamine (30 μM) in midbrain, but not forebrain GABAergic neurons. All agonists, except dopamine, elicited similar [(3)H]-GABA release from forebrain and midbrain cultures. Dopamine (30 μM) did not stimulate significant [(3)H]-GABA release in midbrain cultures, although it was effective in forebrain cultures. This study shows that differentiating neurons toward a midbrain fate restricts the expression of forebrain markers. Forebrain differentiation results in the expression of forebrain and midbrain markers. All GABA(+) neurons contain NPY, and show similar agonist-induced elevations of [Ca(2+)](i) and [(3)H]-GABA release. This study indicates that the pharmacological phenotype of these particular neurons may be independent of the addition of

  14. Replicating receptive fields of simple and complex cells in primary visual cortex in a neuronal network model with temporal and population sparseness and reliability.

    Science.gov (United States)

    Tanaka, Takuma; Aoyagi, Toshio; Kaneko, Takeshi

    2012-10-01

    We propose a new principle for replicating receptive field properties of neurons in the primary visual cortex. We derive a learning rule for a feedforward network, which maintains a low firing rate for the output neurons (resulting in temporal sparseness) and allows only a small subset of the neurons in the network to fire at any given time (resulting in population sparseness). Our learning rule also sets the firing rates of the output neurons at each time step to near-maximum or near-minimum levels, resulting in neuronal reliability. The learning rule is simple enough to be written in spatially and temporally local forms. After the learning stage is performed using input image patches of natural scenes, output neurons in the model network are found to exhibit simple-cell-like receptive field properties. When the output of these simple-cell-like neurons are input to another model layer using the same learning rule, the second-layer output neurons after learning become less sensitive to the phase of gratings than the simple-cell-like input neurons. In particular, some of the second-layer output neurons become completely phase invariant, owing to the convergence of the connections from first-layer neurons with similar orientation selectivity to second-layer neurons in the model network. We examine the parameter dependencies of the receptive field properties of the model neurons after learning and discuss their biological implications. We also show that the localized learning rule is consistent with experimental results concerning neuronal plasticity and can replicate the receptive fields of simple and complex cells.

  15. A Knockin Reporter Allows Purification and Characterization of mDA Neurons from Heterogeneous Populations

    Directory of Open Access Journals (Sweden)

    Ninuo Xia

    2017-03-01

    Full Text Available Generation of midbrain dopaminergic (mDA neurons from human pluripotent stem cells provides a platform for inquiry into basic and translational studies of Parkinson’s disease (PD. However, heterogeneity in differentiation in vitro makes it difficult to identify mDA neurons in culture or in vivo following transplantation. Here, we report the generation of a human embryonic stem cell (hESC line with a tyrosine hydroxylase (TH-RFP (red fluorescent protein reporter. We validated that RFP faithfully mimicked TH expression during differentiation. Use of this TH-RFP reporter cell line enabled purification of mDA-like neurons from heterogeneous cultures with subsequent characterization of neuron transcriptional and epigenetic programs (global binding profiles of H3K27ac, H3K4me1, and 5-hydroxymethylcytosine [5hmC] at four different stages of development. We anticipate that the tools and data described here will contribute to the development of mDA neurons for applications in disease modeling and/or drug screening and cell replacement therapies for PD.

  16. A Knockin Reporter Allows Purification and Characterization of mDA Neurons from Heterogeneous Populations.

    Science.gov (United States)

    Xia, Ninuo; Fang, Fang; Zhang, Pengbo; Cui, Jun; Tep-Cullison, Chhavy; Hamerley, Tim; Lee, Hyun Joo; Palmer, Theo; Bothner, Brian; Lee, Jin Hyung; Pera, Renee Reijo

    2017-03-07

    Generation of midbrain dopaminergic (mDA) neurons from human pluripotent stem cells provides a platform for inquiry into basic and translational studies of Parkinson's disease (PD). However, heterogeneity in differentiation in vitro makes it difficult to identify mDA neurons in culture or in vivo following transplantation. Here, we report the generation of a human embryonic stem cell (hESC) line with a tyrosine hydroxylase (TH)-RFP (red fluorescent protein) reporter. We validated that RFP faithfully mimicked TH expression during differentiation. Use of this TH-RFP reporter cell line enabled purification of mDA-like neurons from heterogeneous cultures with subsequent characterization of neuron transcriptional and epigenetic programs (global binding profiles of H3K27ac, H3K4me1, and 5-hydroxymethylcytosine [5hmC]) at four different stages of development. We anticipate that the tools and data described here will contribute to the development of mDA neurons for applications in disease modeling and/or drug screening and cell replacement therapies for PD. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Leader neurons in population bursts of 2D living neural networks

    International Nuclear Information System (INIS)

    Eckmann, J-P; Zbinden, Cyrille; Jacobi, Shimshon; Moses, Elisha; Marom, Shimon

    2008-01-01

    Eytan and Marom (2006 J. Neurosci. 26 8465-76) recently showed that the spontaneous bursting activity of rat neuron cultures includes 'first-to-fire' cells that consistently fire earlier than others. Here, we analyze the behavior of these neurons in long-term recordings of spontaneous activity of rat hippocampal and rat cortical neuron cultures from three different laboratories. We identify precursor events that may either subside ('aborted bursts') or can lead to a full-blown burst ('pre-bursts'). We find that the activation in the pre-burst typically has a first neuron ('leader'), followed by a localized response in its neighborhood. Locality is diminished in the bursts themselves. The long-term dynamics of the leaders is relatively robust, evolving with a half-life of 23-34 h. Stimulation of the culture alters the leader distribution, but the distribution stabilizes within about 1 h. We show that the leaders carry information about the identity of the burst, as measured by the signature of the number of spikes per neuron in a burst. The number of spikes from leaders in the first few spikes of a precursor event is furthermore shown to be predictive with regard to the transition into a burst (pre-burst versus aborted burst). We conclude that the leaders play a role in the development of the bursts and conjecture that they are part of an underlying sub-network that is excited first and then acts as a nucleation center for the burst

  18. Vagal stimulation targets select populations of intrinsic cardiac neurons to control neurally induced atrial fibrillation

    Science.gov (United States)

    Salavatian, Siamak; Beaumont, Eric; Longpré, Jean-Philippe; Armour, J. Andrew; Vinet, Alain; Jacquemet, Vincent; Shivkumar, Kalyanam

    2016-01-01

    Mediastinal nerve stimulation (MNS) reproducibly evokes atrial fibrillation (AF) by excessive and heterogeneous activation of intrinsic cardiac (IC) neurons. This study evaluated whether preemptive vagus nerve stimulation (VNS) impacts MNS-induced evoked changes in IC neural network activity to thereby alter susceptibility to AF. IC neuronal activity in the right atrial ganglionated plexus was directly recorded in anesthetized canines (n = 8) using a linear microelectrode array concomitant with right atrial electrical activity in response to: 1) epicardial touch or great vessel occlusion vs. 2) stellate or vagal stimulation. From these stressors, post hoc analysis (based on the Skellam distribution) defined IC neurons so recorded as afferent, efferent, or convergent (afferent and efferent inputs) local circuit neurons (LCN). The capacity of right-sided MNS to modify IC activity in the induction of AF was determined before and after preemptive right (RCV)- vs. left (LCV)-sided VNS (15 Hz, 500 μs; 1.2× bradycardia threshold). Neuronal (n = 89) activity at baseline (0.11 ± 0.29 Hz) increased during MNS-induced AF (0.51 ± 1.30 Hz; P < 0.001). Convergent LCNs were preferentially activated by MNS. Preemptive RCV reduced MNS-induced changes in LCN activity (by 70%) while mitigating MNS-induced AF (by 75%). Preemptive LCV reduced LCN activity by 60% while mitigating AF potential by 40%. IC neuronal synchrony increased during neurally induced AF, a local neural network response mitigated by preemptive VNS. These antiarrhythmic effects persisted post-VNS for, on average, 26 min. In conclusion, VNS preferentially targets convergent LCNs and their interactive coherence to mitigate the potential for neurally induced AF. The antiarrhythmic properties imposed by VNS exhibit memory. PMID:27591222

  19. Vagus nerve stimulation improves locomotion and neuronal populations in a model of Parkinson's disease.

    Science.gov (United States)

    Farrand, Ariana Q; Helke, Kristi L; Gregory, Rebecca A; Gooz, Monika; Hinson, Vanessa K; Boger, Heather A

    Parkinson's disease (PD) is a progressive, neurodegenerative disorder with no disease-modifying therapies, and symptomatic treatments are often limited by debilitating side effects. In PD, locus coeruleus noradrenergic (LC-NE) neurons degenerate prior to substantia nigra dopaminergic (SN-DA) neurons. Vagus nerve stimulation (VNS) activates LC neurons, and decreases pro-inflammatory markers, allowing improvement of LC targets, making it a potential PD therapeutic. To assess therapeutic potential of VNS in a PD model. To mimic the progression of PD degeneration, rats received a systemic injection of noradrenergic neurotoxin DSP-4, followed one week later by bilateral intrastriatal injection of dopaminergic neurotoxin 6-hydroxydopamine. At this time, a subset of rats also had vagus cuffs implanted. After eleven days, rats received a precise VNS regimen twice a day for ten days, and locomotion was measured during each afternoon session. Immediately following final stimulation, rats were euthanized, and left dorsal striatum, bilateral SN and LC were sectioned for immunohistochemical detection of monoaminergic neurons (tyrosine hydroxylase, TH), α-synuclein, astrocytes (GFAP) and microglia (Iba-1). VNS significantly increased locomotion of lesioned rats. VNS also resulted in increased expression of TH in striatum, SN, and LC; decreased SN α-synuclein expression; and decreased expression of glial markers in the SN and LC of lesioned rats. Additionally, saline-treated rats after VNS, had higher LC TH and lower SN Iba-1. Our findings of increased locomotion, beneficial effects on LC-NE and SN-DA neurons, decreased α-synuclein density in SN TH-positive neurons, and neuroinflammation suggest VNS has potential as a novel PD therapeutic. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Different Populations of Human Locus Ceruleus Neurons Contain Heavy Metals or Hyperphosphorylated Tau: Implications for Amyloid-β and Tau Pathology in Alzheimer's Disease.

    Science.gov (United States)

    Pamphlett, Roger; Kum Jew, Stephen

    2015-01-01

    A marked loss of locus ceruleus (LC) neurons is a striking pathological feature of Alzheimer's disease (AD). LC neurons are particularly prone to taking up circulating toxicants such as heavy metals, and hyperphosphorylated tau (tau(HYP)) appears early in these neurons. In an attempt to find out if both heavy metals and tau(HYP) could be damaging LC neurons, we looked in the LC neurons of 21 sporadic AD patients and 43 non-demented controls for the heavy metals mercury, bismuth, and silver using autometallography, and for tau(HYP) using AT8 immunostaining. Heavy metals or tau(HYP) were usually seen in separate LC neurons, and rarely co-existed within the same neuron. The number of heavy metal-containing LC neurons did not correlate with the number containing tau(HYP). Heavy metals therefore appear to occupy a mostly different population of LC neurons to those containing tau(HYP), indicating that the LC in AD is vulnerable to two different assaults. Reduced brain noradrenaline from LC damage is linked to amyloid-β deposition, and tau(HYP) in the LC may seed neurofibrillary tangles in other neurons. A model is described, incorporating the present findings, that proposes that the LC plays a part in both the amyloid-β and tau pathologies of AD.

  1. Semiphysiological versus Empirical Modelling of the Population Pharmacokinetics of Free and Total Cefazolin during Pregnancy

    Directory of Open Access Journals (Sweden)

    J. G. Coen van Hasselt

    2014-01-01

    Full Text Available This work describes a first population pharmacokinetic (PK model for free and total cefazolin during pregnancy, which can be used for dose regimen optimization. Secondly, analysis of PK studies in pregnant patients is challenging due to study design limitations. We therefore developed a semiphysiological modeling approach, which leveraged gestation-induced changes in creatinine clearance (CrCL into a population PK model. This model was then compared to the conventional empirical covariate model. First, a base two-compartmental PK model with a linear protein binding was developed. The empirical covariate model for gestational changes consisted of a linear relationship between CL and gestational age. The semiphysiological model was based on the base population PK model and a separately developed mixed-effect model for gestation-induced change in CrCL. Estimates for baseline clearance (CL were 0.119 L/min (RSE 58% and 0.142 L/min (RSE 44% for the empirical and semiphysiological models, respectively. Both models described the available PK data comparably well. However, as the semiphysiological model was based on prior knowledge of gestation-induced changes in renal function, this model may have improved predictive performance. This work demonstrates how a hybrid semiphysiological population PK approach may be of relevance in order to derive more informative inferences.

  2. Gene expression profiling of two distinct neuronal populations in the rodent spinal cord

    DEFF Research Database (Denmark)

    Ryge, Jesper; Westerdahl, Ann Charlotte; Alstøm, Preben

    2008-01-01

    Background: In the field of neuroscience microarray gene expression profiles on anatomically defined brain structures are being used increasingly to study both normal brain functions as well as pathological states. Fluorescent tracing techniques in brain tissue that identifies distinct neuronal p...

  3. Generalized rate-code model for neuron ensembles with finite populations

    International Nuclear Information System (INIS)

    Hasegawa, Hideo

    2007-01-01

    We have proposed a generalized Langevin-type rate-code model subjected to multiplicative noise, in order to study stationary and dynamical properties of an ensemble containing a finite number N of neurons. Calculations using the Fokker-Planck equation have shown that, owing to the multiplicative noise, our rate model yields various kinds of stationary non-Gaussian distributions such as Γ, inverse-Gaussian-like, and log-normal-like distributions, which have been experimentally observed. The dynamical properties of the rate model have been studied with the use of the augmented moment method (AMM), which was previously proposed by the author from a macroscopic point of view for finite-unit stochastic systems. In the AMM, the original N-dimensional stochastic differential equations (DEs) are transformed into three-dimensional deterministic DEs for the means and fluctuations of local and global variables. The dynamical responses of the neuron ensemble to pulse and sinusoidal inputs calculated by the AMM are in good agreement with those obtained by direct simulation. The synchronization in the neuronal ensemble is discussed. The variabilities of the firing rate and of the interspike interval are shown to increase with increasing magnitude of multiplicative noise, which may be a conceivable origin of the observed large variability in cortical neurons

  4. SEIR Model of Rumor Spreading in Online Social Network with Varying Total Population Size

    International Nuclear Information System (INIS)

    Dong Suyalatu; Deng Yan-Bin; Huang Yong-Chang

    2017-01-01

    Based on the infectious disease model with disease latency, this paper proposes a new model for the rumor spreading process in online social network. In this paper what we establish an SEIR rumor spreading model to describe the online social network with varying total number of users and user deactivation rate. We calculate the exact equilibrium points and reproduction number for this model. Furthermore, we perform the rumor spreading process in the online social network with increasing population size based on the original real world Facebook network. The simulation results indicate that the SEIR model of rumor spreading in online social network with changing total number of users can accurately reveal the inherent characteristics of rumor spreading process in online social network . (paper)

  5. SEIR Model of Rumor Spreading in Online Social Network with Varying Total Population Size

    Science.gov (United States)

    Dong, Suyalatu; Deng, Yan-Bin; Huang, Yong-Chang

    2017-10-01

    Based on the infectious disease model with disease latency, this paper proposes a new model for the rumor spreading process in online social network. In this paper what we establish an SEIR rumor spreading model to describe the online social network with varying total number of users and user deactivation rate. We calculate the exact equilibrium points and reproduction number for this model. Furthermore, we perform the rumor spreading process in the online social network with increasing population size based on the original real world Facebook network. The simulation results indicate that the SEIR model of rumor spreading in online social network with changing total number of users can accurately reveal the inherent characteristics of rumor spreading process in online social network. Supported by National Natural Science Foundation of China under Grant Nos. 11275017 and 11173028

  6. Study of GABAergic extra-synaptic tonic inhibition in single neurons and neural populations by traversing neural scales: application to propofol-induced anaesthesia.

    Science.gov (United States)

    Hutt, Axel; Buhry, Laure

    2014-12-01

    Anaesthetic agents are known to affect extra-synaptic GABAergic receptors, which induce tonic inhibitory currents. Since these receptors are very sensitive to small concentrations of agents, they are supposed to play an important role in the underlying neural mechanism of general anaesthesia. Moreover anaesthetic agents modulate the encephalographic activity (EEG) of subjects and hence show an effect on neural populations. To understand better the tonic inhibition effect in single neurons on neural populations and hence how it affects the EEG, the work considers single neurons and neural populations in a steady-state and studies numerically and analytically the modulation of their firing rate and nonlinear gain with respect to different levels of tonic inhibition. We consider populations of both type-I (Leaky Integrate-and-Fire model) and type-II (Morris-Lecar model) neurons. To bridge the single neuron description to the population description analytically, a recently proposed statistical approach is employed which allows to derive new analytical expressions for the population firing rate for type-I neurons. In addition, the work shows the derivation of a novel transfer function for type-I neurons as considered in neural mass models and studies briefly the interaction of synaptic and extra-synaptic inhibition. We reveal a strong subtractive and divisive effect of tonic inhibition in type-I neurons, i.e. a shift of the firing rate to higher excitation levels accompanied by a change of the nonlinear gain. Tonic inhibition shortens the excitation window of type-II neurons and their populations while maintaining the nonlinear gain. The gained results are interpreted in the context of recent experimental findings under propofol-induced anaesthesia.

  7. Production of high quality brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) RNA from isolated populations of rat spinal cord motor neurons obtained by Laser Capture Microdissection (LCM).

    Science.gov (United States)

    Mehta, Prachi; Premkumar, Brian; Morris, Renée

    2016-08-03

    The mammalian central nervous system (CNS) is composed of multiple cellular elements, making it challenging to segregate one particular cell type to study their gene expression profile. For instance, as motor neurons represent only 5-10% of the total cell population of the spinal cord, meaningful transcriptional analysis on these neurons is almost impossible to achieve from homogenized spinal cord tissue. A major challenge faced by scientists is to obtain good quality RNA from small amounts of starting material. In this paper, we used Laser Capture Microdissection (LCM) techniques to identify and isolate spinal cord motor neurons. The present analysis revealed that perfusion with paraformaldehyde (PFA) does not alter RNA quality. RNA integrity numbers (RINs) of tissue samples from rubrospinal tract (RST)-transected, intact spinal cord or from whole spinal cord homogenate were all above 8, which indicates intact, high-quality RNA. Levels of mRNA for brain-derived neurotrophic factor (BDNF) or for its tropomyosin receptor kinase B (TrkB) were not affected by rubrospinal tract (RST) transection, a surgical procedure that deprive motor neurons from one of their main supraspinal input. The isolation of pure populations of neurons with LCM techniques allows for robust transcriptional characterization that cannot be achieved with spinal cord homogenates. Such preparations of pure population of motor neurons will provide valuable tools to advance our understanding of the molecular mechanisms underlying spinal cord injury and neuromuscular diseases. In the near future, LCM techniques might be instrumental to the success of gene therapy for these debilitating conditions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Total Body Capacitance for Estimating Human Basal Metabolic Rate in an Egyptian Population

    Science.gov (United States)

    M. Abdel-Mageed, Samir; I. Mohamed, Ehab

    2016-01-01

    Determining basal metabolic rate (BMR) is important for estimating total energy needs in the human being yet, concerns have been raised regarding the suitability of sex-specific equations based on age and weight for its calculation on an individual or population basis. It has been shown that body cell mass (BCM) is the body compartment responsible for BMR. The objectives of this study were to investigate the relationship between total body capacitance (TBC), which is considered as an expression for BCM, and BMR and to develop a formula for calculating BMR in comparison with widely used equations. Fifty healthy nonsmoking male volunteers [mean age (± SD): 24.93 ± 4.15 year and body mass index (BMI): 25.63 ± 3.59 kg/m2] and an equal number of healthy nonsmoking females matched for age and BMI were recruited for the study. TBC and BMR were measured for all participants using octopolar bioelectric impedance analysis and indirect calorimetry techniques, respectively. A significant regressing equation based on the covariates: sex, weight, and TBC for estimating BMR was derived (R=0.96, SEE=48.59 kcal, and P<0.0001), which will be useful for nutritional and health status assessment for both individuals and populations. PMID:27127453

  9. Voltage-Dependent Rhythmogenic Property of Respiratory Pre-Bötzinger Complex Glutamatergic, Dbx1-Derived, and Somatostatin-Expressing Neuron Populations Revealed by Graded Optogenetic Inhibition.

    Science.gov (United States)

    Koizumi, Hidehiko; Mosher, Bryan; Tariq, Mohammad F; Zhang, Ruli; Koshiya, Naohiro; Smith, Jeffrey C

    2016-01-01

    The rhythm of breathing in mammals, originating within the brainstem pre-Bötzinger complex (pre-BötC), is presumed to be generated by glutamatergic neurons, but this has not been directly demonstrated. Additionally, developmental expression of the transcription factor Dbx1 or expression of the neuropeptide somatostatin (Sst), has been proposed as a marker for the rhythmogenic pre-BötC glutamatergic neurons, but it is unknown whether these other two phenotypically defined neuronal populations are functionally equivalent to glutamatergic neurons with regard to rhythm generation. To address these problems, we comparatively investigated, by optogenetic approaches, the roles of pre-BötC glutamatergic, Dbx1-derived, and Sst-expressing neurons in respiratory rhythm generation in neonatal transgenic mouse medullary slices in vitro and also more intact adult perfused brainstem-spinal cord preparations in situ. We established three different triple-transgenic mouse lines with Cre-driven Archaerhodopsin-3 (Arch) expression selectively in glutamatergic, Dbx1-derived, or Sst-expressing neurons for targeted photoinhibition. In each line, we identified subpopulations of rhythmically active, Arch-expressing pre-BötC inspiratory neurons by whole-cell recordings in medullary slice preparations in vitro, and established that Arch-mediated hyperpolarization of these inspiratory neurons was laser power dependent with equal efficacy. By site- and population-specific graded photoinhibition, we then demonstrated that inspiratory frequency was reduced by each population with the same neuronal voltage-dependent frequency control mechanism in each state of the respiratory network examined. We infer that enough of the rhythmogenic pre-BötC glutamatergic neurons also have the Dbx1 and Sst expression phenotypes, and thus all three phenotypes share the same voltage-dependent frequency control property.

  10. Voltage-Dependent Rhythmogenic Property of Respiratory Pre-Bötzinger Complex Glutamatergic, Dbx1-Derived, and Somatostatin-Expressing Neuron Populations Revealed by Graded Optogenetic Inhibition123

    Science.gov (United States)

    Koizumi, Hidehiko; Mosher, Bryan; Tariq, Mohammad F.; Zhang, Ruli

    2016-01-01

    Abstract The rhythm of breathing in mammals, originating within the brainstem pre-Bötzinger complex (pre-BötC), is presumed to be generated by glutamatergic neurons, but this has not been directly demonstrated. Additionally, developmental expression of the transcription factor Dbx1 or expression of the neuropeptide somatostatin (Sst), has been proposed as a marker for the rhythmogenic pre-BötC glutamatergic neurons, but it is unknown whether these other two phenotypically defined neuronal populations are functionally equivalent to glutamatergic neurons with regard to rhythm generation. To address these problems, we comparatively investigated, by optogenetic approaches, the roles of pre-BötC glutamatergic, Dbx1-derived, and Sst-expressing neurons in respiratory rhythm generation in neonatal transgenic mouse medullary slices in vitro and also more intact adult perfused brainstem-spinal cord preparations in situ. We established three different triple-transgenic mouse lines with Cre-driven Archaerhodopsin-3 (Arch) expression selectively in glutamatergic, Dbx1-derived, or Sst-expressing neurons for targeted photoinhibition. In each line, we identified subpopulations of rhythmically active, Arch-expressing pre-BötC inspiratory neurons by whole-cell recordings in medullary slice preparations in vitro, and established that Arch-mediated hyperpolarization of these inspiratory neurons was laser power dependent with equal efficacy. By site- and population-specific graded photoinhibition, we then demonstrated that inspiratory frequency was reduced by each population with the same neuronal voltage-dependent frequency control mechanism in each state of the respiratory network examined. We infer that enough of the rhythmogenic pre-BötC glutamatergic neurons also have the Dbx1 and Sst expression phenotypes, and thus all three phenotypes share the same voltage-dependent frequency control property. PMID:27275007

  11. Immunotoxic destruction of distinct catecholaminergic neuron populations disrupts the reproductive response to glucoprivation in female rats.

    Science.gov (United States)

    I'Anson, Helen; Sundling, Lois A; Roland, Shannon M; Ritter, Sue

    2003-10-01

    We tested the hypothesis that hindbrain catecholamine (norepinephrine or epinephrine) neurons, in addition to their essential role in glucoprivic feeding, are responsible for suppressing estrous cycles during chronic glucoprivation. Normally cycling female rats were given bilateral injections of the retrogradely transported ribosomal toxin, saporin, conjugated to monoclonal dopamine beta-hydroxylase antibody (DSAP) into the paraventricular nucleus (PVN) of the hypothalamus to selectively destroy norepinephrine and epinephrine neurons projecting to the PVN. Controls were injected with unconjugated saporin. After recovery, we assessed the lesion effects on estrous cyclicity under basal conditions and found that DSAP did not alter estrous cycle length. Subsequently, we examined effects of chronic 2-deoxy-d-glucose-induced glucoprivation on cycle length. After two normal 4- to 5-d cycles, rats were injected with 2-deoxy-d-glucose (200 mg/kg every 6 h for 72 h) beginning 24 h after detection of estrus. Chronic glucoprivation increased cycle length in seven of eight unconjugated saporin rats but in only one of eight DSAP rats. Immunohistochemical results confirmed loss of dopamine beta-hydroxylase immunoreactivity in PVN. Thus, hindbrain catecholamine neurons with projections to the PVN are required for inhibition of reproductive function during chronic glucose deficit but are not required for normal estrous cyclicity when metabolic fuels are in abundance.

  12. Beverage Consumption Habits in Italian Population: Association with Total Water Intake and Energy Intake

    Directory of Open Access Journals (Sweden)

    Lorenza Mistura

    2016-10-01

    Full Text Available Background: The aim of this study was to investigate total water intake (TWI from water, beverages and foods among Italian adults and the elderly. Methods: Data of 2607 adults and the elderly, aged 18–75 years from the last national food consumption survey, INRAN-SCAI 2005-06, were used to evaluate the TWI. The INRAN-SCAI 2005-06 survey was conducted on a representative sample of 3323 individuals aged 0.1 to 97.7 years. A 3-day semi-structured diary was used for participants to record the consumption of all foods, beverages and nutritional supplements. Results: On average, TWI was 1.8 L for men and 1.7 L for women. More than 75% of women and 90% of men did not comply with the European Food Safety Authority (EFSA Adequate Intake. The contribution of beverages to the total energy intake (EI was 6% for the total sample. Water was the most consumed beverage, followed by alcoholic beverages for men and hot beverages for women. Conclusion: According to the present results, adults and elderly Italians do not reach the adequate intake for water as suggested by the EFSA and by the national reference level of nutrient and energy intake. Data on water consumption should also be analyzed in single socio-demographic groups in order to identify sub-groups of the population that need more attention and to plan more targeted interventions.

  13. Total phenolic content, radical scavenging properties, and essential oil composition of Origanum species from different populations.

    Science.gov (United States)

    Dambolena, José S; Zunino, María P; Lucini, Enrique I; Olmedo, Rubén; Banchio, Erika; Bima, Paula J; Zygadlo, Julio A

    2010-01-27

    The aim of this work was to compare the antiradical activity, total phenol content (TPC), and essential oil composition of Origanum vulgare spp. virens, Origanum x applii, Origanum x majoricum, and O. vulgare spp. vulgare cultivated in Argentina in different localities. The experiment was conducted in the research station of La Consulta (INTA-Mendoza), the research station of Santa Lucia (INTA-San Juan), and Agronomy Faculty of National University of La Pampa, from 2007 to 2008. The composition of the essential oils of oregano populations was independent of cultivation conditions. In total, 39 compounds were identified in essential oils of oregano from Argentina by means of GC-MS. Thymol and trans-sabinene hydrate were the most prominent compounds, followed by gamma-terpinene, terpinen-4-ol, and alpha-terpinene. O. vulgare vulgare is the only Origanum studied which is rich in gamma-terpinene. Among tested oregano, O. x majoricum showed the highest essential oil content, 3.9 mg g(-1) dry matter. The plant extract of O. x majoricum had greater total phenol content values, 19.36 mg/g dry weight, than the rest of oregano studied. To find relationships among TPC, free radical scavenging activity (FRSA), and climate variables, canonical correlations were calculated. The results obtained allow us to conclude that 70% of the TPC and FRSA variability can be explained by the climate variables (R(2) = 0.70; p = 8.3 x 10(-6)), the temperature being the most important climatic variable.

  14. Integration of silicon-based neural probes and micro-drive arrays for chronic recording of large populations of neurons in behaving animals.

    Science.gov (United States)

    Michon, Frédéric; Aarts, Arno; Holzhammer, Tobias; Ruther, Patrick; Borghs, Gustaaf; McNaughton, Bruce; Kloosterman, Fabian

    2016-08-01

    Understanding how neuronal assemblies underlie cognitive function is a fundamental question in system neuroscience. It poses the technical challenge to monitor the activity of populations of neurons, potentially widely separated, in relation to behaviour. In this paper, we present a new system which aims at simultaneously recording from a large population of neurons from multiple separated brain regions in freely behaving animals. The concept of the new device is to combine the benefits of two existing electrophysiological techniques, i.e. the flexibility and modularity of micro-drive arrays and the high sampling ability of electrode-dense silicon probes. Newly engineered long bendable silicon probes were integrated into a micro-drive array. The resulting device can carry up to 16 independently movable silicon probes, each carrying 16 recording sites. Populations of neurons were recorded simultaneously in multiple cortical and/or hippocampal sites in two freely behaving implanted rats. Current approaches to monitor neuronal activity either allow to flexibly record from multiple widely separated brain regions (micro-drive arrays) but with a limited sampling density or to provide denser sampling at the expense of a flexible placement in multiple brain regions (neural probes). By combining these two approaches and their benefits, we present an alternative solution for flexible and simultaneous recordings from widely distributed populations of neurons in freely behaving rats.

  15. Allogeneic blood transfusion and prognosis following total hip replacement: a population-based follow up study

    DEFF Research Database (Denmark)

    Pedersen, Alma B; Mehnert, Frank; Overgaard, Søren

    2009-01-01

    BACKGROUND: Allogeneic red blood cell transfusion is frequently used in total hip replacement surgery (THR). However, data on the prognosis of transfused patients are sparse. In this study we compared the risk of complications following THR in transfused and non-transfused patients. METHODS......: A population-based follow-up study was performed using data from medical databases in Denmark. We identified 28,087 primary THR procedures performed from 1999 to 2007, from which we computed a propensity score for red blood cell transfusion based on detailed data on patient-, procedure-, and hospital......-related characteristics. We were able to match 2,254 transfused with 2,254 non-transfused THR patients using the propensity score. RESULTS: Of the 28,087 THR patients, 9,063 (32.3%) received at least one red blood cell transfusion within 8 days of surgery. Transfused patients had higher 90-day mortality compared...

  16. Evaluation of the contribution of smoking to total blood polonium-210 in Saudi population

    Energy Technology Data Exchange (ETDEWEB)

    Shabana, E.I. E-mail: eshabana@kacst.edu.sa; Elaziz, M.A. Abd; Al-Arifi, M.N.; Al-Dhawailie, A.A.; Al-Bokari, M.M-A

    2000-01-01

    A preliminary study of {sup 210}Po concentrations in the blood of some smokers and nonsmokers is presented in order to evaluate the contribution of smoking to total blood {sup 210}Po in Saudi population. Blood samples were collected from 30 volunteers and analyzed by high resolution {alpha}-spectrometry using a radiochemical technique. The technique is based on the separation of polonium from other components of the sample by wet ashing with an HNO{sub 3}/H{sub 2}O{sub 2} oxidizing mixture and spontaneous deposition on a silver disc under the relevant conditions for {alpha}-particle counting. The results indicated that a significant fraction (about 30%) of blood {sup 210}Po is related to smoking.

  17. Song tutoring in presinging zebra finch juveniles biases a small population of higher-order song-selective neurons toward the tutor song.

    Science.gov (United States)

    Adret, Patrice; Meliza, C Daniel; Margoliash, Daniel

    2012-10-01

    We explored physiological changes correlated with song tutoring by recording the responses of caudal nidopallium neurons of zebra finches aged P21-P24 (days post hatching) to a broad spectrum of natural and synthetic stimuli. Those birds raised with their fathers tended to show behavioral evidence of song memorization but not of singing; thus auditory responses were not confounded by the birds' own vocalizations. In study 1, 37 of 158 neurons (23%) in 17 of 22 tutored and untutored birds were selective for only 1 of 10 stimuli comprising broadband signals, early juvenile songs and calls, female calls, and adult songs. Approximately 30% of the selective neurons (12/37 neurons in 9 birds) were selective for adult conspecific songs. All these were found in the song system nuclei HVC and paraHVC. Of 122 neurons (17 birds) in tutored birds, all of the conspecific song-selective neurons (8 neurons in 6 birds) were selective for the adult tutor song; none was selective for unfamiliar song. In study 2 with a different sampling strategy, we found that 11 of 12 song-selective neurons in 6 of 7 birds preferred the tutor song; none preferred unfamiliar or familiar conspecific songs. Most of these neurons were found in caudal lateral nidopallium (NCL) below HVC. Thus by the time a bird begins to sing, there are small numbers of tutor song-selective neurons distributed in several forebrain regions. We hypothesize that a small population of higher-order auditory neurons is innately selective for complex features of behaviorally relevant stimuli and these responses are modified by specific perceptual/social experience during development.

  18. Dietary acrylamide exposure of the French population: results of the second French Total Diet Study.

    Science.gov (United States)

    Sirot, Véronique; Hommet, Frédéric; Tard, Alexandra; Leblanc, Jean-Charles

    2012-03-01

    Acrylamide is a heat-induced carcinogen compound that is found in some foods consequently to cooking or other thermal processes. In the second French Total Diet Study (TDS), acrylamide was analysed in 192 food samples collected in mainland France to be representative of the population diet and prepared "as consumed". Highest mean concentrations were found in potato chips/crisps (954 μg/kg), French fries and other fried potatoes (724 μg/kg), and salted biscuits other than potato chips (697 μg/kg). Exposure of general adult and child populations was assessed by combining analytical results with national consumption data. Mean acrylamide exposure was assessed to be 0.43±0.33 μg/kg of body weight (bw) per day for adults and 0.69±0.58 μg/kg bw/day for children. Although the exposure assessed is lower than in previous evaluations, the calculated margins of exposure, based on benchmark dose limits defined for carcinogenic effects, remain very low especially for young children (below 100 at the 95th percentile of exposure), indicating a health concern. It is therefore advisable to continue efforts in order to reduce dietary exposure to acrylamide. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Improvement in quality of lifesix months after primary total hip arthroplasty in a Pakistani population.

    Science.gov (United States)

    Zubairi, Akbar Jaleel; Bin Mahmood, Syed Usman; Ali, Moiz; Noordin, Shahryar

    2016-10-01

    This prospective, cohort study was carried out to assess the improvement in quality of life of patients undergoing elective primary total hip arthroplasty (THA). It was conducted at the orthopaedic department of the Aga Khan University Hospital, Karachi, from June 2014 to May 2015, and comprised patients who had undergone THA. A total of 89 patients having a mean age of 41.5±12.0 years with a baseline core outcomes measure index (COMI)-hip score of > 3.5 were included. A decrease in COMI-hip score by >3 points six months post-operatively was considered improvement in quality of life. Patient satisfaction with restriction to squatting was assessed separately. The mean reduction in COMI-hip was 4.9±1.3 with 83(93%) patients experiencing significant improvement in quality of life. Age >50 years and American Society of Anaesthesiologists (ASA) level >III was significantly associated with no improvement in quality of life. Most patients were satisfied with their disability to squat irrespective of COMI-hip score. THA was found to be associated with significant improvement in quality of life and COMI-hip score was applicable in our population despite its inability to assess disability with restriction in squatting.

  20. Association of Coffee Consumption With Total and Cause-Specific Mortality Among Nonwhite Populations.

    Science.gov (United States)

    Park, Song-Yi; Freedman, Neal D; Haiman, Christopher A; Le Marchand, Loïc; Wilkens, Lynne R; Setiawan, Veronica Wendy

    2017-08-15

    Coffee consumption has been associated with reduced risk for death in prospective cohort studies; however, data in nonwhites are sparse. To examine the association of coffee consumption with risk for total and cause-specific death. The MEC (Multiethnic Cohort), a prospective population-based cohort study established between 1993 and 1996. Hawaii and Los Angeles, California. 185 855 African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites aged 45 to 75 years at recruitment. Outcomes were total and cause-specific mortality between 1993 and 2012. Coffee intake was assessed at baseline by means of a validated food-frequency questionnaire. 58 397 participants died during 3 195 484 person-years of follow-up (average follow-up, 16.2 years). Compared with drinking no coffee, coffee consumption was associated with lower total mortality after adjustment for smoking and other potential confounders (1 cup per day: hazard ratio [HR], 0.88 [95% CI, 0.85 to 0.91]; 2 to 3 cups per day: HR, 0.82 [CI, 0.79 to 0.86]; ≥4 cups per day: HR, 0.82 [CI, 0.78 to 0.87]; P for trend coffee. Significant inverse associations were observed in 4 ethnic groups; the association in Native Hawaiians did not reach statistical significance. Inverse associations were also seen in never-smokers, younger participants (coffee was associated with lower risk for death in African Americans, Japanese Americans, Latinos, and whites. National Cancer Institute.

  1. Preprotachykinin A is expressed by a distinct population of excitatory neurons in the mouse superficial spinal dorsal horn including cells that respond to noxious and pruritic stimuli.

    Science.gov (United States)

    Gutierrez-Mecinas, Maria; Bell, Andrew M; Marin, Alina; Taylor, Rebecca; Boyle, Kieran A; Furuta, Takahiro; Watanabe, Masahiko; Polgár, Erika; Todd, Andrew J

    2017-03-01

    The superficial dorsal horn, which is the main target for nociceptive and pruritoceptive primary afferents, contains a high density of excitatory interneurons. Our understanding of their roles in somatosensory processing has been restricted by the difficulty of distinguishing functional populations among these cells. We recently defined 3 nonoverlapping populations among the excitatory neurons, based on the expression of neurotensin, neurokinin B, and gastrin-releasing peptide. Here we identify and characterise another population: neurons that express the tachykinin peptide substance P. We show with immunocytochemistry that its precursor protein (preprotachykinin A, PPTA) can be detected in ∼14% of lamina I-II neurons, and these are concentrated in the outer part of lamina II. Over 80% of the PPTA-positive cells lack the transcription factor Pax2 (which determines an inhibitory phenotype), and these account for ∼15% of the excitatory neurons in this region. They are different from the neurotensin, neurokinin B, or gastrin-releasing peptide neurons, although many of them contain somatostatin, which is widely expressed among superficial dorsal horn excitatory interneurons. We show that many of these cells respond to noxious thermal and mechanical stimuli and to intradermal injection of pruritogens. Finally, we demonstrate that these cells can also be identified in a knock-in Cre mouse line (Tac1), although our findings suggest that there is an additional population of neurons that transiently express PPTA. This population of substance P-expressing excitatory neurons is likely to play an important role in the transmission of signals that are perceived as pain and itch.

  2. Morphological changes in different populations of bladder afferent neurons detected by herpes simplex virus (HSV) vectors with cell-type-specific promoters in mice with spinal cord injury.

    Science.gov (United States)

    Shimizu, Nobutaka; Doyal, Mark F; Goins, William F; Kadekawa, Katsumi; Wada, Naoki; Kanai, Anthony J; de Groat, William C; Hirayama, Akihide; Uemura, Hirotsugu; Glorioso, Joseph C; Yoshimura, Naoki

    2017-11-19

    Functional and morphological changes in C-fiber bladder afferent pathways are reportedly involved in neurogenic detrusor overactivity (NDO) after spinal cord injury (SCI). This study examined the morphological changes in different populations of bladder afferent neurons after SCI using replication-defective herpes simplex virus (HSV) vectors encoding the mCherry reporter driven by neuronal cell-type-specific promoters. Spinal intact (SI) and SCI mice were injected into the bladder wall with HSV mCherry vectors driven by the cytomegalovirus (CMV) promoter, CGRP promoter, TRPV1 promoter or neurofilament 200 (NF200) promoter. Two weeks after vector inoculation into the bladder wall, L1 and L6 dorsal root ganglia (DRG) were removed bilaterally for immunofluorescent staining using anti-mCherry antibody. The number of CMV promoter vector-labeled neurons was not altered after SCI. The number of CGRP and TRPV1 promoter vector-labeled neurons was significantly increased whereas the number of NF200 vector-labeled neurons was decreased in L6 DRG after SCI. The median size of CGRP promoter-labeled C-fiber neurons was increased from 247.0 in SI mice to 271.3μm 2 in SCI mice whereas the median cell size of TRPV1 promoter vector-labeled neurons was decreased from 245.2 in SI mice to 216.5μm 2 in SCI mice. CGRP and TRPV1 mRNA levels of laser-captured bladder afferent neurons labeled with Fast Blue were significantly increased in SCI mice compared to SI mice. Thus, using a novel HSV vector-mediated neuronal labeling technique, we found that SCI induces expansion of the CGRP- and TRPV1-expressing C-fiber cell population, which could contribute to C-fiber afferent hyperexcitability and NDO after SCI. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Hippocampal neuron populations are reduced in vervet monkeys with fetal alcohol exposure

    DEFF Research Database (Denmark)

    Burke, Mark W; Ptito, Maurice; Ervin, Frank R

    2015-01-01

    of pregnancy. Here, we report significant numerical reductions in the principal hippocampal neurons of fetal alcohol-exposed (FAE) offspring, as compared to age-matched, similarly housed conspecifics with isocaloric sucrose exposure. These deficits, particularly marked in CA1 and CA3, are present neonatally......Prenatal exposure to beverage alcohol is a major cause of mild mental retardation and developmental delay. In nonendangered alcohol-preferring vervet monkeys, we modeled the most common nondysmorphic form of fetal alcohol syndrome disorder with voluntary drinking during the third trimester...... and persist through infancy (5 months) and juvenile (2 years) stages. Although the volumes of hippocampal subdivisions in FAE animals are not atypical at birth, by age 2, they are only 65-70% of those estimated in age-matched controls. These data suggest that moderate, naturalistic alcohol consumption during...

  4. National Incidence of Patient Safety Indicators in the Total Hip Arthroplasty Population.

    Science.gov (United States)

    Tanenbaum, Joseph E; Knapik, Derrick M; Wera, Glenn D; Fitzgerald, Steven J

    2017-09-01

    The Centers for Medicare & Medicaid Services use the incidence of patient safety indicators (PSIs) to determine health care value and hospital reimbursement. The national incidence of PSI has not been quantified in the total hip arthroplasty (THA) population, and it is unknown if patient insurance status is associated with PSI incidence after THA. All patients in the Nationwide Inpatient Sample (NIS) who underwent THA in 2013 were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. The incidence of PSI was determined using the International Classification of Diseases, Ninth Revision, diagnosis code algorithms published by the Centers for Medicare & Medicaid Services and the Agency for Healthcare Research and Quality. The association of insurance status and the incidence of PSI during the inpatient episode was determined by comparing privately insured and Medicare patients with Medicaid/self-pay patients using a logistic regression model that controlled for patient demographics, patient comorbidities, and hospital characteristics. In 2013, the NIS included 68,644 hospitalizations with primary THA performed during the inpatient episode. During this period, 429 surgically relevant PSI were recorded in the NIS. The estimated national incidence rate of PSI after primary THA was 0.63%. In our secondary analysis, the privately insured cohort had significantly lower odds of experiencing one or more PSIs relative to the Medicaid/self-pay cohort (odds ratio, 0.47; 95% confidence interval, 0.29-0.76). The national incidence of PSI among THA patients is relatively low. However, primary insurance status is associated with the incidence of one or more PSIs after THA. As value-based payment becomes more widely adopted in the United States, quality benchmarks and penalty thresholds need to account for these differences in risk-adjustment models to promote and maintain access to care in the underinsured population. Copyright

  5. A decrease in total bilirubin predicted hyper-LDL cholesterolemia in a health screening population.

    Science.gov (United States)

    Oda, Eiji

    2014-08-01

    To investigate cross-sectional and longitudinal associations between serum total bilirubin (TB) and LDL cholesterol. It is a retrospective observational study. Cross-sectional and longitudinal associations between TB and hyper-LDL cholesterolemia were investigated in a health screening population. Odds ratios (ORs) of coexisting hyper-LDL cholesterolemia for TB were calculated in 3,866 subjects, Spearman's correlation coefficients between baseline TB and LDL cholesterol at baseline and after 4 years were calculated in 1,735 subjects who did not use antihyperlipidemic drugs and hazard ratios (HRs) of incident hyper-LDL cholesterolemia for TB were calculated in 1,992 followed subjects. The ORs (p values) of coexisting hyper-LDL cholesterolemia for each 1 SD increase in TB was 1.04 (0.998) adjusted for sex, age, smoking, LDL cholesterol and other confounders. Spearman's correlation coefficients (p values) between baseline TB and LDL cholesterol at baseline and after 4 years and changes in LDL cholesterol were -0.026 (0.271), -0.078 (0.001) and -0.062 (0.010), respectively. Among 1,992 followed subjects, 481 developed hyper-LDL cholesterolemia during 4 years (60.4 per 1,000 person-years). The HRs (95% confidence intervals; p values) of incident hyper-LDL cholesterolemia for each 1 SD increase in TB was 0.86 (0.77-0.96; 0.006) adjusted for sex, age, smoking, LDL cholesterol, body mass index, triglycerides, HDL cholesterol, fasting glucose and other confounders. The quintiles of TB were significantly associated with the incident hyper-LDL cholesterolemia adjusted for the above covariates (p for trend = 0.008). A decrease in TB predicted incident hyper-LDL cholesterolemia in a health screening population. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. The expression of Toll-like receptor 4, 7 and co-receptors in neurochemical sub-populations of rat trigeminal ganglion sensory neurons.

    Science.gov (United States)

    Helley, M P; Abate, W; Jackson, S K; Bennett, J H; Thompson, S W N

    2015-12-03

    The recent discovery that mammalian nociceptors express Toll-like receptors (TLRs) has raised the possibility that these cells directly detect and respond to pathogens with implications for either direct nociceptor activation or sensitization. A range of neuronal TLRs have been identified, however a detailed description regarding the distribution of expression of these receptors within sub-populations of sensory neurons is lacking. There is also some debate as to the composition of the TLR4 receptor complex on sensory neurons. Here we use a range of techniques to quantify the expression of TLR4, TLR7 and some associated molecules within neurochemically-identified sub-populations of trigeminal (TG) and dorsal root (DRG) ganglion sensory neurons. We also detail the pattern of expression and co-expression of two isoforms of lysophosphatidylcholine acyltransferase (LPCAT), a phospholipid remodeling enzyme previously shown to be involved in the lipopolysaccharide-dependent TLR4 response in monocytes, within sensory ganglia. Immunohistochemistry shows that both TLR4 and TLR7 preferentially co-localize with transient receptor potential vallinoid 1 (TRPV1) and purinergic receptor P2X ligand-gated ion channel 3 (P2X3), markers of nociceptor populations, within both TG and DRG. A gene expression profile shows that TG sensory neurons express a range of TLR-associated molecules. LPCAT1 is expressed by a proportion of both nociceptors and non-nociceptive neurons. LPCAT2 immunostaining is absent from neuronal profiles within both TG and DRG and is confined to non-neuronal cell types under naïve conditions. Together, our results show that nociceptors express the molecular machinery required to directly respond to pathogenic challenge independently from the innate immune system. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Subtype-Specific Genes that Characterize Subpopulations of Callosal Projection Neurons in Mouse Identify Molecularly Homologous Populations in Macaque Cortex.

    Science.gov (United States)

    Fame, Ryann M; Dehay, Colette; Kennedy, Henry; Macklis, Jeffrey D

    2017-03-01

    Callosal projection neurons (CPN) interconnect the neocortical hemispheres via the corpus callosum and are implicated in associative integration of multimodal information. CPN have undergone differential evolutionary elaboration, leading to increased diversity of cortical neurons-and more extensive and varied connections in neocortical gray and white matter-in primates compared with rodents. In mouse, distinct sets of genes are enriched in discrete subpopulations of CPN, indicating the molecular diversity of rodent CPN. Elements of rodent CPN functional and organizational diversity might thus be present in the further elaborated primate cortex. We address the hypothesis that genes controlling mouse CPN subtype diversity might reflect molecular patterns shared among mammals that arose prior to the divergence of rodents and primates. We find that, while early expression of the examined CPN-enriched genes, and postmigratory expression of these CPN-enriched genes in deep layers are highly conserved (e.g., Ptn, Nnmt, Cited2, Dkk3), in contrast, the examined genes expressed by superficial layer CPN show more variable levels of conservation (e.g., EphA3, Chn2). These results suggest that there has been evolutionarily differential retraction and elaboration of superficial layer CPN subpopulations between mouse and macaque, with independent derivation of novel populations in primates. Together, these data inform future studies regarding CPN subpopulations that are unique to primates and rodents, and indicate putative evolutionary relationships. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Neuroprotective Effect of Total and Sequential Extract of Scrophularia striata Boiss. in Rat Cerebellar Granule Neurons Following Glutamate- Induced Neurotoxicity: An In-vitro Study

    Science.gov (United States)

    Salavati, Parvin; Ramezani, Mina; Monsef-Esfahani, Hamid R; Hajiagha, Reza; Parsa, Maliheh; Tavajohi, Shoreh; Ostad, Seyed Nasser

    2013-01-01

    Neuroprotective effect of the extract from aerial parts of Scrophularia striata Boiss (Scrophulariaceae) was investigated against glutamate-induced neurotoxicity on cultured rat pups Cerebellar Granule Neurons (CGNs). CGNs from 8 days old Sprague-Dawley rat were prepared and cultured. The experiments were performed after 8 days in culture. The plant was collected from the northeastern part (Ruin region) of Iran and air-dried at room temperature. The total extract was prepared with maceration of prepared powder in ethanol 80% for three times. Sequential extracts were obtained using dried and powdered aerial parts with increasingly polar solvents: petroleum ether, chloroform, ethyl acetate and methanol 80% solution. Cultured cells were exposed to 125 μM of glutamate for 12 h following a 24 h of incubation with test fractions at concentration of 10 mcg/mL. Morphological assay was performed using invert light microscope after fixation and staining with haematoxylin. Neuronal viability was measured using MTT assay. Statistical analysis was done using SPSS software. One way analysis of variance (ANOVA) was performed by Tukey post-hoc test. Values were considered statistically significant when p-value ≤ 0.05. Results of this study showed a significant neuroprotective activity of high polarity methanolic fraction of aerial parts of Scrophularia striata against glutamate-induced neurotoxicity in a dosedependent manner. Treatment with 10 mcg/mL of the fractions showed the best result. PMID:24250613

  9. Neurons other than motor neurons in motor neuron disease.

    Science.gov (United States)

    Ruffoli, Riccardo; Biagioni, Francesca; Busceti, Carla L; Gaglione, Anderson; Ryskalin, Larisa; Gambardella, Stefano; Frati, Alessandro; Fornai, Francesco

    2017-11-01

    Amyotrophic lateral sclerosis (ALS) is typically defined by a loss of motor neurons in the central nervous system. Accordingly, morphological analysis for decades considered motor neurons (in the cortex, brainstem and spinal cord) as the neuronal population selectively involved in ALS. Similarly, this was considered the pathological marker to score disease severity ex vivo both in patients and experimental models. However, the concept of non-autonomous motor neuron death was used recently to indicate the need for additional cell types to produce motor neuron death in ALS. This means that motor neuron loss occurs only when they are connected with other cell types. This concept originally emphasized the need for resident glia as well as non-resident inflammatory cells. Nowadays, the additional role of neurons other than motor neurons emerged in the scenario to induce non-autonomous motor neuron death. In fact, in ALS neurons diverse from motor neurons are involved. These cells play multiple roles in ALS: (i) they participate in the chain of events to produce motor neuron loss; (ii) they may even degenerate more than and before motor neurons. In the present manuscript evidence about multi-neuronal involvement in ALS patients and experimental models is discussed. Specific sub-classes of neurons in the whole spinal cord are reported either to degenerate or to trigger neuronal degeneration, thus portraying ALS as a whole spinal cord disorder rather than a disease affecting motor neurons solely. This is associated with a novel concept in motor neuron disease which recruits abnormal mechanisms of cell to cell communication.

  10. Total Lignans of Schisandra chinensis Ameliorates Aβ1-42-Induced Neurodegeneration with Cognitive Impairment in Mice and Primary Mouse Neuronal Cells.

    Directory of Open Access Journals (Sweden)

    Xu Zhao

    Full Text Available Lignan compounds extracted from Schisandra chinensis (Turcz. Baill. have been reported to possess various biological activities, and have potential in the treatment of Alzheimer's disease. This study was designed to investigate the effects of total lignans of Schisandra chinensis (TLS on cognitive function and neurodegeneration in the model of AD induced by Aβ1-42 in vivo and in vitro. It was found that intragastric infusion with TLS (50 and 200 mg/kg to Aβ1-42-induced mice significantly increased the number of avoidances in the shuttle-box test and swimming time in the target quadrant in the Morris water maze test. TLS at dose of 200 mg/kg significantly restored the activities of total antioxidant capacity (T-AOC, as well as the level of malondialdehyde (MDA both in the hippocampus and cerebral cortex in mice. Results of histopathological examination indicated that TLS noticeably ameliorated the neurodegeneration in the hippocampus in mice. On the other hand, TLS (100 μM could protect the Aβ1-42-induced primary mouse neuronal cells by blocking the decrease of mitochondrial membrane potential (MMP, change the expressions of Bcl-2 (important regulator in the mitochondria apoptosis pathway. Moreover, TLS also decreased the activity of β-secretase 1 (BACE1, crucial protease contributes to the hydrolysis of amyloid precursor protein (APP, and inhibited the expression of JKN/p38, which involved in the MAPKs signaling pathways in both mice and primary mouse neuronal cells. In summary, TLS might protect against cognitive deficits and neurodegeneration by releasing the damage of oxidative stress, inhibiting the expression of BACE1 and the MAPKs inflammatory signaling pathways.

  11. Effects of kisspeptin1 on electrical activity of an extrahypothalamic population of gonadotropin-releasing hormone neurons in medaka (Oryzias latipes).

    Science.gov (United States)

    Zhao, Yali; Wayne, Nancy L

    2012-01-01

    Kisspeptin (product of the kiss1 gene) is the most potent known activator of the hypothalamo-pituitary-gonadal axis. Both kiss1 and the kisspeptin receptor are highly expressed in the hypothalamus of vertebrates, and low doses of kisspeptin have a robust and long-lasting stimulatory effect on the rate of action potential firing of hypophysiotropic gonadotropin releasing hormone-1 (GnRH1) neurons in mice. Fish have multiple populations of GnRH neurons distinguished by their location in the brain and the GnRH gene that they express. GnRH3 neurons located in the terminal nerve (TN) associated with the olfactory bulb are neuromodulatory and do not play a direct role in regulating pituitary-gonadal function. In medaka fish, the electrical activity of TN-GnRH3 neurons is modulated by visual cues from conspecifics, and is thought to act as a transmitter of information from the external environment to the central nervous system. TN-GnRH3 neurons also play a role in sexual motivation and arousal states, making them an important population of neurons to study for understanding coordination of complex behaviors. We investigated the role of kisspeptin in regulating electrical activity of TN-GnRH3 neurons in adult medaka. Using electrophysiology in an intact brain preparation, we show that a relatively brief treatment with 100 nM of kisspeptin had a long-lasting stimulatory effect on the electrical activity of an extrahypothalamic population of GnRH neurons. Dose-response analysis suggests a relatively narrow activational range of this neuropeptide. Further, blocking action potential firing with tetrodotoxin and blocking synaptic transmission with a low Ca(2+)/high Mg(2+) solution inhibited the stimulatory action of kisspeptin on electrical activity, indicating that kisspeptin is acting indirectly through synaptic regulation to excite TN-GnRH3 neurons. Our findings provide a new perspective on kisspeptin's broader functions within the central nervous system, through its

  12. Allogeneic blood transfusion and prognosis following total hip replacement: a population-based follow up study

    Directory of Open Access Journals (Sweden)

    Overgaard Soren

    2009-12-01

    Full Text Available Abstract Background Allogeneic red blood cell transfusion is frequently used in total hip replacement surgery (THR. However, data on the prognosis of transfused patients are sparse. In this study we compared the risk of complications following THR in transfused and non-transfused patients. Methods A population-based follow-up study was performed using data from medical databases in Denmark. We identified 28,087 primary THR procedures performed from 1999 to 2007, from which we computed a propensity score for red blood cell transfusion based on detailed data on patient-, procedure-, and hospital-related characteristics. We were able to match 2,254 transfused with 2,254 non-transfused THR patients using the propensity score. Results Of the 28,087 THR patients, 9,063 (32.3% received at least one red blood cell transfusion within 8 days of surgery. Transfused patients had higher 90-day mortality compared with matched non-transfused patients: the adjusted OR was 2.2 (95% confidence interval (CI: 1.2-3.8. Blood transfusion was also associated with increased odds of pneumonia (OR 2.1; CI: 1.2-3.8, whereas the associations with cardiovascular or cerebrovascular events (OR 1.4; CI: 0.9-2.2 and venous thromboembolism (OR 1.2; CI: 0.7-2.1 did not reach statistical significance. The adjusted OR of reoperation due to infection was 0.6 (CI: 0.1-2.9. Conclusions Red blood cell transfusion was associated with an adverse prognosis following primary THR, in particular with increased odds of death and pneumonia. Although the odds estimates may partly reflect unmeasured bias due to blood loss, they indicate the need for careful assessment of the risk versus benefit of transfusion even in relation to routine THR procedures.

  13. Daily total physical activity level and total cancer risk in men and women: results from a large-scale population-based cohort study in Japan.

    Science.gov (United States)

    Inoue, Manami; Yamamoto, Seiichiro; Kurahashi, Norie; Iwasaki, Motoki; Sasazuki, Shizuka; Tsugane, Shoichiro

    2008-08-15

    The impact of total physical activity level on cancer risk has not been fully clarified, particularly in non-Western, relatively lean populations. The authors prospectively examined the association between daily total physical activity (using a metabolic equivalents/day score) and subsequent cancer risk in the Japan Public Health Center-based Prospective Study. A total of 79,771 general-population Japanese men and women aged 45-74 years who responded to a questionnaire in 1995-1999 were followed for total cancer incidence (4,334 cases) through 2004. Compared with subjects in the lowest quartile, increased daily physical activity was associated with a significantly decreased risk of cancer in both sexes. In men, hazard ratios for the second, third, and highest quartiles were 1.00 (95% confidence interval (CI): 0.90, 1.11), 0.96 (95% CI: 0.86, 1.07), and 0.87 (95% CI: 0.78, 0.96), respectively (p for trend = 0.005); in women, hazard ratios were 0.93 (95% CI: 0.82, 1.05), 0.84 (95% CI: 0.73, 0.96), and 0.84 (95% CI: 0.73, 0.97), respectively (p for trend = 0.007). The decreased risk was more clearly observed in women than in men, especially among the elderly and those who regularly engaged in leisure-time sports or physical exercise. By site, decreased risks were observed for cancers of the colon, liver, and pancreas in men and for cancer of the stomach in women. Increased daily physical activity may be beneficial in preventing cancer in a relatively lean population.

  14. Targeting Neurotrophins to Specific Populations of Neurons: NGF, BDNF, and NT-3 and Their Relevance for Treatment of Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Kathleen M. Keefe

    2017-03-01

    Full Text Available Neurotrophins are a family of proteins that regulate neuronal survival, synaptic function, and neurotransmitter release, and elicit the plasticity and growth of axons within the adult central and peripheral nervous system. Since the 1950s, these factors have been extensively studied in traumatic injury models. Here we review several members of the classical family of neurotrophins, the receptors they bind to, and their contribution to axonal regeneration and sprouting of sensory and motor pathways after spinal cord injury (SCI. We focus on nerve growth factor (NGF, brain derived neurotrophic factor (BDNF, and neurotrophin-3 (NT-3, and their effects on populations of neurons within diverse spinal tracts. Understanding the cellular targets of neurotrophins and the responsiveness of specific neuronal populations will allow for the most efficient treatment strategies in the injured spinal cord.

  15. Targeting Neurotrophins to Specific Populations of Neurons: NGF, BDNF, and NT-3 and Their Relevance for Treatment of Spinal Cord Injury

    Science.gov (United States)

    Keefe, Kathleen M.; Sheikh, Imran S.; Smith, George M.

    2017-01-01

    Neurotrophins are a family of proteins that regulate neuronal survival, synaptic function, and neurotransmitter release, and elicit the plasticity and growth of axons within the adult central and peripheral nervous system. Since the 1950s, these factors have been extensively studied in traumatic injury models. Here we review several members of the classical family of neurotrophins, the receptors they bind to, and their contribution to axonal regeneration and sprouting of sensory and motor pathways after spinal cord injury (SCI). We focus on nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), and their effects on populations of neurons within diverse spinal tracts. Understanding the cellular targets of neurotrophins and the responsiveness of specific neuronal populations will allow for the most efficient treatment strategies in the injured spinal cord. PMID:28273811

  16. Targeting Neurotrophins to Specific Populations of Neurons: NGF, BDNF, and NT-3 and Their Relevance for Treatment of Spinal Cord Injury.

    Science.gov (United States)

    Keefe, Kathleen M; Sheikh, Imran S; Smith, George M

    2017-03-03

    Neurotrophins are a family of proteins that regulate neuronal survival, synaptic function, and neurotransmitter release, and elicit the plasticity and growth of axons within the adult central and peripheral nervous system. Since the 1950s, these factors have been extensively studied in traumatic injury models. Here we review several members of the classical family of neurotrophins, the receptors they bind to, and their contribution to axonal regeneration and sprouting of sensory and motor pathways after spinal cord injury (SCI). We focus on nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), and their effects on populations of neurons within diverse spinal tracts. Understanding the cellular targets of neurotrophins and the responsiveness of specific neuronal populations will allow for the most efficient treatment strategies in the injured spinal cord.

  17. Lateral hypothalamic thyrotropin-releasing hormone neurons: distribution and relationship to histochemically defined cell populations in the rat.

    Science.gov (United States)

    Horjales-Araujo, E; Hellysaz, A; Broberger, C

    2014-09-26

    The lateral hypothalamic area (LHA) constitutes a large component of the hypothalamus, and has been implicated in several aspects of motivated behavior. The LHA is of particular relevance to behavioral state control and the maintenance of arousal. Due to the cellular heterogeneity of this region, however, only some subpopulations of LHA cells have been properly anatomically characterized. Here, we have focused on cells expressing thyrotropin-releasing hormone (TRH), a peptide found in the LHA that has been implicated as a promoter of arousal. Immunofluorescence and in situ hybridization were used to map the LHA TRH population in the rat, and cells were observed to form a large ventral cluster that extended throughout almost the entire rostro-caudal axis of the hypothalamus. Almost no examples of coexistence were seen when sections were double-stained for TRH and markers of other LHA populations, including the peptides hypocretin/orexin, melanin-concentrating hormone and neurotensin. In the juxtaparaventricular area, however, a discrete group of TRH-immunoreactive cells were also stained with antisera against enkephalin and urocortin 3. Innervation from the metabolically sensitive hypothalamic arcuate nucleus was investigated by double-staining for peptide markers of the two centrally projecting groups of arcuate neurons, agouti gene-related peptide and α-melanocyte-stimulating hormone, respectively; both populations of terminals were observed forming close appositions on TRH cells in the LHA. The present study indicates that TRH-expressing cells form a unique population in the LHA that may serve as a link between metabolic signals and the generation of arousal. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Differential Activation of Fast-Spiking and Regular-Firing Neuron Populations During Movement and Reward in the Dorsal Medial Frontal Cortex

    Science.gov (United States)

    Insel, Nathan; Barnes, Carol A.

    2015-01-01

    The medial prefrontal cortex is thought to be important for guiding behavior according to an animal's expectations. Efforts to decode the region have focused not only on the question of what information it computes, but also how distinct circuit components become engaged during behavior. We find that the activity of regular-firing, putative projection neurons contains rich information about behavioral context and firing fields cluster around reward sites, while activity among putative inhibitory and fast-spiking neurons is most associated with movement and accompanying sensory stimulation. These dissociations were observed even between adjacent neurons with apparently reciprocal, inhibitory–excitatory connections. A smaller population of projection neurons with burst-firing patterns did not show clustered firing fields around rewards; these neurons, although heterogeneous, were generally less selective for behavioral context than regular-firing cells. The data suggest a network that tracks an animal's behavioral situation while, at the same time, regulating excitation levels to emphasize high valued positions. In this scenario, the function of fast-spiking inhibitory neurons is to constrain network output relative to incoming sensory flow. This scheme could serve as a bridge between abstract sensorimotor information and single-dimensional codes for value, providing a neural framework to generate expectations from behavioral state. PMID:24700585

  19. Adaptation in Coding by Large Populations of Neurons in the Retina

    Science.gov (United States)

    Ioffe, Mark L.

    A comprehensive theory of neural computation requires an understanding of the statistical properties of the neural population code. The focus of this work is the experimental study and theoretical analysis of the statistical properties of neural activity in the tiger salamander retina. This is an accessible yet complex system, for which we control the visual input and record from a substantial portion--greater than a half--of the ganglion cell population generating the spiking output. Our experiments probe adaptation of the retina to visual statistics: a central feature of sensory systems which have to adjust their limited dynamic range to a far larger space of possible inputs. In Chapter 1 we place our work in context with a brief overview of the relevant background. In Chapter 2 we describe the experimental methodology of recording from 100+ ganglion cells in the tiger salamander retina. In Chapter 3 we first present the measurements of adaptation of individual cells to changes in stimulation statistics and then investigate whether pairwise correlations in fluctuations of ganglion cell activity change across different stimulation conditions. We then transition to a study of the population-level probability distribution of the retinal response captured with maximum-entropy models. Convergence of the model inference is presented in Chapter 4. In Chapter 5 we first test the empirical presence of a phase transition in such models fitting the retinal response to different experimental conditions, and then proceed to develop other characterizations which are sensitive to complexity in the interaction matrix. This includes an analysis of the dynamics of sampling at finite temperature, which demonstrates a range of subtle attractor-like properties in the energy landscape. These are largely conserved when ambient illumination is varied 1000-fold, a result not necessarily apparent from the measured low-order statistics of the distribution. Our results form a consistent

  20. Different populations of parvalbumin- and calbindin-D28k-immunoreactive neurons contain GABA and accumulate 3H-D-aspartate in the dorsal horn of the rat spinal cord.

    Science.gov (United States)

    Antal, M; Polgár, E; Chalmers, J; Minson, J B; Llewellyn-Smith, I; Heizmann, C W; Somogyi, P

    1991-12-01

    The colocalization of parvalbumin (PV), calbindin-D28k (CaBP), GABA immunoreactivities, and the ability to accumulate 3H-D-aspartate selectively were investigated in neurons of laminae I-IV of the dorsal horn of the rat spinal cord. Following injection of 3H-D-aspartate into the basal dorsal horn (laminae IV-VI), perikarya selectively accumulating 3H-D-aspartate were detected in araldite embedded semithin sections by autoradiography, and consecutive semithin sections were treated to reveal PV, CaBP and GABA by postembedding immunocytochemistry. Perikarya accumulating 3H-D-aspartate were found exclusively in laminae I-III, and no labelled somata were found in deeper layers or in the intermediolateral column although the labelled amino acid clearly spread to these regions. More than half of the labelled cells were localized in lamina II. In this layer, 16.4% of 3H-D-aspartate-labelled perikarya were also stained for CaBP. In contrast to CaBP, PV or GABA was never detected in neurons accumulating 3H-D-aspartate. A high proportion of PV-immunoreactive perikarya were also stained for GABA in laminae II and III (70.0% and 61.2% respectively). However, the majority of CaBP-immunoreactive perikarya were GABA-negative. GABA-immunoreactivity was found in less than 2% of the total population of cells stained for CaBP in laminae I-IV. A significant proportion of the GABA-negative but PV-immunoreactive neurons also showed CaBP-immunoreactivity in laminae II and IV. These results show that out of the two calcium-binding proteins, CaBP is a characteristic protein of a small subpopulation of neurons using excitatory amino acids and PV is a characteristic protein of a subpopulation of neurons utilizing GABA as a transmitter. However, both proteins are present in additional subgroups of neurons, and neuronal populations using inhibitory or excitatory amino acid transmitters are heterogeneous with regard to their content of calcium-binding proteins in the dorsal horn of the rat

  1. Kisspeptins modulate the biology of multiple populations of gonadotropin-releasing hormone neurons during embryogenesis and adulthood in zebrafish (Danio rerio).

    Science.gov (United States)

    Zhao, Yali; Lin, Meng-Chin A; Mock, Allan; Yang, Ming; Wayne, Nancy L

    2014-01-01

    Kisspeptin1 (product of the Kiss1 gene) is the key neuropeptide that gates puberty and maintains fertility by regulating the gonadotropin-releasing hormone (GnRH) neuronal system in mammals. Inactivating mutations in Kiss1 and the kisspeptin receptor (GPR54/Kiss1r) are associated with pubertal failure and infertility. Kiss2, a paralogous gene for kiss1, has been recently identified in several vertebrates including zebrafish. Using our transgenic zebrafish model system in which the GnRH3 promoter drives expression of emerald green fluorescent protein, we investigated the effects of kisspeptins on development of the GnRH neuronal system during embryogenesis and on electrical activity during adulthood. Quantitative PCR showed detectable levels of kiss1 and kiss2 mRNA by 1 day post fertilization, increasing throughout embryonic and larval development. Early treatment with Kiss1 or Kiss2 showed that both kisspeptins stimulated proliferation of trigeminal GnRH3 neurons located in the peripheral nervous system. However, only Kiss1, but not Kiss2, stimulated proliferation of terminal nerve and hypothalamic populations of GnRH3 neurons in the central nervous system. Immunohistochemical analysis of synaptic vesicle protein 2 suggested that Kiss1, but not Kiss2, increased synaptic contacts on the cell body and along the terminal nerve-GnRH3 neuronal processes during embryogenesis. In intact brain of adult zebrafish, whole-cell patch clamp recordings of GnRH3 neurons from the preoptic area and hypothalamus revealed opposite effects of Kiss1 and Kiss2 on spontaneous action potential firing frequency and membrane potential. Kiss1 increased spike frequency and depolarized membrane potential, whereas Kiss2 suppressed spike frequency and hyperpolarized membrane potential. We conclude that in zebrafish, Kiss1 is the primary stimulator of GnRH3 neuronal development in the embryo and an activator of stimulating hypophysiotropic neuron activities in the adult, while Kiss2 plays an

  2. Kisspeptins modulate the biology of multiple populations of gonadotropin-releasing hormone neurons during embryogenesis and adulthood in zebrafish (Danio rerio.

    Directory of Open Access Journals (Sweden)

    Yali Zhao

    Full Text Available Kisspeptin1 (product of the Kiss1 gene is the key neuropeptide that gates puberty and maintains fertility by regulating the gonadotropin-releasing hormone (GnRH neuronal system in mammals. Inactivating mutations in Kiss1 and the kisspeptin receptor (GPR54/Kiss1r are associated with pubertal failure and infertility. Kiss2, a paralogous gene for kiss1, has been recently identified in several vertebrates including zebrafish. Using our transgenic zebrafish model system in which the GnRH3 promoter drives expression of emerald green fluorescent protein, we investigated the effects of kisspeptins on development of the GnRH neuronal system during embryogenesis and on electrical activity during adulthood. Quantitative PCR showed detectable levels of kiss1 and kiss2 mRNA by 1 day post fertilization, increasing throughout embryonic and larval development. Early treatment with Kiss1 or Kiss2 showed that both kisspeptins stimulated proliferation of trigeminal GnRH3 neurons located in the peripheral nervous system. However, only Kiss1, but not Kiss2, stimulated proliferation of terminal nerve and hypothalamic populations of GnRH3 neurons in the central nervous system. Immunohistochemical analysis of synaptic vesicle protein 2 suggested that Kiss1, but not Kiss2, increased synaptic contacts on the cell body and along the terminal nerve-GnRH3 neuronal processes during embryogenesis. In intact brain of adult zebrafish, whole-cell patch clamp recordings of GnRH3 neurons from the preoptic area and hypothalamus revealed opposite effects of Kiss1 and Kiss2 on spontaneous action potential firing frequency and membrane potential. Kiss1 increased spike frequency and depolarized membrane potential, whereas Kiss2 suppressed spike frequency and hyperpolarized membrane potential. We conclude that in zebrafish, Kiss1 is the primary stimulator of GnRH3 neuronal development in the embryo and an activator of stimulating hypophysiotropic neuron activities in the adult, while

  3. Circulating Total Bilirubin and Risk of Incident Cardiovascular Disease in the General Population

    NARCIS (Netherlands)

    Kunutsor, Setor K.; Bakker, Stephan J. L.; Gansevoort, Ronald T.; Chowdhury, Rajiv; Dullaart, Robin P. F.

    OBJECTIVE: To assess the association of circulating total bilirubin and cardiovascular disease (CVD) risk in a new prospective study and to determine whether adding information on total bilirubin values to established cardiovascular risk factors is associated with improvement in prediction of CVD

  4. Total mortality by transferrin saturation levels: two general population studies and a metaanalysis

    DEFF Research Database (Denmark)

    Ellervik, Christina; Tybjærg-Hansen, Anne; Nordestgaard, Børge G

    2011-01-01

    There is evidence for increased mortality in patients with clinically overt hereditary hemochromatosis. Whether increased transferrin saturation (TS), as a proxy for iron overload is associated with increased mortality in the general population is largely unknown.......There is evidence for increased mortality in patients with clinically overt hereditary hemochromatosis. Whether increased transferrin saturation (TS), as a proxy for iron overload is associated with increased mortality in the general population is largely unknown....

  5. Transferrin saturation ratio and risk of total and cardiovascular mortality in the general population.

    LENUS (Irish Health Repository)

    Stack, A G

    2014-08-01

    The transferrin saturation (TSAT) ratio is a commonly used indicator of iron deficiency and iron overload in clinical practice but precise relationships with total and cardiovascular mortality are unclear.

  6. COMPARISON OF ESCHERICHIA COLI, TOTAL COLIFORM, AND FECAL COLIFORM POPULATIONS AS INDICATORS OF WASTEWATER TREATMENT EFFICIENCY

    Science.gov (United States)

    Escherichia coli, total coliform, and fecal coliform data were collected from two wastewater treatment facilities, a subsurface constructed wetlands, and the receiving stream. Results are presented from individual wastewater treatment process streams, final effluent and river sit...

  7. Meta-analysis of relationships between human offtake, total mortality and population dynamics of gray wolves (Canis lupus).

    Science.gov (United States)

    Creel, Scott; Rotella, Jay J

    2010-09-29

    Following the growth and geographic expansion of wolf (Canis lupus) populations reintroduced to Yellowstone National Park and central Idaho in 1995-1996, Rocky Mountain wolves were removed from the endangered species list in May 2009. Idaho and Montana immediately established hunting seasons with quotas equaling 20% of the regional wolf population. Combining hunting with predator control, 37.1% of Montana and Idaho wolves were killed in the year of delisting. Hunting and predator control are well-established methods to broaden societal acceptance of large carnivores, but it is unprecedented for a species to move so rapidly from protection under the Endangered Species Act to heavy direct harvest, and it is important to use all available data to assess the likely consequences of these changes in policy. For wolves, it is widely argued that human offtake has little effect on total mortality rates, so that a harvest of 28-50% per year can be sustained. Using previously published data from 21 North American wolf populations, we related total annual mortality and population growth to annual human offtake. Contrary to current conventional wisdom, there was a strong association between human offtake and total mortality rates across North American wolf populations. Human offtake was associated with a strongly additive or super-additive increase in total mortality. Population growth declined as human offtake increased, even at low rates of offtake. Finally, wolf populations declined with harvests substantially lower than the thresholds identified in current state and federal policies. These results should help to inform management of Rocky Mountain wolves.

  8. Meta-analysis of relationships between human offtake, total mortality and population dynamics of gray wolves (Canis lupus.

    Directory of Open Access Journals (Sweden)

    Scott Creel

    Full Text Available Following the growth and geographic expansion of wolf (Canis lupus populations reintroduced to Yellowstone National Park and central Idaho in 1995-1996, Rocky Mountain wolves were removed from the endangered species list in May 2009. Idaho and Montana immediately established hunting seasons with quotas equaling 20% of the regional wolf population. Combining hunting with predator control, 37.1% of Montana and Idaho wolves were killed in the year of delisting. Hunting and predator control are well-established methods to broaden societal acceptance of large carnivores, but it is unprecedented for a species to move so rapidly from protection under the Endangered Species Act to heavy direct harvest, and it is important to use all available data to assess the likely consequences of these changes in policy. For wolves, it is widely argued that human offtake has little effect on total mortality rates, so that a harvest of 28-50% per year can be sustained. Using previously published data from 21 North American wolf populations, we related total annual mortality and population growth to annual human offtake. Contrary to current conventional wisdom, there was a strong association between human offtake and total mortality rates across North American wolf populations. Human offtake was associated with a strongly additive or super-additive increase in total mortality. Population growth declined as human offtake increased, even at low rates of offtake. Finally, wolf populations declined with harvests substantially lower than the thresholds identified in current state and federal policies. These results should help to inform management of Rocky Mountain wolves.

  9. The Two Populations of Kisspeptin Neurons Are Involved in the Ram-Induced LH Pulsatile Secretion and LH Surge in Anestrous Ewes.

    Science.gov (United States)

    Fabre-Nys, Claude; Cognié, Juliette; Dufourny, Laurence; Ghenim, Meriem; Martinet, Stephanie; Lasserre, Olivier; Lomet, Didier; Millar, Robert P; Ohkura, Satoshi; Suetomi, Yuta

    2017-11-01

    Exposure to a ram during spring stimulates luteinizing hormone (LH) secretion and can induce ovulation in sexually quiescent ewes ("ram effect"). Kisspeptin (Kiss) present in the arcuate nucleus (ARC) and the preoptic area (POA) is a potent stimulators of LH secretion. Our aim was to investigate whether Kiss neurons mediate the increase in LH secretion during the ram effect. With double immunofluorescent detection, we identified Kiss neurons (Kiss IR) activated (Fos IR) by exposure to a ram for 2 hours (M2) or 12 hours (M12) or to ewes for 2 hours (C). The density of cells Kiss + Fos IR and the proportion of Kiss IR cells that were also Fos IR cells were higher in M2 and M12 than in C in ARC (P populations of Kiss neurons are involved in the ram-induced pulsatile LH secretion and in the LH surge. Copyright © 2017 Endocrine Society.

  10. A Population of Projection Neurons that Inhibits the Lateral Horn but Excites the Antennal Lobe through Chemical Synapses in Drosophila

    Directory of Open Access Journals (Sweden)

    Kazumichi Shimizu

    2017-05-01

    Full Text Available In the insect olfactory system, odor information is transferred from the antennal lobe (AL to higher brain areas by projection neurons (PNs in multiple AL tracts (ALTs. In several species, one of the ALTs, the mediolateral ALT (mlALT, contains some GABAergic PNs; in the Drosophila brain, the great majority of ventral PNs (vPNs are GABAergic and project through this tract to the lateral horn (LH. Most excitatory PNs (ePNs, project through the medial ALT (mALT to the mushroom body (MB and the LH. Recent studies have shown that GABAergic vPNs play inhibitory roles at their axon terminals in the LH. However, little is known about the properties and functions of vPNs at their dendritic branches in the AL. Here, we used optogenetic and patch clamp techniques to investigate the functional roles of vPNs in the AL. Surprisingly, our results show that specific activation of vPNs reliably elicits strong excitatory postsynaptic potentials (EPSPs in ePNs. Moreover, the connections between vPNs and ePNs are mediated by direct chemical synapses. Neither pulses of GABA, nor pharmagological, or genetic blockade of GABAergic transmission gave results consistent with the involvement of GABA in vPN-ePN excitatory transmission. These unexpected results suggest new roles for the vPN population in olfactory information processing.

  11. A population of kisspeptin/neurokinin B neurons in the arcuate nucleus may be the central target of the male effect phenomenon in goats.

    Science.gov (United States)

    Sakamoto, Kohei; Wakabayashi, Yoshihiro; Yamamura, Takashi; Tanaka, Tomomi; Takeuchi, Yukari; Mori, Yuji; Okamura, Hiroaki

    2013-01-01

    Exposure of females to a male pheromone accelerates pulsatile gonadotropin-releasing hormone (GnRH) secretion in goats. Recent evidence has suggested that neurons in the arcuate nucleus (ARC) containing kisspeptin and neurokinin B (NKB) play a pivotal role in the control of GnRH secretion. Therefore, we hypothesized that these neurons may be the central target of the male pheromone. To test this hypothesis, we examined whether NKB signaling is involved in the pheromone action, and whether ARC kisspeptin/NKB neurons receive input from the medial nucleus of the amygdala (MeA)--the nucleus suggested to relay pheromone signals. Ovariectomized goats were implanted with a recording electrode aimed at a population of ARC kisspeptin/NKB neurons, and GnRH pulse generator activity, represented by characteristic increases in multiple-unit activity (MUA) volleys, was measured. Pheromone exposure induced an MUA volley and luteinizing hormone (LH) pulse in control animals, whereas the MUA and LH responses to the pheromone were completely suppressed by the treatment with an NKB receptor antagonist. These results indicate that NKB signaling is a prerequisite for pheromone action. In ovariectomized goats, an anterograde tracer was injected into the MeA, and possible connections between the MeA and ARC kisspeptin/NKB neurons were examined. Histochemical observations demonstrated that a subset of ARC kisspeptin/NKB neurons receive efferent projections from the MeA. These results suggest that the male pheromone signal is conveyed via the MeA to ARC kisspeptin neurons, wherein the signal stimulates GnRH pulse generator activity through an NKB signaling-mediated mechanism in goats.

  12. Do health care workforce, population, and service provision significantly contribute to the total health expenditure? An econometric analysis of Serbia.

    Science.gov (United States)

    Santric-Milicevic, M; Vasic, V; Terzic-Supic, Z

    2016-08-15

    In times of austerity, the availability of econometric health knowledge assists policy-makers in understanding and balancing health expenditure with health care plans within fiscal constraints. The objective of this study is to explore whether the health workforce supply of the public health care sector, population number, and utilization of inpatient care significantly contribute to total health expenditure. The dependent variable is the total health expenditure (THE) in Serbia from the years 2003 to 2011. The independent variables are the number of health workers employed in the public health care sector, population number, and inpatient care discharges per 100 population. The statistical analyses include the quadratic interpolation method, natural logarithm and differentiation, and multiple linear regression analyses. The level of significance is set at P Total health expenditure increased by 1.21 standard deviations, with an increase in health workforce growth rate by 1 standard deviation. Furthermore, this rate decreased by 1.12 standard deviations, with an increase in (negative) population growth rate by 1 standard deviation. Finally, the growth rate increased by 0.38 standard deviation, with an increase of the growth rate of inpatient care discharges per 100 population by 1 standard deviation (P < 0.001). Study results demonstrate that the government has been making an effort to control strongly health budget growth. Exploring causality relationships between health expenditure and health workforce is important for countries that are trying to consolidate their public health finances and achieve universal health coverage at the same time.

  13. Serotonin 2C receptor activates a distinct population of arcuate pro-opiomelanocortin neurons via TRPC channels

    Science.gov (United States)

    Serotonin 2C receptors (5-HT2CRs) expressed by pro-opiomelanocortin (POMC) neurons of hypothalamic arcuate nucleus regulate food intake, energy homeostasis ,and glucose metabolism. However, the cellular mechanisms underlying the effects of 5-HT to regulate POMC neuronal activity via 5-HT2CRs have no...

  14. Progressive risk assessment of polychlorinated biphenyls through a Total Diet Study in the Korean population

    International Nuclear Information System (INIS)

    Shin, Eun-su; Nguyen, Khanh-Hoang; Kim, Jongchul; Kim, Cho-il; Chang, Yoon-Seok

    2015-01-01

    Human exposure to polychlorinated biphenyls (PCBs) from foods was investigated through a Total Diet Study (TDS) for the first time in Korea. A representative food list was developed from food intake data. Non-selected foods were also included in the TDS through the mapping process to anticipate practical risk assessment. For better representativeness, data (2008–2011) from the Korea National Health and Nutrition Examination Survey (KNHANES) were combined with the TDS data set. And also, we estimated the dietary exposure to PCBs from various food items using a ‘best-fit’ mapping process and assessed the differences in PCB exposures by sex and age. In this study, we examined total PCBs (62 congeners) including dioxin-like PCBs (DL-PCBs) and indicator PCBs, which are congeners that are mainly detected in various environmental matrices. The average dietary exposure (3.94 ng/kg body weight/day) that was estimated through food intake was 19.7% of the World Health Organization (WHO) recommendation. - Highlights: • A total of 282 samples, composed of the most consumed foodstuffs in Korea, were analysed and shown in detail. • The contamination status of total PCBs in food was assessed, through their various condition on cooking methods. • The dietary intakes of PCBs in various food groups were estimated in different region, gender and age groups. • The improved and systematic food selection process was applied such as ‘mapping process’. - This study is to ensure food safety through total analysis of PCBs with the improved risk assessment method.

  15. Nonlinear development of the populations of neurons expressing c-Fos under sustained electrical intracochlear stimulation in the rat auditory brainstem.

    Science.gov (United States)

    Rosskothen-Kuhl, Nicole; Illing, Robert-Benjamin

    2010-08-06

    The immediate-early-gene c-fos is among the first genes to be expressed following sensory-invoked neuronal activity. Its gene product c-Fos forms the limiting monomer of the heterodimeric activator protein-1 transcription factor that triggers various genes involved in neuroplastic remodeling. This study investigated the pattern of c-Fos expression in anteroventral (AVCN) and dorsal cochlear nucleus (DCN) and central inferior colliculus (CIC) after 45 min, 73 min, 2 h, 3:15 h and 5 h of unilateral electrical intracochlear stimulation (EIS) at 50 Hz in anaesthetized rats. Following EIS, tonotopic c-Fos expression was observed for each stimulation time in ipsilateral AVCN, DCN bilaterally, and contralateral CIC. By counting c-Fos positive nuclei, we discovered temporal non-linearities in the size of the respective population of c-Fos expressing neurons. In all regions investigated, the populations significantly increased from 73 min to 2 h but decreased towards 3:15 h. In AVCN, the number rose again by 5 h of EIS. Remarkably, the same was noted for neurons with large nuclei in deep DCN. In both regions, the population of responsive neurons shifted spatially: In central AVCN, the density of c-Fos positive cells increased significantly from 2 to 5h with medial and lateral regions remaining unchanged. In DCN, the density of large c-Fos positive nuclei fell in the upper and rose in the deep layers from 45 min to 5h of EIS. In conclusion, spatiotemporally varying recruitments of neuronal subpopulations into cellular networks responding to specific patterns of sensory activity take place in the auditory brainstem. Copyright 2010 Elsevier B.V. All rights reserved.

  16. The Impact of Coercive Migrations on the Changes of Total Population Flux in the War-Engulfed Croatian Counties

    Directory of Open Access Journals (Sweden)

    Ana Pažanin

    2006-01-01

    Full Text Available The author deals with the war impact and the impact of coercive migrations on the changes of total population fl ux between two censuses. On the eve of and during the Croatian War of Independence, the migration of population of the Republic of Croatia from the war-engulfed areas to the free areas of the country or to the foreign countries increased. The war in Bosnia and Herzegovina has caused a new wave of refugees from that country and a further migrational fl ux in our country. In the article, the author has established, on the case of the war-engulfed areas of eleven Croatian counties, that the war and coercive migrations have caused a decline of population, the growth of aged population, as well as changes in national and confessional structure.

  17. Worldwide Experience with the Syncardia Total Artificial Heart in the Pediatric Population.

    Science.gov (United States)

    Morales, David L S; Lorts, Angela; Rizwan, Raheel; Zafar, Farhan; Arabia, Francisco A; Villa, Chet R

    Individual centers have documented the use of the Syncardia Total Artificial Heart (TAH) in adolescents with heart failure; however, the number of patients at any given center is small. Herein, we describe the worldwide experience for all patients ≤21 years old supported with the TAH between May 2005 and May 2015 (n = 43). The number of patients experiencing a positive outcome at 60, 90, and 120 days were 30 (70%), 27 (63%), and 25 (58%), respectively. Successful bridge to transplantation varied by diagnosis, but outcomes reported are similar to adults supported with the TAH or biventricular assist devices.

  18. Estimating total economic merit for the Portuguese Holstein cattle population under new economic conditions

    Directory of Open Access Journals (Sweden)

    Joana B.M. Almeida

    2013-12-01

    Full Text Available The objective of this study was to develop a total economic merit index that identifies more profitable animals using Portugal as a case study to illustrate the recent economic changes in milk production. Economic values were estimated following future global prices and EU policy, and taking into consideration the priorities of the Portuguese dairy sector. Economic values were derived using an objective system analysis with a positive approach, that involved the comparison of several alternatives, using real technical and economic data from national dairy farms. The estimated relative economic values revealed a high importance of production traits, low for morphological traits and a value of zero for somatic cell score. According to several future market expectations, three scenarios for milk production were defined: a realistic, a pessimistic and an optimistic setting, each with projected future economic values. Responses to selection and efficiency of selection of the indices were compared to a fourth scenario that represents the current selection situation in Portugal, based on individual estimated breeding values for milk yield. Although profit resulting from sale of milk per average lactation in the optimistic scenario was higher than in the realistic scenario, the volatility of future economic conditions and uncertainty about the future milk pricing system should be considered. Due to this market instability, genetic improvement programs require new definitions of profit functions for the near future. Effective genetic progress direction must be verified so that total economic merit formulae can be adjusted and selection criteria redirected to the newly defined target goals.

  19. POPULATION Total Population NMHD 2000

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The 2006 Second Edition TIGER/Line files are an extract of selected geographic and cartographic information from the Census TIGER database. The geographic coverage...

  20. POPULATION Total Population BGs 2000

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — TIGER, TIGER/Line, and Census TIGER are registered trademarks of the Bureau of the Census. The Redistricting Census 2000 TIGER/Line files are an extract of selected...

  1. POPULATION Total Population COS 2000

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — TIGER, TIGER/Line, and Census TIGER are registered trademarks of the Bureau of the Census. The Redistricting Census 2000 TIGER/Line files are an extract of selected...

  2. POPULATION Total Population CTs 2000

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — TIGER, TIGER/Line, and Census TIGER are registered trademarks of the Bureau of the Census. The Redistricting Census 2000 TIGER/Line files are an extract of selected...

  3. POPULATION Total Population NMSD 2000

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The 2006 Second Edition TIGER/Line files are an extract of selected geographic and cartographic information from the Census TIGER database. The geographic coverage...

  4. A high dietary glycemic index increases total mortality in a Mediterranean population at high cardiovascular risk.

    Directory of Open Access Journals (Sweden)

    Itandehui Castro-Quezada

    Full Text Available OBJECTIVE: Different types of carbohydrates have diverse glycemic response, thus glycemic index (GI and glycemic load (GL are used to assess this variation. The impact of dietary GI and GL in all-cause mortality is unknown. The objective of this study was to estimate the association between dietary GI and GL and risk of all-cause mortality in the PREDIMED study. MATERIAL AND METHODS: The PREDIMED study is a randomized nutritional intervention trial for primary cardiovascular prevention based on community-dwelling men and women at high risk of cardiovascular disease. Dietary information was collected at baseline and yearly using a validated 137-item food frequency questionnaire (FFQ. We assigned GI values of each item by a 5-step methodology, using the International Tables of GI and GL Values. Deaths were ascertained through contact with families and general practitioners, review of medical records and consultation of the National Death Index. Cox regression models were used to estimate multivariable-adjusted hazard ratios (HR and their 95% CI for mortality, according to quartiles of energy-adjusted dietary GI/GL. To assess repeated measures of exposure, we updated GI and GL intakes from the yearly FFQs and used Cox models with time-dependent exposures. RESULTS: We followed 3,583 non-diabetic subjects (4.7 years of follow-up, 123 deaths. As compared to participants in the lowest quartile of baseline dietary GI, those in the highest quartile showed an increased risk of all-cause mortality [HR = 2.15 (95% CI: 1.15-4.04; P for trend  = 0.012]. In the repeated-measures analyses using as exposure the yearly updated information on GI, we observed a similar association. Dietary GL was associated with all-cause mortality only when subjects were younger than 75 years. CONCLUSIONS: High dietary GI was positively associated with all-cause mortality in elderly population at high cardiovascular risk.

  5. Cre-expressing neurons in the cortical white matter of Ntsr1-Cre GN220 mice.

    Science.gov (United States)

    Sundberg, Sofie C; Granseth, Björn

    2018-03-23

    Genetically modified mouse strains that express Cre-recombinase in specific neuronal sub-populations have become widely used tools for investigating neuronal function. The Ntsr1-Cre GN220 mouse expresses this enzyme in corticothalamic neurons in layer 6 of cerebral cortex. We observed that about 7% of Cre-expressing cells in the primary visual cortex are found within the white matter bordering layer 6. By using the immunohistochemical marker for layer 6 neurons, Forkhead box protein 2 (FoxP2), and fluorescently conjugated latex beads injected into the dorsal lateral geniculate nucleus, we show that about half of these cells are similar to and could belong to the layer 6 corticothalamic neuron population. The other half seems to be a distinct white matter (WM) neuron sub-population that we estimate to constitute 2-4% of the total cortical Cre-expressing population. Staining for the neuronal marker Neuronal nuclei (NeuN) revealed that about 15-40% of WM neurons are Cre-expressing. Thus, the potential contribution from WM neurons needs to be considered when interpreting the results from experiments using the Ntsr1-Cre GN220 mouse for investigating corticothalamic neuronal function. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. High nitrate to phosphorus regime attenuates negative effects of rising pCO2 on total population carbon accumulation

    Directory of Open Access Journals (Sweden)

    S. A. Krug

    2012-03-01

    Full Text Available The ongoing rise in atmospheric pCO2 and consequent increase in ocean acidification have direct effects on marine calcifying phytoplankton, which potentially alters carbon export. To date it remains unclear, firstly, how nutrient regime, in particular by coccolithophores preferred phosphate limitation, interacts with pCO2 on particulate carbon accumulation; secondly, how direct physiological responses on the cellular level translate into total population response. In this study, cultures of Emiliania huxleyi were full-factorially exposed to two different N:P regimes and three different pCO2 levels. Cellular biovolume and PIC and POC content significantly declined in response to pCO2 in both nutrient regimes. Cellular PON content significantly increased in the Redfield treatment and decreased in the high N:P regime. Cell abundance significantly declined in the Redfield and remained constant in the high N:P regime. We hypothesise that in the high N:P regime severe phosphorous limitation could be compensated either by reduced inorganic phosphorous demand and/or by enzymatic uptake of organic phosphorous. In the Redfield regime we suggest that enzymatic phosphorous uptake to supplement enhanced phosphorous demand with pCO2 was not possible and thus cell abundance declined. These hypothesised different physiological responses of E. huxleyi among the nutrient regimes significantly altered population carrying capacities along the pCO2 gradient. This ultimately led to the attenuated total population response in POC and PIC content and biovolume to increased pCO2 in the high N:P regime. Our results point to the fact that the physiological (i.e. cellular PIC and POC response to ocean acidification cannot be linearly extrapolated to total population response and thus carbon export. It is therefore necessary to consider both effects of nutrient limitation on cell physiology and their consequences for population size when predicting the influence of

  7. Amylin and GLP-1 target different populations of area postrema neurons that are both modulated by nutrient stimuli.

    Science.gov (United States)

    Züger, Daniela; Forster, Karoline; Lutz, Thomas A; Riediger, Thomas

    2013-03-15

    The area postrema mediates the hypophagic effect of the pancreatic hormone amylin and is also sensitive to glucagon-like peptide 1 (GLP-1). Protein seems to modulate amylin responsiveness because amylin seems to produce a stronger hypophagic effect and a stronger c-Fos expression when protein is absent from the diet. Accordingly, amylin induces a stronger c-Fos expression in the AP when injected in fasted compared to ad libitum fed rats. Here we tested the hypothesis that diet-derived protein attenuates the amylin dependent suppression of feeding and AP activation using isocaloric diets that differed in their protein content. Moreover, we investigated whether peripheral amino acid injection attenuates amylin-induced c-Fos expression in fasted rats. Since recent evidence suggests that GLP-1 may also reduce eating via the AP we tested whether 24 h fasting also increases neuronal AP responsiveness to GLP-1 similar to the fasting-induced increase in amylin responsiveness. Finally, we used the calcitonin receptor (CTR) as an immunohistochemical marker for amylin-receptive AP neurons to investigate whether amylin's target neurons differ from GLP-1 responsive AP neurons. We also dissociated amylin responsive cells from neurons implicated in other AP-mediated functions such as aversion or blood pressure regulation. For this purpose, we conducted c-Fos/CTR double staining after LiCl or angiotensin II treatment, respectively. Amylin (5 μg/kg s.c.) was more effective to reduce the intake of a 1% vs. an 8% or 18% protein diet and to induce c-Fos expression in the AP in rats receiving 1% vs. 18% protein diet. Increased protein intake was associated with increased blood amino acid levels. Peripheral injection of amino acids (1 g/kg i.p.) attenuated the amylin-induced AP activation in 24 h fasted rats. Similar to amylin, GLP-1 (100 μg/kg i.p.) elicited a significant c-Fos response only in fasted but not in ad libitum fed rats. However, in contrast to a high co-localization of

  8. Early Statin Use and the Progression of Alzheimer Disease: A Total Population-Based Case-Control Study.

    Science.gov (United States)

    Lin, Feng-Cheng; Chuang, Yun-Shiuan; Hsieh, Hui-Min; Lee, Tzu-Chi; Chiu, Kuei-Fen; Liu, Ching-Kuan; Wu, Ming-Tsang

    2015-11-01

    The protective effect of statin on Alzheimer disease (AD) is still controversial, probably due to the debate about when to start the use of statin and the lack of any large-scale randomized evidence that actually supports the hypothesis. The purpose of this study was to examine the protective effect of early statin use on mild-to-moderate AD in the total Taiwanese population.This was a total population-based case-control study, using the total population of Taiwanese citizens seen in general medical practice; therefore, the findings can be applied to the general population. The study patients were those with newly diagnosed dementia (ICD-9 290.x) and prescribed any acetylcholinesterase inhibitors (AChEI) from the Taiwan National Health Insurance dataset in 1997 to 2008. The newly diagnosed eligible mild-to-moderate AD patients were traced from the dates of their index dates, which was defined as the first day to receive any AChEI treatment, back to 1 year (exposure period) to categorize them into AD with early statin use and without early statin use. Early statin use was defined as patients using statin before AChEI treatment. Alzheimer disease patients with early statin use were those receiving any statin treatment during the exposure period. Then, we used propensity-score-matched strategy to match these 2 groups as 1:1. The matched study patients were followed-up from their index dates. The primary outcome was the discontinuation of AChEI treatment, indicating AD progression.There were 719 mild-to-moderate AD-paired patients with early statin use and without early statin use for analyses. Alzheimer disease progression was statistically lower in AD patients with early statin use than those without (P = 0.00054). After adjusting for other covariates, mild-to-moderate AD patients with early stain use exhibited a 0.85-risk (95% CI = 0.76-0.95, P = 0.0066) to have AD progression than those without.Early statin use was significantly associated with a reduction in AD

  9. Social life factors affecting the mortality, longevity, and birth rate of total Japanese population: effects of rapid industrialization and urbanization.

    Science.gov (United States)

    Araki, S; Uchida, E; Murata, K

    1990-12-01

    employment were positively related to the birth rate. The birth rate is higher in rural areas. Mortality of professional, engineering, and administrative workers was slightly lower than the total working population, while sales workers, those in farming, fishing, and forestry, and in personal and domestic service had significantly higher mortality. The mortality of the nonworking population was 6-8 times higher than sales, transportation, and communication, and personal and domestic service as well as the total population.

  10. NKX6.1 induced pluripotent stem cell reporter lines for isolation and analysis of functionally relevant neuronal and pancreas populations

    Directory of Open Access Journals (Sweden)

    Shailesh Kumar Gupta

    2018-05-01

    Full Text Available Recent studies have reported significant advances in the differentiation of human pluripotent stem cells to clinically relevant cell types such as the insulin producing beta-like cells and motor neurons. However, many of the current differentiation protocols lead to heterogeneous cell cultures containing cell types other than the targeted cell fate. Genetically modified human pluripotent stem cells reporting the expression of specific genes are of great value for differentiation protocol optimization and for the purification of relevant cell populations from heterogeneous cell cultures. Here we present the generation of human induced pluripotent stem cell (iPSC lines with a GFP reporter inserted in the endogenous NKX6.1 locus. Characterization of the reporter lines demonstrated faithful GFP labelling of NKX6.1 expression during pancreas and motor neuron differentiation. Cell sorting and gene expression profiling by RNA sequencing revealed that NKX6.1-positive cells from pancreatic differentiations closely resemble human beta cells. Furthermore, functional characterization of the isolated cells demonstrated that glucose-stimulated insulin secretion is mainly confined to the NKX6.1-positive cells. We expect that the NKX6.1-GFP iPSC lines and the results presented here will contribute to the further refinement of differentiation protocols and characterization of hPSC-derived beta cells and motor neurons for disease modelling and cell replacement therapies. Keywords: Human induced pluripotent stem cells, NKX6.1, Reporter cell line, Directed differentiation, hiPSC-derived beta cells

  11. Exposure to household endotoxin and total and allergen-specific IgE in the US population

    International Nuclear Information System (INIS)

    Min, Kyoung-Bok; Min, Jin-Young

    2015-01-01

    Background: Although endotoxin has strong pro-inflammatory properties, endotoxin-allergy relationship in adults and children have been inconsistent. Objectives: We investigated the association between household endotoxin levels and total immunoglobulin E (IgE) or specific IgE in the US general population, classified into three age ranges: children/adolescent, adults, and older adults. Methods: We analyzed the 2005–2006 National Health and Nutrition Examination Surveys. A total of 5220 participants for whom serum IgE and household endotoxin data were available was included in the analyses. Results: Exposure to endotoxin reduced the risk for allergic sensitization, especially in specific IgE to plants (OR in Quartile 3 = 0.58; 95% CI = 0.44–0.76) and pets (OR in Quartile 3 = 0.62; 95% CI = 0.41–0.92), for children/adolescents. In contrast, the risk among adults and older adults increased with increasing endotoxin levels. Conclusions: Our findings suggest that the effect of endotoxin on allergic reaction is likely to depend on age. - Highlights: • Findings regarding the endotoxin-allergy relationship in adults and children are inconsistent. • We investigated the association of endotoxin with total and specific IgE in US population. • The association between endotoxin levels and allergic markers is likely to depend on age. • Exposure to endotoxin reduced the risk for allergic sensitization for children/adolescents. • The risk among adults and older adults increased with increasing endotoxin levels. - Exposure to endotoxin reduced the risk for allergic sensitization for children/adolescents, but decreased the risk among adults and older

  12. Evolution and Development of the Inner Ear Efferent System: Transforming a Motor Neuron Population to Connect to the Most Unusual Motor Protein via Ancient Nicotinic Receptors

    Directory of Open Access Journals (Sweden)

    Bernd Fritzsch

    2017-04-01

    Full Text Available All craniate chordates have inner ears with hair cells that receive input from the brain by cholinergic centrifugal fibers, the so-called inner ear efferents (IEEs. Comparative data suggest that IEEs derive from facial branchial motor (FBM neurons that project to the inner ear instead of facial muscles. Developmental data showed that IEEs develop adjacent to FBMs and segregation from IEEs might depend on few transcription factors uniquely associated with IEEs. Like other cholinergic terminals in the peripheral nervous system (PNS, efferent terminals signal on hair cells through nicotinic acetylcholine channels, likely composed out of alpha 9 and alpha 10 units (Chrna9, Chrna10. Consistent with the evolutionary ancestry of IEEs is the even more conserved ancestry of Chrna9 and 10. The evolutionary appearance of IEEs may reflect access of FBMs to a novel target, possibly related to displacement or loss of mesoderm-derived muscle fibers by the ectoderm-derived ear vesicle. Experimental transplantations mimicking this possible aspect of ear evolution showed that different motor neurons of the spinal cord or brainstem form cholinergic synapses on hair cells when ears replace somites or eyes. Transplantation provides experimental evidence in support of the evolutionary switch of FBM neurons to become IEEs. Mammals uniquely evolved a prestin related motor system to cause shape changes in outer hair cells regulated by the IEEs. In summary, an ancient motor neuron population drives in craniates via signaling through highly conserved Chrna receptors a uniquely derived cellular contractility system that is essential for hearing in mammals.

  13. Recovery of the Erythropoietin-Sensitive Stem-Cell Population following Total-Body X-Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Byron, J. W. [Paterson Laboratories, Christie Hospital and Holt Radium Institute, Manchester (United Kingdom)

    1968-08-15

    Erythropoietin acts upon haemopoietic stem cells to initiate their differentiation into the erythroid series. This effect may be used in polycythaemic mice to estimate changes in the erythropoietin-sensitive stem-cell population following total-body irradiation (TBR). Generally, single doses of erythropoietin, less than that needed for maximum stem-cell response, are used to estimate changes in the stem-cell population. The validity of results using this test is based upon accepting several assumptions regarding erythropoietin kinetics. These are: (a) the contribution of endogenous erythropoietin is always negligible; (b) the origin of the dose-response curve to erythropoietin alters only because of changes in stem-cell numbers; (c) the proportion of stem cells responding to a given concentration of erythropoietin is independent of stem-cell numbers; (d) the slope of the dose-response curve does not alter; and (e) competition between erythropoietin and other factors for the stem cells remains unchanged. The studies to be reported indicate that some of these assumptions m a y not always be valid. Following 150 rad TBR, changes in erythropoietin dose-response curves were not always due to changes in the size of the stem-cell population, but also due to changes in erythropoietin kinetics. Changes in erythropoietin kinetics could be corrected for by using doses of erythropoietin which at any particular time after TBR gave maximum stem-cell response; through full dose-response studies, the nature of changes in erythropoietin kinetics following TBR could be established. These studies appear to explain discrepancies in results obtained in different laboratories using the erythropoietin test. The effect of 150 rad TBR on the erythropoietin-sensitive stem-cell population is an initial depression within 30 min to 20% of normal followed by a second depression (post-irradiation dip) at about 12 h. Twenty-four hours after TBR there is a recovery to the initial depression. This

  14. Neuropeptide Y-immunoreactive neurons in the cerebral cortex of humans and other haplorrhine primates

    Science.gov (United States)

    Raghanti, Mary Ann; Conley, Tiffini; Sudduth, Jessica; Erwin, Joseph M.; Stimpson, Cheryl D.; Hof, Patrick R.; Sherwood, Chet C.

    2012-01-01

    We examined the distribution of neurons immunoreactive for neuropeptide Y (NPY) in the posterior part of the superior temporal cortex (Brodmann's area 22 or area Tpt) of humans and nonhuman haplorrhine primates. NPY has been implicated in learning and memory and the density of NPY-expressing cortical neurons and axons is reduced in depression, bipolar disorder, schizophrenia, and Alzheimer's disease. Due to the role that NPY plays in both cognition and neurodegenerative diseases, we tested the hypothesis that the density of cortical and interstitial neurons expressing NPY was increased in humans relative to other primate species. The study sample included great apes (chimpanzee and gorilla), Old World monkeys (pigtailed macaque, moor macaque, and baboon) and New World monkeys (squirrel monkey and capuchin). Stereologic methods were used to estimate the density of NPY-immunoreactive (-ir) neurons in layers I-VI of area Tpt and the subjacent white matter. Adjacent Nissl-stained sections were used to calculate local densities of all neurons. The ratio of NPY-ir neurons to total neurons within area Tpt and the total density of NPY-ir neurons within the white matter were compared among species. Overall, NPY-ir neurons represented only an average of 0.006% of the total neuron population. While there were significant differences among species, phylogenetic trends in NPY-ir neuron distributions were not observed and humans did not differ from other primates. However, variation among species warrants further investigation into the distribution of this neuromodulator system. PMID:23042407

  15. Total and Differential Leukocyte Counts in Relation to Incidence of Diabetes Mellitus: A Prospective Population-Based Cohort Study.

    Science.gov (United States)

    Borné, Yan; Smith, J Gustav; Nilsson, Peter M; Melander, Olle; Hedblad, Bo; Engström, Gunnar

    2016-01-01

    High concentrations of leukocytes in blood have been associated with diabetes mellitus. This prospective study aimed to explore whether total and differential leukocyte counts are associated with incidence of diabetes. A missense variant R262W in the SH2B3 (SH2B adaptor protein 3) gene, coding for a protein that negatively regulates hematopoietic cell proliferation, was also studied in relation to incidence of diabetes. Leukocyte count and its subtypes (neutrophils, lymphocytes and mixed cells) were analyzed in 26,667 men and women, 45-73 years old, from the population-based Malmö Diet and Cancer study. Information about the R262W polymorphism (rs3184504) in SH2B3 was genotyped in 24,489 subjects. Incidence of diabetes was studied during a mean follow-up of 14 years. Cox proportional hazards regression was used to examine incidence of diabetes by total and differential leukocyte counts. Mendelian randomization analysis using R262W as an instrumental variable was performed with two-stage least squares regression. A total of 2,946 subjects developed diabetes during the follow-up period. After taking several possible confounders into account, concentrations of total leukocyte count, neutrophils and lymphocytes were all significantly associated with incidence of diabetes. The adjusted hazard ratios (95% confidence interval; quartile 4 vs quartile 1) were 1.37 (1.22-1.53) for total leukocytes, 1.33 (1.19-1.49) for neutrophils and 1.29 (1.15-1.44) for lymphocytes. The R262W polymorphism was strongly associated with leukocytes (0.11x109 cells/l per T allele, p = 1.14 x10-12), lymphocytes (p = 4.3 x10-16), neutrophils (p = 8.0 x10-6) and mixed cells (p = 3.0 x10-6). However, there was no significant association between R262W and fasting glucose, HbA1c or incidence of diabetes. Concentrations of total leukocytes, neutrophils and lymphocytes are associated with incidence of diabetes. However, the lack of association with the R262W polymorphism suggests that the associations

  16. Correlation between resting state fMRI total neuronal activity and PET metabolism in healthy controls and patients with disorders of consciousness.

    Science.gov (United States)

    Soddu, Andrea; Gómez, Francisco; Heine, Lizette; Di Perri, Carol; Bahri, Mohamed Ali; Voss, Henning U; Bruno, Marie-Aurélie; Vanhaudenhuyse, Audrey; Phillips, Christophe; Demertzi, Athena; Chatelle, Camille; Schrouff, Jessica; Thibaut, Aurore; Charland-Verville, Vanessa; Noirhomme, Quentin; Salmon, Eric; Tshibanda, Jean-Flory Luaba; Schiff, Nicholas D; Laureys, Steven

    2016-01-01

    The mildly invasive 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a well-established imaging technique to measure 'resting state' cerebral metabolism. This technique made it possible to assess changes in metabolic activity in clinical applications, such as the study of severe brain injury and disorders of consciousness. We assessed the possibility of creating functional MRI activity maps, which could estimate the relative levels of activity in FDG-PET cerebral metabolic maps. If no metabolic absolute measures can be extracted, our approach may still be of clinical use in centers without access to FDG-PET. It also overcomes the problem of recognizing individual networks of independent component selection in functional magnetic resonance imaging (fMRI) resting state analysis. We extracted resting state fMRI functional connectivity maps using independent component analysis and combined only components of neuronal origin. To assess neuronality of components a classification based on support vector machine (SVM) was used. We compared the generated maps with the FDG-PET maps in 16 healthy controls, 11 vegetative state/unresponsive wakefulness syndrome patients and four locked-in patients. The results show a significant similarity with ρ = 0.75 ± 0.05 for healthy controls and ρ = 0.58 ± 0.09 for vegetative state/unresponsive wakefulness syndrome patients between the FDG-PET and the fMRI based maps. FDG-PET, fMRI neuronal maps, and the conjunction analysis show decreases in frontoparietal and medial regions in vegetative patients with respect to controls. Subsequent analysis in locked-in syndrome patients produced also consistent maps with healthy controls. The constructed resting state fMRI functional connectivity map points toward the possibility for fMRI resting state to estimate relative levels of activity in a metabolic map.

  17. Disability in society-medical and non-medical determinants for disability pension in a Norwegian total county population study.

    Science.gov (United States)

    Krokstad, Steinar; Westin, Steinar

    2004-05-01

    The objective of this study was to describe sociomedical determinants and developments for the medically based disability pension in Norway by linking individual based data from a county health survey to data on disability from the National Insurance Administration. Two cross-sectional total population health surveys with an approximate 10-year interval were conducted in Nord-Trøndelag county, HUNT I (1984-86) and HUNT II (1995-97), which allows for analyses of changes over time, supplied with official incidence data on disability pension. The large-scale variations and overall increasing incidence rates of disability pension in Norway during the last 20 years also applied to the county of Nord-Trøndelag. The prevalence of disability pension generally increased in the population from the mid-1980s to the mid-1990s. A striking finding was a consistent pattern of increasing prevalence of disability pension with decreasing socio-economic status and education. A geographic pattern for disability pension prevalence on a municipality level suggested that structural and cultural factors were important in determining the level of disability in society. Medical determinants alone cannot explain either the dramatic variations or the overall increased incidence rates of disability pension in the last two decades in Norway. The results demonstrate the importance of social, non-medical and contextual determinants for disability pension, how these determinants result in important prevalence differences by socio-economic status, and their impact on the level of disability in society.

  18. Assessment of the Swedish EQ-5D experience-based value sets in a total hip replacement population.

    Science.gov (United States)

    Nemes, Szilárd; Burström, Kristina; Zethraeus, Niklas; Eneqvist, Ted; Garellick, Göran; Rolfson, Ola

    2015-12-01

    All patients undergoing elective total hip replacement (THR) in Sweden are asked to complete a survey, including the EQ-5D. Thus far, EQ-5D values have been presented using the UK TTO value set based on hypothetical values. Shift to the use of the recently introduced Swedish experience-based value set, derived from a representative Swedish population, is an appealing alternative. To investigate how accurate the Swedish experience-based VAS value set predicts observed EQ VAS values and to compare correlations between Swedish and UK value sets including two provisional value sets derived from the THR population. Pre- and one-year postoperative data from 56,062 THR patients from the Swedish Hip Arthroplasty Register were used. Agreement between the observed and the predicted EQ VAS values was assessed with correlation. Based on pre- and postoperative data, we constructed two provisional VAS value sets. Correlations between observed and calculated values using the Swedish VAS value set were moderate (r = 0.46) in preoperative data and high (r = 0.72) in postoperative data. Correlations between UK and register-based value sets were constantly lower compared to Swedish value sets. Register-based values and Swedish values were highly correlated. The Swedish value sets are more accurate in terms of representation of the Swedish THR patients than the currently used UK TTO value set. We find it feasible to use the experience-based Swedish value sets for further presentation of EQ-5D values in the Swedish THR population.

  19. Neuraxial anesthesia improves long-term survival after total joint replacement: a retrospective nationwide population-based study in Taiwan.

    Science.gov (United States)

    Chen, Wei-Hung; Hung, Kuo-Chuan; Tan, Ping-Heng; Shi, Hon-Yi

    2015-04-01

    This study explored the effects of general (GA) and neuraxial (NA) anesthesia on the outcomes of primary total joint replacement (TJR) in terms of postoperative mortality, length of stay (LOS), and hospital treatment costs. From 1997 to 2010, this nationwide population-based study retrospectively evaluated 7,977 patients in Taiwan who underwent primary total hip or knee replacement. We generated two propensity-score-matched subgroups, each containing an equal number of patients who underwent TJR with either GA or NA. Of the 7,977 patients, 2,990 (37.5%) underwent GA and 4,987 (62.5%) underwent NA. Propensity-score matching was used to create comparable GA and NA groups adjusted for age, sex, comorbidities, surgery type, hospital volume, and surgeon volume. Survival over the first three years following surgery was similar. The proportion of patients alive up to 14 years postoperatively for those undergoing NA was 58.2% (95% confidence interval [CI] 50.4 to 66.0), and for those undergoing GA it was 57.3% (95% CI 51.4 to 63.2). Neuraxial anesthesia was associated with lower median [interquartile range; IQR] hospital treatment cost ($4,079 [3,805-4,444] vs $4,113 [3,812-4,568]; P anesthesia costs are removed. The mechanism underlying the association between NA and long-term survival is unknown.

  20. Mental Health Services Use Predicted by Number of Mental Health Problems and Gender in a Total Population Study

    Directory of Open Access Journals (Sweden)

    Maj-Britt Posserud

    2013-01-01

    Full Text Available We examined the relationship between service use and the number of problem areas as reported by parents and teachers on questionnaires among children aged 7–9 years old in the Bergen Child Study, a total population study including more than 9000 children. A problem area was counted as present if the child scored above the 95th percentile on parent and/or teacher questionnaire. A total number of 13 problem areas were included. Odd ratios (ORs for contact with child and adolescent mental health services (CAMH, school psychology services (SPS, health visiting nurse/physician, and school support were calculated with gender as covariate. The number of symptom areas was highly predictive of service use, showing a dose-response relationship for all services. Children scoring on ≥4 problem areas had a more than hundredfold risk of being in contact with CAMH services compared to children without problems. The mean number of problem areas for children in CAMH and SPS was 6.1 and 4.4 respectively, strongly supporting the ESSENCE model predicting multisymptomatology in children in specialized services. Even after controlling for number of problem areas, boys were twice as likely as girls to be in contact with CAMH, replicating previous findings of female gender being a strong barrier to mental health services.

  1. Bioaccumulation of trace metals and total petroleum and genotoxicity responses in an edible fish population as indicators of marine pollution.

    Science.gov (United States)

    D'Costa, Avelyno; Shyama, S K; Praveen Kumar, M K

    2017-08-01

    The present study reports the genetic damage and the concentrations of trace metals and total petroleum hydrocarbons prevailing in natural populations of an edible fish, Arius arius in different seasons along the coast of Goa, India as an indicator of the pollution status of coastal water. Fish were collected from a suspected polluted site and a reference site in the pre-monsoon, monsoon and post-monsoon seasons. Physico-chemical parameters as well as the concentrations of total petroleum hydrocarbons (TPH) and trace metals in the water and sediment as well as the tissues of fish collected from these sites were recorded. The genotoxicity status of the fish was assessed employing the micronucleus test and comet assay. A positive correlation (p<0.001) was observed between the tail DNA and micronuclei in all the fish collected. Multiple regression analysis revealed that tissue and environmental pollutant concentrations and genotoxicity were positively associated and higher in the tissues of the fish collected from the polluted site. Pollution indicators and genotoxicity tests, combined with other physiological or biochemical parameters represent an essential integrated approach for efficient monitoring of aquatic ecosystems in Goa. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Beverage Consumption Habits and Association with Total Water and Energy Intakes in the Spanish Population: Findings of the ANIBES Study.

    Science.gov (United States)

    Nissensohn, Mariela; Sánchez-Villegas, Almudena; Ortega, Rosa M; Aranceta-Bartrina, Javier; Gil, Ángel; González-Gross, Marcela; Varela-Moreiras, Gregorio; Serra-Majem, Lluis

    2016-04-20

    Inadequate hydration is a public health issue that imposes a significant economic burden. In Spain, data of total water intake (TWI) are scarce. There is a clear need for a national study that quantifies water and beverage intakes and explores associations between the types of beverages and energy intakes. The Anthropometry, Intake and Energy Balance Study ANIBES is a national survey of diet and nutrition conducted among a representative sample of 2285 healthy participants aged 9-75 years in Spain. Food and beverage intakes were assessed in a food diary over three days. Day and time of beverage consumption were also recorded. On average, TWI was 1.7 L (SE 21.2) for men and 1.6 L (SE 18.9) for women. More than 75% of participants had inadequate TWI, according to European Food Safety Authority (EFSA) recommendations. Mean total energy intake (EI) was 1810 kcal/day (SE 11.1), of which 12% was provided by beverages. Water was the most consumed beverage, followed by milk. The contribution of alcoholic drinks to the EI was near 3%. For caloric soft drinks, a relatively low contribution to the EI was obtained, only 2%. Of eight different types of beverages, the variety score was positively correlated with TWI (r = 0.39) and EI (r = 0.23), suggesting that beverage variety is an indicator of higher consumption of food and drinks. The present study demonstrates that well-conducted surveys such as the ANIBES study have the potential to yield rich contextual value data that can emphasize the need to undertake appropriate health and nutrition policies to increase the total water intake at the population level promoting a healthy Mediterranean hydration pattern.

  3. Beverage Consumption Habits and Association with Total Water and Energy Intakes in the Spanish Population: Findings of the ANIBES Study

    Science.gov (United States)

    Nissensohn, Mariela; Sánchez-Villegas, Almudena; Ortega, Rosa M.; Aranceta-Bartrina, Javier; Gil, Ángel; González-Gross, Marcela; Varela-Moreiras, Gregorio; Serra-Majem, Lluis

    2016-01-01

    Background: Inadequate hydration is a public health issue that imposes a significant economic burden. In Spain, data of total water intake (TWI) are scarce. There is a clear need for a national study that quantifies water and beverage intakes and explores associations between the types of beverages and energy intakes. Methods: The Anthropometry, Intake and Energy Balance Study ANIBES is a national survey of diet and nutrition conducted among a representative sample of 2285 healthy participants aged 9–75 years in Spain. Food and beverage intakes were assessed in a food diary over three days. Day and time of beverage consumption were also recorded. Results: On average, TWI was 1.7 L (SE 21.2) for men and 1.6 L (SE 18.9) for women. More than 75% of participants had inadequate TWI, according to European Food Safety Authority (EFSA) recommendations. Mean total energy intake (EI) was 1810 kcal/day (SE 11.1), of which 12% was provided by beverages. Water was the most consumed beverage, followed by milk. The contribution of alcoholic drinks to the EI was near 3%. For caloric soft drinks, a relatively low contribution to the EI was obtained, only 2%. Of eight different types of beverages, the variety score was positively correlated with TWI (r = 0.39) and EI (r = 0.23), suggesting that beverage variety is an indicator of higher consumption of food and drinks. Conclusions: The present study demonstrates that well-conducted surveys such as the ANIBES study have the potential to yield rich contextual value data that can emphasize the need to undertake appropriate health and nutrition policies to increase the total water intake at the population level promoting a healthy Mediterranean hydration pattern. PMID:27104564

  4. Changes in the Total Fecal Bacterial Population in Individual Horses Maintained on a Restricted Diet Over 6 Weeks

    Directory of Open Access Journals (Sweden)

    Kirsty Dougal

    2017-08-01

    Full Text Available Twelve mature (aged 5–16 years horses and ponies of mixed breed and type were fed restricted (1.25% BM Dry matter quantities of one of two fiber based diets formulated to be iso-caloric. Diet 1 comprised of 0.8% body mass (BM of chaff based complete feed plus 0.45% BM low energy grass hay (the same hay used for both diets. Diet 2 comprised 0.1% BM of a nutrient balancer plus 1.15% BM grass hay. Fecal samples were collected at week 10 and week 16. DNA was extracted and the V1-V2 regions of 16SrDNA were 454-pyrosequenced to investigate the bacterial microbiome of the horse. The two most abundant phyla found in both diets and sampling periods were the Firmicutes and Bacteroidetes. There was a clear reduction in Bacteroidetes with a concordant increase in Firmicutes over time. There was a limited degree of stability within the bacterial community of the hindgut of horses, with 65% of bacteria retained, over a 6 week period whilst on a uniform diet. The presence of a core community defined by being present in all samples (each animal/diet combination included in the study and being present at 0.1% relative abundance (or greater was identified. In total 65 operational taxonomic units (OTUs were identified that fit the definition of core making up 21–28% of the total sequences recovered. As with total population the most abundant phyla were the Bacteroidetes followed by the Firmicutes, however there was no obvious shift in phyla due to period. Indeed, when the relative abundance of OTUs was examined across diets and periods there was no significant effect of diet or period alone or in combination on the relative abundance of the core OTUs.

  5. Beverage Consumption Habits and Association with Total Water and Energy Intakes in the Spanish Population: Findings of the ANIBES Study

    Directory of Open Access Journals (Sweden)

    Mariela Nissensohn

    2016-04-01

    Full Text Available Background: Inadequate hydration is a public health issue that imposes a significant economic burden. In Spain, data of total water intake (TWI are scarce. There is a clear need for a national study that quantifies water and beverage intakes and explores associations between the types of beverages and energy intakes. Methods: The Anthropometry, Intake and Energy Balance Study ANIBES is a national survey of diet and nutrition conducted among a representative sample of 2285 healthy participants aged 9–75 years in Spain. Food and beverage intakes were assessed in a food diary over three days. Day and time of beverage consumption were also recorded. Results: On average, TWI was 1.7 L (SE 21.2 for men and 1.6 L (SE 18.9 for women. More than 75% of participants had inadequate TWI, according to European Food Safety Authority (EFSA recommendations. Mean total energy intake (EI was 1810 kcal/day (SE 11.1, of which 12% was provided by beverages. Water was the most consumed beverage, followed by milk. The contribution of alcoholic drinks to the EI was near 3%. For caloric soft drinks, a relatively low contribution to the EI was obtained, only 2%. Of eight different types of beverages, the variety score was positively correlated with TWI (r = 0.39 and EI (r = 0.23, suggesting that beverage variety is an indicator of higher consumption of food and drinks. Conclusions: The present study demonstrates that well-conducted surveys such as the ANIBES study have the potential to yield rich contextual value data that can emphasize the need to undertake appropriate health and nutrition policies to increase the total water intake at the population level promoting a healthy Mediterranean hydration pattern.

  6. Biological Variation and Reference Change Value Data for Serum Neuron-Specific Enolase in a Turkish Population.

    Science.gov (United States)

    Matyar, Selcuk; Goruroglu Ozturk, Ozlem; Ziyanoglu Karacor, Esin; Yuzbasioglu Ariyurek, Sedefgul; Sahin, Gulhan; Kibar, Filiz; Yaman, Akgun; Inal, Tamer

    2016-11-01

    Neuron-specific enolase (NSE) is a recognized biomarker for the assessment of cerebral injury in neurological disorders. This study aims to report a definitive assessment of the biological variation (BV) components of this biomarker, including within-subject BV (CVI), between-subject BV (CVG), index of individuality (II), and reference change value (RCV), in a cohort of Turkish participants using an experimental protocol. Six blood specimens were collected from each of the 13 apparently healthy volunteers (seven women, six men; ranging in age from 23 to 36) on the same day, every 2 weeks for 2 months. Serum specimens were stored at -20°C until analysis. Neuron-specific enolase levels were evaluated in serum samples using an electrochemiluminescence (ECLIA) immunoassay kit with a Roche Cobas e 411 auto-analyser. ANOVA test was used to calculate the variations. The CVI and CVG for NSE were 21.5% and 28.8%, respectively. Analytical variation (CVA) was calculated as 10.2%. Additionally, II and RCV were calculated as 0.74 and 66% (95% confident interval, CI), respectively. As the performance index (PI) was found to be less than 2 (PI = 0.95), it is concluded that the NSE measurements have a desirable performance for analytical imprecision. Since the II was found to be less than 1 (II: 0.74), the reference values will be of little use. Thus, RCV would provide better information for deciding whether a significant change has occurred. © 2016 Wiley Periodicals, Inc.

  7. Measure of synchrony in the activity of intrinsic cardiac neurons

    International Nuclear Information System (INIS)

    Longpré, Jean-Philippe; Salavatian, Siamak; Jacquemet, Vincent; Beaumont, Eric; Armour, J Andrew; Ardell, Jeffrey L

    2014-01-01

    Recent multielectrode array recordings in ganglionated plexi of canine atria have opened the way to the study of population dynamics of intrinsic cardiac neurons. These data provide critical insights into the role of local processing that these ganglia play in the regulation of cardiac function. Low firing rates, marked non-stationarity, interplay with the cardiovascular and pulmonary systems and artifacts generated by myocardial activity create new constraints not present in brain recordings for which almost all neuronal analysis techniques have been developed. We adapted and extended the jitter-based synchrony index (SI) to (1) provide a robust and computationally efficient tool for assessing the level and statistical significance of SI between cardiac neurons, (2) estimate the bias on SI resulting from neuronal activity possibly hidden in myocardial artifacts, (3) quantify the synchrony or anti-synchrony between neuronal activity and the phase in the cardiac and respiratory cycles. The method was validated on firing time series from a total of 98 individual neurons identified in 8 dog experiments. SI ranged from −0.14 to 0.66, with 23 pairs of neurons with SI > 0.1. The estimated bias due to artifacts was typically <1%. Strongly cardiovascular- and pulmonary-related neurons (SI > 0.5) were found. Results support the use of jitter-based SI in the context of intrinsic cardiac neurons. (paper)

  8. Knowledge and attitude towards total knee arthroplasty among the public in Saudi Arabia: a nationwide population-based study.

    Science.gov (United States)

    Al-Mohrej, Omar A; Alshammari, Faris O; Aljuraisi, Abdulrahman M; Bin Amer, Lujain A; Masuadi, Emad M; Al-Kenani, Nader S

    2018-04-01

    Studies on total knee arthroplasty (TKA) in Saudi Arabia are scarce, and none have reported the knowledge and attitude of the procedure in Saudi Arabia. Our study aims to measure the knowledge and attitude of TKA among the adult Saudi population. To encompass a representative sample of this cross-sectional survey, all 13 administrative areas were used as ready-made geographical clusters. For each cluster, stratified random sampling was performed to maximize participation in the study. In each area, random samples of mobile phone numbers were selected with a probability proportional to the administrative area population size. Sample size calculation was based on the assumption that 50% of the participants would have some level of knowledge, with a 2% margin of error and 95% confidence level. To reach our intended sample size of 1540, we contacted 1722 participants with a response rate of 89.4%. The expected percentage of public knowledge was 50%; however, the actual percentage revealed by this study was much lower (29.7%). A stepwise multiple logistic regression was used to assess the factors that positively affected the knowledge score regarding TKA. Age [P = 0.016 with OR of 0.47], higher income [P = 0.001 with OR of 0.52] and participants with a positive history of TKA or that have known someone who underwent the surgery [P Saudi Arabia concerning TKA, its indications and results. We recommend that doctors use the results of our survey to assess their conversations with their patients, and to determine whether the results of the procedure are adequately clarified.

  9. The dramatic increase in total knee replacement utilization rates in the United States cannot be fully explained by growth in population size and the obesity epidemic.

    Science.gov (United States)

    Losina, Elena; Thornhill, Thomas S; Rome, Benjamin N; Wright, John; Katz, Jeffrey N

    2012-02-01

    Total knee replacement utilization in the United States more than doubled from 1999 to 2008. Although the reasons for this increase have not been examined rigorously, some have attributed the increase to population growth and the obesity epidemic. Our goal was to investigate whether the rapid increase in total knee replacement use over the past decade can be sufficiently attributed to changes in these two factors. We used data from the Nationwide Inpatient Sample to estimate changes in total knee replacement utilization rates from 1999 to 2008, stratified by age (eighteen to forty-four years, forty-five to sixty-four years, and sixty-five years or older). We obtained data on obesity prevalence and U.S. population growth from federal sources. We compared the rate of change in total knee replacement utilization with the rates of population growth and change in obesity prevalence from 1999 to 2008. In 2008, 615,050 total knee replacements were performed in the United States adult population, 134% more than in 1999. During the same time period, the overall population size increased by 11%. While the population of forty-five to sixty-four-year-olds grew by 29%, the number of total knee replacements in this age group more than tripled. The number of obese and non-obese individuals in the United States increased by 23% and 4%, respectively. Assuming unchanged indications for total knee replacement among obese and non-obese individuals with knee osteoarthritis over the last decade, these changes fail to account for the 134% growth in total knee replacement use. Population growth and obesity cannot fully explain the rapid expansion of total knee replacements in the last decade, suggesting that other factors must also be involved. The disproportionate increase in total knee replacements among younger patients may be a result of a growing number of knee injuries and expanding indications for the procedure.

  10. Variation in Use of Pediatric Cardiology Subspecialty Care: A Total Population Study in California, 1983 to 2011.

    Science.gov (United States)

    Chamberlain, Lisa J; Fernandes, Susan M; Saynina, Olga; Grady, Stafford; Sanders, Lee; Staves, Kelly; Wise, Paul H

    2015-07-07

    American Academy of Pediatrics guidelines emphasize regionalized systems of care for pediatric chronic illness. There remains a paucity of information on the status of regionalized systems of care for pediatric congenital heart disease (CHD). This study evaluated variations in use of pediatric cardiology specialty care centers (PCSCC) for pediatric patients with CHD in California between 1983 and 2011. We performed a retrospective, total population analysis of pediatric CHD patients using the California Office of Statewide Health Planning and Development unmasked database. PCSCCs were identified by California's Title V program. There were 164,310 discharges meeting inclusion criterion. Discharges from PCSCCs grew from 58% to 88% between 1983 and 2011. Regionalized care was highest for surgical (96%) versus nonsurgical (71%) admissions. Admissions with a public payer increased from 42% (1983) to 61% (2011). Total bed days nearly doubled, and median length of stay increased from 2 to 3 days (nonspecialty care) and from 4 to 5 days (specialty care). There was a decrease in the pediatric CHD in-hospital death rate from 5.1 to 2.3 per 100,000 between 1983 and 2011, and a shift toward a larger percent of deaths occurring in the newborn period. California's inpatient regionalized specialty care of pediatric CHD has increased substantially since 1983, especially for surgical CHD discharges. The death rate has decreased, the number of bed days has increased, and a large proportion of these discharges now have public payers. Health care reform efforts must consider these shifts while protecting advances in regionalization of pediatric CHD care. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  11. Contribution of Water from Food and Fluids to Total Water Intake: Analysis of a French and UK Population Surveys.

    Science.gov (United States)

    Guelinckx, Isabelle; Tavoularis, Gabriel; König, Jürgen; Morin, Clémentine; Gharbi, Hakam; Gandy, Joan

    2016-10-14

    Little has been published on the contribution of food moisture (FM) to total water intake (TWI); therefore, the European Food Safety Authority assumed FM to contribute 20%-30% to TWI. The aim of the present analysis was to estimate and compare TWI, the percentage of water from FM and from fluids in population samples of France and UK. Data from 2 national nutrition surveys (Enquête Comportements et Consommations Alimentaires en France (CCAF) 2013 and the National Diet and Nutrition Survey (NDNS) 2008/2009-2011/2012) were analyzed for TWI and the contribution of water from FM and fluids. Children and adults TWI were significantly lower in France than in the UK. The contribution of water from foods was lower in the UK than in France (27% vs. 36%). As TWI increased, the proportion of water from fluids increased, suggesting that low drinkers did not compensate by increasing intake of water-rich foods. In addition, 80%-90% of the variance in TWI was explained by differences in water intake from fluids. More data on the contribution of FM to TWI is needed to develop more robust dietary recommendations on TWI and guidance on fluid intake for the general public.

  12. Cortical Divergent Projections in Mice Originate from Two Sequentially Generated, Distinct Populations of Excitatory Cortical Neurons with Different Initial Axonal Outgrowth Characteristics.

    Science.gov (United States)

    Hatanaka, Yumiko; Namikawa, Tomohiro; Yamauchi, Kenta; Kawaguchi, Yasuo

    2016-05-01

    Excitatory cortical neurons project to various subcortical and intracortical regions, and exhibit diversity in their axonal connections. Although this diversity may develop from primary axons, how many types of axons initially occur remains unknown. Using a sparse-labeling in utero electroporation method, we investigated the axonal outgrowth of these neurons in mice and correlated the data with axonal projections in adults. Examination of lateral cortex neurons labeled during the main period of cortical neurogenesis (E11.5-E15.5) indicated that axonal outgrowth commonly occurs in the intermediate zone. Conversely, the axonal direction varied; neurons labeled before E12.5 and the earliest cortical plate neurons labeled at E12.5 projected laterally, whereas neurons labeled thereafter projected medially. The expression of Ctip2 and Satb2 and the layer destinations of these neurons support the view that lateral and medial projection neurons are groups of prospective subcortical and callosal projection neurons, respectively. Consistently, birthdating experiments demonstrated that presumptive lateral projection neurons were generated earlier than medial projection neurons, even within the same layer. These results suggest that the divergent axonal connections of excitatory cortical neurons begin from two types of primary axons, which originate from two sequentially generated distinct subpopulations: early-born lateral (subcortical) and later-born medial (callosal) projection neuron groups. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Use of vitamin supplements and risk of total cancer and cardiovascular disease among the Japanese general population: A population-based survey

    Directory of Open Access Journals (Sweden)

    Ishihara Junko

    2011-07-01

    Full Text Available Abstract Background Despite the popular use of vitamin supplements and several prospective cohort studies investigating their effect on cancer incidence and cardiovascular disease (CVD, scientific data supporting their benefits remain controversial. Inconsistent results may be partly explained by the fact that use of supplements is an inconsistent behavior in individuals. We examined whether vitamin supplement use patterns affect cancer and CVD risk in a population-based cohort study in Japan. Methods A total of 28,903 men and 33,726 women in the Japan Public Health Center-based Prospective Study cohort, who answered questions about vitamin supplement use in the first survey from 1990-1994 and the second survey from 1995-1998, were categorized into four groups (never use, past use, recent use, and consistent use and followed to the end of 2006 for cancer and 2005 for CVD. Sex-specific hazard ratios (HRs and 95% confidence intervals (95% CIs were used to describe the relative risks of cancer and CVD associated with vitamin supplement use. Results During follow-up, 4501 cancer and 1858 CVD cases were identified. Multivariate adjusted analysis revealed no association of any pattern of vitamin supplement use with the risk of cancer and CVD in men. In women, consistent use was associated with lower risk of CVD (HR 0.60, 95% CI 0.41-0.89, whereas past (HR 1.17, 95% CI 1.02-1.33 and recent use (HR 1.24, 95% CI 1.01-1.52 were associated with higher risk of cancer. Conclusions To our knowledge, this is the first prospective cohort study to examine simultaneously the associations between vitamin supplement use patterns and risk of cancer and CVD. This prospective cohort study demonstrated that vitamin supplement use has little effect on the risk of cancer or CVD in men. In women, however, consistent vitamin supplement use might reduce the risk of CVD. Elevated risk of cancer associated with past and recent use of vitamin supplements in women may be partly

  14. Use of Hip Arthroscopy and Risk of Conversion to Total Hip Arthroplasty: A Population-Based Analysis.

    Science.gov (United States)

    Schairer, William W; Nwachukwu, Benedict U; McCormick, Frank; Lyman, Stephen; Mayman, David

    2016-04-01

    To use population-level data to (1) evaluate the conversion rate of total hip arthroplasty (THA) within 2 years of hip arthroscopy and (2) assess the influence of age, arthritis, and obesity on the rate of conversion to THA. We used the State Ambulatory Surgery Databases and State Inpatient Databases for California and Florida from 2005 through 2012, which contain 100% of patient visits. Hip arthroscopy patients were tracked for subsequent primary THA within 2 years. Out-of-state patients and patients with less than 2 years follow-up were excluded. Multivariate analysis identified risks for subsequent hip arthroplasty after arthroscopy. We identified 7,351 patients who underwent hip arthroscopy with 2 years follow-up. The mean age was 43.9 ± 13.7 years, and 58.8% were female patients. Overall, 11.7% of patients underwent THA conversion within 2 years. The conversion rate was lowest in patients aged younger than 40 years (3.0%) and highest in the 60- to 69-year-old group (35.0%) (P arthroscopy. Patients treated at high-volume hip arthroscopy centers had a lower THA conversion rate than those treated at low-volume centers (15.1% v 9.7%, P arthroscopy is performed in patients of various ages, including middle-aged and elderly patients. Older patients have a higher rate of conversion to THA, as do patients with osteoarthritis or obesity. Level III, retrospective comparative study. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  15. Predictors for adolescent visits to practitioners of complementary and alternative medicine in a total population (the Young-HUNT Studies.

    Directory of Open Access Journals (Sweden)

    Aslak Steinsbekk

    Full Text Available AIM: To investigate the factors predicting adolescent visits to practitioners of complementary and alternative medicine (CAM. METHODS: A longitudinal cohort study conducted in an adolescent total population in Central Norway (The Nord-Trøndelag Health Studies (HUNT. In Young-HUNT 1, all inhabitants aged 13 to 19 years (N = 8944, 89% response rate were invited to participate, and the youngest group (13 to 15 year olds was surveyed again 4 years later (Young-HUNT 2, N = 2429, 82% response rate. The participants completed a comprehensive questionnaire on health and life style which included a question regarding visits to a CAM practitioner in the last 12 months. RESULTS: One in eleven (8.7%, 95%CI 7.6-9.8% had visited a CAM practitioner, an increase of 26% in 4 years (1.8% points. The final multivariable analysis predicted increased odds of an adolescent becoming a CAM visitor four years later (p<0.05 if she or he had previously visited a CAM practitioner (adjOR 3.4, had musculoskeletal pain (adjOR 1.5, had migraine (adjOR 2.3, used asthma medicines (adjOR 1.8 or suffered from another disease lasting more than three months (adjOR 2.1. Being male predicted reduced odds of visiting a CAM practitioner in the future (adjOR 0.6. CONCLUSION: We can conclude from this study that future visits to a CAM practitioner are predicted by both predisposing factors (being female, having visited a CAM practitioner previously and medical need factors (having had musculoskeletal pain, migraine, used asthma medicines or experienced another disease lasting more than three months. None of the specific variables associated with CAM visits were predictive for CAM visits four years later.

  16. Monitoring dolphins in an urban marine system: total and effective population size estimates of Indo-Pacific bottlenose dolphins in Moreton Bay, Australia.

    Directory of Open Access Journals (Sweden)

    Ina C Ansmann

    Full Text Available Moreton Bay, Queensland, Australia is an area of high biodiversity and conservation value and home to two sympatric sub-populations of Indo-Pacific bottlenose dolphins (Tursiops aduncus. These dolphins live in close proximity to major urban developments. Successful management requires information regarding their abundance. Here, we estimate total and effective population sizes of bottlenose dolphins in Moreton Bay using photo-identification and genetic data collected during boat-based surveys in 2008-2010. Abundance (N was estimated using open population mark-recapture models based on sighting histories of distinctive individuals. Effective population size (Ne was estimated using the linkage disequilibrium method based on nuclear genetic data at 20 microsatellite markers in skin samples, and corrected for bias caused by overlapping generations (Ne c. A total of 174 sightings of dolphin groups were recorded and 365 different individuals identified. Over the whole of Moreton Bay, a population size N of 554 ± 22.2 (SE (95% CI: 510-598 was estimated. The southern bay sub-population was small at an estimated N = 193 ± 6.4 (SE (95% CI: 181-207, while the North sub-population was more numerous, with 446 ± 56 (SE (95% CI: 336-556 individuals. The small estimated effective population size of the southern sub-population (Ne c = 56, 95% CI: 33-128 raises conservation concerns. A power analysis suggested that to reliably detect small (5% declines in size of this population would require substantial survey effort (>4 years of annual mark-recapture surveys at the precision levels achieved here. To ensure that ecological as well as genetic diversity within this population of bottlenose dolphins is preserved, we consider that North and South sub-populations should be treated as separate management units. Systematic surveys over smaller areas holding locally-adapted sub-populations are suggested as an alternative method for increasing ability to detect

  17. Comparison of Muscle Recovery Following Bi-cruciate Substituting versus Posterior Stabilized Total Knee Arthroplasty in the Asian Population.

    Science.gov (United States)

    Takubo, Akihito; Ryu, Keinosuke; Iriuchishima, Takanori; Tokuhashi, Yasuaki

    2017-09-01

    The purpose of this study was to compare muscle recovery in the lower extremities following the newly developed bi-cruciate substituting (BCS) to posterior stabilized (PS) total knee arthroplasty (TKA) in the Asian population. Forty-one knees in 41 patients undergoing BCS-TKA (41 female, average age: 71 ± 8.8) and 34 knees in 34 patients undergoing PS-TKA (33 female, average age: 73 ± 7.2) were included in this study. The maximum isometric power of the quadriceps and hamstring muscles was measured preoperatively, and at 1, 3, 6, and 12 months after surgery using a handheld dynamometer. Postoperative muscle recovery was calculated regarding preoperative muscle power as 100%. Pre- and postoperative range of knee motion, femorotibial angle, and clinical scores (Knee Society score and function score) were also compared. No significant difference in sex, age, preoperative quadriceps, or preoperative hamstring power was observed between the BCS and PS-TKA groups. When regarding the preoperative muscle power as 100%, quadriceps power at 1, 3, 6, and 12 months following BCS-TKA was 61.2 ± 22%, 86.3 ± 28.3%, 97 ± 27.4%, and 112.4 ± 30.8%, respectively. Quadriceps power at 1, 3, 6, and 12 months following PS-TKA was 72.4 ± 20.8%, 84 ± 16.9%, 95 ± 20.7%, and 110.8 ± 27%, respectively. Hamstring power at 1, 3, 6, and 12 months following BCS-TKA was 96.3 ± 30%, 111.4 ± 35%, 120 ± 37%, and 125 ± 31%, respectively. Hamstring power at 1, 3, 6, and 12 months following PS-TKA was 95 ± 25%, 112.4 ± 27%, 117 ± 38.5%, and 120.4 ± 18.5%, respectively. No significant difference in muscle power recovery was observed at 3 ( p  = 0.995), 6 ( p  = 0.944), and 12 ( p  = 0.917) months after surgery between the two groups. No significant difference of the clinical score was observed between the groups (Knee Society score: p  = 0.479, function score: p  = 0.342). No significant

  18. Age-related changes of neurochemically different subpopulations of cardiac spinal afferent neurons in rats.

    Science.gov (United States)

    Guić, Maja Marinović; Runtić, Branka; Košta, Vana; Aljinović, Jure; Grković, Ivica

    2013-08-01

    This study investigated the effect of aging on cardiac spinal afferent neurons in the rat. A patch loaded with retrograde tracer Fast Blue (FB) was applied to all chambers of the rat heart. Morphological and neurochemical characteristics of labeled cardiac spinal afferent neurons were assessed in young (2 months) and old (2 years) rats using markers for likely unmyelinated (isolectin B4; IB4) and myelinated (neurofilament 200; N52) neurons. The number of cardiac spinal afferent neurons decreased in senescence to 15% of that found in young rats (1604 vs. 248). The size of neuronal soma as well as proportion of IB4+ neurons increased significantly, whereas the proportion of N52+ neurons decreased significantly in senescence. Unlike somatic spinal afferents, neurochemically different populations of cardiac spinal afferent neurons experience morphological and neurochemical changes related to aging. A major decrease in total number of cardiac spinal afferent neurons occurs in senescence. The proportion of N52+ neurons decreased in senescence, but it seems that nociceptive innervation is preserved due to increased proportion and size of IB4+ unmyelinated neurons. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Differential regulation of synaptic and extrasynaptic α4 GABA(A) receptor populations by protein kinase A and protein kinase C in cultured cortical neurons.

    Science.gov (United States)

    Bohnsack, John Peyton; Carlson, Stephen L; Morrow, A Leslie

    2016-06-01

    The GABAA α4 subunit exists in two distinct populations of GABAA receptors. Synaptic GABAA α4 receptors are localized at the synapse and mediate phasic inhibitory neurotransmission, while extrasynaptic GABAA receptors are located outside of the synapse and mediate tonic inhibitory transmission. These receptors have distinct pharmacological and biophysical properties that contribute to interest in how these different subtypes are regulated under physiological and pathological states. We utilized subcellular fractionation procedures to separate these populations of receptors in order to investigate their regulation by protein kinases in cortical cultured neurons. Protein kinase A (PKA) activation decreases synaptic α4 expression while protein kinase C (PKC) activation increases α4 subunit expression, and these effects are associated with increased β3 S408/409 or γ2 S327 phosphorylation respectively. In contrast, PKA activation increases extrasynaptic α4 and δ subunit expression, while PKC activation has no effect. Our findings suggest synaptic and extrasynaptic GABAA α4 subunit expression can be modulated by PKA to inform the development of more specific therapeutics for neurological diseases that involve deficits in GABAergic transmission. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Population Pharmacokinetics of Telapristone (CDB-4124) and its Active Monodemethylated Metabolite CDB-4453, with a Mixture Model for Total Clearance

    OpenAIRE

    Morris, Denise; Podolski, Joseph; Kirsch, Alan; Wiehle, Ronald; Fleckenstein, Lawrence

    2011-01-01

    Telapristone is a selective progesterone antagonist that is being developed for the long-term treatment of symptoms associated with endometriosis and uterine fibroids. The population pharmacokinetics of telapristone (CDB-4124) and CDB-4453 was investigated using nonlinear mixed-effects modeling. Data from two clinical studies (n?=?32) were included in the analysis. A two-compartment (parent) one compartment (metabolite) mixture model (with two populations for apparent clearance) with first-or...

  1. Expression of the transient receptor potential channels TRPV1, TRPA1 and TRPM8 in mouse trigeminal primary afferent neurons innervating the dura

    Science.gov (United States)

    2012-01-01

    Background Migraine and other headache disorders affect a large percentage of the population and cause debilitating pain. Activation and sensitization of the trigeminal primary afferent neurons innervating the dura and cerebral vessels is a crucial step in the “headache circuit”. Many dural afferent neurons respond to algesic and inflammatory agents. Given the clear role of the transient receptor potential (TRP) family of channels in both sensing chemical stimulants and mediating inflammatory pain, we investigated the expression of TRP channels in dural afferent neurons. Methods We used two fluorescent tracers to retrogradely label dural afferent neurons in adult mice and quantified the abundance of peptidergic and non-peptidergic neuron populations using calcitonin gene-related peptide immunoreactivity (CGRP-ir) and isolectin B4 (IB4) binding as markers, respectively. Using immunohistochemistry, we compared the expression of TRPV1 and TRPA1 channels in dural afferent neurons with the expression in total trigeminal ganglion (TG) neurons. To examine the distribution of TRPM8 channels, we labeled dural afferent neurons in mice expressing farnesylated enhanced green fluorescent protein (EGFPf) from a TRPM8 locus. We used nearest-neighbor measurement to predict the spatial association between dural afferent neurons and neurons expressing TRPA1 or TRPM8 channels in the TG. Results and conclusions We report that the size of dural afferent neurons is significantly larger than that of total TG neurons and facial skin afferents. Approximately 40% of dural afferent neurons exhibit IB4 binding. Surprisingly, the percentage of dural afferent neurons containing CGRP-ir is significantly lower than those of total TG neurons and facial skin afferents. Both TRPV1 and TRPA1 channels are expressed in dural afferent neurons. Furthermore, nearest-neighbor measurement indicates that TRPA1-expressing neurons are clustered around a subset of dural afferent neurons. Interestingly, TRPM

  2. Bcl-2 over-expression fails to prevent age-related loss of calretinin positive neurons in the mouse dentate gyrus

    Directory of Open Access Journals (Sweden)

    Han Mingbo

    2006-08-01

    Full Text Available Abstract Background Cognitive performance declines with increasing age. Possible cellular mechanisms underlying this age-related functional decline remain incompletely understood. Early studies attributed this functional decline to age-related neuronal loss. Subsequent studies using unbiased stereological techniques found little or no neuronal loss during aging. However, studies using specific cellular markers found age-related loss of specific neuronal types. To test whether there is age-related loss of specific neuronal populations in the hippocampus, and subsequently, whether over-expression of the B-cell lymphoma protein-2 (Bcl-2 in these neurons could delay possible age-related neuronal loss, we examined calretinin (CR positive neurons in the mouse dentate gyrus during aging. Result In normal mice, there was an age-related loss of CR positive cells in the dentate gyrus. At the same region, there was no significant decrease of total numbers of neurons, which suggested that age-related loss of CR positive cells was due to the decrease of CR expression in these cells instead of cell death. In the transgenic mouse line over-expressing Bcl-2 in neurons, there was an age-related loss of CR positive cells. Interestingly, there was also an age-related neuronal loss in this transgenic mouse line. Conclusion These data suggest an age-related loss of CR positive neurons but not total neuronal loss in normal mice and this age-related neuronal change is not prevented by Bcl-2 over-expression.

  3. Intratelencephalic corticostriatal neurons equally excite striatonigral and striatopallidal neurons and their discharge activity is selectively reduced in experimental parkinsonism

    OpenAIRE

    Ballion, B. (B.); Mallet, N. (Nicolas); Bezard, E. (E.); Lanciego, J.L. (José Luis); Gonon, F. (Francois)

    2008-01-01

    Striatonigral and striatopallidal neurons form distinct populations of striatal projection neurons. Their discharge activity is imbalanced after dopaminergic degeneration in Parkinson's disease. Striatal projection neurons receive massive cortical excitatory inputs from bilateral intratelencephalic (IT) neurons projecting to both the ipsilateral and contralateral striatum and from collateral axons of ipsilateral neurons that send their main axon through the pyramidal tract (PT). Previous anat...

  4. A Prospective Study of Venous Thromboembolic Prophylaxis Using Foot Pumps Following Total Knee Replacement in a Chinese Population

    Directory of Open Access Journals (Sweden)

    Yiu-Chung Wong

    2013-06-01

    Conclusion: The rate of proximal DVT after TKR was low (4.5% without pharmacological prophylaxis. We advise against the use of pharmacological prophylaxis in Chinese population for TKRs because of the low risk of proximal DVT and its possible bleeding complications. Foot pump did not lower the rate of DVTfurther, and its use for DVT prophylaxis in TKR is not necessary.

  5. Estimates of Total Dietary Folic Acid Intake in the Australian Population Following Mandatory Folic Acid Fortification of Bread

    Directory of Open Access Journals (Sweden)

    Jacinta Dugbaza

    2012-01-01

    Full Text Available Mandatory folic acid fortification of wheat flour for making bread was implemented in Australia in September 2009, to improve the dietary folate status of women of child-bearing age, and help reduce the incidence of neural tube defects in the population. This paper presents estimates of folic acid intake in the target population and other subgroups of the Australian population following implementation of the mandatory folic acid fortification standard. In June/July 2010 one hundred samples from seven bread categories were purchased from around the country and individually analysed for the amount of folic acid they contained. A modification to the triple enzyme microbiological method was used to measure folic acid in the individual bread samples. The folic acid analytical values together with national food consumption data were used to generate estimates of the population’s folic acid intake from fortified foods. Food Standards Australia New Zealand’s (FSANZ custom-built dietary modelling program (DIAMOND was used for the estimates. The mean amount of folic acid found in white bread was 200 μg/100 g which demonstrated that folic-acid-fortified wheat flour was used to bake the bread. The intake estimates indicated an increase in mean folic acid intake of 159 μg per day for the target group. Other sub-groups of the population also showed increases in estimated mean daily intake of folic acid.

  6. Anxiogenic drug administration and elevated plus-maze exposure in rats activate populations of relaxin-3 neurons in the nucleus incertus and serotonergic neurons in the dorsal raphe nucleus.

    Science.gov (United States)

    Lawther, A J; Clissold, M L; Ma, S; Kent, S; Lowry, C A; Gundlach, A L; Hale, M W

    2015-09-10

    Anxiety is a complex and adaptive emotional state controlled by a distributed and interconnected network of brain regions, and disruption of these networks is thought to give rise to the behavioral symptoms associated with anxiety disorders in humans. The dorsal raphe nucleus (DR), which contains the majority of forebrain-projecting serotonergic neurons, is implicated in the control of anxiety states and anxiety-related behavior via neuromodulatory effects on these networks. Relaxin-3 is the native neuropeptide ligand for the Gi/o-protein-coupled receptor, RXFP3, and is primarily expressed in the nucleus incertus (NI), a tegmental region immediately caudal to the DR. RXFP3 activation has been shown to modulate anxiety-related behavior in rodents, and RXFP3 mRNA is expressed in the DR. In this study, we examined the response of relaxin-3-containing neurons in the NI and serotonergic neurons in the DR following pharmacologically induced anxiety and exposure to an aversive environment. We administered the anxiogenic drug FG-7142 or vehicle to adult male Wistar rats and, 30 min later, exposed them to either the elevated plus-maze or home cage control conditions. Immunohistochemical detection of c-Fos was used to determine activation of serotonergic neurons in the DR and relaxin-3 neurons in the NI, measured 2h following drug injection. Analysis revealed that FG-7142 administration and exposure to the elevated plus-maze are both associated with an increase in c-Fos expression in relaxin-3-containing neurons in the NI and in serotonergic neurons in dorsal and ventrolateral regions of the DR. These data are consistent with the hypothesis that relaxin-3 systems in the NI and serotonin systems in the DR interact to form part of a network involved in the control of anxiety-related behavior. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Population pharmacokinetics of telapristone (CDB-4124) and its active monodemethylated metabolite CDB-4453, with a mixture model for total clearance.

    Science.gov (United States)

    Morris, Denise; Podolski, Joseph; Kirsch, Alan; Wiehle, Ronald; Fleckenstein, Lawrence

    2011-12-01

    Telapristone is a selective progesterone antagonist that is being developed for the long-term treatment of symptoms associated with endometriosis and uterine fibroids. The population pharmacokinetics of telapristone (CDB-4124) and CDB-4453 was investigated using nonlinear mixed-effects modeling. Data from two clinical studies (n = 32) were included in the analysis. A two-compartment (parent) one compartment (metabolite) mixture model (with two populations for apparent clearance) with first-order absorption and elimination adequately described the pharmacokinetics of telapristone and CDB-4453. Telapristone was rapidly absorbed with an absorption rate constant (Ka) of 1.26 h(-1). Moderate renal impairment resulted in a 74% decrease in Ka. The population estimates for oral clearance (CL/F) for the two populations were 11.6 and 3.34 L/h, respectively, with 25% of the subjects being allocated to the high-clearance group. Apparent volume of distribution for the central compartment (V2/F) was 37.4 L, apparent inter-compartmental clearance (Q/F) was 21.9 L/h, and apparent peripheral volume of distribution for the parent (V4/F) was 120 L. The ratio of the fraction of telapristone converted to CDB-4453 to the distribution volume of CDB-4453 (Fmet(est)) was 0.20/L. Apparent volume of distribution of the metabolite compartment (V3/F) was fixed to 1 L and apparent clearance of the metabolite (CLM/F) was 2.43 L/h. A two-compartment parent-metabolite model adequately described the pharmacokinetics of telapristone and CDB-4453. The clearance of telapristone was separated into two populations and could be the result of metabolism via polymorphic CYP3A5.

  8. Genome-wide association study for levels of total serum IgE identifies HLA-C in a Japanese population.

    Directory of Open Access Journals (Sweden)

    Yohei Yatagai

    Full Text Available Most of the previously reported loci for total immunoglobulin E (IgE levels are related to Th2 cell-dependent pathways. We undertook a genome-wide association study (GWAS to identify genetic loci responsible for IgE regulation. A total of 479,940 single nucleotide polymorphisms (SNPs were tested for association with total serum IgE levels in 1180 Japanese adults. Fine-mapping with SNP imputation demonstrated 6 candidate regions: the PYHIN1/IFI16, MHC classes I and II, LEMD2, GRAMD1B, and chr13∶60576338 regions. Replication of these candidate loci in each region was assessed in 2 independent Japanese cohorts (n = 1110 and 1364, respectively. SNP rs3130941 in the HLA-C region was consistently associated with total IgE levels in 3 independent populations, and the meta-analysis yielded genome-wide significance (P = 1.07×10(-10. Using our GWAS results, we also assessed the reproducibility of previously reported gene associations with total IgE levels. Nine of 32 candidate genes identified by a literature search were associated with total IgE levels after correction for multiple testing. Our findings demonstrate that SNPs in the HLA-C region are strongly associated with total serum IgE levels in the Japanese population and that some of the previously reported genetic associations are replicated across ethnic groups.

  9. Feedforward and feedback inhibition in neostriatal GABAergic spiny neurons.

    Science.gov (United States)

    Tepper, James M; Wilson, Charles J; Koós, Tibor

    2008-08-01

    There are two distinct inhibitory GABAergic circuits in the neostriatum. The feedforward circuit consists of a relatively small population of GABAergic interneurons that receives excitatory input from the neocortex and exerts monosynaptic inhibition onto striatal spiny projection neurons. The feedback circuit comprises the numerous spiny projection neurons and their interconnections via local axon collaterals. This network has long been assumed to provide the majority of striatal GABAergic inhibition and to sharpen and shape striatal output through lateral inhibition, producing increased activity in the most strongly excited spiny cells at the expense of their less strongly excited neighbors. Recent results, mostly from recording experiments of synaptically connected pairs of neurons, have revealed that the two GABAergic circuits differ markedly in terms of the total number of synapses made by each, the strength of the postsynaptic response detected at the soma, the extent of presynaptic convergence and divergence and the net effect of the activation of each circuit on the postsynaptic activity of the spiny neuron. These data have revealed that the feedforward inhibition is powerful and widespread, with spiking in a single interneuron being capable of significantly delaying or even blocking the generation of spikes in a large number of postsynaptic spiny neurons. In contrast, the postsynaptic effects of spiking in a single presynaptic spiny neuron on postsynaptic spiny neurons are weak when measured at the soma, and unable to significantly affect spike timing or generation. Further, reciprocity of synaptic connections between spiny neurons is only rarely observed. These results suggest that the bulk of the fast inhibition that has the strongest effects on spiny neuron spike timing comes from the feedforward interneuronal system whereas the axon collateral feedback system acts principally at the dendrites to control local excitability as well as the overall level of

  10. Population dynamics of the fast-growing sub-populations of Pseudomonas and total bacteria, and their protozoan grazers, revealed by fenpropimorph treatment

    DEFF Research Database (Denmark)

    Thirup, L; Ekelund, Flemming; Johnsen, Kaare Eske

    2000-01-01

    The population dynamics of indigenous soil bacteria and protozoa on decaying barley roots were followed by using litter bags buried in laboratory-incubated soil. The soil was either non-treated or treated with the fungicide fenpropimorph (in the formulation Corbel) at concentrations corresponding...... of protozoa corresponding to the two subpopulations was followed. The results strongly indicate a predatory association between the protozoa and bacteria. This was shown by a tight temporal association, and by a stimulation of bacteria following predatory release when protozoa were inhibited by fenpropimorph...

  11. Dietary determinants of serum total cholesterol among middle-aged and older adults: a population-based cross-sectional study in Dar es Salaam, Tanzania.

    Science.gov (United States)

    Kakarmath, Sujay S; Zack, Rachel M; Leyna, Germana H; Fahimi, Saman; Liu, Enju; Fawzi, Wafaie W; Lukmanji, Zohra; Killewo, Japhet; Sacks, Frank; Danaei, Goodarz

    2017-06-06

    To assess the dietary determinants of serum total cholesterol. Cross-sectional population-based study. Peri-urban region of Dar es Salaam, Tanzania. 347 adults aged 40 years and older from the Dar es Salaam Urban Cohort Hypertension Study. Serum total cholesterol measured using a point-of-care device. Mean serum total cholesterol level was 204 mg/dL (IQR 169-236 mg/dL) in women and 185 mg/dL (IQR 152-216 mg/dL) in men. After adjusting for demographic, socioeconomic, lifestyle and dietary factors, participants who reported using palm oil as the major cooking oil had serum total cholesterol higher by 15 mg/dL (95% CI 1 to 29 mg/dL) compared with those who reported using sunflower oil. Consumption of one or more servings of meat per day (p for trend=0.017) and less than five servings of fruits and vegetables per day (p for trend=0.024) were also associated with higher serum total cholesterol. A combination of using palm oil for cooking, eating more than one serving of meat per day and fewer than five servings of fruits and vegetables per day, was associated with 46 mg/dL (95% CI 16 to 76 mg/dL) higher serum total cholesterol. Using palm oil for cooking was associated with higher serum total cholesterol levels in this peri-urban population in Dar es Salaam. Reduction of saturated fat content of edible oil may be considered as a population-based strategy for primary prevention of cardiovascular diseases. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. Intake of vitamin A and carotenoids from the Italian population--results of an Italian total diet study.

    Science.gov (United States)

    Lucarini, Massimo; Lanzi, Sabina; D'Evoli, Laura; Aguzzi, Altero; Lombardi-Boccia, Ginevra

    2006-05-01

    The present study focused on vitamin A and carotenoids (alpha-and beta-carotene, lutein and zeaxanthin, beta-cryptoxanthin, lycopene) daily intake from the Italian total diet. The input of some food groups (cereals, vegetables, fruits, milk and dairy, meat and meat products, fish) most responsible for major and minor contributions to the daily intake of these molecules was evaluated. Furthermore the contribution to the dietary intake of beta-carotene and lutein of the most consumed vegetables in the market basket of the Italian total diet (beets, brassica vegetables, carrots, chicory, courgette (zucchini), green beans, lettuce, peas, pepper, spinach, tomatoes) was also investigated. Vitamin A daily intake was 855 mg/person/day. The vegetables food group made the greatest contribution (37%), followed by the meat and meat products food group (23%). The Italian total diet provided 14.3 mg/person/day of carotenoids; lycopene was the highest (7.4 mg/day), followed by lutein + zeaxanthin (4 mg/day), beta-carotene (2.6 mg/day), alpha-carotene (0.15 mg/day), and beta-cryptoxanthin (0.17 mg/day). Carrots and tomatoes were the main sources of beta-carotene in the diet, otherwise the daily consumption of leafy vegetables (spinach, beets, lettuce) made the main contribution to lutein + zeaxanthin daily intake.

  13. Evaluation of seasonality on total water intake, water loss and water balance in the general population in Greece.

    Science.gov (United States)

    Malisova, O; Bountziouka, V; Panagiotakos, D Β; Zampelas, A; Kapsokefalou, M

    2013-07-01

    Water balance is achieved when water intake from solid and fluid foods and drinking water meets water losses, mainly in sweat, urine and faeces. Seasonality, particularly in Mediterranean countries that have a hot summer, may affect water loss and consequently water balance. Water balance has not been estimated before on a population level and the effect of seasonality has not been evaluated. The present study aimed to compare water balance, intake and loss in summer and winter in a sample of the general population in Greece. The Water Balance Questionnaire (WBQ) was used to evaluate water balance, estimating water intake and loss in summer (n = 480) and in winter (n = 412) on a stratified sample of the general population in Athens, Greece. In winter, mean (SD) water balance was -63 (1478) mL/day(-1) , mean (SD)water intake was 2892 (987) mL/day(-1) and mean (quartile range) water loss was 2637 (1810-3922) mL/day(-1) . In summer, mean (SD) water balance was -58 (2150) mL/day(-1) , mean (SD) water intake was 3875 (1373) mL/day(-1) and mean (quartile range) water loss was 3635 (2365-5258) mL/day(-1) . Water balance did not differ between summer and winter (P = 0.96); however, the data distribution was different; in summer, approximately 8% more participants were falling in the low and high water balance categories. Differences in water intake from different sources were identified (P balance in summer and winter was not different. However, water intake and loss were approximately 40% higher in summer than in winter. More people were falling in the low and high water balance categories in summer when comparing the distribution on water balance in winter. © 2013 The Authors Journal of Human Nutrition and Dietetics © 2013 The British Dietetic Association Ltd.

  14. Betel quid chewing as a source of manganese exposure: total daily intake of manganese in a Bangladeshi population.

    Science.gov (United States)

    Al-Rmalli, Shaban W; Jenkins, Richard O; Haris, Parvez I

    2011-02-07

    A relationship between betel quid chewing in Bangladeshi populations and the development of skin lesions and tremor has been previously reported, for people exposed to high levels of arsenic (As) through drinking contaminated groundwater. Exposure to manganese (Mn) is also known to induce neurotoxicity and levels of Mn in Bangladeshi groundwater are also high. The present study evaluates betel quid chewing as an overlooked source of Mn exposure in a Bangladeshi population. Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine (1) urinary Mn levels for 15 chewers and 22 non-chewers from the ethnic Bangladeshi community in the United Kingdom, and (2) Mn levels in betel quids, its individual components and other Bangladeshi foods. Betel quid chewers displayed a significantly higher (P = 0.009) mean Mn concentration in urine (1.93 μg L(-1)) compared to non-chewers (0.62 μg L(-1)). High levels of Mn were detected in Piper betel leaves with an overall average of 135 mg kg(-1) (range 26 -518 mg kg(-1)). The mean concentration of Mn in betel quid was 41 mg kg(-1) (SD 27) and the daily intake of Mn in the Bangladeshi population was estimated to be 20.3 mg/day. Chewing six betel quids could contribute up to 18% of the maximum recommended daily intake of Mn. We have demonstrated that Mn in betel quids is an overlooked source of exposure to Mn in humans. Chewers display a 3.1 fold increased urinary Mn concentration compared to non-chewers. The practice of betel quid chewing contributes a high proportion of the maximum recommended daily intake of Mn, which could make chewers in Bangladesh more vulnerable to Mn neurotoxicity.

  15. Postresuscitative Changes of Brain-Derived Neurotrophic Factor (BDNF Protein Expression: Association With Neuronal Death

    Directory of Open Access Journals (Sweden)

    M. Sh. Avrushchenko

    2017-01-01

    Full Text Available Aim of the study: to evaluate expression level of BDNF and its association with the postresuscitative neuronal death in highly hypoxia-sensitive brain regions.Materials and methods. Cardiac arrest in adult albino male rats was evoked by intrathoracic clamping of supracardiac bundle of vessels for 10 min. Pyramidal neurons of the hippocampus and Purkinje cells of the cerebellum were analyzed at various time points after resuscitation (days 1, 4, 7, 14. Shame-operated rats served as controls. The expression of BDNF protein was immunohistochemically determined. The BDNF expression level was determined by evalution on the base of the average optical density. The number of neurons with different BDNF expression levels and the total number of neurons per 1 mm of the layer length were computed. Image analysis systems (Intel personal computer, Olympus BX-41 microscope, ImageScopeM, ImageJ 1,48v and MS Excel 2007 software packages were used in the study. Data statistical processing was performed with the aid of Statistica 7.0 program and Kolmogorov-Smirnov λ-test, Mann-Whitney U-test and Student's t-test.Results. The dynamics of postresuscitative shifts of BDNF immunoreactivity in neuronal populations of hippocampal pyramidal cells and cerebellar Purkinje cells was established. It was shown that the level of BDNF expression within the two neuronal populations decreased, that was accompanied by neuronal death. In the Purkinje cell population the neuronal death occurred by the 4th day after resuscitation, while in the hippocampus, it occurs only by the 7th day. Notably, only BDNF-negative neurons or neurons with low level of BDNF expression died in both neuronal populations.Conclusion. The results of the study indicate the existence of an interrelation between the shifts in BDNF expression and the postresuscitative neuronal death. It was shown that only the cells with none or poor BDNF expression underwent death in highly hypoxia-sensitive neuronal

  16. The effect of tranexamic acid in unilateral and bilateral total knee arthroplasty in the South Asian population: A retrospective cohort study.

    Science.gov (United States)

    Mufarrih, Syed Hamza; Malik, Azeem Tariq; Qureshi, Nada Qaisar; Lakdawala, Riaz Hussain; Rabbani, Muhammad Umar; Ali, Arif; Noordin, Shahryar

    2018-04-01

    Together with evidence of higher bleeding tendencies, the vulnerability of the South-Asian population to anemia secondary to a higher prevalence of hemoglobinopathies and micronutrient deficiencies merits further exploration of the effects of tranexamic acid on this population. Additionally, limited access to self-care facilities and certain sociocultural beliefs and practices may not be conducive to a speedy recovery from surgical complications. The aim of this study is to investigate the effects of intraoperative administration of tranexamic acid during total knee arthroplasty when considering the South-Asian population. Medical record files of 355 patients who underwent total knee arthroplasty (2007-2015) were reviewed to collect data regarding patient characteristics, surgical variables and post-operative complications. Unilateral and Bilateral total knee arthroplasty were studied separately. Analysis was done using t-test, Mann-Whitney U test, chi-square and Fisher's exact square where appropriate. The threshold for significance was p tranexamic acid caused a significant reduction in estimated blood loss (p-value=0.011), total operative time, calculated blood loss, and hemoglobin change (p-valuetranexamic acid only caused a significant reduction in calculated blood loss (p-value tranexamic acid vs. those who did not, there was a significant increase in length of hospital stay (ptranexamic acid effectively reduces intraoperative blood loss, it does not have an effect on the need for post-operative blood transfusions. The increased length of stay and special care unit admissions associated with tranexamic acid use should be explored further to reveal the complete safety profile of tranexamic acid administration in the South-Asian population during total knee arthroplasty. Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  17. A Case Report: Cornerstone Health Care Reduced the Total Cost of Care Through Population Segmentation and Care Model Redesign.

    Science.gov (United States)

    Green, Dale E; Hamory, Bruce H; Terrell, Grace E; O'Connell, Jasmine

    2017-08-01

    Over the course of a single year, Cornerstone Health Care, a multispecialty group practice in North Carolina, redesigned the underlying care models for 5 of its highest-risk populations-late-stage congestive heart failure, oncology, Medicare-Medicaid dual eligibles, those with 5 or more chronic conditions, and the most complex patients with multiple late-stage chronic conditions. At the 1-year mark, the results of the program were analyzed. Overall costs for the patients studied were reduced by 12.7% compared to the year before enrollment. All fully implemented programs delivered between 10% and 16% cost savings. The key area for savings factor was hospitalization, which was reduced by 30% across all programs. The greatest area of cost increase was "other," a category that consisted in large part of hospice services. Full implementation was key; 2 primary care sites that reverted to more traditional models failed to show the same pattern of savings.

  18. Evaluation of Distal Femoral Rotational Alignment with Spiral CT Scan before Total Knee Arthroplasty (A Study in Iranian Population

    Directory of Open Access Journals (Sweden)

    Mahmoud Jabalameli

    2016-04-01

    Full Text Available Background: Evaluating the landmarks for rotation of the distal femur is a challenge for orthopedic surgeons. Although the posterior femoral condyle axis is a good landmark for surgeons, the surgical transepicondylar axis may be a better option with the help of preoperative CT scanning. The purpose of this study was to ascertain relationships among the axes’ guiding distal femur rotational alignment in preoperative CT scans of Iranian patients who were candidates for total knee arthroplasty and the effects of age, gender, and knee alignment on these relationships. Methods: One hundred and eight cases who were admitted to two university hospitals for total knee arthroplasty were included in this study. The rotation of the distal femur was evaluated using single axial CT images through the femoral epicondyle. Four lines were drawn digitally in this view: anatomical and surgical transepicondylar axes, posterior condylar axis and the Whiteside anteroposterior line. The alignment of the extremity was evaluated in the standing alignment view. Then the angles were measured along these lines and their relationship was evaluated. Results: The mean angle between the anatomical transepicondylar axis and posterior condylar axis and between the surgical transepicondylar axis and posterior condylar axis were 5.9 ± 1.6 degrees and 1.6±1.7 degrees respectively. The mean angle between the Whiteside’s anteroposterior line and the line perpendicular to the posterior condylar axis was 3.7±2.1 degrees. Significant differences existed between the two genders in these relationships. No significant correlation between the age of patients and angles of the distal femur was detected. The anatomical surgical transepicondylar axis was in 4.3 degrees external rotation in relation to the surgical transepicondylar axis. Conclusion: Preoperative CT scanning can help accurately determine rotational landmarks of the distal femur. If one of the reference axes cannot be

  19. 5-HT2 and 5-HT7 receptor agonists facilitate plantar stepping in chronic spinal rats through actions on different populations of spinal neurons

    Directory of Open Access Journals (Sweden)

    Urszula eSlawinska

    2014-08-01

    Full Text Available There is considerable evidence from research in neonatal and adult rat and mouse preparations to warrant the conclusion that activation of 5-HT2 and 5-HT1A/7 receptors leads to activation of the spinal cord circuitry for locomotion. These receptors are involved in control of locomotor movements, but it is not clear how they are implicated in the responses to 5-HT agonists observed after spinal cord injury. Here we used agonists that are efficient in promoting locomotor recovery in paraplegic rats, 8-OHDPAT (acting on 5-HT1A/7 receptors and quipazine (acting on 5-HT2 receptors, to examine this issue. Analysis of intra- and interlimb coordination confirmed that the locomotor performance was significantly improved by either drug, but the data revealed marked differences in their mode of action. Interlimb coordination was significantly better after 8-OHDPAT application, and the activity of the extensor soleus muscle was significantly longer during the stance phase of locomotor movements enhanced by quipazine. Our results show that activation of both receptors facilitates locomotion, but their effects are likely exerted on different populations of spinal neurons. Activation of 5-HT2 receptors facilitates the output stage of the locomotor system, in part by directly activating motoneurons, and also through activation of interneurons of the locomotor CPG. Activation of 5-HT7/1A receptors facilitates the activity of the locomotor CPG, without direct actions on the output components of the locomotor system, including motoneurons. Although our findings show that the combined use of these two drugs results in production of well-coordinated weight supported locomotion with a reduced need for exteroceptive stimulation, they also indicate that there might be some limitations to the utility of combined treatment. Sensory feedback and some intraspinal circuitry recruited by the drugs can conflict with the locomotor activation.

  20. Metabolic syndrome and its components with neuron-specific enolase: a cross-sectional study in large health check-up population in China.

    Science.gov (United States)

    Wang, Shu-Yi; Zha, Xiao-Juan; Zhu, Xin-Ying; Li, Wen-Bo; Ma, Jun; Wu, Ze-Wei; Wu, Huan; Jiang, Ming-Fei; Wen, Yu-Feng

    2018-04-10

    This study was aimed at investigating the relationship between neuron-specific enolase (NSE) and components of metabolic syndrome (MS). Cross-sectional study. Chinese health check-up population. 40 684 health check-up people were enrolled in this study from year 2014 to 2016. OR and coefficient for MS. The percentage of abnormal NSE and MS was 26.85% and 8.85%, respectively. There were significant differences in sex, body mass index, drinking habit, triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), blood pressure and MS between low-NSE and high-NSE groups. In logistic regression analysis, elevated NSE was present in MS, higher body mass index, hypertriglyceridaemia, hypertension and low-HDL groups. Stepwise linear analysis showed a negative correlation between NSE and fasting blood glucose (FBG) (<6.0 mmol/L), and a positive correlation between NSE and TGs (<20 mmol/L), systolic blood pressure (75-200 mm Hg), HDL-C (0.75-2.50 mmol/L), diastolic blood pressure (<70 mm Hg) and FBG (6.00-20.00 mmol/L). Furthermore, MS was positively correlated with NSE within the range of 2.00-7.50 ng/mL, but had a negative correlation with NSE within the range of 7.50-23.00 ng/mL. There are associations between NSE with MS and its components. The result suggests that NSE may be a potential predictor of MS. Further research could be conducted in discussing the potential mechanism involved. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. Differential regulation of the phosphorylation of Trimethyl-lysine27 histone H3 at serine 28 in distinct populations of striatal projection neurons.

    Science.gov (United States)

    Bonito-Oliva, Alessandra; Södersten, Erik; Spigolon, Giada; Hu, Xiaochen; Hellysaz, Arash; Falconi, Anastasia; Gomes, Ana-Luisa; Broberger, Christian; Hansen, Klaus; Fisone, Gilberto

    2016-08-01

    Phosphorylation of histone H3 (H3) on serine 28 (S28) at genomic regions marked by trimethylation of lysine 27 (H3K27me3) often correlates with increased expression of genes normally repressed by Polycomb group proteins (PcG). We show that amphetamine, an addictive psychostimulant, and haloperidol, a typical antipsychotic drug, increase the phosphorylation of H3 at S28 and that this effect occurs in the context of H3K27me3. The increases in H3K27me3S28p occur in distinct populations of projection neurons located in the striatum, the major component of the basal ganglia. Genetic inactivation of the protein phosphatase-1 inhibitor, dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32), reduces the phosphorylation of H3K27me3S28 produced by amphetamine and haloperidol. In contrast, knockout of the mitogen- and stress activated kinase 1 (MSK1), which is implicated in the phosphorylation of histone H3, decreases the effect of amphetamine, but not that of haloperidol. Chromatin immunoprecipitation analysis shows that amphetamine and haloperidol increase the phosphorylation of H3K27me3S28 at the promoter regions of Atf3, Npas4 and Lipg, three genes repressed by PcG. These results identify H3K27me3S28p as a potential mediator of the effects exerted by amphetamine and haloperidol, and suggest that these drugs may act by re-activating PcG repressed target genes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. 5-HT₂ and 5-HT₇ receptor agonists facilitate plantar stepping in chronic spinal rats through actions on different populations of spinal neurons.

    Science.gov (United States)

    Sławińska, Urszula; Miazga, Krzysztof; Jordan, Larry M

    2014-01-01

    There is considerable evidence from research in neonatal and adult rat and mouse preparations to warrant the conclusion that activation of 5-HT2 and 5-HT1A/7 receptors leads to activation of the spinal cord circuitry for locomotion. These receptors are involved in control of locomotor movements, but it is not clear how they are implicated in the responses to 5-HT agonists observed after spinal cord injury. Here we used agonists that are efficient in promoting locomotor recovery in paraplegic rats, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OHDPAT) (acting on 5-HT1A/7 receptors) and quipazine (acting on 5-HT2 receptors), to examine this issue. Analysis of intra- and interlimb coordination confirmed that the locomotor performance was significantly improved by either drug, but the data revealed marked differences in their mode of action. Interlimb coordination was significantly better after 8-OHDPAT application, and the activity of the extensor soleus muscle was significantly longer during the stance phase of locomotor movements enhanced by quipazine. Our results show that activation of both receptors facilitates locomotion, but their effects are likely exerted on different populations of spinal neurons. Activation of 5-HT2 receptors facilitates the output stage of the locomotor system, in part by directly activating motoneurons, and also through activation of interneurons of the locomotor central pattern generator (CPG). Activation of 5-HT7/1A receptors facilitates the activity of the locomotor CPG, without direct actions on the output components of the locomotor system, including motoneurons. Although our findings show that the combined use of these two drugs results in production of well-coordinated weight supported locomotion with a reduced need for exteroceptive stimulation, they also indicate that there might be some limitations to the utility of combined treatment. Sensory feedback and some intraspinal circuitry recruited by the drugs can conflict with the

  3. Motor Neurons

    DEFF Research Database (Denmark)

    Hounsgaard, Jorn

    2017-01-01

    Motor neurons translate synaptic input from widely distributed premotor networks into patterns of action potentials that orchestrate motor unit force and motor behavior. Intercalated between the CNS and muscles, motor neurons add to and adjust the final motor command. The identity and functional...... in in vitro preparations is far from complete. Nevertheless, a foundation has been provided for pursuing functional significance of intrinsic response properties in motoneurons in vivo during motor behavior at levels from molecules to systems....

  4. Lack of CCR5 modifies glial phenotypes and population of the nigral dopaminergic neurons, but not MPTP-induced dopaminergic neurodegeneration.

    Science.gov (United States)

    Choi, Dong-Young; Lee, Myung Koo; Hong, Jin Tae

    2013-01-01

    Constitutive expression of C-C chemokine receptor (CCR) 5 has been detected in astrocytes, microglia and neurons, but its physiological roles in the central nervous system are obscure. The bidirectional interactions between neuron and glial cells through CCR5 and its ligands were thought to be crucial for maintaining normal neuronal activities. No study has described function of CCR5 in the dopaminergic neurodegeneration in Parkinson's disease. In order to examine effects of CCR5 on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration, we employed CCR5 wild type (WT) and knockout (KO) mice. Immunostainings for tyrosine hydroxylase (TH) exhibited that CCR5 KO mice had lower number of TH-positive neurons even in the absence of MPTP. Difference in MPTP (15mg/kg×4 times, 2hr interval)-mediated loss of TH-positive neurons was subtle between CCR5 WT and KO mice, but there was larger dopamine depletion, behavioral impairments and microglial activation in CCR5 deficient mice. Intriguingly, CCR5 KO brains contained higher immunoreactivity for monoamine oxidase (MAO) B which was mainly localized within astrocytes. In agreement with upregulation of MAO B, concentration of MPP+ was higher in the substantia nigra and striatum of CCR5 KO mice after MPTP injection. We found remarkable activation of p38 MAPK in CCR5 deficient mice, which positively regulates MAO B expression. These results indicate that CCR5 deficiency modifies the nigrostriatal dopaminergic neuronal system and bidirectional interaction between neurons and glial cells via CCR5 might be important for dopaminergic neuronal survival. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Demonstration of extensive GABA synthesis in the small population of GAD positive neurons in cerebellar cultures by the use of pharmacological tools

    DEFF Research Database (Denmark)

    Sonnewald, Ursula; Kortner, Trond M; Qu, Hong

    2006-01-01

    by labeling from [U-(13)C]glutamine added on day 7. Altogether the findings show continuous GABA synthesis and degradation throughout the culture period in the cerebellar neurons. At 10 microM AOAA, GABA synthesis from [U-(13)C]glutamine was not affected, indicating that transaminases are not involved in GABA...... that GABA synthesis is taking place via GAD in a subpopulation of the cerebellar neurons, throughout the culture period....

  6. Total body calcium by neutron activation analysis in normals and osteoporotic populations: a discriminator of significant bone mass loss

    International Nuclear Information System (INIS)

    Ott, S.M.; Murano, R.; Lewellen, T.K.; Nelp, W.B.; Chesnut, C.M.

    1983-01-01

    Measurements of total body calcium by neutron activation (TBC) in 94 normal individuals and 86 osteoporotic patients are reported. The ability of TBC to discriminate normal from osteoporotic females was evaluated with decision analysis. Bone mineral content (BMC) by single-photon absorptiometry was also measured. TBC was higher in males (range 826 to 1363 gm vs 537 to 1054 in females) and correlated with height in all normals. In females over age 55 there was a negative correlation with age. Thus, for normals an algorithm was derived to allow comparison between measured TBC and that predicted by sex, age, and height (TBCp). In the 28 normal females over age 55, the TBC was 764 +/- 115 gm vs. 616 +/- 90 in the osteoporotics. In 63 of the osteoporotic females an estimated height, from tibial length, was used to predict TBC. In normals the TBC/TBCp ratio was 1.00 +/- 0.12, whereas in osteoporotic females it was 0.80 +/- 0.12. A receiver operating characteristic curve showed better discrimination of osteoporosis with TBC/TBCp than with wrist BMC. By using Bayes' theorem, with a 25% prevalence of osteoporosis (estimate for postmenopausal women), the posttest probability of disease was 90% when the TBC/TBCp ratio was less than 0.84. The authors conclude that a low TBC/TBCp ratio is very helpful in determining osteoporosis

  7. Does tranexamic acid increase the risk of thromboembolism after bilateral simultaneous total knee arthroplasties in Asian Population?

    Science.gov (United States)

    Kim, Young-Hoo; Park, Jang-Won; Kim, Jun-Shik; Seo, Dong-Hyuk

    2018-01-01

    To ascertain whether tranexamic acid reduces the blood loss and transfusion rate and volumes; increase the prevalence of deep vein thrombosis (DVT); and investigate factors associated with DVT in patients undergoing primary bilateral total knee arthroplasties (TKAs) without use of chemical thromboprophylaxis. There were 874 patients (1748 knees) in the control group who did not receive tranexamic acid and 871 patients (1742 knees) in the study group who received tranexamic acid. Mechanical compression device was applied without any chemical thromboprophylaxis. Transfusion rates and volumes were recorded. DVT was diagnosed using both sonogram and venogram at 7 or 8 day post-operatively. Intra- and post-operative blood loss and transfusion volumes were significantly lower in the tranexamic acid group. The prevalence of DVT was 14% (245 of 1748 knees) in the control group and 18% (314 of 1742 knees) in the tranexamic acid group. Pre- and post-operative perfusion lung scans revealed no evidence of PE in any patients in either group. Coagulation or thrombophilic data or molecular genetic testing was not significantly different between the two groups. The use of tranexamic acid reduces the volume of blood transfusion and does not increase the prevalence of DVT or PE in the patients who did not receive routine chemical thromboprophylaxis after primary bilateral simultaneous sequential TKAs in Asian patients.

  8. Cost-effectiveness of total hip and knee replacements for the Australian population with osteoarthritis: discrete-event simulation model.

    Directory of Open Access Journals (Sweden)

    Hideki Higashi

    Full Text Available BACKGROUND: Osteoarthritis constitutes a major musculoskeletal burden for the aged Australians. Hip and knee replacement surgeries are effective interventions once all conservative therapies to manage the symptoms have been exhausted. This study aims to evaluate the cost-effectiveness of hip and knee replacements in Australia. To our best knowledge, the study is the first attempt to account for the dual nature of hip and knee osteoarthritis in modelling the severities of right and left joints separately. METHODOLOGY/PRINCIPAL FINDINGS: We developed a discrete-event simulation model that follows up the individuals with osteoarthritis over their lifetimes. The model defines separate attributes for right and left joints and accounts for several repeat replacements. The Australian population with osteoarthritis who were 40 years of age or older in 2003 were followed up until extinct. Intervention effects were modelled by means of disability-adjusted life-years (DALYs averted. Both hip and knee replacements are highly cost effective (AUD 5,000 per DALY and AUD 12,000 per DALY respectively under an AUD 50,000/DALY threshold level. The exclusion of cost offsets, and inclusion of future unrelated health care costs in extended years of life, did not change the findings that the interventions are cost-effective (AUD 17,000 per DALY and AUD 26,000 per DALY respectively. However, there was a substantial difference between hip and knee replacements where surgeries administered for hips were more cost-effective than for knees. CONCLUSIONS/SIGNIFICANCE: Both hip and knee replacements are cost-effective interventions to improve the quality of life of people with osteoarthritis. It was also shown that the dual nature of hip and knee OA should be taken into account to provide more accurate estimation on the cost-effectiveness of hip and knee replacements.

  9. Daily total physical activity level and premature death in men and women: results from a large-scale population-based cohort study in Japan (JPHC study).

    Science.gov (United States)

    Inoue, Manami; Iso, Hiroyasu; Yamamoto, Seiichiro; Kurahashi, Norie; Iwasaki, Motoki; Sasazuki, Shizuka; Tsugane, Shoichiro

    2008-07-01

    The impact of daily total physical activity level on premature deaths has not been fully clarified in non-Western, relatively lean populations. We prospectively examined the association between daily total physical activity level (METs/day) and subsequent risk of all-cause mortality and mortalities from cancer, heart disease, and cerebrovascular disease. A total of 83,034 general Japanese citizens ages 45-74 years who responded to the questionnaire in 1995-1999 were followed for any cause of death through December 2005. Mutlivariate-adjusted hazard ratios were calculated with a Cox proportional hazards model controlling for potential confounding factors. During follow-up, a total of 4564 deaths were recorded. Compared with subjects in the lowest quartile, increased daily total physical activity was associated with a significantly decreased risk of all-cause mortality in both sexes (hazard ratios for the second, third, and highest quartiles were: men, 0.79, 0.82, 0.73 and women, 0.75, 0.64, 0.61, respectively). The decreased risk was observed regardless of age, frequency of leisure-time sports or physical exercise, or obesity status, albeit with a degree of risk attenuation among those with a high body mass index. A significantly decreased risk was similarly observed for death from cancer and heart disease in both sexes, and from cerebrovascular disease in women. Greater daily total physical activity level, either from occupation, daily life, or leisure time, may be of benefit in preventing premature death.

  10. Association of coffee intake with total and cause-specific mortality in a Japanese population: the Japan Public Health Center-based Prospective Study.

    Science.gov (United States)

    Saito, Eiko; Inoue, Manami; Sawada, Norie; Shimazu, Taichi; Yamaji, Taiki; Iwasaki, Motoki; Sasazuki, Shizuka; Noda, Mitsuhiko; Iso, Hiroyasu; Tsugane, Shoichiro

    2015-05-01

    Despite the rising consumption of coffee worldwide, few prospective cohort studies assessed the association of coffee intake with mortality including total and major causes of death. We aimed to investigate the association between habitual coffee drinking and mortality from all causes, cancer, heart disease, cerebrovascular disease, respiratory disease, injuries, and other causes of death in a large-scale, population-based cohort study in Japan. We studied 90,914 Japanese persons aged between 40 and 69 y without a history of cancer, cerebrovascular disease, or ischemic heart disease at the time of the baseline study. Subjects were followed up for an average of 18.7 y, during which 12,874 total deaths were reported. The association between coffee intake and risk of total and cause-specific mortality was assessed by using a Cox proportional hazards regression model with adjustment for potential confounders. We showed an inverse association between coffee intake and total mortality in both men and women. HRs (95% CIs) for total death in subjects who consumed coffee compared with those who never drank coffee were 0.91 (0.86-0.95) for 5 cups/d (P-trend Coffee was inversely associated with mortality from heart disease, cerebrovascular disease, and respiratory disease. With this prospective study, we suggest that the habitual intake of coffee is associated with lower risk of total mortality and 3 leading causes of death in Japan. © 2015 American Society for Nutrition.

  11. [Application of the data from China Total Diet Study to assess the distribution of lead exposure in different age-gender population groups].

    Science.gov (United States)

    Li, Xiaowei; Liu, Qing; Liu, Liping; Wu, Yongning

    2012-05-01

    To assess the distribution of dietary lead exposure in different age-gender groups of Chinese residents by using the data from China Total Diet Study, and combining the new risk assessment and the PTWI withdrawn by JECFA. Methods Combining the lead concentrations of dietary samples with the food consumption data from China Total Diet Study in 2007 to obtain the distribution of dietary intake and dietary source of lead in different age-gender population groups. Dietary lead exposure of different age-gender population groups in China was in the range of 48.7 -116.7 microg/d. The status of higher lead exposure in younger age groups was not optimistic, as the mean and median margins of exposure (MOE) have been less than 1.0 (0.1 - 0.3). The main sources of dietary lead were cereals and vegetables, which covering 57% of total lead exposure. Lowering the dietary lead exposure of Chinese residents is necessary, especially of infants and children.

  12. Boundary curves of individual items in the distribution of total depressive symptom scores approximate an exponential pattern in a general population.

    Science.gov (United States)

    Tomitaka, Shinichiro; Kawasaki, Yohei; Ide, Kazuki; Akutagawa, Maiko; Yamada, Hiroshi; Furukawa, Toshiaki A; Ono, Yutaka

    2016-01-01

    Previously, we proposed a model for ordinal scale scoring in which individual thresholds for each item constitute a distribution by each item. This lead us to hypothesize that the boundary curves of each depressive symptom score in the distribution of total depressive symptom scores follow a common mathematical model, which is expressed as the product of the frequency of the total depressive symptom scores and the probability of the cumulative distribution function of each item threshold. To verify this hypothesis, we investigated the boundary curves of the distribution of total depressive symptom scores in a general population. Data collected from 21,040 subjects who had completed the Center for Epidemiologic Studies Depression Scale (CES-D) questionnaire as part of a national Japanese survey were analyzed. The CES-D consists of 20 items (16 negative items and four positive items). The boundary curves of adjacent item scores in the distribution of total depressive symptom scores for the 16 negative items were analyzed using log-normal scales and curve fitting. The boundary curves of adjacent item scores for a given symptom approximated a common linear pattern on a log normal scale. Curve fitting showed that an exponential fit had a markedly higher coefficient of determination than either linear or quadratic fits. With negative affect items, the gap between the total score curve and boundary curve continuously increased with increasing total depressive symptom scores on a log-normal scale, whereas the boundary curves of positive affect items, which are not considered manifest variables of the latent trait, did not exhibit such increases in this gap. The results of the present study support the hypothesis that the boundary curves of each depressive symptom score in the distribution of total depressive symptom scores commonly follow the predicted mathematical model, which was verified to approximate an exponential mathematical pattern.

  13. Boundary curves of individual items in the distribution of total depressive symptom scores approximate an exponential pattern in a general population

    Directory of Open Access Journals (Sweden)

    Shinichiro Tomitaka

    2016-10-01

    Full Text Available Background Previously, we proposed a model for ordinal scale scoring in which individual thresholds for each item constitute a distribution by each item. This lead us to hypothesize that the boundary curves of each depressive symptom score in the distribution of total depressive symptom scores follow a common mathematical model, which is expressed as the product of the frequency of the total depressive symptom scores and the probability of the cumulative distribution function of each item threshold. To verify this hypothesis, we investigated the boundary curves of the distribution of total depressive symptom scores in a general population. Methods Data collected from 21,040 subjects who had completed the Center for Epidemiologic Studies Depression Scale (CES-D questionnaire as part of a national Japanese survey were analyzed. The CES-D consists of 20 items (16 negative items and four positive items. The boundary curves of adjacent item scores in the distribution of total depressive symptom scores for the 16 negative items were analyzed using log-normal scales and curve fitting. Results The boundary curves of adjacent item scores for a given symptom approximated a common linear pattern on a log normal scale. Curve fitting showed that an exponential fit had a markedly higher coefficient of determination than either linear or quadratic fits. With negative affect items, the gap between the total score curve and boundary curve continuously increased with increasing total depressive symptom scores on a log-normal scale, whereas the boundary curves of positive affect items, which are not considered manifest variables of the latent trait, did not exhibit such increases in this gap. Discussion The results of the present study support the hypothesis that the boundary curves of each depressive symptom score in the distribution of total depressive symptom scores commonly follow the predicted mathematical model, which was verified to approximate an

  14. [Mirror neurons].

    Science.gov (United States)

    Rubia Vila, Francisco José

    2011-01-01

    Mirror neurons were recently discovered in frontal brain areas of the monkey. They are activated when the animal makes a specific movement, but also when the animal observes the same movement in another animal. Some of them also respond to the emotional expression of other animals of the same species. These mirror neurons have also been found in humans. They respond to or "reflect" actions of other individuals in the brain and are thought to represent the basis for imitation and empathy and hence the neurobiological substrate for "theory of mind", the potential origin of language and the so-called moral instinct.

  15. Optimal fetal growth for the Caucasian singleton and assessment of appropriateness of fetal growth: an analysis of a total population perinatal database

    Directory of Open Access Journals (Sweden)

    Lawrence David M

    2005-05-01

    Full Text Available Abstract Background The appropriateness of an individual's intra uterine growth is now considered an important determinant of both short and long term outcomes, yet currently used measures have several shortcomings. This study demonstrates a method of assessing appropriateness of intrauterine growth based on the estimation of each individual's optimal newborn dimensions from routinely available perinatal data. Appropriateness of growth can then be inferred from the ratio of the value of the observed dimension to that of the optimal dimension. Methods Fractional polynomial regression models including terms for non-pathological determinants of fetal size (gestational duration, fetal gender and maternal height, age and parity were used to predict birth weight, birth length and head circumference from a population without any major risk factors for sub-optimal intra-uterine growth. This population was selected from a total population of all singleton, Caucasian births in Western Australia 1998–2002. Births were excluded if the pregnancy was exposed to factors known to influence fetal growth pathologically. The values predicted by these models were treated as the optimal values, given infant gender, gestational age, maternal height, parity, and age. Results The selected sample (N = 62,746 comprised 60.5% of the total Caucasian singleton birth cohort. Equations are presented that predict optimal birth weight, birth length and head circumference given gestational duration, fetal gender, maternal height, age and parity. The best fitting models explained 40.5% of variance for birth weight, 32.2% for birth length, and 25.2% for head circumference at birth. Conclusion Proportion of optimal birth weight (length or head circumference provides a method of assessing appropriateness of intrauterine growth that is less dependent on the health of the reference population or the quality of their morphometric data than is percentile position on a birth weight

  16. Total and cause-specific mortality by elevated transferrin saturation and hemochromatosis genotype in individuals with diabetes - two general population studies

    DEFF Research Database (Denmark)

    Ellervik, Christina; Mandrup-Poulsen, Thomas; Tybjærg-Hansen, Anne

    2013-01-01

    ObjectiveMortality is increased in patients with hereditary hemochromatosis, in individuals from the general population with increased transferrin saturation(TS), and also in patients with diabetes type 1 and increased TS from a highly specialised diabetes clinic. Thus, we have recommended targeted...... and hemochromatosis genotype(HFE) C282Y/C282Y in individuals with diabetes(type 1,N=118;type 2,N=3228;total,N=3346).ResultsThe cumulative survival was reduced in individuals with diabetes with TS≥50% vs....

  17. Total physical activity might not be a good measure in the relationship with HDL cholesterol and triglycerides in a multi-ethnic population: a cross-sectional study

    Science.gov (United States)

    2011-01-01

    Background Evidence suggests that physical activity (PA) has a beneficial effect on high-density lipoprotein cholesterol (HDL) and triglycerides. However, observational studies show contrasting results for this association between different ethnic groups. It is unclear whether this is due to differences in the PA composition. The aim of this study was to assess the relationship of the total PA, along with its intensity and duration, with HDL and triglycerides in a multi-ethnic population. Methods The study population was sampled from the SUNSET study and included: 502 European- Dutch, 338 Hindustani-Surinamese, and 596 African-Surinamese participants living in Amsterdam, the Netherlands. We assessed PA with the SQUASH questionnaire. We calculated age-sex-adjusted betas, geometric mean ratios (GMRs), and prevalence ratios (PRs) to assess the relationship of PA with HDL and triglycerides. Results In the adjusted models, the highest total PA tertile compared to the lowest tertile was beneficially associated with HDL (beta: 0.08, 95% CI: 0.00, 0.16 and PR low HDL 0.59, 95% CI: 0.39, 0.88) and triglycerides (GMR: 0.93, 95% CI: 0.83, 1.03 and PR: 0.56, 95% CI: 0.29, 1.08) for the African-Surinamese. No statistically significant associations appeared for total PA among the European-Dutch and Hindustani-Surinamese. The adjusted models with the intensity score and HDL showed beneficial associations for the European-Dutch (beta: 0.06, 95% CI: 0.03, 0.10) and African-Surinamese (beta: 0.06, 0.02, 0.10), for log triglycerides for the European-Dutch (beta: -0.08, 95% CI: -0.12, 0.03), Hindustani-Surinamese (beta: -0.06, 95% CI: -0.16, 0.03), and African-Surinamese (beta: -0.04, 95% CI: -0.10, 0.01). Excepting HDL in African-Surinamese, the duration score was unrelated to HDL and triglycerides in any group. Conclusions Activity intensity related beneficially to blood lipids in almost every ethnic group. The activity duration was unrelated to blood lipids, while the total PA

  18. Total physical activity might not be a good measure in the relationship with HDL cholesterol and triglycerides in a multi-ethnic population: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    de Munter Jeroen SL

    2011-11-01

    Full Text Available Abstract Background Evidence suggests that physical activity (PA has a beneficial effect on high-density lipoprotein cholesterol (HDL and triglycerides. However, observational studies show contrasting results for this association between different ethnic groups. It is unclear whether this is due to differences in the PA composition. The aim of this study was to assess the relationship of the total PA, along with its intensity and duration, with HDL and triglycerides in a multi-ethnic population. Methods The study population was sampled from the SUNSET study and included: 502 European- Dutch, 338 Hindustani-Surinamese, and 596 African-Surinamese participants living in Amsterdam, the Netherlands. We assessed PA with the SQUASH questionnaire. We calculated age-sex-adjusted betas, geometric mean ratios (GMRs, and prevalence ratios (PRs to assess the relationship of PA with HDL and triglycerides. Results In the adjusted models, the highest total PA tertile compared to the lowest tertile was beneficially associated with HDL (beta: 0.08, 95% CI: 0.00, 0.16 and PR low HDL 0.59, 95% CI: 0.39, 0.88 and triglycerides (GMR: 0.93, 95% CI: 0.83, 1.03 and PR: 0.56, 95% CI: 0.29, 1.08 for the African-Surinamese. No statistically significant associations appeared for total PA among the European-Dutch and Hindustani-Surinamese. The adjusted models with the intensity score and HDL showed beneficial associations for the European-Dutch (beta: 0.06, 95% CI: 0.03, 0.10 and African-Surinamese (beta: 0.06, 0.02, 0.10, for log triglycerides for the European-Dutch (beta: -0.08, 95% CI: -0.12, 0.03, Hindustani-Surinamese (beta: -0.06, 95% CI: -0.16, 0.03, and African-Surinamese (beta: -0.04, 95% CI: -0.10, 0.01. Excepting HDL in African-Surinamese, the duration score was unrelated to HDL and triglycerides in any group. Conclusions Activity intensity related beneficially to blood lipids in almost every ethnic group. The activity duration was unrelated to blood lipids, while

  19. Relationship between the mechanisms of gamma rhythm generation and the magnitude of the macroscopic phase response function in a population of excitatory and inhibitory modified quadratic integrate-and-fire neurons

    Science.gov (United States)

    Akao, Akihiko; Ogawa, Yutaro; Jimbo, Yasuhiko; Ermentrout, G. Bard; Kotani, Kiyoshi

    2018-01-01

    Gamma oscillations are thought to play an important role in brain function. Interneuron gamma (ING) and pyramidal interneuron gamma (PING) mechanisms have been proposed as generation mechanisms for these oscillations. However, the relation between the generation mechanisms and the dynamical properties of the gamma oscillation are still unclear. Among the dynamical properties of the gamma oscillation, the phase response function (PRF) is important because it encodes the response of the oscillation to inputs. Recently, the PRF for an inhibitory population of modified theta neurons that generate an ING rhythm was computed by the adjoint method applied to the associated Fokker-Planck equation (FPE) for the model. The modified theta model incorporates conductance-based synapses as well as the voltage and current dynamics. Here, we extended this previous work by creating an excitatory-inhibitory (E-I) network using the modified theta model and described the population dynamics with the corresponding FPE. We conducted a bifurcation analysis of the FPE to find parameter regions which generate gamma oscillations. In order to label the oscillatory parameter regions by their generation mechanisms, we defined ING- and PING-type gamma oscillation in a mathematically plausible way based on the driver of the inhibitory population. We labeled the oscillatory parameter regions by these generation mechanisms and derived PRFs via the adjoint method on the FPE in order to investigate the differences in the responses of each type of oscillation to inputs. PRFs for PING and ING mechanisms are derived and compared. We found the amplitude of the PRF for the excitatory population is larger in the PING case than in the ING case. Finally, the E-I population of the modified theta neuron enabled us to analyze the PRFs of PING-type gamma oscillation and the entrainment ability of E and I populations. We found a parameter region in which PRFs of E and I are both purely positive in the case of

  20. An expandable embryonic stem cell-derived Purkinje neuron progenitor population that exhibits in vivo maturation in the adult mouse cerebellum

    NARCIS (Netherlands)

    Higuera, Gustavo A; Iaffaldano, Grazia; Bedar, Meiwand; Shpak, Guy; Broersen, Robin; Munshi, Shashini T; Dupont, Catherine; Gribnau, Joost; de Vrij, Femke M S; Kushner, Steven A; De Zeeuw, Chris I

    2017-01-01

    The directed differentiation of patient-derived induced pluripotent stem cells into cell-type specific neurons has inspired the development of therapeutic discovery for neurodegenerative diseases. Many forms of ataxia result from degeneration of cerebellar Purkinje cells, but thus far it has not

  1. An expandable embryonic stem cell-derived Purkinje neuron progenitor population that exhibits in vivo maturation in the adult mouse cerebellum

    NARCIS (Netherlands)

    G.A. Higuera (Gustavo A.); Iaffaldano, G. (Grazia); Bedar, M. (Meiwand); G. Shpak (Guy); R. Broersen (Robin); S.T. Munshi (Shashini T.); Dupont, C. (Catherine); J.H. Gribnau (Joost); F.M.S. Vrij (Femke); S.A. Kushner (Steven); C.I. de Zeeuw (Chris)

    2017-01-01

    textabstractThe directed differentiation of patient-derived induced pluripotent stem cells into cell-type specific neurons has inspired the development of therapeutic discovery for neurodegenerative diseases. Many forms of ataxia result from degeneration of cerebellar Purkinje cells, but thus far it

  2. USE OF HIGH CONTENT IMAGE ANALYSES TO DETECT CHEMICAL-MEDIATED EFFECTS ON NEURITE SUB-POPULATIONS IN PRIMARY RAT CORTICAL NEURONS

    Science.gov (United States)

    Traditional developmental neurotoxicity tests performed in vivo are costly, time-consuming and utilize a large number of animals. In order to address these inefficiencies, in vitro models of neuronal development have been used in a first tier screening approach for developmenta...

  3. Real-time web-based assessment of total population risk of future emergency department utilization: statewide prospective active case finding study.

    Science.gov (United States)

    Hu, Zhongkai; Jin, Bo; Shin, Andrew Y; Zhu, Chunqing; Zhao, Yifan; Hao, Shiying; Zheng, Le; Fu, Changlin; Wen, Qiaojun; Ji, Jun; Li, Zhen; Wang, Yong; Zheng, Xiaolin; Dai, Dorothy; Culver, Devore S; Alfreds, Shaun T; Rogow, Todd; Stearns, Frank; Sylvester, Karl G; Widen, Eric; Ling, Xuefeng B

    2015-01-13

    An easily accessible real-time Web-based utility to assess patient risks of future emergency department (ED) visits can help the health care provider guide the allocation of resources to better manage higher-risk patient populations and thereby reduce unnecessary use of EDs. Our main objective was to develop a Health Information Exchange-based, next 6-month ED risk surveillance system in the state of Maine. Data on electronic medical record (EMR) encounters integrated by HealthInfoNet (HIN), Maine's Health Information Exchange, were used to develop the Web-based surveillance system for a population ED future 6-month risk prediction. To model, a retrospective cohort of 829,641 patients with comprehensive clinical histories from January 1 to December 31, 2012 was used for training and then tested with a prospective cohort of 875,979 patients from July 1, 2012, to June 30, 2013. The multivariate statistical analysis identified 101 variables predictive of future defined 6-month risk of ED visit: 4 age groups, history of 8 different encounter types, history of 17 primary and 8 secondary diagnoses, 8 specific chronic diseases, 28 laboratory test results, history of 3 radiographic tests, and history of 25 outpatient prescription medications. The c-statistics for the retrospective and prospective cohorts were 0.739 and 0.732 respectively. Integration of our method into the HIN secure statewide data system in real time prospectively validated its performance. Cluster analysis in both the retrospective and prospective analyses revealed discrete subpopulations of high-risk patients, grouped around multiple "anchoring" demographics and chronic conditions. With the Web-based population risk-monitoring enterprise dashboards, the effectiveness of the active case finding algorithm has been validated by clinicians and caregivers in Maine. The active case finding model and associated real-time Web-based app were designed to track the evolving nature of total population risk, in a

  4. Neurons from the adult human dentate nucleus: neural networks in the neuron classification.

    Science.gov (United States)

    Grbatinić, Ivan; Marić, Dušica L; Milošević, Nebojša T

    2015-04-07

    Topological (central vs. border neuron type) and morphological classification of adult human dentate nucleus neurons according to their quantified histomorphological properties using neural networks on real and virtual neuron samples. In the real sample 53.1% and 14.1% of central and border neurons, respectively, are classified correctly with total of 32.8% of misclassified neurons. The most important result present 62.2% of misclassified neurons in border neurons group which is even greater than number of correctly classified neurons (37.8%) in that group, showing obvious failure of network to classify neurons correctly based on computational parameters used in our study. On the virtual sample 97.3% of misclassified neurons in border neurons group which is much greater than number of correctly classified neurons (2.7%) in that group, again confirms obvious failure of network to classify neurons correctly. Statistical analysis shows that there is no statistically significant difference in between central and border neurons for each measured parameter (p>0.05). Total of 96.74% neurons are morphologically classified correctly by neural networks and each one belongs to one of the four histomorphological types: (a) neurons with small soma and short dendrites, (b) neurons with small soma and long dendrites, (c) neuron with large soma and short dendrites, (d) neurons with large soma and long dendrites. Statistical analysis supports these results (pneurons can be classified in four neuron types according to their quantitative histomorphological properties. These neuron types consist of two neuron sets, small and large ones with respect to their perykarions with subtypes differing in dendrite length i.e. neurons with short vs. long dendrites. Besides confirmation of neuron classification on small and large ones, already shown in literature, we found two new subtypes i.e. neurons with small soma and long dendrites and with large soma and short dendrites. These neurons are

  5. GABA accumulating neurons are relatively resistant to chronic hypoxia in vitro: An autoradiographic study

    International Nuclear Information System (INIS)

    Sher, P.K.; Hu, S.

    1990-01-01

    Whether there is preferential loss of certain types of nerve cells or specific cellular functions after hypoxic or ischemic insults remains unclear. To evaluate this phenomenon in vitro, the vulnerability of GABAergic neurons to hypoxia was investigated both quantitatively and with autoradiography. Immature neuronal cortical cultures obtained from fetal mice were subjected to chronic hypoxia (5% O2) for 24 h or 48 h and then returned to the normoxic condition for 48 h. The shorter hypoxic exposure resulted in significantly reduced numbers of neurons in comparison to the longer exposure and also to controls (29% and 26%, respectively; p less than 0.001). LDH efflux, a reliable indicator of cell damage, also was higher after the shorter exposure insult. Nevertheless, in these same 24 h hypoxic cultures there was prominent sparing of those neurons which accumulate GABA: by 48 h of recovery GABAergic neurons constituted 29.3 +/- 2.0% of the remaining neuronal population in comparison to 11.6 +/- 0.6 and 14.4 +/- 0.8% for controls and 48 h hypoxia, respectively; (p less than 0.001). Although total GABA uptake per neuron was significantly decreased after both types of insult, there was a concomitant increase in glial GABA uptake (i.e., that which could be displaced by beta-alanine). These observations suggest that certain GABAergic cortical neurons are relatively more resistant to chronic hypoxia than the general neuronal population and that depression of overall neuronal GABA uptake may be associated with enhanced glial GABA uptake

  6. Development of a polyclonal anti-dugong immunoglobulin G (IgG) antibody with evaluation of total plasma IgG in a living dugong (Dugong dugon) population.

    Science.gov (United States)

    Wong, Arthur; Lanyon, Janet M; McKee, Sara J; Linedale, Richard; Woolford, Lucy; Long, Trevor; Leggatt, Graham R

    2018-06-01

    Species-specific antibodies (Ab) for the measurement of immunoglobulins (Ig) are valuable tools for determining the humoral immune status of threatened and endangered wildlife species such as dugongs. However, no studies have reported antibody reagents against dugong immunoglobulin. The object of this study was to develop an Ab with specificity for dugong IgG and apply this tool to survey total IgG levels in plasma samples from a live wild population of dugongs in southern Queensland, Australia. Dugong IgG was isolated from plasma by protein A/G column chromatography and a polyclonal antiserum was successfully raised against the dugong IgG through immunization of mice. The anti-dugong antiserum was reactive with dugong serum but not immunoglobulin from other species such as rats and humans. When tested against a panel of dugong plasma samples, relative IgG levels from dugongs (n = 116) showed biologically relevant relationships with pregnancy status and a principal component of Body Mass Index (BMI)/globulin/fecal glucocorticosteroid (chronic stress) levels combined, which together accounted for 9.2% of the variation in total Ig levels. Together these data suggest that dugongs show variation in total IgG and that this correlates with some physiological parameters of dugong health. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Total Effective Xenoestrogen Burden in Serum Samples and Risk for Breast Cancer in a Population-Based Multicase–Control Study in Spain

    Science.gov (United States)

    Pastor-Barriuso, Roberto; Fernández, Mariana F.; Castaño-Vinyals, Gemma; Whelan, Denis; Pérez-Gómez, Beatriz; Llorca, Javier; Villanueva, Cristina M.; Guevara, Marcela; Molina-Molina, José-Manuel; Artacho-Cordón, Francisco; Barriuso-Lapresa, Laura; Tusquets, Ignasi; Dierssen-Sotos, Trinidad; Aragonés, Nuria; Olea, Nicolás; Kogevinas, Manolis; Pollán, Marina

    2016-01-01

    Background: Most studies on endocrine-disrupting chemicals and breast cancer have focused on single compounds and have produced inconclusive findings. Objectives: We assessed the combined estrogenic effects of mixtures of xenoestrogens in serum and their relationship to breast cancer risk. Methods: A total of 186 incident pretreatment breast cancer cases and 196 frequency-matched controls were randomly sampled from a large population-based multicase–control study in Spain. The total effective xenoestrogen burden attributable to organohalogenated xenoestrogens (TEXB-α) and endogenous hormones and more polar xenoestrogens (TEXB-β) was determined in serum samples using high-performance liquid chromatography and E-Screen bioassay. Odds ratios for breast cancer comparing tertiles of serum TEXB-α and TEXB-β were estimated using logistic models, and smooth risk trends were obtained using spline models. Results: Cases had higher geometric mean TEXB-α and TEXB-β levels (8.32 and 9.94 Eeq pM/mL, respectively) than controls (2.99 and 5.96 Eeq pM/mL, respectively). The fully adjusted odds ratios for breast cancer (95% confidence intervals) comparing the second and third tertiles of TEXB-α with the first tertile were 1.77 (0.76, 4.10) and 3.45 (1.50, 7.97), respectively, and those for TEXB-β were 2.35 (1.10, 5.03) and 4.01 (1.88, 8.56), respectively. A steady increase in risk was evident across all detected TEXB-α levels and a sigmoidal trend was observed for TEXB-β. Individual xenoestrogens showed weak and opposing associations with breast cancer risk. Conclusions: This is the first study to show a strong positive association between serum total xenoestrogen burden and breast cancer risk, highlighting the importance of evaluating xenoestrogen mixtures, rather than single compounds, when studying hormone-related cancers. Citation: Pastor-Barriuso R, Fernández MF, Castaño-Vinyals G, Whelan D, Pérez-Gómez B, Llorca J, Villanueva CM, Guevara M, Molina-Molina JM

  8. Schizophrenia Spectrum Disorders in a Danish 22q11.2 Deletion Syndrome Cohort Compared to the Total Danish Population-A Nationwide Register Study

    DEFF Research Database (Denmark)

    Vangkilde, Anders; Olsen, Line; Hoeffding, Louise K

    2016-01-01

    OBJECTIVE: Cross-sectional studies have shown associations between 22q11.2 deletion syndrome and schizophrenia. However, large-scale prospective studies have been lacking. We, therefore, conducted the first large-scale population based study on the risk of being diagnosed with schizophrenia...... in persons identified with 22q11.2 deletion syndrome. METHODS: Danish nationwide registers were linked to establish a cohort consisting of all Danish citizens born during 1955-2004 and the cohort was followed from January 1, 1994 until December 31, 2013. Data were analyzed using survival analyses...... and adjusted for calendar year, age, sex, and parental mental health history. RESULTS: A total of 156 individuals with 22q11.2 deletion syndrome were identified, out of which 6 individuals were diagnosed with schizophrenia spectrum disorders following identification with 22q11 deletion syndrome. Identified...

  9. Mechanism-based population modelling for assessment of L-cell function based on total GLP-1 response following an oral glucose tolerance test

    DEFF Research Database (Denmark)

    Møller, Jonas B.; Jusko, William J.; Gao, Wei

    2011-01-01

    was to build a mechanism-based population model that describes the time course of total GLP-1 and provides indices for capability of secretion in each subject. The goal was thus to model the secretion of GLP-1, and not its effect on insulin production. Single 75 g doses of glucose were administered orally......GLP-1 is an insulinotropic hormone that synergistically with glucose gives rise to an increased insulin response. Its secretion is increased following a meal and it is thus of interest to describe the secretion of this hormone following an oral glucose tolerance test (OGTT). The aim of this study....... The individual estimates of absorption rate constants were used in the model for GLP-1 secretion. Estimation of parameters was performed using the FOCE method with interaction implemented in NONMEM VI. The final transit/indirect-response model obtained for GLP-1 production following an OGTT included two...

  10. Prevalence and risk factors for HIV, hepatitis B, and hepatitis C in people with severe mental illness: a total population study of Sweden.

    Science.gov (United States)

    Bauer-Staeb, Clarissa; Jörgensen, Lena; Lewis, Glyn; Dalman, Christina; Osborn, David P J; Hayes, Joseph F

    2017-09-01

    Severe mental illness is associated with increased morbidity and mortality. The elevated risk of blood-borne viruses (BBVs) in people with severe mental illness is of concern, but the full extent of this problem is unclear. We aimed to determine the prevalence of and risk factors for BBVs in people with severe mental illness. In this nationwide, population-based, cross-sectional study, we estimated the point prevalence of HIV, hepatitis B (HBV), and hepatitis C (HCV) in people with severe mental illness, including the total adult (≥18 years) Swedish population. We defined severe mental illness as a clinical diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, or other psychotic illness according to the Swedish version of the International Statistical Classification of Diseases version 8, 9, or 10. We used multivariable logistic regression to determine the odds of BBVs in individuals with severe mental illness, relative to the general population, and to identify independent risk factors (age, sex, immigration status, socioeconomic status, education, and substance misuse) for BBV infection. We also did a sensitivity analysis excluding BBV diagnoses made before the introduction of the Register for Infection Disease Control (1997). Of 6 815 931 adults in Sweden, 97 797 (1·43%) individuals had a diagnosis of severe mental illness. Prevalence of BBVs was elevated in people with severe mental illness, of which 230 (0·24%) had HIV, 518 (0·53%) had HBV, and 4476 (4·58%) had HCV. After accounting for sociodemographic characteristics, the odds of HIV were 2·57 (95% CI 2·25-2·94, pmental illness than in the general population, whereas the odds of HBV were 2·29 (2·09-2·51, pmental illness and identify interventions preventing infection. Targeting of comorbid substance misuse would have particular effect on reduction of BBV prevalence in this population. Medical Research Council and Swedish Research Council. Copyright © 2017 The Author

  11. Descending Command Neurons in the Brainstem that Halt Locomotion

    DEFF Research Database (Denmark)

    Bouvier, Julien; Caggiano, Vittorio; Leiras, Roberto

    2015-01-01

    identifiable brainstem populations to a potential locomotor stop signal, we used developmental genetics and considered a discrete neuronal population in the reticular formation: the V2a neurons. We find that those neurons constitute a major excitatory pathway to locomotor areas of the ventral spinal cord....... Selective activation of V2a neurons of the rostral medulla stops ongoing locomotor activity, owing to an inhibition of premotor locomotor networks in the spinal cord. Moreover, inactivation of such neurons decreases spontaneous stopping in vivo. Therefore, the V2a "stop neurons" represent a glutamatergic...

  12. Evaluation of apoptosis and micronucleation induced by reactor neutron beams with two different cadmium ratios in total and quiescent cell populations within solid tumors

    International Nuclear Information System (INIS)

    Masunaga, Shin-ichiro; Ono, Koji; Sakurai, Yoshinori; Takagaki, Masao; Kobayashi, Tooru; Kinashi, Yuko; Suzuki, Minoru

    2001-01-01

    Purpose: Response of quiescent (Q) and total tumor cells in solid tumors to reactor neutron beam irradiation with two different cadmium (Cd) ratios was examined in terms of micronucleus (MN) frequency and apoptosis frequency, using four different tumor cell lines. Methods and Materials: C57BL mice bearing EL4 tumors, C3H/He mice bearing SCC VII or FM3A tumors, and Balb/c mice bearing EMT6/KU tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. Thirty min after i.p. injection of sodium borocaptate- 10 B (BSH), or 3 h after oral administration of p-boronophenylalanine- 10 B (BPA), the tumors were irradiated with neutron beams. The tumors without 10 B-compound administration were irradiated with neutron beams or γ-rays. This neutron beam irradiation was performed using neutrons with two different Cd ratios. The tumors were then excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the MN frequency in cells without BrdU labeling (=Q cells) was determined using immunofluorescence staining for BrdU. Meanwhile, for apoptosis assay, 6 h after irradiation, tumor cell suspensions obtained in the same manner were fixed, and the apoptosis frequency in Q cells was also determined with immunofluorescence staining for BrdU. The MN and apoptosis frequencies in total (P+Q) tumor cells were determined from the tumors that were not pretreated with BrdU. Results: Without 10 B-compounds, the sensitivity difference between total and Q cells was reduced by neutron beam irradiation. Under our particular neutron beam irradiation condition, relative biological effectiveness (RBE) of neutrons was larger in Q cells than in total cells, and the RBE values were larger for low Cd-ratio than high Cd-ratio neutrons. With 10 B-compounds, both frequencies were increased for each cell population, especially for total cells. BPA

  13. Does cerebellar neuronal integrity relate to cognitive ability?

    International Nuclear Information System (INIS)

    Rae, C.; Lee, M.; Dixon, R.M.; Blamire, A.; Thompson, C.; Styles, P.; Radda, G.K.; University of Sydney, NSW; Karmiloff-Smith, A.; Grant, J.

    1998-01-01

    Full text: Magnetic resonance spectroscopy (MRS) allows the non-invasive measurement of metabolite levels in the brain. One of these is N-acetylaspartate (NA), a molecule found solely in neurones, synthesised there by mitochondria. This compound can be considered as a marker of 1) neuronal density and 2) neuronal mitochondria function. We recently completed a joint MRS and neuropsychological investigation of Williams-Beuren syndrome (WBS), a rare (1/20,000) autosomal dominant disorder caused by a deletion which includes the elastin locus and LIM-kinase. The syndrome has an associated behavioural and cognitive profile which includes hyperactivity, hyperacusis and excessive sociability. Spatial skills are severely affected, while verbal skills are left relatively intact Our investigation showed loss of NA from the cerebellum in WBS compared with normal controls, with the subject population as a whole displaying a continuum of cerebellar NA concentration. Ability at cognitive tests, including the Weschler IQ scale and various verbal and spatial tests, was shown to correlate significantly and positively with the concentration of NA in the cerebellum. This finding can be interpreted in one of two ways: 1. Our sampling of cerebellar metabolite levels represents a 'global' sampling of total brain neuronal density and, as such, is independent of cerebellar integrity. 2. Cerebellar neuronal integrity is associated with performance at cognitive tests. If the latter interpretation is shown to be the case, it will have important implications for our current understanding of cerebellar function. Copyright (1998) Australian Neuroscience Society

  14. The total body length and body weight examination among gabus Sentani fish population, Oxyeleotris heterodon, Weber 1907 (Pisces: Eleotridae) of Sentani lake, Papua, Indonesia

    Science.gov (United States)

    Sriyani, E. D.; Abinawanto, Bowolaksono, A.

    2017-07-01

    The gabus Sentani fish lived in the Sentani Lake, Papua, since million years ago. Nowadays, the population of those species is getting extinct because of the overexploitation, whereas the culture effort of this species has not been developed, yet. The purpose of the study was to examine the total body length and body weight collected from some villages surrounding Sentani Lake such as Ifar village, Sosiri village, and Putali village. The body weight average of gabus fish from Ifar village, Sosiri village, and Putali village were 373.53 g, 426.86 g, and 118.34 g respectively. While the total body length average of gabus Sentani fish from Ifar village, Sosiri village, and Putali village were 279.30 mm, 223.30 mm and 222.06 mm, respectively. The growth model was W = 0.021067L3.086 with R2 value was 35.8 %, and r value was 0.598. Gabus Sentani fish, Oxyeleotris heterodon (Weber 1907) exhibited positive allometric (b > 3).

  15. Job strain among blue-collar and white-collar employees as a determinant of total mortality: a 28-year population-based follow-up

    Science.gov (United States)

    Seitsamo, Jorma; von Bonsdorff, Monika E; Ilmarinen, Juhani; Nygård, Clas-Håkan; Rantanen, Taina

    2012-01-01

    Objectives To investigate the effect of job demand, job control and job strain on total mortality among white-collar and blue-collar employees working in the public sector. Design 28-year prospective population-based follow-up. Setting Several municipals in Finland. Participants 5731 public sector employees from the Finnish Longitudinal Study on Municipal Employees Study aged 44–58 years at baseline. Outcomes Total mortality from 1981 to 2009 among individuals with complete data on job strain in midlife, categorised according to job demand and job control: high job strain (high job demands and low job control), active job (high job demand and high job control), passive job (low job demand and low job control) and low job strain (low job demand and high job control). Results 1836 persons died during the follow-up. Low job control among men increased (age-adjusted HR 1.26, 95% CI 1.12 to 1.42) and high job demand among women decreased the risk for total mortality HR 0.82 (95% CI 0.71 to 0.95). Adjustment for occupational group, lifestyle and health factors attenuated the association for men. In the analyses stratified by occupational group, high job strain increased the risk of mortality among white-collar men (HR 1.52, 95% CI 1.09 to 2.13) and passive job among blue-collar men (HR 1.28, 95% CI 1.05 to 1.47) compared with men with low job strain. Adjustment for lifestyle and health factors attenuated the risks. Among white-collar women having an active job decreased the risk for mortality (HR 0.78, 95% CI 0.60 to 1.00). Conclusion The impact of job strain on mortality was different according to gender and occupational group among middle-aged public sector employees. PMID:22422919

  16. Pathogenesis of motor neuron disease

    Institute of Scientific and Technical Information of China (English)

    Xuefei Wang

    2006-01-01

    OBJECTIVE: To summarize and analyze the factors and theories related to the attack of motor neuron disease, and comprehensively investigate the pathogenesis of motor neuron disease.DATA SOURCES: A search of Pubmed database was undertaken to identify articles about motor neuron disease published in English from January 1994 to June 2006 by using the keywords of "neurodegenerative diseases". Other literatures were collected by retrieving specific journals and articles.STUDY SELECTION: The data were checked primarily, articles related to the pathogenesis of motor neuron disease were involved, and those obviously irrelated to the articles were excluded.DATA EXTRACTION: Totally 54 articles were collected, 30 of them were involved, and the other 24 were excluded.DATA SYNTHESIS: The pathogenesis of motor neuron disease has multiple factors, and the present related theories included free radical oxidation, excitotoxicity, genetic and immune factors, lack of neurotrophic factor,injury of neurofilament, etc. The studies mainly come from transgenic animal models, cell culture in vitro and patients with familial motor neuron disease, but there are still many restrictions and disadvantages.CONCLUSION: It is necessary to try to find whether there is internal association among different mechanisms,comprehensively investigate the pathogenesis of motor neuron diseases, in order to provide reliable evidence for the clinical treatment.

  17. Region specific regulation of glutamic acid decarboxylase mRNA expression by dopamine neurons in rat brain.

    Science.gov (United States)

    Lindefors, N; Brene, S; Herrera-Marschitz, M; Persson, H

    1989-01-01

    In situ hybridization histochemistry and RNA blots were used to study the expression of glutamic acid decarboxylase (GAD) mRNA in rats with or without a unilateral lesion of midbrain dopamine neurons. Two populations of GAD mRNA positive neurons were found in the intact caudate-putamen, substantia nigra and fronto-parietal cortex. In caudate-putamen, only one out of ten of the GAD mRNA positive neurons expressed high levels, while in substantia nigra every second of the positive neurons expressed high levels of GAD mRNA. Relatively few, but intensively labelled neurons were found in the intact fronto-parietal cerebral cortex. In addition, one out of six of the GAD mRNA positive neurons in the fronto-parietal cortex showed a low labeling. On the ipsilateral side, the forebrain dopamine deafferentation induced an increase in the number of neurons expressing high levels of GAD mRNA in caudate-putamen, and a decrease in fronto-parietal cortex. A smaller decrease was also seen in substantia nigra. However, the total number of GAD mRNA positive neurons were not significantly changed in any of these brain regions. The changes in the levels of GAD mRNA after the dopamine lesion were confirmed by RNA blot analysis. Hence, midbrain dopamine neurons appear to control neuronal expression of GAD mRNA by a tonic down-regulation in a fraction of GAD mRNA positive neurons in caudate-putamen, and a tonic up-regulation in a fraction of GAD mRNA positive neurons in fronto-parietal cortex and substantia nigra.

  18. Increased risk for diabetes development in subjects with large variation in total cholesterol levels in 2,827,950 Koreans: A nationwide population-based study.

    Directory of Open Access Journals (Sweden)

    Eun-Jung Rhee

    Full Text Available Recent studies suggest a role for hyperlipidemia in the development of diabetes. The aim of this study is to analyze the relationship between variations of total cholesterol (TC levels and the risk for type 2 diabetes development from a Korean nationwide population-based database.We examined the General Health Check-up sub-dataset of the Korean National Health Insurance Service (NHIS of 2,827,950 participants who had at least three health check-ups between 2002 and 2007, and were not reported to have diabetes during that time. The variations of TC levels between the examinations were calculated as follows: [Formula: see text]. The examinees were divided into 10 groups according to TC variation, and the hazard ratio for diabetes development from 2007 to 2013, were analyzed.During the follow-up period, 3.4% of the participants had developed diabetes. The hazard ratio (HR for diabetes development relative to the overall risk in the whole study population started to be higher than 1.0 from eighth decile of TC variation. The highest decile group showed an increased HR for diabetes development after adjustment for confounding variables (1.139; 95% confidence interval 1.116~1.163. These results were similar regardless of the use of anti-hyperlipidemic medication and baseline TC levels.The participants with a large variation in TC levels showed an increased risk for diabetes development, independent of the use of anti-hyperlipidemic medications. These results suggest a relationship between fluctuations in lipid levels and the development of type 2 diabetes.

  19. We are family--parents, siblings, and eating disorders in a prospective total-population study of 250,000 Swedish males and females.

    Science.gov (United States)

    Ahrén, Jennie C; Chiesa, Flaminia; Koupil, Ilona; Magnusson, Cecilia; Dalman, Christina; Goodman, Anna

    2013-11-01

    We examined how parental characteristics and other aspects of family background were associated with the development of eating disorders (ED) in males and females. We used register data and record linkage to create the prospective, total-population study the Stockholm Youth Cohort. This cohort comprises all children and adolescents who were ever residents in Stockholm County between 2001 and 2007, plus their parents and siblings. Individuals born between 1984 and 1995 (N = 249, 884) were followed up for ED from age 12 to end of 2007. We used Cox regression modeling to investigate how ED incidence was associated with family socioeconomic position, parental age, and family composition. In total, 3,251 cases of ED (2,971 females; 280 males) were recorded. Higher parental education independently predicted a higher rate of ED in females [e.g., adjusted hazard ratio (HR) 1.69 (95% CI: 1.42, 2.02) for degree-level vs. elementary-level maternal education], but not in males [HR 0.73 (95% CI: 0.42, 1.28), p siblings was associated with lower rate of ED [e.g., fully adjusted HR 0.92 (95% CI: 0.88, 0.97) per sibling], whereas an increasing number of half-siblings was associated with a higher rate [HR 1.05 (95% CI: 1.01, 1.09) per sibling]. The effect of parental education on ED rate varies between males and females, whereas the effect of number of siblings varies according to whether they are full or half-siblings. A deeper understanding of these associations and their underlying mechanisms may provide etiological insights and inform the design of preventive interventions. Copyright © 2013 Wiley Periodicals, Inc.

  20. The morphological and chemical characteristics of striatal neurons immunoreactive for the alpha1-subunit of the GABA(A) receptor in the rat.

    Science.gov (United States)

    Waldvogel, H J; Kubota, Y; Trevallyan, S C; Kawaguchi, Y; Fritschy, J M; Mohler, H; Faull, R L

    1997-10-01

    The distribution, morphology and chemical characteristics of neurons immunoreactive for the alpha1-subunit of the GABA(A) receptor in the striatum of the basal ganglia in the rat brain were investigated at the light, confocal and electron microscope levels using single, double and triple immunohistochemical labelling techniques. The results showed that alpha1-subunit immunoreactive neurons were sparsely distributed throughout the rat striatum. Double and triple labelling results showed that all the alpha1-subunit-immunoreactive neurons were positive for glutamate decarboxylase and immunoreactive for the beta2,3 and gamma2 subunits of the GABA(A) receptor. Three types of alpha1-subunit-immunoreactive neurons were identified in the striatum on the basis of cellular morphology and chemical characteristics. The most numerous alpha1-subunit-immunoreactive neurons were medium-sized, aspiny neurons with a widely branching dendritic tree. They were parvalbumin-negative and were located mainly in the dorsolateral regions of the striatum. Electron microscopy showed that these neurons had an indented nuclear membrane, typical of striatal interneurons, and were surrounded by small numbers of axon terminals which established alpha1-subunit-immunoreactive synaptic contacts with the soma and dendrites. These cells were classified as type 1 alpha1-subunit-immunoreactive neurons and comprised 75% of the total population of alpha1-subunit-immunoreactive neurons in the striatum. The remaining alpha1-subunit-immunoreactive neurons comprised of a heterogeneous population of large-sized neurons localized in the ventral and medial regions of the striatum. The most numerous large-sized cells were parvalbumin-negative, had two to three relatively short branching dendrites and were designated type 2 alpha1-subunit-immunoreactive neurons. Electron microscopy showed that the type 2 neurons were characterized by a highly convoluted nuclear membrane and were sparsely covered with small axon

  1. Tranexamic acid reduces blood loss and need of blood transfusion in total knee arthroplasty: A prospective, randomized, double-blind study in Indian population

    Directory of Open Access Journals (Sweden)

    Abhishek Shinde

    2015-01-01

    Full Text Available Introduction: For quite a few years, tranexamic acid (TEA has been used during total knee arthroplasty (TKA to reduce blood loss. However, no consensus exits regarding its timing and doses. Materials and Methods: We conducted a prospective, randomized double-blinded study of 56 patients in the Indian population undergoing TKA from 2011 to 2012. A dose of 10 mg/kg body weight of TEA (three doses was given in one group and normal saline was administered in the other. Results: The mean blood loss in the TEA unilateral group was 295 mL ± 218 mL and in the placebo group was 482 mL ± 186 mL (P < 0.005. In the bilateral TEA group, the mean blood loss was 596 mL ± 235 mL and in the placebo group was 1349 mL ± 41 mL (P < 0.005. Conclusion: The number of patients requiring blood transfusion reduced substantially. There was no increase in the risk of deep vein thrombosis (DVT and pulmonary embolism. TEA reduces intraoperative and postoperative blood loss and thus reduces the need of allogenic blood transfusion.

  2. Heritability, assortative mating and gender differences in violent crime: results from a total population sample using twin, adoption, and sibling models.

    Science.gov (United States)

    Frisell, Thomas; Pawitan, Yudi; Långström, Niklas; Lichtenstein, Paul

    2012-01-01

    Research addressing genetic and environmental determinants to antisocial behaviour suggests substantial variability across studies. Likewise, evidence for etiologic gender differences is mixed, and estimates might be biased due to assortative mating. We used longitudinal Swedish total population registers to estimate the heritability of objectively measured violent offending (convictions) in classic twin (N = 36,877 pairs), adoptee-parent (N = 5,068 pairs), adoptee-sibling (N = 10,610 pairs), and sibling designs (N = 1,521,066 pairs). Type and degree of assortative mating were calculated from comparisons between spouses of siblings and half-siblings, and across consecutive spouses. Heritability estimates for the liability of violent offending agreed with previously reported heritability for self-reported antisocial behaviour. While the sibling model yielded estimates similar to the twin model (A ≈ 55%, C ≈ 13%), adoptee-models appeared to underestimate familial effects (A ≈ 20-30%, C ≈ 0%). Assortative mating was moderate to strong (r (spouse) = 0.4), appeared to result from both phenotypic assortment and social homogamy, but had only minor effect on variance components. Finally, we found significant gender differences in the etiology of violent crime.

  3. Essential roles of mitochondrial depolarization in neuron loss through microglial activation and attraction toward neurons.

    Science.gov (United States)

    Nam, Min-Kyung; Shin, Hyun-Ah; Han, Ji-Hye; Park, Dae-Wook; Rhim, Hyangshuk

    2013-04-10

    As life spans increased, neurodegenerative disorders that affect aging populations have also increased. Progressive neuronal loss in specific brain regions is the most common cause of neurodegenerative disease; however, key determinants mediating neuron loss are not fully understood. Using a model of mitochondrial membrane potential (ΔΨm) loss, we found only 25% cell loss in SH-SY5Y (SH) neuronal mono-cultures, but interestingly, 85% neuronal loss occurred when neurons were co-cultured with BV2 microglia. SH neurons overexpressing uncoupling protein 2 exhibited an increase in neuron-microglia interactions, which represent an early step in microglial phagocytosis of neurons. This result indicates that ΔΨm loss in SH neurons is an important contributor to recruitment of BV2 microglia. Notably, we show that ΔΨm loss in BV2 microglia plays a crucial role in microglial activation and phagocytosis of damaged SH neurons. Thus, our study demonstrates that ΔΨm loss in both neurons and microglia is a critical determinant of neuron loss. These findings also offer new insights into neuroimmunological and bioenergetical aspects of neurodegenerative disease. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Npas4: Linking Neuronal Activity to Memory.

    Science.gov (United States)

    Sun, Xiaochen; Lin, Yingxi

    2016-04-01

    Immediate-early genes (IEGs) are rapidly activated after sensory and behavioral experience and are believed to be crucial for converting experience into long-term memory. Neuronal PAS domain protein 4 (Npas4), a recently discovered IEG, has several characteristics that make it likely to be a particularly important molecular link between neuronal activity and memory: it is among the most rapidly induced IEGs, is expressed only in neurons, and is selectively induced by neuronal activity. By orchestrating distinct activity-dependent gene programs in different neuronal populations, Npas4 affects synaptic connections in excitatory and inhibitory neurons, neural circuit plasticity, and memory formation. It may also be involved in circuit homeostasis through negative feedback and psychiatric disorders. We summarize these findings and discuss their implications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Supplementation of increasing amounts of linseed oil to dairy cows fed total mixed rations: effects on digestion, ruminal fermentation characteristics, protozoal populations, and milk fatty acid composition.

    Science.gov (United States)

    Benchaar, C; Romero-Pérez, G A; Chouinard, P Y; Hassanat, F; Eugene, M; Petit, H V; Côrtes, C

    2012-08-01

    The effect of linseed oil (LO) supplementation on nutrient digestibility, forage (i.e., timothy hay) in sacco ruminal degradation, ruminal fermentation characteristics, protozoal populations, milk production, and milk fatty acid (FA) profile in dairy cows was investigated. Four ruminally cannulated, primiparous lactating cows were used in a 4 × 4 Latin square design (28-d periods). They were fed a total mixed ration (50:50 forage:concentrate (F:C) ratio [dry matter (DM) basis] without supplementation (control, CTL), or supplemented (wt/wt; DM basis) with LO at 2, 3, or 4%. Supplementation with LO had no effect on DM intake (19 kg/d) and apparent total-tract digestibility of nutrients (organic matter, neutral detergent fiber, acid detergent fiber, starch, and gross energy). Ruminal pH, ammonia, and total volatile FA concentrations were not changed by LO supplementation to diets. Extent of changes in volatile FA pattern and effective ruminal degradability of DM of timothy hay were minor. Neither the total numbers nor the genera distribution of protozoa was changed by the addition of increasing amounts of LO to the diet. Milk yield increased linearly (26.1, 27.3, 27.4, and 28.4 kg/d for CTL to LO4, respectively) as the amount of LO added to the diet increased. Milk fat content was not affected by LO supplementation, whereas milk protein content decreased linearly with increasing amounts of LO in the diet. Milk fat proportions of several intermediates of ruminal biohydrogenation of polyunsaturated FA (i.e., trans-10 18:1, trans-11 18:1, cis-9,trans-11 18:2, trans-11,cis-15 18:2, and cis-9,trans-11,cis-15 18:3) increased linearly with LO addition to the diet. The proportion of cis-9,cis-12 18:2 decreased linearly (2.06, 1.99, 1.91, and 1.83% for CTL to LO4, respectively) as the amount of LO in the diet increased. Milk fat content of cis-9,cis-12,cis-15 18:3 increased as the level of LO in the diet increased up to 3% but no further increase was observed when 4% of LO

  6. Attractor dynamics in local neuronal networks

    Directory of Open Access Journals (Sweden)

    Jean-Philippe eThivierge

    2014-03-01

    Full Text Available Patterns of synaptic connectivity in various regions of the brain are characterized by the presence of synaptic motifs, defined as unidirectional and bidirectional synaptic contacts that follow a particular configuration and link together small groups of neurons. Recent computational work proposes that a relay network (two populations communicating via a third, relay population of neurons can generate precise patterns of neural synchronization. Here, we employ two distinct models of neuronal dynamics and show that simulated neural circuits designed in this way are caught in a global attractor of activity that prevents neurons from modulating their response on the basis of incoming stimuli. To circumvent the emergence of a fixed global attractor, we propose a mechanism of selective gain inhibition that promotes flexible responses to external stimuli. We suggest that local neuronal circuits may employ this mechanism to generate precise patterns of neural synchronization whose transient nature delimits the occurrence of a brief stimulus.

  7. The influence of aging on the number of neurons and levels of non-phosporylated neurofilament proteins in the central auditory system of rats

    Directory of Open Access Journals (Sweden)

    Jana eBurianová

    2015-03-01

    Full Text Available In the present study, an unbiased stereological method was used to determine the number of all neurons in Nissl stained sections of the inferior colliculus (IC, medial geniculate body (MGB and auditory cortex (AC in rats (strains Long Evans and Fischer 344 and their changes with aging. In addition, using the optical fractionator and western blot technique, we also evaluated the number of SMI-32-immunoreactive(-ir neurons and levels of non-phosphorylated neurofilament proteins in the IC, MGB, AC, and visual cortex (VC of young and old rats of the two strains. The SMI-32 positive neuronal population comprises about 10% of all neurons in the rat IC, MGB and AC and represents a prevalent population of large neurons with highly myelinated and projecting processes. In both Long Evans and Fischer 344 rats, the total number of neurons in the IC was roughly similar to that in the AC. With aging, we found a rather mild and statistically non-significant decline in the total number of neurons in all three analyzed auditory regions in both rat strains. In contrast to this, the absolute number of SMI-32-ir neurons in both Long Evans and Fischer 344 rats significantly decreased with aging in all the examined structures. The western blot technique also revealed a significant age-related decline in the levels of non-phosphorylated neurofilaments in the auditory brain structures, 30-35%. Our results demonstrate that presbycusis in rats is not likely to be primarily associated with changes in the total number of neurons. On the other hand, the pronounced age-related decline in the number of neurons containing non-phosphorylated neurofilaments as well as their protein levels in the central auditory system may contribute to age-related deterioration of hearing function.

  8. Neurochemistry of neurons in the ventrolateral medulla activated by hypotension: Are the same neurons activated by glucoprivation?

    Science.gov (United States)

    Parker, Lindsay M; Le, Sheng; Wearne, Travis A; Hardwick, Kate; Kumar, Natasha N; Robinson, Katherine J; McMullan, Simon; Goodchild, Ann K

    2017-06-15

    Previous studies have demonstrated that a range of stimuli activate neurons, including catecholaminergic neurons, in the ventrolateral medulla. Not all catecholaminergic neurons are activated and other neurochemical content is largely unknown hence whether stimulus specific populations exist is unclear. Here we determine the neurochemistry (using in situ hybridization) of catecholaminergic and noncatecholaminergic neurons which express c-Fos immunoreactivity throughout the rostrocaudal extent of the ventrolateral medulla, in Sprague Dawley rats treated with hydralazine or saline. Distinct neuronal populations containing PPCART, PPPACAP, and PPNPY mRNAs, which were largely catecholaminergic, were activated by hydralazine but not saline. Both catecholaminergic and noncatecholaminergic neurons containing preprotachykinin and prepro-enkephalin (PPE) mRNAs were also activated, with the noncatecholaminergic population located in the rostral C1 region. Few GlyT2 neurons were activated. A subset of these data was then used to compare the neuronal populations activated by 2-deoxyglucose evoked glucoprivation (Brain Structure and Function (2015) 220:117). Hydralazine activated more neurons than 2-deoxyglucose but similar numbers of catecholaminergic neurons. Commonly activated populations expressing PPNPY and PPE mRNAs were defined. These likely include PPNPY expressing catecholaminergic neurons projecting to vasopressinergic and corticotrophin releasing factor neurons in the paraventricular nucleus, which when activated result in elevated plasma vasopressin and corticosterone. Stimulus specific neurons included noncatecholaminergic neurons and a few PPE positive catecholaminergic neuron but neurochemical codes were largely unidentified. Reasons for the lack of identification of stimulus specific neurons, readily detectable using electrophysiology in anaesthetized preparations and for which neural circuits can be defined, are discussed. © 2017 Wiley Periodicals, Inc.

  9. Disparities in total knee replacement: Population losses in quality-adjusted life years due to differential offer, acceptance, and complication rates for Black Americans.

    Science.gov (United States)

    Kerman, Hannah M; Smith, Savannah R; Smith, Karen C; Collins, Jamie E; Suter, Lisa G; Katz, Jeffrey N; Losina, Elena

    2018-01-24

    Total knee replacement (TKR) is an effective treatment for end-stage knee osteoarthritis (OA). American racial minorities undergo fewer TKRs than Whites. We estimated quality-adjusted life years (QALYs) lost for Black knee OA patients due to differences in TKR offer, acceptance, and complication rates. We used the Osteoarthritis Policy Model, a computer simulation of knee OA, to predict QALY outcomes for Black and White knee OA patients with and without TKR. We estimated per-person QALYs gained from TKR as the difference between QALYs with current TKR use and QALYs when no TKR was performed. We estimated average, per-person QALY losses in Blacks as the difference between QALYs gained with White rates of TKR and QALYs gained with Black rates of TKR. We calculated population-level QALY losses by multiplying per-person QALY losses by the number of persons with advanced knee OA. Finally, we estimated QALYs lost specifically due to lower TKR offer and acceptance and higher complications among Black knee OA patients. Black men and women gain 64,100 QALYs from current TKR use. With white offer and complications rates, they would gain an additional 72,000 QALYs. Because these additional gains are unrealized, we call this a loss of 72,000 QALYs. Black Americans lose 67,500 QALYs because of lower offer, 15,800 QALYs because of lower acceptance, and 2,600 QALYs because of higher complications. Black Americans lose 72,000 QALYs due to disparities in TKR offer and complication rates. Programs to decrease disparities in TKR use are urgently needed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Smoking, body weight, physical exercise, and risk of lower limb total joint replacement in a population-based cohort of men.

    Science.gov (United States)

    Mnatzaganian, George; Ryan, Philip; Norman, Paul E; Davidson, David C; Hiller, Janet E

    2011-08-01

    To assess the associations of smoking, body weight, and physical activity with risk of undergoing total joint replacement (TJR) in a population-based cohort of men. A cohort study of 11,388 men that integrated clinical data with hospital morbidity data and mortality records was undertaken. The risk of undergoing TJR was modeled on baseline weight, height, comorbidity, socioeconomic status, years of smoking, and exercise in 3 separate age groups, using Cox proportional hazards regressions and competing risk regressions (CRRs). Dose-response relationships between weight and risk of TJR and between smoking and risk of TJR were observed. Being overweight independently increased the risk of TJR, while smoking lowered the risk. The decreased risk among smokers was demonstrated in both Cox and CRR models and became apparent after 23 years of exposure. Men who were in the highest quartile (≥48 years of smoking) were 42-51% less likely to undergo TJR than men who had never smoked. Tests for trend in the log hazard ratios (HRs) across both smoking and weight quantiles yielded significant P values. Vigorous exercise increased the hazard of TJR; however, the association reached statistical significance only in the 70-74-year-old age group (adjusted HR 1.64 [95% confidence interval 1.19-2.24]). Adjusting for Deyo-Charlson Index or Elixhauser's comorbidity measures did not eliminate these associations. Our findings indicate that being overweight and reporting vigorous physical activity increase the risk of TJR. This study is the first to demonstrate a strong inverse dose-response relationship between duration of smoking and risk of TJR. More research is needed to better understand the role of smoking in the pathogenesis of osteoarthritis. Copyright © 2011 by the American College of Rheumatology.

  11. Modelling strategic interventions in a population with a total fertility rate of 8.3: a cross-sectional study of Idjwi Island, DRC

    Directory of Open Access Journals (Sweden)

    Thomson Dana R

    2012-11-01

    Full Text Available Abstract Background Idjwi, an island of approximately 220,000 people, is located in eastern DRC and functions semi-autonomously under the governance of two kings (mwamis. At more than 8 live births per woman, Idjwi has one of the highest total fertility rates (TFRs in the world. Rapid population growth has led to widespread environmental degradation and food insecurity. Meanwhile family planning services are largely unavailable. Methods At the invitation of local leaders, we conducted a representative survey of 2,078 households in accordance with MEASURE DHS protocols, and performed ethnographic interviews and focus groups with key informants and vulnerable subpopulations. Modelling proximate determinates of fertility, we evaluated how the introduction of contraceptives and/or extended periods of breastfeeding could reduce the TFR. Results Over half of all women reported an unmet need for spacing or limiting births, and nearly 70% named a specific modern method of contraception they would prefer to use; pills (25.4% and injectables (26.5% were most desired. We predicted that an increased length of breastfeeding (from 10 to 21 months or an increase in contraceptive prevalence (from 1% to 30%, or a combination of both could reduce TFR on Idjwi to 6, the average desired number of children. Increasing contraceptive prevalence to 15% could reduce unmet need for contraception by 8%. Conclusions To meet women’s need and desire for fertility control, we recommend adding family planning services at health centers with NGO support, pursuing a community health worker program, promoting extended breastfeeding, and implementing programs to end sexual- and gender-based violence toward women.

  12. Calcium signals in olfactory neurons.

    Science.gov (United States)

    Tareilus, E; Noé, J; Breer, H

    1995-11-09

    Laser scanning confocal microscopy in combination with the fluorescent calcium indicators Fluo-3 and Fura-Red was employed to estimate the intracellular concentration of free calcium ions in individual olfactory receptor neurons and to monitor temporal and spatial changes in the Ca(2+)-level upon stimulation. The chemosensory cells responded to odorants with a significant increase in the calcium concentration, preferentially in the dendritic knob. Applying various stimulation paradigma, it was found that in a population of isolated cells, subsets of receptor neurons display distinct patterns of responsiveness.

  13. Total protein

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003483.htm Total protein To use the sharing features on this page, please enable JavaScript. The total protein test measures the total amount of two classes ...

  14. Degree of synchronization modulated by inhibitory neurons in clustered excitatory-inhibitory recurrent networks

    Science.gov (United States)

    Li, Huiyan; Sun, Xiaojuan; Xiao, Jinghua

    2018-01-01

    An excitatory-inhibitory recurrent neuronal network is established to numerically study the effect of inhibitory neurons on the synchronization degree of neuronal systems. The obtained results show that, with the number of inhibitory neurons and the coupling strength from an inhibitory neuron to an excitatory neuron increasing, inhibitory neurons can not only reduce the synchronization degree when the synchronization degree of the excitatory population is initially higher, but also enhance it when it is initially lower. Meanwhile, inhibitory neurons could also help the neuronal networks to maintain moderate synchronized states. In this paper, we call this effect as modulation effect of inhibitory neurons. With the obtained results, it is further revealed that the ratio of excitatory neurons to inhibitory neurons being nearly 4 : 1 is an economic and affordable choice for inhibitory neurons to realize this modulation effect.

  15. Dietary exposure assessment of Chinese population to tetrabromobisphenol-A, hexabromocyclododecane and decabrominated diphenyl ether: Results of the 5th Chinese Total Diet Study

    International Nuclear Information System (INIS)

    Shi, Zhixiong; Zhang, Lei; Zhao, Yunfeng; Sun, Zhiwei; Zhou, Xianqing; Li, Jingguang; Wu, Yongning

    2017-01-01

    Based on the 5th Chinese Total Diet Study (TDS) carried out in 2011, the dietary exposure of Chinese population to three currently used brominated flame retardants (BFRs), tetrabromobisphenol A (TBBPA), hexabromocyclododecane (HBCD) and decabrominated diphenyl ether (BDE-209), was estimated and the related health risks were assessed. Levels of the three BFRs were determined in 80 composite samples from four animal-origin food groups. The average levels of BFRs in various food groups ranged from 0.671 to 5.76 ng/g lipid weight (lw). The levels of TBBPA were lower than those of HBCD but higher than those of BDE-209. Moreover, average contamination levels of TBBPA and HBCD in TDS 2011 were found to be 3 to 30 times higher than those observed in TDS 2007 in the four food groups, indicating an increase in TBBPA and HBCD in the environment during 2007–2011. The average estimated daily intakes (EDIs) of TBBPA, HBCD and BDE-209 via food consumption for a “standard Chinese man” were 1.34, 1.51 and 0.96 ng/kg bw/day, respectively. Meat and meat products were found to be the major contributor to the daily dietary intake because the consumption of meat and meat products were significantly higher than that of other food groups in China. In comparison, the levels and EDIs of BFRs in this study were found to be higher than those in most studies worldwide. However, the large margin of exposure (MOE), with at least 1.1 × 10 5 calculated following the European Food Safety Authority (EFSA) approach, indicates that the estimated dietary exposure to these three BFRs is unlikely to raise significant health concerns. In addition, a comparison between the contamination levels of TBBPA, HBCD, BDE-209 and some novel BFRs in food samples from TDS 2011 indicated an obvious shift in the industrial production and usage pattern between PBDE and non-PBDE BFRs in China. - Highlights: • In a national survey, TBBPA, HBCD and BDE-209 were measured in food composites collected from 20

  16. Use of neuronal networks in the modeling of the doses that receives the Cuban population by potassium-40 contained in their organism

    International Nuclear Information System (INIS)

    Zerquera, Juan Tomas; Prendes Alonso, Miguel; Lopez Bejerano, Gladys M.; Acosta Rodriguez, Nancy

    2001-01-01

    The potassium 40 constitutes the main source natural present in the organism that influences in the effective dose that people receive. With the objective of evaluating the contribution from this component to the doses received by the Cuban population, a study was developed in order to evaluate the doses for this cause. A representative sample was selected based on the distribution of Cuban population by sex and ages. The measurements were carried out in the Whole Body Counter of the Center for Radiation Protection and Hygiene. For the estimate of the doses an uniform distribution of potassium was assumed in the whole body and the methodology was used recommended by the ICRP. The values of annual effective dose varies between 93 and 209 mSv for the feminine sex and 102 and 212 mSv for the masculine sex. With the obtained values they were the adjustment coefficients for the functions dose-age for each one of the sexes. At the same time it was possible to model the estimate of the doses by means of a neural network that, trained with the obtained experimental data, it allows to estimate the due doses directly to the potassium 40 starting from the sex data, age, height and corporal weight. The effective dose mediates yearly for the public's members it was estimated in 149 ± 6 mSv, starting from the experimental data and the Cuban population's specific characteristics. (author)

  17. Total algorithms

    NARCIS (Netherlands)

    Tel, G.

    We define the notion of total algorithms for networks of processes. A total algorithm enforces that a "decision" is taken by a subset of the processes, and that participation of all processes is required to reach this decision. Total algorithms are an important building block in the design of

  18. Accurate counting of neurons in frozen sections: some necessary precautions.

    OpenAIRE

    Cooper, J D; Payne, J N; Horobin, R W

    1988-01-01

    In 30 microns frozen sections of rat midbrain the retrograde axonal transport of diamidino yellow, a fluorescent tracer, was used to demonstrate a population of neurons in the substantia nigra. However, when visualisation was carried out using the routine Nissl method a significant proportion of neurons failed to stain. As the presence of the retrograde tracer did not affect Nissl staining of such cells, such incomplete staining, with consequent underestimation of neuronal populations, is pro...

  19. GDE2 regulates subtype-specific motor neuron generation through inhibition of Notch signaling.

    Science.gov (United States)

    Sabharwal, Priyanka; Lee, Changhee; Park, Sungjin; Rao, Meenakshi; Sockanathan, Shanthini

    2011-09-22

    The specification of spinal interneuron and motor neuron identities initiates within progenitor cells, while motor neuron subtype diversification is regulated by hierarchical transcriptional programs implemented postmitotically. Here we find that mice lacking GDE2, a six-transmembrane protein that triggers motor neuron generation, exhibit selective losses of distinct motor neuron subtypes, specifically in defined subsets of limb-innervating motor pools that correlate with the loss of force-generating alpha motor neurons. Mechanistically, GDE2 is expressed by postmitotic motor neurons but utilizes extracellular glycerophosphodiester phosphodiesterase activity to induce motor neuron generation by inhibiting Notch signaling in neighboring motor neuron progenitors. Thus, neuronal GDE2 controls motor neuron subtype diversity through a non-cell-autonomous feedback mechanism that directly regulates progenitor cell differentiation, implying that subtype specification initiates within motor neuron progenitor populations prior to their differentiation into postmitotic motor neurons. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Carbon monoxide improves neuronal differentiation and yield by increasing the functioning and number of mitochondria.

    Science.gov (United States)

    Almeida, Ana S; Sonnewald, Ursula; Alves, Paula M; Vieira, Helena L A

    2016-08-01

    The process of cell differentiation goes hand-in-hand with metabolic adaptations, which are needed to provide energy and new metabolites. Carbon monoxide (CO) is an endogenous cytoprotective molecule able to inhibit cell death and improve mitochondrial metabolism. Neuronal differentiation processes were studied using the NT2 cell line, which is derived from human testicular embryonic teratocarcinoma and differentiates into post-mitotic neurons upon retinoic acid treatment. CO-releasing molecule A1 (CORM-A1) was used do deliver CO into cell culture. CO treatment improved NT2 neuronal differentiation and yield, since there were more neurons and the total cell number increased following the differentiation process. CO supplementation enhanced the mitochondrial population in post-mitotic neurons derived from NT2 cells, as indicated by an increase in mitochondrial DNA. CO treatment during neuronal differentiation increased the extent of the classical metabolic change that occurs during neuronal differentiation, from glycolytic to more oxidative metabolism, by decreasing the ratio of lactate production and glucose consumption. The expression of pyruvate and lactate dehydrogenases was higher, indicating an augmented oxidative metabolism. Moreover, these findings were corroborated by an increased percentage of (13) C incorporation from [U-(13) C]glucose into the tricarboxylic acid cycle metabolites malate and citrate, and also glutamate and aspartate in CO-treated cells. Finally, under low levels of oxygen (5%), which enhances glycolytic metabolism, some of the enhancing effects of CO on mitochondria were not observed. In conclusion, our data show that CO improves neuronal and mitochondrial yield by stimulation of tricarboxylic acid cycle activity, and thus oxidative metabolism of NT2 cells during the process of neuronal differentiation. The process of cell differentiation is coupled with metabolic adaptations. Carbon monoxide (CO) is an endogenous cytoprotective

  1. Boundary curves of individual items in the distribution of total depressive symptom scores approximate an exponential pattern in a general population

    OpenAIRE

    Tomitaka, Shinichiro; Kawasaki, Yohei; Ide, Kazuki; Akutagawa, Maiko; Yamada, Hiroshi; Furukawa, Toshiaki A.; Ono, Yutaka

    2016-01-01

    [Background]Previously, we proposed a model for ordinal scale scoring in which individual thresholds for each item constitute a distribution by each item. This lead us to hypothesize that the boundary curves of each depressive symptom score in the distribution of total depressive symptom scores follow a common mathematical model, which is expressed as the product of the frequency of the total depressive symptom scores and the probability of the cumulative distribution function of each item th...

  2. Neuronal Migration Disorders

    Science.gov (United States)

    ... Understanding Sleep The Life and Death of a Neuron Genes At Work In The Brain Order Publications ... birth defects caused by the abnormal migration of neurons in the developing brain and nervous system. In ...

  3. Motor Neuron Diseases

    Science.gov (United States)

    ... and other neurodegenerative diseases to better understand the function of neurons and other support cells and identify candidate therapeutic ... and other neurodegenerative diseases to better understand the function of neurons and other support cells and identify candidate therapeutic ...

  4. Parkin Mutations Reduce the Complexity of Neuronal Processes in iPSC-derived Human Neurons

    Science.gov (United States)

    Ren, Yong; Jiang, Houbo; Hu, Zhixing; Fan, Kevin; Wang, Jun; Janoschka, Stephen; Wang, Xiaomin; Ge, Shaoyu; Feng, Jian

    2015-01-01

    Parkinson’s disease (PD) is characterized by the degeneration of nigral dopaminergic (DA) neurons and non-DA neurons in many parts of the brain. Mutations of parkin, an E3 ubiquitin ligase that strongly binds to microtubules, are the most frequent cause of recessively inherited Parkinson’s disease. The lack of robust PD phenotype in parkin knockout mice suggests a unique vulnerability of human neurons to parkin mutations. Here, we show that the complexity of neuronal processes as measured by total neurite length, number of terminals, number of branch points and Sholl analysis, was greatly reduced in induced pluripotent stem cell (iPSC)-derived TH+ or TH− neurons from PD patients with parkin mutations. Consistent with these, microtubule stability was significantly decreased by parkin mutations in iPSC-derived neurons. Overexpression of parkin, but not its PD-linked mutant nor GFP, restored the complexity of neuronal processes and the stability of microtubules. Consistent with these, the microtubule-depolymerizing agent colchicine mimicked the effect of parkin mutations by decreasing neurite length and complexity in control neurons while the microtubule-stabilizing drug taxol mimicked the effect of parkin overexpression by enhancing the morphology of parkin-deficient neurons. The results suggest that parkin maintains the morphological complexity of human neurons by stabilizing microtubules. PMID:25332110

  5. Study on total mercury and methylmercury levels in hair and tissues of typical human populations exposed to mercury in China by NAA and GC(EC)

    International Nuclear Information System (INIS)

    Chai Chifang; Qian Qinfang; Feng Weiyu; Sun Jianguo; Li Xinji; Lu Yilun; Zhang Xioumei; Zhang Shen

    1992-01-01

    Since the first Research Coordination Meeting in Vienna, 10-13 June 1991, China has been putting the research emphasis on two aspects for studying mercury exposure to the population. The first is a methodology for methylmercury analysis. The second is the collection and analysis of representative hair samples. The main activities during this study period are summarized in this paper. 8 tabs

  6. Total external dose equivalent and effective dose derived to the Piedmont population in the period 30 Apr 1986 - 22 Sep 1987

    International Nuclear Information System (INIS)

    Cortissone, C.; Giacomelli, R.; Spezzano, P.; Porzio, L.

    1988-01-01

    Some dosimetric evaluations concerning the population of the Piemonte Region, obtained after the measurements made following the Chernobyl accident, are reported. The individual effective mean dose equivalent derived from the exposure and intake in the period April 30, 1986 - September 22, 1987, is about 0.50 mSv

  7. The Association between Total Protein and Vegetable Protein Intake and Low Muscle Mass among the Community-Dwelling Elderly Population in Northern Taiwan

    Directory of Open Access Journals (Sweden)

    Ru-Yi Huang

    2016-06-01

    Full Text Available Sarcopenia, highly linked with fall, frailty, and disease burden, is an emerging problem in aging society. Higher protein intake has been suggested to maintain nitrogen balance. Our objective was to investigate whether pre-sarcopenia status was associated with lower protein intake. A total of 327 community-dwelling elderly people were recruited for a cross-sectional study. We adopted the multivariate nutrient density model to identify associations between low muscle mass and dietary protein intake. The general linear regression models were applied to estimate skeletal muscle mass index across the quartiles of total protein and vegetable protein density. Participants with diets in the lowest quartile of total protein density (<13.2% were at a higher risk for low muscle mass (odds ratio (OR 3.03, 95% confidence interval (CI 1.37–6.72 than those with diets in the highest quartile (≥17.2%. Similarly, participants with diets in the lowest quartile of vegetable protein density (<5.8% were at a higher risk for low muscle mass (OR 2.34, 95% CI 1.14–4.83 than those with diets in the highest quartile (≥9.4%. Furthermore, the estimated skeletal muscle mass index increased significantly across the quartiles of total protein density (p = 0.023 and vegetable protein density (p = 0.025. Increasing daily intakes of total protein and vegetable protein densities appears to confer protection against pre-sarcopenia status.

  8. Inhibitory neurons modulate spontaneous signaling in cultured cortical neurons: density-dependent regulation of excitatory neuronal signaling

    International Nuclear Information System (INIS)

    Serra, Michael; Guaraldi, Mary; Shea, Thomas B

    2010-01-01

    Cortical neuronal activity depends on a balance between excitatory and inhibitory influences. Culturing of neurons on multi-electrode arrays (MEAs) has provided insight into the development and maintenance of neuronal networks. Herein, we seeded MEAs with murine embryonic cortical/hippocampal neurons at different densities ( 1000 cells mm −2 ) and monitored resultant spontaneous signaling. Sparsely seeded cultures displayed a large number of bipolar, rapid, high-amplitude individual signals with no apparent temporal regularity. By contrast, densely seeded cultures instead displayed clusters of signals at regular intervals. These patterns were observed even within thinner and thicker areas of the same culture. GABAergic neurons (25% of total neurons in our cultures) mediated the differential signal patterns observed above, since addition of the inhibitory antagonist bicuculline to dense cultures and hippocampal slice cultures induced the signal pattern characteristic of sparse cultures. Sparsely seeded cultures likely lacked sufficient inhibitory neurons to modulate excitatory activity. Differential seeding of MEAs can provide a unique model for analyses of pertubation in the interaction between excitatory and inhibitory function during aging and neuropathological conditions where dysregulation of GABAergic neurons is a significant component

  9. Total dietary fiber intakes in the US population are related to whole grain consumption: results from the National Health and Nutrition Examination Survey 2009 to 2010.

    Science.gov (United States)

    Reicks, Marla; Jonnalagadda, Satya; Albertson, Ann M; Joshi, Nandan

    2014-03-01

    Whole grain (WG) foods have been shown to reduce chronic disease risk and overweight. Total dietary fiber is associated with WG and its health benefits. The purpose was to determine whether associations exist between WG intake (no-WG intake, 0 ounce equivalent [oz eq]; low, >0-cereals and yeast breads/rolls in the high WG intake group compared with the no-WG intake group. Major WG sources for children/adolescents and adults included yeast bread/rolls (24% and 27%, respectively), RTE cereals (25% and 20%, respectively), and oatmeal (12% and 21%, respectively). Among those with the highest WG intake, WG RTE cereal with no added bran was the greatest contributor to total dietary fiber compared with other RTE cereal types. Whole grain foods make a substantial contribution to total dietary fiber intake and should be promoted to meet recommendations. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Totally James

    Science.gov (United States)

    Owens, Tom

    2006-01-01

    This article presents an interview with James Howe, author of "The Misfits" and "Totally Joe". In this interview, Howe discusses tolerance, diversity and the parallels between his own life and his literature. Howe's four books in addition to "The Misfits" and "Totally Joe" and his list of recommended books with lesbian, gay, bisexual, transgender,…

  11. Neuron Morphology Influences Axon Initial Segment Plasticity.

    Science.gov (United States)

    Gulledge, Allan T; Bravo, Jaime J

    2016-01-01

    In most vertebrate neurons, action potentials are initiated in the axon initial segment (AIS), a specialized region of the axon containing a high density of voltage-gated sodium and potassium channels. It has recently been proposed that neurons use plasticity of AIS length and/or location to regulate their intrinsic excitability. Here we quantify the impact of neuron morphology on AIS plasticity using computational models of simplified and realistic somatodendritic morphologies. In small neurons (e.g., dentate granule neurons), excitability was highest when the AIS was of intermediate length and located adjacent to the soma. Conversely, neurons having larger dendritic trees (e.g., pyramidal neurons) were most excitable when the AIS was longer and/or located away from the soma. For any given somatodendritic morphology, increasing dendritic membrane capacitance and/or conductance favored a longer and more distally located AIS. Overall, changes to AIS length, with corresponding changes in total sodium conductance, were far more effective in regulating neuron excitability than were changes in AIS location, while dendritic capacitance had a larger impact on AIS performance than did dendritic conductance. The somatodendritic influence on AIS performance reflects modest soma-to-AIS voltage attenuation combined with neuron size-dependent changes in AIS input resistance, effective membrane time constant, and isolation from somatodendritic capacitance. We conclude that the impact of AIS plasticity on neuron excitability will depend largely on somatodendritic morphology, and that, in some neurons, a shorter or more distally located AIS may promote, rather than limit, action potential generation.

  12. Dietary total flavonoids intake and risk of mortality from all causes and cardiovascular disease in the general population: A systematic review and meta-analysis of cohort studies.

    Science.gov (United States)

    Liu, Xue-Ming; Liu, Yu-Jian; Huang, Yao; Yu, Hong-Jie; Yuan, Shuai; Tang, Bo-Wen; Wang, Pei-Gang; He, Qi-Qiang

    2017-06-01

    Epidemiologic studies assessing the association between dietary total flavonoids intake and the risk of mortality from cardiovascular disease (CVD) and all causes have yielded inconsistent results. Therefore, we conducted a dose-response meta-analysis to investigate this association. We searched PubMed and Embase databases from January 1966 through May 2016 and examined the references of retrieved articles to identify relevant prospective cohort studies. The random-effect model was used to calculate the summary risk estimates and dose-response analysis was performed. Ten studies were included in the present meta-analysis. The relative risk (RR) of all-cause mortality for the highest versus lowest category of total flavonoids intake was 0.82 (95% confidence interval (CI): 0.72-0.92). Dose-response analysis showed that those consuming 200 mg/day of total flavonoids had the lowest risk of all-cause mortality. Furthermore, a marginally significant association was found between dietary total flavonoids consumption and risk of death from CVD (summary RR: 0.85; 95% CI: 0.70-1.03; P = 0.099) and coronary heart diseases (summary RR: 0.74; 95% CI: 0.54-1.02; P = 0.069), respectively. The meta-analysis provides strong evidence for the recommendation of consuming flavonoids-rich food to reduce risks of mortality from all causes as part of a healthy diet among general adults. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Habitual Physical Activity After Total Knee Replacement : analysis in 830 patients and comparison with a sex-and age-matched normative population (vol 92, pg 1109, 2012)

    NARCIS (Netherlands)

    Kersten, Roel F. M. R.; Stevens, Martin; van Raay, Jos J. A. M.; Bulstra, Sjoerd K.; van den Akker-Scheek, Inge

    Background. Previous studies on physical activity after total knee arthroplasty (TKA) concentrated mainly on a return to sports activities. Objective. The objectives of this study were to determine the habitual physical activity behavior of people who had undergone TKA (TKA group) 1 to 5 years after

  14. Serum tree IGF-I, total IGF-I, IGFBP-1 and IGFBP-3 levels in an elderly population : relation to age and sex steroid levels

    NARCIS (Netherlands)

    Janssen, JAMJL; Stolk, RP; Pols, HAP; Grobbee, DE; de Jong, FH; Lamberts, SWJ

    BACKGROUND Most previous studies concerning the relationship between IGF-I and age used assays measuring total IGF-I, Although free IGF-I is considered of greater biological relevance, little is known about its relationship with sex steroids levels in elderly healthy subjects, MEASUREMENTS In a

  15. Population PKPD modeling of BACE1 inhibitor-induced reduction in Aβ levels in vivo and correlation to in vitro potency in primary cortical neurons from mouse and guinea pig.

    Science.gov (United States)

    Janson, Juliette; Eketjäll, Susanna; Tunblad, Karin; Jeppsson, Fredrik; Von Berg, Stefan; Niva, Camilla; Radesäter, Ann-Cathrin; Fälting, Johanna; Visser, Sandra A G

    2014-03-01

    The aims were to quantify the in vivo time-course between the oral dose, the plasma and brain exposure and the inhibitory effect on Amyloid β (Aβ) in brain and cerebrospinal fluid, and to establish the correlation between in vitro and in vivo potency of novel β-secretase (BACE1) inhibitors. BACE1-mediated inhibition of Aβ was quantified in in vivo dose- and/or time-response studies and in vitro in SH-SY5Y cells, N2A cells, and primary cortical neurons (PCN). An indirect response model with inhibition on Aβ production rate was used to estimate unbound in vivo IC 50 in a population pharmacokinetic-pharmacodynamic modeling approach. Estimated in vivo inhibitory potencies varied between 1 and 1,000 nM. The turnover half-life of Aβ40 in brain was predicted to be 0.5 h in mouse and 1 h in guinea pig. An excellent correlation between PCN and in vivo potency was observed. Moreover, a strong correlation in potency was found between human SH-SY5Y cells and mouse PCN, being 4.5-fold larger in SH-SY5Y cells. The strong in vivo-in vitro correlation increased the confidence in using human cell lines for screening and optimization of BACE1 inhibitors. This can optimize the design and reduce the number of preclinical in vivo effect studies.

  16. Increased neuronal firing in resting and sleep in areas of the macaque medial prefrontal cortex.

    Science.gov (United States)

    Gabbott, Paul L; Rolls, Edmund T

    2013-06-01

    The medial prefrontal cortex (mPFC) of humans and macaques is an integral part of the default mode network and is a brain region that shows increased activation in the resting state. A previous paper from our laboratory reported significantly increased firing rates of neurons in the macaque subgenual cingulate cortex, Brodmann area (BA) 25, during disengagement from a task and also during slow wave sleep [E.T. Rolls et al. (2003) J. Neurophysiology, 90, 134-142]. Here we report the finding that there are neurons in other areas of mPFC that also increase their firing rates during disengagement from a task, drowsiness and eye-closure. During the neurophysiological recording of single mPFC cells (n = 249) in BAs 9, 10, 13 m, 14c, 24b and especially pregenual area 32, populations of neurons were identified whose firing rates altered significantly with eye-closure compared with eye-opening. Three types of neuron were identified: Type 1 cells (28.1% of the total population) significantly increased (mean + 329%; P ≪ 0.01) their average firing rate with eye-closure, from 3.1 spikes/s when awake to 10.2 spikes/s when asleep; Type 2 cells (6.0%) significantly decreased (mean -68%; P areas of mPFC, implicated in the anterior default mode network, there is a substantial population of neurons that significantly increase their firing rates during periods of eye-closure. Such neurons may be part of an interconnected network of distributed brain regions that are more active during periods of relaxed wakefulness than during attention-demanding tasks. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  17. Hypothalamic neurones governing glucose homeostasis.

    Science.gov (United States)

    Coppari, R

    2015-06-01

    The notion that the brain directly controls the level of glucose in the blood (glycaemia) independent of its known action on food intake and body weight has been known ever since 1849. That year, the French physiologist Dr Claude Bernard reported that physical puncture of the floor of the fourth cerebral ventricle rapidly leads to an increased level of sugar in the blood (and urine) in rabbits. Despite this important discovery, it took approximately 150 years before significant efforts aimed at understanding the underlying mechanism of brain-mediated control of glucose metabolism were made. Technological developments allowing for genetically-mediated manipulation of selected molecular pathways in a neurone-type-specific fashion unravelled the importance of specific molecules in specific neuronal populations. These neuronal pathways govern glucose metabolism in the presence and even in the absence of insulin. Also, a peculiarity of these pathways is that certain biochemically-defined neurones govern glucose metabolism in a tissue-specific fashion. © 2015 British Society for Neuroendocrinology.

  18. An empirical study using range of motion and pain score as determinants for continuous passive motion: outcomes following total knee replacement surgery in an adult population.

    Science.gov (United States)

    Tabor, Danielle

    2013-01-01

    The continuous passive motion (CPM) machine is one means by which to rehabilitate the knee after total knee replacement surgery. This study sought to determine which total knee replacement patients, if any, benefit from the use of the CPM machine. For the study period, most patients received active physical therapy. Patients were placed in the CPM machine if, on postoperative day 1, they had a range of motion less than or equal to 45° and/or pain score of 8 or greater on a numeric rating scale of 0-10, 0 being no pain and 10 being the worst pain. Both groups of patients healed at similar rates. The incidence of adverse events, length of stay, and functional outcomes was comparable between groups. Given the demonstrated lack of relative benefit to the patient and the cost of the CPM, this study supported discontinuing the routine use of the CPM.

  19. A new system of computer-assisted navigation leading to reduction in operating time in uncemented total hip replacement in a matched population.

    Science.gov (United States)

    Chaudhry, Fouad A; Ismail, Sanaa Z; Davis, Edward T

    2018-05-01

    Computer-assisted navigation techniques are used to optimise component placement and alignment in total hip replacement. It has developed in the last 10 years but despite its advantages only 0.3% of all total hip replacements in England and Wales are done using computer navigation. One of the reasons for this is that computer-assisted technology increases operative time. A new method of pelvic registration has been developed without the need to register the anterior pelvic plane (BrainLab hip 6.0) which has shown to improve the accuracy of THR. The purpose of this study was to find out if the new method reduces the operating time. This was a retrospective analysis of comparing operating time in computer navigated primary uncemented total hip replacement using two methods of registration. Group 1 included 128 cases that were performed using BrainLab versions 2.1-5.1. This version relied on the acquisition of the anterior pelvic plane for registration. Group 2 included 128 cases that were performed using the newest navigation software, BrainLab hip 6.0 (registration possible with the patient in the lateral decubitus position). The operating time was 65.79 (40-98) minutes using the old method of registration and was 50.87 (33-74) minutes using the new method of registration. This difference was statistically significant. The body mass index (BMI) was comparable in both groups. The study supports the use of new method of registration in improving the operating time in computer navigated primary uncemented total hip replacements.

  20. Total energy intake may be more associated with glycemic control compared to each proportion of macronutrients in the korean diabetic population.

    Science.gov (United States)

    Kang, Hye Mi; Kim, Dong-Jun

    2012-08-01

    Major macronutrients for energy intake vary among countries and cultures. Carbohydrates, including rice, are the major component of daily energy intake in Korea. The aim of this study was to examine the association of daily energy intake or each proportion of macronutrients, especially carbohydrates, with glycemic control in diabetic Koreans. A total of 334 individuals with diabetes (175 men, age 57.4±0.8 years; 159 women, age 60.9±0.9 years) who participated in the 2005 Korean National Health and Nutrition Examination Survey were examined. Glycemic control was categorized based on concentration of glycated hemoglobin (HbA1c; HbA1c ≤6.5%; 6.6% to 8.0%; ≥8.1%). Dietary intake was assessed by using a 24-recall item questionnaire. High total energy intake was associated with poor glycemic control (HbA1c ≤6.5%, 1,824±75 kcal; 6.6% to 8.0%, 1,990±57 kcal; ≥8.1%, 2,144±73 kcal; P value for trend=0.002). Each proportion of protein, fat, or carbohydrate was not associated with glycemic control. Even after adjusting for several parameters, the association of daily energy intake with glycemic control still persisted. Total energy intake may be more closely related to glycemic control than each proportionof macronutrients in Korean diabetics.

  1. Total Energy Intake May Be More Associated with Glycemic Control Compared to Each Proportion of Macronutrients in the Korean Diabetic Population

    Directory of Open Access Journals (Sweden)

    Hye Mi Kang

    2012-08-01

    Full Text Available BackgroundMajor macronutrients for energy intake vary among countries and cultures. Carbohydrates, including rice, are the major component of daily energy intake in Korea. The aim of this study was to examine the association of daily energy intake or each proportion of macronutrients, especially carbohydrates, with glycemic control in diabetic Koreans.MethodsA total of 334 individuals with diabetes (175 men, age 57.4±0.8 years; 159 women, age 60.9±0.9 years who participated in the 2005 Korean National Health and Nutrition Examination Survey were examined. Glycemic control was categorized based on concentration of glycated hemoglobin (HbA1c; HbA1c ≤6.5%; 6.6% to 8.0%; ≥8.1%. Dietary intake was assessed by using a 24-recall item questionnaire.ResultsHigh total energy intake was associated with poor glycemic control (HbA1c ≤6.5%, 1,824±75 kcal; 6.6% to 8.0%, 1,990±57 kcal; ≥8.1%, 2,144±73 kcal; P value for trend=0.002. Each proportion of protein, fat, or carbohydrate was not associated with glycemic control. Even after adjusting for several parameters, the association of daily energy intake with glycemic control still persisted.ConclusionTotal energy intake may be more closely related to glycemic control than each proportionof macronutrients in Korean diabetics.

  2. Conditional expression of Pomc in the Lepr-positive subpopulation of POMC neurons is sufficient for normal energy homeostasis and metabolism.

    Science.gov (United States)

    Lam, Daniel D; Attard, Courtney A; Mercer, Aaron J; Myers, Martin G; Rubinstein, Marcelo; Low, Malcolm J

    2015-04-01

    Peptides derived from the proopiomelanocortin (POMC) precursor are critical for the normal regulation of many physiological parameters, and POMC deficiency results in severe obesity and metabolic dysfunction. Conversely, augmentation of central nervous system melanocortin function is a promising therapeutic avenue for obesity and diabetes but is confounded by detrimental cardiovascular effects including hypertension. Because the hypothalamic population of POMC-expressing neurons is neurochemically and neuroanatomically heterogeneous, there is interest in the possible dissociation of functionally distinct POMC neuron subpopulations. We used a Cre recombinase-dependent and hypothalamus-specific reactivatable PomcNEO allele to restrict Pomc expression to hypothalamic neurons expressing leptin receptor (Lepr) in mice. In contrast to mice with total hypothalamic Pomc deficiency, which are severely obese, mice with Lepr-restricted Pomc expression displayed fully normal body weight, food consumption, glucose homeostasis, and locomotor activity. Thus, Lepr+ POMC neurons, which constitute approximately two-thirds of the total POMC neuron population, are sufficient for normal regulation of these parameters. This functional dissociation approach represents a promising avenue for isolating therapeutically relevant POMC neuron subpopulations.

  3. Responses of neurons to extreme osmomechanical stress.

    Science.gov (United States)

    Wan, X; Harris, J A; Morris, C E

    1995-05-01

    Neurons are often regarded as fragile cells, easily destroyed by mechanical and osmotic insult. The results presented here demonstrate that this perception needs revision. Using extreme osmotic swelling, we show that molluscan neurons are astonishingly robust. In distilled water, a heterogeneous population of Lymnaea stagnalis CNS neurons swelled to several times their initial volume, yet had a ST50 (survival time for 50% of cells) > 60 min. Cells that were initially bigger survived longer. On return to normal medium, survivors were able, over the next 24 hr, to rearborize. Reversible membrane capacitance changes corresponding to about 0.7 muF/cm2 of apparent surface area accompanied neuronal swelling and shrinking in hypo- and hyperosmotic solutions; reversible changes in cell surface area evidently contributed to the neurons' ability to accommodate hydrostatic pressures then recover. The reversible membrane area/capacitance changes were not dependent on extracellular Ca2+. Neurons were monitored for potassium currents during direct mechanical inflation and during osmotically driven inflation. The latter but not the former stimulus routinely elicited small potassium currents, suggesting that tension increases activate the currents only if additional disruption of the cortex has occurred. Under stress in distilled water, a third of the neurons displayed a quite unexpected behavior: prolonged writhing of peripheral regions of the soma. This suggested that a plasma membrane-linked contractile machinery (presumably actomyosin) might contribute to the neurons' mechano-osmotic robustness by restricting water influx. Consistent with this possibility, 1 mM N-ethyl-maleimide, which inhibits myosin ATPase, decreased the ST50 to 18 min, rendered the survival time independent of initial size, and abolished writhing activity. For neurons, active mechanical resistance of the submembranous cortex, along with the mechanical compliance supplied by insertion or eversion of membrane

  4. Reliable activation of immature neurons in the adult hippocampus.

    Directory of Open Access Journals (Sweden)

    Lucas A Mongiat

    Full Text Available Neurons born in the adult dentate gyrus develop, mature, and connect over a long interval that can last from six to eight weeks. It has been proposed that, during this period, developing neurons play a relevant role in hippocampal signal processing owing to their distinctive electrical properties. However, it has remained unknown whether immature neurons can be recruited into a network before synaptic and functional maturity have been achieved. To address this question, we used retroviral expression of green fluorescent protein to identify developing granule cells of the adult mouse hippocampus and investigate the balance of afferent excitation, intrinsic excitability, and firing behavior by patch clamp recordings in acute slices. We found that glutamatergic inputs onto young neurons are significantly weaker than those of mature cells, yet stimulation of cortical excitatory axons elicits a similar spiking probability in neurons at either developmental stage. Young neurons are highly efficient in transducing ionic currents into membrane depolarization due to their high input resistance, which decreases substantially in mature neurons as the inward rectifier potassium (Kir conductance increases. Pharmacological blockade of Kir channels in mature neurons mimics the high excitability characteristic of young neurons. Conversely, Kir overexpression induces mature-like firing properties in young neurons. Therefore, the differences in excitatory drive of young and mature neurons are compensated by changes in membrane excitability that render an equalized firing activity. These observations demonstrate that the adult hippocampus continuously generates a population of highly excitable young neurons capable of information processing.

  5. Thalamocortical Projection Neuron and Interneuron Numbers in the Visual Thalamic Nuclei of the Adult C57BL/6 Mouse.

    Science.gov (United States)

    Evangelio, Marian; García-Amado, María; Clascá, Francisco

    2018-01-01

    A key parameter to constrain predictive, bottom-up circuit models of a given brain domain is the number and position of the neuronal populations involved. These include not only the neurons whose bodies reside within the domain, but also the neurons in distant regions that innervate the domain. The mouse visual cortex receives its main subcortical input from the dorsal lateral geniculate nucleus (dLGN) and the lateral posterior (LP) complex of the thalamus. The latter consists of three different nuclei: lateral posterior lateral (LPL), lateral posterior medial rostral (LPMR), and lateral posterior medial caudal (LPMC), each exhibiting specific patterns of connections with the various visual cortical areas. Here, we have determined the number of thalamocortical projection neurons and interneurons in the LP complex and dLGN of the adult C57BL/6 male mouse. We combined Nissl staining and histochemical and immunolabeling methods for consistently delineating nuclei borders, and applied unbiased stereological cell counting methods. Thalamic interneurons were identified using GABA immunolabeling. The C57BL/6 dLGN contains ∼21,200 neurons, while LP complex contains ∼31,000 total neurons. The dLGN and LP are the only nuclei of the mouse dorsal thalamus containing substantial numbers GABA-immunoreactive interneurons. These interneurons, however, are scarcer than previously estimated; they are 5.6% of dLGN neurons and just 1.9% of the LP neurons. It can be thus inferred that the dLGN contains ∼20,000 and the LP complex ∼30,400 thalamocortical projection neurons (∼12,000 in LPL, 15,200 in LPMR, and 4,200 in LPMC). The present dataset is relevant for constraining models of mouse visual thalamocortical circuits, as well as for quantitative comparisons between genetically modified mouse strains, or across species.

  6. Increasing trends in childlessness in recent birth cohorts - a registry-based study of the total Danish male population born from 1945 to 1980

    DEFF Research Database (Denmark)

    Priskorn, L; Holmboe, Sarah; Jacobsen, R

    2012-01-01

    The fertility rate has recently declined in many parts of the World, including Europe. To a large extent, this change can be explained by the socio-economic development. However, increasing fertility problems and widespread occurrence of poor semen quality could in part explain the few births....... The objective of this registry based study was to investigate birth cohort related trends in fertility and childlessness among Danish men. The study population comprised all 1 616 677 men in Denmark born from 1945 to 1980 of whom 1 359 975 (84.1%) were native Danes. Data were obtained from Statistics Denmark...... and contained information from The National Danish Birth Registry and The Danish In Vitro Fertilization (IVF) Registry. For consecutive birth cohorts of native Danish men cumulative fertility rates at age 45 declined from 1.91 children per man in the 1945 birth cohort to 1.71 for men born in 1960...

  7. Cortical cell and neuron density estimates in one chimpanzee hemisphere.

    Science.gov (United States)

    Collins, Christine E; Turner, Emily C; Sawyer, Eva Kille; Reed, Jamie L; Young, Nicole A; Flaherty, David K; Kaas, Jon H

    2016-01-19

    The density of cells and neurons in the neocortex of many mammals varies across cortical areas and regions. This variability is, perhaps, most pronounced in primates. Nonuniformity in the composition of cortex suggests regions of the cortex have different specializations. Specifically, regions with densely packed neurons contain smaller neurons that are activated by relatively few inputs, thereby preserving information, whereas regions that are less densely packed have larger neurons that have more integrative functions. Here we present the numbers of cells and neurons for 742 discrete locations across the neocortex in a chimpanzee. Using isotropic fractionation and flow fractionation methods for cell and neuron counts, we estimate that neocortex of one hemisphere contains 9.5 billion cells and 3.7 billion neurons. Primary visual cortex occupies 35 cm(2) of surface, 10% of the total, and contains 737 million densely packed neurons, 20% of the total neurons contained within the hemisphere. Other areas of high neuron packing include secondary visual areas, somatosensory cortex, and prefrontal granular cortex. Areas of low levels of neuron packing density include motor and premotor cortex. These values reflect those obtained from more limited samples of cortex in humans and other primates.

  8. Plasma Extracellular Vesicles Enriched for Neuronal Origin: A Potential Window into Brain Pathologic Processes

    Directory of Open Access Journals (Sweden)

    Maja Mustapic

    2017-05-01

    Full Text Available Our team has been a pioneer in harvesting extracellular vesicles (EVs enriched for neuronal origin from peripheral blood and using them as a biomarker discovery platform for neurological disorders. This methodology has demonstrated excellent diagnostic and predictive performance for Alzheimer's and other neurodegenerative diseases in multiple studies, providing a strong proof of concept for this approach. Here, we describe our methodology in detail and offer further evidence that isolated EVs are enriched for neuronal origin. In addition, we present evidence that EVs enriched for neuronal origin represent a more sensitive and accurate base for biomarkers than plasma, serum, or non-enriched total plasma EVs. Finally, we proceed to investigate the protein content of EVs enriched for neuronal origin and compare it with other relevant enriched and non-enriched populations of plasma EVs. Neuronal-origin enriched plasma EVs contain higher levels of signaling molecules of great interest for cellular metabolism, survival, and repair, which may be useful as biomarkers and to follow response to therapeutic interventions in a mechanism-specific manner.

  9. Single-Cell Imaging of Bioenergetic Responses to Neuronal Excitotoxicity and Oxygen and Glucose Deprivation

    OpenAIRE

    Connolly, Niamh M; Düssmann, Heiko; Anilkumar, Ujval; Huber, Heinrich J; Prehn, Jochen HM

    2014-01-01

    Excitotoxicity is a condition occurring during cerebral ischemia, seizures, and chronic neurodegeneration. It is characterized by overactivation of glutamate receptors, leading to excessive Ca2+/Na+ influx into neurons, energetic stress, and subsequent neuronal injury.We and others have previously investigated neuronal populations to study how bioenergetic parameters determine neuronal injury; however, such experiments are often confounded by population-based heterogeneity and the contributio...

  10. Statistics of Visual Responses to Image Object Stimuli from Primate AIT Neurons to DNN Neurons.

    Science.gov (United States)

    Dong, Qiulei; Wang, Hong; Hu, Zhanyi

    2018-02-01

    Under the goal-driven paradigm, Yamins et al. ( 2014 ; Yamins & DiCarlo, 2016 ) have shown that by optimizing only the final eight-way categorization performance of a four-layer hierarchical network, not only can its top output layer quantitatively predict IT neuron responses but its penultimate layer can also automatically predict V4 neuron responses. Currently, deep neural networks (DNNs) in the field of computer vision have reached image object categorization performance comparable to that of human beings on ImageNet, a data set that contains 1.3 million training images of 1000 categories. We explore whether the DNN neurons (units in DNNs) possess image object representational statistics similar to monkey IT neurons, particularly when the network becomes deeper and the number of image categories becomes larger, using VGG19, a typical and widely used deep network of 19 layers in the computer vision field. Following Lehky, Kiani, Esteky, and Tanaka ( 2011 , 2014 ), where the response statistics of 674 IT neurons to 806 image stimuli are analyzed using three measures (kurtosis, Pareto tail index, and intrinsic dimensionality), we investigate the three issues in this letter using the same three measures: (1) the similarities and differences of the neural response statistics between VGG19 and primate IT cortex, (2) the variation trends of the response statistics of VGG19 neurons at different layers from low to high, and (3) the variation trends of the response statistics of VGG19 neurons when the numbers of stimuli and neurons increase. We find that the response statistics on both single-neuron selectivity and population sparseness of VGG19 neurons are fundamentally different from those of IT neurons in most cases; by increasing the number of neurons in different layers and the number of stimuli, the response statistics of neurons at different layers from low to high do not substantially change; and the estimated intrinsic dimensionality values at the low

  11. Total and regional brain volumes in a population-based normative sample from 4 to 18 years: the NIH MRI Study of Normal Brain Development.

    Science.gov (United States)

    2012-01-01

    Using a population-based sampling strategy, the National Institutes of Health (NIH) Magnetic Resonance Imaging Study of Normal Brain Development compiled a longitudinal normative reference database of neuroimaging and correlated clinical/behavioral data from a demographically representative sample of healthy children and adolescents aged newborn through early adulthood. The present paper reports brain volume data for 325 children, ages 4.5-18 years, from the first cross-sectional time point. Measures included volumes of whole-brain gray matter (GM) and white matter (WM), left and right lateral ventricles, frontal, temporal, parietal and occipital lobe GM and WM, subcortical GM (thalamus, caudate, putamen, and globus pallidus), cerebellum, and brainstem. Associations with cross-sectional age, sex, family income, parental education, and body mass index (BMI) were evaluated. Key observations are: 1) age-related decreases in lobar GM most prominent in parietal and occipital cortex; 2) age-related increases in lobar WM, greatest in occipital, followed by the temporal lobe; 3) age-related trajectories predominantly curvilinear in females, but linear in males; and 4) small systematic associations of brain tissue volumes with BMI but not with IQ, family income, or parental education. These findings constitute a normative reference on regional brain volumes in children and adolescents.

  12. Differential sensitivity to nicotine among hypothalamic magnocellular neurons

    DEFF Research Database (Denmark)

    Mikkelsen, J D; Jacobsen, Julie; Kiss, Adrian Emil

    2012-01-01

    The magnocellular neurons in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) either contain vasopressin or oxytocin. Even though both hormones are released after systemic administration of nicotine, the mechanism through which the two populations of neurons are activated...... is not known. This study was carried out in the rat to investigate the effect of increasing doses of nicotine on subsets of magnocellular neurons containing either oxytocin or vasopressin....

  13. Neuronal Population Activity in Spinal Motor Circuits

    DEFF Research Database (Denmark)

    Berg, Rune W.

    2017-01-01

    The core elements of stereotypical movements such as locomotion, scratching and breathing are generated by networks in the lower brainstem and the spinal cord. Ensemble activities in spinal motor networks had until recently been merely a black box, but with the emergence of ultra-thin Silicon multi......-electrode technology it was possible to reveal the spiking activity of larger parts of the network. A series of experiments revealed unexpected features of spinal networks, such as multiple spiking regimes and lognormal firing rate distributions. The lognormality renders the widespread idea of a typical firing rate...

  14. Protein malnutrition during gestation and early life decreases neuronal size in the medial prefrontal cortex of post-pubertal rats

    Directory of Open Access Journals (Sweden)

    Roelf J. Cruz-Rizzolo

    2017-12-01

    Full Text Available Retrospective studies in human populations indicate that protein deprivation during pregnancy and early life (early protein malnutrition, EPM is associated with cognitive impairments, learning disabilities and may represent a risk factor for the late onset of some psychiatric disorders, fundamentally schizophrenia, a condition where the prefrontal cortex plays an important role. The purpose of this study was to analyze whether EPM affects structural aspects of the rat medial prefrontal cortex (mPFC, such as cortical volume, neuronal density and neuronal soma size, which seem altered in patients with schizophrenia. For this, a rat model of EPM (5% casein from conception to postnatal day 60 was adopted and the rat mPFC volume, total number of neurons and average neuronal volume were evaluated on postnatal day 60 (post-pubertal animals by histo- and immunohistochemical techniques using unbiased stereological analysis. EPM did not alter the number of NeuN+ neurons in the rat mPFC. However, a very significant decrease in mPFC volume and average neuronal size was observed in malnourished rats. Although the present study does not establish causal relationships between malnutrition and schizophrenia, our results may indicate a similar structural phenomenon in these two situations.

  15. Context-aware modeling of neuronal morphologies

    Directory of Open Access Journals (Sweden)

    Benjamin eTorben-Nielsen

    2014-09-01

    Full Text Available Neuronal morphologies are pivotal for brain functioning: physical overlap between dendrites and axons constrain the circuit topology, and the precise shape and composition of dendrites determine the integration of inputs to produce an output signal. At the same time, morphologies are highly diverse and variant. The variance, presumably, originates from neurons developing in a densely packed brain substrate where they interact (e.g., repulsion or attraction with other actors in this substrate. However, when studying neurons their context is never part of the analysis and they are treated as if they existed in isolation.Here we argue that to fully understand neuronal morphology and its variance it is important to consider neurons in relation to each other and to other actors in the surrounding brain substrate, i.e., their context. We propose a context-aware computational framework, NeuroMaC, in which large numbers of neurons can be grown simultaneously according to growth rules expressed in terms of interactions between the developing neuron and the surrounding brain substrate.As a proof of principle, we demonstrate that by using NeuroMaC we can generate accurate virtual morphologies of distinct classes both in isolation and as part of neuronal forests. Accuracy is validated against population statistics of experimentally reconstructed morphologies. We show that context-aware generation of neurons can explain characteristics of variation. Indeed, plausible variation is an inherent property of the morphologies generated by context-aware rules. We speculate about the applicability of this framework to investigate morphologies and circuits, to classify healthy and pathological morphologies, and to generate large quantities of morphologies for large-scale modeling.

  16. The rise and fall of mesodiencephalic dopaminergic neurons : Molecular programming by transcription factors Engrailed 1, Pitx3, and Nkx2.9 during the development of mesodiencephalic neurons

    NARCIS (Netherlands)

    Kouwenhoven, W.M.

    2016-01-01

    The mid- and hindbrain harbor two essential monoaminergic neuronal populations: the mesodiencephalic dopaminergic (mdDA) neurons in the midbrain and the serotonergic (5HT) neurons in the hindbrain. Both systems innervate multiple regions in the forebrain and are involved in the guidance of our mood,

  17. Associations of Walking Speed, Grip Strength, and Standing Balance With Total and Cause-Specific Mortality in a General Population of Japanese Elders.

    Science.gov (United States)

    Nofuji, Yu; Shinkai, Shoji; Taniguchi, Yu; Amano, Hidenori; Nishi, Mariko; Murayama, Hiroshi; Fujiwara, Yoshinori; Suzuki, Takao

    2016-02-01

    Walking speed, grip strength, and standing balance are key components of physical performance in older people. The present study aimed to evaluate (1) associations of these physical performance measures with cause-specific mortality, (2) independent associations of individual physical performance measures with mortality, and (3) the added value of combined use of the 3 physical performance measures in predicting all-cause and cause-specific mortality. Prospective cohort study with a follow-up of 10.5 years. Tokyo Metropolitan Institute of Gerontology Longitudinal Interdisciplinary Study on Aging (TMIG-LISA), Japan. A total of 1085 initially nondisabled older Japanese aged 65 to 89 years. Usual walking speed, grip strength, and standing balance were measured at baseline survey. During follow-up, 324 deaths occurred (122 of cardiovascular disease, 75 of cancer, 115 of other causes, and 12 of unknown causes). All 3 physical performance measures were significantly associated with all-cause, cardiovascular, and other-cause mortality, but not with cancer mortality, independent of potential confounders. When all 3 physical performance measures were simultaneously entered into the model, each was significantly independently associated with all-cause and cardiovascular mortality. The C statistics for all-cause and cardiovascular mortality were significantly increased by adding grip strength and standing balance to walking speed (P balance predicted all-cause, cardiovascular, and other-cause mortality, but not cancer mortality, independent of covariates. Moreover, these 3 components of physical performance were independently associated with all-cause and cardiovascular mortality and their combined use increased prognostic power. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  18. The total cholesterol to high-density lipoprotein cholesterol as a predictor of poor outcomes in a Chinese population with acute ischaemic stroke.

    Science.gov (United States)

    Chen, Lifang; Xu, Jianing; Sun, Hao; Wu, Hao; Zhang, Jinsong

    2017-11-01

    High admission cholesterol has been associated with better outcome after acute ischaemic stroke (AIS), but a paradox not completely illustrated. The purpose of this study was to investigate the effect of the total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) on short-term survival after AIS. Consecutive patients admitted in 2013 and 2015 were enrolled in the present study. The logistic regression analysis was conducted to evaluate predictors of 3-month outcomes. The primary endpoint was death. Secondary endpoint was good (modified Rankin Scale score 0-2 or equal to prestrike modified Rankin Scale score) at 3 months. Of 871 patients enrolled in the final analysis, 94 (10.8%) individuals died during 3 months of observation. The serum TC and TC/HDL-C levels at admission were significantly associated with stroke outcomes at 3 months, and the HDL-C level was only correlated with the good outcomes at 3 months. Mortality risk was markedly decreased for patients with high TC/HDL-C ratio (odds ratio: 0.23, 95% confidence interval [CI]: 0.10-0.50 for Q4:Q1; P-trend <.001) after adjustment. The effect of TC/HDL-C ratio on the probability of good outcomes was still obvious (odds ratio: 2.18, 95% CI: 1.40-3.39 for Q4:Q1; P-trend=.029). According to the receiver operating characteristic analyses, the best discriminating factor was a TG/HDL-C ≥3.37 (area under the ROC curve [AUC]=0.643, sensitivity 61.3%, specificity 61.7%) as well as the TC/HDL-C ≥4.09 for good outcomes (AUC: 0.587, sensitivity 63.9%, specificity 79.7%). High TC/HDL-C ratio may be associated with increased short-term survival and better outcomes after AIS. © 2017 Wiley Periodicals, Inc.

  19. Influence of dietary protein and fructooligosaccharides on fecal fermentative end-products, fecal bacterial populations and apparent total tract digestibility in dogs.

    Science.gov (United States)

    Pinna, Carlo; Vecchiato, Carla Giuditta; Bolduan, Carmen; Grandi, Monica; Stefanelli, Claudio; Windisch, Wilhelm; Zaghini, Giuliano; Biagi, Giacomo

    2018-03-20

    Feeding dogs with diets rich in protein may favor putrefactive fermentations in the hindgut, negatively affecting the animal's intestinal environment. Conversely, prebiotics may improve the activity of health-promoting bacteria and prevent bacterial proteolysis in the colon. The aim of this study was to evaluate the effects of dietary supplementation with fructooligosaccharides (FOS) on fecal microbiota and apparent total tract digestibility (ATTD) in dogs fed kibbles differing in protein content. Twelve healthy adult dogs were used in a 4 × 4 replicated Latin Square design to determine the effects of four diets: 1) Low protein diet (LP, crude protein (CP) 229 g/kg dry matter (DM)); 2) High protein diet (HP, CP 304 g/kg DM); 3) Diet 1 + 1.5 g of FOS/kg; 4) Diet 2 + 1.5 g of FOS/kg. The diets contained silica at 5 g/kg as a digestion marker. Differences in protein content were obtained using different amounts of a highly digestible swine greaves meal. Each feeding period lasted 28 d, with a 12 d wash-out in between periods. Fecal samples were collected from dogs at 0, 21 and 28 d of each feeding period. Feces excreted during the last five days of each feeding period were collected and pooled in order to evaluate ATTD. Higher fecal ammonia concentrations were observed both when dogs received the HP diets (p < 0.001) and the supplementation with FOS (p < 0.05). The diets containing FOS resulted in greater ATTD of DM, Ca, Mg, Na, Zn, and Fe (p < 0.05) while HP diets were characterized by lower crude ash ATTD (p < 0.05). Significant interactions were observed between FOS and protein concentration in regards to fecal pH (p < 0.05), propionic acid (p < 0.05), acetic to propionic acid and acetic + n-butyric to propionic acid ratios (p < 0.01), bifidobacteria (p < 0.05) and ATTD of CP (p < 0.05) and Mn (p < 0.001). A relatively moderate increase of dietary protein resulted in higher concentrations of ammonia in

  20. NeuronMetrics: software for semi-automated processing of cultured neuron images.

    Science.gov (United States)

    Narro, Martha L; Yang, Fan; Kraft, Robert; Wenk, Carola; Efrat, Alon; Restifo, Linda L

    2007-03-23

    Using primary cell culture to screen for changes in neuronal morphology requires specialized analysis software. We developed NeuronMetrics for semi-automated, quantitative analysis of two-dimensional (2D) images of fluorescently labeled cultured neurons. It skeletonizes the neuron image using two complementary image-processing techniques, capturing fine terminal neurites with high fidelity. An algorithm was devised to span wide gaps in the skeleton. NeuronMetrics uses a novel strategy based on geometric features called faces to extract a branch number estimate from complex arbors with numerous neurite-to-neurite contacts, without creating a precise, contact-free representation of the neurite arbor. It estimates total neurite length, branch number, primary neurite number, territory (the area of the convex polygon bounding the skeleton and cell body), and Polarity Index (a measure of neuronal polarity). These parameters provide fundamental information about the size and shape of neurite arbors, which are critical factors for neuronal function. NeuronMetrics streamlines optional manual tasks such as removing noise, isolating the largest primary neurite, and correcting length for self-fasciculating neurites. Numeric data are output in a single text file, readily imported into other applications for further analysis. Written as modules for ImageJ, NeuronMetrics provides practical analysis tools that are easy to use and support batch processing. Depending on the need for manual intervention, processing time for a batch of approximately 60 2D images is 1.0-2.5 h, from a folder of images to a table of numeric data. NeuronMetrics' output accelerates the quantitative detection of mutations and chemical compounds that alter neurite morphology in vitro, and will contribute to the use of cultured neurons for drug discovery.

  1. Motor neuron disease in blacks | Cosnett | South African Medical ...

    African Journals Online (AJOL)

    A series of 86 black, Indian and white patients with motor neuron disease were analysed retrospectively. Although the material does not allow statistically valid conclusions, there are sufficient cases among blacks to allow two prima facie observations in this population group: (i) motor neuron disease has an earlier age of ...

  2. A possible role of the non-GAT1 GABA transporters in transfer of GABA from GABAergic to glutamatergic neurons in mouse cerebellar neuronal cultures

    DEFF Research Database (Denmark)

    Suñol, C; Babot, Z; Cristòfol, R

    2010-01-01

    Cultures of dissociated cerebellum from 7-day-old mice were used to investigate the mechanism involved in synthesis and cellular redistribution of GABA in these cultures consisting primarily of glutamatergic granule neurons and a smaller population of GABAergic Golgi and stellate neurons......3 transporters. Only a small population of cells were immuno-stained for GAD while many cells exhibited VGlut-1 like immuno-reactivity which, however, never co-localized with GAD positive neurons. This likely reflects the small number of GABAergic neurons compared to the glutamatergic granule......M concentrations (95%). Essentially all neurons showed GABA like immunostaining albeit with differences in intensity. The results indicate that GABA which is synthesized in a small population of GAD-positive neurons is redistributed to essentially all neurons including the glutamatergic granule cells. GAT1...

  3. NEURON and Python.

    Science.gov (United States)

    Hines, Michael L; Davison, Andrew P; Muller, Eilif

    2009-01-01

    The NEURON simulation program now allows Python to be used, alone or in combination with NEURON's traditional Hoc interpreter. Adding Python to NEURON has the immediate benefit of making available a very extensive suite of analysis tools written for engineering and science. It also catalyzes NEURON software development by offering users a modern programming tool that is recognized for its flexibility and power to create and maintain complex programs. At the same time, nothing is lost because all existing models written in Hoc, including graphical user interface tools, continue to work without change and are also available within the Python context. An example of the benefits of Python availability is the use of the xml module in implementing NEURON's Import3D and CellBuild tools to read MorphML and NeuroML model specifications.

  4. Total Water Management - Report

    Science.gov (United States)

    There is a growing need for urban water managers to take a more holistic view of their water resource systems as population growth, urbanization, and current operations put different stresses on the environment and urban infrastructure. Total Water Management (TWM) is an approac...

  5. Scaling of brain metabolism with a fixed energy budget per neuron: implications for neuronal activity, plasticity and evolution.

    Science.gov (United States)

    Herculano-Houzel, Suzana

    2011-03-01

    It is usually considered that larger brains have larger neurons, which consume more energy individually, and are therefore accompanied by a larger number of glial cells per neuron. These notions, however, have never been tested. Based on glucose and oxygen metabolic rates in awake animals and their recently determined numbers of neurons, here I show that, contrary to the expected, the estimated glucose use per neuron is remarkably constant, varying only by 40% across the six species of rodents and primates (including humans). The estimated average glucose use per neuron does not correlate with neuronal density in any structure. This suggests that the energy budget of the whole brain per neuron is fixed across species and brain sizes, such that total glucose use by the brain as a whole, by the cerebral cortex and also by the cerebellum alone are linear functions of the number of neurons in the structures across the species (although the average glucose consumption per neuron is at least 10× higher in the cerebral cortex than in the cerebellum). These results indicate that the apparently remarkable use in humans of 20% of the whole body energy budget by a brain that represents only 2% of body mass is explained simply by its large number of neurons. Because synaptic activity is considered the major determinant of metabolic cost, a conserved energy budget per neuron has several profound implications for synaptic homeostasis and the regulation of firing rates, synaptic plasticity, brain imaging, pathologies, and for brain scaling in evolution.

  6. Scaling of brain metabolism with a fixed energy budget per neuron: implications for neuronal activity, plasticity and evolution.

    Directory of Open Access Journals (Sweden)

    Suzana Herculano-Houzel

    Full Text Available It is usually considered that larger brains have larger neurons, which consume more energy individually, and are therefore accompanied by a larger number of glial cells per neuron. These notions, however, have never been tested. Based on glucose and oxygen metabolic rates in awake animals and their recently determined numbers of neurons, here I show that, contrary to the expected, the estimated glucose use per neuron is remarkably constant, varying only by 40% across the six species of rodents and primates (including humans. The estimated average glucose use per neuron does not correlate with neuronal density in any structure. This suggests that the energy budget of the whole brain per neuron is fixed across species and brain sizes, such that total glucose use by the brain as a whole, by the cerebral cortex and also by the cerebellum alone are linear functions of the number of neurons in the structures across the species (although the average glucose consumption per neuron is at least 10× higher in the cerebral cortex than in the cerebellum. These results indicate that the apparently remarkable use in humans of 20% of the whole body energy budget by a brain that represents only 2% of body mass is explained simply by its large number of neurons. Because synaptic activity is considered the major determinant of metabolic cost, a conserved energy budget per neuron has several profound implications for synaptic homeostasis and the regulation of firing rates, synaptic plasticity, brain imaging, pathologies, and for brain scaling in evolution.

  7. Scaling of Brain Metabolism with a Fixed Energy Budget per Neuron: Implications for Neuronal Activity, Plasticity and Evolution

    Science.gov (United States)

    Herculano-Houzel, Suzana

    2011-01-01

    It is usually considered that larger brains have larger neurons, which consume more energy individually, and are therefore accompanied by a larger number of glial cells per neuron. These notions, however, have never been tested. Based on glucose and oxygen metabolic rates in awake animals and their recently determined numbers of neurons, here I show that, contrary to the expected, the estimated glucose use per neuron is remarkably constant, varying only by 40% across the six species of rodents and primates (including humans). The estimated average glucose use per neuron does not correlate with neuronal density in any structure. This suggests that the energy budget of the whole brain per neuron is fixed across species and brain sizes, such that total glucose use by the brain as a whole, by the cerebral cortex and also by the cerebellum alone are linear functions of the number of neurons in the structures across the species (although the average glucose consumption per neuron is at least 10× higher in the cerebral cortex than in the cerebellum). These results indicate that the apparently remarkable use in humans of 20% of the whole body energy budget by a brain that represents only 2% of body mass is explained simply by its large number of neurons. Because synaptic activity is considered the major determinant of metabolic cost, a conserved energy budget per neuron has several profound implications for synaptic homeostasis and the regulation of firing rates, synaptic plasticity, brain imaging, pathologies, and for brain scaling in evolution. PMID:21390261

  8. Neurochemical, morphologic, and laminar characterization of cortical projection neurons in the cingulate motor areas of the macaque monkey

    Science.gov (United States)

    Nimchinsky, E. A.; Hof, P. R.; Young, W. G.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

    1996-01-01

    The primate cingulate gyrus contains multiple cortical areas that can be distinguished by several neurochemical features, including the distribution of neurofilament protein-enriched pyramidal neurons. In addition, connectivity and functional properties indicate that there are multiple motor areas in the cortex lining the cingulate sulcus. These motor areas were targeted for analysis of potential interactions among regional specialization, connectivity, and cellular characteristics such as neurochemical profile and morphology. Specifically, intracortical injections of retrogradely transported dyes and intracellular injection were combined with immunocytochemistry to investigate neurons projecting from the cingulate motor areas to the putative forelimb region of the primary motor cortex, area M1. Two separate groups of neurons projecting to area M1 emanated from the cingulate sulcus, one anterior and one posterior, both of which furnished commissural and ipsilateral connections with area M1. The primary difference between the two populations was laminar origin, with the anterior projection originating largely in deep layers, and the posterior projection taking origin equally in superficial and deep layers. With regard to cellular morphology, the anterior projection exhibited more morphologic diversity than the posterior projection. Commissural projections from both anterior and posterior fields originated largely in layer VI. Neurofilament protein distribution was a reliable tool for localizing the two projections and for discriminating between them. Comparable proportions of the two sets of projection neurons contained neurofilament protein, although the density and distribution of the total population of neurofilament protein-enriched neurons was very different in the two subareas of origin. Within a projection, the participating neurons exhibited a high degree of morphologic heterogeneity, and no correlation was observed between somatodendritic morphology and

  9. Spinal cord: motor neuron diseases.

    Science.gov (United States)

    Rezania, Kourosh; Roos, Raymond P

    2013-02-01

    Spinal cord motor neuron diseases affect lower motor neurons in the ventral horn. This article focuses on the most common spinal cord motor neuron disease, amyotrophic lateral sclerosis, which also affects upper motor neurons. Also discussed are other motor neuron diseases that only affect the lower motor neurons. Despite the identification of several genes associated with familial amyotrophic lateral sclerosis, the pathogenesis of this complex disease remains elusive. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Estrogens modulate ventrolateral ventromedial hypothalamic glucose-inhibited neurons

    Directory of Open Access Journals (Sweden)

    Ammy M. Santiago

    2016-10-01

    Full Text Available Objective: Brain regulation of glucose homeostasis is sexually dimorphic; however, the impact sex hormones have on specific neuronal populations within the ventromedial hypothalamic nucleus (VMN, a metabolically sensitive brain region, has yet to be fully characterized. Glucose-excited (GE and -inhibited (GI neurons are located throughout the VMN and may play a critical role in glucose and energy homeostasis. Within the ventrolateral portion of the VMN (VL-VMN, glucose sensing neurons and estrogen receptor (ER distributions overlap. We therefore tested the hypothesis that VL-VMN glucose sensing neurons were sexually dimorphic and regulated by 17β-estradiol (17βE. Methods: Electrophysiological recordings of VL-VMN glucose sensing neurons in brain slices isolated from age- and weight-matched female and male mice were performed in the presence and absence of 17βE. Results: We found a new class of VL-VMN GI neurons whose response to low glucose was transient despite continued exposure to low glucose. Heretofore, we refer to these newly identified VL-VMN GI neurons as ‘adapting’ or AdGI neurons. We found a sexual dimorphic response to low glucose, with male nonadapting GI neurons, but not AdGI neurons, responding more robustly to low glucose than those from females. 17βE blunted the response of both nonadapting GI and AdGI neurons to low glucose in both males and females, which was mediated by activation of estrogen receptor β and inhibition of AMP-activated kinase. In contrast, 17βE had no impact on GE or non-glucose sensing neurons in either sex. Conclusion: These data suggest sex differences and estrogenic regulation of VMN hypothalamic glucose sensing may contribute to the sexual dimorphism in glucose homeostasis. Author Video: Author Video Watch what authors say about their articles Keywords: 17β-estradiol, AMP-activated kinase, Glucose excited neurons, Glucose inhibited neurons, Ventromedial hypothalamic nucleus, Sexual dimorphism

  11. Automatically tracking neurons in a moving and deforming brain.

    Directory of Open Access Journals (Sweden)

    Jeffrey P Nguyen

    2017-05-01

    Full Text Available Advances in optical neuroimaging techniques now allow neural activity to be recorded with cellular resolution in awake and behaving animals. Brain motion in these recordings pose a unique challenge. The location of individual neurons must be tracked in 3D over time to accurately extract single neuron activity traces. Recordings from small invertebrates like C. elegans are especially challenging because they undergo very large brain motion and deformation during animal movement. Here we present an automated computer vision pipeline to reliably track populations of neurons with single neuron resolution in the brain of a freely moving C. elegans undergoing large motion and deformation. 3D volumetric fluorescent images of the animal's brain are straightened, aligned and registered, and the locations of neurons in the images are found via segmentation. Each neuron is then assigned an identity using a new time-independent machine-learning approach we call Neuron Registration Vector Encoding. In this approach, non-rigid point-set registration is used to match each segmented neuron in each volume with a set of reference volumes taken from throughout the recording. The way each neuron matches with the references defines a feature vector which is clustered to assign an identity to each neuron in each volume. Finally, thin-plate spline interpolation is used to correct errors in segmentation and check consistency of assigned identities. The Neuron Registration Vector Encoding approach proposed here is uniquely well suited for tracking neurons in brains undergoing large deformations. When applied to whole-brain calcium imaging recordings in freely moving C. elegans, this analysis pipeline located 156 neurons for the duration of an 8 minute recording and consistently found more neurons more quickly than manual or semi-automated approaches.

  12. Total Thyroidectomy

    Directory of Open Access Journals (Sweden)

    Lopez Moris E

    2016-06-01

    Full Text Available Total thyroidectomy is a surgery that removes all the thyroid tissue from the patient. The suspect of cancer in a thyroid nodule is the most frequent indication and it is presume when previous fine needle puncture is positive or a goiter has significant volume increase or symptomes. Less frequent indications are hyperthyroidism when it is refractory to treatment with Iodine 131 or it is contraindicated, and in cases of symptomatic thyroiditis. The thyroid gland has an important anatomic relation whith the inferior laryngeal nerve and the parathyroid glands, for this reason it is imperative to perform extremely meticulous dissection to recognize each one of these elements and ensure their preservation. It is also essential to maintain strict hemostasis, in order to avoid any postoperative bleeding that could lead to a suffocating neck hematoma, feared complication that represents a surgical emergency and endangers the patient’s life.It is essential to run a formal technique, without skipping steps, and maintain prudence and patience that should rule any surgical act.

  13. Crosstalks between kisspeptin neurons and somatostatin neurons are not photoperiod dependent in the ewe hypothalamus.

    Science.gov (United States)

    Dufourny, Laurence; Lomet, Didier

    2017-12-01

    Seasonal reproduction is under the control of gonadal steroid feedback, itself synchronized by day-length or photoperiod. As steroid action on GnRH neurons is mostly indirect and therefore exerted through interneurons, we looked for neuroanatomical interactions between kisspeptin (KP) neurons and somatostatin (SOM) neurons, two populations targeted by sex steroids, in three diencephalic areas involved in the central control of ovulation and/or sexual behavior: the arcuate nucleus (ARC), the preoptic area (POA) and the ventrolateral part of the ventromedial hypothalamus (VMHvl). KP is the most potent secretagogue of GnRH secretion while SOM has been shown to centrally inhibit LH pulsatile release. Notably, hypothalamic contents of these two neuropeptides vary with photoperiod in specific seasonal species. Our hypothesis is that SOM inhibits KP neuron activity and therefore indirectly modulate GnRH release and that this effect may be seasonally regulated. We used sections from ovariectomized estradiol-replaced ewes killed after photoperiodic treatment mimicking breeding or anestrus season. We performed triple immunofluorescent labeling to simultaneously detect KP, SOM and synapsin, a marker for synaptic vesicles. Sections from the POA and from the mediobasal hypothalamus were examined using a confocal microscope. Randomly selected KP or SOM neurons were observed in the POA and ARC. SOM neurons were also observed in the VMHvl. In both the ARC and POA, nearly all KP neurons presented numerous SOM contacts. SOM neurons presented KP terminals more frequently in the ARC than in the POA and VMHvl. Quantitative analysis failed to demonstrate major seasonal variations of KP and SOM interactions. Our data suggest a possible inhibitory action of SOM on all KP neurons in both photoperiodic statuses. On the other hand, the physiological significance of KP modulation of SOM neuron activity and vice versa remain to be determined. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Cochlear nucleus neuron analysis in individuals with presbycusis.

    Science.gov (United States)

    Hinojosa, Raul; Nelson, Erik G

    2011-12-01

    The aim of this study was to analyze the cochlear nucleus neuron population in individuals with normal hearing and presbycusis. Retrospective study of archival human temporal bone and brain stem tissues. Using strict inclusion criteria, the temporal bones and cochlear nuclei from six normal hearing individuals and four individuals with presbycusis were selected for analysis. The spiral ganglion cell population, the cochlear nucleus neuron population, and the cell body size of the neurons were quantified in these cases. A relationship was not observed between age and the spiral ganglion cell population in the normal hearing group. Presbycusis subjects exhibited a reduced spiral ganglion cell population. The mean cochlear nucleus neuron population was observed to be significantly higher in the presbycusis group (mean ± standard deviation: 114,170 ± 10,570) compared to the normal hearing group (91,470 ± 9,510) (P = .019). This difference was predominantly the result of greater multipolar and granule cell neuron populations. Only the fusiform neuron type exhibited a significantly different mean cell body cross-sectional area between the normal hearing group (242 ± 27) and the presbycusis group (300 ± 37) (P = .033). This investigation is the first time, to our knowledge, that the populations of the eight neuron types in the cochlear nucleus have been quantified in both normal hearing individuals and individuals with presbycusis. The data support the concept that presbycusis is not an effect of aging alone but instead may be a condition that predisposes one to hearing loss with advancing age and is characterized by a congenitally elevated cochlear nucleus neuron population. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

  15. Neuronal-glial trafficking

    International Nuclear Information System (INIS)

    Bachelard, H.S.

    2001-01-01

    Full text: The name 'glia' originates from the Greek word for glue, because astro glia (or astrocytes) were thought only to provide an anatomical framework for the electrically-excitable neurones. However, awareness that astrocytes perform vital roles in protecting the neurones, which they surround, emerged from evidence that they act as neuroprotective K + -sinks, and that they remove potentially toxic extracellular glutamate from the vicinity of the neurones. The astrocytes convert the glutamate to non-toxic glutamine which is returned to the neurones and used to replenish transmitter glutamate. This 'glutamate-glutamine cycle' (established in the 1960s by Berl and his colleagues) also contributes to protecting the neurones against a build-up of toxic ammonia. Glial cells also supply the neurones with components for free-radical scavenging glutathione. Recent studies have revealed that glial cells play a more positive interactive role in furnishing the neurones with fuels. Studies using radioactive 14 C, 13 C-MRS and 15 N-GCMS have revealed that glia produce alanine, lactate and proline for consumption by neurones, with increased formation of neurotransmitter glutamate. On neuronal activation the release of NH 4 + and glutamate from the neurones stimulates glucose uptake and glycolysis in the glia to produce more alanine, which can be regarded as an 'alanine-glutamate cycle' Use of 14 C-labelled precursors provided early evidence that neurotransmitter GABA may be partly derived from glial glutamine, and this has been confirmed recently in vivo by MRS isotopomer analysis of the GABA and glutamine labelled from 13 C-acetate. Relative rates of intermediary metabolism in glia and neurones can be calculated using a combination of [1- 13 C] glucose and [1,2- 13 C] acetate. When glutamate is released by neurones there is a net neuronal loss of TCA intermediates which have to be replenished. Part of this is derived from carboxylation of pyruvate, (pyruvate carboxylase

  16. Distribution, structure and projections of the frog intracardiac neurons.

    Science.gov (United States)

    Batulevicius, Darius; Skripkiene, Gertruda; Batuleviciene, Vaida; Skripka, Valdas; Dabuzinskiene, Anita; Pauza, Dainius H

    2012-05-21

    Histochemistry for acetylcholinesterase was used to determine the distribution of intracardiac neurons in the frog Rana temporaria. Seventy-nine intracardiac neurons from 13 frogs were labelled iontophoretically by the intracellular markers Alexa Fluor 568 and Lucifer Yellow CH to determine their structure and projections. Total neuronal number per frog heart was (Mean ± SE) 1374 ± 56. Largest collections of neurons were found in the interatrial septum (46%), atrioventricular junction (25%) and venal sinus (12%). Among the intracellularly labelled neurons, we found the cells of unipolar (71%), multipolar (20%) and bipolar (9%) types. Multiple processes originated from the neuron soma, hillock and proximal axon. These processes projected onto adjacent neuron somata and cardiac muscle fibers within the interatrial septum. Average total length of the processes from proximal axon was 348 ± 50 μm. Average total length of processes from soma and hillock was less, 118 ± 27 μm and 109 ± 24 μm, respectively. The somata of 59% of neurons had bubble- or flake-shaped extensions. Most neurons from the major nerves in the interatrial septum sent their axons towards the ventricle. In contrast, most neurons from the ventral part of the interatrial septum sent their axons towards the atria. Our findings contradict to a view that the frog intracardiac ganglia contain only non-dendritic neurons of the unipolar type. We conclude that the frog intracardiac neurons are structurally complex and diverse. This diversity may account for the complicated integrative functions of the frog intrinsic cardiac ganglia. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. AgRP Neurons Can Increase Food Intake during Conditions of Appetite Suppression and Inhibit Anorexigenic Parabrachial Neurons.

    Science.gov (United States)

    Essner, Rachel A; Smith, Alison G; Jamnik, Adam A; Ryba, Anna R; Trutner, Zoe D; Carter, Matthew E

    2017-09-06

    neurons that induce appetite can cause obesity, whereas an abnormal amount of activity in neurons that suppress appetite can cause malnutrition and a severe reduction in body weight. The purpose of this study was to determine whether a population of neurons known to induce appetite ("AgRP neurons") could induce food intake to overcome appetite-suppression following administration of various appetite-suppressing compounds. We found that stimulating AgRP neurons could overcome various forms of appetite suppression and decrease neural activity in a separate population of appetite-suppressing neurons, providing new insights into how the brain regulates food intake. Copyright © 2017 the authors 0270-6474/17/378678-10$15.00/0.

  18. Multi-class oscillating systems of interacting neurons

    DEFF Research Database (Denmark)

    Ditlevsen, Susanne; Löcherbach, Eva

    2017-01-01

    We consider multi-class systems of interacting nonlinear Hawkes processes modeling several large families of neurons and study their mean field limits. As the total number of neurons goes to infinity we prove that the evolution within each class can be described by a nonlinear limit differential...

  19. Lea County Block Groups, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  20. Valencia County Block Groups, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  1. Dona Ana County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  2. Quay County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  3. New Mexico Census Tracts, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  4. Torrance County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  5. Catron County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  6. Cibola County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  7. Lincoln County Block Groups, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  8. Los Alamos County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  9. Grant County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  10. New Mexico Counties, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  11. Quay County Block Groups, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  12. San Juan County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  13. Socorro County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  14. San Miguel County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  15. Otero County Block Groups, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  16. Roosevelt County Block Groups, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  17. Eddy County Block Groups, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  18. Sandoval County Block Groups, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  19. Socorro County Block Groups, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  20. Lea County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  1. Hidalgo County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  2. Catron County Block Groups, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  3. Bernalillo County Block Groups, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  4. Chaves County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  5. Curry County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  6. Chaves County Block Groups, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  7. Bernalillo County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  8. Roosevelt County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  9. Valencia County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  10. Torrance County Block Groups, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  11. Otero County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  12. Colfax County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  13. Union County Block Groups, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  14. Eddy County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  15. Guadalupe County Block Groups, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  16. Sierra County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  17. De Baca County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  18. Union County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  19. Harding County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  20. Santa Fe County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  1. Taos County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  2. Lincoln County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  3. Guadalupe County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  4. Mora County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  5. Sandoval County Blocks, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  6. Sierra County Block Groups, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  7. Hidalgo County Block Groups, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  8. Colfax County Block Groups, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  9. Grant County Block Groups, Total Population (2010)

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The once-a-decade decennial census was conducted in April 2010 by the U.S. Census Bureau. This count of every resident in the United States was mandated by Article...

  10. Direct projections from hypothalamic orexin neurons to brainstem cardiac vagal neurons.

    Science.gov (United States)

    Dergacheva, Olga; Yamanaka, Akihiro; Schwartz, Alan R; Polotsky, Vsevolod Y; Mendelowitz, David

    2016-12-17

    Orexin neurons are known to augment the sympathetic control of cardiovascular function, however the role of orexin neurons in parasympathetic cardiac regulation remains unclear. To test the hypothesis that orexin neurons contribute to parasympathetic control we selectively expressed channelrhodopsin-2 (ChR2) in orexin neurons in orexin-Cre transgenic rats and examined postsynaptic currents in cardiac vagal neurons (CVNs) in the dorsal motor nucleus of the vagus (DMV). Simultaneous photostimulation and recording in ChR2-expressing orexin neurons in the lateral hypothalamus resulted in reliable action potential firing as well as large whole-cell currents suggesting a strong expression of ChR2 and reliable optogenetic excitation. Photostimulation of ChR2-expressing fibers in the DMV elicited short-latency (ranging from 3.2ms to 8.5ms) postsynaptic currents in 16 out of 44 CVNs tested. These responses were heterogeneous and included excitatory glutamatergic (63%) and inhibitory GABAergic (37%) postsynaptic currents. The results from this study suggest different sub-population of orexin neurons may exert diverse influences on brainstem CVNs and therefore may play distinct functional roles in parasympathetic control of the heart. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Single neuron computation

    CERN Document Server

    McKenna, Thomas M; Zornetzer, Steven F

    1992-01-01

    This book contains twenty-two original contributions that provide a comprehensive overview of computational approaches to understanding a single neuron structure. The focus on cellular-level processes is twofold. From a computational neuroscience perspective, a thorough understanding of the information processing performed by single neurons leads to an understanding of circuit- and systems-level activity. From the standpoint of artificial neural networks (ANNs), a single real neuron is as complex an operational unit as an entire ANN, and formalizing the complex computations performed by real n

  12. Mesmerising mirror neurons.

    Science.gov (United States)

    Heyes, Cecilia

    2010-06-01

    Mirror neurons have been hailed as the key to understanding social cognition. I argue that three currents of thought-relating to evolution, atomism and telepathy-have magnified the perceived importance of mirror neurons. When they are understood to be a product of associative learning, rather than an adaptation for social cognition, mirror neurons are no longer mesmerising, but they continue to raise important questions about both the psychology of science and the neural bases of social cognition. Copyright 2010 Elsevier Inc. All rights reserved.

  13. The mirror neuron system.

    Science.gov (United States)

    Cattaneo, Luigi; Rizzolatti, Giacomo

    2009-05-01

    Mirror neurons are a class of neurons, originally discovered in the premotor cortex of monkeys, that discharge both when individuals perform a given motor act and when they observe others perform that same motor act. Ample evidence demonstrates the existence of a cortical network with the properties of mirror neurons (mirror system) in humans. The human mirror system is involved in understanding others' actions and their intentions behind them, and it underlies mechanisms of observational learning. Herein, we will discuss the clinical implications of the mirror system.

  14. Neurochemical phenotype of cytoglobin‑expressing neurons in the rat hippocampus

    DEFF Research Database (Denmark)

    Hundahl, Christian Ansgar; Fahrenkrug, Jan; Hannibal, Jens

    2014-01-01

    in a subpopulation of brain neurons. Recently, it has been shown that stress upregulates Cygb expression in the brain and the majority of neuronal nitric oxide synthase (nNOS)-positive neurons, an enzyme that produces NO, co-express Cygb. However, there are more neurons expressing Cygb than nNOS, thus a large number...... of Cygb neurons remain uncharacterized by the neurochemical content. The aim of the present study was to provide an additional and more detailed neurochemical phenotype of Cygb-expressing neurons in the rat hippocampus. The rat hippocampus was chosen due to the abundance of Cygb, as well as this limbic...... structure being an important target in a number of neurodegenerative diseases. Using triple immunohistochemistry, it was demonstrated that nearly all the parvalbumin- and heme oxygenase 1-positive neurons co-express Cygb and to a large extent, these neuron populations are distinct from the population...

  15. Neurons Containing Orexin or Melanin Concentrating Hormone Reciprocally Regulate Wake and Sleep

    Directory of Open Access Journals (Sweden)

    Roda Rani eKonadhode

    2015-01-01

    Full Text Available There is considerable amount of data on arousal neurons whereas there is a paucity of knowledge regarding neurons that make us fall asleep. Indeed, current network models of sleep-wake regulation list many arousal neuronal populations compared to only one sleep group located in the preoptic area. There are neurons outside the preoptic area that are active during sleep, but they have never been selectively manipulated. Indeed, none of the sleep-active neurons have been selectively stimulated. To close this knowledge gap we used optogenetics to selectively manipulate neurons containing melanin concentrating hormone (MCH. The MCH neurons are located in the posterior hypothalamus intermingled with the orexin arousal neurons. Our data indicated that optogenetic stimulation of MCH neurons in wildtype mice (J Neuroscience, 2013 robustly increased both non-REM and REM sleep. MCH neuron stimulation increased sleep during the animal’s normal active period, which is compelling evidence that stimulation of MCH neurons has a powerful effect in counteracting the strong arousal signal from all of the arousal neurons. The MCH neurons represent the only group of sleep-active neurons that when selectively stimulated induce sleep. From a translational perspective this is potentially useful in sleep disorders, such as insomnia, where sleep needs to be triggered against a strong arousal drive. Our studies indicate that the MCH neurons belong within an overall model of sleep-wake regulation.

  16. An introduction to modeling neuronal dynamics

    CERN Document Server

    Börgers, Christoph

    2017-01-01

    This book is intended as a text for a one-semester course on Mathematical and Computational Neuroscience for upper-level undergraduate and beginning graduate students of mathematics, the natural sciences, engineering, or computer science. An undergraduate introduction to differential equations is more than enough mathematical background. Only a slim, high school-level background in physics is assumed, and none in biology. Topics include models of individual nerve cells and their dynamics, models of networks of neurons coupled by synapses and gap junctions, origins and functions of population rhythms in neuronal networks, and models of synaptic plasticity. An extensive online collection of Matlab programs generating the figures accompanies the book. .

  17. Failure of Neuronal Maturation in Alzheimer Disease Dentate Gyrus

    Science.gov (United States)

    Li, Bin; Yamamori, Hidenaga; Tatebayashi, Yoshitaka; Shafit-Zagardo, Bridget; Tanimukai, Hitoshi; Chen, She; Iqbal, Khalid; Grundke-Iqbal, Inge

    2011-01-01

    The dentate gyrus, an important anatomic structure of the hippocampal formation, is one of the major areas in which neurogenesis takes place in the adult mammalian brain. Neurogenesis in the dentate gyrus is thought to play an important role in hippocampus-dependent learning and memory. Neurogenesis has been reported to be increased in the dentate gyrus of patients with Alzheimer disease, but it is not known whether the newly generated neurons differentiate into mature neurons. In this study, the expression of the mature neuronal marker high molecular weight microtubule-associated protein (MAP) isoforms MAP2a and b was found to be dramatically decreased in Alzheimer disease dentate gyrus, as determined by immunohistochemistry and in situ hybridization. The total MAP2, including expression of the immature neuronal marker, the MAP2c isoform, was less affected. These findings suggest that newly generated neurons in Alzheimer disease dentate gyrus do not become mature neurons, although neuroproliferation is increased. PMID:18091557

  18. A Quantitative Golgi Study of Dendritic Morphology in the Mice Striatal Medium Spiny Neurons

    Directory of Open Access Journals (Sweden)

    Ana Hladnik

    2017-04-01

    Full Text Available In this study we have provided a detailed quantitative morphological analysis of medium spiny neurons (MSNs in the mice dorsal striatum and determined the consistency of values among three groups of animals obtained in different set of experiments. Dendritic trees of 162 Golgi Cox (FD Rapid GolgiStain Kit impregnated MSNs from 15 adult C57BL/6 mice were 3-dimensionally reconstructed using Neurolucida software, and parameters of dendritic morphology have been compared among experimental groups. The parameters of length and branching pattern did not show statistically significant difference and were highly consistent among groups. The average neuronal soma surface was between 160 μm2 and 180 μm2, and the cells had 5–6 primary dendrites with close to 40 segments per neuron. Sholl analysis confirmed regular pattern of dendritic branching. The total length of dendrites was around 2100 μm with the average length of individual branching (intermediate segment around 22 μm and for the terminal segment around 100 μm. Even though each experimental group underwent the same strictly defined protocol in tissue preparation and Golgi staining, we found inconsistency in dendritic volume and soma surface. These changes could be methodologically influenced during the Golgi procedure, although without affecting the dendritic length and tree complexity. Since the neuronal activity affects the dendritic thickness, it could not be excluded that observed volume inconsistency was related with functional states of neurons prior to animal sacrifice. Comprehensive analyses of tree complexity and dendritic length provided here could serve as an additional tool for understanding morphological variability in the most numerous neuronal population of the striatum. As reference values they could provide basic ground for comparisons with the results obtained in studies that use various models of genetically modified mice in explaining different pathological conditions that

  19. Dicer maintains the identity and function of proprioceptive sensory neurons.

    Science.gov (United States)

    O'Toole, Sean M; Ferrer, Monica M; Mekonnen, Jennifer; Zhang, Haihan; Shima, Yasuyuki; Ladle, David R; Nelson, Sacha B

    2017-03-01

    Neuronal cell identity is established during development and must be maintained throughout an animal's life (Fishell G, Heintz N. Neuron 80: 602-612, 2013). Transcription factors critical for establishing neuronal identity can be required for maintaining it (Deneris ES, Hobert O. Nat Neurosci 17: 899-907, 2014). Posttranscriptional regulation also plays an important role in neuronal differentiation (Bian S, Sun T. Mol Neurobiol 44: 359-373, 2011), but its role in maintaining cell identity is less established. To better understand how posttranscriptional regulation might contribute to cell identity, we examined the proprioceptive neurons in the dorsal root ganglion (DRG), a highly specialized sensory neuron class, with well-established properties that distinguish them from other neurons in the ganglion. By conditionally ablating Dicer in mice, using parvalbumin (Pvalb)-driven Cre recombinase, we impaired posttranscriptional regulation in the proprioceptive sensory neuron population. Knockout (KO) animals display a progressive form of ataxia at the beginning of the fourth postnatal week that is accompanied by a cell death within the DRG. Before cell loss, expression profiling shows a reduction of proprioceptor specific genes and an increased expression of nonproprioceptive genes normally enriched in other ganglion neurons. Furthermore, although central connections of these neurons are intact, the peripheral connections to the muscle are functionally impaired. Posttranscriptional regulation is therefore necessary to retain the transcriptional identity and support functional specialization of the proprioceptive sensory neurons. NEW & NOTEWORTHY We have demonstrated that selectively impairing Dicer in parvalbumin-positive neurons, which include the proprioceptors, triggers behavioral changes, a lack of muscle connectivity, and a loss of transcriptional identity as observed through RNA sequencing. These results suggest that Dicer and, most likely by extension, micro

  20. An empirical analysis of the precision of estimating the numbers of neurons and glia in human neocortex using a fractionator-design with sub-sampling

    DEFF Research Database (Denmark)

    Lyck, L.; Santamaria, I.D.; Pakkenberg, B.

    2009-01-01

    Improving histomorphometric analysis of the human neocortex by combining stereological cell counting with immunchistochemical visualisation of specific neuronal and glial cell populations is a methodological challenge. To enable standardized immunohistochemical staining, the amount of brain tissue...... at each level of sampling was determined empirically. The methodology was tested in three brains analysing the contribution of the multi-step sampling procedure to the precision on the estimated total numbers of immunohistochemically defined NeuN expressing (NeuN(+)) neurons and CD45(+) microglia...

  1. Neuromorphic Silicon Neuron Circuits

    Science.gov (United States)

    Indiveri, Giacomo; Linares-Barranco, Bernabé; Hamilton, Tara Julia; van Schaik, André; Etienne-Cummings, Ralph; Delbruck, Tobi; Liu, Shih-Chii; Dudek, Piotr; Häfliger, Philipp; Renaud, Sylvie; Schemmel, Johannes; Cauwenberghs, Gert; Arthur, John; Hynna, Kai; Folowosele, Fopefolu; Saighi, Sylvain; Serrano-Gotarredona, Teresa; Wijekoon, Jayawan; Wang, Yingxue; Boahen, Kwabena

    2011-01-01

    Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain–machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance-based Hodgkin–Huxley models to bi-dimensional generalized adaptive integrate and fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips. PMID:21747754

  2. Neuromorphic silicon neuron circuits

    Directory of Open Access Journals (Sweden)

    Giacomo eIndiveri

    2011-05-01

    Full Text Available Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain-machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance based Hodgkin-Huxley models to bi-dimensional generalized adaptive Integrate and Fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips.

  3. Asynchronous Rate Chaos in Spiking Neuronal Circuits.

    Directory of Open Access Journals (Sweden)

    Omri Harish

    2015-07-01

    Full Text Available The brain exhibits temporally complex patterns of activity with features similar to those of chaotic systems. Theoretical studies over the last twenty years have described various computational advantages for such regimes in neuronal systems. Nevertheless, it still remains unclear whether chaos requires specific cellular properties or network architectures, or whether it is a generic property of neuronal circuits. We investigate the dynamics of networks of excitatory-inhibitory (EI spiking neurons with random sparse connectivity operating in the regime of balance of excitation and inhibition. Combining Dynamical Mean-Field Theory with numerical simulations, we show that chaotic, asynchronous firing rate fluctuations emerge generically for sufficiently strong synapses. Two different mechanisms can lead to these chaotic fluctuations. One mechanism relies on slow I-I inhibition which gives rise to slow subthreshold voltage and rate fluctuations. The decorrelation time of these fluctuations is proportional to the time constant of the inhibition. The second mechanism relies on the recurrent E-I-E feedback loop. It requires slow excitation but the inhibition can be fast. In the corresponding dynamical regime all neurons exhibit rate fluctuations on the time scale of the excitation. Another feature of this regime is that the population-averaged firing rate is substantially smaller in the excitatory population than in the inhibitory population. This is not necessarily the case in the I-I mechanism. Finally, we discuss the neurophysiological and computational significance of our results.

  4. Asynchronous Rate Chaos in Spiking Neuronal Circuits

    Science.gov (United States)

    Harish, Omri; Hansel, David

    2015-01-01

    The brain exhibits temporally complex patterns of activity with features similar to those of chaotic systems. Theoretical studies over the last twenty years have described various computational advantages for such regimes in neuronal systems. Nevertheless, it still remains unclear whether chaos requires specific cellular properties or network architectures, or whether it is a generic property of neuronal circuits. We investigate the dynamics of networks of excitatory-inhibitory (EI) spiking neurons with random sparse connectivity operating in the regime of balance of excitation and inhibition. Combining Dynamical Mean-Field Theory with numerical simulations, we show that chaotic, asynchronous firing rate fluctuations emerge generically for sufficiently strong synapses. Two different mechanisms can lead to these chaotic fluctuations. One mechanism relies on slow I-I inhibition which gives rise to slow subthreshold voltage and rate fluctuations. The decorrelation time of these fluctuations is proportional to the time constant of the inhibition. The second mechanism relies on the recurrent E-I-E feedback loop. It requires slow excitation but the inhibition can be fast. In the corresponding dynamical regime all neurons exhibit rate fluctuations on the time scale of the excitation. Another feature of this regime is that the population-averaged firing rate is substantially smaller in the excitatory population than in the inhibitory population. This is not necessarily the case in the I-I mechanism. Finally, we discuss the neurophysiological and computational significance of our results. PMID:26230679

  5. Association of Habitual Patterns and Types of Physical Activity and Inactivity with MRI-Determined Total Volumes of Visceral and Subcutaneous Abdominal Adipose Tissue in a General White Population.

    Directory of Open Access Journals (Sweden)

    Karina Fischer

    Full Text Available Population-based evidence for the role of habitual physical activity (PA in the accumulation of visceral (VAT and subcutaneous (SAAT abdominal adipose tissue is limited. We investigated if usual patterns and types of self-reported PA and inactivity were associated with VAT and SAAT in a general white population. Total volumes of VAT and SAAT were quantified by magnetic resonance imaging in 583 men and women (61 ± 11.9 y; BMI 27.2 ± 4.4 kg/m2. Past-year PA and inactivity were self-reported by questionnaire. Exploratory activity patterns (APAT were derived by principal components analysis. Cross-sectional associations between individual activities, total PA in terms of metabolic equivalents (PA MET, or overall APAT and either VAT or SAAT were analyzed by multivariable-adjusted robust or generalized linear regression models. Whereas vigorous-intensity PA (VPA was negatively associated with both VAT and SAAT, associations between total PA MET, moderate-intensity PA (MPA, or inactivity and VAT and/or SAAT depended on sex. There was also evidence of a threshold effect in some of these relationships. Total PA MET was more strongly associated with VAT in men (B = -3.3 ± 1.4; P = 0.02 than women (B = -2.1 ± 1.1; P = 0.07, but was more strongly associated with SAAT in women (B = -5.7 ± 2.5; P = 0.05 than men (B = -1.7 ± 1.6; P = 0.3. Men (-1.52 dm3 or -1.89 dm3 and women (-1.15 dm3 or -2.61 dm3 in the highest (>6.8 h/wk VPA or second (4.0-6.8 h/wk VPA tertile of an APAT rich in VPA, had lower VAT and SAAT, respectively, than those in the lowest (<4.0 h/wk VPA tertile (P ≤ 0.016; P trend ≤ 0.0005. They also had lower VAT and SAAT than those with APAT rich in MPA and/or inactivity only. In conclusion, our results suggest that in white populations, habitual APAT rich in MPA might be insufficient to impact on accumulation of VAT or SAAT. APAT including ≥ 4.0-6.8 h/wk VPA, by contrast, are more strongly associated with lower VAT and SAAT.

  6. Untuned But Not Irrelevant: The Role of Untuned Neurons In Sensory Information Coding

    OpenAIRE

    Zylberberg, Joel

    2017-01-01

    In the sensory systems, most neurons' firing rates are tuned to at least one aspect of the stimulus. Other neurons are appear to be untuned, meaning that their firing rates do not depend on the stimulus. Previous work on information coding in neural populations has ignored untuned neurons, based on the tacit assumption that they are unimportant. Recent experimental work has questioned this assumption, showing that in some circumstances, neurons with no apparent stimulus tuning can contribute ...

  7. NeuronBank: a tool for cataloging neuronal circuitry

    Directory of Open Access Journals (Sweden)

    Paul S Katz

    2010-04-01

    Full Text Available The basic unit of any nervous system is the neuron. Therefore, understanding the operation of nervous systems ultimately requires an inventory of their constituent neurons and synaptic connectivity, which form neural circuits. The presence of uniquely identifiable neurons or classes of neurons in many invertebrates has facilitated the construction of cellular-level connectivity diagrams that can be generalized across individuals within a species. Homologous neurons can also be recognized across species. Here we describe NeuronBank.org, a web-based tool that we are developing for cataloging, searching, and analyzing neuronal circuitry within and across species. Information from a single species is represented in an individual branch of NeuronBank. Users can search within a branch or perform queries across branches to look for similarities in neuronal circuits across species. The branches allow for an extensible ontology so that additional characteristics can be added as knowledge grows. Each entry in NeuronBank generates a unique accession ID, allowing it to be easily cited. There is also an automatic link to a Wiki page allowing an encyclopedic explanation of the entry. All of the 44 previously published neurons plus one previously unpublished neuron from the mollusc, Tritonia diomedea, have been entered into a branch of NeuronBank as have 4 previously published neurons from the mollusc, Melibe leonina. The ability to organize information about neuronal circuits will make this information more accessible, ultimately aiding research on these important models.

  8. Understanding metal homeostasis in primary cultured neurons. Studies using single neuron subcellular and quantitative metallomics.

    Science.gov (United States)

    Colvin, Robert A; Lai, Barry; Holmes, William R; Lee, Daewoo

    2015-07-01

    The purpose of this study was to demonstrate how single cell quantitative and subcellular metallomics inform us about both the spatial distribution and cellular mechanisms of metal buffering and homeostasis in primary cultured neurons from embryonic rat brain, which are often used as models of human disease involving metal dyshomeostasis. The present studies utilized synchrotron radiation X-ray fluorescence (SRXRF) and focused primarily on zinc and iron, two abundant metals in neurons that have been implicated in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Total single cell contents for calcium, iron, zinc, copper, manganese, and nickel were determined. Resting steady state zinc showed a diffuse distribution in both soma and processes, best defined by the mass profile of the neuron with an enrichment in the nucleus compared with the cytoplasm. Zinc buffering and homeostasis was studied using two modes of cellular zinc loading - transporter and ionophore (pyrithione) mediated. Single neuron zinc contents were shown to statistically significantly increase by either loading method - ionophore: 160 million to 7 billion; transporter 160 million to 280 million atoms per neuronal soma. The newly acquired and buffered zinc still showed a diffuse distribution. Soma and processes have about equal abilities to take up zinc via transporter mediated pathways. Copper levels are distributed diffusely as well, but are relatively higher in the processes relative to zinc levels. Prior studies have observed iron puncta in certain cell types, but others have not. In the present study, iron puncta were characterized in several primary neuronal types. The results show that iron puncta could be found in all neuronal types studied and can account for up to 50% of the total steady state content of iron in neuronal soma. Although other metals can be present in iron puncta, they are predominantly iron containing and do not appear to be

  9. Communication among neurons.

    Science.gov (United States)

    Marner, Lisbeth

    2012-04-01

    The communication among neurons is the prerequisite for the working brain. To understand the cellular, neurochemical, and structural basis of this communication, and the impacts of aging and disease on brain function, quantitative measures are necessary. This thesis evaluates several quantitative neurobiological methods with respect to possible bias and methodological issues. Stereological methods are suited for the unbiased estimation of number, length, and volumes of components of the nervous system. Stereological estimates of the total length of myelinated nerve fibers were made in white matter of post mortem brains, and the impact of aging and diseases as Schizophrenia and Alzheimer's disease were evaluated. Although stereological methods are in principle unbiased, shrinkage artifacts are difficult to account for. Positron emission tomography (PET) recordings, in conjunction with kinetic modeling, permit the quantitation of radioligand binding in brain. The novel serotonin 5-HT4 antagonist [11C]SB207145 was used as an example of the validation process for quantitative PET receptor imaging. Methods based on reference tissue as well as methods based on an arterial plasma input function were evaluated with respect to precision and accuracy. It was shown that [11C]SB207145 binding had high sensitivity to occupancy by unlabeled ligand, necessitating high specific activity in the radiosynthesis to avoid bias. The established serotonin 5-HT2A ligand [18F]altanersin was evaluated in a two-year follow-up study in elderly subjects. Application of partial volume correction of the PET data diminished the reliability of the measures, but allowed for the correct distinction between changes due to brain atrophy and receptor availability. Furthermore, a PET study of patients with Alzheimer's disease with the serotonin transporter ligand [11C]DASB showed relatively preserved serotonergic projections, despite a marked decrease in 5-HT2A receptor binding. Possible confounders are

  10. Genetic activation, inactivation and deletion reveal a limited and nuanced role for somatostatin-containing basal forebrain neurons in behavioral state control.

    Science.gov (United States)

    Anaclet, Christelle; De Luca, Roberto; Venner, Anne; Malyshevskaya, Olga; Lazarus, Michael; Arrigoni, Elda; Fuller, Patrick M

    2018-05-07

    Recent studies have identified an especially important role for basal forebrain GABAergic (BF VGAT ) neurons in the regulation of behavioral waking and fast cortical rhythms associated with cognition. However, BF VGAT neurons comprise several neurochemically and anatomically distinct sub-populations, including parvalbumin- and somatostatin-containing BF VGAT neurons (BF Parv and BF SOM ), and it was recently reported that optogenetic activation of BF SOM neurons increases the probability of a wakefulness to non-rapid-eye movement (NREM) sleep transition when stimulated during the animal's rest period. This finding was unexpected given that most BF SOM neurons are not NREM sleep active and that central administration of the synthetic SOM analog, octreotide, suppresses NREM sleep or increases REM sleep. Here we employed a combination of genetically-driven chemogenetic and optogenetic activation, chemogenetic inhibition and ablation approaches to further explore the in vivo role of BF SOM neurons in arousal control. Our findings indicate that acute activation or inhibition of BF SOM neurons is neither wakefulness- nor NREM sleep-promoting, is without significant effect on the EEG, and that chronic loss of these neurons is without effect on total 24h sleep amounts, although a small but significant increase in waking was observed in the lesioned mice during the early active period. Our in vitro cell recordings further reveal electrophysiological heterogeneity in BF SOM neurons, specifically suggesting at least two distinct sub-populations. Taken together our data support the more nuanced view that BF SOM are electrically heterogeneous and are not NREM sleep- or wake-promoting per se , but may exert, in particular during the early active period, a modest inhibitory influence on arousal circuitry. SIGNIFICANCE STATEMENT The cellular basal forebrain (BF) is a highly complex area of the brain that is implicated in a wide-range of higher-level neurobiological processes

  11. Three-dimensional distribution of sensory stimulation-evoked neuronal activity of spinal dorsal horn neurons analyzed by in vivo calcium imaging.

    Directory of Open Access Journals (Sweden)

    Kazuhiko Nishida

    Full Text Available The spinal dorsal horn comprises heterogeneous populations of interneurons and projection neurons, which form neuronal circuits crucial for processing of primary sensory information. Although electrophysiological analyses have uncovered sensory stimulation-evoked neuronal activity of various spinal dorsal horn neurons, monitoring these activities from large ensembles of neurons is needed to obtain a comprehensive view of the spinal dorsal horn circuitry. In the present study, we established in vivo calcium imaging of multiple spinal dorsal horn neurons by using a two-photon microscope and extracted three-dimensional neuronal activity maps of these neurons in response to cutaneous sensory stimulation. For calcium imaging, a fluorescence resonance energy transfer (FRET-based calcium indicator protein, Yellow Cameleon, which is insensitive to motion artifacts of living animals was introduced into spinal dorsal horn neurons by in utero electroporation. In vivo calcium imaging following pinch, brush, and heat stimulation suggests that laminar distribution of sensory stimulation-evoked neuronal activity in the spinal dorsal horn largely corresponds to that of primary afferent inputs. In addition, cutaneous pinch stimulation elicited activities of neurons in the spinal cord at least until 2 spinal segments away from the central projection field of primary sensory neurons responsible for the stimulated skin point. These results provide a clue to understand neuronal processing of sensory information in the spinal dorsal horn.

  12. Three-dimensional distribution of sensory stimulation-evoked neuronal activity of spinal dorsal horn neurons analyzed by in vivo calcium imaging.

    Science.gov (United States)

    Nishida, Kazuhiko; Matsumura, Shinji; Taniguchi, Wataru; Uta, Daisuke; Furue, Hidemasa; Ito, Seiji

    2014-01-01

    The spinal dorsal horn comprises heterogeneous populations of interneurons and projection neurons, which form neuronal circuits crucial for processing of primary sensory information. Although electrophysiological analyses have uncovered sensory stimulation-evoked neuronal activity of various spinal dorsal horn neurons, monitoring these activities from large ensembles of neurons is needed to obtain a comprehensive view of the spinal dorsal horn circuitry. In the present study, we established in vivo calcium imaging of multiple spinal dorsal horn neurons by using a two-photon microscope and extracted three-dimensional neuronal activity maps of these neurons in response to cutaneous sensory stimulation. For calcium imaging, a fluorescence resonance energy transfer (FRET)-based calcium indicator protein, Yellow Cameleon, which is insensitive to motion artifacts of living animals was introduced into spinal dorsal horn neurons by in utero electroporation. In vivo calcium imaging following pinch, brush, and heat stimulation suggests that laminar distribution of sensory stimulation-evoked neuronal activity in the spinal dorsal horn largely corresponds to that of primary afferent inputs. In addition, cutaneous pinch stimulation elicited activities of neurons in the spinal cord at least until 2 spinal segments away from the central projection field of primary sensory neurons responsible for the stimulated skin point. These results provide a clue to understand neuronal processing of sensory information in the spinal dorsal horn.

  13. Membrane potential dye imaging of ventromedial hypothalamus neurons from adult mice to study glucose sensing.

    Science.gov (United States)

    Vazirani, Reema P; Fioramonti, Xavier; Routh, Vanessa H

    2013-11-27

    Studies of neuronal activity are often performed using neurons from rodents less than 2 months of age due to the technical difficulties associated with increasing connective tissue and decreased neuronal viability that occur with age. Here, we describe a methodology for the dissociation of healthy hypothalamic neurons from adult-aged mice. The ability to study neurons from adult-aged mice allows the use of disease models that manifest at a later age and might be more developmentally accurate for certain studies. Fluorescence imaging of dissociated neurons can be used to study the activity of a population of neurons, as opposed to using electrophysiology to study a single neuron. This is particularly useful when studying a heterogeneous neuronal population in which the desired neuronal type is rare such as for hypothalamic glucose sensing neurons. We utilized membrane potential dye imaging of adult ventromedial hypothalamic neurons to study their responses to changes in extracellular glucose. Glucose sensing neurons are believed to play a role in central regulation of energy balance. The ability to study glucose sensing in adult rodents is particularly useful since the predominance of diseases related to dysfunctional energy balance (e.g. obesity) increase with age.

  14. Comparative analyses of the neuron numbers and volumes of the amygdaloid complex in old and new world primates.

    Science.gov (United States)

    Carlo, C N; Stefanacci, L; Semendeferi, K; Stevens, C F

    2010-04-15

    The amygdaloid complex (AC), a key component of the limbic system, is a brain region critical for the detection and interpretation of emotionally salient information. Therefore, changes in its structure and function are likely to provide correlates of mood and emotion disorders, diseases that afflict a large portion of the human population. Previous gross comparisons of the AC in control and diseased individuals have, however, mainly failed to discover these expected correlations with diseases. We have characterized AC nuclei in different nonhuman primate species to establish a baseline for more refined comparisons between the normal and the diseased amygdala. AC nuclei volume and neuron number in 19 subdivisions are reported from 13 Old and New World primate brains, spanning five primate species, and compared with corresponding data from humans. Analysis of the four largest AC nuclei revealed that volume and neuron number of one component, the central nucleus, has a negative allometric relationship with total amygdala volume and neuron number, which is in contrast with the isometric relationship found in the other AC nuclei (for both neuron number and volume). Neuron density decreases across all four nuclei according to a single power law with an exponent of about minus one-half. Because we have included quantitative comparisons with great apes and humans, our conclusions apply to human brains, and our scaling laws can potentially be used to study the anatomical correlates of the amygdala in disorders involving pathological emotion processing. (c) 2009 Wiley-Liss, Inc.

  15. Neuronal avalanches and learning

    Energy Technology Data Exchange (ETDEWEB)

    Arcangelis, Lucilla de, E-mail: dearcangelis@na.infn.it [Department of Information Engineering and CNISM, Second University of Naples, 81031 Aversa (Italy)

    2011-05-01

    Networks of living neurons represent one of the most fascinating systems of biology. If the physical and chemical mechanisms at the basis of the functioning of a single neuron are quite well understood, the collective behaviour of a system of many neurons is an extremely intriguing subject. Crucial ingredient of this complex behaviour is the plasticity property of the network, namely the capacity to adapt and evolve depending on the level of activity. This plastic ability is believed, nowadays, to be at the basis of learning and memory in real brains. Spontaneous neuronal activity has recently shown features in common to other complex systems. Experimental data have, in fact, shown that electrical information propagates in a cortex slice via an avalanche mode. These avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems and successful models have been developed to describe their behaviour. In this contribution we discuss a statistical mechanical model for the complex activity in a neuronal network. The model implements the main physiological properties of living neurons and is able to reproduce recent experimental results. Then, we discuss the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules, in particular the exclusive OR (XOR) and a random rule with three inputs. The learning dynamics exhibits universal features as function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

  16. Neuronal avalanches and learning

    International Nuclear Information System (INIS)

    Arcangelis, Lucilla de

    2011-01-01

    Networks of living neurons represent one of the most fascinating systems of biology. If the physical and chemical mechanisms at the basis of the functioning of a single neuron are quite well understood, the collective behaviour of a system of many neurons is an extremely intriguing subject. Crucial ingredient of this complex behaviour is the plasticity property of the network, namely the capacity to adapt and evolve depending on the level of activity. This plastic ability is believed, nowadays, to be at the basis of learning and memory in real brains. Spontaneous neuronal activity has recently shown features in common to other complex systems. Experimental data have, in fact, shown that electrical information propagates in a cortex slice via an avalanche mode. These avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems and successful models have been developed to describe their behaviour. In this contribution we discuss a statistical mechanical model for the complex activity in a neuronal network. The model implements the main physiological properties of living neurons and is able to reproduce recent experimental results. Then, we discuss the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules, in particular the exclusive OR (XOR) and a random rule with three inputs. The learning dynamics exhibits universal features as function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

  17. HCS-Neurons: identifying phenotypic changes in multi-neuron images upon drug treatments of high-content screening.

    Science.gov (United States)

    Charoenkwan, Phasit; Hwang, Eric; Cutler, Robert W; Lee, Hua-Chin; Ko, Li-Wei; Huang, Hui-Ling; Ho, Shinn-Ying

    2013-01-01

    High-content screening (HCS) has become a powerful tool for drug discovery. However, the discovery of drugs targeting neurons is still hampered by the inability to accurately identify and quantify the phenotypic changes of multiple neurons in a single image (named multi-neuron image) of a high-content screen. Therefore, it is desirable to develop an automated image analysis method for analyzing multi-neuron images. We propose an automated analysis method with novel descriptors of neuromorphology features for analyzing HCS-based multi-neuron images, called HCS-neurons. To observe multiple phenotypic changes of neurons, we propose two kinds of descriptors which are neuron feature descriptor (NFD) of 13 neuromorphology features, e.g., neurite length, and generic feature descriptors (GFDs), e.g., Haralick texture. HCS-neurons can 1) automatically extract all quantitative phenotype features in both NFD and GFDs, 2) identify statistically significant phenotypic changes upon drug treatments using ANOVA and regression analysis, and 3) generate an accurate classifier to group neurons treated by different drug concentrations using support vector machine and an intelligent feature selection method. To evaluate HCS-neurons, we treated P19 neurons with nocodazole (a microtubule depolymerizing drug which has been shown to impair neurite development) at six concentrations ranging from 0 to 1000 ng/mL. The experimental results show that all the 13 features of NFD have statistically significant difference with respect to changes in various levels of nocodazole drug concentrations (NDC) and the phenotypic changes of neurites were consistent to the known effect of nocodazole in promoting neurite retraction. Three identified features, total neurite length, average neurite length, and average neurite area were able to achieve an independent test accuracy of 90.28% for the six-dosage classification problem. This NFD module and neuron image datasets are provided as a freely downloadable

  18. The superior colliculus of the camel: a neuronal-specific nuclear protein (NeuN) and neuropeptide study

    Science.gov (United States)

    Mensah-Brown, E P K; Garey, L J

    2006-01-01

    In this study we examined the superior colliculus of the midbrain of the one-humped (dromedary) camel, Camelus dromedarius, using Nissl staining and anti-neuronal-specific nuclear protein (NeuN) immunohistochemistry for total neuronal population as well as for the enkephalins, somatostatin (SOM) and substance P (SP). It was found that, unlike in most mammals, the superior colliculus is much larger than the inferior colliculus. The superior colliculus is concerned with visual reflexes and the co-ordination of head, neck and eye movements, which are certainly of importance to this animal with large eyes, head and neck, and apparently good vision. The basic neuronal architecture and lamination of the superior colliculus are similar to that in other mammals. However, we describe for the first time an unusually large content of neurons in the superior colliculus with strong immunoreactivity for met-enkephalin, an endogenous opioid. We classified the majority of these neurons as small (perimeters of 40–50 µm), and localized diffusely throughout the superficial grey and stratum opticum. In addition, large pyramidal-like neurons with perimeters of 100 µm and above were present in the intermediate grey layer. Large unipolar cells were located immediately dorsal to the deep grey layer. By contrast, small neurons (perimeters of 40–50 µm) immunopositive to SOM and SP were located exclusively in the superficial grey layer. We propose that this system may be associated with a pain-inhibiting pathway that has been described from the periaqueductal grey matter, juxtaposing the deep layers of the superior colliculus, to the lower brainstem and spinal cord. Such pain inhibition could be important in relation to the camel's life in the harsh environment of its native deserts, often living in very high temperatures with no shade and a diet consisting largely of thorny branches. PMID:16441568

  19. Physiological characterisation of human iPS-derived dopaminergic neurons.

    Directory of Open Access Journals (Sweden)

    Elizabeth M Hartfield

    Full Text Available Human induced pluripotent stem cells (hiPSCs offer the potential to study otherwise inaccessible cell types. Critical to this is the directed differentiation of hiPSCs into functional cell lineages. This is of particular relevance to research into neurological disease, such as Parkinson's disease (PD, in which midbrain dopaminergic neurons degenerate during disease progression but are unobtainable until post-mortem. Here we report a detailed study into the physiological maturation over time of human dopaminergic neurons in vitro. We first generated and differentiated hiPSC lines into midbrain dopaminergic neurons and performed a comprehensive characterisation to confirm dopaminergic functionality by demonstrating dopamine synthesis, release, and re-uptake. The neuronal cultures include cells positive for both tyrosine hydroxylase (TH and G protein-activated inward rectifier potassium channel 2 (Kir3.2, henceforth referred to as GIRK2, representative of the A9 population of substantia nigra pars compacta (SNc neurons vulnerable in PD. We observed for the first time the maturation of the slow autonomous pace-making (<10 Hz and spontaneous synaptic activity typical of mature SNc dopaminergic neurons using a combination of calcium imaging and electrophysiology. hiPSC-derived neurons exhibited inositol tri-phosphate (IP3 receptor-dependent release of intracellular calcium from the endoplasmic reticulum in neuronal processes as calcium waves propagating from apical and distal dendrites, and in the soma. Finally, neurons were susceptible to the dopamine neuron-specific toxin 1-methyl-4-phenylpyridinium (MPP+ which reduced mitochondrial membrane potential and altered mitochondrial morphology. Mature hiPSC-derived dopaminergic neurons provide a neurophysiologically-defined model of previously inaccessible vulnerable SNc dopaminergic neurons to bridge the gap between clinical PD and animal models.

  20. Association of total energy intake and macronutrient consumption with colorectal cancer risk: results from a large population-based case-control study in Newfoundland and Labrador and Ontario, Canada.

    Science.gov (United States)

    Sun, Zhuoyu; Liu, Lin; Wang, Peizhong Peter; Roebothan, Barbara; Zhao, Jin; Dicks, Elizabeth; Cotterchio, Michelle; Buehler, Sharon; Campbell, Peter T; McLaughlin, John R; Parfrey, Patrick S

    2012-03-26

    Diet is regarded as one of the most important environmental factors associated with colorectal cancer (CRC) risk. A recent report comprehensively concluded that total energy intake does not have a simple relationship with CRC risk, and that the data were inconsistent for carbohydrate, cholesterol and protein. The objective of this study was to identify the associations of CRC risk with dietary intakes of total energy, protein, fat, carbohydrate, fiber, and alcohol using data from a large case-control study conducted in Newfoundland and Labrador (NL) and Ontario (ON), Canada. Incident colorectal cancer cases (n = 1760) were identified from population-based cancer registries in the provinces of ON (1997-2000) and NL (1999-2003). Controls (n = 2481) were a random sample of residents in each province, aged 20-74 years. Family history questionnaire (FHQ), personal history questionnaire (PHQ), and food frequency questionnaire (FFQ) were used to collect study data. Logistic regression was used to evaluate the association of intakes of total energy, macronutrients and alcohol with CRC risk. Total energy intake was associated with higher risk of CRC (OR: 1.56; 95% CI: 1.21-2.01, p-trend = 0.02, 5th versus 1st quintile), whereas inverse associations emerged for intakes of protein (OR: 0.85, 95%CI: 0.69-1.00, p-trend = 0.06, 5th versus 1st quintile), carbohydrate (OR: 0.81, 95%CI: 0.63-1.00, p-trend = 0.05, 5th versus 1st quintile) and total dietary fiber (OR: 0.84, 95% CI:0.67-0.99, p-trend = 0.04, 5th versus 1st quintile). Total fat, alcohol, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, and cholesterol were not associated with CRC risk. This study provides further evidence that high energy intake may increase risk of incident CRC, whereas diets high in protein, fiber, and carbohydrate may reduce the risk of the disease.