WorldWideScience

Sample records for neural differentiation behavior

  1. Differential effects of ethanol on feline rage and predatory attack behavior: an underlying neural mechanism.

    Science.gov (United States)

    Schubert, K; Shaikh, M B; Han, Y; Poherecky, L; Siegel, A

    1996-08-01

    Previous studies have shown that, at certain dose levels, ethanol can exert a powerful, facilitatory effect on aggressive behavior in both animals and humans. In the cat, however, it was discovered that ethanol differentially alters two forms of aggression that are common to this species. Defensive rage behavior is significantly enhanced, whereas predatory attack behavior is suppressed by ethanol administration. One possible mechanism governing alcohol's potentiation of defensive rage behavior is that it acts on the descending pathway from the medial hypothalamus to the midbrain periaqueductal gray (PAG)-an essential pathway for the expression of defensive rage behavior that uses excitatory amino acids as a neurotransmitter. This hypothesis is supported by the finding that the excitatory effects of alcohol on defensive rage behavior are blocked by administration of the N-methyl-D-aspartate antagonist alpha-2-amino-7-phosphoheptanoic acid (AP-7) when microinjected into the periaqueductal gray, a primary neuronal target of descending fibers from the medial hypothalamus that mediate the expression of defensive rage behavior. Thus, the present study establishes for the first time a specific component of the neural circuit for defensive rage behavior over which the potentiating effects of ethanol are mediated.

  2. Differentiating neural systems mediating the acquisition versus expression of goal-directed and habitual behavioral control

    Science.gov (United States)

    Liljeholm, Mimi; Dunne, Simon; O'Doherty, John P.

    2015-01-01

    Considerable behavioral data indicates that operant actions can become habitual, as evidenced by insensitivity to changes in the action-outcome contingency and in subjective outcome values. Notably, although several studies have investigated the neural substrates of habits, none has clearly differentiated the areas of the human brain that support habit formation from those that implement habitual control. We scanned participants with fMRI as they learned and performed an operant task in which the conditional structure of the environment encouraged either goal-directed encoding of the consequences of actions, or a habit-like mapping of actions to antecedent cues. Participants were also scanned during a subsequent assessment of insensitivity to outcome devaluation. We identified dissociable roles of the cerebellum and ventral striatum, across learning and test performance, in behavioral insensitivity to outcome devaluation. We also show that the inferior parietal lobule – an area previously implicated in several aspects of goal-directed action selection, including the attribution of intent and awareness of agency – predicts sensitivity to outcome devaluation. Finally, we reveal a potential functional homology between the human subgenual cortex and rodent infralimbic cortex in the implementation of habitual control. In summary, our findings suggest a broad systems division, at the cortical and subcortical levels, between brain areas mediating the encoding and expression of action-outcome and stimulus-response associations. PMID:25892332

  3. Exogenous attention to fear: Differential behavioral and neural responses to snakes and spiders.

    Science.gov (United States)

    Soares, Sandra C; Kessel, Dominique; Hernández-Lorca, María; García-Rubio, María J; Rodrigues, Paulo; Gomes, Nuno; Carretié, Luis

    2017-05-01

    Research has consistently shown that threat stimuli automatically attract attention in order to activate the defensive response systems. Recent findings have provided evidence that snakes tuned the visual system of evolving primates for their astute detection, particularly under challenging perceptual conditions. The goal of the present study was to measure behavioral and electrophysiological indices of exogenous attention to snakes, compared with spiders - matched for rated fear levels but for which sources of natural selection are less well grounded, and to innocuous animals (birds), which were presented as distracters, while participants were engaged in a letter discrimination task. Duration of stimuli, consisting in a letter string and a concurrent distracter, was either presented for 180 or 360ms to explore if the stimulus duration was a modulating effect of snakes in capturing attention. Results showed a specific early (P1) exogenous attention-related brain potential with maximal amplitude to snakes in both durations, which was followed by an enhanced late attention-related potential (LPP) showing enhanced amplitudes to spiders, particularly under the longer exposure durations. These results suggest that exogenous attention to different classes of threat stimuli follows a gradual process, with the most evolutionary-driven stimulus, i.e., snakes, being more efficient at attracting early exogenous attention, thus more dependent on bottom-up processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Chondroitin sulfate effects on neural stem cell differentiation.

    Science.gov (United States)

    Canning, David R; Brelsford, Natalie R; Lovett, Neil W

    2016-01-01

    We have investigated the role chondroitin sulfate has on cell interactions during neural plate formation in the early chick embryo. Using tissue culture isolates from the prospective neural plate, we have measured neural gene expression profiles associated with neural stem cell differentiation. Removal of chondroitin sulfate from stage 4 neural plate tissue leads to altered associations of N-cadherin-positive neural progenitors and causes changes in the normal sequence of neural marker gene expression. Absence of chondroitin sulfate in the neural plate leads to reduced Sox2 expression and is accompanied by an increase in the expression of anterior markers of neural regionalization. Results obtained in this study suggest that the presence of chondroitin sulfate in the anterior chick embryo is instrumental in maintaining cells in the neural precursor state.

  5. An introduction to neural network methods for differential equations

    CERN Document Server

    Yadav, Neha; Kumar, Manoj

    2015-01-01

    This book introduces a variety of neural network methods for solving differential equations arising in science and engineering. The emphasis is placed on a deep understanding of the neural network techniques, which has been presented in a mostly heuristic and intuitive manner. This approach will enable the reader to understand the working, efficiency and shortcomings of each neural network technique for solving differential equations. The objective of this book is to provide the reader with a sound understanding of the foundations of neural networks, and a comprehensive introduction to neural network methods for solving differential equations together with recent developments in the techniques and their applications. The book comprises four major sections. Section I consists of a brief overview of differential equations and the relevant physical problems arising in science and engineering. Section II illustrates the history of neural networks starting from their beginnings in the 1940s through to the renewed...

  6. Neural network error correction for solving coupled ordinary differential equations

    Science.gov (United States)

    Shelton, R. O.; Darsey, J. A.; Sumpter, B. G.; Noid, D. W.

    1992-01-01

    A neural network is presented to learn errors generated by a numerical algorithm for solving coupled nonlinear differential equations. The method is based on using a neural network to correctly learn the error generated by, for example, Runge-Kutta on a model molecular dynamics (MD) problem. The neural network programs used in this study were developed by NASA. Comparisons are made for training the neural network using backpropagation and a new method which was found to converge with fewer iterations. The neural net programs, the MD model and the calculations are discussed.

  7. Antagonistic neural networks underlying differentiated leadership roles

    Science.gov (United States)

    Boyatzis, Richard E.; Rochford, Kylie; Jack, Anthony I.

    2014-01-01

    The emergence of two distinct leadership roles, the task leader and the socio-emotional leader, has been documented in the leadership literature since the 1950s. Recent research in neuroscience suggests that the division between task-oriented and socio-emotional-oriented roles derives from a fundamental feature of our neurobiology: an antagonistic relationship between two large-scale cortical networks – the task-positive network (TPN) and the default mode network (DMN). Neural activity in TPN tends to inhibit activity in the DMN, and vice versa. The TPN is important for problem solving, focusing of attention, making decisions, and control of action. The DMN plays a central role in emotional self-awareness, social cognition, and ethical decision making. It is also strongly linked to creativity and openness to new ideas. Because activation of the TPN tends to suppress activity in the DMN, an over-emphasis on task-oriented leadership may prove deleterious to social and emotional aspects of leadership. Similarly, an overemphasis on the DMN would result in difficulty focusing attention, making decisions, and solving known problems. In this paper, we will review major streams of theory and research on leadership roles in the context of recent findings from neuroscience and psychology. We conclude by suggesting that emerging research challenges the assumption that role differentiation is both natural and necessary, in particular when openness to new ideas, people, emotions, and ethical concerns are important to success. PMID:24624074

  8. Antagonistic Neural Networks Underlying Differentiated Leadership Roles

    Directory of Open Access Journals (Sweden)

    Richard Eleftherios Boyatzis

    2014-03-01

    Full Text Available The emergence of two distinct leadership roles, the task leader and the socio-emotional leader, has been documented in the leadership literature since the 1950’s. Recent research in neuroscience suggests that the division between task oriented and socio-emotional oriented roles derives from a fundamental feature of our neurobiology: an antagonistic relationship between two large-scale cortical networks -- the Task Positive Network (TPN and the Default Mode Network (DMN. Neural activity in TPN tends to inhibit activity in the DMN, and vice versa. The TPN is important for problem solving, focusing of attention, making decisions, and control of action. The DMN plays a central role in emotional self-awareness, social cognition, and ethical decision making. It is also strongly linked to creativity and openness to new ideas. Because activation of the TPN tends to suppress activity in the DMN, an over-emphasis on task oriented leadership may prove deleterious to social and emotional aspects of leadership. Similarly, an overemphasis on the DMN would result in difficulty focusing attention, making decisions and solving known problems. In this paper, we will review major streams of theory and research on leadership roles in the context of recent findings from neuroscience and psychology. We conclude by suggesting that emerging research challenges the assumption that role differentiation is both natural and necessary, in particular when openness to new ideas, people, emotions, and ethical concerns are important to success.

  9. Antagonistic neural networks underlying differentiated leadership roles.

    Science.gov (United States)

    Boyatzis, Richard E; Rochford, Kylie; Jack, Anthony I

    2014-01-01

    The emergence of two distinct leadership roles, the task leader and the socio-emotional leader, has been documented in the leadership literature since the 1950s. Recent research in neuroscience suggests that the division between task-oriented and socio-emotional-oriented roles derives from a fundamental feature of our neurobiology: an antagonistic relationship between two large-scale cortical networks - the task-positive network (TPN) and the default mode network (DMN). Neural activity in TPN tends to inhibit activity in the DMN, and vice versa. The TPN is important for problem solving, focusing of attention, making decisions, and control of action. The DMN plays a central role in emotional self-awareness, social cognition, and ethical decision making. It is also strongly linked to creativity and openness to new ideas. Because activation of the TPN tends to suppress activity in the DMN, an over-emphasis on task-oriented leadership may prove deleterious to social and emotional aspects of leadership. Similarly, an overemphasis on the DMN would result in difficulty focusing attention, making decisions, and solving known problems. In this paper, we will review major streams of theory and research on leadership roles in the context of recent findings from neuroscience and psychology. We conclude by suggesting that emerging research challenges the assumption that role differentiation is both natural and necessary, in particular when openness to new ideas, people, emotions, and ethical concerns are important to success.

  10. Framing effects: behavioral dynamics and neural basis.

    Science.gov (United States)

    Zheng, Hongming; Wang, X T; Zhu, Liqi

    2010-09-01

    This study examined the neural basis of framing effects using life-death decision problems framed either positively in terms of lives saved or negatively in terms of lives lost in large group and small group contexts. Using functional MRI we found differential brain activations to the verbal and social cues embedded in the choice problems. In large group contexts, framing effects were significant where participants were more risk seeking under the negative (loss) framing than under the positive (gain) framing. This behavioral difference in risk preference was mainly regulated by the activation in the right inferior frontal gyrus, including the homologue of the Broca's area. In contrast, framing effects diminished in small group contexts while the insula and parietal lobe in the right hemisphere were distinctively activated, suggesting an important role of emotion in switching choice preference from an indecisive mode to a more consistent risk-taking inclination, governed by a kith-and-kin decision rationality. Copyright 2010 Elsevier Ltd. All rights reserved.

  11. Chemo-mechanical control of neural stem cell differentiation

    Science.gov (United States)

    Geishecker, Emily R.

    , immunocytochemistry (ICC), and neurite measurements. Data indicates that chemo-mechanical signaling is highly combinatorial in directing differentiation of C17.2s along a neuronal lineage in vitro. Chapter 4 discusses the design, synthesis, and characterization of a novel nanomaterial platform to investigate ligand-receptor binding. PEGylated nanoparticles were successfully synthesized and found to be relatively homogenous in size and morphology, as observed by transmission electron microscopy. However, successful binding of RGD peptide to the nanoparticle was not confirmed. Finally, a method for proteomic analysis of the C17.2 secretome is discussed in Chapter 5. Secreted proteins are of great importance as they can both influence cell behaviors as well as act as biomarkers of differentiation. Methods have been selected and optimized for protein extraction and two dimensional gel electrophoresis to be followed by mass spectrometry and protein identification. A temporal analysis of unique proteins expressed by C17.2s will result in a differentiation timeline. Deducing the dynamics of neuronal cell secretions will greatly contribute to the characterization of the C17.2 cell line and improve its relevance as a neural stem cell model. Overall, results illustrate the importance of chemical and mechanical cues in manipulating neural stem cell fate. These material platforms in combination with the further characterization of the C17.2 neural stem cells could have a great impact in the fields of neuronal biology, translational therapeutics, and pharmaceutical research.

  12. Neural and Behavioral Correlates of Song Prosody

    Science.gov (United States)

    Gordon, Reyna Leigh

    2010-01-01

    This dissertation studies the neural basis of song, a universal human behavior. The relationship of words and melodies in the perception of song at phonological, semantic, melodic, and rhythmic levels of processing was investigated using the fine temporal resolution of Electroencephalography (EEG). The observations reported here may shed light on…

  13. Differentiation state determines neural effects on microvascular endothelial cells

    International Nuclear Information System (INIS)

    Muffley, Lara A.; Pan, Shin-Chen; Smith, Andria N.; Ga, Maricar; Hocking, Anne M.; Gibran, Nicole S.

    2012-01-01

    Growing evidence indicates that nerves and capillaries interact paracrinely in uninjured skin and cutaneous wounds. Although mature neurons are the predominant neural cell in the skin, neural progenitor cells have also been detected in uninjured adult skin. The aim of this study was to characterize differential paracrine effects of neural progenitor cells and mature sensory neurons on dermal microvascular endothelial cells. Our results suggest that neural progenitor cells and mature sensory neurons have unique secretory profiles and distinct effects on dermal microvascular endothelial cell proliferation, migration, and nitric oxide production. Neural progenitor cells and dorsal root ganglion neurons secrete different proteins related to angiogenesis. Specific to neural progenitor cells were dipeptidyl peptidase-4, IGFBP-2, pentraxin-3, serpin f1, TIMP-1, TIMP-4 and VEGF. In contrast, endostatin, FGF-1, MCP-1 and thrombospondin-2 were specific to dorsal root ganglion neurons. Microvascular endothelial cell proliferation was inhibited by dorsal root ganglion neurons but unaffected by neural progenitor cells. In contrast, microvascular endothelial cell migration in a scratch wound assay was inhibited by neural progenitor cells and unaffected by dorsal root ganglion neurons. In addition, nitric oxide production by microvascular endothelial cells was increased by dorsal root ganglion neurons but unaffected by neural progenitor cells. -- Highlights: ► Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell proliferation. ► Neural progenitor cells, not dorsal root ganglion neurons, regulate microvascular endothelial cell migration. ► Neural progenitor cells and dorsal root ganglion neurons do not effect microvascular endothelial tube formation. ► Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell production of nitric oxide. ► Neural progenitor cells and dorsal root

  14. New results for global exponential synchronization in neural networks via functional differential inclusions.

    Science.gov (United States)

    Wang, Dongshu; Huang, Lihong; Tang, Longkun

    2015-08-01

    This paper is concerned with the synchronization dynamical behaviors for a class of delayed neural networks with discontinuous neuron activations. Continuous and discontinuous state feedback controller are designed such that the neural networks model can realize exponential complete synchronization in view of functional differential inclusions theory, Lyapunov functional method and inequality technique. The new proposed results here are very easy to verify and also applicable to neural networks with continuous activations. Finally, some numerical examples show the applicability and effectiveness of our main results.

  15. Neural Reactivity to Emotional Faces May Mediate the Relationship between Childhood Empathy and Adolescent Prosocial Behavior

    Science.gov (United States)

    Flournoy, John C.; Pfeifer, Jennifer H.; Moore, William E.; Tackman, Allison M.; Masten, Carrie L.; Mazziotta, John C.; Iacoboni, Marco; Dapretto, Mirella

    2016-01-01

    Reactivity to others' emotions not only can result in empathic concern (EC), an important motivator of prosocial behavior, but can also result in personal distress (PD), which may hinder prosocial behavior. Examining neural substrates of emotional reactivity may elucidate how EC and PD differentially influence prosocial behavior. Participants…

  16. Solving differential equations with unknown constitutive relations as recurrent neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Hagge, Tobias J.; Stinis, Panagiotis; Yeung, Enoch H.; Tartakovsky, Alexandre M.

    2017-12-08

    We solve a system of ordinary differential equations with an unknown functional form of a sink (reaction rate) term. We assume that the measurements (time series) of state variables are partially available, and use a recurrent neural network to “learn” the reaction rate from this data. This is achieved by including discretized ordinary differential equations as part of a recurrent neural network training problem. We extend TensorFlow’s recurrent neural network architecture to create a simple but scalable and effective solver for the unknown functions, and apply it to a fedbatch bioreactor simulation problem. Use of techniques from recent deep learning literature enables training of functions with behavior manifesting over thousands of time steps. Our networks are structurally similar to recurrent neural networks, but differ in purpose, and require modified training strategies.

  17. Two pore channel 2 differentially modulates neural differentiation of mouse embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Zhe-Hao Zhang

    Full Text Available Nicotinic acid adenine dinucleotide phosphate (NAADP is an endogenous Ca(2+ mobilizing nucleotide presented in various species. NAADP mobilizes Ca(2+ from acidic organelles through two pore channel 2 (TPC2 in many cell types and it has been previously shown that NAADP can potently induce neuronal differentiation in PC12 cells. Here we examined the role of TPC2 signaling in the neural differentiation of mouse embryonic stem (ES cells. We found that the expression of TPC2 was markedly decreased during the initial ES cell entry into neural progenitors, and the levels of TPC2 gradually rebounded during the late stages of neurogenesis. Correspondingly, TPC2 knockdown accelerated mouse ES cell differentiation into neural progenitors but inhibited these neural progenitors from committing to neurons. Overexpression of TPC2, on the other hand, inhibited mouse ES cell from entering the early neural lineage. Interestingly, TPC2 knockdown had no effect on the differentiation of astrocytes and oligodendrocytes of mouse ES cells. Taken together, our data indicate that TPC2 signaling plays a temporal and differential role in modulating the neural lineage entry of mouse ES cells, in that TPC2 signaling inhibits ES cell entry to early neural progenitors, but is required for late neuronal differentiation.

  18. In vitro and in vivo effects on neural crest stem cell differentiation by conditional activation of Runx1 short isoform and its effect on neuropathic pain behavior

    DEFF Research Database (Denmark)

    Kanaykina, Nadezda; Abelson, Klas; King, Dale

    2010-01-01

    INTRODUCTION: Runx1, a Runt domain transcription factor, controls the differentiation of nociceptors that express the neurotrophin receptor Ret, regulates the expression of many ion channels and receptors, and controls the lamina-specific innervation pattern of nociceptive afferents in the spinal...

  19. Behavioral, Cognitive and Neural Markers of Asperger Syndrome

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    Farnaz Faridi

    2017-09-01

    Full Text Available Asperger syndrome (AS is a subtype of Autism Spectrum Disorder (ASD characterized by major problems in social and nonverbal communication, together with limited and repetitive forms of behavior and interests. The linguistic and cognitive development in AS is preserved which help us to differentiate it from other subtypes of ASD. However, significant effects of AS on cognitive abilities and brain functions still need to be researched. Although a clear cut pathology for Asperger has not been identified yet, recent studies have largely focused on brain imaging techniques to investigate AS. In this regard, we carried out a systematic review on behavioral, cognitive, and neural markers (specifically using MRI and fMRI studies on AS. In this paper, behavior, motor skills and language capabilities of individuals with Asperger are compared to those in healthy controls. In addition, common findings across MRI and fMRI based studies associated with behavior and cognitive disabilities are highlighted. 

  20. Neural Circuit Mechanisms of Social Behavior.

    Science.gov (United States)

    Chen, Patrick; Hong, Weizhe

    2018-04-04

    We live in a world that is largely socially constructed, and we are constantly involved in and fundamentally influenced by a broad array of complex social interactions. Social behaviors among conspecifics, either conflictive or cooperative, are exhibited by all sexually reproducing animal species and are essential for the health, survival, and reproduction of animals. Conversely, impairment in social function is a prominent feature of several neuropsychiatric disorders, such as autism spectrum disorders and schizophrenia. Despite the importance of social behaviors, many fundamental questions remain unanswered. How is social sensory information processed and integrated in the nervous system? How are different social behavioral decisions selected and modulated in brain circuits? Here we discuss conceptual issues and recent advances in our understanding of brain regions and neural circuit mechanisms underlying the regulation of social behaviors. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Protein signaling pathways in differentiation of neural stem cells

    Czech Academy of Sciences Publication Activity Database

    Skalníková, Helena; Vodička, Petr; Pelech, S.; Motlík, Jan; Gadher, S. J.; Kovářová, Hana

    2008-01-01

    Roč. 8, - (2008), s. 4547-4559 ISSN 1615-9853 R&D Projects: GA MŠk 1M0538 Institutional research plan: CEZ:AV0Z50450515 Keywords : antibody microarray * differentiation * neural stem cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.586, year: 2008

  2. Biophysical characteristics reveal neural stem cell differentiation potential.

    Directory of Open Access Journals (Sweden)

    Fatima H Labeed

    Full Text Available Distinguishing human neural stem/progenitor cell (huNSPC populations that will predominantly generate neurons from those that produce glia is currently hampered by a lack of sufficient cell type-specific surface markers predictive of fate potential. This limits investigation of lineage-biased progenitors and their potential use as therapeutic agents. A live-cell biophysical and label-free measure of fate potential would solve this problem by obviating the need for specific cell surface markers.We used dielectrophoresis (DEP to analyze the biophysical, specifically electrophysiological, properties of cortical human and mouse NSPCs that vary in differentiation potential. Our data demonstrate that the electrophysiological property membrane capacitance inversely correlates with the neurogenic potential of NSPCs. Furthermore, as huNSPCs are continually passaged they decrease neuron generation and increase membrane capacitance, confirming that this parameter dynamically predicts and negatively correlates with neurogenic potential. In contrast, differences in membrane conductance between NSPCs do not consistently correlate with the ability of the cells to generate neurons. DEP crossover frequency, which is a quantitative measure of cell behavior in DEP, directly correlates with neuron generation of NSPCs, indicating a potential mechanism to separate stem cells biased to particular differentiated cell fates.We show here that whole cell membrane capacitance, but not membrane conductance, reflects and predicts the neurogenic potential of human and mouse NSPCs. Stem cell biophysical characteristics therefore provide a completely novel and quantitative measure of stem cell fate potential and a label-free means to identify neuron- or glial-biased progenitors.

  3. Differential neural network configuration during human path integration

    Science.gov (United States)

    Arnold, Aiden E. G. F; Burles, Ford; Bray, Signe; Levy, Richard M.; Iaria, Giuseppe

    2014-01-01

    Path integration is a fundamental skill for navigation in both humans and animals. Despite recent advances in unraveling the neural basis of path integration in animal models, relatively little is known about how path integration operates at a neural level in humans. Previous attempts to characterize the neural mechanisms used by humans to visually path integrate have suggested a central role of the hippocampus in allowing accurate performance, broadly resembling results from animal data. However, in recent years both the central role of the hippocampus and the perspective that animals and humans share similar neural mechanisms for path integration has come into question. The present study uses a data driven analysis to investigate the neural systems engaged during visual path integration in humans, allowing for an unbiased estimate of neural activity across the entire brain. Our results suggest that humans employ common task control, attention and spatial working memory systems across a frontoparietal network during path integration. However, individuals differed in how these systems are configured into functional networks. High performing individuals were found to more broadly express spatial working memory systems in prefrontal cortex, while low performing individuals engaged an allocentric memory system based primarily in the medial occipito-temporal region. These findings suggest that visual path integration in humans over short distances can operate through a spatial working memory system engaging primarily the prefrontal cortex and that the differential configuration of memory systems recruited by task control networks may help explain individual biases in spatial learning strategies. PMID:24808849

  4. Coordination: Neural, Behavioral and Social Dynamics

    CERN Document Server

    Fuchs, Armin

    2008-01-01

    One of the most striking features of Coordination Dynamics is its interdisciplinary character. The problems we are trying to solve in this field range from behavioral phenomena of interlimb coordination and coordination between stimuli and movements (perception-action tasks) through neural activation patterns that can be observed during these tasks to clinical applications and social behavior. It is not surprising that close collaboration among scientists from different fields as psychology, kinesiology, neurology and even physics are imperative to deal with the enormous difficulties we are facing when we try to understand a system as complex as the human brain. The chapters in this volume are not simply write-ups of the lectures given by the experts at the meeting but are written in a way that they give sufficient introductory information to be comprehensible and useful for all interested scientists and students.

  5. Ferritin nanoparticles for improved self-renewal and differentiation of human neural stem cells.

    Science.gov (United States)

    Lee, Jung Seung; Yang, Kisuk; Cho, Ann-Na; Cho, Seung-Woo

    2018-01-01

    Biomaterials that promote the self-renewal ability and differentiation capacity of neural stem cells (NSCs) are desirable for improving stem cell therapy to treat neurodegenerative diseases. Incorporation of micro- and nanoparticles into stem cell culture has gained great attention for the control of stem cell behaviors, including proliferation and differentiation. In this study, ferritin, an iron-containing natural protein nanoparticle, was applied as a biomaterial to improve the self-renewal and differentiation of NSCs and neural progenitor cells (NPCs). Ferritin nanoparticles were added to NSC or NPC culture during cell growth, allowing for incorporation of ferritin nanoparticles during neurosphere formation. Compared to neurospheres without ferritin treatment, neurospheres with ferritin nanoparticles showed significantly promoted self-renewal and cell-cell interactions. When spontaneous differentiation of neurospheres was induced during culture without mitogenic factors, neuronal differentiation was enhanced in the ferritin-treated neurospheres. In conclusion, we found that natural nanoparticles can be used to improve the self-renewal ability and differentiation potential of NSCs and NPCs, which can be applied in neural tissue engineering and cell therapy for neurodegenerative diseases.

  6. Constructing general partial differential equations using polynomial and neural networks.

    Science.gov (United States)

    Zjavka, Ladislav; Pedrycz, Witold

    2016-01-01

    Sum fraction terms can approximate multi-variable functions on the basis of discrete observations, replacing a partial differential equation definition with polynomial elementary data relation descriptions. Artificial neural networks commonly transform the weighted sum of inputs to describe overall similarity relationships of trained and new testing input patterns. Differential polynomial neural networks form a new class of neural networks, which construct and solve an unknown general partial differential equation of a function of interest with selected substitution relative terms using non-linear multi-variable composite polynomials. The layers of the network generate simple and composite relative substitution terms whose convergent series combinations can describe partial dependent derivative changes of the input variables. This regression is based on trained generalized partial derivative data relations, decomposed into a multi-layer polynomial network structure. The sigmoidal function, commonly used as a nonlinear activation of artificial neurons, may transform some polynomial items together with the parameters with the aim to improve the polynomial derivative term series ability to approximate complicated periodic functions, as simple low order polynomials are not able to fully make up for the complete cycles. The similarity analysis facilitates substitutions for differential equations or can form dimensional units from data samples to describe real-world problems. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Absence of Rybp Compromises Neural Differentiation of Embryonic Stem Cells

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    Gergo Kovacs

    2016-01-01

    Full Text Available Rybp (Ring1 and Yy1 Binding Protein is a transcriptional regulator and member of the noncanonical polycomb repressive complex 1 with essential role in early embryonic development. We have previously described that alteration of Rybp dosage in mouse models induced striking neural tube defects (NTDs, exencephaly, and disorganized neurocortex. In this study we further investigated the role of Rybp in neural differentiation by utilising wild type (rybp+/+ and rybp null mutant (rybp-/- embryonic stem cells (ESCs and tried to uncover underlying molecular events that are responsible for the observed phenotypic changes. We found that rybp null mutant ESCs formed less matured neurons, astrocytes, and oligodendrocytes from existing progenitors than wild type cells. Furthermore, lack of rybp coincided with altered gene expression of key neural markers including Pax6 and Plagl1 pinpointing a possible transcriptional circuit among these genes.

  8. Neural stem cell sex dimorphism in aromatase (CYP19 expression: a basis for differential neural fate

    Directory of Open Access Journals (Sweden)

    Jay Waldron

    2010-11-01

    Full Text Available Jay Waldron1, Althea McCourty1, Laurent Lecanu1,21The Research Institute of the McGill University Health Centre, Montreal, Canada; 2Department of Medicine, McGill University, Quebec, CanadaPurpose: Neural stem cell (NSC transplantation and pharmacologic activation of endogenous neurogenesis are two approaches that trigger a great deal of interest as brain repair strategies. However, the success rate of clinical attempts using stem cells to restore neurologic functions altered either after traumatic brain injury or as a consequence of neurodegenerative disease remains rather disappointing. This suggests that factors affecting the fate of grafted NSCs are largely understudied and remain to be characterized. We recently reported that aging differentially affects the neurogenic properties of male and female NSCs. Although the sex steroids androgens and estrogens participate in the regulation of neurogenesis, to our knowledge, research on how gender-based differences affect the capacity of NSCs to differentiate and condition their neural fate is lacking. In the present study, we explored further the role of cell sex as a determining factor of the neural fate followed by differentiating NSCs and its relationship with a potential differential expression of aromatase (CYP19, the testosterone-metabolizing enzyme.Results: Using NSCs isolated from the subventricular zone of three-month-old male and female Long-Evans rats and maintained as neurospheres, we showed that differentiation triggered by retinoic acid resulted in a neural phenotype that depends on cell sex. Differentiated male NSCs mainly expressed markers of neuronal fate, including ßIII-tubulin, microtubule associated protein 2, growth-associated protein 43, and doublecortin. In contrast, female NSCs essentially expressed the astrocyte marker glial fibrillary acidic protein. Quantification of the expression of aromatase showed a very low level of expression in undifferentiated female NSCs

  9. High Glucose Inhibits Neural Stem Cell Differentiation Through Oxidative Stress and Endoplasmic Reticulum Stress.

    Science.gov (United States)

    Chen, Xi; Shen, Wei-Bin; Yang, Penghua; Dong, Daoyin; Sun, Winny; Yang, Peixin

    2018-06-01

    Maternal diabetes induces neural tube defects by suppressing neurogenesis in the developing neuroepithelium. Our recent study further revealed that high glucose inhibited embryonic stem cell differentiation into neural lineage cells. However, the mechanism whereby high glucose suppresses neural differentiation is unclear. To investigate whether high glucose-induced oxidative stress and endoplasmic reticulum (ER) stress lead to the inhibition of neural differentiation, the effect of high glucose on neural stem cell (the C17.2 cell line) differentiation was examined. Neural stem cells were cultured in normal glucose (5 mM) or high glucose (25 mM) differentiation medium for 3, 5, and 7 days. High glucose suppressed neural stem cell differentiation by significantly decreasing the expression of the neuron marker Tuj1 and the glial cell marker GFAP and the numbers of Tuj1 + and GFAP + cells. The antioxidant enzyme superoxide dismutase mimetic Tempol reversed high glucose-decreased Tuj1 and GFAP expression and restored the numbers of neurons and glial cells differentiated from neural stem cells. Hydrogen peroxide treatment imitated the inhibitory effect of high glucose on neural stem cell differentiation. Both high glucose and hydrogen peroxide triggered ER stress, whereas Tempol blocked high glucose-induced ER stress. The ER stress inhibitor, 4-phenylbutyrate, abolished the inhibition of high glucose or hydrogen peroxide on neural stem cell differentiation. Thus, oxidative stress and its resultant ER stress mediate the inhibitory effect of high glucose on neural stem cell differentiation.

  10. Differentiating neural reward responsiveness in autism versus ADHD

    Directory of Open Access Journals (Sweden)

    Gregor Kohls

    2014-10-01

    Full Text Available Although attention deficit hyperactivity disorders (ADHD and autism spectrum disorders (ASD share certain neurocognitive characteristics, it has been hypothesized to differentiate the two disorders based on their brain's reward responsiveness to either social or monetary reward. Thus, the present fMRI study investigated neural activation in response to both reward types in age and IQ-matched boys with ADHD versus ASD relative to typically controls (TDC. A significant group by reward type interaction effect emerged in the ventral striatum with greater activation to monetary versus social reward only in TDC, whereas subjects with ADHD responded equally strong to both reward types, and subjects with ASD showed low striatal reactivity across both reward conditions. Moreover, disorder-specific neural abnormalities were revealed, including medial prefrontal hyperactivation in response to social reward in ADHD versus ventral striatal hypoactivation in response to monetary reward in ASD. Shared dysfunction was characterized by fronto-striato-parietal hypoactivation in both clinical groups when money was at stake. Interestingly, lower neural activation within parietal circuitry was associated with higher autistic traits across the entire study sample. In sum, the present findings concur with the assumption that both ASD and ADHD display distinct and shared neural dysfunction in response to reward.

  11. NFIX Regulates Neural Progenitor Cell Differentiation During Hippocampal Morphogenesis

    Science.gov (United States)

    Heng, Yee Hsieh Evelyn; McLeay, Robert C.; Harvey, Tracey J.; Smith, Aaron G.; Barry, Guy; Cato, Kathleen; Plachez, Céline; Little, Erica; Mason, Sharon; Dixon, Chantelle; Gronostajski, Richard M.; Bailey, Timothy L.; Richards, Linda J.; Piper, Michael

    2014-01-01

    Neural progenitor cells have the ability to give rise to neurons and glia in the embryonic, postnatal and adult brain. During development, the program regulating whether these cells divide and self-renew or exit the cell cycle and differentiate is tightly controlled, and imbalances to the normal trajectory of this process can lead to severe functional consequences. However, our understanding of the molecular regulation of these fundamental events remains limited. Moreover, processes underpinning development of the postnatal neurogenic niches within the cortex remain poorly defined. Here, we demonstrate that Nuclear factor one X (NFIX) is expressed by neural progenitor cells within the embryonic hippocampus, and that progenitor cell differentiation is delayed within Nfix−/− mice. Moreover, we reveal that the morphology of the dentate gyrus in postnatal Nfix−/− mice is abnormal, with fewer subgranular zone neural progenitor cells being generated in the absence of this transcription factor. Mechanistically, we demonstrate that the progenitor cell maintenance factor Sry-related HMG box 9 (SOX9) is upregulated in the hippocampus of Nfix−/− mice and demonstrate that NFIX can repress Sox9 promoter-driven transcription. Collectively, our findings demonstrate that NFIX plays a central role in hippocampal morphogenesis, regulating the formation of neuronal and glial populations within this structure. PMID:23042739

  12. Differential theory of learning for efficient neural network pattern recognition

    Science.gov (United States)

    Hampshire, John B., II; Vijaya Kumar, Bhagavatula

    1993-09-01

    We describe a new theory of differential learning by which a broad family of pattern classifiers (including many well-known neural network paradigms) can learn stochastic concepts efficiently. We describe the relationship between a classifier's ability to generate well to unseen test examples and the efficiency of the strategy by which it learns. We list a series of proofs that differential learning is efficient in its information and computational resource requirements, whereas traditional probabilistic learning strategies are not. The proofs are illustrated by a simple example that lends itself to closed-form analysis. We conclude with an optical character recognition task for which three different types of differentially generated classifiers generalize significantly better than their probabilistically generated counterparts.

  13. A new perspective on behavioral inconsistency and neural noise in aging: Compensatory speeding of neural communication

    Directory of Open Access Journals (Sweden)

    S. Lee Hong

    2012-09-01

    Full Text Available This paper seeks to present a new perspective on the aging brain. Here, we make connections between two key phenomena of brain aging: 1 increased neural noise or random background activity; and 2 slowing of brain activity. Our perspective proposes the possibility that the slowing of neural processing due to decreasing nerve conduction velocities leads to a compensatory speeding of neuron firing rates. These increased firing rates lead to a broader distribution of power in the frequency spectrum of neural oscillations, which we propose, can just as easily be interpreted as neural noise. Compensatory speeding of neural activity, as we present, is constrained by the: A availability of metabolic energy sources; and B competition for frequency bandwidth needed for neural communication. We propose that these constraints lead to the eventual inability to compensate for age-related declines in neural function that are manifested clinically as deficits in cognition, affect, and motor behavior.

  14. Bitter taste stimuli induce differential neural codes in mouse brain.

    Directory of Open Access Journals (Sweden)

    David M Wilson

    Full Text Available A growing literature suggests taste stimuli commonly classified as "bitter" induce heterogeneous neural and perceptual responses. Here, the central processing of bitter stimuli was studied in mice with genetically controlled bitter taste profiles. Using these mice removed genetic heterogeneity as a factor influencing gustatory neural codes for bitter stimuli. Electrophysiological activity (spikes was recorded from single neurons in the nucleus tractus solitarius during oral delivery of taste solutions (26 total, including concentration series of the bitter tastants quinine, denatonium benzoate, cycloheximide, and sucrose octaacetate (SOA, presented to the whole mouth for 5 s. Seventy-nine neurons were sampled; in many cases multiple cells (2 to 5 were recorded from a mouse. Results showed bitter stimuli induced variable gustatory activity. For example, although some neurons responded robustly to quinine and cycloheximide, others displayed concentration-dependent activity (p<0.05 to quinine but not cycloheximide. Differential activity to bitter stimuli was observed across multiple neurons recorded from one animal in several mice. Across all cells, quinine and denatonium induced correlated spatial responses that differed (p<0.05 from those to cycloheximide and SOA. Modeling spatiotemporal neural ensemble activity revealed responses to quinine/denatonium and cycloheximide/SOA diverged during only an early, at least 1 s wide period of the taste response. Our findings highlight how temporal features of sensory processing contribute differences among bitter taste codes and build on data suggesting heterogeneity among "bitter" stimuli, data that challenge a strict monoguesia model for the bitter quality.

  15. Neural Reactivity to Emotional Faces Mediates the Relationship Between Childhood Empathy and Adolescent Prosocial Behavior

    Science.gov (United States)

    Flournoy, John C.; Pfeifer, Jennifer H.; Moore, William E.; Tackman, Allison; Masten, Carrie L.; Mazziotta, John C.; Iacoboni, Marco; Dapretto, Mirella

    2017-01-01

    Reactivity to others' emotions can result in empathic concern (EC), an important motivator of prosocial behavior, but can also result in personal distress (PD), which may hinder prosocial behavior. Examining neural substrates of emotional reactivity may elucidate how EC and PD differentially influence prosocial behavior. Participants (N=57) provided measures of EC, PD, prosocial behavior, and neural responses to emotional expressions at age 10 and 13. Initial EC predicted subsequent prosocial behavior. Initial EC and PD predicted subsequent reactivity to emotions in the inferior frontal gyrus (IFG) and inferior parietal lobule, respectively. Activity in the IFG, a region linked to mirror neuron processes, as well as cognitive control and language, mediated the relation between initial EC and subsequent prosocial behavior. PMID:28262939

  16. Differentiation between non-neural and neural contributors to ankle joint stiffness in cerebral palsy.

    Science.gov (United States)

    de Gooijer-van de Groep, Karin L; de Vlugt, Erwin; de Groot, Jurriaan H; van der Heijden-Maessen, Hélène C M; Wielheesen, Dennis H M; van Wijlen-Hempel, Rietje M S; Arendzen, J Hans; Meskers, Carel G M

    2013-07-23

    Spastic paresis in cerebral palsy (CP) is characterized by increased joint stiffness that may be of neural origin, i.e. improper muscle activation caused by e.g. hyperreflexia or non-neural origin, i.e. altered tissue viscoelastic properties (clinically: "spasticity" vs. "contracture"). Differentiation between these components is hard to achieve by common manual tests. We applied an assessment instrument to obtain quantitative measures of neural and non-neural contributions to ankle joint stiffness in CP. Twenty-three adolescents with CP and eleven healthy subjects were seated with their foot fixated to an electrically powered single axis footplate. Passive ramp-and-hold rotations were applied over full ankle range of motion (RoM) at low and high velocities. Subject specific tissue stiffness, viscosity and reflexive torque were estimated from ankle angle, torque and triceps surae EMG activity using a neuromuscular model. In CP, triceps surae reflexive torque was on average 5.7 times larger (p = .002) and tissue stiffness 2.1 times larger (p = .018) compared to controls. High tissue stiffness was associated with reduced RoM (p therapy.

  17. Neural stem cell proliferation and differentiation in the conductive PEDOT-HA/Cs/Gel scaffold for neural tissue engineering.

    Science.gov (United States)

    Wang, Shuping; Guan, Shui; Xu, Jianqiang; Li, Wenfang; Ge, Dan; Sun, Changkai; Liu, Tianqing; Ma, Xuehu

    2017-09-26

    Engineering scaffolds with excellent electro-activity is increasingly important in tissue engineering and regenerative medicine. Herein, conductive poly(3,4-ethylenedioxythiophene) doped with hyaluronic acid (PEDOT-HA) nanoparticles were firstly synthesized via chemical oxidant polymerization. A three-dimensional (3D) PEDOT-HA/Cs/Gel scaffold was then developed by introducing PEDOT-HA nanoparticles into a chitosan/gelatin (Cs/Gel) matrix. HA, as a bridge, not only was used as a dopant, but also combined PEDOT into the Cs/Gel via chemical crosslinking. The PEDOT-HA/Cs/Gel scaffold was used as a conductive substrate for neural stem cell (NSC) culture in vitro. The results demonstrated that the PEDOT-HA/Cs/Gel scaffold had excellent biocompatibility for NSC proliferation and differentiation. 3D confocal fluorescence images showed cells attached on the channel surface of Cs/Gel and PEDOT-HA/Cs/Gel scaffolds with a normal neuronal morphology. Compared to the Cs/Gel scaffold, the PEDOT-HA/Cs/Gel scaffold not only promoted NSC proliferation with up-regulated expression of Ki67, but also enhanced NSC differentiation into neurons and astrocytes with up-regulated expression of β tubulin-III and GFAP, respectively. It is expected that this electro-active and bio-active PEDOT-HA/Cs/Gel scaffold will be used as a conductive platform to regulate NSC behavior for neural tissue engineering.

  18. Neural Behavior Chain Learning of Mobile Robot Actions

    Directory of Open Access Journals (Sweden)

    Lejla Banjanovic-Mehmedovic

    2012-01-01

    Full Text Available This paper presents a visual/motor behavior learning approach, based on neural networks. We propose Behavior Chain Model (BCM in order to create a way of behavior learning. Our behavior-based system evolution task is a mobile robot detecting a target and driving/acting towards it. First, the mapping relations between the image feature domain of the object and the robot action domain are derived. Second, a multilayer neural network for offline learning of the mapping relations is used. This learning structure through neural network training process represents a connection between the visual perceptions and motor sequence of actions in order to grip a target. Last, using behavior learning through a noticed action chain, we can predict mobile robot behavior for a variety of similar tasks in similar environment. Prediction results suggest that the methodology is adequate and could be recognized as an idea for designing different mobile robot behaviour assistance.

  19. Function of FEZF1 during early neural differentiation of human embryonic stem cells.

    Science.gov (United States)

    Liu, Xin; Su, Pei; Lu, Lisha; Feng, Zicen; Wang, Hongtao; Zhou, Jiaxi

    2018-01-01

    The understanding of the mechanism underlying human neural development has been hampered due to lack of a cellular system and complicated ethical issues. Human embryonic stem cells (hESCs) provide an invaluable model for dissecting human development because of unlimited self-renewal and the capacity to differentiate into nearly all cell types in the human body. In this study, using a chemical defined neural induction protocol and molecular profiling, we identified Fez family zinc finger 1 (FEZF1) as a potential regulator of early human neural development. FEZF1 is rapidly up-regulated during neural differentiation in hESCs and expressed before PAX6, a well-established marker of early human neural induction. We generated FEZF1-knockout H1 hESC lines using CRISPR-CAS9 technology and found that depletion of FEZF1 abrogates neural differentiation of hESCs. Moreover, loss of FEZF1 impairs the pluripotency exit of hESCs during neural specification, which partially explains the neural induction defect caused by FEZF1 deletion. However, enforced expression of FEZF1 itself fails to drive neural differentiation in hESCs, suggesting that FEZF1 is necessary but not sufficient for neural differentiation from hESCs. Taken together, our findings identify one of the earliest regulators expressed upon neural induction and provide insight into early neural development in human.

  20. In-vitro differentiation induction of neural stem cells

    NARCIS (Netherlands)

    Balasubramaniyan, Veerakumar

    2006-01-01

    Neurale stamcellen maken de drie belangrijkste celtypes van ons zenuwstelsel aan. Veerakumar Balasubramaniyan onderzocht hoe neurale stamcellen kunnen worden aangezet tot het aanmaken van specifieke neurale celtypes. Met behulp van genetische technieken lukte het hem oligodendrocyten te verkrijgen:

  1. Imaging of human differentiated 3D neural aggregates using light sheet fluorescence microscopy

    Science.gov (United States)

    Gualda, Emilio J.; Simão, Daniel; Pinto, Catarina; Alves, Paula M.; Brito, Catarina

    2014-01-01

    The development of three dimensional (3D) cell cultures represents a big step for the better understanding of cell behavior and disease in a more natural like environment, providing not only single but multiple cell type interactions in a complex 3D matrix, highly resembling physiological conditions. Light sheet fluorescence microscopy (LSFM) is becoming an excellent tool for fast imaging of such 3D biological structures. We demonstrate the potential of this technique for the imaging of human differentiated 3D neural aggregates in fixed and live samples, namely calcium imaging and cell death processes, showing the power of imaging modality compared with traditional microscopy. The combination of light sheet microscopy and 3D neural cultures will open the door to more challenging experiments involving drug testing at large scale as well as a better understanding of relevant biological processes in a more realistic environment. PMID:25161607

  2. Imaging of human differentiated 3D neural aggregates using light sheet fluorescence microscopy

    Directory of Open Access Journals (Sweden)

    Emilio J Gualda

    2014-08-01

    Full Text Available The development of three dimensional cell cultures represents a big step for the better understanding of cell behavior and disease in a more natural like environment, providing not only single but multiple cell type interactions in a complex three dimensional matrix, highly resembling physiological conditions. Light sheet fluorescence microscopy is becoming an excellent tool for fast imaging of such three-dimensional biological structures. We demonstrate the potential of this technique for the imaging of human differentiated 3D neural aggregates in fixed and live samples, namely calcium imaging and cell death processes, showing the power of imaging modality compared with traditional microscopy. The combination of light sheet microscopy and 3D neural cultures will open the door to more challenging experiments involving drug testing at large scale as well as a better understanding of relevant biological processes in a more realistic environment.

  3. Biocompatible Electroactive Tetra(aniline)-Conjugated Peptide Nanofibers for Neural Differentiation.

    Science.gov (United States)

    Arioz, Idil; Erol, Ozlem; Bakan, Gokhan; Dikecoglu, F Begum; Topal, Ahmet E; Urel, Mustafa; Dana, Aykutlu; Tekinay, Ayse B; Guler, Mustafa O

    2018-01-10

    Peripheral nerve injuries cause devastating problems for the quality of patients' lives, and regeneration following damage to the peripheral nervous system is limited depending on the degree of the damage. Use of nanobiomaterials can provide therapeutic approaches for the treatment of peripheral nerve injuries. Electroactive biomaterials, in particular, can provide a promising cure for the regeneration of nerve defects. Here, a supramolecular electroactive nanosystem with tetra(aniline) (TA)-containing peptide nanofibers was developed and utilized for nerve regeneration. Self-assembled TA-conjugated peptide nanofibers demonstrated electroactive behavior. The electroactive self-assembled peptide nanofibers formed a well-defined three-dimensional nanofiber network mimicking the extracellular matrix of the neuronal cells. Neurite outgrowth was improved on the electroactive TA nanofiber gels. The neural differentiation of PC-12 cells was more advanced on electroactive peptide nanofiber gels, and these biomaterials are promising for further use in therapeutic neural regeneration applications.

  4. ESC-Derived BDNF-Overexpressing Neural Progenitors Differentially Promote Recovery in Huntington's Disease Models by Enhanced Striatal Differentiation

    Directory of Open Access Journals (Sweden)

    Tina Zimmermann

    2016-10-01

    Full Text Available Huntington's disease (HD is characterized by fatal motoric failures induced by loss of striatal medium spiny neurons. Neuronal cell death has been linked to impaired expression and axonal transport of the neurotrophin BDNF (brain-derived neurotrophic factor. By transplanting embryonic stem cell-derived neural progenitors overexpressing BDNF, we combined cell replacement and BDNF supply as a potential HD therapy approach. Transplantation of purified neural progenitors was analyzed in a quinolinic acid (QA chemical and two genetic HD mouse models (R6/2 and N171-82Q on the basis of distinct behavioral parameters, including CatWalk gait analysis. Explicit rescue of motor function by BDNF neural progenitors was found in QA-lesioned mice, whereas genetic mouse models displayed only minor improvements. Tumor formation was absent, and regeneration was attributed to enhanced neuronal and striatal differentiation. In addition, adult neurogenesis was preserved in a BDNF-dependent manner. Our findings provide significant insight for establishing therapeutic strategies for HD to ameliorate neurodegenerative symptoms.

  5. Neural basis of imprinting behavior in chicks.

    Science.gov (United States)

    Nakamori, Tomoharu; Maekawa, Fumihiko; Sato, Katsushige; Tanaka, Kohichi; Ohki-Hamazaki, Hiroko

    2013-01-01

    Newly hatched chicks memorize the characteristics of the first moving object they encounter, and subsequently show a preference for it. This "imprinting" behavior is an example of infant learning and is elicited by visual and/or auditory cues. Visual information of imprinting stimuli in chicks is first processed in the visual Wulst (VW), a telencephalic area corresponding to the mammalian visual cortex, congregates in the core region of the hyperpallium densocellulare (HDCo) cells, and transmitted to the intermediate medial mesopallium (IMM), a region similar to the mammalian association cortex. The imprinting memory is stored in the IMM, and activities of IMM neurons are altered by imprinting. Imprinting also induces functional and structural plastic changes of neurons in the circuit that links the VW and the IMM. Of these neurons, the activity of the HDCo cells is strongly influenced by imprinting. Expression and modulation of NR2B subunit-containing N-methyl-D-aspartate (NMDA) receptors in the HDCo cells are crucial for plastic changes in this circuit as well as the process of visual imprinting. Thus, elucidation of cellular and molecular mechanisms underlying the plastic changes that occurred in the HDCo cells may provide useful knowledge about infant learning. © 2012 The Authors Development, Growth & Differentiation © 2012 Japanese Society of Developmental Biologists.

  6. System Identification Using Multilayer Differential Neural Networks: A New Result

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    J. Humberto Pérez-Cruz

    2012-01-01

    Full Text Available In previous works, a learning law with a dead zone function was developed for multilayer differential neural networks. This scheme requires strictly a priori knowledge of an upper bound for the unmodeled dynamics. In this paper, the learning law is modified in such a way that this condition is relaxed. By this modification, the tuning process is simpler and the dead-zone function is not required anymore. On the basis of this modification and by using a Lyapunov-like analysis, a stronger result is here demonstrated: the exponential convergence of the identification error to a bounded zone. Besides, a value for upper bound of such zone is provided. The workability of this approach is tested by a simulation example.

  7. Enteric neural crest cells regulate vertebrate stomach patterning and differentiation.

    Science.gov (United States)

    Faure, Sandrine; McKey, Jennifer; Sagnol, Sébastien; de Santa Barbara, Pascal

    2015-01-15

    In vertebrates, the digestive tract develops from a uniform structure where reciprocal epithelial-mesenchymal interactions pattern this complex organ into regions with specific morphologies and functions. Concomitant with these early patterning events, the primitive GI tract is colonized by the vagal enteric neural crest cells (vENCCs), a population of cells that will give rise to the enteric nervous system (ENS), the intrinsic innervation of the GI tract. The influence of vENCCs on early patterning and differentiation of the GI tract has never been evaluated. In this study, we report that a crucial number of vENCCs is required for proper chick stomach development, patterning and differentiation. We show that reducing the number of vENCCs by performing vENCC ablations induces sustained activation of the BMP and Notch pathways in the stomach mesenchyme and impairs smooth muscle development. A reduction in vENCCs also leads to the transdifferentiation of the stomach into a stomach-intestinal mixed phenotype. In addition, sustained Notch signaling activity in the stomach mesenchyme phenocopies the defects observed in vENCC-ablated stomachs, indicating that inhibition of the Notch signaling pathway is essential for stomach patterning and differentiation. Finally, we report that a crucial number of vENCCs is also required for maintenance of stomach identity and differentiation through inhibition of the Notch signaling pathway. Altogether, our data reveal that, through the regulation of mesenchyme identity, vENCCs act as a new mediator in the mesenchymal-epithelial interactions that control stomach development. © 2015. Published by The Company of Biologists Ltd.

  8. New numerical approximation for solving fractional delay differential equations of variable order using artificial neural networks

    Science.gov (United States)

    Zúñiga-Aguilar, C. J.; Coronel-Escamilla, A.; Gómez-Aguilar, J. F.; Alvarado-Martínez, V. M.; Romero-Ugalde, H. M.

    2018-02-01

    In this paper, we approximate the solution of fractional differential equations with delay using a new approach based on artificial neural networks. We consider fractional differential equations of variable order with the Mittag-Leffler kernel in the Liouville-Caputo sense. With this new neural network approach, an approximate solution of the fractional delay differential equation is obtained. Synaptic weights are optimized using the Levenberg-Marquardt algorithm. The neural network effectiveness and applicability were validated by solving different types of fractional delay differential equations, linear systems with delay, nonlinear systems with delay and a system of differential equations, for instance, the Newton-Leipnik oscillator. The solution of the neural network was compared with the analytical solutions and the numerical simulations obtained through the Adams-Bashforth-Moulton method. To show the effectiveness of the proposed neural network, different performance indices were calculated.

  9. A canonical neural mechanism for behavioral variability

    Science.gov (United States)

    Darshan, Ran; Wood, William E.; Peters, Susan; Leblois, Arthur; Hansel, David

    2017-05-01

    The ability to generate variable movements is essential for learning and adjusting complex behaviours. This variability has been linked to the temporal irregularity of neuronal activity in the central nervous system. However, how neuronal irregularity actually translates into behavioural variability is unclear. Here we combine modelling, electrophysiological and behavioural studies to address this issue. We demonstrate that a model circuit comprising topographically organized and strongly recurrent neural networks can autonomously generate irregular motor behaviours. Simultaneous recordings of neurons in singing finches reveal that neural correlations increase across the circuit driving song variability, in agreement with the model predictions. Analysing behavioural data, we find remarkable similarities in the babbling statistics of 5-6-month-old human infants and juveniles from three songbird species and show that our model naturally accounts for these `universal' statistics.

  10. cables1 Is Required for Embryonic Neural Development: Molecular, Cellular, and Behavioral Evidence From the Zebrafish

    Science.gov (United States)

    GROENEWEG, JOLIJN W.; WHITE, YVONNE A.R.; KOKEL, DAVID; PETERSON, RANDALL T.; ZUKERBERG, LAWRENCE R.; BERIN, INNA; RUEDA, BO R.; WOOD, ANTONY W.

    2014-01-01

    SUMMARY In vitro studies have suggested that the Cables1 gene regulates epithelial cell proliferation, whereas other studies suggest a role in promoting neural differentiation. In efforts to clarify the functions of Cables1 in vivo, we conducted gain- and loss-of-function studies targeting its ortholog (cables1) in the zebrafish embryo. Similar to rodents, zebrafish cables1 mRNA expression is detected most robustly in embryonic neural tissues. Antisense knockdown of cables1 leads to increased numbers of apoptotic cells, particularly in brain tissue, in addition to a distinct behavioral phenotype, characterized by hyperactivity in response to stimulation. Apoptosis and the behavioral abnormality could be rescued by co-expression of a morpholino-resistant cables1 construct. Suppression of p53 expression in cables1 morphants partially rescued both apoptosis and the behavioral phenotype, suggesting that the phenotype of cables1 morphants is due in part to p53-dependent apoptosis. Alterations in the expression patterns of several neural transcription factors were observed in cables1 morphants during early neurulation, suggesting that cables1 is required for early neural differentiation. Ectopic overexpression of cables1 strongly disrupted embryonic morphogenesis, while overexpression of a cables1 mutant lacking the C-terminal cyclin box had little effect, suggesting functional importance of the cyclin box. Lastly, marked reductions in p35, but not Cdk5, were observed in cables1 morphants. Collectively, these data suggest that cables1 is important for neural differentiation during embryogenesis, in a mechanism that likely involves interactions with the Cdk5/p35 kinase pathway. PMID:21268180

  11. Characterization of human neural differentiation from pluripotent stem cells using proteomics/PTMomics

    DEFF Research Database (Denmark)

    Braga, Marcella Nunes de Melo; Meyer, Morten; Zeng, Xianmin

    2015-01-01

    Stem cells are unspecialized cells capable of self-renewal and to differentiate into the large variety of cells in the body. The possibility to differentiate these cells into neural precursors and neural cells in vitro provides the opportunity to study neural development, nerve cell biology, neur...... differentiation from pluripotent stem cells. Moreover, some of the challenges in stem cell biology, differentiation, and proteomics/PTMomics that are not exclusive to neural development will be discussed.......Stem cells are unspecialized cells capable of self-renewal and to differentiate into the large variety of cells in the body. The possibility to differentiate these cells into neural precursors and neural cells in vitro provides the opportunity to study neural development, nerve cell biology...... the understanding of molecular processes in cells. Substantial advances in PTM enrichment methods and mass spectrometry has allowed the characterization of a subset of PTMs in large-scale studies. This review focuses on the current state-of-the-art of proteomic, as well as PTMomic studies related to human neural...

  12. Infant differential behavioral responding to discrete emotions.

    Science.gov (United States)

    Walle, Eric A; Reschke, Peter J; Camras, Linda A; Campos, Joseph J

    2017-10-01

    Emotional communication regulates the behaviors of social partners. Research on individuals' responding to others' emotions typically compares responses to a single negative emotion compared with responses to a neutral or positive emotion. Furthermore, coding of such responses routinely measure surface level features of the behavior (e.g., approach vs. avoidance) rather than its underlying function (e.g., the goal of the approach or avoidant behavior). This investigation examined infants' responding to others' emotional displays across 5 discrete emotions: joy, sadness, fear, anger, and disgust. Specifically, 16-, 19-, and 24-month-old infants observed an adult communicate a discrete emotion toward a stimulus during a naturalistic interaction. Infants' responses were coded to capture the function of their behaviors (e.g., exploration, prosocial behavior, and security seeking). The results revealed a number of instances indicating that infants use different functional behaviors in response to discrete emotions. Differences in behaviors across emotions were clearest in the 24-month-old infants, though younger infants also demonstrated some differential use of behaviors in response to discrete emotions. This is the first comprehensive study to identify differences in how infants respond with goal-directed behaviors to discrete emotions. Additionally, the inclusion of a function-based coding scheme and interpersonal paradigms may be informative for future emotion research with children and adults. Possible developmental accounts for the observed behaviors and the benefits of coding techniques emphasizing the function of social behavior over their form are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  13. Understanding the Implications of Neural Population Activity on Behavior

    Science.gov (United States)

    Briguglio, John

    Learning how neural activity in the brain leads to the behavior we exhibit is one of the fundamental questions in Neuroscience. In this dissertation, several lines of work are presented to that use principles of neural coding to understand behavior. In one line of work, we formulate the efficient coding hypothesis in a non-traditional manner in order to test human perceptual sensitivity to complex visual textures. We find a striking agreement between how variable a particular texture signal is and how sensitive humans are to its presence. This reveals that the efficient coding hypothesis is still a guiding principle for neural organization beyond the sensory periphery, and that the nature of cortical constraints differs from the peripheral counterpart. In another line of work, we relate frequency discrimination acuity to neural responses from auditory cortex in mice. It has been previously observed that optogenetic manipulation of auditory cortex, in addition to changing neural responses, evokes changes in behavioral frequency discrimination. We are able to account for changes in frequency discrimination acuity on an individual basis by examining the Fisher information from the neural population with and without optogenetic manipulation. In the third line of work, we address the question of what a neural population should encode given that its inputs are responses from another group of neurons. Drawing inspiration from techniques in machine learning, we train Deep Belief Networks on fake retinal data and show the emergence of Garbor-like filters, reminiscent of responses in primary visual cortex. In the last line of work, we model the state of a cortical excitatory-inhibitory network during complex adaptive stimuli. Using a rate model with Wilson-Cowan dynamics, we demonstrate that simple non-linearities in the signal transferred from inhibitory to excitatory neurons can account for real neural recordings taken from auditory cortex. This work establishes and tests

  14. The neural basis of bounded rational behavior

    Directory of Open Access Journals (Sweden)

    Coricelli, Giorgio

    2012-03-01

    Full Text Available Bounded rational behaviour is commonly observed in experimental games and in real life situations. Neuroeconomics can help to understand the mental processing underlying bounded rationality and out-of-equilibrium behaviour. Here we report results from recent studies on the neural basis of limited steps of reasoning in a competitive setting —the beauty contest game. We use functional magnetic resonance imaging (fMRI to study the neural correlates of human mental processes in strategic games. We apply a cognitive hierarchy model to classify subject’s choices in the experimental game according to the degree of strategic reasoning so that we can identify the neural substrates of different levels of strategizing. We found a correlation between levels of strategic reasoning and activity in a neural network related to mentalizing, i.e. the ability to think about other’s thoughts and mental states. Moreover, brain data showed how complex cognitive processes subserve the higher level of reasoning about others. We describe how a cognitive hierarchy model fits both behavioural and brain data.

    La racionalidad limitada es un fenómeno observado de manera frecuente tanto en juegos experimentales como en situaciones cotidianas. La Neuroeconomía puede mejorar la comprensión de los procesos mentales que caracterizan la racionalidad limitada; en paralelo nos puede ayudar a comprender comportamientos que violan el equilibrio. Nuestro trabajo presenta resultados recientes sobre la bases neuronales del razonamiento estratégico (y sus límite en juegos competitivos —como el juego del “beauty contest”. Estudiamos las bases neuronales del comportamiento estratégico en juegos con interacción entre sujetos usando resonancia magnética funcional (fMRI. Las decisiones de los participantes se clasifican acorde al grado de razonamiento estratégico: el llamado modelo de Jerarquías Cognitivas. Los resultados muestran una correlación entre niveles de

  15. Autoshaped choice in artificial neural networks: implications for behavioral economics and neuroeconomics.

    Science.gov (United States)

    Burgos, José E; García-Leal, Óscar

    2015-05-01

    An existing neural network model of conditioning was used to simulate autoshaped choice. In this phenomenon, pigeons first receive an autoshaping procedure with two keylight stimuli X and Y separately paired with food in a forward-delay manner, intermittently for X and continuously for Y. Then pigeons receive unreinforced choice test trials of X and Y concurrently present. Most pigeons choose Y. This preference for a more valuable response alternative is a form of economic behavior that makes the phenomenon relevant to behavioral economics. The phenomenon also suggests a role for Pavlovian contingencies in economic behavior. The model used, in contrast to others, predicts autoshaping and automaintenance, so it is uniquely positioned to predict autoshaped choice. The model also contemplates neural substrates of economic behavior in neuroeconomics, such as dopaminergic and hippocampal systems. A feedforward neural network architecture was designed to simulate a neuroanatomical differentiation between two environment-behavior relations X-R1 and Y-R2, [corrected] where R1 and R2 denote two different emitted responses (not unconditionally elicited by the reward). Networks with this architecture received a training protocol that simulated an autoshaped-choice procedure. Most networks simulated the phenomenon. Implications for behavioral economics and neuroeconomics, limitations, and the issue of model appraisal are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Integrating Neural Circuits Controlling Female Sexual Behavior.

    Science.gov (United States)

    Micevych, Paul E; Meisel, Robert L

    2017-01-01

    The hypothalamus is most often associated with innate behaviors such as is hunger, thirst and sex. While the expression of these behaviors important for survival of the individual or the species is nested within the hypothalamus, the desire (i.e., motivation) for them is centered within the mesolimbic reward circuitry. In this review, we will use female sexual behavior as a model to examine the interaction of these circuits. We will examine the evidence for a hypothalamic circuit that regulates consummatory aspects of reproductive behavior, i.e., lordosis behavior, a measure of sexual receptivity that involves estradiol membrane-initiated signaling in the arcuate nucleus (ARH), activating β-endorphin projections to the medial preoptic nucleus (MPN), which in turn modulate ventromedial hypothalamic nucleus (VMH) activity-the common output from the hypothalamus. Estradiol modulates not only a series of neuropeptides, transmitters and receptors but induces dendritic spines that are for estrogenic induction of lordosis behavior. Simultaneously, in the nucleus accumbens of the mesolimbic system, the mating experience produces long term changes in dopamine signaling and structure. Sexual experience sensitizes the response of nucleus accumbens neurons to dopamine signaling through the induction of a long lasting early immediate gene. While estrogen alone increases spines in the ARH, sexual experience increases dendritic spine density in the nucleus accumbens. These two circuits appear to converge onto the medial preoptic area where there is a reciprocal influence of motivational circuits on consummatory behavior and vice versa . While it has not been formally demonstrated in the human, such circuitry is generally highly conserved and thus, understanding the anatomy, neurochemistry and physiology can provide useful insight into the motivation for sexual behavior and other innate behaviors in humans.

  17. Integrating Neural Circuits Controlling Female Sexual Behavior

    Directory of Open Access Journals (Sweden)

    Paul E. Micevych

    2017-06-01

    Full Text Available The hypothalamus is most often associated with innate behaviors such as is hunger, thirst and sex. While the expression of these behaviors important for survival of the individual or the species is nested within the hypothalamus, the desire (i.e., motivation for them is centered within the mesolimbic reward circuitry. In this review, we will use female sexual behavior as a model to examine the interaction of these circuits. We will examine the evidence for a hypothalamic circuit that regulates consummatory aspects of reproductive behavior, i.e., lordosis behavior, a measure of sexual receptivity that involves estradiol membrane-initiated signaling in the arcuate nucleus (ARH, activating β-endorphin projections to the medial preoptic nucleus (MPN, which in turn modulate ventromedial hypothalamic nucleus (VMH activity—the common output from the hypothalamus. Estradiol modulates not only a series of neuropeptides, transmitters and receptors but induces dendritic spines that are for estrogenic induction of lordosis behavior. Simultaneously, in the nucleus accumbens of the mesolimbic system, the mating experience produces long term changes in dopamine signaling and structure. Sexual experience sensitizes the response of nucleus accumbens neurons to dopamine signaling through the induction of a long lasting early immediate gene. While estrogen alone increases spines in the ARH, sexual experience increases dendritic spine density in the nucleus accumbens. These two circuits appear to converge onto the medial preoptic area where there is a reciprocal influence of motivational circuits on consummatory behavior and vice versa. While it has not been formally demonstrated in the human, such circuitry is generally highly conserved and thus, understanding the anatomy, neurochemistry and physiology can provide useful insight into the motivation for sexual behavior and other innate behaviors in humans.

  18. Inductive differentiation of two neural lineages reconstituted in a microculture system from Xenopus early gastrula cells.

    Science.gov (United States)

    Mitani, S; Okamoto, H

    1991-05-01

    Neural induction of ectoderm cells has been reconstituted and examined in a microculture system derived from dissociated early gastrula cells of Xenopus laevis. We have used monoclonal antibodies as specific markers to monitor cellular differentiation from three distinct ectoderm lineages in culture (N1 for CNS neurons from neural tube, Me1 for melanophores from neural crest and E3 for skin epidermal cells from epidermal lineages). CNS neurons and melanophores differentiate when deep layer cells of the ventral ectoderm (VE, prospective epidermis region; 150 cells/culture) and an appropriate region of the marginal zone (MZ, prospective mesoderm region; 5-150 cells/culture) are co-cultured, but not in cultures of either cell type on their own; VE cells cultured alone yield epidermal cells as we have previously reported. The extent of inductive neural differentiation in the co-culture system strongly depends on the origin and number of MZ cells initially added to culture wells. The potency to induce CNS neurons is highest for dorsal MZ cells and sharply decreases as more ventrally located cells are used. The same dorsoventral distribution of potency is seen in the ability of MZ cells to inhibit epidermal differentiation. In contrast, the ability of MZ cells to induce melanophores shows the reverse polarity, ventral to dorsal. These data indicate that separate developmental mechanisms are used for the induction of neural tube and neural crest lineages. Co-differentiation of CNS neurons or melanophores with epidermal cells can be obtained in a single well of co-cultures of VE cells (150) and a wide range of numbers of MZ cells (5 to 100). Further, reproducible differentiation of both neural lineages requires intimate association between cells from the two gastrula regions; virtually no differentiation is obtained when cells from the VE and MZ are separated in a culture well. These results indicate that the inducing signals from MZ cells for both neural tube and neural

  19. Error estimation in the neural network solution of ordinary differential equations.

    Science.gov (United States)

    Filici, Cristian

    2010-06-01

    In this article a method of error estimation for the neural approximation of the solution of an Ordinary Differential Equation is presented. Some examples of the application of the method support the theory presented. Copyright 2010. Published by Elsevier Ltd.

  20. Covalent growth factor tethering to direct neural stem cell differentiation and self-organization.

    Science.gov (United States)

    Ham, Trevor R; Farrag, Mahmoud; Leipzig, Nic D

    2017-04-15

    Tethered growth factors offer exciting new possibilities for guiding stem cell behavior. However, many of the current methods present substantial drawbacks which can limit their application and confound results. In this work, we developed a new method for the site-specific covalent immobilization of azide-tagged growth factors and investigated its utility in a model system for guiding neural stem cell (NSC) behavior. An engineered interferon-γ (IFN-γ) fusion protein was tagged with an N-terminal azide group, and immobilized to two different dibenzocyclooctyne-functionalized biomimetic polysaccharides (chitosan and hyaluronan). We successfully immobilized azide-tagged IFN-γ under a wide variety of reaction conditions, both in solution and to bulk hydrogels. To understand the interplay between surface chemistry and protein immobilization, we cultured primary rat NSCs on both materials and showed pronounced biological effects. Expectedly, immobilized IFN-γ increased neuronal differentiation on both materials. Expression of other lineage markers varied depending on the material, suggesting that the interplay of surface chemistry and protein immobilization plays a large role in nuanced cell behavior. We also investigated the bioactivity of immobilized IFN-γ in a 3D environment in vivo and found that it sparked the robust formation of neural tube-like structures from encapsulated NSCs. These findings support a wide range of potential uses for this approach and provide further evidence that adult NSCs are capable of self-organization when exposed to the proper microenvironment. For stem cells to be used effectively in regenerative medicine applications, they must be provided with the appropriate cues and microenvironment so that they integrate with existing tissue. This study explores a new method for guiding stem cell behavior: covalent growth factor tethering. We found that adding an N-terminal azide-tag to interferon-γ enabled stable and robust Cu-free 'click

  1. Measuring Customer Behavior with Deep Convolutional Neural Networks

    Directory of Open Access Journals (Sweden)

    Veaceslav Albu

    2016-03-01

    Full Text Available In this paper, we propose a neural network model for human emotion and gesture classification. We demonstrate that the proposed architecture represents an effective tool for real-time processing of customer's behavior for distributed on-land systems, such as information kiosks, automated cashiers and ATMs. The proposed approach combines most recent biometric techniques with the neural network approach for real-time emotion and behavioral analysis. In the series of experiments, emotions of human subjects were recorded, recognized, and analyzed to give statistical feedback of the overall emotions of a number of targets within a certain time frame. The result of the study allows automatic tracking of user’s behavior based on a limited set of observations.

  2. Capacity of Human Dental Follicle Cells to Differentiate into Neural Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Shingo Kanao

    2017-01-01

    Full Text Available The dental follicle is an ectomesenchymal tissue surrounding the developing tooth germ. Human dental follicle cells (hDFCs have the capacity to commit to differentiation into multiple cell types. Here we investigated the capacity of hDFCs to differentiate into neural cells and the efficiency of a two-step strategy involving floating neurosphere-like bodies for neural differentiation. Undifferentiated hDFCs showed a spindle-like morphology and were positive for neural markers such as nestin, β-III-tubulin, and S100β. The cellular morphology of several cells was neuronal-like including branched dendrite-like processes and neurites. Next, hDFCs were used for neurosphere formation in serum-free medium containing basic fibroblast growth factor, epidermal growth factor, and B27 supplement. The number of cells with neuronal-like morphology and that were strongly positive for neural markers increased with sphere formation. Gene expression of neural markers also increased in hDFCs with sphere formation. Next, gene expression of neural markers was examined in hDFCs during neuronal differentiation after sphere formation. Expression of Musashi-1 and Musashi-2, MAP2, GFAP, MBP, and SOX10 was upregulated in hDFCs undergoing neuronal differentiation via neurospheres, whereas expression of nestin and β-III-tubulin was downregulated. In conclusion, hDFCs may be another optimal source of neural/glial cells for cell-based therapies to treat neurological diseases.

  3. Mediator Med23 deficiency enhances neural differentiation of murine embryonic stem cells through modulating BMP signaling.

    Science.gov (United States)

    Zhu, Wanqu; Yao, Xiao; Liang, Yan; Liang, Dan; Song, Lu; Jing, Naihe; Li, Jinsong; Wang, Gang

    2015-02-01

    Unraveling the mechanisms underlying early neural differentiation of embryonic stem cells (ESCs) is crucial to developing cell-based therapies of neurodegenerative diseases. Neural fate acquisition is proposed to be controlled by a 'default' mechanism, for which the molecular regulation is not well understood. In this study, we investigated the functional roles of Mediator Med23 in pluripotency and lineage commitment of murine ESCs. Unexpectedly, we found that, despite the largely unchanged pluripotency and self-renewal of ESCs, Med23 depletion rendered the cells prone to neural differentiation in different differentiation assays. Knockdown of two other Mediator subunits, Med1 and Med15, did not alter the neural differentiation of ESCs. Med15 knockdown selectively inhibited endoderm differentiation, suggesting the specificity of cell fate control by distinctive Mediator subunits. Gene profiling revealed that Med23 depletion attenuated BMP signaling in ESCs. Mechanistically, MED23 modulated Bmp4 expression by controlling the activity of ETS1, which is involved in Bmp4 promoter-enhancer communication. Interestingly, med23 knockdown in zebrafish embryos also enhanced neural development at early embryogenesis, which could be reversed by co-injection of bmp4 mRNA. Taken together, our study reveals an intrinsic, restrictive role of MED23 in early neural development, thus providing new molecular insights for neural fate determination. © 2015. Published by The Company of Biologists Ltd.

  4. The neural basis of visual behaviors in the larval zebrafish.

    Science.gov (United States)

    Portugues, Ruben; Engert, Florian

    2009-12-01

    We review visually guided behaviors in larval zebrafish and summarise what is known about the neural processing that results in these behaviors, paying particular attention to the progress made in the last 2 years. Using the examples of the optokinetic reflex, the optomotor response, prey tracking and the visual startle response, we illustrate how the larval zebrafish presents us with a very promising model vertebrate system that allows neurocientists to integrate functional and behavioral studies and from which we can expect illuminating insights in the near future. Copyright 2009 Elsevier Ltd. All rights reserved.

  5. Dopaminergic differentiation of human neural stem cells mediated by co-cultured rat striatal brain slices

    DEFF Research Database (Denmark)

    Anwar, Mohammad Raffaqat; Andreasen, Christian Maaløv; Lippert, Solvej Kølvraa

    2008-01-01

    differentiation, we co-cultured cells from a human neural forebrain-derived stem cell line (hNS1) with rat striatal brain slices. In brief, coronal slices of neonatal rat striatum were cultured on semiporous membrane inserts placed in six-well trays overlying monolayers of hNS1 cells. After 12 days of co......Properly committed neural stem cells constitute a promising source of cells for transplantation in Parkinson's disease, but a protocol for controlled dopaminergic differentiation is not yet available. To establish a setting for identification of secreted neural compounds promoting dopaminergic...

  6. Early life stress accelerates behavioral and neural maturation of the hippocampus in male mice.

    Science.gov (United States)

    Bath, K; Manzano-Nieves, G; Goodwill, H

    2016-06-01

    Early life stress (ELS) increases the risk for later cognitive and emotional dysfunction. ELS is known to truncate neural development through effects on suppressing cell birth, increasing cell death, and altering neuronal morphology, effects that have been associated with behavioral profiles indicative of precocious maturation. However, how earlier silencing of growth drives accelerated behavioral maturation has remained puzzling. Here, we test the novel hypothesis that, ELS drives a switch from growth to maturation to accelerate neural and behavioral development. To test this, we used a mouse model of ELS, fragmented maternal care, and a cross-sectional dense sampling approach focusing on hippocampus and measured effects of ELS on the ontogeny of behavioral development and biomarkers of neural maturation. Consistent with previous work, ELS was associated with an earlier developmental decline in expression of markers of cell proliferation (Ki-67) and differentiation (doublecortin). However, ELS also led to a precocious arrival of Parvalbumin-positive cells, led to an earlier switch in NMDA receptor subunit expression (marker of synaptic maturity), and was associated with an earlier rise in myelin basic protein expression (key component of the myelin sheath). In addition, in a contextual fear-conditioning task, ELS accelerated the timed developmental suppression of contextual fear. Together, these data provide support for the hypothesis that ELS serves to switch neurodevelopment from processes of growth to maturation and promotes accelerated development of some forms of emotional learning. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Effect of ionizing radiation on the differentiation of neural stem cells

    International Nuclear Information System (INIS)

    Liu Ping; Tu Yu

    2010-01-01

    In order to investigate the effect of ionizing radiation on neural stem cells differentiation, we cultured neural stem cells of newborn rat in serum-free media containing EGF or bFGF. The neural stem cells were divided into 4 groups, which were irradiated by γ-rays with doses of 0, 0.5, 1, and 2 Gy. The irradiated cells were cultured under the same condition for 7 days, and the nestin content of neural stem cell was detected by immunofluorescence. The same method was carried out with irradiated cells in the culture medium after removing EGF, bFGF for 7 days, NSE and GFAP expression content and nestin were also detected by immunofluorescence. It has been found that the irradiated neural stem cells can express less nestin and differentiate more neurons compared to that of control group. Results show that ionizing radiation can induce the differentiation of the neural stem cells and make the neural stem cells differentiate more neuron. (authors)

  8. Cracking the Neural Code for Sensory Perception by Combining Statistics, Intervention, and Behavior.

    Science.gov (United States)

    Panzeri, Stefano; Harvey, Christopher D; Piasini, Eugenio; Latham, Peter E; Fellin, Tommaso

    2017-02-08

    The two basic processes underlying perceptual decisions-how neural responses encode stimuli, and how they inform behavioral choices-have mainly been studied separately. Thus, although many spatiotemporal features of neural population activity, or "neural codes," have been shown to carry sensory information, it is often unknown whether the brain uses these features for perception. To address this issue, we propose a new framework centered on redefining the neural code as the neural features that carry sensory information used by the animal to drive appropriate behavior; that is, the features that have an intersection between sensory and choice information. We show how this framework leads to a new statistical analysis of neural activity recorded during behavior that can identify such neural codes, and we discuss how to combine intersection-based analysis of neural recordings with intervention on neural activity to determine definitively whether specific neural activity features are involved in a task. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. The differentiation of embryonic stem cells seeded on electrospun nanofibers into neural lineages.

    Science.gov (United States)

    Xie, Jingwei; Willerth, Stephanie M; Li, Xiaoran; Macewan, Matthew R; Rader, Allison; Sakiyama-Elbert, Shelly E; Xia, Younan

    2009-01-01

    Due to advances in stem cell biology, embryonic stem (ES) cells can be induced to differentiate into a particular mature cell lineage when cultured as embryoid bodies. Although transplantation of ES cells-derived neural progenitor cells has been demonstrated with some success for either spinal cord injury repair in small animal model, control of ES cell differentiation into complex, viable, higher ordered tissues is still challenging. Mouse ES cells have been induced to become neural progenitors by adding retinoic acid to embryoid body cultures for 4 days. In this study, we examine the use of electrospun biodegradable polymers as scaffolds not only for enhancing the differentiation of mouse ES cells into neural lineages but also for promoting and guiding the neurite outgrowth. A combination of electrospun fiber scaffolds and ES cells-derived neural progenitor cells could lead to the development of a better strategy for nerve injury repair.

  10. Numerical Solution of Fuzzy Differential Equations with Z-numbers Using Bernstein Neural Networks

    Directory of Open Access Journals (Sweden)

    Raheleh Jafari

    2017-01-01

    Full Text Available The uncertain nonlinear systems can be modeled with fuzzy equations or fuzzy differential equations (FDEs by incorporating the fuzzy set theory. The solutions of them are applied to analyze many engineering problems. However, it is very difficult to obtain solutions of FDEs. In this paper, the solutions of FDEs are approximated by two types of Bernstein neural networks. Here, the uncertainties are in the sense of Z-numbers. Initially the FDE is transformed into four ordinary differential equations (ODEs with Hukuhara differentiability. Then neural models are constructed with the structure of ODEs. With modified back propagation method for Z- number variables, the neural networks are trained. The theory analysis and simulation results show that these new models, Bernstein neural networks, are effective to estimate the solutions of FDEs based on Z-numbers.

  11. Neural systems supporting and affecting economically relevant behavior

    Directory of Open Access Journals (Sweden)

    Braeutigam S

    2012-05-01

    Full Text Available Sven BraeutigamOxford Centre for Human Brain Activity, University of Oxford, Oxford, United KingdomAbstract: For about a hundred years, theorists and traders alike have tried to unravel and understand the mechanisms and hidden rules underlying and perhaps determining economically relevant behavior. This review focuses on recent developments in neuroeconomics, where the emphasis is placed on two directions of research: first, research exploiting common experiences of urban inhabitants in industrialized societies to provide experimental paradigms with a broader real-life content; second, research based on behavioral genetics, which provides an additional dimension for experimental control and manipulation. In addition, possible limitations of state-of-the-art neuroeconomics research are addressed. It is argued that observations of neuronal systems involved in economic behavior converge to some extent across the technologies and paradigms used. Conceptually, the data available as of today raise the possibility that neuroeconomic research might provide evidence at the neuronal level for the existence of multiple systems of thought and for the importance of conflict. Methodologically, Bayesian approaches in particular may play an important role in identifying mechanisms and establishing causality between patterns of neural activity and economic behavior.Keywords: neuroeconomics, behavioral genetics, decision-making, consumer behavior, neural system

  12. Replicable Expansion and Differentiation of Neural Precursors from Adult Canine Skin

    Directory of Open Access Journals (Sweden)

    Thomas Duncan

    2017-08-01

    Full Text Available Repopulation of brain circuits by neural precursors is a potential therapeutic strategy for neurodegenerative disorders; however, choice of cell is critical. Previously, we introduced a two-step culture system that generates a high yield of neural precursors from small samples of adult canine skin. Here, we probe their gene and protein expression profiles in comparison with dermal fibroblasts and brain-derived neural stem cells and characterize their neuronal potential. To date, we have produced >50 skin-derived neural precursor (SKN lines. SKNs can be cultured in a highly replicable fashion and uniformly express a panel of identifying markers. Upon differentiation, they self-upregulate neural specification genes, generating neurons with basic electrophysiological functionality. This unique population of neural precursors, derived from mature skin, overcomes many of the practical issues that have limited clinical translation of alternative cell types. Easily accessible, neuronally committed, and patient specific, SKNs may have potential for the treatment of brain disorders.

  13. Neural and Behavioral Correlates of PTSD and Alcohol Use

    Science.gov (United States)

    2014-12-01

    Rezayof A, Hosseini SS, Zarrindast MR (2009) Effects of Morphine on Rat Behaviour in the Elevated Plus Maze: The Role of Central Amygdala Dopamine...The current research takes a multi-level approach to study the psychological , behavioral, cognitive and neural relationships between PTSD and alcohol...presented with combat-associated stimuli, an effect mediated by the anterior cingulate cortex. PTSD was associated with heightened anterior cingulate

  14. The neural and behavioral correlates of social evaluation in childhood

    Directory of Open Access Journals (Sweden)

    Michelle Achterberg

    2017-04-01

    Full Text Available Being accepted or rejected by peers is highly salient for developing social relations in childhood. We investigated the behavioral and neural correlates of social feedback and subsequent aggression in 7–10-year-old children, using the Social Network Aggression Task (SNAT. Participants viewed pictures of peers that gave positive, neutral or negative feedback to the participant’s profile. Next, participants could blast a loud noise towards the peer, as an index of aggression. We included three groups (N = 19, N = 28 and N = 27 and combined the results meta-analytically. Negative social feedback resulted in the most behavioral aggression, with large combined effect-sizes. Whole brain condition effects for each separate sample failed to show robust effects, possibly due to the small samples. Exploratory analyses over the combined test and replication samples confirmed heightened activation in the medial prefrontal cortex (mPFC after negative social feedback. Moreover, meta-analyses of activity in predefined regions of interest showed that negative social feedback resulted in more neural activation in the amygdala, anterior insula and the mPFC/anterior cingulate cortex. Together, the results show that social motivation is already highly salient in middle childhood, and indicate that the SNAT is a valid paradigm for assessing the neural and behavioral correlates of social evaluation in children.

  15. Neural differentiation of mouse embryonic stem cells as a tool to assess developmental neurotoxicity in vitro.

    Science.gov (United States)

    Visan, Anke; Hayess, Katrin; Sittner, Dana; Pohl, Elena E; Riebeling, Christian; Slawik, Birgitta; Gulich, Konrad; Oelgeschläger, Michael; Luch, Andreas; Seiler, Andrea E M

    2012-10-01

    Mouse embryonic stem cells (mESCs) represent an attractive cellular system for in vitro studies in developmental biology as well as toxicology because of their potential to differentiate into all fetal cell lineages. The present study aims to establish an in vitro system for developmental neurotoxicity testing employing mESCs. We developed a robust and reproducible protocol for fast and efficient differentiation of the mESC line D3 into neural cells, optimized with regard to chemical testing. Morphological examination and immunocytochemical staining confirmed the presence of different neural cell types, including neural progenitors, neurons, astrocytes, oligodendrocytes, and radial glial cells. Neurons derived from D3 cells expressed the synaptic proteins PSD95 and synaptophysin, and the neurotransmitters serotonin and γ-aminobutyric acid. Calcium ion imaging revealed the presence of functionally active glutamate and dopamine receptors. In addition, flow cytometry analysis of the neuron-specific marker protein MAP2 on day 12 after induction of differentiation demonstrated a concentration dependent effect of the neurodevelopmental toxicants methylmercury chloride, chlorpyrifos, and lead acetate on neuronal differentiation. The current study shows that D3 mESCs differentiate efficiently into neural cells involving a neurosphere-like state and that this system is suitable to detect adverse effects of neurodevelopmental toxicants. Therefore, we propose that the protocol for differentiation of mESCs into neural cells described here could constitute one component of an in vitro testing strategy for developmental neurotoxicity. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. From behavior to neural dynamics: An integrated theory of attention

    Science.gov (United States)

    Buschman, Timothy J.; Kastner, Sabine

    2015-01-01

    The brain has a limited capacity and therefore needs mechanisms to selectively enhance the information most relevant to one’s current behavior. We refer to these mechanisms as ‘attention’. Attention acts by increasing the strength of selected neural representations and preferentially routing them through the brain’s large-scale network. This is a critical component of cognition and therefore has been a central topic in cognitive neuroscience. Here we review a diverse literature that has studied attention at the level of behavior, networks, circuits and neurons. We then integrate these disparate results into a unified theory of attention. PMID:26447577

  17. Identification of neural transcription factors required for the differentiation of three neuronal subtypes in the sea urchin embryo.

    Science.gov (United States)

    Slota, Leslie A; McClay, David R

    2018-03-15

    Correct patterning of the nervous system is essential for an organism's survival and complex behavior. Embryologists have used the sea urchin as a model for decades, but our understanding of sea urchin nervous system patterning is incomplete. Previous histochemical studies identified multiple neurotransmitters in the pluteus larvae of several sea urchin species. However, little is known about how, where and when neural subtypes are differentially specified during development. Here, we examine the molecular mechanisms of neuronal subtype specification in 3 distinct neural subtypes in the Lytechinus variegatus larva. We show that these subtypes are specified through Delta/Notch signaling and identify a different transcription factor required for the development of each neural subtype. Our results show achaete-scute and neurogenin are proneural for the serotonergic neurons of the apical organ and cholinergic neurons of the ciliary band, respectively. We also show that orthopedia is not proneural but is necessary for the differentiation of the cholinergic/catecholaminergic postoral neurons. Interestingly, these transcription factors are used similarly during vertebrate neurogenesis. We believe this study is a starting point for building a neural gene regulatory network in the sea urchin and for finding conserved deuterostome neurogenic mechanisms. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Differentiation between non-neural and neural contributors to ankle joint stiffness in cerebral palsy

    NARCIS (Netherlands)

    De Gooijer-van de Groep, K.L.; De Vlugt, E.; De Groot, J.H.; Van der Heijden-Maessen, H.C.M.; Wielheesen, D.H.M.; Van Wijlen-Hempel, R.M.S.; Arendzen, J.H.; Meskers, C.G.M.

    2013-01-01

    Background Spastic paresis in cerebral palsy (CP) is characterized by increased joint stiffness that may be of neural origin, i.e. improper muscle activation caused by e.g. hyperreflexia or non-neural origin, i.e. altered tissue viscoelastic properties (clinically: “spasticity” vs. “contracture”).

  19. Slit/Robo1 signaling regulates neural tube development by balancing neuroepithelial cell proliferation and differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Guang; Li, Yan; Wang, Xiao-yu [Key Laboratory for Regenerative Medicine of The Ministry of Education, Department of Histology and Embryology, School of Medicine, Jinan University, Guangzhou 510632 (China); Han, Zhe [Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510224 (China); Chuai, Manli [College of Life Sciences Biocentre, University of Dundee, Dundee DD1 5EH (United Kingdom); Wang, Li-jing [Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510224 (China); Ho Lee, Kenneth Ka [Stem Cell and Regeneration Thematic Research Programme, School of Biomedical Sciences, Chinese University of Hong Kong, Shatin (Hong Kong); Geng, Jian-guo, E-mail: jgeng@umich.edu [Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510224 (China); Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI 48109 (United States); Yang, Xuesong, E-mail: yang_xuesong@126.com [Key Laboratory for Regenerative Medicine of The Ministry of Education, Department of Histology and Embryology, School of Medicine, Jinan University, Guangzhou 510632 (China)

    2013-05-01

    development by tightly coordinating cell proliferation and differentiation during neurulation. - Highlights: ► The role of Slit/Robo1 signaling was investigated with chick and mouse models. ► Disturbance of Slit/Robo1 signaling resulted in neural tube defects. ► Slit/Robo1 signaling regulated the proliferation of neural tube cells. ► Slit/Robo1 signaling modulated the differentiation of neural tube cells. ► Slit/Robo1 signaling balanced the proliferation and differentiation of neural tube.

  20. Differentiation of neurons from neural precursors generated in floating spheres from embryonic stem cells

    Directory of Open Access Journals (Sweden)

    Forrester Jeff

    2009-09-01

    Full Text Available Abstract Background Neural differentiation of embryonic stem (ES cells is usually achieved by induction of ectoderm in embryoid bodies followed by the enrichment of neuronal progenitors using a variety of factors. Obtaining reproducible percentages of neural cells is difficult and the methods are time consuming. Results Neural progenitors were produced from murine ES cells by a combination of nonadherent conditions and serum starvation. Conversion to neural progenitors was accompanied by downregulation of Oct4 and NANOG and increased expression of nestin. ES cells containing a GFP gene under the control of the Sox1 regulatory regions became fluorescent upon differentiation to neural progenitors, and ES cells with a tau-GFP fusion protein became fluorescent upon further differentiation to neurons. Neurons produced from these cells upregulated mature neuronal markers, or differentiated to glial and oligodendrocyte fates. The neurons gave rise to action potentials that could be recorded after application of fixed currents. Conclusion Neural progenitors were produced from murine ES cells by a novel method that induced neuroectoderm cells by a combination of nonadherent conditions and serum starvation, in contrast to the embryoid body method in which neuroectoderm cells must be selected after formation of all three germ layers.

  1. Neural substrates for sexual and thermoregulatory behavior in the male leopard gecko, Eublepharis macularius.

    Science.gov (United States)

    Edwards, Nora; Kriegsfeld, Lance; Crews, David

    2004-12-10

    The preoptic area-anterior hypothalamus (POAH) continuum is critical for the integration of environmental, physiological, and behavioral cues associated with reproduction in vertebrates. In the present study, radiofrequency lesions in the POAH abolished sexual behavior in the leopard gecko (Eublepharis macularius). Furthermore, results suggest a differential effect of POAH lesions on those behaviors regarded as appetitive (tail vibration and grip) and those regarded as consummatory (mounting and copulation), with consummatory behaviors being affected to a greater extent. E. macularius is an ectothermic vertebrate that modulates body temperature behaviorally relative to ambient temperature. In vertebrates, the POAH is also an important integrator of thermoregulation. Thus, the present study investigated whether lesions that disrupt reproductive behavior also disrupt body temperature regulation. While virtually all males displayed diurnal rhythms in thermoregulatory behavior prior to surgery, this pattern was abolished in a small proportion of animals bearing POAH lesions. Lesions that abolished thermoregulatory rhythms involved the suprachiasmatic nucleus (SCN), whereas lesions confined to the POAH, while dramatically influencing sexual behavior, did not affect thermoregulatory rhythms or temperature set point. Together, these findings identify the POAH as an important neural locus regulating sexual behavior but not thermoregulation and suggest that the SCN acts as a pacemaker controlling daily behavioral temperature regulation in this species.

  2. Neural networks dynamic hysteresis model for piezoceramic actuator based on hysteresis operator of first-order differential equation

    International Nuclear Information System (INIS)

    Dang Xuanju; Tan Yonghong

    2005-01-01

    A new neural networks dynamic hysteresis model for piezoceramic actuator is proposed by combining the Preisach model with diagonal recurrent neural networks. The Preisach model is based on elementary rate-independent operators and is not suitable for modeling piezoceramic actuator across a wide frequency band because of the rate-dependent hysteresis characteristic of the piezoceramic actuator. The structure of the developed model is based on the structure of the Preisach model, in which the rate-independent relay hysteresis operators (cells) are replaced by the rate-dependent hysteresis operators of first-order differential equation. The diagonal recurrent neural networks being modified by an adjustable factor can be used to model the hysteresis behavior of the pizeoceramic actuator because its structure is similar to the structure of the modified Preisach model. Therefore, the proposed model not only possesses that of the Preisach model, but also can be used for describing its dynamic hysteresis behavior. Through the experimental results of both the approximation and the prediction, the effectiveness of the neural networks dynamic hysteresis model for the piezoceramic actuator is demonstrated

  3. Power Transformer Differential Protection Based on Neural Network Principal Component Analysis, Harmonic Restraint and Park's Plots

    OpenAIRE

    Tripathy, Manoj

    2012-01-01

    This paper describes a new approach for power transformer differential protection which is based on the wave-shape recognition technique. An algorithm based on neural network principal component analysis (NNPCA) with back-propagation learning is proposed for digital differential protection of power transformer. The principal component analysis is used to preprocess the data from power system in order to eliminate redundant information and enhance hidden pattern of differential current to disc...

  4. IDH1R132H in Neural Stem Cells: Differentiation Impaired by Increased Apoptosis.

    Directory of Open Access Journals (Sweden)

    Kamila Rosiak

    Full Text Available The high frequency of mutations in the isocitrate dehydrogenase 1 (IDH1 gene in diffuse gliomas indicates its importance in the process of gliomagenesis. These mutations result in loss of the normal function and acquisition of the neomorphic activity converting α-ketoglutarate to 2-hydroxyglutarate. This potential oncometabolite may induce the epigenetic changes, resulting in the deregulated expression of numerous genes, including those related to the differentiation process or cell survivability.Neural stem cells were derived from human induced pluripotent stem cells following embryoid body formation. Neural stem cells transduced with mutant IDH1R132H, empty vector, non-transduced and overexpressing IDH1WT controls were differentiated into astrocytes and neurons in culture. The neuronal and astrocytic differentiation was determined by morphology and expression of lineage specific markers (MAP2, Synapsin I and GFAP as determined by real-time PCR and immunocytochemical staining. Apoptosis was evaluated by real-time observation of Caspase-3 activation and measurement of PARP cleavage by Western Blot.Compared with control groups, cells expressing IDH1R132H retained an undifferentiated state and lacked morphological changes following stimulated differentiation. The significant inhibitory effect of IDH1R132H on neuronal and astrocytic differentiation was confirmed by immunocytochemical staining for markers of neural stem cells. Additionally, real-time PCR indicated suppressed expression of lineage markers. High percentage of apoptotic cells was detected within IDH1R132H-positive neural stem cells population and their derivatives, if compared to normal neural stem cells and their derivatives. The analysis of PARP and Caspase-3 activity confirmed apoptosis sensitivity in mutant protein-expressing neural cells.Our study demonstrates that expression of IDH1R132H increases apoptosis susceptibility of neural stem cells and their derivatives. Robust

  5. Differentiation of Equine Mesenchymal Stromal Cells into Cells of Neural Lineage: Potential for Clinical Applications

    Directory of Open Access Journals (Sweden)

    Claudia Cruz Villagrán

    2014-01-01

    Full Text Available Mesenchymal stromal cells (MSCs are able to differentiate into extramesodermal lineages, including neurons. Positive outcomes were obtained after transplantation of neurally induced MSCs in laboratory animals after nerve injury, but this is unknown in horses. Our objectives were to test the ability of equine MSCs to differentiate into cells of neural lineage in vitro, to assess differences in morphology and lineage-specific protein expression, and to investigate if horse age and cell passage number affected the ability to achieve differentiation. Bone marrow-derived MSCs were obtained from young and adult horses. Following demonstration of stemness, MSCs were neurally induced and microscopically assessed at different time points. Results showed that commercially available nitrogen-coated tissue culture plates supported proliferation and differentiation. Morphological changes were immediate and all the cells displayed a neural crest-like cell phenotype. Expression of neural progenitor proteins, was assessed via western blot or immunofluorescence. In our study, MSCs generated from young and middle-aged horses did not show differences in their ability to undergo differentiation. The effect of cell passage number, however, is inconsistent and further experiments are needed. Ongoing work is aimed at transdifferentiating these cells into Schwann cells for transplantation into a peripheral nerve injury model in horses.

  6. Noncoding RNA in the Transcriptional Landscape of Human Neural Progenitor Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Patrick eHecht

    2015-10-01

    Full Text Available Increasing evidence suggests that noncoding RNAs play key roles in cellular processes, particularly in the brain. The present study used RNA sequencing to identify the transcriptional landscape of two human neural progenitor cell lines, SK-N-SH and ReNcell CX, as they differentiate into human cortical projection neurons. Protein coding genes were found to account for 54.8% and 57.0% of expressed genes, respectively, and alignment of RNA sequencing reads revealed that only 25.5-28.1% mapped to exonic regions of the genome. Differential expression analysis in the two cell lines identified altered gene expression in both protein coding and noncoding RNAs as they undergo neural differentiation with 222 differentially expressed genes observed in SK-N-SH cells and 19 differentially expressed genes in ReNcell CX. Interestingly, genes showing differential expression in SK-N-SH cells are enriched in genes implicated in autism spectrum disorder, but not in gene sets related to cancer or Alzheimer’s disease. Weighted gene co-expression network analysis (WGCNA was used to detect modules of co-expressed protein coding and noncoding RNAs in SK-N-SH cells and found four modules to be associated with neural differentiation. These modules contain varying levels of noncoding RNAs ranging from 10.7% to 49.7% with gene ontology suggesting roles in numerous cellular processes important for differentiation. These results indicate that noncoding RNAs are highly expressed in human neural progenitor cells and likely hold key regulatory roles in gene networks underlying neural differentiation and neurodevelopmental disorders.

  7. Neural differentiation of adipose-derived stem cells isolated from GFP transgenic mice

    International Nuclear Information System (INIS)

    Fujimura, Juri; Ogawa, Rei; Mizuno, Hiroshi; Fukunaga, Yoshitaka; Suzuki, Hidenori

    2005-01-01

    Taking advantage of homogeneously marked cells from green fluorescent protein (GFP) transgenic mice, we have recently reported that adipose-derived stromal cells (ASCs) could differentiate into mesenchymal lineages in vitro. In this study, we performed neural induction using ASCs from GFP transgenic mice and were able to induce these ASCs into neuronal and glial cell lineages. Most of the neurally induced cells showed bipolar or multipolar appearance morphologically and expressed neuronal markers. Electron microscopy revealed their neuronal morphology. Some cells also showed glial phenotypes, as shown immunocytochemically. The present study clearly shows that ASCs derived from GFP transgenic mice differentiate into neural lineages in vitro, suggesting that these cells might provide an ideal source for further neural stem cell research with possible therapeutic application for neurological disorders

  8. Differentiation of isolated human umbilical cord mesenchymal stem cells into neural stem cells

    Science.gov (United States)

    Chen, Song; Zhang, Wei; Wang, Ji-Ming; Duan, Hong-Tao; Kong, Jia-Hui; Wang, Yue-Xin; Dong, Meng; Bi, Xue; Song, Jian

    2016-01-01

    AIM To investigate whether umbilical cord human mesenchymal stem cell (UC-MSC) was able to differentiate into neural stem cell and neuron in vitro. METHODS The umbilical cords were obtained from pregnant women with their written consent and the approval of the Clinic Ethnics Committee. UC-MSC were isolated by adherent culture in the medium contains 20% fetal bovine serum (FBS), then they were maintained in the medium contain 10% FBS and induced to neural cells in neural differentiation medium. We investigated whether UC-MSC was able to differentiate into neural stem cell and neuron in vitro by using flow cytometry, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunofluorescence (IF) analyzes. RESULTS A substantial number of UC-MSC was harvested using the tissue explants adherent method at about 2wk. Flow cytometric study revealed that these cells expressed common markers of MSCs, such as CD105 (SH2), CD73 (SH3) and CD90. After induction of differentiation of neural stem cells, the cells began to form clusters; RT-PCR and IF showed that the neuron specific enolase (NSE) and neurogenic differentiation 1-positive cells reached 87.3%±14.7% and 72.6%±11.8%, respectively. Cells showed neuronal cell differentiation after induced, including neuron-like protrusions, plump cell body, obviously and stronger refraction. RT-PCR and IF analysis showed that microtubule-associated protein 2 (MAP2) and nuclear factor-M-positive cells reached 43.1%±10.3% and 69.4%±19.5%, respectively. CONCLUSION Human umbilical cord derived MSCs can be cultured and proliferated in vitro and differentiate into neural stem cells, which may be a valuable source for cell therapy of neurodegenerative eye diseases. PMID:26949608

  9. Differentiation of isolated human umbilical cord mesenchymal stem cells into neural stem cells

    Directory of Open Access Journals (Sweden)

    Song Chen

    2016-01-01

    Full Text Available AIM: To investigate whether umbilical cord human mesenchymal stem cell (UC-MSC was able to differentiate into neural stem cell and neuron in vitro. METHODS: The umbilical cords were obtained from pregnant women with their written consent and the approval of the Clinic Ethnics Committee. UC-MSC were isolated by adherent culture in the medium contains 20% fetal bovine serum (FBS, then they were maintained in the medium contain 10% FBS and induced to neural cells in neural differentiation medium. We investigated whether UC-MSC was able to differentiate into neural stem cell and neuron in vitro by using flow cytometry, reverse transcriptase-polymerase chain reaction (RT-PCR and immunofluorescence (IF analyzes. RESULTS: A substantial number of UC-MSC was harvested using the tissue explants adherent method at about 2wk. Flow cytometric study revealed that these cells expressed common markers of MSCs, such as CD105 (SH2, CD73 (SH3 and CD90. After induction of differentiation of neural stem cells, the cells began to form clusters; RT-PCR and IF showed that the neuron specific enolase (NSE and neurogenic differentiation 1-positive cells reached 87.3%±14.7% and 72.6%±11.8%, respectively. Cells showed neuronal cell differentiation after induced, including neuron-like protrusions, plump cell body, obviously and stronger refraction. RT-PCR and IF analysis showed that microtubule-associated protein 2 (MAP2 and nuclear factor-M-positive cells reached 43.1%±10.3% and 69.4%±19.5%, respectively. CONCLUSION: Human umbilical cord derived MSCs can be cultured and proliferated in vitro and differentiate into neural stem cells, which may be a valuable source for cell therapy of neurodegenerative eye diseases.

  10. Temporally Regulated Neural Crest Transcription Factors Distinguish Neuroectodermal Tumors of Varying Malignancy and Differentiation

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    Timothy R. Gershon

    2005-06-01

    Full Text Available Neuroectodermal tumor cells, like neural crest (NC cells, are pluripotent, proliferative, and migratory. We tested the hypothesis that genetic programs essential to NC development are activated in neuroectodermal tumors. We examined the expression of transcription factors PAX3, PAX7, AP-2α, and SOX10 in human embryos and neuroectodermal tumors: neurofibroma, schwannoma, neuroblastoma, malignant nerve sheath tumor, melanoma, medulloblastoma, supratentorial primitive neuroectodermal tumor, and Ewing's sarcoma. We also examined the expression of P0, ERBB3, and STX, targets of SOX10, AP-2α, and PAX3, respectively. PAX3, AP-2α, and SOX10 were expressed sequentially in human NC development, whereas PAX7 was restricted to mesoderm. Tumors expressed PAX3, AP-2α, SOX10, and PAX7 in specific combinations. SOX10 and AP-2α were expressed in relatively differentiated neoplasms. The early NC marker, PAX3, and its homologue, PAX7, were detected in poorly differentiated tumors and tumors with malignant potential. Expression of NC transcription factors and target genes correlated. Transcription factors essential to NC development are thus present in neuroectodermal tumors. Correlation of specific NC transcription factors with phenotype, and with expression of specific downstream genes, provides evidence that these transcription factors actively influence gene expression and tumor behavior. These findings suggest that PAX3, PAX7, AP-2α, and SOX10 are potential markers of prognosis and targets for therapeutic intervention.

  11. Proteome-wide analysis of neural stem cell differentiation to facilitate transition to cell replacement therapies

    Czech Academy of Sciences Publication Activity Database

    Žižková, Martina; Suchá, Rita; Tylečková, Jiřina; Jarkovská, Karla; Mairychová, Kateřina; Kotrčová, Eva; Marsala, M.; Gadher, S. J.; Kovářová, Hana

    2015-01-01

    Roč. 12, č. 1 (2015), s. 83-95 ISSN 1478-9450 R&D Projects: GA MŠk ED2.1.00/03.0124; GA TA ČR(CZ) TA01011466 Institutional support: RVO:67985904 Keywords : cell therapy * immunomodulation * neural stem cell differentiation * neural subpopulation * neurodegenerative disease Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.465, year: 2015

  12. In vitro differentiation of neural cells from human adipose tissue derived stromal cells.

    Science.gov (United States)

    Dave, Shruti D; Patel, Chetan N; Vanikar, Aruna V; Trivedi, Hargovind L

    2018-01-01

    Stem cells, including neural stem cells (NSCs), are endowed with self-renewal capability and hence hold great opportunity for the institution of replacement/protective therapy. We propose a method for in vitro generation of stromal cells from human adipose tissue and their differentiation into neural cells. Ten grams of donor adipose tissue was surgically resected from the abdominal wall of the human donor after the participants' informed consents. The resected adipose tissue was minced and incubated for 1 hour in the presence of an enzyme (collagenase-type I) at 37 0 C followed by its centrifugation. After centrifugation, the supernatant and pellets were separated and cultured in a medium for proliferation at 37 0 C with 5% CO2 for 9-10 days in separate tissue culture dishes for generation of mesenchymal stromal cells (MSC). At the end of the culture, MSC were harvested and analyzed. The harvested MSC were subjected for further culture for their differentiation into neural cells for 5-7 days using differentiation medium mainly comprising of neurobasal medium. At the end of the procedure, culture cells were isolated and studied for expression of transcriptional factor proteins: orthodenticle homolog-2 (OTX-2), beta-III-tubulin (β3-Tubulin), glial-fibrillary acid protein (GFAP) and synaptophysin-β2. In total, 50 neural cells-lines were generated. In vitro generated MSC differentiated neural cells' mean quantum was 5.4 ± 6.9 ml with the mean cell count being, 5.27 ± 2.65 × 10 3/ μl. All of them showed the presence of OTX-2, β3-Tubulin, GFAP, synaptophysin-β2. Neural cells can be differentiated in vitro from MSC safely and effectively. In vitro generated neural cells represent a potential therapy for recovery from spinal cord injuries and neurodegenerative disease.

  13. Prolonged Expansion Induces Spontaneous Neural Progenitor Differentiation from Human Gingiva-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Rajan, Thangavelu Soundara; Scionti, Domenico; Diomede, Francesca; Piattelli, Adriano; Bramanti, Placido; Mazzon, Emanuela; Trubiani, Oriana

    2017-12-01

    Neural crest-derived mesenchymal stem cells (MSCs) obtained from dental tissues received considerable interest in regenerative medicine, particularly in nerve regeneration owing to their embryonic origin and ease of harvest. Proliferation efficacy and differentiation capacity into diverse cell lineages propose dental MSCs as an in vitro tool for disease modeling. In this study, we investigated the spontaneous differentiation efficiency of dental MSCs obtained from human gingiva tissue (hGMSCs) into neural progenitor cells after extended passaging. At passage 41, the morphology of hGMSCs changed from typical fibroblast-like shape into sphere-shaped cells with extending processes. Next-generation transcriptomics sequencing showed increased expression of neural progenitor markers such as NES, MEIS2, and MEST. In addition, de novo expression of neural precursor genes, such as NRN1, PHOX2B, VANGL2, and NTRK3, was noticed in passage 41. Immunocytochemistry results showed suppression of neurogenesis repressors TP53 and p21, whereas Western blot results revealed the expression of neurotrophic factors BDNF and NT3 at passage 41. Our results showed the spontaneous efficacy of hGMSCs to differentiate into neural precursor cells over prolonged passages and that these cells may assist in producing novel in vitro disease models that are associated with neural development.

  14. In vivo differentiation of induced pluripotent stem cells into neural stem cells by chimera formation.

    Science.gov (United States)

    Choi, Hyun Woo; Hong, Yean Ju; Kim, Jong Soo; Song, Hyuk; Cho, Ssang Gu; Bae, Hojae; Kim, Changsung; Byun, Sung June; Do, Jeong Tae

    2017-01-01

    Like embryonic stem cells, induced pluripotent stem cells (iPSCs) can differentiate into all three germ layers in an in vitro system. Here, we developed a new technology for obtaining neural stem cells (NSCs) from iPSCs through chimera formation, in an in vivo environment. iPSCs contributed to the neural lineage in the chimera, which could be efficiently purified and directly cultured as NSCs in vitro. The iPSC-derived, in vivo-differentiated NSCs expressed NSC markers, and their gene-expression pattern more closely resembled that of fetal brain-derived NSCs than in vitro-differentiated NSCs. This system could be applied for differentiating pluripotent stem cells into specialized cell types whose differentiation protocols are not well established.

  15. An automated high throughput screening-compatible assay to identify regulators of stem cell neural differentiation.

    Science.gov (United States)

    Casalino, Laura; Magnani, Dario; De Falco, Sandro; Filosa, Stefania; Minchiotti, Gabriella; Patriarca, Eduardo J; De Cesare, Dario

    2012-03-01

    The use of Embryonic Stem Cells (ESCs) holds considerable promise both for drug discovery programs and the treatment of degenerative disorders in regenerative medicine approaches. Nevertheless, the successful use of ESCs is still limited by the lack of efficient control of ESC self-renewal and differentiation capabilities. In this context, the possibility to modulate ESC biological properties and to obtain homogenous populations of correctly specified cells will help developing physiologically relevant screens, designed for the identification of stem cell modulators. Here, we developed a high throughput screening-suitable ESC neural differentiation assay by exploiting the Cell(maker) robotic platform and demonstrated that neural progenies can be generated from ESCs in complete automation, with high standards of accuracy and reliability. Moreover, we performed a pilot screening providing proof of concept that this assay allows the identification of regulators of ESC neural differentiation in full automation.

  16. Aging differentially affects male and female neural stem cell neurogenic properties

    Directory of Open Access Journals (Sweden)

    Jay Waldron

    2010-09-01

    Full Text Available Jay Waldron1, Althea McCourty1, Laurent Lecanu1,21The Research Institute of the McGill University Health Centre, Montreal, Canada; 2Department of Medicine, McGill University, Montreal, Quebec, CanadaPurpose: Neural stem cell transplantation as a brain repair strategy is a very promising technology. However, despite many attempts, the clinical success remains very deceiving. Despite clear evidence that sexual dimorphism rules many aspects of human biology, the occurrence of a sex difference in neural stem cell biology is largely understudied. Herein, we propose to determine whether gender is a dimension that drives the fate of neural stem cells through aging. Should it occur, we believe that neural stem cell sexual dimorphism and its variation during aging should be taken into account to refine clinical approaches of brain repair strategies.Methods: Neural stem cells were isolated from the subventricular zone of three- and 20-month-old male and female Long-Evans rats. Expression of the estrogen receptors, ERα and ERβ, progesterone receptor, androgen receptor, and glucocorticoid receptor was analyzed and quantified by Western blotting on undifferentiated neural stem cells. A second set of neural stem cells was treated with retinoic acid to trigger differentiation, and the expression of neuronal, astroglial, and oligodendroglial markers was determined using Western blotting.Conclusion: We provided in vitro evidence that the fate of neural stem cells is affected by sex and aging. Indeed, young male neural stem cells mainly expressed markers of neuronal and oligodendroglial fate, whereas young female neural stem cells underwent differentiation towards an astroglial phenotype. Aging resulted in a lessened capacity to express neuron and astrocyte markers. Undifferentiated neural stem cells displayed sexual dimorphism in the expression of steroid receptors, in particular ERα and ERβ, and the expression level of several steroid receptors increased

  17. applications of artificial neural networks to resolution of differential ...

    African Journals Online (AJOL)

    spisska

    Disturbed Differential Pulse Polarographic Peaks in the Region of Hydrogen ... represent the experimental behaviour of the system when the exact description is ... equations and the values of physico-chemical constants.8 The characteristics ...

  18. MicroRNA let-7b regulates neural stem cell proliferation and differentiation by targeting nuclear receptor TLX signaling.

    Science.gov (United States)

    Zhao, Chunnian; Sun, GuoQiang; Li, Shengxiu; Lang, Ming-Fei; Yang, Su; Li, Wendong; Shi, Yanhong

    2010-02-02

    Neural stem cell self-renewal and differentiation is orchestrated by precise control of gene expression involving nuclear receptor TLX. Let-7b, a member of the let-7 microRNA family, is expressed in mammalian brains and exhibits increased expression during neural differentiation. However, the role of let-7b in neural stem cell proliferation and differentiation remains unknown. Here we show that let-7b regulates neural stem cell proliferation and differentiation by targeting the stem cell regulator TLX and the cell cycle regulator cyclin D1. Overexpression of let-7b led to reduced neural stem cell proliferation and increased neural differentiation, whereas antisense knockdown of let-7b resulted in enhanced proliferation of neural stem cells. Moreover, in utero electroporation of let-7b to embryonic mouse brains led to reduced cell cycle progression in neural stem cells. Introducing an expression vector of Tlx or cyclin D1 that lacks the let-7b recognition site rescued let-7b-induced proliferation deficiency, suggesting that both TLX and cyclin D1 are important targets for let-7b-mediated regulation of neural stem cell proliferation. Let-7b, by targeting TLX and cyclin D1, establishes an efficient strategy to control neural stem cell proliferation and differentiation.

  19. Microscale architecture in biomaterial scaffolds for spatial control of neural cell behavior

    Science.gov (United States)

    Meco, Edi; Lampe, Kyle J.

    2018-02-01

    Biomaterial scaffolds mimic aspects of the native central nervous system (CNS) extracellular matrix (ECM) and have been extensively utilized to influence neural cell (NC) behavior in in vitro and in vivo settings. These biomimetic scaffolds support NC cultures, can direct the differentiation of NCs, and have recapitulated some native NC behavior in an in vitro setting. However, NC transplant therapies and treatments used in animal models of CNS disease and injury have not fully restored functionality. The observed lack of functional recovery occurs despite improvements in transplanted NC viability when incorporating biomaterial scaffolds and the potential of NC to replace damaged native cells. The behavior of NCs within biomaterial scaffolds must be directed in order to improve the efficacy of transplant therapies and treatments. Biomaterial scaffold topography and imbedded bioactive cues, designed at the microscale level, can alter NC phenotype, direct migration, and differentiation. Microscale patterning in biomaterial scaffolds for spatial control of NC behavior has enhanced the capabilities of in vitro models to capture properties of the native CNS tissue ECM. Patterning techniques such as lithography, electrospinning and 3D bioprinting can be employed to design the microscale architecture of biomaterial scaffolds. Here, the progress and challenges of the prevalent biomaterial patterning techniques of lithography, electrospinning, and 3D bioprinting are reported. This review analyzes NC behavioral response to specific microscale topographical patterns and spatially organized bioactive cues.

  20. Microscale Architecture in Biomaterial Scaffolds for Spatial Control of Neural Cell Behavior

    Directory of Open Access Journals (Sweden)

    Edi Meco

    2018-02-01

    Full Text Available Biomaterial scaffolds mimic aspects of the native central nervous system (CNS extracellular matrix (ECM and have been extensively utilized to influence neural cell (NC behavior in in vitro and in vivo settings. These biomimetic scaffolds support NC cultures, can direct the differentiation of NCs, and have recapitulated some native NC behavior in an in vitro setting. However, NC transplant therapies and treatments used in animal models of CNS disease and injury have not fully restored functionality. The observed lack of functional recovery occurs despite improvements in transplanted NC viability when incorporating biomaterial scaffolds and the potential of NC to replace damaged native cells. The behavior of NCs within biomaterial scaffolds must be directed in order to improve the efficacy of transplant therapies and treatments. Biomaterial scaffold topography and imbedded bioactive cues, designed at the microscale level, can alter NC phenotype, direct migration, and differentiation. Microscale patterning in biomaterial scaffolds for spatial control of NC behavior has enhanced the capabilities of in vitro models to capture properties of the native CNS tissue ECM. Patterning techniques such as lithography, electrospinning and three-dimensional (3D bioprinting can be employed to design the microscale architecture of biomaterial scaffolds. Here, the progress and challenges of the prevalent biomaterial patterning techniques of lithography, electrospinning, and 3D bioprinting are reported. This review analyzes NC behavioral response to specific microscale topographical patterns and spatially organized bioactive cues.

  1. Long Noncoding RNA-1604 Orchestrates Neural Differentiation through the miR-200c/ZEB Axis.

    Science.gov (United States)

    Weng, Rong; Lu, Chenqi; Liu, Xiaoqin; Li, Guoping; Lan, Yuanyuan; Qiao, Jing; Bai, Mingliang; Wang, Zhaojie; Guo, Xudong; Ye, Dan; Jiapaer, Zeyidan; Yang, Yiwei; Xia, Chenliang; Wang, Guiying; Kang, Jiuhong

    2018-03-01

    Clarifying the regulatory mechanisms of embryonic stem cell (ESC) neural differentiation is helpful not only for understanding neural development but also for obtaining high-quality neural progenitor cells required by stem cell therapy of neurodegenerative diseases. Here, we found that long noncoding RNA 1604 (lncRNA-1604) was highly expressed in cytoplasm during neural differentiation, and knockdown of lncRNA-1604 significantly repressed neural differentiation of mouse ESCs both in vitro and in vivo. Bioinformatics prediction and mechanistic analysis revealed that lncRNA-1604 functioned as a novel competing endogenous RNA of miR-200c and regulated the core transcription factors ZEB1 and ZEB2 during neural differentiation. Furthermore, we also demonstrated the critical role of miR-200c and ZEB1/2 in mouse neural differentiation. Either introduction of miR-200c sponge or overexpression of ZEB1/2 significantly reversed the lncRNA-1604 knockdown-induced repression of mouse ESC neural differentiation. Collectively, these findings not only identified a previously unknown role of lncRNA-1604 and ZEB1/2 but also elucidated a new regulatory lncRNA-1604/miR-200c/ZEB axis in neural differentiation. Stem Cells 2018;36:325-336. © 2017 AlphaMed Press.

  2. Alternating current electric field effects on neural stem cell viability and differentiation.

    Science.gov (United States)

    Matos, Marvi A; Cicerone, Marcus T

    2010-01-01

    Methods utilizing stem cells hold tremendous promise for tissue engineering applications; however, many issues must be worked out before these therapies can be routinely applied. Utilization of external cues for preimplantation expansion and differentiation offers a potentially viable approach to the use of stem cells in tissue engineering. The studies reported here focus on the response of murine neural stem cells encapsulated in alginate hydrogel beads to alternating current electric fields. Cell viability and differentiation was studied as a function of electric field magnitude and frequency. We applied fields of frequency (0.1-10) Hz, and found a marked peak in neural stem cell viability under oscillatory electric fields with a frequency of 1 Hz. We also found an enhanced propensity for astrocyte differentiation over neuronal differentiation in the 1 Hz cultures, as compared to the other field frequencies we studied. Published 2010 American Institute of Chemical Engineers

  3. Proposers’ Economic Status Affects Behavioral and Neural Responses to Unfairness

    Directory of Open Access Journals (Sweden)

    Yijie Zheng

    2017-05-01

    Full Text Available Economic status played an important role in the modulation of economic decision making. The present fMRI study aimed at investigating how economic status modulated behavioral and neural responses to unfairness in a modified Ultimatum Game (UG. During scanning, participants played as responders in the UG, and they were informed of the economic status of proposers before receiving offers. At the behavioral level, higher rejection rates and lower fairness ratings were revealed when proposers were in high economic status than in low economic status. Besides, the most time-consuming decisions tended to occur at lower unfairness level when the proposers were in high (relative to low economic status. At the neural level, stronger activation of left thalamus was revealed when fair offers were proposed by proposers in high rather than in low economic status. Greater activation of right medial prefrontal cortex was revealed during acceptance to unfair offers in high economic status condition rather than in low economic status condition. Taken together, these findings shed light on the significance of proposers’ economic status in responders’ social decision making in UG.

  4. Novel perspectives of neural stem cell differentiation: from neurotransmitters to therapeutics.

    Science.gov (United States)

    Trujillo, Cleber A; Schwindt, Telma T; Martins, Antonio H; Alves, Janaína M; Mello, Luiz Eugênio; Ulrich, Henning

    2009-01-01

    In the past years, many reports have described the existence of neural progenitor and stem cells in the adult central nervous system capable of generating new neurons, astrocytes, and oligodendrocytes. This discovery has overturned the central assumption in the neuroscience field, of no new neurons being originated in the brain after birth and provided the fundaments to understand the molecular basis of neural differentiation and to develop new therapies for neural tissue repair. Although the mechanisms underlying cell fate during neural development are not yet understood, the importance of intrinsic and extrinsic factors and of an appropriate microenvironment is well known. In this context, emerging evidence strongly suggests that glial cells play a key role in controlling multiple steps of neurogenesis. Those cells, of particular radial glia, are important for migration, cell specification, and integration of neurons into a functional neural network. This review aims to present an update in the neurogenesis area and highlight the modulation of neural stem cell differentiation by neurotransmitters, growth factors, and their receptors, with possible applications for cell therapy strategies of neurological disorders.

  5. Neural foundations to moral reasoning and antisocial behavior

    Science.gov (United States)

    Yang, Yaling

    2006-01-01

    A common feature of the antisocial, rule-breaking behavior that is central to criminal, violent and psychopathic individuals is the failure to follow moral guidelines. This review summarizes key findings from brain imaging research on both antisocial behavior and moral reasoning, and integrates these findings into a neural moral model of antisocial behavior. Key areas found to be functionally or structurally impaired in antisocial populations include dorsal and ventral regions of the prefrontal cortex (PFC), amygdala, hippocampus, angular gyrus, anterior cingulate and temporal cortex. Regions most commonly activated in moral judgment tasks consist of the polar/medial and ventral PFC, amygdala, angular gyrus and posterior cingulate. It is hypothesized that the rule-breaking behavior common to antisocial, violent and psychopathic individuals is in part due to impairments in some of the structures (dorsal and ventral PFC, amygdala and angular gyrus) subserving moral cognition and emotion. Impairments to the emotional component that comprises the feeling of what is moral is viewed as the primary deficit in antisocials, although some disruption to the cognitive and cognitive-emotional components of morality (particularly self-referential thinking and emotion regulation) cannot be ruled out. While this neurobiological predisposition is likely only one of several biosocial processes involved in the etiology of antisocial behavior, it raises significant moral issues for the legal system and neuroethics. PMID:18985107

  6. FGF signalling regulates chromatin organisation during neural differentiation via mechanisms that can be uncoupled from transcription.

    Directory of Open Access Journals (Sweden)

    Nishal S Patel

    Full Text Available Changes in higher order chromatin organisation have been linked to transcriptional regulation; however, little is known about how such organisation alters during embryonic development or how it is regulated by extrinsic signals. Here we analyse changes in chromatin organisation as neural differentiation progresses, exploiting the clear spatial separation of the temporal events of differentiation along the elongating body axis of the mouse embryo. Combining fluorescence in situ hybridisation with super-resolution structured illumination microscopy, we show that chromatin around key differentiation gene loci Pax6 and Irx3 undergoes both decompaction and displacement towards the nuclear centre coincident with transcriptional onset. Conversely, down-regulation of Fgf8 as neural differentiation commences correlates with a more peripheral nuclear position of this locus. During normal neural differentiation, fibroblast growth factor (FGF signalling is repressed by retinoic acid, and this vitamin A derivative is further required for transcription of neural genes. We show here that exposure to retinoic acid or inhibition of FGF signalling promotes precocious decompaction and central nuclear positioning of differentiation gene loci. Using the Raldh2 mutant as a model for retinoid deficiency, we further find that such changes in higher order chromatin organisation are dependent on retinoid signalling. In this retinoid deficient condition, FGF signalling persists ectopically in the elongating body, and importantly, we find that inhibiting FGF receptor (FGFR signalling in Raldh2-/- embryos does not rescue differentiation gene transcription, but does elicit both chromatin decompaction and nuclear position change. These findings demonstrate that regulation of higher order chromatin organisation during differentiation in the embryo can be uncoupled from the machinery that promotes transcription and, for the first time, identify FGF as an extrinsic signal that

  7. Neural mechanisms of context-dependent processing of CO2 avoidance behavior in fruit flies.

    Science.gov (United States)

    Siju, K P; Bräcker, Lasse B; Grunwald Kadow, I C

    2014-01-01

    The fruit fly, Drosophila melanogaster, innately avoids even low levels of CO2. CO2 is part of the so-called Drosophila stress odor produced by stressed flies, but also a byproduct of fermenting fruit, a main food source, making the strong avoidance behavior somewhat surprising. Therefore, we addressed whether feeding states might influence the fly's behavior and processing of CO2. In a recent report, we showed that this innate behavior is differentially processed and modified according to the feeding state of the fly. Interestingly, we found that hungry flies require the function of the mushroom body, a higher brain center required for olfactory learning and memory, but thought to be dispensable for innate olfactory behaviors. In addition, we anatomically and functionally characterized a novel bilateral projection neuron connecting the CO2 sensory input to the mushroom body. This neuron was essential for processing of CO2 in the starved fly but not in the fed fly. In this Extra View article, we provide evidence for the potential involvement of the neuromodulator dopamine in state-dependent CO2 avoidance behavior. Taken together, our work demonstrates that CO2 avoidance behavior is mediated by alternative neural pathways in a context-dependent manner. Furthermore, it shows that the mushroom body is not only involved in processing of learned olfactory behavior, as previously suggested, but also in context-dependent innate olfaction.

  8. Neural plasticity and behavior - sixty years of conceptual advances.

    Science.gov (United States)

    Sweatt, J David

    2016-10-01

    This brief review summarizes 60 years of conceptual advances that have demonstrated a role for active changes in neuronal connectivity as a controller of behavior and behavioral change. Seminal studies in the first phase of the six-decade span of this review firmly established the cellular basis of behavior - a concept that we take for granted now, but which was an open question at the time. Hebbian plasticity, including long-term potentiation and long-term depression, was then discovered as being important for local circuit refinement in the context of memory formation and behavioral change and stabilization in the mammalian central nervous system. Direct demonstration of plasticity of neuronal circuit function in vivo, for example, hippocampal neurons forming place cell firing patterns, extended this concept. However, additional neurophysiologic and computational studies demonstrated that circuit development and stabilization additionally relies on non-Hebbian, homoeostatic, forms of plasticity, such as synaptic scaling and control of membrane intrinsic properties. Activity-dependent neurodevelopment was found to be associated with cell-wide adjustments in post-synaptic receptor density, and found to occur in conjunction with synaptic pruning. Pioneering cellular neurophysiologic studies demonstrated the critical roles of transmembrane signal transduction, NMDA receptor regulation, regulation of neural membrane biophysical properties, and back-propagating action potential in critical time-dependent coincidence detection in behavior-modifying circuits. Concerning the molecular mechanisms underlying these processes, regulation of gene transcription was found to serve as a bridge between experience and behavioral change, closing the 'nature versus nurture' divide. Both active DNA (de)methylation and regulation of chromatin structure have been validated as crucial regulators of gene transcription during learning. The discovery of protein synthesis dependence on the

  9. Expression of cardiac neural crest and heart genes isolated by modified differential display.

    Science.gov (United States)

    Martinsen, Brad J; Groebner, Nathan J; Frasier, Allison J; Lohr, Jamie L

    2003-08-01

    The invasion of the cardiac neural crest (CNC) into the outflow tract (OFT) and subsequent outflow tract septation are critical events during vertebrate heart development. We have performed four modified differential display screens in the chick embryo to identify genes that may be involved in CNC, OFT, secondary heart field, and heart development. The screens included differential display of RNA isolated from three different axial segments containing premigratory cranial neural crest cells; of RNA from distal outflow tract, proximal outflow tract, and atrioventricular tissue of embryonic chick hearts; and of RNA isolated from left and right cranial tissues, including the early heart fields. These screens have resulted in the identification of the five cDNA clones presented here, which are expressed in the cardiac neural crest, outflow tract and developing heart in patterns that are unique in heart development.

  10. Neural Differentiation of Lexico-Syntactic Categories or Semantic Features?

    NARCIS (Netherlands)

    Kellenbach, ML; Wijers, AA; Hovius, M; Mulder, Juul; Mulder, Gysbertus

    2002-01-01

    Event-related potentials (ERPs) were used to investigate whether processing differences between nouns and verbs can be accounted for by the differential salience of visual-perceptual and motor attributes in their semantic specifications. Three subclasses of nouns and verbs were selected, which

  11. Pulsed DC Electric Field-Induced Differentiation of Cortical Neural Precursor Cells.

    Directory of Open Access Journals (Sweden)

    Hui-Fang Chang

    Full Text Available We report the differentiation of neural stem and progenitor cells solely induced by direct current (DC pulses stimulation. Neural stem and progenitor cells in the adult mammalian brain are promising candidates for the development of therapeutic neuroregeneration strategies. The differentiation of neural stem and progenitor cells depends on various in vivo environmental factors, such as nerve growth factor and endogenous EF. In this study, we demonstrated that the morphologic and phenotypic changes of mouse neural stem and progenitor cells (mNPCs could be induced solely by exposure to square-wave DC pulses (magnitude 300 mV/mm at frequency of 100-Hz. The DC pulse stimulation was conducted for 48 h, and the morphologic changes of mNPCs were monitored continuously. The length of primary processes and the amount of branching significantly increased after stimulation by DC pulses for 48 h. After DC pulse treatment, the mNPCs differentiated into neurons, astrocytes, and oligodendrocytes simultaneously in stem cell maintenance medium. Our results suggest that simple DC pulse treatment could control the fate of NPCs. With further studies, DC pulses may be applied to manipulate NPC differentiation and may be used for the development of therapeutic strategies that employ NPCs to treat nervous system disorders.

  12. Properties of Neural Crest-Like Cells Differentiated from Human Embryonic Stem Cells

    Czech Academy of Sciences Publication Activity Database

    Křivánek, J.; Švandová, Eva; Králik, J.; Hajda, S.; Fedr, Radek; Vinařský, V.; Jaroš, J.; Souček, Karel

    2014-01-01

    Roč. 60, č. 2014 (2014), s. 30-38 ISSN 0015-5500 R&D Projects: GA ČR(CZ) GAP304/11/1418 Institutional support: RVO:68081707 Keywords : stem cell differentiation * neural crest * odontogenesis Subject RIV: BO - Biophysics; ED - Physiology (UZFG-Y) Impact factor: 1.000, year: 2014

  13. Pulsed DC Electric Field-Induced Differentiation of Cortical Neural Precursor Cells.

    Science.gov (United States)

    Chang, Hui-Fang; Lee, Ying-Shan; Tang, Tang K; Cheng, Ji-Yen

    2016-01-01

    We report the differentiation of neural stem and progenitor cells solely induced by direct current (DC) pulses stimulation. Neural stem and progenitor cells in the adult mammalian brain are promising candidates for the development of therapeutic neuroregeneration strategies. The differentiation of neural stem and progenitor cells depends on various in vivo environmental factors, such as nerve growth factor and endogenous EF. In this study, we demonstrated that the morphologic and phenotypic changes of mouse neural stem and progenitor cells (mNPCs) could be induced solely by exposure to square-wave DC pulses (magnitude 300 mV/mm at frequency of 100-Hz). The DC pulse stimulation was conducted for 48 h, and the morphologic changes of mNPCs were monitored continuously. The length of primary processes and the amount of branching significantly increased after stimulation by DC pulses for 48 h. After DC pulse treatment, the mNPCs differentiated into neurons, astrocytes, and oligodendrocytes simultaneously in stem cell maintenance medium. Our results suggest that simple DC pulse treatment could control the fate of NPCs. With further studies, DC pulses may be applied to manipulate NPC differentiation and may be used for the development of therapeutic strategies that employ NPCs to treat nervous system disorders.

  14. The Neural Basis of and a Common Neural Circuitry in Different Types of Pro-social Behavior

    Directory of Open Access Journals (Sweden)

    Jun Luo

    2018-06-01

    Full Text Available Pro-social behaviors are voluntary behaviors that benefit other people or society as a whole, such as charitable donations, cooperation, trust, altruistic punishment, and fairness. These behaviors have been widely described through non self-interest decision-making in behavioral experimental studies and are thought to be increased by social preference motives. Importantly, recent studies using a combination of neuroimaging and brain stimulation, designed to reveal the neural mechanisms of pro-social behaviors, have found that a wide range of brain areas, specifically the prefrontal cortex, anterior insula, anterior cingulate cortex, and amygdala, are correlated or causally related with pro-social behaviors. In this review, we summarize the research on the neural basis of various kinds of pro-social behaviors and describe a common shared neural circuitry of these pro-social behaviors. We introduce several general ways in which experimental economics and neuroscience can be combined to develop important contributions to understanding social decision-making and pro-social behaviors. Future research should attempt to explore the neural circuitry between the frontal lobes and deeper brain areas.

  15. Differentiation-Dependent Motility-Responses of Developing Neural Progenitors to Optogenetic Stimulation

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    Tímea Köhidi

    2017-12-01

    Full Text Available During neural tissue genesis, neural stem/progenitor cells are exposed to bioelectric stimuli well before synaptogenesis and neural circuit formation. Fluctuations in the electrochemical potential in the vicinity of developing cells influence the genesis, migration and maturation of neuronal precursors. The complexity of the in vivo environment and the coexistence of various progenitor populations hinder the understanding of the significance of ionic/bioelectric stimuli in the early phases of neuronal differentiation. Using optogenetic stimulation, we investigated the in vitro motility responses of radial glia-like neural stem/progenitor populations to ionic stimuli. Radial glia-like neural stem cells were isolated from CAGloxpStoploxpChR2(H134-eYFP transgenic mouse embryos. After transfection with Cre-recombinase, ChR2(channelrhodopsin-2-expressing and non-expressing cells were separated by eYFP fluorescence. Expression of light-gated ion channels were checked by patch clamp and fluorescence intensity assays. Neurogenesis by ChR2-expressing and non-expressing cells was induced by withdrawal of EGF from the medium. Cells in different (stem cell, migrating progenitor and maturing precursor stages of development were illuminated with laser light (λ = 488 nm; 1.3 mW/mm2; 300 ms in every 5 min for 12 h. The displacement of the cells was analyzed on images taken at the end of each light pulse. Results demonstrated that the migratory activity decreased with the advancement of neuronal differentiation regardless of stimulation. Light-sensitive cells, however, responded on a differentiation-dependent way. In non-differentiated ChR2-expressing stem cell populations, the motility did not change significantly in response to light-stimulation. The displacement activity of migrating progenitors was enhanced, while the motility of differentiating neuronal precursors was markedly reduced by illumination.

  16. Targeted neural differentiation of murine mesenchymal stem cells by a protocol simulating the inflammatory site of neural injury

    Czech Academy of Sciences Publication Activity Database

    Chudíčková, Milada; Brůža, M.; Zajícová, Alena; Trošan, Peter; Svobodová, Lucie; Javorková, Eliška; Kubinová, Šárka; Holáň, Vladimír

    2017-01-01

    Roč. 11, č. 5 (2017), s. 1588-1597 ISSN 1932-6254 R&D Projects: GA ČR(CZ) GAP304/11/0653; GA ČR(CZ) GA14-12580S; GA ČR(CZ) GAP301/11/1568; GA MŠk(CZ) ED1.1.00/02.0109; GA MŠk(CZ) LO1309 Institutional support: RVO:68378041 Keywords : mouse * adipose-derived mesenchymal stem cells * neural differentiation Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Cell biology Impact factor: 3.989, year: 2016

  17. Selective neuronal differentiation of neural stem cells induced by nanosecond microplasma agitation.

    Science.gov (United States)

    Xiong, Z; Zhao, S; Mao, X; Lu, X; He, G; Yang, G; Chen, M; Ishaq, M; Ostrikov, K

    2014-03-01

    An essential step for therapeutic and research applications of stem cells is their ability to differentiate into specific cell types. Neuronal cells are of great interest for medical treatment of neurodegenerative diseases and traumatic injuries of central nervous system (CNS), but efforts to produce these cells have been met with only modest success. In an attempt of finding new approaches, atmospheric-pressure room-temperature microplasma jets (MPJs) are shown to effectively direct in vitro differentiation of neural stem cells (NSCs) predominantly into neuronal lineage. Murine neural stem cells (C17.2-NSCs) treated with MPJs exhibit rapid proliferation and differentiation with longer neurites and cell bodies eventually forming neuronal networks. MPJs regulate ~75% of NSCs to differentiate into neurons, which is a higher efficiency compared to common protein- and growth factors-based differentiation. NSCs exposure to quantized and transient (~150 ns) micro-plasma bullets up-regulates expression of different cell lineage markers as β-Tubulin III (for neurons) and O4 (for oligodendrocytes), while the expression of GFAP (for astrocytes) remains unchanged, as evidenced by quantitative PCR, immunofluorescence microscopy and Western Blot assay. It is shown that the plasma-increased nitric oxide (NO) production is a factor in the fate choice and differentiation of NSCs followed by axonal growth. The differentiated NSC cells matured and produced mostly cholinergic and motor neuronal progeny. It is also demonstrated that exposure of primary rat NSCs to the microplasma leads to quite similar differentiation effects. This suggests that the observed effect may potentially be generic and applicable to other types of neural progenitor cells. The application of this new in vitro strategy to selectively differentiate NSCs into neurons represents a step towards reproducible and efficient production of the desired NSC derivatives. Published by Elsevier B.V.

  18. Selective neuronal differentiation of neural stem cells induced by nanosecond microplasma agitation

    Directory of Open Access Journals (Sweden)

    Z. Xiong

    2014-03-01

    Full Text Available An essential step for therapeutic and research applications of stem cells is their ability to differentiate into specific cell types. Neuronal cells are of great interest for medical treatment of neurodegenerative diseases and traumatic injuries of central nervous system (CNS, but efforts to produce these cells have been met with only modest success. In an attempt of finding new approaches, atmospheric-pressure room-temperature microplasma jets (MPJs are shown to effectively direct in vitro differentiation of neural stem cells (NSCs predominantly into neuronal lineage. Murine neural stem cells (C17.2-NSCs treated with MPJs exhibit rapid proliferation and differentiation with longer neurites and cell bodies eventually forming neuronal networks. MPJs regulate ~75% of NSCs to differentiate into neurons, which is a higher efficiency compared to common protein- and growth factors-based differentiation. NSCs exposure to quantized and transient (~150 ns micro-plasma bullets up-regulates expression of different cell lineage markers as β-Tubulin III (for neurons and O4 (for oligodendrocytes, while the expression of GFAP (for astrocytes remains unchanged, as evidenced by quantitative PCR, immunofluorescence microscopy and Western Blot assay. It is shown that the plasma-increased nitric oxide (NO production is a factor in the fate choice and differentiation of NSCs followed by axonal growth. The differentiated NSC cells matured and produced mostly cholinergic and motor neuronal progeny. It is also demonstrated that exposure of primary rat NSCs to the microplasma leads to quite similar differentiation effects. This suggests that the observed effect may potentially be generic and applicable to other types of neural progenitor cells. The application of this new in vitro strategy to selectively differentiate NSCs into neurons represents a step towards reproducible and efficient production of the desired NSC derivatives.

  19. Rolling Force Prediction in Heavy Plate Rolling Based on Uniform Differential Neural Network

    Directory of Open Access Journals (Sweden)

    Fei Zhang

    2016-01-01

    Full Text Available Accurate prediction of the rolling force is critical to assuring the quality of the final product in steel manufacturing. Exit thickness of plate for each pass is calculated from roll gap, mill spring, and predicted roll force. Ideal pass scheduling is dependent on a precise prediction of the roll force in each pass. This paper will introduce a concept that allows obtaining the material model parameters directly from the rolling process on an industrial scale by the uniform differential neural network. On the basis of the characteristics that the uniform distribution can fully characterize the solution space and enhance the diversity of the population, uniformity research on differential evolution operator is made to get improved crossover with uniform distribution. When its original function is transferred with a transfer function, the uniform differential evolution algorithms can quickly solve complex optimization problems. Neural network structure and weights threshold are optimized by uniform differential evolution algorithm, and a uniform differential neural network is formed to improve rolling force prediction accuracy in process control system.

  20. Arctigenin protects against neuronal hearing loss by promoting neural stem cell survival and differentiation.

    Science.gov (United States)

    Huang, Xinghua; Chen, Mo; Ding, Yan; Wang, Qin

    2017-03-01

    Neuronal hearing loss has become a prevalent health problem. This study focused on the function of arctigenin (ARC) in promoting survival and neuronal differentiation of mouse cochlear neural stem cells (NSCs), and its protection against gentamicin (GMC) induced neuronal hearing loss. Mouse cochlea was used to isolate NSCs, which were subsequently cultured in vitro. The effects of ARC on NSC survival, neurosphere formation, differentiation of NSCs, neurite outgrowth, and neural excitability in neuronal network in vitro were examined. Mechanotransduction ability demonstrated by intact cochlea, auditory brainstem response (ABR), and distortion product optoacoustic emissions (DPOAE) amplitude in mice were measured to evaluate effects of ARC on GMC-induced neuronal hearing loss. ARC increased survival, neurosphere formation, neuron differentiation of NSCs in mouse cochlear in vitro. ARC also promoted the outgrowth of neurites, as well as neural excitability of the NSC-differentiated neuron culture. Additionally, ARC rescued mechanotransduction capacity, restored the threshold shifts of ABR and DPOAE in our GMC ototoxicity murine model. This study supports the potential therapeutic role of ARC in promoting both NSCs proliferation and differentiation in vitro to functional neurons, thus supporting its protective function in the therapeutic treatment of neuropathic hearing loss in vivo. © 2017 Wiley Periodicals, Inc.

  1. 3D porous chitosan scaffolds suit survival and neural differentiation of dental pulp stem cells.

    Science.gov (United States)

    Feng, Xingmei; Lu, Xiaohui; Huang, Dan; Xing, Jing; Feng, Guijuan; Jin, Guohua; Yi, Xin; Li, Liren; Lu, Yuanzhou; Nie, Dekang; Chen, Xiang; Zhang, Lei; Gu, Zhifeng; Zhang, Xinhua

    2014-08-01

    A key aspect of cell replacement therapy in brain injury treatment is construction of a suitable biomaterial scaffold that can effectively carry and transport the therapeutic cells to the target area. In the present study, we created small 3D porous chitosan scaffolds through freeze-drying, and showed that these can support and enhance the differentiation of dental pulp stem cells (DPSCs) to nerve cells in vitro. The DPSCs were collected from the dental pulp of adult human third molars. At a swelling rate of ~84.33 ± 10.92 %, the scaffold displayed high porosity and interconnectivity of pores, as revealed by SEM. Cell counting kit-8 assay established the biocompatibility of the chitosan scaffold, supporting the growth and survival of DPSCs. The successful neural differentiation of DPSCs was assayed by RT-PCR, western blotting, and immunofluorescence. We found that the scaffold-attached DPSCs showed high expression of Nestin that decreased sharply following induction of differentiation. Exposure to the differentiation media also increased the expression of neural molecular markers Microtubule-associated protein 2, glial fibrillary acidic protein, and 2',3'-cyclic nucleotide phosphodiesterase. This study demonstrates that the granular 3D chitosan scaffolds are non-cytotoxic, biocompatible, and provide a conducive and favorable micro-environment for attachment, survival, and neural differentiation of DPSCs. These scaffolds have enormous potential to facilitate future advances in treatment of brain injury.

  2. The Puzzle of Visual Development: Behavior and Neural Limits.

    Science.gov (United States)

    Kiorpes, Lynne

    2016-11-09

    The development of visual function takes place over many months or years in primate infants. Visual sensitivity is very poor near birth and improves over different times courses for different visual functions. The neural mechanisms that underlie these processes are not well understood despite many decades of research. The puzzle arises because research into the factors that limit visual function in infants has found surprisingly mature neural organization and adult-like receptive field properties in very young infants. The high degree of visual plasticity that has been documented during the sensitive period in young children and animals leaves the brain vulnerable to abnormal visual experience. Abnormal visual experience during the sensitive period can lead to amblyopia, a developmental disorder of vision affecting ∼3% of children. This review provides a historical perspective on research into visual development and the disorder amblyopia. The mismatch between the status of the primary visual cortex and visual behavior, both during visual development and in amblyopia, is discussed, and several potential resolutions are considered. It seems likely that extrastriate visual areas further along the visual pathways may set important limits on visual function and show greater vulnerability to abnormal visual experience. Analyses based on multiunit, population activity may provide useful representations of the information being fed forward from primary visual cortex to extrastriate processing areas and to the motor output. Copyright © 2016 the authors 0270-6474/16/3611384-10$15.00/0.

  3. Differentiating Agar wood Oil Quality Using Artificial Neural Network

    International Nuclear Information System (INIS)

    Nurlaila Ismail; Nor Azah Mohd Ali; Mailina Jamil; Saiful Nizam Tajuddin; Mohd Nasir Taib

    2013-01-01

    Agar wood oil is well known as expensive oil extracted from the resinous of fragrant heartwood. The oil is getting high demand in the market especially from the Middle East countries, China and Japan because of its unique odor. As part of an on-going research in grading the agar wood oil quality, the application of Artificial Neural Network (ANN) is proposed in this study to analyze agar wood oil quality using its chemical profiles. The work involves of selected agar wood oil from low and high quality, the extraction of chemical compounds using GC-MS and Z-score to identify of the significant compounds as input to the network. The ANN programming algorithm was developed and computed automatically via Matlab software version R2010a. Back-propagation training algorithm and sigmoid transfer function were used to optimize the parameters in the training network. The result obtained showed the capability of ANN in analyzing the agar wood oil quality hence beneficial for the further application such as grading and classification for agar wood oil. (author)

  4. Non-neural androgen receptors affect sexual differentiation of brain and behaviour.

    Science.gov (United States)

    Monks, D A; Swift-Gallant, A

    2018-02-01

    Although gonadal testosterone is the principal endocrine factor that promotes masculine traits in mammals, the development of a male phenotype requires local production of both androgenic and oestrogenic signals within target tissues. Much of our knowledge concerning androgenic components of testosterone signalling in sexual differentiation comes from studies of androgen receptor (Ar) loss of function mutants. Here, we review these studies of loss of Ar function and of AR overexpression either globally or selectively in the nervous system of mice. Global and neural mutations affect socio-sexual behaviour and the neuroanatomy of these mice in a sexually differentiated manner. Some masculine traits are affected by both global and neural mutation, indicative of neural mediation, whereas other masculine traits are affected only by global mutation, indicative of an obligatory non-neural androgen target. These results support a model in which multiple sites of androgen action coordinate to produce masculine phenotypes. Furthermore, AR overexpression does not always have a phenotype opposite to that of loss of Ar function mutants, indicative of a nonlinear relationship between androgen dose and masculine phenotype in some cases. Potential mechanisms of Ar gene function in non-neural targets in producing masculine phenotypes are discussed. © 2017 British Society for Neuroendocrinology.

  5. Three-dimensional neural differentiation of embryonic stem cells with ACM induction in microfibrous matrices in bioreactors.

    Science.gov (United States)

    Liu, Ning; Ouyang, Anli; Li, Yan; Yang, Shang-Tian

    2013-01-01

    The clinical use of pluripotent stem cell (PSC)-derived neural cells requires an efficient differentiation process for mass production in a bioreactor. Toward this goal, neural differentiation of murine embryonic stem cells (ESCs) in three-dimensional (3D) polyethylene terephthalate microfibrous matrices was investigated in this study. To streamline the process and provide a platform for process integration, the neural differentiation of ESCs was induced with astrocyte-conditioned medium without the formation of embryoid bodies, starting from undifferentiated ESC aggregates expanded in a suspension bioreactor. The 3D neural differentiation was able to generate a complex neural network in the matrices. When compared to 2D differentiation, 3D differentiation in microfibrous matrices resulted in a higher percentage of nestin-positive cells (68% vs. 54%) and upregulated gene expressions of nestin, Nurr1, and tyrosine hydroxylase. High purity of neural differentiation in 3D microfibrous matrix was also demonstrated in a spinner bioreactor with 74% nestin + cells. This study demonstrated the feasibility of a scalable process based on 3D differentiation in microfibrous matrices for the production of ESC-derived neural cells. © 2013 American Institute of Chemical Engineers.

  6. Neural and Hormonal Control of Postecdysial Behaviors in Insects

    Science.gov (United States)

    White, Benjamin H.; Ewer, John

    2016-01-01

    The shedding of the old exoskeleton that occurs in insects at the end of a molt (a process called ecdysis) is typically followed by the expansion and tanning of a new one. At the adult molt, these postecdysial processes include expanding and hardening the wings. Here we describe recent advances in understanding the neural and hormonal control of wing expansion and hardening, focusing on work done in Drosophila where genetic manipulations have permitted a detailed investigation of postecdysial processes and their modulation by sensory input. To place this work in context, we briefly review recent progress in understanding the neuroendocrine regulation of ecdysis, which appears to be largely conserved across insect species. Investigations into the neuroendocrine networks that regulate ecdysial and postecdysial behaviors, will provide insights into how stereotyped, yet environmentally-responsive, sequences are generated, as well as into how they develop and evolve. PMID:24160420

  7. VEGF-mediated angiogenesis stimulates neural stem cell proliferation and differentiation in the premature brain

    International Nuclear Information System (INIS)

    Sun, Jinqiao; Sha, Bin; Zhou, Wenhao; Yang, Yi

    2010-01-01

    This study investigated the effects of angiogenesis on the proliferation and differentiation of neural stem cells in the premature brain. We observed the changes in neurogenesis that followed the stimulation and inhibition of angiogenesis by altering vascular endothelial growth factor (VEGF) expression in a 3-day-old rat model. VEGF expression was overexpressed by adenovirus transfection and down-regulated by siRNA interference. Using immunofluorescence assays, Western blot analysis, and real-time PCR methods, we observed angiogenesis and the proliferation and differentiation of neural stem cells. Immunofluorescence assays showed that the number of vWF-positive areas peaked at day 7, and they were highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at every time point. The number of neural stem cells, neurons, astrocytes, and oligodendrocytes in the subventricular zone gradually increased over time in the VEGF up-regulation group. Among the three groups, the number of these cells was highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at the same time point. Western blot analysis and real-time PCR confirmed these results. These data suggest that angiogenesis may stimulate the proliferation of neural stem cells and differentiation into neurons, astrocytes, and oligodendrocytes in the premature brain.

  8. Extended passaging increases the efficiency of neural differentiation from induced pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Koehler Karl R

    2011-08-01

    Full Text Available Abstract Background The use of induced pluripotent stem cells (iPSCs for the functional replacement of damaged neurons and in vitro disease modeling is of great clinical relevance. Unfortunately, the capacity of iPSC lines to differentiate into neurons is highly variable, prompting the need for a reliable means of assessing the differentiation capacity of newly derived iPSC cell lines. Extended passaging is emerging as a method of ensuring faithful reprogramming. We adapted an established and efficient embryonic stem cell (ESC neural induction protocol to test whether iPSCs (1 have the competence to give rise to functional neurons with similar efficiency as ESCs and (2 whether the extent of neural differentiation could be altered or enhanced by increased passaging. Results Our gene expression and morphological analyses revealed that neural conversion was temporally delayed in iPSC lines and some iPSC lines did not properly form embryoid bodies during the first stage of differentiation. Notably, these deficits were corrected by continual passaging in an iPSC clone. iPSCs with greater than 20 passages (late-passage iPSCs expressed higher expression levels of pluripotency markers and formed larger embryoid bodies than iPSCs with fewer than 10 passages (early-passage iPSCs. Moreover, late-passage iPSCs started to express neural marker genes sooner than early-passage iPSCs after the initiation of neural induction. Furthermore, late-passage iPSC-derived neurons exhibited notably greater excitability and larger voltage-gated currents than early-passage iPSC-derived neurons, although these cells were morphologically indistinguishable. Conclusions These findings strongly suggest that the efficiency neuronal conversion depends on the complete reprogramming of iPSCs via extensive passaging.

  9. Chondroitin sulfate proteoglycans regulate the growth, differentiation and migration of multipotent neural precursor cells through the integrin signaling pathway

    Directory of Open Access Journals (Sweden)

    Lü He-Zuo

    2009-10-01

    Full Text Available Abstract Background Neural precursor cells (NPCs are defined by their ability to proliferate, self-renew, and retain the potential to differentiate into neurons and glia. Deciphering the factors that regulate their behaviors will greatly aid in their use as potential therapeutic agents or targets. Chondroitin sulfate proteoglycans (CSPGs are prominent components of the extracellular matrix (ECM in the central nervous system (CNS and are assumed to play important roles in controlling neuronal differentiation and development. Results In the present study, we demonstrated that CSPGs were constitutively expressed on the NPCs isolated from the E16 rat embryonic brain. When chondroitinase ABC was used to abolish the function of endogenous CSPGs on NPCs, it induced a series of biological responses including the proliferation, differentiation and migration of NPCs, indicating that CSPGs may play a critical role in NPC development and differentiation. Finally, we provided evidence suggesting that integrin signaling pathway may be involved in the effects of CSPGs on NPCs. Conclusion The present study investigating the influence and mechanisms of CSPGs on the differentiation and migration of NPCs should help us to understand the basic biology of NPCs during CNS development and provide new insights into developing new strategies for the treatment of the neurological disorders in the CNS.

  10. Neural differentiation potential of human bone marrow-derived mesenchymal stromal cells: misleading marker gene expression

    Directory of Open Access Journals (Sweden)

    Montzka Katrin

    2009-03-01

    Full Text Available Abstract Background In contrast to pluripotent embryonic stem cells, adult stem cells have been considered to be multipotent, being somewhat more restricted in their differentiation capacity and only giving rise to cell types related to their tissue of origin. Several studies, however, have reported that bone marrow-derived mesenchymal stromal cells (MSCs are capable of transdifferentiating to neural cell types, effectively crossing normal lineage restriction boundaries. Such reports have been based on the detection of neural-related proteins by the differentiated MSCs. In order to assess the potential of human adult MSCs to undergo true differentiation to a neural lineage and to determine the degree of homogeneity between donor samples, we have used RT-PCR and immunocytochemistry to investigate the basal expression of a range of neural related mRNAs and proteins in populations of non-differentiated MSCs obtained from 4 donors. Results The expression analysis revealed that several of the commonly used marker genes from other studies like nestin, Enolase2 and microtubule associated protein 1b (MAP1b are already expressed by undifferentiated human MSCs. Furthermore, mRNA for some of the neural-related transcription factors, e.g. Engrailed-1 and Nurr1 were also strongly expressed. However, several other neural-related mRNAs (e.g. DRD2, enolase2, NFL and MBP could be identified, but not in all donor samples. Similarly, synaptic vesicle-related mRNA, STX1A could only be detected in 2 of the 4 undifferentiated donor hMSC samples. More significantly, each donor sample revealed a unique expression pattern, demonstrating a significant variation of marker expression. Conclusion The present study highlights the existence of an inter-donor variability of expression of neural-related markers in human MSC samples that has not previously been described. This donor-related heterogeneity might influence the reproducibility of transdifferentiation protocols as

  11. Asymptotic behavior of second-order impulsive differential equations

    Directory of Open Access Journals (Sweden)

    Haifeng Liu

    2011-02-01

    Full Text Available In this article, we study the asymptotic behavior of all solutions of 2-th order nonlinear delay differential equation with impulses. Our main tools are impulsive differential inequalities and the Riccati transformation. We illustrate the results by an example.

  12. Differentiated cells derived from fetal neural stem cells improve motor deficits in a rat model of Parkinson’s disease

    Institute of Scientific and Technical Information of China (English)

    Wei Wang; Hao Song; Aifang Shen; Chao Chen; Yanming Liu; Yabing Dong; Fabin Han

    2015-01-01

    Objective: Parkinson’s disease(PD), which is one of the most common neuro‐degenerative disorders, is characterized by the loss of dopamine(DA) neurons in the substantia nigra in the midbrain. Experimental and clinical studies have shown that fetal neural stem cells(NSCs) have therapeutic effects in neurological disorders. The aim of this study was to examine whether cells that were differentiated from NSCs had therapeutic effects in a rat model of PD. Methods: NSCs were isolated from 14‐week‐old embryos and induced to differentiate into neurons, DA neurons, and glial cells, and these cells were characterized by their expression of the following markers: βⅢ‐tubulin and microtubule‐associated protein 2(neurons), tyrosine hydroxylase(DA neurons), and glial fibrillary acidic protein(glial cells). After a 6‐hydroxydopamine(6‐OHDA)‐lesioned rat model of PD was generated, the differentiated cells were transplanted into the striata of the 6‐OHDA‐lesioned PD rats. Results: The motor behaviors of the PD rats were assessed by the number of apomorphine‐induced rotation turns. The results showed that the NSCs differentiated in vitro into neurons and DA neurons with high efficiencies. After transplantation into the striata of the PD rats, the differentiated cells significantly improved the motor deficits of the transplanted PD rats compared to those of the control nontransplanted PD rats by decreasing the apomorphine‐induced turn cycles as early as 4 weeks after transplantation. Immunofluorescence analyses showed that the differentiated DA neurons survived more than 16 weeks. Conclusions: Our results showed that cells that were differentiated from NSCs had therapeutic effects in a rat PD model, which suggests that differentiated cells may be an effective treatment for patients with PD.

  13. A regulatory transcriptional loop controls proliferation and differentiation in Drosophila neural stem cells.

    Directory of Open Access Journals (Sweden)

    Tetsuo Yasugi

    Full Text Available Neurogenesis is initiated by a set of basic Helix-Loop-Helix (bHLH transcription factors that specify neural progenitors and allow them to generate neurons in multiple rounds of asymmetric cell division. The Drosophila Daughterless (Da protein and its mammalian counterparts (E12/E47 act as heterodimerization factors for proneural genes and are therefore critically required for neurogenesis. Here, we demonstrate that Da can also be an inhibitor of the neural progenitor fate whose absence leads to stem cell overproliferation and tumor formation. We explain this paradox by demonstrating that Da induces the differentiation factor Prospero (Pros whose asymmetric segregation is essential for differentiation in one of the two daughter cells. Da co-operates with the bHLH transcription factor Asense, whereas the other proneural genes are dispensible. After mitosis, Pros terminates Asense expression in one of the two daughter cells. In da mutants, pros is not expressed, leading to the formation of lethal transplantable brain tumors. Our results define a transcriptional feedback loop that regulates the balance between self-renewal and differentiation in Drosophila optic lobe neuroblasts. They indicate that initiation of a neural differentiation program in stem cells is essential to prevent tumorigenesis.

  14. Temperament and Parenting Styles in Early Childhood Differentially Influence Neural Response to Peer Evaluation in Adolescence

    OpenAIRE

    Guyer, Amanda E.; Jarcho, Johanna M.; Pérez-Edgar, Koraly; Degnan, Kathryn A.; Pine, Daniel S.; Fox, Nathan A.; Nelson, Eric E.

    2015-01-01

    Behavioral inhibition (BI) is a temperament characterized by social reticence and withdrawal from unfamiliar or novel contexts and conveys risk for social anxiety disorder. Developmental outcomes associated with this temperament can be influenced by children’s caregiving context. The convergence of a child’s temperamental disposition and rearing environment is ultimately expressed at both the behavioral and neural levels in emotional and cognitive response patterns to social challenges. The p...

  15. Modulation of neural circuits: how stimulus context shapes innate behavior in Drosophila.

    Science.gov (United States)

    Su, Chih-Ying; Wang, Jing W

    2014-12-01

    Remarkable advances have been made in recent years in our understanding of innate behavior and the underlying neural circuits. In particular, a wealth of neuromodulatory mechanisms have been uncovered that can alter the input-output relationship of a hereditary neural circuit. It is now clear that this inbuilt flexibility allows animals to modify their behavioral responses according to environmental cues, metabolic demands and physiological states. Here, we discuss recent insights into how modulation of neural circuits impacts innate behavior, with a special focus on how environmental cues and internal physiological states shape different aspects of feeding behavior in Drosophila. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. A Reward-Based Behavioral Platform to Measure Neural Activity during Head-Fixed Behavior

    Directory of Open Access Journals (Sweden)

    Andrew H. Micallef

    2017-05-01

    Full Text Available Understanding the neural computations that contribute to behavior requires recording from neurons while an animal is behaving. This is not an easy task as most subcellular recording techniques require absolute head stability. The Go/No-Go sensory task is a powerful decision-driven task that enables an animal to report a binary decision during head-fixation. Here we discuss how to set up an Ardunio and Python based platform system to control a Go/No-Go sensory behavior paradigm. Using an Arduino micro-controller and Python-based custom written program, a reward can be delivered to the animal depending on the decision reported. We discuss the various components required to build the behavioral apparatus that can control and report such a sensory stimulus paradigm. This system enables the end user to control the behavioral testing in real-time and therefore it provides a strong custom-made platform for probing the neural basis of behavior.

  17. Adolescents' behavioral and neural responses to e-cigarette advertising.

    Science.gov (United States)

    Chen, Yvonnes; Fowler, Carina H; Papa, Vlad B; Lepping, Rebecca J; Brucks, Morgan G; Fox, Andrew T; Martin, Laura E

    2018-03-01

    Although adolescents are a group heavily targeted by the e-cigarette industry, research in cue-reactivity has not previously examined adolescents' behavioral and neural responses to e-cigarette advertising. This study addressed this gap through two experiments. In Experiment One, adult traditional cigarette smokers (n = 41) and non-smokers (n = 41) answered questions about e-cigarette and neutral advertising images. The 40 e-cigarette advertising images that most increased desire to use the product were matched to 40 neutral advertising images with similar content. In Experiment Two, the 80 advertising images selected in Experiment One were presented to adolescents (n = 30) during an functional magnetic resonance imaging brain scan. There was a range of traditional cigarette smoking across the sample with some adolescents engaging in daily smoking and others who had never smoked. Adolescents self-reported that viewing the e-cigarette advertising images increased their desire to smoke. Additionally, all participants regardless of smoking statuses showed significantly greater brain activation to e-cigarette advertisements in areas associated with cognitive control (left middle frontal gyrus), reward (right medial frontal gyrus), visual processing/attention (left lingual gyrus/fusiform gyrus, right inferior parietal lobule, left posterior cingulate, left angular gyrus) and memory (right parahippocampus, left insula). Further, an exploratory analysis showed that compared with age-matched non-smokers (n = 7), adolescent smokers (n = 7) displayed significantly greater neural activation to e-cigarette advertising images in the left inferior temporal gyrus/fusiform gyrus, compared with their responses to neutral advertising images. Overall, participants' brain responses to e-cigarette advertisements suggest a need to further investigate the long-run impact of e-cigarette advertising on adolescents. © 2017 Society for the Study of Addiction.

  18. Roles of bHLH genes in neural stem cell differentiation

    International Nuclear Information System (INIS)

    Kageyama, Ryoichiro; Ohtsuka, Toshiyuki; Hatakeyama, Jun; Ohsawa, Ryosuke

    2005-01-01

    Neural stem cells change their characteristics over time during development: they initially proliferate only and then give rise to neurons first and glial cells later. In the absence of the repressor-type basic helix-loop-helix (bHLH) genes Hes1, Hes3 and Hes5, neural stem cells do not proliferate sufficiently but prematurely differentiate into neurons and become depleted without making the later born cell types such as astrocytes and ependymal cells. Thus, Hes genes are essential for maintenance of neural stem cells to make cells not only in correct numbers but also in full diversity. Hes genes antagonize the activator-type bHLH genes, which include Mash1, Math and Neurogenin. The activator-type bHLH genes promote the neuronal fate determination and induce expression of Notch ligands such as Delta. These ligands activate Notch signaling and upregulate Hes1 and Hes5 expression in neighboring cells, thereby maintaining these cells undifferentiated. Thus, the activator-type and repressor-type bHLH genes regulate each other, allowing only subsets of cells to undergo differentiation while keeping others to stay neural stem cells. This regulation is essential for generation of complex brain structures of appropriate size, shape and cell arrangement

  19. Differential Neural Networks for Identification and Filtering in Nonlinear Dynamic Games

    Directory of Open Access Journals (Sweden)

    Emmanuel García

    2014-01-01

    Full Text Available This paper deals with the problem of identifying and filtering a class of continuous-time nonlinear dynamic games (nonlinear differential games subject to additive and undesired deterministic perturbations. Moreover, the mathematical model of this class is completely unknown with the exception of the control actions of each player, and even though the deterministic noises are known, their power (or their effect is not. Therefore, two differential neural networks are designed in order to obtain a feedback (perfect state information pattern for the mentioned class of games. In this way, the stability conditions for two state identification errors and for a filtering error are established, the upper bounds of these errors are obtained, and two new learning laws for each neural network are suggested. Finally, an illustrating example shows the applicability of this approach.

  20. Neural differentiation of adipose-derived stem cells by indirect co-culture with Schwann cells

    Directory of Open Access Journals (Sweden)

    Li Xiaojie

    2009-01-01

    Full Text Available To investigate whether adipose-derived stem cells (ADSCs could be subject to neural differentiation induced only by Schwann cell (SC factors, we co-cultured ADSCs and SCs in transwell culture dishes. Immunoassaying, Western blot analysis, and RT-PCR were performed (1, 3, 7, 14 d and the co-cultured ADSCs showed gene and protein expression of S-100, Nestin, and GFAP. Further, qRT-PCR disclosed relative quantitative differences in the above three gene expressions. We think ADSCs can undergo induced neural differentiation by being co-cultured with SCs, and such differentia­tions begin 1 day after co-culture, become apparent after 7 days, and thereafter remain stable till the 14th day.

  1. Odor Discrimination in Drosophila: From Neural Population Codes to Behavior

    Science.gov (United States)

    Parnas, Moshe; Lin, Andrew C.; Huetteroth, Wolf; Miesenböck, Gero

    2013-01-01

    Summary Taking advantage of the well-characterized olfactory system of Drosophila, we derive a simple quantitative relationship between patterns of odorant receptor activation, the resulting internal representations of odors, and odor discrimination. Second-order excitatory and inhibitory projection neurons (ePNs and iPNs) convey olfactory information to the lateral horn, a brain region implicated in innate odor-driven behaviors. We show that the distance between ePN activity patterns is the main determinant of a fly’s spontaneous discrimination behavior. Manipulations that silence subsets of ePNs have graded behavioral consequences, and effect sizes are predicted by changes in ePN distances. ePN distances predict only innate, not learned, behavior because the latter engages the mushroom body, which enables differentiated responses to even very similar odors. Inhibition from iPNs, which scales with olfactory stimulus strength, enhances innate discrimination of closely related odors, by imposing a high-pass filter on transmitter release from ePN terminals that increases the distance between odor representations. PMID:24012006

  2. A proteomic approach to studying the differentiation of neural stem cells

    Czech Academy of Sciences Publication Activity Database

    Skalníková, Helena; Halada, Petr; Vodička, Petr; Motlík, Jan; Řehulka, Pavel; Horning, O.; Chmelík, Josef; Norregaard Jensen, O.; Kovářová, Hana

    2007-01-01

    Roč. 7, 11 (2007), s. 1825-1838 ISSN 1615-9853 R&D Projects: GA MŠk 1M0538; GA MŠk LC545 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50200510; CEZ:AV0Z40310501 Keywords : differentiation * neural stem cells * two-dimensional gel electrophoresis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.479, year: 2007

  3. [Inhibitory effect of murine cytomegalovirus infection on neural stem cells' differentiation and its mechanisms].

    Science.gov (United States)

    Zhou, Yu-feng; Fang, Feng; Dong, Yong-sui; Zhou, Hua; Zhen, Hong; Liu, Jin; Li, Ge

    2006-07-01

    Cytomegalovirus (CMV) is the leading infectious cause of congenital anomalies of the central nervous system caused by intrauterine infection. However, the exact pathogenesis of these brain abnormalities has not been fully elucidated. It has been reported that periependymitis, periventricular necrosis and calcification are the most frequent findings in the brains of congenital CMV infection. Because a number of multipotential neural stem cells (NSCs) have been identified from ventricular zone, it is possible that NSCs in this area are primary targets for viral infection, which seems to be primarily responsible for the generation of the brain abnormalities. Therefore, the objective of the present study was to investigate the effect and mechanism of murine cytomegalovirus (MCMV) infection on neural stem cells' differentiation in vitro and its role in the mechanisms of brain abnormalities caused by congenital cytomegalovirus infection. NSCs were prepared from fetal BALB/c mouse and were infected with recombinant MCMV RM461 inserted with a report gene LacZ at 1 multiplicity of infection (MOI = 1). The effect of MCMV infection on neural stem cells' differentiation was observed by detecting the ratio of nestin, GFAP and NSE positive cells with immunohistochemistry and flow cytometry on day 2 postinfection. The effects of MCMV infection on gene expression of Wnt-1 and neurogenin 1 (Ngn1) related to neural differentiation were detected by RT-PCR. NSCs isolated from embryonic mouse brains strongly expressed nestin, a specific marker of NSCs and had the capacity to differentiate into NF-200 and NSE positive neurons or GFAP positive astrocytes. At MOI = 1, the results of flow cytometry assay showed that nestin positive cells' proportion in the infection group [(62.2 +/- 1.8)%] was higher than that in the normal group [(37.2 +/- 2.4)%] (t = 4.62, P differentiation, which may be primary causes of disorders of brain development in congenital CMV infection. The decreased

  4. Suppression of MicroRNA let-7a Expression by Agmatine Regulates Neural Stem Cell Differentiation.

    Science.gov (United States)

    Song, Juhyun; Oh, Yumi; Kim, Jong Youl; Cho, Kyoung Joo; Lee, Jong Eun

    2016-11-01

    Neural stem cells (NSCs) effectively reverse some severe central nervous system (CNS) disorders, due to their ability to differentiate into neurons. Agmatine, a biogenic amine, has cellular protective effects and contributes to cellular proliferation and differentiation in the CNS. Recent studies have elucidated the function of microRNA let-7a (let-7a) as a regulator of cell differentiation with roles in regulating genes associated with CNS neurogenesis. This study aimed to investigate whether agmatine modulates the expression of crucial regulators of NSC differentiation including DCX, TLX, c-Myc, and ERK by controlling let-7a expression. Our data suggest that high levels of let-7a promoted the expression of TLX and c-Myc, as well as repressed DCX and ERK expression. In addition, agmatine attenuated expression of TLX and increased expression of ERK by negatively regulating let-7a. Our study therefore enhances the present understanding of the therapeutic potential of NSCs in CNS disorders.

  5. [Comprehensive regulation effect of traditional Chinese medicine on proliferation and differentiation of neural stem cells].

    Science.gov (United States)

    Wang, Hong-Jin; Li, Jing-Jing; Ke, Hui; Xu, Xiao-Yu

    2017-11-01

    Since the discovery of neural stem cells(NSCs) in embryonic and adult mammalian central nervous systems, new approaches for proliferation and differentiation of NSCs have been put forward. One of the approaches to promote the clinical application of NSCs is to search effective methods to regulate the proliferation and differentiation. This problem is urgently to be solved in the medical field. Previous studies have shown that traditional Chinese medicine could promote the proliferation and differentiation of NSCs by regulating the relevant signaling pathway in vivo and in vitro. Domestic and foreign literatures for regulating the proliferation and differentiation of neural stem cells in recent 10 years and the reports for their target and signaling pathways were analyzed in this paper. Traditional Chinese medicine could regulate the proliferation and differentiation of NSCs through signaling pathways of Notch, PI3K/Akt, Wnt/β-catenin and GFs. However, studies about NSCs and traditional Chinese medicine should be further deepened; the mechanism of multiple targets and the comprehensive regulation function of traditional Chinese medicine should be clarified. Copyright© by the Chinese Pharmaceutical Association.

  6. Bioinspired nanocomplex for spatiotemporal imaging of sequential mRNA expression in differentiating neural stem cells.

    Science.gov (United States)

    Wang, Zhe; Zhang, Ruili; Wang, Zhongliang; Wang, He-Fang; Wang, Yu; Zhao, Jun; Wang, Fu; Li, Weitao; Niu, Gang; Kiesewetter, Dale O; Chen, Xiaoyuan

    2014-12-23

    Messenger RNA plays a pivotal role in regulating cellular activities. The expression dynamics of specific mRNA contains substantial information on the intracellular milieu. Unlike the imaging of stationary mRNAs, real-time intracellular imaging of the dynamics of mRNA expression is of great value for investigating mRNA biology and exploring specific cellular cascades. In addition to advanced imaging methods, timely extracellular stimulation is another key factor in regulating the mRNA expression repertoire. The integration of effective stimulation and imaging into a single robust system would significantly improve stimulation efficiency and imaging accuracy, producing fewer unwanted artifacts. In this study, we developed a multifunctional nanocomplex to enable self-activating and spatiotemporal imaging of the dynamics of mRNA sequential expression during the neural stem cell differentiation process. This nanocomplex showed improved enzymatic stability, fast recognition kinetics, and high specificity. With a mechanism regulated by endogenous cell machinery, this nanocomplex realized the successive stimulating motif release and the dynamic imaging of chronological mRNA expression during neural stem cell differentiation without the use of transgenetic manipulation. The dynamic imaging montage of mRNA expression ultimately facilitated genetic heterogeneity analysis. In vivo lateral ventricle injection of this nanocomplex enabled endogenous neural stem cell activation and labeling at their specific differentiation stages. This nanocomplex is highly amenable as an alternative tool to explore the dynamics of intricate mRNA activities in various physiological and pathological conditions.

  7. Effects and mechanisms of melatonin on neural differentiation of induced pluripotent stem cells.

    Science.gov (United States)

    Shu, Tao; Wu, Tao; Pang, Mao; Liu, Chang; Wang, Xuan; Wang, Juan; Liu, Bin; Rong, Limin

    2016-06-03

    Melatonin, a lipophilic molecule mainly synthesized in the pineal gland, has properties of antioxidation, anti-inflammation, and antiapoptosis to improve neuroprotective functions. Here, we investigate effects and mechanisms of melatonin on neural differentiation of induced pluripotent stem cells (iPSCs). iPSCs were induced into neural stem cells (NSCs), then further differentiated into neurons in medium with or without melatonin, melatonin receptor antagonist (Luzindole) or Phosphatidylinositide 3 kinase (PI3K) inhibitor (LY294002). Melatonin significantly promoted the number of neurospheres and cell viability. In addition, Melatonin markedly up-regulated gene and protein expression of Nestin and MAP2. However, Luzindole or LY294002 attenuated these increase. The expression of pAKT/AKT were increased by Melatonin, while Luzindole or LY294002 declined these melatonin-induced increase. These results suggest that melatonin significantly increased neural differentiation of iPSCs via activating PI3K/AKT signaling pathway through melatonin receptor. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Neural differentiation of novel multipotent progenitor cells from cryopreserved human umbilical cord blood

    International Nuclear Information System (INIS)

    Lee, Myoung Woo; Moon, Young Joon; Yang, Mal Sook; Kim, Sun Kyung; Jang, In Keun; Eom, Young-woo; Park, Joon Seong; Kim, Hugh C.; Song, Kye Yong; Park, Soon Cheol; Lim, Hwan Sub; Kim, Young Jin

    2007-01-01

    Umbilical cord blood (UCB) is a rich source of hematopoietic stem cells, with practical and ethical advantages. To date, the presence of other stem cells in UCB remains to be established. We investigated whether other stem cells are present in cryopreserved UCB. Seeded mononuclear cells formed adherent colonized cells in optimized culture conditions. Over a 4- to 6-week culture period, colonized cells gradually developed into adherent mono-layer cells, which exhibited homogeneous fibroblast-like morphology and immunophenotypes, and were highly proliferative. Isolated cells were designated 'multipotent progenitor cells (MPCs)'. Under appropriate conditions for 2 weeks, MPCs differentiated into neural tissue-specific cell types, including neuron, astrocyte, and oligodendrocyte. Differentiated cells presented their respective markers, specifically, NF-L and NSE for neurons, GFAP for astrocytes, and myelin/oligodendrocyte for oligodendrocytes. In this study, we successfully isolated MPCs from cryopreserved UCB, which differentiated into the neural tissue-specific cell types. These findings suggest that cryopreserved human UCB is a useful alternative source of neural progenitor cells, such as MPCs, for experimental and therapeutic applications

  9. Let7a involves in neural stem cell differentiation relating with TLX level

    Energy Technology Data Exchange (ETDEWEB)

    Song, Juhyun [Department of Anatomy, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cho, Kyoung Joo; Oh, Yumi [Department of Anatomy, Yonsei University College of Medicine, Seoul (Korea, Republic of); BK21 Plus Project for Medical Sciences, and Brain Research Institute, Yonsei University College of Medicine, Seoul (Korea, Republic of); Lee, Jong Eun, E-mail: jelee@yuhs.ac [Department of Anatomy, Yonsei University College of Medicine, Seoul (Korea, Republic of); BK21 Plus Project for Medical Sciences, and Brain Research Institute, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-07-10

    Neural stem cells (NSCs) have the potential for differentiation into neurons known as a groundbreaking therapeutic solution for central nervous system (CNS) diseases. To resolve the therapeutic efficiency of NSCs, recent researchers have focused on the study on microRNA's role in CNS. Some micro RNAs have been reported significant functions in NSC self-renewal and differentiation through the post-transcriptional regulation of neurogenesis genes. MicroRNA-Let7a (Let7a) has known as the regulator of diverse cellular mechanisms including cell differentiation and proliferation. In present study, we investigated whether Let7a regulates NSC differentiation by targeting the nuclear receptor TLX, which is an essential regulator of NSC self-renewal, proliferation and differentiation. We performed the following experiments: western blot analysis, TaqMan assay, RT-PCR, and immunocytochemistry to confirm the alteration of NSCs. Our data showed that let7a play important roles in controlling NSC fate determination. Thus, manipulating Let-7A and TLX could be a novel strategy to enhance the efficiency of NSC's neuronal differentiation for CNS disorders. - Highlights: • Let7a influences on NSC differentiation and proliferation. • Let7a involves in mainly NSC differentiation rather than proliferation. • Let7a positively regulates the TLX expression.

  10. Let7a involves in neural stem cell differentiation relating with TLX level

    International Nuclear Information System (INIS)

    Song, Juhyun; Cho, Kyoung Joo; Oh, Yumi; Lee, Jong Eun

    2015-01-01

    Neural stem cells (NSCs) have the potential for differentiation into neurons known as a groundbreaking therapeutic solution for central nervous system (CNS) diseases. To resolve the therapeutic efficiency of NSCs, recent researchers have focused on the study on microRNA's role in CNS. Some micro RNAs have been reported significant functions in NSC self-renewal and differentiation through the post-transcriptional regulation of neurogenesis genes. MicroRNA-Let7a (Let7a) has known as the regulator of diverse cellular mechanisms including cell differentiation and proliferation. In present study, we investigated whether Let7a regulates NSC differentiation by targeting the nuclear receptor TLX, which is an essential regulator of NSC self-renewal, proliferation and differentiation. We performed the following experiments: western blot analysis, TaqMan assay, RT-PCR, and immunocytochemistry to confirm the alteration of NSCs. Our data showed that let7a play important roles in controlling NSC fate determination. Thus, manipulating Let-7A and TLX could be a novel strategy to enhance the efficiency of NSC's neuronal differentiation for CNS disorders. - Highlights: • Let7a influences on NSC differentiation and proliferation. • Let7a involves in mainly NSC differentiation rather than proliferation. • Let7a positively regulates the TLX expression

  11. High baseline activity in inferior temporal cortex improves neural and behavioral discriminability during visual categorization

    Science.gov (United States)

    Emadi, Nazli; Rajimehr, Reza; Esteky, Hossein

    2014-01-01

    Spontaneous firing is a ubiquitous property of neural activity in the brain. Recent literature suggests that this baseline activity plays a key role in perception. However, it is not known how the baseline activity contributes to neural coding and behavior. Here, by recording from the single neurons in the inferior temporal cortex of monkeys performing a visual categorization task, we thoroughly explored the relationship between baseline activity, the evoked response, and behavior. Specifically we found that a low-frequency (baseline activity. This enhancement of the baseline activity was then followed by an increase in the neural selectivity and the response reliability and eventually a higher behavioral performance. PMID:25404900

  12. MANF Promotes Differentiation and Migration of Neural Progenitor Cells with Potential Neural Regenerative Effects in Stroke

    DEFF Research Database (Denmark)

    Tseng, Kuan-Yin; Anttila, Jenni E; Khodosevich, Konstantin

    2018-01-01

    die shortly after injury or are unable to arrive at the infarct boundary. In this study, we demonstrate for the first time that endogenous mesencephalic astrocyte-derived neurotrophic factor (MANF) protects NSCs against oxygen-glucose-deprivation-induced injury and has a crucial role in regulating NPC...... migration. In NSC cultures, MANF protein administration did not affect growth of cells but triggered neuronal and glial differentiation, followed by activation of STAT3. In SVZ explants, MANF overexpression facilitated cell migration and activated the STAT3 and ERK1/2 pathway. Using a rat model of cortical...... stroke, intracerebroventricular injections of MANF did not affect cell proliferation in the SVZ, but promoted migration of doublecortin (DCX)+ cells toward the corpus callosum and infarct boundary on day 14 post-stroke. Long-term infusion of MANF into the peri-infarct zone increased the recruitment...

  13. Classification of behavior using unsupervised temporal neural networks

    International Nuclear Information System (INIS)

    Adair, K.L.

    1998-03-01

    Adding recurrent connections to unsupervised neural networks used for clustering creates a temporal neural network which clusters a sequence of inputs as they appear over time. The model presented combines the Jordan architecture with the unsupervised learning technique Adaptive Resonance Theory, Fuzzy ART. The combination yields a neural network capable of quickly clustering sequential pattern sequences as the sequences are generated. The applicability of the architecture is illustrated through a facility monitoring problem

  14. The neural components of empathy: Predicting daily prosocial behavior

    Science.gov (United States)

    Rameson, Lian T.; Lieberman, Matthew D.

    2014-01-01

    Previous neuroimaging studies on empathy have not clearly identified neural systems that support the three components of empathy: affective congruence, perspective-taking, and prosocial motivation. These limitations stem from a focus on a single emotion per study, minimal variation in amount of social context provided, and lack of prosocial motivation assessment. In the current investigation, 32 participants completed a functional magnetic resonance imaging session assessing empathic responses to individuals experiencing painful, anxious, and happy events that varied in valence and amount of social context provided. They also completed a 14-day experience sampling survey that assessed real-world helping behaviors. The results demonstrate that empathy for positive and negative emotions selectively activates regions associated with positive and negative affect, respectively. In addition, the mirror system was more active during empathy for context-independent events (pain), whereas the mentalizing system was more active during empathy for context-dependent events (anxiety, happiness). Finally, the septal area, previously linked to prosocial motivation, was the only region that was commonly activated across empathy for pain, anxiety, and happiness. Septal activity during each of these empathic experiences was predictive of daily helping. These findings suggest that empathy has multiple input pathways, produces affect-congruent activations, and results in septally mediated prosocial motivation. PMID:22887480

  15. The neural components of empathy: predicting daily prosocial behavior.

    Science.gov (United States)

    Morelli, Sylvia A; Rameson, Lian T; Lieberman, Matthew D

    2014-01-01

    Previous neuroimaging studies on empathy have not clearly identified neural systems that support the three components of empathy: affective congruence, perspective-taking, and prosocial motivation. These limitations stem from a focus on a single emotion per study, minimal variation in amount of social context provided, and lack of prosocial motivation assessment. In the current investigation, 32 participants completed a functional magnetic resonance imaging session assessing empathic responses to individuals experiencing painful, anxious, and happy events that varied in valence and amount of social context provided. They also completed a 14-day experience sampling survey that assessed real-world helping behaviors. The results demonstrate that empathy for positive and negative emotions selectively activates regions associated with positive and negative affect, respectively. In addition, the mirror system was more active during empathy for context-independent events (pain), whereas the mentalizing system was more active during empathy for context-dependent events (anxiety, happiness). Finally, the septal area, previously linked to prosocial motivation, was the only region that was commonly activated across empathy for pain, anxiety, and happiness. Septal activity during each of these empathic experiences was predictive of daily helping. These findings suggest that empathy has multiple input pathways, produces affect-congruent activations, and results in septally mediated prosocial motivation.

  16. Neural correlates of behavior therapy for Tourette's disorder.

    Science.gov (United States)

    Deckersbach, Thilo; Chou, Tina; Britton, Jennifer C; Carlson, Lindsay E; Reese, Hannah E; Siev, Jedidiah; Scahill, Lawrence; Piacentini, John C; Woods, Douglas W; Walkup, John T; Peterson, Alan L; Dougherty, Darin D; Wilhelm, Sabine

    2014-12-30

    Tourette's disorder, also called Tourette syndrome (TS), is characterized by motor and vocal tics that can cause significant impairment in daily functioning. Tics are believed to be due to failed inhibition of both associative and motor cortico-striato-thalamo-cortical pathways. Comprehensive Behavioral Intervention for Tics (CBIT), which is an extension of Habit Reversal Therapy (HRT), teaches patients to become more aware of sensations that reliably precede tics (premonitory urges) and to initiate competing movements that inhibit the occurrence of tics. In this study, we used functional magnetic resonance imaging (fMRI) to investigate the neural changes associated with CBIT treatment in subjects with TS. Eight subjects with TS were matched with eight healthy controls in gender, education, age, and handedness. Subjects completed the Visuospatial Priming (VSP) task, a measure of response inhibition, during fMRI scanning before and after CBIT treatment (or waiting period for controls). For TS subjects, we found a significant decrease in striatal (putamen) activation from pre- to post-treatment. Change in VSP task-related activation from pre- to post-treatment in Brodmann's area 47 (the inferior frontal gyrus) was negatively correlated with changes in tic severity. CBIT may promote normalization of aberrant cortico-striato-thalamo-cortical associative and motor pathways in individuals with TS. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Probing neural cell behaviors through micro-/nano-patterned chitosan substrates

    International Nuclear Information System (INIS)

    Sung, Chun-Yen; Yang, Chung-Yao; Yeh, J Andrew; Chen, Wen-Shiang; Wang, Yang-Kao; Cheng, Chao-Min

    2015-01-01

    In this study, we describe the development of surface-modified chitosan substrates to examine topographically related Neuro-2a cell behaviors. Different functional groups can be modified on chitosan surfaces to probe Neuro-2a cell morphology. To prepare chitosan substrates with micro/nano-scaled features, we demonstrated an easy-to-handle method that combined photolithography, inductively coupled plasma reactive ion etching, Ag nanoparticle-assisted etching, and solution casting. The results show that Neuro-2a cells preferred to adhere to a flat chitosan surface rather than a nanotextured chitosan surface as evidenced by greater immobilization and differentiation, suggesting that surface topography is crucial for neural patterning. In addition, we developed chitosan substrates with different geometric patterns and flat region depth; this allowed us to re-arrange or re-pattern Neuro-2a cell colonies at desired locations. We found that a polarity-induced micropattern provided the most suitable surface pattern for promoting neural network formation on a chitosan substrate. The cellular polarity of single Neuro-2a cell spreading correlated to a diamond-like geometry and neurite outgrowth was induced from the corners toward the grooves of the structures. This study provide greater insight into neurobiology, including neurotransmitter screening, electrophysiological stimulation platforms, and biomedical engineering. (paper)

  18. Behavioral and neural responses to infant and adult tears : The impact of maternal love withdrawal

    NARCIS (Netherlands)

    Hendricx-Riem, M.M.E.; van IJzendoorn, M.H.; De Carli, P.; Vingerhoets, A.J.J.M.; Bakermans-Kranenburg, M. J.

    2017-01-01

    The current study examined behavioral and neural responses to infant and adult tears, taking into account childhood experiences with parental love-withdrawal. With functional MRI (fMRI), we measured neural reactivity to pictures of infants and adults with and without tears on their faces in

  19. Isolation, characterization, and differentiation of multipotent neural progenitor cells from human cerebrospinal fluid in fetal cystic myelomeningocele

    Directory of Open Access Journals (Sweden)

    Mario Marotta

    2017-07-01

    Full Text Available Despite benefits of prenatal in utero repair of myelomeningocele, a severe type of spina bifida aperta, many of these patients will still suffer mild to severe impairment. One potential source of stem cells for new regenerative medicine-based therapeutic approaches for spinal cord injury repair is neural progenitor cells (NPCs in cerebrospinal fluid (CSF. To this aim, we extracted CSF from the cyst surrounding the exposed neural placode during the surgical repair of myelomeningocele in 6 fetuses (20 to 26 weeks of gestation. In primary cultured CSF-derived cells, neurogenic properties were confirmed by in vitro differentiation into various neural lineage cell types, and NPC markers expression (TBR2, CD15, SOX2 were detected by immunofluorescence and RT-PCR analysis. Differentiation into three neural lineages was corroborated by arbitrary differentiation (depletion of growths factors or explicit differentiation as neuronal, astrocyte, or oligodendrocyte cell types using specific induction mediums. Differentiated cells showed the specific expression of neural differentiation markers (βIII-tubulin, GFAP, CNPase, oligo-O1. In myelomeningocele patients, CSF-derived cells could become a potential source of NPCs with neurogenic capacity. Our findings support the development of innovative stem-cell-based therapeutics by autologous transplantation of CSF-derived NPCs in damaged spinal cords, such as myelomeningocele, thus promoting neural tissue regeneration in fetuses.

  20. Oxygen-controlled automated neural differentiation of mouse embryonic stem cells.

    Science.gov (United States)

    Mondragon-Teran, Paul; Tostoes, Rui; Mason, Chris; Lye, Gary J; Veraitch, Farlan S

    2013-03-01

    Automation and oxygen tension control are two tools that provide significant improvements to the reproducibility and efficiency of stem cell production processes. the aim of this study was to establish a novel automation platform capable of controlling oxygen tension during both the cell-culture and liquid-handling steps of neural differentiation processes. We built a bespoke automation platform, which enclosed a liquid-handling platform in a sterile, oxygen-controlled environment. An airtight connection was used to transfer cell culture plates to and from an automated oxygen-controlled incubator. Our results demonstrate that our system yielded comparable cell numbers, viabilities, metabolism profiles and differentiation efficiencies when compared with traditional manual processes. Interestingly, eliminating exposure to ambient conditions during the liquid-handling stage resulted in significant improvements in the yield of MAP2-positive neural cells, indicating that this level of control can improve differentiation processes. This article describes, for the first time, an automation platform capable of maintaining oxygen tension control during both the cell-culture and liquid-handling stages of a 2D embryonic stem cell differentiation process.

  1. Silicon nanowires enhanced proliferation and neuronal differentiation of neural stem cell with vertically surface microenvironment.

    Science.gov (United States)

    Yan, Qiuting; Fang, Lipao; Wei, Jiyu; Xiao, Guipeng; Lv, Meihong; Ma, Quanhong; Liu, Chunfeng; Wang, Wang

    2017-09-01

    Owing to its biocompatibility, noncytotoxicity, biodegradability and three-dimensional structure, vertically silicon nanowires (SiNWs) arrays are a promising scaffold material for tissue engineering, regenerative medicine and relevant medical applications. Recently, its osteogenic differentiation effects, reorganization of cytoskeleton and regulation of the fate on stem cells have been demonstrated. However, it still remains unknown whether SiNWs arrays could affect the proliferation and neuronal differentiation of neural stem cells (NSCs) or not. In the present study, we have employed vertically aligned SiNWs arrays as culture systems for NSCs and proved that the scaffold material could promote the proliferation and neuronal differentiation of NSCs while maintaining excellent cell viability and stemness. Immunofluorescence imaging analysis, Western blot and RT-PCR results reveal that NSCs proliferation and neuronal differentiation efficiency on SiNWs arrays are significant greater than that on silicon wafers. These results implicate SiNWs arrays could offer a powerful platform for NSCs research and NSCs-based therapy in the field of neural tissue engineering.

  2. A phenotypic structure and neural correlates of compulsive behaviors in adolescents.

    Directory of Open Access Journals (Sweden)

    Chantale Montigny

    Full Text Available A compulsivity spectrum has been hypothesized to exist across Obsessive-Compulsive disorder (OCD, Eating Disorders (ED, substance abuse (SA and binge-drinking (BD. The objective was to examine the validity of this compulsivity spectrum, and differentiate it from an externalizing behaviors dimension, but also to look at hypothesized personality and neural correlates.A community-sample of adolescents (N=1938; mean age 14.5 years, and their parents were recruited via high-schools in 8 European study sites. Data on adolescents' psychiatric symptoms, DSM diagnoses (DAWBA and substance use behaviors (AUDIT and ESPAD were collected through adolescent- and parent-reported questionnaires and interviews. The phenotypic structure of compulsive behaviors was then tested using structural equation modeling. The model was validated using personality variables (NEO-FFI and TCI, and Voxel-Based Morphometry (VBM analysis.Compulsivity symptoms best fit a higher-order two factor model, with ED and OCD loading onto a compulsivity factor, and BD and SA loading onto an externalizing factor, composed also of ADHD and conduct disorder symptoms. The compulsivity construct correlated with neuroticism (r=0.638; p ≤ 0.001, conscientiousness (r=0.171; p ≤ 0.001, and brain gray matter volume in left and right orbitofrontal cortex, right ventral striatum and right dorsolateral prefrontal cortex. The externalizing factor correlated with extraversion (r=0.201; p ≤ 0.001, novelty-seeking (r=0.451; p ≤ 0.001, and negatively with gray matter volume in the left inferior and middle frontal gyri.Results suggest that a compulsivity spectrum exists in an adolescent, preclinical sample and accounts for variance in both OCD and ED, but not substance-related behaviors, and can be differentiated from an externalizing spectrum.

  3. A phenotypic structure and neural correlates of compulsive behaviors in adolescents.

    Science.gov (United States)

    Montigny, Chantale; Castellanos-Ryan, Natalie; Whelan, Robert; Banaschewski, Tobias; Barker, Gareth J; Büchel, Christian; Gallinat, Jürgen; Flor, Herta; Mann, Karl; Paillère-Martinot, Marie-Laure; Nees, Frauke; Lathrop, Mark; Loth, Eva; Paus, Tomas; Pausova, Zdenka; Rietschel, Marcella; Schumann, Gunter; Smolka, Michael N; Struve, Maren; Robbins, Trevor W; Garavan, Hugh; Conrod, Patricia J

    2013-01-01

    A compulsivity spectrum has been hypothesized to exist across Obsessive-Compulsive disorder (OCD), Eating Disorders (ED), substance abuse (SA) and binge-drinking (BD). The objective was to examine the validity of this compulsivity spectrum, and differentiate it from an externalizing behaviors dimension, but also to look at hypothesized personality and neural correlates. A community-sample of adolescents (N=1938; mean age 14.5 years), and their parents were recruited via high-schools in 8 European study sites. Data on adolescents' psychiatric symptoms, DSM diagnoses (DAWBA) and substance use behaviors (AUDIT and ESPAD) were collected through adolescent- and parent-reported questionnaires and interviews. The phenotypic structure of compulsive behaviors was then tested using structural equation modeling. The model was validated using personality variables (NEO-FFI and TCI), and Voxel-Based Morphometry (VBM) analysis. Compulsivity symptoms best fit a higher-order two factor model, with ED and OCD loading onto a compulsivity factor, and BD and SA loading onto an externalizing factor, composed also of ADHD and conduct disorder symptoms. The compulsivity construct correlated with neuroticism (r=0.638; p ≤ 0.001), conscientiousness (r=0.171; p ≤ 0.001), and brain gray matter volume in left and right orbitofrontal cortex, right ventral striatum and right dorsolateral prefrontal cortex. The externalizing factor correlated with extraversion (r=0.201; p ≤ 0.001), novelty-seeking (r=0.451; p ≤ 0.001), and negatively with gray matter volume in the left inferior and middle frontal gyri. Results suggest that a compulsivity spectrum exists in an adolescent, preclinical sample and accounts for variance in both OCD and ED, but not substance-related behaviors, and can be differentiated from an externalizing spectrum.

  4. A Phenotypic Structure and Neural Correlates of Compulsive Behaviors in Adolescents

    Science.gov (United States)

    Montigny, Chantale; Castellanos-Ryan, Natalie; Whelan, Robert; Banaschewski, Tobias; Barker, Gareth J.; Büchel, Christian; Gallinat, Jürgen; Flor, Herta; Mann, Karl; Paillère-Martinot, Marie-Laure; Nees, Frauke; Lathrop, Mark; Loth, Eva; Paus, Tomas; Pausova, Zdenka; Rietschel, Marcella; Schumann, Gunter; Smolka, Michael N.; Struve, Maren; Robbins, Trevor W.; Garavan, Hugh; Conrod, Patricia J.

    2013-01-01

    Background A compulsivity spectrum has been hypothesized to exist across Obsessive-Compulsive disorder (OCD), Eating Disorders (ED), substance abuse (SA) and binge-drinking (BD). The objective was to examine the validity of this compulsivity spectrum, and differentiate it from an externalizing behaviors dimension, but also to look at hypothesized personality and neural correlates. Method A community-sample of adolescents (N=1938; mean age 14.5 years), and their parents were recruited via high-schools in 8 European study sites. Data on adolescents’ psychiatric symptoms, DSM diagnoses (DAWBA) and substance use behaviors (AUDIT and ESPAD) were collected through adolescent- and parent-reported questionnaires and interviews. The phenotypic structure of compulsive behaviors was then tested using structural equation modeling. The model was validated using personality variables (NEO-FFI and TCI), and Voxel-Based Morphometry (VBM) analysis. Results Compulsivity symptoms best fit a higher-order two factor model, with ED and OCD loading onto a compulsivity factor, and BD and SA loading onto an externalizing factor, composed also of ADHD and conduct disorder symptoms. The compulsivity construct correlated with neuroticism (r=0.638; p≤0.001), conscientiousness (r=0.171; p≤0.001), and brain gray matter volume in left and right orbitofrontal cortex, right ventral striatum and right dorsolateral prefrontal cortex. The externalizing factor correlated with extraversion (r=0.201; p≤0.001), novelty-seeking (r=0.451; p≤0.001), and negatively with gray matter volume in the left inferior and middle frontal gyri. Conclusions Results suggest that a compulsivity spectrum exists in an adolescent, preclinical sample and accounts for variance in both OCD and ED, but not substance-related behaviors, and can be differentiated from an externalizing spectrum. PMID:24244633

  5. Differential Neural Responses to Food Images in Women with Bulimia versus Anorexia Nervosa

    Science.gov (United States)

    Brooks, Samantha J.; O′Daly, Owen G.; Uher, Rudolf; Friederich, Hans-Christoph; Giampietro, Vincent; Brammer, Michael; Williams, Steven C. R.; Schiöth, Helgi B.; Treasure, Janet; Campbell, Iain C.

    2011-01-01

    Background Previous fMRI studies show that women with eating disorders (ED) have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, differential neural activation to thinking about eating food, between women with anorexia nervosa (AN) and bulimia nervosa (BN) is not known. Methods We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls [HC]) while they view food images during functional Magnetic Resonance Imaging (fMRI). Results In response to food (vs non-food) images, women with BN showed greater neural activation in the visual cortex, right dorsolateral prefrontal cortex, right insular cortex and precentral gyrus, women with AN showed greater activation in the right dorsolateral prefrontal cortex, cerebellum and right precuneus. HC women activated the cerebellum, right insular cortex, right medial temporal lobe and left caudate. Direct comparisons revealed that compared to HC, the BN group showed relative deactivation in the bilateral superior temporal gyrus/insula, and visual cortex, and compared to AN had relative deactivation in the parietal lobe and dorsal posterior cingulate cortex, but greater activation in the caudate, superior temporal gyrus, right insula and supplementary motor area. Conclusions Women with AN and BN activate top-down cognitive control in response to food images, yet women with BN have increased activation in reward and somatosensory regions, which might impinge on cognitive control over food consumption and binge eating. PMID:21799807

  6. The 128-channel fully differential digital integrated neural recording and stimulation interface.

    Science.gov (United States)

    Shahrokhi, Farzaneh; Abdelhalim, Karim; Serletis, Demitre; Carlen, Peter L; Genov, Roman

    2010-06-01

    We present a fully differential 128-channel integrated neural interface. It consists of an array of 8 X 16 low-power low-noise signal-recording and generation circuits for electrical neural activity monitoring and stimulation, respectively. The recording channel has two stages of signal amplification and conditioning with and a fully differential 8-b column-parallel successive approximation (SAR) analog-to-digital converter (ADC). The total measured power consumption of each recording channel, including the SAR ADC, is 15.5 ¿W. The measured input-referred noise is 6.08 ¿ Vrms over a 5-kHz bandwidth, resulting in a noise efficiency factor of 5.6. The stimulation channel performs monophasic or biphasic voltage-mode stimulation, with a maximum stimulation current of 5 mA and a quiescent power dissipation of 51.5 ¿W. The design is implemented in 0.35-¿m complementary metal-oxide semiconductor technology with the channel pitch of 200 ¿m for a total die size of 3.4 mm × 2.5 mm and a total power consumption of 9.33 mW. The neural interface was validated in in vitro recording of a low-Mg(2+)/high-K(+) epileptic seizure model in an intact hippocampus of a mouse.

  7. Differentiation of insulin-producing cells from human neural progenitor cells.

    Directory of Open Access Journals (Sweden)

    Yuichi Hori

    2005-04-01

    Full Text Available BACKGROUND: Success in islet-transplantation-based therapies for type 1 diabetes, coupled with a worldwide shortage of transplant-ready islets, has motivated efforts to develop renewable sources of islet-replacement tissue. Islets and neurons share features, including common developmental programs, and in some species brain neurons are the principal source of systemic insulin. METHODS AND FINDINGS: Here we show that brain-derived human neural progenitor cells, exposed to a series of signals that regulate in vivo pancreatic islet development, form clusters of glucose-responsive insulin-producing cells (IPCs. During in vitro differentiation of neural progenitor cells with this novel method, genes encoding essential known in vivo regulators of pancreatic islet development were expressed. Following transplantation into immunocompromised mice, IPCs released insulin C-peptide upon glucose challenge, remained differentiated, and did not form detectable tumors. CONCLUSION: Production of IPCs solely through extracellular factor modulation in the absence of genetic manipulations may promote strategies to derive transplantable islet-replacement tissues from human neural progenitor cells and other types of multipotent human stem cells.

  8. Differential neural responses to food images in women with bulimia versus anorexia nervosa.

    Science.gov (United States)

    Brooks, Samantha J; O'Daly, Owen G; Uher, Rudolf; Friederich, Hans-Christoph; Giampietro, Vincent; Brammer, Michael; Williams, Steven C R; Schiöth, Helgi B; Treasure, Janet; Campbell, Iain C

    2011-01-01

    Previous fMRI studies show that women with eating disorders (ED) have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, differential neural activation to thinking about eating food, between women with anorexia nervosa (AN) and bulimia nervosa (BN) is not known. We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls [HC]) while they view food images during functional Magnetic Resonance Imaging (fMRI). In response to food (vs non-food) images, women with BN showed greater neural activation in the visual cortex, right dorsolateral prefrontal cortex, right insular cortex and precentral gyrus, women with AN showed greater activation in the right dorsolateral prefrontal cortex, cerebellum and right precuneus. HC women activated the cerebellum, right insular cortex, right medial temporal lobe and left caudate. Direct comparisons revealed that compared to HC, the BN group showed relative deactivation in the bilateral superior temporal gyrus/insula, and visual cortex, and compared to AN had relative deactivation in the parietal lobe and dorsal posterior cingulate cortex, but greater activation in the caudate, superior temporal gyrus, right insula and supplementary motor area. Women with AN and BN activate top-down cognitive control in response to food images, yet women with BN have increased activation in reward and somatosensory regions, which might impinge on cognitive control over food consumption and binge eating.

  9. Acceleration of astrocytic differentiation in neural stem cells surviving X-irradiation.

    Science.gov (United States)

    Ozeki, Ayumi; Suzuki, Keiji; Suzuki, Masatoshi; Ozawa, Hiroki; Yamashita, Shunichi

    2012-03-28

    Neural stem cells (NSCs) are highly susceptible to DNA double-strand breaks; however, little is known about the effects of radiation in cells surviving radiation. Although the nestin-positive NSCs predominantly became glial fibrillary acidic protein (GFAP)-positive in differentiation-permissive medium, little or no cells were GFAP positive in proliferation-permissive medium. We found that more than half of the cells surviving X-rays became GFAP positive in proliferation-permissive medium. Moreover, localized irradiation stimulated differentiation of cells outside the irradiated area. These results indicate for the first time that ionizing radiation is able to stimulate astrocyte-specific differentiation of surviving NSCs, whose process is mediated both by the direct activation of nuclear factor-κB and by the indirect bystander effect induced by X-irradiation.

  10. Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells

    DEFF Research Database (Denmark)

    Dreyer-Andersen, Nanna; Almeida, Ana Sofia; Jensen, Pia

    2018-01-01

    cells constitute an alternative source of cells for transplantation in Parkinson's disease, but efficient protocols for controlled dopaminergic differentiation need to be developed. Short-term, low-level carbon monoxide (CO) exposure has been shown to affect signaling in several tissues, resulting...... in both protection and generation of reactive oxygen species. The present study investigated the effect of CO produced by a novel CO-releasing molecule on dopaminergic differentiation of human neural stem cells. Short-term exposure to 25 ppm CO at days 0 and 4 significantly increased the relative content...... of β-tubulin III-immunoreactive immature neurons and tyrosine hydroxylase expressing catecholaminergic neurons, as assessed 6 days after differentiation. Also the number of microtubule associated protein 2-positive mature neurons had increased significantly. Moreover, the content of apoptotic cells...

  11. Increasing Human Neural Stem Cell Transplantation Dose Alters Oligodendroglial and Neuronal Differentiation after Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Katja M. Piltti

    2017-06-01

    Full Text Available Multipotent human central nervous system-derived neural stem cells transplanted at doses ranging from 10,000 (low to 500,000 (very high cells differentiated predominantly into the oligodendroglial lineage. However, while the number of engrafted cells increased linearly in relationship to increasing dose, the proportion of oligodendrocytic cells declined. Increasing dose resulted in a plateau of engraftment, enhanced neuronal differentiation, and increased distal migration caudal to the transplantation sites. Dose had no effect on terminal sensory recovery or open-field locomotor scores. However, total human cell number and decreased oligodendroglial proportion were correlated with hindlimb girdle coupling errors. Conversely, greater oligodendroglial proportion was correlated with increased Ab step pattern, decreased swing speed, and increased paw intensity, consistent with improved recovery. These data suggest that transplant dose, and/or target niche parameters can regulate donor cell engraftment, differentiation/maturation, and lineage-specific migration profiles.

  12. Spatial patterns of persistent neural activity vary with the behavioral context of short-term memory.

    Science.gov (United States)

    Daie, Kayvon; Goldman, Mark S; Aksay, Emre R F

    2015-02-18

    A short-term memory can be evoked by different inputs and control separate targets in different behavioral contexts. To address the circuit mechanisms underlying context-dependent memory function, we determined through optical imaging how memory is encoded at the whole-network level in two behavioral settings. Persistent neural activity maintaining a memory of desired eye position was imaged throughout the oculomotor integrator after saccadic or optokinetic stimulation. While eye position was encoded by the amplitude of network activity, the spatial patterns of firing were context dependent: cells located caudally generally were most persistent following saccadic input, whereas cells located rostrally were most persistent following optokinetic input. To explain these data, we computationally identified four independent modes of network activity and found these were differentially accessed by saccadic and optokinetic inputs. These results show how a circuit can simultaneously encode memory value and behavioral context, respectively, in its amplitude and spatial pattern of persistent firing. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. 3D differentiation of neural stem cells in macroporous photopolymerizable hydrogel scaffolds.

    Directory of Open Access Journals (Sweden)

    Hang Li

    Full Text Available Neural stem/progenitor cells (NSPCs are the stem cell of the adult central nervous system (CNS. These cells are able to differentiate into the major cell types found in the CNS (neurons, oligodendrocytes, astrocytes, thus NSPCs are the mechanism by which the adult CNS could potentially regenerate after injury or disorder. Microenviromental factors are critical for guiding NSPC differentiation and are thus important for neural tissue engineering. In this study, D-mannitol crystals were mixed with photocrosslinkable methacrylamide chitosan (MAC as a porogen to enhance pore size during hydrogel formation. D-mannitol was admixed to MAC at 5, 10 and 20 wt% D-mannitol per total initial hydrogel weight. D-mannitol crystals were observed to dissolve and leave the scaffold within 1 hr. Quantification of resulting average pore sizes showed that D-mannitol addition resulted in larger average pore size (5 wt%, 4060±160 µm(2, 10 wt%, 6330±1160 µm(2, 20 wt%, 7600±1550 µm(2 compared with controls (0 wt%, 3150±220 µm(2. Oxygen diffusion studies demonstrated that larger average pore area resulted in enhanced oxygen diffusion through scaffolds. Finally, the differentiation responses of NSPCs to phenotypic differentiation conditions were studied for neurons, astrocytes and oligodendrocytes in hydrogels of varied porosity over 14 d. Quantification of total cell numbers at day 7 and 14, showed that cell numbers decreased with increased porosity and over the length of the culture. At day 14 immunohistochemistry quantification for primary cell types demonstrated significant differentiation to the desired cells types, and that total percentages of each cell type was greatest when scaffolds were more porous. These results suggest that larger pore sizes in MAC hydrogels effectively promote NSPC 3D differentiation.

  14. Dissociable Patterns of Neural Activity during Response Inhibition in Depressed Adolescents with and without Suicidal Behavior

    Science.gov (United States)

    Pan, Lisa A.; Batezati-Alves, Silvia C.; Almeida, Jorge R. C.; Segreti, AnnaMaria; Akkal, Dalila; Hassel, Stefanie; Lakdawala, Sara; Brent, David A.; Phillips, Mary L.

    2011-01-01

    Objectives: Impaired attentional control and behavioral control are implicated in adult suicidal behavior. Little is known about the functional integrity of neural circuitry supporting these processes in suicidal behavior in adolescence. Method: Functional magnetic resonance imaging was used in 15 adolescent suicide attempters with a history of…

  15. Seeing Jesus in toast: Neural and behavioral correlates of face pareidolia

    OpenAIRE

    Liu, Jiangang; Li, Jun; Feng, Lu; Li, Ling; Tian, Jie; Lee, Kang

    2014-01-01

    Face pareidolia is the illusory perception of non-existent faces. The present study, for the first time, contrasted behavioral and neural responses of face pareidolia with those of letter pareidolia to explore face-specific behavioral and neural responses during illusory face processing. Participants were shown pure-noise images but were led to believe that 50% of them contained either faces or letters; they reported seeing faces or letters illusorily 34% and 38% of the time, respectively. Th...

  16. Modulation of neural circuits: how stimulus context shapes innate behavior in Drosophila

    OpenAIRE

    Su, Chih-Ying; Wang, Jing W.

    2014-01-01

    Remarkable advances have been made in recent years in our understanding of innate behavior and the underlying neural circuits. In particular, a wealth of neuromodulatory mechanisms have been uncovered that can alter the input-output relationship of a hereditary neural circuit. It is now clear that this inbuilt flexibility allows animals to modify their behavioral responses according to environmental cues, metabolic demands and physiological states. Here, we discuss recent insights into how mo...

  17. Let7a involves in neural stem cell differentiation relating with TLX level.

    Science.gov (United States)

    Song, Juhyun; Cho, Kyoung Joo; Oh, Yumi; Lee, Jong Eun

    2015-07-10

    Neural stem cells (NSCs) have the potential for differentiation into neurons known as a groundbreaking therapeutic solution for central nervous system (CNS) diseases. To resolve the therapeutic efficiency of NSCs, recent researchers have focused on the study on microRNA's role in CNS. Some micro RNAs have been reported significant functions in NSC self-renewal and differentiation through the post-transcriptional regulation of neurogenesis genes. MicroRNA-Let7a (Let7a) has known as the regulator of diverse cellular mechanisms including cell differentiation and proliferation. In present study, we investigated whether Let7a regulates NSC differentiation by targeting the nuclear receptor TLX, which is an essential regulator of NSC self-renewal, proliferation and differentiation. We performed the following experiments: western blot analysis, TaqMan assay, RT-PCR, and immunocytochemistry to confirm the alteration of NSCs. Our data showed that let7a play important roles in controlling NSC fate determination. Thus, manipulating Let-7A and TLX could be a novel strategy to enhance the efficiency of NSC's neuronal differentiation for CNS disorders. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Melatonin enhances neural stem cell differentiation and engraftment by increasing mitochondrial function.

    Science.gov (United States)

    Mendivil-Perez, Miguel; Soto-Mercado, Viviana; Guerra-Librero, Ana; Fernandez-Gil, Beatriz I; Florido, Javier; Shen, Ying-Qiang; Tejada, Miguel A; Capilla-Gonzalez, Vivian; Rusanova, Iryna; Garcia-Verdugo, José M; Acuña-Castroviejo, Darío; López, Luis Carlos; Velez-Pardo, Carlos; Jimenez-Del-Rio, Marlene; Ferrer, José M; Escames, Germaine

    2017-09-01

    Neural stem cells (NSCs) are regarded as a promising therapeutic approach to protecting and restoring damaged neurons in neurodegenerative diseases (NDs) such as Parkinson's disease and Alzheimer's disease (PD and AD, respectively). However, new research suggests that NSC differentiation is required to make this strategy effective. Several studies have demonstrated that melatonin increases mature neuronal markers, which reflects NSC differentiation into neurons. Nevertheless, the possible involvement of mitochondria in the effects of melatonin during NSC differentiation has not yet been fully established. We therefore tested the impact of melatonin on NSC proliferation and differentiation in an attempt to determine whether these actions depend on modulating mitochondrial activity. We measured proliferation and differentiation markers, mitochondrial structural and functional parameters as well as oxidative stress indicators and also evaluated cell transplant engraftment. This enabled us to show that melatonin (25 μM) induces NSC differentiation into oligodendrocytes and neurons. These effects depend on increased mitochondrial mass/DNA/complexes, mitochondrial respiration, and membrane potential as well as ATP synthesis in NSCs. It is also interesting to note that melatonin prevented oxidative stress caused by high levels of mitochondrial activity. Finally, we found that melatonin enriches NSC engraftment in the ND mouse model following transplantation. We concluded that a combined therapy involving transplantation of NSCs pretreated with pharmacological doses of melatonin could efficiently restore neuronal cell populations in PD and AD mouse models depending on mitochondrial activity promotion. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Omega-3 Polyunsaturated Fatty Acids Enhance Neuronal Differentiation in Cultured Rat Neural Stem Cells

    Directory of Open Access Journals (Sweden)

    Masanori Katakura

    2013-01-01

    Full Text Available Polyunsaturated fatty acids (PUFAs can induce neurogenesis and recovery from brain diseases. However, the exact mechanisms of the beneficial effects of PUFAs have not been conclusively described. We recently reported that docosahexaenoic acid (DHA induced neuronal differentiation by decreasing Hes1 expression and increasing p27kip1 expression, which causes cell cycle arrest in neural stem cells (NSCs. In the present study, we examined the effect of eicosapentaenoic acid (EPA and arachidonic acid (AA on differentiation, expression of basic helix-loop-helix transcription factors (Hes1, Hes6, and NeuroD, and the cell cycle of cultured NSCs. EPA also increased mRNA levels of Hes1, an inhibitor of neuronal differentiation, Hes6, an inhibitor of Hes1, NeuroD, and Map2 mRNA and Tuj-1-positive cells (a neuronal marker, indicating that EPA induced neuronal differentiation. EPA increased the mRNA levels of p21cip1 and p27kip1, a cyclin-dependent kinase inhibitor, which indicated that EPA induced cell cycle arrest. Treatment with AA decreased Hes1 mRNA but did not affect NeuroD and Map2 mRNA levels. Furthermore, AA did not affect the number of Tuj-1-positive cells or cell cycle progression. These results indicated that EPA could be involved in neuronal differentiation by mechanisms alternative to those of DHA, whereas AA did not affect neuronal differentiation in NSCs.

  20. Novel adaptive neural control of flexible air-breathing hypersonic vehicles based on sliding mode differentiator

    Directory of Open Access Journals (Sweden)

    Bu Xiangwei

    2015-08-01

    Full Text Available A novel adaptive neural control strategy is exploited for the longitudinal dynamics of a generic flexible air-breathing hypersonic vehicle (FAHV. By utilizing functional decomposition method, the dynamics of FAHV is decomposed into the velocity subsystem and the altitude subsystem. For each subsystem, only one neural network is employed for the unknown function approximation. To further reduce the computational burden, minimal-learning parameter (MLP technology is used to estimate the norm of ideal weight vectors rather than their elements. By introducing sliding mode differentiator (SMD to estimate the newly defined variables, there is no need for the strict-feedback form and virtual controller. Hence the developed control law is considerably simpler than the ones derived from back-stepping scheme. Finally, simulation studies are made to illustrate the effectiveness of the proposed control approach in spite of the flexible effects, system uncertainties and varying disturbances.

  1. Design and Implementation of Behavior Recognition System Based on Convolutional Neural Network

    Directory of Open Access Journals (Sweden)

    Yu Bo

    2017-01-01

    Full Text Available We build a set of human behavior recognition system based on the convolution neural network constructed for the specific human behavior in public places. Firstly, video of human behavior data set will be segmented into images, then we process the images by the method of background subtraction to extract moving foreground characters of body. Secondly, the training data sets are trained into the designed convolution neural network, and the depth learning network is constructed by stochastic gradient descent. Finally, the various behaviors of samples are classified and identified with the obtained network model, and the recognition results are compared with the current mainstream methods. The result show that the convolution neural network can study human behavior model automatically and identify human’s behaviors without any manually annotated trainings.

  2. Neural Differentiation of Human Adipose Tissue-Derived Stem Cells Involves Activation of the Wnt5a/JNK Signalling

    Directory of Open Access Journals (Sweden)

    Sujeong Jang

    2015-01-01

    Full Text Available Stem cells are a powerful resource for cell-based transplantation therapies, but understanding of stem cell differentiation at the molecular level is not clear yet. We hypothesized that the Wnt pathway controls stem cell maintenance and neural differentiation. We have characterized the transcriptional expression of Wnt during the neural differentiation of hADSCs. After neural induction, the expressions of Wnt2, Wnt4, and Wnt11 were decreased, but the expression of Wnt5a was increased compared with primary hADSCs in RT-PCR analysis. In addition, the expression levels of most Fzds and LRP5/6 ligand were decreased, but not Fzd3 and Fzd5. Furthermore, Dvl1 and RYK expression levels were downregulated in NI-hADSCs. There were no changes in the expression of ß-catenin and GSK3ß. Interestingly, Wnt5a expression was highly increased in NI-hADSCs by real time RT-PCR analysis and western blot. Wnt5a level was upregulated after neural differentiation and Wnt3, Dvl2, and Naked1 levels were downregulated. Finally, we found that the JNK expression was increased after neural induction and ERK level was decreased. Thus, this study shows for the first time how a single Wnt5a ligand can activate the neural differentiation pathway through the activation of Wnt5a/JNK pathway by binding Fzd3 and Fzd5 and directing Axin/GSK-3ß in hADSCs.

  3. Synaptic plasticity in a recurrent neural network for versatile and adaptive behaviors of a walking robot

    DEFF Research Database (Denmark)

    Grinke, Eduard; Tetzlaff, Christian; Wörgötter, Florentin

    2015-01-01

    correlation-based learning with synaptic scaling is applied to adequately change the connections of the network. By doing so, we can effectively exploit neural dynamics (i.e., hysteresis effects and single attractors) in the network to generate different turning angles with short-term memory for a walking...... dynamics, plasticity, sensory feedback, and biomechanics. Generating such versatile and adaptive behaviors for a many degrees-of-freedom (DOFs) walking robot is a challenging task. Thus, in this study, we present a bio-inspired approach to solve this task. Specifically, the approach combines neural...... mechanisms with plasticity, exteroceptive sensory feedback, and biomechanics. The neural mechanisms consist of adaptive neural sensory processing and modular neural locomotion control. The sensory processing is based on a small recurrent neural network consisting of two fully connected neurons. Online...

  4. The effect of rules on differential reinforcement of other behavior.

    Science.gov (United States)

    Watts, Amanda C; Wilder, David A; Gregory, Meagan K; Leon, Yanerys; Ditzian, Kyle

    2013-01-01

    Previous research on the treatment of problem behavior has shown differential reinforcement of other behavior (DRO) to be an effective behavior-reduction procedure. However, the extent to which presession descriptions of the DRO contingency enhance intervention effects has not been examined. In the current study, we compared a condition in which a presession rule that described the DRO contingency was given to a condition in which no rule was given for 4 participants. The target behavior was toy play, which served as an analogue to problem behavior maintained by automatic reinforcement. Results showed that DRO was more efficient for 1 participant and more effective for 2 participants when a rule was given. © Society for the Experimental Analysis of Behavior.

  5. The Effects of Low-Dose Bisphenol A and Bisphenol F on Neural Differentiation of a Fetal Brain-Derived Neural Progenitor Cell Line.

    Science.gov (United States)

    Fujiwara, Yuki; Miyazaki, Wataru; Koibuchi, Noriyuki; Katoh, Takahiko

    2018-01-01

    Environmental chemicals are known to disrupt the endocrine system in humans and to have adverse effects on several organs including the developing brain. Recent studies indicate that exposure to environmental chemicals during gestation can interfere with neuronal differentiation, subsequently affecting normal brain development in newborns. Xenoestrogen, bisphenol A (BPA), which is widely used in plastic products, is one such chemical. Adverse effects of exposure to BPA during pre- and postnatal periods include the disruption of brain function. However, the effect of BPA on neural differentiation remains unclear. In this study, we explored the effects of BPA or bisphenol F (BPF), an alternative compound for BPA, on neural differentiation using ReNcell, a human fetus-derived neural progenitor cell line. Maintenance in growth factor-free medium initiated the differentiation of ReNcell to neuronal cells including neurons, astrocytes, and oligodendrocytes. We exposed the cells to BPA or BPF for 3 days from the period of initiation and performed real-time PCR for neural markers such as β III-tubulin and glial fibrillary acidic protein (GFAP), and Olig2. The β III-tubulin mRNA level decreased in response to BPA, but not BPF, exposure. We also observed that the number of β III-tubulin-positive cells in the BPA-exposed group was less than that of the control group. On the other hand, there were no changes in the MAP2 mRNA level. These results indicate that BPA disrupts neural differentiation in human-derived neural progenitor cells, potentially disrupting brain development.

  6. The Effects of Low-Dose Bisphenol A and Bisphenol F on Neural Differentiation of a Fetal Brain-Derived Neural Progenitor Cell Line

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    Yuki Fujiwara

    2018-02-01

    Full Text Available Environmental chemicals are known to disrupt the endocrine system in humans and to have adverse effects on several organs including the developing brain. Recent studies indicate that exposure to environmental chemicals during gestation can interfere with neuronal differentiation, subsequently affecting normal brain development in newborns. Xenoestrogen, bisphenol A (BPA, which is widely used in plastic products, is one such chemical. Adverse effects of exposure to BPA during pre- and postnatal periods include the disruption of brain function. However, the effect of BPA on neural differentiation remains unclear. In this study, we explored the effects of BPA or bisphenol F (BPF, an alternative compound for BPA, on neural differentiation using ReNcell, a human fetus-derived neural progenitor cell line. Maintenance in growth factor-free medium initiated the differentiation of ReNcell to neuronal cells including neurons, astrocytes, and oligodendrocytes. We exposed the cells to BPA or BPF for 3 days from the period of initiation and performed real-time PCR for neural markers such as β III-tubulin and glial fibrillary acidic protein (GFAP, and Olig2. The β III-tubulin mRNA level decreased in response to BPA, but not BPF, exposure. We also observed that the number of β III-tubulin-positive cells in the BPA-exposed group was less than that of the control group. On the other hand, there were no changes in the MAP2 mRNA level. These results indicate that BPA disrupts neural differentiation in human-derived neural progenitor cells, potentially disrupting brain development.

  7. Personality psychopathology differentiates risky behaviors among women with bulimia nervosa.

    Science.gov (United States)

    Pearson, Carolyn M; Pisetsky, Emily M; Goldschmidt, Andrea B; Lavender, Jason M; Wonderlich, Stephen A; Crosby, Ross D; Engel, Scott G; Mitchell, James E; Crow, Scott J; Peterson, Carol B

    2016-07-01

    Individuals with bulimia nervosa (BN) frequently endorse risky behaviors such as self-harm and substance use. However, no studies of BN to date have examined factors associated with engaging in individual or co-occurring risky behaviors. Given that individuals with BN often have personality psychopathology, which has been linked to symptoms and course of illness, this study sought to examine how personality may differentiate engagement in risky behaviors among BN individuals. A sample of 133 women with BN completed self-report measures of personality psychopathology at baseline, and then reported on bulimic and risky behaviors (e.g., substance misuse, self-harm) over 2 weeks using ecological momentary assessment. A series of hierarchical multiple regression analyses were conducted to examine the unique associations between state-level predictor variables (each risky behavior, e.g., substance misuse, and combination of risky behaviors, e.g., substance misuse plus self-harm) and trait-level personality constructs. Substance misuse behavior, above and beyond all other risky behaviors, was significantly associated with higher scores on trait dissocial behavior (P = 0.004). Substance misuse in BN has a unique association with dissocial behavior, a personality trait characterized by hostility, impulsivity, and entitlement. These results suggest that targeting personality variables may help facilitate more effective treatment of risky behaviors, including substance use in BN. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:681-688). © 2016 Wiley Periodicals, Inc.

  8. Mode of effective connectivity within a putative neural network differentiates moral cognitions related to care and justice ethics.

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    Cáceda, Ricardo; James, G Andrew; Ely, Timothy D; Snarey, John; Kilts, Clinton D

    2011-02-25

    Moral sensitivity refers to the interpretive awareness of moral conflict and can be justice or care oriented. Justice ethics is associated primarily with human rights and the application of moral rules, whereas care ethics is related to human needs and a situational approach involving social emotions. Among the core brain regions involved in moral issue processing are: medial prefrontal cortex, anterior (ACC) and posterior (PCC) cingulate cortex, posterior superior temporal sulcus (pSTS), insula and amygdala. This study sought to inform the long standing debate of whether care and justice moral ethics represent one or two different forms of cognition. Model-free and model-based connectivity analysis were used to identify functional neural networks underlying care and justice ethics for a moral sensitivity task. In addition to modest differences in patterns of associated neural activity, distinct modes of functional and effective connectivity were observed for moral sensitivity for care and justice issues that were modulated by individual variation in moral ability. These results support a neurobiological differentiation between care and justice ethics and suggest that human moral behavior reflects the outcome of integrating opposing rule-based, self-other perspectives, and emotional responses.

  9. Mode of Effective Connectivity within a Putative Neural Network Differentiates Moral Cognitions Related to Care and Justice Ethics

    Science.gov (United States)

    Cáceda, Ricardo; James, G. Andrew; Ely, Timothy D.; Snarey, John; Kilts, Clinton D.

    2011-01-01

    Background Moral sensitivity refers to the interpretive awareness of moral conflict and can be justice or care oriented. Justice ethics is associated primarily with human rights and the application of moral rules, whereas care ethics is related to human needs and a situational approach involving social emotions. Among the core brain regions involved in moral issue processing are: medial prefrontal cortex, anterior (ACC) and posterior (PCC) cingulate cortex, posterior superior temporal sulcus (pSTS), insula and amygdala. This study sought to inform the long standing debate of whether care and justice moral ethics represent one or two different forms of cognition. Methodology/Principal Findings Model-free and model-based connectivity analysis were used to identify functional neural networks underlying care and justice ethics for a moral sensitivity task. In addition to modest differences in patterns of associated neural activity, distinct modes of functional and effective connectivity were observed for moral sensitivity for care and justice issues that were modulated by individual variation in moral ability. Conclusions/Significance These results support a neurobiological differentiation between care and justice ethics and suggest that human moral behavior reflects the outcome of integrating opposing rule-based, self-other perspectives, and emotional responses. PMID:21364916

  10. Mode of effective connectivity within a putative neural network differentiates moral cognitions related to care and justice ethics.

    Directory of Open Access Journals (Sweden)

    Ricardo Cáceda

    Full Text Available BACKGROUND: Moral sensitivity refers to the interpretive awareness of moral conflict and can be justice or care oriented. Justice ethics is associated primarily with human rights and the application of moral rules, whereas care ethics is related to human needs and a situational approach involving social emotions. Among the core brain regions involved in moral issue processing are: medial prefrontal cortex, anterior (ACC and posterior (PCC cingulate cortex, posterior superior temporal sulcus (pSTS, insula and amygdala. This study sought to inform the long standing debate of whether care and justice moral ethics represent one or two different forms of cognition. METHODOLOGY/PRINCIPAL FINDINGS: Model-free and model-based connectivity analysis were used to identify functional neural networks underlying care and justice ethics for a moral sensitivity task. In addition to modest differences in patterns of associated neural activity, distinct modes of functional and effective connectivity were observed for moral sensitivity for care and justice issues that were modulated by individual variation in moral ability. CONCLUSIONS/SIGNIFICANCE: These results support a neurobiological differentiation between care and justice ethics and suggest that human moral behavior reflects the outcome of integrating opposing rule-based, self-other perspectives, and emotional responses.

  11. Effects of Substrate and Co-Culture on Neural Progenitor Cell Differentiation

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    Jones, Erin Boote [Iowa State Univ., Ames, IA (United States)

    2008-01-01

    In recent years the study of stem and progenitor cells has moved to the forefront of research. Since the isolation of human hematopoietic stem cells in 1988 and the subsequent discovery of a self renewing population of multipotent cells in many tissues, many researchers have envisioned a better understanding of development and potential clinical usage in intractable diseases. Both these goals, however, depend on a solid understanding of the intracellular and extracellular forces that cause stem cells to differentiate to a specific cell fate. Many diseases of large scale cell loss have been suggested as candidates for stem cell based treatments. It is proposed that replacing the function of the damaged or defective cells by specific differentiation of stem or progenitor cells could treat the disease. Before cells can be directed to specific lineages, the mechanisms of differentiation must be better understood. Differentiation in vivo is an intensively complex system that is difficult to study. The goal of this research is to develop further understanding of the effects of soluble and extracellular matrix (ECM) cues on the differentiation of neural progenitor cells with the use of a simplified in vitro culture system. Specific research objectives are to study the differentiation of neural progenitor cells in response to astrocyte conditioned medium and protein substrate composition and concentration. In an effort to reveal the mechanism of the conditioned medium interaction, a test for the presence of a feedback loop between progenitor cells and astrocytes is presented along with an examination of conditioned medium storage temperature, which can reveal enzymatic dependencies. An examination of protein substrate composition and concentration will help to reveal the role of any ECM interactions on differentiation. This thesis is organized into a literature review covering recent advances in use of external modulators of differentiation such as surface coatings, co

  12. Phospholipase D1 increases Bcl-2 expression during neuronal differentiation of rat neural stem cells.

    Science.gov (United States)

    Park, Shin-Young; Ma, Weina; Yoon, Sung Nyo; Kang, Min Jeong; Han, Joong-Soo

    2015-01-01

    We studied the possible role of phospholipase D1 (PLD1) in the neuronal differentiation, including neurite formation of neural stem cells. PLD1 protein and PLD activity increased during neuronal differentiation. Bcl-2 also increased. Downregulation of PLD1 by transfection with PLD1 siRNA or a dominant-negative form of PLD1 (DN-PLD1) inhibited both neurite outgrowth and Bcl-2 expression. PLD activity was dramatically reduced by a PLCγ (phospholipase Cγ) inhibitor (U73122), a Ca(2+)chelator (BAPTA-AM), and a PKCα (protein kinase Cα) inhibitor (RO320432). Furthermore, treatment with arachidonic acid (AA) which is generated by the action of PLA2 (phospholipase A2) on phosphatidic acid (a PLD1 product), increased the phosphorylation of p38 MAPK and CREB, as well as Bcl-2 expression, indicating that PLA2 is involved in the differentiation process resulting from PLD1 activation. PGE2 (prostaglandin E2), a cyclooxygenase product of AA, also increased during neuronal differentiation. Moreover, treatment with PGE2 increased the phosphorylation of p38 MAPK and CREB, as well as Bcl-2 expression, and this effect was inhibited by a PKA inhibitor (Rp-cAMP). As expected, inhibition of p38 MAPK resulted in loss of CREB activity, and when CREB activity was blocked with CREB siRNA, Bcl-2 production also decreased. We also showed that the EP4 receptor was required for the PKA/p38MAPK/CREB/Bcl-2 pathway. Taken together, these observations indicate that PLD1 is activated by PLCγ/PKCα signaling and stimulate Bcl-2 expression through PLA2/Cox2/EP4/PKA/p38MAPK/CREB during neuronal differentiation of rat neural stem cells.

  13. Biphasic electrical currents stimulation promotes both proliferation and differentiation of fetal neural stem cells.

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    Keun-A Chang

    2011-04-01

    Full Text Available The use of non-chemical methods to differentiate stem cells has attracted researchers from multiple disciplines, including the engineering and the biomedical fields. No doubt, growth factor based methods are still the most dominant of achieving some level of proliferation and differentiation control--however, chemical based methods are still limited by the quality, source, and amount of the utilized reagents. Well-defined non-chemical methods to differentiate stem cells allow stem cell scientists to control stem cell biology by precisely administering the pre-defined parameters, whether they are structural cues, substrate stiffness, or in the form of current flow. We have developed a culture system that allows normal stem cell growth and the option of applying continuous and defined levels of electric current to alter the cell biology of growing cells. This biphasic current stimulator chip employing ITO electrodes generates both positive and negative currents in the same culture chamber without affecting surface chemistry. We found that biphasic electrical currents (BECs significantly increased the proliferation of fetal neural stem cells (NSCs. Furthermore, BECs also promoted the differentiation of fetal NSCs into neuronal cells, as assessed using immunocytochemistry. Our results clearly show that BECs promote both the proliferation and neuronal differentiation of fetal NSCs. It may apply to the development of strategies that employ NSCs in the treatment of various neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases.

  14. A new module in neural differentiation control: two microRNAs upregulated by retinoic acid, miR-9 and -103, target the differentiation inhibitor ID2.

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    Daniela Annibali

    Full Text Available The transcription factor ID2 is an important repressor of neural differentiation strongly implicated in nervous system cancers. MicroRNAs (miRNAs are increasingly involved in differentiation control and cancer development. Here we show that two miRNAs upregulated on differentiation of neuroblastoma cells--miR-9 and miR-103--restrain ID2 expression by directly targeting the coding sequence and 3' untranslated region of the ID2 encoding messenger RNA, respectively. Notably, the two miRNAs show an inverse correlation with ID2 during neuroblastoma cell differentiation induced by retinoic acid. Overexpression of miR-9 and miR-103 in neuroblastoma cells reduces proliferation and promotes differentiation, as it was shown to occur upon ID2 inhibition. Conversely, an ID2 mutant that cannot be targeted by either miRNA prevents retinoic acid-induced differentiation more efficient than wild-type ID2. These findings reveal a new regulatory module involving two microRNAs upregulated during neural differentiation that directly target expression of the key differentiation inhibitor ID2, suggesting that its alteration may be involved in neural cancer development.

  15. Andrographolide Promotes Neural Differentiation of Rat Adipose Tissue-Derived Stromal Cells through Wnt/β-Catenin Signaling Pathway

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    Yan Liang

    2017-01-01

    Full Text Available Adipose tissue-derived stromal cells (ADSCs are a high-yield source of pluripotent stem cells for use in cell-based therapies. We explored the effect of andrographolide (ANDRO, one of the ingredients of the medicinal herb extract on the neural differentiation of rat ADSCs and associated molecular mechanisms. We observed that rat ADSCs were small and spindle-shaped and expressed multiple stem cell markers including nestin. They were multipotent as evidenced by adipogenic, osteogenic, chondrogenic, and neural differentiation under appropriate conditions. The proportion of cells exhibiting neural-like morphology was higher, and neurites developed faster in the ANDRO group than in the control group in the same neural differentiation medium. Expression levels of the neural lineage markers MAP2, tau, GFAP, and β-tubulin III were higher in the ANDRO group. ANDRO induced a concentration-dependent increase in Wnt/β-catenin signaling as evidenced by the enhanced expression of nuclear β-catenin and the inhibited form of GSK-3β (pSer9. Thus, this study shows for the first time how by enhancing the neural differentiation of ADSCs we expect that ANDRO pretreatment may increase the efficacy of adult stem cell transplantation in nervous system diseases, but more exploration is needed.

  16. Tracking differentiating neural progenitors in pluripotent cultures using microRNA-regulated lentiviral vectors.

    Science.gov (United States)

    Sachdeva, Rohit; Jönsson, Marie E; Nelander, Jenny; Kirkeby, Agnete; Guibentif, Carolina; Gentner, Bernhard; Naldini, Luigi; Björklund, Anders; Parmar, Malin; Jakobsson, Johan

    2010-06-22

    In this study, we have used a microRNA-regulated lentiviral reporter system to visualize and segregate differentiating neuronal cells in pluripotent cultures. Efficient suppression of transgene expression, specifically in undifferentiated pluripotent cells, was achieved by using a lentiviral vector expressing a fluorescent reporter gene regulated by microRNA-292. Using this strategy, it was possible to track progeny from murine ES, human ES cells, and induced pluripotent stem cells as they differentiated toward the neural lineage. In addition, this strategy was successfully used to FACS purify neuronal progenitors for molecular analysis and transplantation. FACS enrichment reduced tumor formation and increased survival of ES cell-derived neuronal progenitors after transplantation. The properties and versatility of the microRNA-regulated vectors allows broad use of these vectors in stem cell applications.

  17. Hippocalcin Is Required for Astrocytic Differentiation through Activation of Stat3 in Hippocampal Neural Precursor Cells.

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    Min-Jeong Kang

    2016-10-01

    Full Text Available Hippocalcin (Hpca is a neuronal calcium sensor protein expressed in the mammalian brain. However, its function in neural stem/precursor cells has not yet been studied. Here, we clarify the function of Hpca in astrocytic differentiation in hippocampal neural precursor cells (HNPCs. When we overexpressed Hpca in HNPCs in the presence or absence of bFGF, expression levels of nerve-growth factors such as neurotrophin-3 (NT-3, neurotrophin-4/5 (NT-4/5 and brain-derived neurotrophic factor (BDNF, together with the proneural basic helix loop helix (bHLH transcription factors neuroD and neurogenin 1 (ngn1, increased significantly. In addition, there was an increase in the number of cells expressing glial fibrillary acidic protein (GFAP, an astrocyte marker, and in dendrite outgrowth, indicating astrocytic differentiation of the HNPCs. Downregulation of Hpca by transfection with Hpca siRNA reduced expression of NT-3, NT-4/5, BDNF, neuroD and ngn1 as well as levels of GFAP protein. Furthermore, overexpression of Hpca increased the phosphorylation of STAT3 (Ser727, and this effect was abolished by treatment with a STAT3 inhibitor (S3I-201, suggesting that STAT3 (Ser727 activation is involved in Hpca-mediated astrocytic differentiation. As expected, treatment with Stat3 siRNA or STAT3 inhibitor caused a complete inhibition of astrogliogenesis induced by Hpca overexpression. Taken together, this is the first report to show that Hpca, acting through Stat3, has an important role in the expression of neurotrophins and proneural bHLH transcription factors, and that it is an essential regulator of astrocytic differentiation and dendrite outgrowth in HNPCs.

  18. Effect of 3D-scaffold formation on differentiation and survival in human neural progenitor cells.

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    Ortinau, Stefanie; Schmich, Jürgen; Block, Stephan; Liedmann, Andrea; Jonas, Ludwig; Weiss, Dieter G; Helm, Christiane A; Rolfs, Arndt; Frech, Moritz J

    2010-11-11

    3D-scaffolds have been shown to direct cell growth and differentiation in many different cell types, with the formation and functionalisation of the 3D-microenviroment being important in determining the fate of the embedded cells. Here we used a hydrogel-based scaffold to investigate the influences of matrix concentration and functionalisation with laminin on the formation of the scaffolds, and the effect of these scaffolds on human neural progenitor cells cultured within them. In this study we used different concentrations of the hydrogel-based matrix PuraMatrix. In some experiments we functionalised the matrix with laminin I. The impact of concentration and treatment with laminin on the formation of the scaffold was examined with atomic force microscopy. Cells from a human fetal neural progenitor cell line were cultured in the different matrices, as well as in a 2D culture system, and were subsequently analysed with antibody stainings against neuronal markers. In parallel, the survival rate of the cells was determined by a live/dead assay. Atomic force microscopy measurements demonstrated that the matrices are formed by networks of isolated PuraMatrix fibres and aggregates of fibres. An increase of the hydrogel concentration led to a decrease in the mesh size of the scaffolds and functionalisation with laminin promoted aggregation of the fibres (bundle formation), which further reduces the density of isolated fibres. We showed that laminin-functionalisation is essential for human neural progenitor cells to build up 3D-growth patterns, and that proliferation of the cells is also affected by the concentration of matrix. In addition we found that 3D-cultures enhanced neuronal differentiation and the survival rate of the cells compared to 2D-cultures. Taken together, we have demonstrated a direct influence of the 3D-scaffold formation on the survival and neuronal differentiation of human neural progenitor cells. These findings emphasize the importance of optimizing 3

  19. Differential Covariance: A New Class of Methods to Estimate Sparse Connectivity from Neural Recordings.

    Science.gov (United States)

    Lin, Tiger W; Das, Anup; Krishnan, Giri P; Bazhenov, Maxim; Sejnowski, Terrence J

    2017-10-01

    With our ability to record more neurons simultaneously, making sense of these data is a challenge. Functional connectivity is one popular way to study the relationship of multiple neural signals. Correlation-based methods are a set of currently well-used techniques for functional connectivity estimation. However, due to explaining away and unobserved common inputs (Stevenson, Rebesco, Miller, & Körding, 2008 ), they produce spurious connections. The general linear model (GLM), which models spike trains as Poisson processes (Okatan, Wilson, & Brown, 2005 ; Truccolo, Eden, Fellows, Donoghue, & Brown, 2005 ; Pillow et al., 2008 ), avoids these confounds. We develop here a new class of methods by using differential signals based on simulated intracellular voltage recordings. It is equivalent to a regularized AR(2) model. We also expand the method to simulated local field potential recordings and calcium imaging. In all of our simulated data, the differential covariance-based methods achieved performance better than or similar to the GLM method and required fewer data samples. This new class of methods provides alternative ways to analyze neural signals.

  20. Differential Covariance: A New Class of Methods to Estimate Sparse Connectivity from Neural Recordings

    Science.gov (United States)

    Lin, Tiger W.; Das, Anup; Krishnan, Giri P.; Bazhenov, Maxim; Sejnowski, Terrence J.

    2017-01-01

    With our ability to record more neurons simultaneously, making sense of these data is a challenge. Functional connectivity is one popular way to study the relationship of multiple neural signals. Correlation-based methods are a set of currently well-used techniques for functional connectivity estimation. However, due to explaining away and unobserved common inputs (Stevenson, Rebesco, Miller, & Körding, 2008), they produce spurious connections. The general linear model (GLM), which models spike trains as Poisson processes (Okatan, Wilson, & Brown, 2005; Truccolo, Eden, Fellows, Donoghue, & Brown, 2005; Pillow et al., 2008), avoids these confounds. We develop here a new class of methods by using differential signals based on simulated intracellular voltage recordings. It is equivalent to a regularized AR(2) model. We also expand the method to simulated local field potential recordings and calcium imaging. In all of our simulated data, the differential covariance-based methods achieved performance better than or similar to the GLM method and required fewer data samples. This new class of methods provides alternative ways to analyze neural signals. PMID:28777719

  1. Investigating the Influence of Biological Sex on the Behavioral and Neural Basis of Face Recognition.

    Science.gov (United States)

    Scherf, K Suzanne; Elbich, Daniel B; Motta-Mena, Natalie V

    2017-01-01

    There is interest in understanding the influence of biological factors, like sex, on the organization of brain function. We investigated the influence of biological sex on the behavioral and neural basis of face recognition in healthy, young adults. In behavior, there were no sex differences on the male Cambridge Face Memory Test (CFMT)+ or the female CFMT+ (that we created) and no own-gender bias (OGB) in either group. We evaluated the functional topography of ventral stream organization by measuring the magnitude and functional neural size of 16 individually defined face-, two object-, and two place-related regions bilaterally. There were no sex differences in any of these measures of neural function in any of the regions of interest (ROIs) or in group level comparisons. These findings reveal that men and women have similar category-selective topographic organization in the ventral visual pathway. Next, in a separate task, we measured activation within the 16 face-processing ROIs specifically during recognition of target male and female faces. There were no sex differences in the magnitude of the neural responses in any face-processing region. Furthermore, there was no OGB in the neural responses of either the male or female participants. Our findings suggest that face recognition behavior, including the OGB, is not inherently sexually dimorphic. Face recognition is an essential skill for navigating human social interactions, which is reflected equally in the behavior and neural architecture of men and women.

  2. Investigating the Influence of Biological Sex on the Behavioral and Neural Basis of Face Recognition

    Science.gov (United States)

    2017-01-01

    Abstract There is interest in understanding the influence of biological factors, like sex, on the organization of brain function. We investigated the influence of biological sex on the behavioral and neural basis of face recognition in healthy, young adults. In behavior, there were no sex differences on the male Cambridge Face Memory Test (CFMT)+ or the female CFMT+ (that we created) and no own-gender bias (OGB) in either group. We evaluated the functional topography of ventral stream organization by measuring the magnitude and functional neural size of 16 individually defined face-, two object-, and two place-related regions bilaterally. There were no sex differences in any of these measures of neural function in any of the regions of interest (ROIs) or in group level comparisons. These findings reveal that men and women have similar category-selective topographic organization in the ventral visual pathway. Next, in a separate task, we measured activation within the 16 face-processing ROIs specifically during recognition of target male and female faces. There were no sex differences in the magnitude of the neural responses in any face-processing region. Furthermore, there was no OGB in the neural responses of either the male or female participants. Our findings suggest that face recognition behavior, including the OGB, is not inherently sexually dimorphic. Face recognition is an essential skill for navigating human social interactions, which is reflected equally in the behavior and neural architecture of men and women. PMID:28497111

  3. Molecular Characterization of Down Syndrome Embryonic Stem Cells Reveals a Role for RUNX1 in Neural Differentiation

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    Tomer Halevy

    2016-10-01

    Full Text Available Down syndrome (DS is the leading genetic cause of mental retardation and is caused by a third copy of human chromosome 21. The different pathologies of DS involve many tissues with a distinct array of neural phenotypes. Here we characterize embryonic stem cell lines with DS (DS-ESCs, and focus on the neural aspects of the disease. Our results show that neural progenitor cells (NPCs differentiated from five independent DS-ESC lines display increased apoptosis and downregulation of forehead developmental genes. Analysis of differentially expressed genes suggested RUNX1 as a key transcription regulator in DS-NPCs. Using genome editing we were able to disrupt all three copies of RUNX1 in DS-ESCs, leading to downregulation of several RUNX1 target developmental genes accompanied by reduced apoptosis and neuron migration. Our work sheds light on the role of RUNX1 and the importance of dosage balance in the development of neural phenotypes in DS.

  4. Trans-differentiation of neural stem cells: a therapeutic mechanism against the radiation induced brain damage.

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    Kyeung Min Joo

    Full Text Available Radiation therapy is an indispensable therapeutic modality for various brain diseases. Though endogenous neural stem cells (NSCs would provide regenerative potential, many patients nevertheless suffer from radiation-induced brain damage. Accordingly, we tested beneficial effects of exogenous NSC supplementation using in vivo mouse models that received whole brain irradiation. Systemic supplementation of primarily cultured mouse fetal NSCs inhibited radiation-induced brain atrophy and thereby preserved brain functions such as short-term memory. Transplanted NSCs migrated to the irradiated brain and differentiated into neurons, astrocytes, or oligodendrocytes. In addition, neurotrophic factors such as NGF were significantly increased in the brain by NSCs, indicating that both paracrine and replacement effects could be the therapeutic mechanisms of NSCs. Interestingly, NSCs also differentiated into brain endothelial cells, which was accompanied by the restoration the cerebral blood flow that was reduced from the irradiation. Inhibition of the VEGF signaling reduced the migration and trans-differentiation of NSCs. Therefore, trans-differentiation of NSCs into brain endothelial cells by the VEGF signaling and the consequential restoration of the cerebral blood flow would also be one of the therapeutic mechanisms of NSCs. In summary, our data demonstrate that exogenous NSC supplementation could prevent radiation-induced functional loss of the brain. Therefore, successful combination of brain radiation therapy and NSC supplementation would provide a highly promising therapeutic option for patients with various brain diseases.

  5. Hypoxia Epigenetically Confers Astrocytic Differentiation Potential on Human Pluripotent Cell-Derived Neural Precursor Cells

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    Tetsuro Yasui

    2017-06-01

    Full Text Available Human neural precursor cells (hNPCs derived from pluripotent stem cells display a high propensity for neuronal differentiation, but they require long-term culturing to differentiate efficiently into astrocytes. The mechanisms underlying this biased fate specification of hNPCs remain elusive. Here, we show that hypoxia confers astrocytic differentiation potential on hNPCs through epigenetic gene regulation, and that this was achieved by cooperation between hypoxia-inducible factor 1α and Notch signaling, accompanied by a reduction of DNA methylation level in the promoter region of a typical astrocyte-specific gene, Glial fibrillary acidic protein. Furthermore, we found that this hypoxic culture condition could be applied to rapid generation of astrocytes from Rett syndrome patient-derived hNPCs, and that these astrocytes impaired neuronal development. Thus, our findings shed further light on the molecular mechanisms regulating hNPC differentiation and provide attractive tools for the development of therapeutic strategies for treating astrocyte-mediated neurological disorders.

  6. Neural Stem Cell Differentiation Using Microfluidic Device-Generated Growth Factor Gradient.

    Science.gov (United States)

    Kim, Ji Hyeon; Sim, Jiyeon; Kim, Hyun-Jung

    2018-04-11

    Neural stem cells (NSCs) have the ability to self-renew and differentiate into multiple nervous system cell types. During embryonic development, the concentrations of soluble biological molecules have a critical role in controlling cell proliferation, migration, differentiation and apoptosis. In an effort to find optimal culture conditions for the generation of desired cell types in vitro , we used a microfluidic chip-generated growth factor gradient system. In the current study, NSCs in the microfluidic device remained healthy during the entire period of cell culture, and proliferated and differentiated in response to the concentration gradient of growth factors (epithermal growth factor and basic fibroblast growth factor). We also showed that overexpression of ASCL1 in NSCs increased neuronal differentiation depending on the concentration gradient of growth factors generated in the microfluidic gradient chip. The microfluidic system allowed us to study concentration-dependent effects of growth factors within a single device, while a traditional system requires multiple independent cultures using fixed growth factor concentrations. Our study suggests that the microfluidic gradient-generating chip is a powerful tool for determining the optimal culture conditions.

  7. Differentiation of neural crest stem cells from nasal mucosa into motor neuron-like cells.

    Science.gov (United States)

    Bagher, Zohreh; Kamrava, Seyed Kamran; Alizadeh, Rafieh; Farhadi, Mohammad; Absalan, Moloud; Falah, Masoumeh; Faghihi, Faezeh; Zare-Sadeghi, Arash; Komeili, Ali

    2018-05-25

    Cell transplantation is a potential therapeutic approach for repairing neuropathological and neurodegenerative disorders of central nervous system by replacing the degenerated cells with new ones. Among a variety of stem cell candidates to provide these new cells, olfactory ectomesenchymal stem cells (OE-MSCs) have attracted a great attention due to their neural crest origin, easy harvest, high proliferation, and autologous transplantation. Since there is no report on differentiation potential of these cells into motor neuron-like cells, we evaluated this potential using Real-time PCR, flowcytometry and immunocytochemistry after the treatment with differentiation cocktail containing retinoic acid and Sonic Hedgehog. Immunocytochemistry staining of the isolated OE-MSCs demonstrated their capability to express nestin and vimentin, as the two markers of primitive neuroectoderm. The motor neuron differentiation of OE-MSCs resulted in changing their morphology into bipolar cells with high expression of motor neuron markers of ChAT, Hb-9 and Islet-1 at the level of mRNA and protein. Consequently, we believe that the OE-MSCs have great potential to differentiate into motor neuron-like cells and can be an ideal stem cell source for the treatment of motor neuron-related disorders of central nervous system. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Melatonin antagonizes interleukin-18-mediated inhibition on neural stem cell proliferation and differentiation.

    Science.gov (United States)

    Li, Zheng; Li, Xingye; Chan, Matthew T V; Wu, William Ka Kei; Tan, DunXian; Shen, Jianxiong

    2017-09-01

    Neural stem cells (NSCs) are self-renewing, pluripotent and undifferentiated cells which have the potential to differentiate into neurons, oligodendrocytes and astrocytes. NSC therapy for tissue regeneration, thus, gains popularity. However, the low survivals rate of the transplanted cell impedes its utilities. In this study, we tested whether melatonin, a potent antioxidant, could promote the NSC proliferation and neuronal differentiation, especially, in the presence of the pro-inflammatory cytokine interleukin-18 (IL-18). Our results showed that melatonin per se indeed exhibited beneficial effects on NSCs and IL-18 inhibited NSC proliferation, neurosphere formation and their differentiation into neurons. All inhibitory effects of IL-18 on NSCs were significantly reduced by melatonin treatment. Moreover, melatonin application increased the production of both brain-derived and glial cell-derived neurotrophic factors (BDNF, GDNF) in IL-18-stimulated NSCs. It was observed that inhibition of BDNF or GDNF hindered the protective effects of melatonin on NSCs. A potentially protective mechanism of melatonin on the inhibition of NSC's differentiation caused IL-18 may attribute to the up-regulation of these two major neurotrophic factors, BNDF and GNDF. The findings indicate that melatonin may play an important role promoting the survival of NSCs in neuroinflammatory diseases. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  9. Fibronectin promotes differentiation of neural crest progenitors endowed with smooth muscle cell potential

    International Nuclear Information System (INIS)

    Costa-Silva, Bruno; Coelho da Costa, Meline; Melo, Fernanda Rosene; Neves, Cynara Mendes; Alvarez-Silva, Marcio; Calloni, Giordano Wosgrau; Trentin, Andrea Goncalves

    2009-01-01

    The neural crest (NC) is a model system used to investigate multipotency during vertebrate development. Environmental factors control NC cell fate decisions. Despite the well-known influence of extracellular matrix molecules in NC cell migration, the issue of whether they also influence NC cell differentiation has not been addressed at the single cell level. By analyzing mass and clonal cultures of mouse cephalic and quail trunk NC cells, we show for the first time that fibronectin (FN) promotes differentiation into the smooth muscle cell phenotype without affecting differentiation into glia, neurons, and melanocytes. Time course analysis indicated that the FN-induced effect was not related to massive cell death or proliferation of smooth muscle cells. Finally, by comparing clonal cultures of quail trunk NC cells grown on FN and collagen type IV (CLIV), we found that FN strongly increased both NC cell survival and the proportion of unipotent and oligopotent NC progenitors endowed with smooth muscle potential. In contrast, melanocytic progenitors were prominent in clonogenic NC cells grown on CLIV. Taken together, these results show that FN promotes NC cell differentiation along the smooth muscle lineage, and therefore plays an important role in fate decisions of NC progenitor cells

  10. Geminin Participates in Differentiation Decisions of Adult Neural Stem Cells Transplanted in the Hemiparkinsonian Mouse Brain.

    Science.gov (United States)

    Taouki, Ioanna; Tasiudi, Eve; Lalioti, Maria-Eleni; Kyrousi, Christina; Skavatsou, Eleni; Kaplani, Konstantina; Lygerou, Zoi; Kouvelas, Elias D; Mitsacos, Adamantia; Giompres, Panagiotis; Taraviras, Stavros

    2017-08-15

    Neural stem cells have been considered as a source of stem cells that can be used for cell replacement therapies in neurodegenerative diseases, as they can be isolated and expanded in vitro and can be used for autologous grafting. However, due to low percentages of survival and varying patterns of differentiation, strategies that will enhance the efficacy of transplantation are under scrutiny. In this article, we have examined whether alterations in Geminin's expression, a protein that coordinates the balance between self-renewal and differentiation, can improve the properties of stem cells transplanted in 6-OHDA hemiparkinsonian mouse model. Our results indicate that, in the absence of Geminin, grafted cells differentiating into dopaminergic neurons were decreased, while an increased number of oligodendrocytes were detected. The number of proliferating multipotent cells was not modified by the absence of Geminin. These findings encourage research related to the impact of Geminin on transplantations for neurodegenerative disorders, as an important molecule in influencing differentiation decisions of the cells composing the graft.

  11. A fixed point approach towards stability of delay differential equations with applications to neural networks

    NARCIS (Netherlands)

    Chen, Guiling

    2013-01-01

    This thesis studies asymptotic behavior and stability of determinsitic and stochastic delay differential equations. The approach used in this thesis is based on fixed point theory, which does not resort to any Liapunov function or Liapunov functional. The main contribution of this thesis is to study

  12. Neural patterning of human induced pluripotent stem cells in 3-D cultures for studying biomolecule-directed differential cellular responses.

    Science.gov (United States)

    Yan, Yuanwei; Bejoy, Julie; Xia, Junfei; Guan, Jingjiao; Zhou, Yi; Li, Yan

    2016-09-15

    Appropriate neural patterning of human induced pluripotent stem cells (hiPSCs) is critical to generate specific neural cells/tissues and even mini-brains that are physiologically relevant to model neurological diseases. However, the capacity of signaling factors that regulate 3-D neural tissue patterning in vitro and differential responses of the resulting neural populations to various biomolecules have not yet been fully understood. By tuning neural patterning of hiPSCs with small molecules targeting sonic hedgehog (SHH) signaling, this study generated different 3-D neuronal cultures that were mainly comprised of either cortical glutamatergic neurons or motor neurons. Abundant glutamatergic neurons were observed following the treatment with an antagonist of SHH signaling, cyclopamine, while Islet-1 and HB9-expressing motor neurons were enriched by an SHH agonist, purmorphamine. In neurons derived with different neural patterning factors, whole-cell patch clamp recordings showed similar voltage-gated Na(+)/K(+) currents, depolarization-evoked action potentials and spontaneous excitatory post-synaptic currents. Moreover, these different neuronal populations exhibited differential responses to three classes of biomolecules, including (1) matrix metalloproteinase inhibitors that affect extracellular matrix remodeling; (2) N-methyl-d-aspartate that induces general neurotoxicity; and (3) amyloid β (1-42) oligomers that cause neuronal subtype-specific neurotoxicity. This study should advance our understanding of hiPSC self-organization and neural tissue development and provide a transformative approach to establish 3-D models for neurological disease modeling and drug discovery. Appropriate neural patterning of human induced pluripotent stem cells (hiPSCs) is critical to generate specific neural cells, tissues and even mini-brains that are physiologically relevant to model neurological diseases. However, the capability of sonic hedgehog-related small molecules to tune

  13. Neural oscillatory deficits in schizophrenia predict behavioral and neurocognitive impairments

    Directory of Open Access Journals (Sweden)

    Antigona eMartinez

    2015-07-01

    Full Text Available Paying attention to visual stimuli is typically accompanied by event-related desynchronizations (ERD of ongoing alpha (7-14 Hz activity in visual cortex. The present study used time-frequency based analyses to investigate the role of impaired alpha ERD in visual processing deficits in schizophrenia (Sz. Subjects viewed sinusoidal gratings of high (HSF and low (LSF spatial frequency designed to test functioning of the parvo- versus magnocellular pathways, respectively. Patients with Sz and healthy controls paid attention selectively to either the LSF or HSF gratings which were presented in random order. Event-related brain potentials (ERPs were recorded to all stimuli. As in our previous study, it was found that Sz patients were selectively impaired at detecting LSF target stimuli and that ERP amplitudes to LSF stimuli were diminished, both for the early sensory-evoked components and for the attend minus unattend difference component (the Selection Negativity, which is generally regarded as a specific index of feature-selective attention. In the time-frequency domain, the differential ERP deficits to LSF stimuli were echoed in a virtually absent theta-band phase locked response to both unattended and attended LSF stimuli (along with relatively intact theta-band activity for HSF stimuli. In contrast to the theta-band evoked responses which were tightly stimulus locked, stimulus-induced desynchronizations of ongoing alpha activity were not tightly stimulus locked and were apparent only in induced power analyses. Sz patients were significantly impaired in the attention-related modulation of ongoing alpha activity for both HSF and LSF stimuli. These deficits correlated with patients’ behavioral deficits in visual information processing as well as with visually based neurocognitive deficits. These findings suggest an additional, pathway-independent, mechanism by which deficits in early visual processing contribute to overall cognitive impairment in

  14. Adult subependymal neural precursors, but not differentiated cells, undergo rapid cathodal migration in the presence of direct current electric fields.

    Directory of Open Access Journals (Sweden)

    Robart Babona-Pilipos

    Full Text Available BACKGROUND: The existence of neural stem and progenitor cells (together termed neural precursor cells in the adult mammalian brain has sparked great interest in utilizing these cells for regenerative medicine strategies. Endogenous neural precursors within the adult forebrain subependyma can be activated following injury, resulting in their proliferation and migration toward lesion sites where they differentiate into neural cells. The administration of growth factors and immunomodulatory agents following injury augments this activation and has been shown to result in behavioural functional recovery following stroke. METHODS AND FINDINGS: With the goal of enhancing neural precursor migration to facilitate the repair process we report that externally applied direct current electric fields induce rapid and directed cathodal migration of pure populations of undifferentiated adult subependyma-derived neural precursors. Using time-lapse imaging microscopy in vitro we performed an extensive single-cell kinematic analysis demonstrating that this galvanotactic phenomenon is a feature of undifferentiated precursors, and not differentiated phenotypes. Moreover, we have shown that the migratory response of the neural precursors is a direct effect of the electric field and not due to chemotactic gradients. We also identified that epidermal growth factor receptor (EGFR signaling plays a role in the galvanotactic response as blocking EGFR significantly attenuates the migratory behaviour. CONCLUSIONS: These findings suggest direct current electric fields may be implemented in endogenous repair paradigms to promote migration and tissue repair following neurotrauma.

  15. Oxytocin and vasopressin neural networks: Implications for social behavioral diversity and translational neuroscience.

    Science.gov (United States)

    Johnson, Zachary V; Young, Larry J

    2017-05-01

    Oxytocin- and vasopressin-related systems are present in invertebrate and vertebrate bilaterian animals, including humans, and exhibit conserved neuroanatomical and functional properties. In vertebrates, these systems innervate conserved neural networks that regulate social learning and behavior, including conspecific recognition, social attachment, and parental behavior. Individual and species-level variation in central organization of oxytocin and vasopressin systems has been linked to individual and species variation in social learning and behavior. In humans, genetic polymorphisms in the genes encoding oxytocin and vasopressin peptides and/or their respective target receptors have been associated with individual variation in social recognition, social attachment phenotypes, parental behavior, and psychiatric phenotypes such as autism. Here we describe both conserved and variable features of central oxytocin and vasopressin systems in the context of social behavioral diversity, with a particular focus on neural networks that modulate social learning, behavior, and salience of sociosensory stimuli during species-typical social contexts. Published by Elsevier Ltd.

  16. Schema benefit vs. proactive interference: Contradicting behavioral outcomes and coexisting neural patterns.

    Science.gov (United States)

    Oren, Noga; Shapira-Lichter, Irit; Lerner, Yulia; Tarrasch, Ricardo; Hendler, Talma; Giladi, Nir; Ash, Elissa L

    2017-09-01

    Prior knowledge can either assist or hinder the ability to learn new information. These contradicting behavioral outcomes, referred to as schema benefit and proactive interference respectively, have been studied separately. Here we examined whether the known neural correlates of each process coexist, and how they are influenced by attentional loading and aging. To this end we used an fMRI task that affected both processes simultaneously by presenting pairs of related short movies in succession. The first movie of each pair provided context for the second movie, which could evoke schema benefit and/or proactive interference. Inclusion of an easy or hard secondary task performed during encoding of the movies, as well as testing both younger (22-35y) and older (65-79y) adults, allowed examining the effect of attentional load and older age on the neural patterns associated with context. Analyses focused on three predefined regions and examined how their inter-subject correlation (inter-SC) and functional connectivity (FC) with the hippocampi changed between the first and second movie. The results in the medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) matched and expanded previous findings: higher inter-SC and lower FC were observed during the second compared to the first movie; yet the differentiation between the first and second movies in these regions was attenuated under high attentional load, pointing to dependency on attentional resources. Instead, at high load there was a significant context effect in the FC of the left ventrolateral prefrontal cortex (vlPFC), and greater FC in the second movie was related to greater proactive interference. Further, older adults showed context effect in the PCC and vlPFC. Intriguingly, older adults with inter-SC mPFC patterns similar to younger adults exhibited schema benefit in our task, while those with inter-SC PCC patterns similar to younger adults showed proactive interference in an independent task. The

  17. Extending unified-theory-of-reinforcement neural networks to steady-state operant behavior.

    Science.gov (United States)

    Calvin, Olivia L; McDowell, J J

    2016-06-01

    The unified theory of reinforcement has been used to develop models of behavior over the last 20 years (Donahoe et al., 1993). Previous research has focused on the theory's concordance with the respondent behavior of humans and animals. In this experiment, neural networks were developed from the theory to extend the unified theory of reinforcement to operant behavior on single-alternative variable-interval schedules. This area of operant research was selected because previously developed neural networks could be applied to it without significant alteration. Previous research with humans and animals indicates that the pattern of their steady-state behavior is hyperbolic when plotted against the obtained rate of reinforcement (Herrnstein, 1970). A genetic algorithm was used in the first part of the experiment to determine parameter values for the neural networks, because values that were used in previous research did not result in a hyperbolic pattern of behavior. After finding these parameters, hyperbolic and other similar functions were fitted to the behavior produced by the neural networks. The form of the neural network's behavior was best described by an exponentiated hyperbola (McDowell, 1986; McLean and White, 1983; Wearden, 1981), which was derived from the generalized matching law (Baum, 1974). In post-hoc analyses the addition of a baseline rate of behavior significantly improved the fit of the exponentiated hyperbola and removed systematic residuals. The form of this function was consistent with human and animal behavior, but the estimated parameter values were not. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. TAM receptors support neural stem cell survival, proliferation and neuronal differentiation.

    Science.gov (United States)

    Ji, Rui; Meng, Lingbin; Jiang, Xin; Cvm, Naresh Kumar; Ding, Jixiang; Li, Qiutang; Lu, Qingxian

    2014-01-01

    Tyro3, Axl and Mertk (TAM) receptor tyrosine kinases play multiple functional roles by either providing intrinsic trophic support for cell growth or regulating the expression of target genes that are important in the homeostatic regulation of immune responses. TAM receptors have been shown to regulate adult hippocampal neurogenesis by negatively regulation of glial cell activation in central nervous system (CNS). In the present study, we further demonstrated that all three TAM receptors were expressed by cultured primary neural stem cells (NSCs) and played a direct growth trophic role in NSCs proliferation, neuronal differentiation and survival. The cultured primary NSCs lacking TAM receptors exhibited slower growth, reduced proliferation and increased apoptosis as shown by decreased BrdU incorporation and increased TUNEL labeling, than those from the WT NSCs. In addition, the neuronal differentiation and maturation of the mutant NSCs were impeded, as characterized by less neuronal differentiation (β-tubulin III+) and neurite outgrowth than their WT counterparts. To elucidate the underlying mechanism that the TAM receptors play on the differentiating NSCs, we examined the expression profile of neurotrophins and their receptors by real-time qPCR on the total RNAs from hippocampus and primary NSCs; and found that the TKO NSC showed a significant reduction in the expression of both nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), but accompanied by compensational increases in the expression of the TrkA, TrkB, TrkC and p75 receptors. These results suggest that TAM receptors support NSCs survival, proliferation and differentiation by regulating expression of neurotrophins, especially the NGF.

  19. Temperament and Parenting Styles in Early Childhood Differentially Influence Neural Response to Peer Evaluation in Adolescence

    Science.gov (United States)

    Guyer, Amanda E.; Jarcho, Johanna M.; Pérez-Edgar, Koraly; Degnan, Kathryn A.; Pine, Daniel S.; Fox, Nathan A.; Nelson, Eric E.

    2015-01-01

    Behavioral inhibition (BI) is a temperament characterized by social reticence and withdrawal from unfamiliar or novel contexts and conveys risk for social anxiety disorder. Developmental outcomes associated with this temperament can be influenced by children’s caregiving context. The convergence of a child’s temperamental disposition and rearing environment is ultimately expressed at both the behavioral and neural levels in emotional and cognitive response patterns to social challenges. The present study used functional neuroimaging to assess the moderating effects of different parenting styles on neural response to peer rejection in two groups of adolescents characterized by their early childhood temperament (Mage = 17.89 years, N= 39, 17 males, 22 females; 18 with BI; 21 without BI). The moderating effects of authoritarian and authoritative parenting styles were examined in three brain regions linked with social anxiety: ventrolateral prefrontal cortex (vlPFC), striatum, and amygdala. In youth characterized with BI in childhood, but not in those without BI, diminished responses to peer rejection in vlPFC were associated with higher levels of authoritarian parenting. In contrast, all youth showed decreased caudate response to peer rejection at higher levels of authoritative parenting. These findings indicate that BI in early life relates to greater neurobiological sensitivity to variance in parenting styles, particularly harsh parenting, in late adolescence. These results are discussed in relation to biopsychosocial models of development. PMID:25588884

  20. Temperament and Parenting Styles in Early Childhood Differentially Influence Neural Response to Peer Evaluation in Adolescence.

    Science.gov (United States)

    Guyer, Amanda E; Jarcho, Johanna M; Pérez-Edgar, Koraly; Degnan, Kathryn A; Pine, Daniel S; Fox, Nathan A; Nelson, Eric E

    2015-07-01

    Behavioral inhibition (BI) is a temperament characterized by social reticence and withdrawal from unfamiliar or novel contexts and conveys risk for social anxiety disorder. Developmental outcomes associated with this temperament can be influenced by children's caregiving context. The convergence of a child's temperamental disposition and rearing environment is ultimately expressed at both the behavioral and neural levels in emotional and cognitive response patterns to social challenges. The present study used functional neuroimaging to assess the moderating effects of different parenting styles on neural response to peer rejection in two groups of adolescents characterized by their early childhood temperament (M(age) = 17.89 years, N = 39, 17 males, 22 females; 18 with BI; 21 without BI). The moderating effects of authoritarian and authoritative parenting styles were examined in three brain regions linked with social anxiety: ventrolateral prefrontal cortex (vlPFC), striatum, and amygdala. In youth characterized with BI in childhood, but not in those without BI, diminished responses to peer rejection in vlPFC were associated with higher levels of authoritarian parenting. In contrast, all youth showed decreased caudate response to peer rejection at higher levels of authoritative parenting. These findings indicate that BI in early life relates to greater neurobiological sensitivity to variance in parenting styles, particularly harsh parenting, in late adolescence. These results are discussed in relation to biopsychosocial models of development.

  1. High baseline activity in inferior temporal cortex improves neural and behavioral discriminability during visual categorization

    Directory of Open Access Journals (Sweden)

    Nazli eEmadi

    2014-11-01

    Full Text Available Spontaneous firing is a ubiquitous property of neural activity in the brain. Recent literature suggests that this baseline activity plays a key role in perception. However, it is not known how the baseline activity contributes to neural coding and behavior. Here, by recording from the single neurons in the inferior temporal cortex of monkeys performing a visual categorization task, we thoroughly explored the relationship between baseline activity, the evoked response, and behavior. Specifically we found that a low-frequency (< 8 Hz oscillation in the spike train, prior and phase-locked to the stimulus onset, was correlated with increased gamma power and neuronal baseline activity. This enhancement of the baseline activity was then followed by an increase in the neural selectivity and the response reliability and eventually a higher behavioral performance.

  2. The neural components of empathy: Predicting daily prosocial behavior

    OpenAIRE

    Morelli, Sylvia A.; Rameson, Lian T.; Lieberman, Matthew D.

    2012-01-01

    Previous neuroimaging studies on empathy have not clearly identified neural systems that support the three components of empathy: affective congruence, perspective-taking, and prosocial motivation. These limitations stem from a focus on a single emotion per study, minimal variation in amount of social context provided, and lack of prosocial motivation assessment. In the current investigation, 32 participants completed a functional magnetic resonance imaging session assessing empathic response...

  3. Marmoset induced pluripotent stem cells: Robust neural differentiation following pretreatment with dimethyl sulfoxide

    Directory of Open Access Journals (Sweden)

    Zhifang Qiu

    2015-07-01

    Full Text Available The marmoset is an important nonhuman primate model for regenerative medicine. For experimental autologous cell therapy based on induced pluripotent (iPS cells in the marmoset, cells must be able to undergo robust and reliable directed differentiation that will not require customization for each specific iPS cell clone. When marmoset iPS cells were aggregated in a hanging drop format for 3 days, followed by exposure to dual SMAD inhibitors and retinoic acid in monolayer culture for 3 days, we found substantial variability in the response of different iPS cell clones. However, when clones were pretreated with 0.05–2% dimethyl sulfoxide (DMSO for 24 hours, all clones showed a very similar maximal response to the directed differentiation scheme. Peak responses were observed at 0.5% DMSO in two clones and at 1% DMSO in a third clone. When patterns of gene expression were examined by microarray analysis, hierarchical clustering showed very similar responses in all 3 clones when they were pretreated with optimal DMSO concentrations. The change in phenotype following exposure to DMSO and the 6 day hanging drop/monolayer treatment was confirmed by immunocytochemistry. Analysis of DNA content in DMSO-exposed cells indicated that it is unlikely that DMSO acts by causing cells to exit from the cell cycle. This approach should be generally valuable in the directed neural differentiation of pluripotent cells for experimental cell therapy.

  4. Emerging role of LRRK2 in human neural progenitor cell cycle progression, survival and differentiation

    Directory of Open Access Journals (Sweden)

    Meyer Anne K

    2009-06-01

    Full Text Available Abstract Despite a comprehensive mapping of the Parkinson's disease (PD-related mRNA and protein leucine-rich repeat kinase 2 (LRRK2 in the mammalian brain, its physiological function in healthy individuals remains enigmatic. Based on its structural features and kinase properties, LRRK2 may interact with other proteins involved in signalling pathways. Here, we show a widespread LRRK2 mRNA and/or protein expression in expanded or differentiated human mesencephalic neural progenitor cells (hmNPCs and in post-mortem substantia nigra PD patients. Using small interfering RNA duplexes targeting LRRK2 in hmNPCs following their differentiation into glia and neurons, we observed a reduced number of dopaminergic neurons due to apoptosis in LRRK2 knockdown samples. LRRK2-deficient hmNPCs exhibited elevated cell cycle- and cell death-related markers. In conclusion, a reduction of LRRK2 expression in hmNPCs severely impaired dopaminergic differentiation and/or survival of dopaminergic neurons most likely via preserving or reactivating the cell cycle.

  5. Neural stem cells promote nerve regeneration through IL12-induced Schwann cell differentiation.

    Science.gov (United States)

    Lee, Don-Ching; Chen, Jong-Hang; Hsu, Tai-Yu; Chang, Li-Hsun; Chang, Hsu; Chi, Ya-Hui; Chiu, Ing-Ming

    2017-03-01

    Regeneration of injured peripheral nerves is a slow, complicated process that could be improved by implantation of neural stem cells (NSCs) or nerve conduit. Implantation of NSCs along with conduits promotes the regeneration of damaged nerve, likely because (i) conduit supports and guides axonal growth from one nerve stump to the other, while preventing fibrous tissue ingrowth and retaining neurotrophic factors; and (ii) implanted NSCs differentiate into Schwann cells and maintain a growth factor enriched microenvironment, which promotes nerve regeneration. In this study, we identified IL12p80 (homodimer of IL12p40) in the cell extracts of implanted nerve conduit combined with NSCs by using protein antibody array and Western blotting. Levels of IL12p80 in these conduits are 1.6-fold higher than those in conduits without NSCs. In the sciatic nerve injury mouse model, implantation of NSCs combined with nerve conduit and IL12p80 improves motor recovery and increases the diameter up to 4.5-fold, at the medial site of the regenerated nerve. In vitro study further revealed that IL12p80 stimulates the Schwann cell differentiation of mouse NSCs through the phosphorylation of signal transducer and activator of transcription 3 (Stat3). These results suggest that IL12p80 can trigger Schwann cell differentiation of mouse NSCs through Stat3 phosphorylation and enhance the functional recovery and the diameter of regenerated nerves in a mouse sciatic nerve injury model. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Emotion identification and aging: Behavioral and neural age-related changes.

    Science.gov (United States)

    Gonçalves, Ana R; Fernandes, Carina; Pasion, Rita; Ferreira-Santos, Fernando; Barbosa, Fernando; Marques-Teixeira, João

    2018-05-01

    Aging is known to alter the processing of facial expressions of emotion (FEE), however the impact of this alteration is less clear. Additionally, there is little information about the temporal dynamics of the neural processing of facial affect. We examined behavioral and neural age-related changes in the identification of FEE using event-related potentials. Furthermore, we analyze the relationship between behavioral/neural responses and neuropsychological functioning. To this purpose, 30 younger adults, 29 middle-aged adults and 26 older adults identified FEE. The behavioral results showed a similar performance between groups. The neural results showed no significant differences between groups for the P100 component and an increased N170 amplitude in the older group. Furthermore, a pattern of asymmetric activation was evident in the N170 component. Results also suggest deficits in facial feature decoding abilities, reflected by a reduced N250 amplitude in older adults. Neuropsychological functioning predicts P100 modulation, but does not seem to influence emotion identification ability. The findings suggest the existence of a compensatory function that would explain the age-equivalent performance in emotion identification. The study may help future research addressing behavioral and neural processes involved on processing of FEE in neurodegenerative conditions. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  7. Adolescent-specific patterns of behavior and neural activity during social reinforcement learning.

    Science.gov (United States)

    Jones, Rebecca M; Somerville, Leah H; Li, Jian; Ruberry, Erika J; Powers, Alisa; Mehta, Natasha; Dyke, Jonathan; Casey, B J

    2014-06-01

    Humans are sophisticated social beings. Social cues from others are exceptionally salient, particularly during adolescence. Understanding how adolescents interpret and learn from variable social signals can provide insight into the observed shift in social sensitivity during this period. The present study tested 120 participants between the ages of 8 and 25 years on a social reinforcement learning task where the probability of receiving positive social feedback was parametrically manipulated. Seventy-eight of these participants completed the task during fMRI scanning. Modeling trial-by-trial learning, children and adults showed higher positive learning rates than did adolescents, suggesting that adolescents demonstrated less differentiation in their reaction times for peers who provided more positive feedback. Forming expectations about receiving positive social reinforcement correlated with neural activity within the medial prefrontal cortex and ventral striatum across age. Adolescents, unlike children and adults, showed greater insular activity during positive prediction error learning and increased activity in the supplementary motor cortex and the putamen when receiving positive social feedback regardless of the expected outcome, suggesting that peer approval may motivate adolescents toward action. While different amounts of positive social reinforcement enhanced learning in children and adults, all positive social reinforcement equally motivated adolescents. Together, these findings indicate that sensitivity to peer approval during adolescence goes beyond simple reinforcement theory accounts and suggest possible explanations for how peers may motivate adolescent behavior.

  8. Chitosan scaffolds induce human dental pulp stem cells to neural differentiation: potential roles for spinal cord injury therapy.

    Science.gov (United States)

    Zhang, Jinlong; Lu, Xiaohui; Feng, Guijuan; Gu, Zhifeng; Sun, Yuyu; Bao, Guofeng; Xu, Guanhua; Lu, Yuanzhou; Chen, Jiajia; Xu, Lingfeng; Feng, Xingmei; Cui, Zhiming

    2016-10-01

    Cell-based transplantation strategies hold great potential for spinal cord injury (SCI) repair. Chitosan scaffolds have therapeutic benefits for spinal cord regeneration. Human dental pulp stem cells (DPSCs) are abundant available stem cells with low immunological incompatibility and can be considered for cell replacement therapy. The purpose of this study is to investigate the role of chitosan scaffolds in the neural differentiation of DPSCs in vitro and to assess the supportive effects of chitosan scaffolds in an animal model of SCI. DPSCs were incubated with chitosan scaffolds. Cell viability and the secretion of neurotrophic factors were analyzed. DPSCs incubated with chitosan scaffolds were treated with neural differentiation medium for 14 days and then neural genes and protein markers were analyzed by Western blot and reverse transcription plus the polymerase chain reaction. Our study revealed a higher cell viability and neural differentiation in the DPSC/chitosan-scaffold group. Compared with the control group, the levels of BDNF, GDNF, b-NGF, and NT-3 were significantly increased in the DPSC/chitosan-scaffold group. The Wnt/β-catenin signaling pathway played a key role in the neural differentiation of DPSCs combined with chitosan scaffolds. Transplantation of DPSCs together with chitosan scaffolds into an SCI rat model resulted in the marked recovery of hind limb locomotor functions. Thus, chitosan scaffolds were non-cytotoxic and provided a conducive and favorable microenvironment for the survival and neural differentiation of DPSCs. Transplantation of DPSCs might therefore be a suitable candidate for treating SCI and other neuronal degenerative diseases.

  9. Neurite extension and neuronal differentiation of human induced pluripotent stem cell derived neural stem cells on polyethylene glycol hydrogels containing a continuous Young's Modulus gradient.

    Science.gov (United States)

    Mosley, Matthew C; Lim, Hyun Ju; Chen, Jing; Yang, Yueh-Hsun; Li, Shenglan; Liu, Ying; Smith Callahan, Laura A

    2017-03-01

    Mechanotransduction in neural cells involves multiple signaling pathways that are not fully understood. Differences in lineage and maturation state are suggested causes for conflicting reports on neural cell mechanosensitivity. To optimize matrices for use in stem cell therapy treatments transplanting human induced pluripotent stem cell derived neural stem cells (hNSC) into lesions after spinal cord injury, the effects of Young's Modulus changes on hNSC behavior must be understood. The present study utilizes polyethylene glycol hydrogels containing a continuous gradient in Young's modulus to examine changes in the Young's Modulus of the culture substrate on hNSC neurite extension and neural differentiation. Changes in the Young's Modulus of the polyethylene glycol hydrogels was found to affect neurite extension and cellular organization on the matrices. hNSC cultured on 907 Pa hydrogels were found to extend longer neurites than hNSC cultured on other tested Young's Moduli hydrogels. The gene expression of β tubulin III and microtubule-associated protein 2 in hNSC was affected by changes in the Young's Modulus of the hydrogel. The combinatory method approach used in the present study demonstrates that hNSC are mechanosensitive and the matrix Young's Modulus should be a design consideration for hNSC transplant applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 824-833, 2017. © 2016 Wiley Periodicals, Inc.

  10. Adaptive Neural Control of Nonaffine Nonlinear Systems without Differential Condition for Nonaffine Function

    Directory of Open Access Journals (Sweden)

    Chaojiao Sun

    2016-01-01

    Full Text Available An adaptive neural control scheme is proposed for nonaffine nonlinear system without using the implicit function theorem or mean value theorem. The differential conditions on nonaffine nonlinear functions are removed. The control-gain function is modeled with the nonaffine function probably being indifferentiable. Furthermore, only a semibounded condition for nonaffine nonlinear function is required in the proposed method, and the basic idea of invariant set theory is then constructively introduced to cope with the difficulty in the control design for nonaffine nonlinear systems. It is rigorously proved that all the closed-loop signals are bounded and the tracking error converges to a small residual set asymptotically. Finally, simulation examples are provided to demonstrate the effectiveness of the designed method.

  11. Effects of neurotrophin-3 on the differentiation of neural stem cells into neurons and oligodendrocytes

    Science.gov (United States)

    Zhu, Guowei; Sun, Chongran; Liu, Weiguo

    2012-01-01

    In this study, cells from the cerebral cortex of fetal rats at pregnant 16 days were harvested and cultured with 20 μg/L neurotrophin-3. After 7 days of culture, immunocytochemical staining showed that, 22.4% of cells were positive for nestin, 10.5% were positive for β-III tubulin (neuronal marker), and 60.6% were positive for glial fibrillary acidic protein, but no cells were positive for O4 (oligodendrocytic marker). At 14 days, there were 5.6% nestin-, 9.6% β-III tubulin-, 81.1% glial fibrillary acidic protein-, and 2.2% O4-positive cells. In cells not treated with neurotrophin-3, some were nestin-positive, while the majority showed positive staining for glial fibrillary acidic protein. Our experimental findings indicate that neurotrophin-3 is a crucial factor for inducing neural stem cells differentiation into neurons and oligodendrocytes. PMID:25657683

  12. The effect of hydrostatic pressure on staurosporine-induced neural differentiation in mouse bone marrow‑derived mesenchymal stem cells.

    Science.gov (United States)

    Javanmard, F; Azadbakht, M; Pourmoradi, M

    2016-01-01

    In this study, the role of hydrostatic pressure on staurosporine-induced neural differentiation in mouse bone marrow mesenchymal stem cells were investigated. The cells were cultured in treatment medium containing 100 nM of staurosporine for 4 hours; then the cells were affected by hydrostatic pressure (0, 25,50, 100 mmHg). The percentage of cell viability by trypan blue staining and the percentage of cell death by Hoechst/PI differential staining were assessed. We obtained the total neurite length. Expression of β-tubulin III and GFAP (Glial fibrillary acidic protein) proteins were also analyzed by immunocytochemistry. The percentage of cell viability in treatments decreased relative to the increase in hydrostatic pressure and time (p Keywords: bone marrow mesenchymal stem cell, hydrostatic pressure, immunocytochemistry, neural differentiation, neurite length, cell differentiation.

  13. Modeling the thermotaxis behavior of C.elegans based on the artificial neural network.

    Science.gov (United States)

    Li, Mingxu; Deng, Xin; Wang, Jin; Chen, Qiaosong; Tang, Yun

    2016-07-03

    ASBTRACT This research aims at modeling the thermotaxis behavior of C.elegans which is a kind of nematode with full clarified neuronal connections. Firstly, this work establishes the motion model which can perform the undulatory locomotion with turning behavior. Secondly, the thermotaxis behavior is modeled by nonlinear functions and the nonlinear functions are learned by artificial neural network. Once the artificial neural networks have been well trained, they can perform the desired thermotaxis behavior. Last, several testing simulations are carried out to verify the effectiveness of the model for thermotaxis behavior. This work also analyzes the different performances of the model under different environments. The testing results reveal the essence of the thermotaxis of C.elegans to some extent, and theoretically support the research on the navigation of the crawling robots.

  14. Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

    Energy Technology Data Exchange (ETDEWEB)

    Manceur, Aziza P. [Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario (Canada); Donnelly Centre, University of Toronto, Toronto, Ontario (Canada); Tseng, Michael [Laboratory of Cellular and Molecular Pathophysiology, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario (Canada); Department of Psychiatry, University of Toronto, Toronto, ON (Canada); Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Holowacz, Tamara [Donnelly Centre, University of Toronto, Toronto, Ontario (Canada); Witterick, Ian [Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Department of Otolaryngology, Head and Neck Surgery, University of Toronto, ON (Canada); Weksberg, Rosanna [Institute of Medical Science, University of Toronto, Toronto, ON (Canada); The Hospital for Sick Children, Research Institute, Program in Genetics and Genomic Biology, Toronto, Ontario Canada (Canada); McCurdy, Richard D. [The Hospital for Sick Children, Research Institute, Program in Genetics and Genomic Biology, Toronto, Ontario Canada (Canada); Warsh, Jerry J. [Laboratory of Cellular and Molecular Pathophysiology, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario (Canada); Department of Psychiatry, University of Toronto, Toronto, ON (Canada); Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Audet, Julie, E-mail: julie.audet@utoronto.ca [Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario (Canada); Donnelly Centre, University of Toronto, Toronto, Ontario (Canada)

    2011-09-10

    The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B) inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.

  15. Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

    International Nuclear Information System (INIS)

    Manceur, Aziza P.; Tseng, Michael; Holowacz, Tamara; Witterick, Ian; Weksberg, Rosanna; McCurdy, Richard D.; Warsh, Jerry J.; Audet, Julie

    2011-01-01

    The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B) inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.

  16. The fiber-optic imaging and manipulation of neural activity during animal behavior.

    Science.gov (United States)

    Miyamoto, Daisuke; Murayama, Masanori

    2016-02-01

    Recent progress with optogenetic probes for imaging and manipulating neural activity has further increased the relevance of fiber-optic systems for neural circuitry research. Optical fibers, which bi-directionally transmit light between separate sites (even at a distance of several meters), can be used for either optical imaging or manipulating neural activity relevant to behavioral circuitry mechanisms. The method's flexibility and the specifications of the light structure are well suited for following the behavior of freely moving animals. Furthermore, thin optical fibers allow researchers to monitor neural activity from not only the cortical surface but also deep brain regions, including the hippocampus and amygdala. Such regions are difficult to target with two-photon microscopes. Optogenetic manipulation of neural activity with an optical fiber has the advantage of being selective for both cell-types and projections as compared to conventional electrophysiological brain tissue stimulation. It is difficult to extract any data regarding changes in neural activity solely from a fiber-optic manipulation device; however, the readout of data is made possible by combining manipulation with electrophysiological recording, or the simultaneous application of optical imaging and manipulation using a bundle-fiber. The present review introduces recent progress in fiber-optic imaging and manipulation methods, while also discussing fiber-optic system designs that are suitable for a given experimental protocol. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  17. Long-term culture and differentiation of CNS precursors derived from anterior human neural rosettes following exposure to ventralizing factors

    International Nuclear Information System (INIS)

    Colleoni, Silvia; Galli, Cesare; Giannelli, Serena G.; Armentero, Marie-Therese; Blandini, Fabio; Broccoli, Vania; Lazzari, Giovanna

    2010-01-01

    In this study we demonstrated that neural rosettes derived from human ES cells can give rise either to neural crest precursors, following expansion in presence of bFGF and EGF, or to dopaminergic precursors after exposure to ventralizing factors Shh and FGF8. Both regionalised precursors are capable of extensive proliferation and differentiation towards the corresponding terminally differentiated cell types. In particular, peripheral neurons, cartilage, bone, smooth muscle cells and also pigmented cells were obtained from neural crest precursors while tyrosine hydroxylase and Nurr1 positive dopaminergic neurons were derived from FGF8 and Shh primed rosette cells. Gene expression and immunocytochemistry analyses confirmed the expression of dorsal and neural crest genes such as Sox10, Slug, p75, FoxD3, Pax7 in neural precursors from bFGF-EGF exposed rosettes. By contrast, priming of rosettes with FGF8 and Shh induced the expression of dopaminergic markers Engrailed1, Pax2, Pitx3, floor plate marker FoxA2 and radial glia markers Blbp and Glast, the latter in agreement with the origin of dopaminergic precursors from floor plate radial glia. Moreover, in vivo transplant of proliferating Shh/FGF8 primed precursors in parkinsonian rats demonstrated engraftment and terminal dopaminergic differentiation. In conclusion, we demonstrated the derivation of long-term self-renewing precursors of selected regional identity as potential cell reservoirs for cell therapy applications, such as CNS degenerative diseases, or for the development of toxicological tests.

  18. Long-term culture and differentiation of CNS precursors derived from anterior human neural rosettes following exposure to ventralizing factors

    Energy Technology Data Exchange (ETDEWEB)

    Colleoni, Silvia, E-mail: silviacolleoni@avantea.it [Laboratorio di Tecnologie della Riproduzione, Avantea, Via Porcellasco 7/f, 26100 Cremona (Italy); Galli, Cesare [Laboratorio di Tecnologie della Riproduzione, Avantea, Via Porcellasco 7/f, 26100 Cremona (Italy); Dipartimento Clinico Veterinario, Universita di Bologna, Via Tolara di Sopra 50, 40064 Ozzano Emilia (Italy); Giannelli, Serena G. [Stem Cells and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan (Italy); Armentero, Marie-Therese; Blandini, Fabio [Laboratory of Functional Neurochemistry, Interdepartmental Research Center for Parkinson' s Disease, Neurological Institute C. Mondino, Via Mondino 2, 27100 Pavia (Italy); Broccoli, Vania, E-mail: broccoli.vania@hsr.it [Stem Cells and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan (Italy); Lazzari, Giovanna, E-mail: giovannalazzari@avantea.it [Laboratorio di Tecnologie della Riproduzione, Avantea, Via Porcellasco 7/f, 26100 Cremona (Italy)

    2010-04-15

    In this study we demonstrated that neural rosettes derived from human ES cells can give rise either to neural crest precursors, following expansion in presence of bFGF and EGF, or to dopaminergic precursors after exposure to ventralizing factors Shh and FGF8. Both regionalised precursors are capable of extensive proliferation and differentiation towards the corresponding terminally differentiated cell types. In particular, peripheral neurons, cartilage, bone, smooth muscle cells and also pigmented cells were obtained from neural crest precursors while tyrosine hydroxylase and Nurr1 positive dopaminergic neurons were derived from FGF8 and Shh primed rosette cells. Gene expression and immunocytochemistry analyses confirmed the expression of dorsal and neural crest genes such as Sox10, Slug, p75, FoxD3, Pax7 in neural precursors from bFGF-EGF exposed rosettes. By contrast, priming of rosettes with FGF8 and Shh induced the expression of dopaminergic markers Engrailed1, Pax2, Pitx3, floor plate marker FoxA2 and radial glia markers Blbp and Glast, the latter in agreement with the origin of dopaminergic precursors from floor plate radial glia. Moreover, in vivo transplant of proliferating Shh/FGF8 primed precursors in parkinsonian rats demonstrated engraftment and terminal dopaminergic differentiation. In conclusion, we demonstrated the derivation of long-term self-renewing precursors of selected regional identity as potential cell reservoirs for cell therapy applications, such as CNS degenerative diseases, or for the development of toxicological tests.

  19. The postischemic environment differentially impacts teratoma or tumor formation after transplantation of human embryonic stem cell-derived neural progenitors

    DEFF Research Database (Denmark)

    Seminatore, Christine; Polentes, Jerome; Ellman, Ditte

    2010-01-01

    Risk of tumorigenesis is a major obstacle to human embryonic and induced pluripotent stem cell therapy. Likely linked to the stage of differentiation of the cells at the time of implantation, formation of teratoma/tumors can also be influenced by factors released by the host tissue. We have...... analyzed the relative effects of the stage of differentiation and the postischemic environment on the formation of adverse structures by transplanted human embryonic stem cell-derived neural progenitors....

  20. Neutralization of LINGO-1 during in vitro differentiation of neural stem cells results in proliferation of immature neurons.

    Directory of Open Access Journals (Sweden)

    Camilla Lööv

    Full Text Available Identifying external factors that can be used to control neural stem cells division and their differentiation to neurons, astrocytes and oligodendrocytes is of high scientific and clinical interest. Here we show that the Nogo-66 receptor interacting protein LINGO-1 is a potent regulator of neural stem cell maturation to neurons. LINGO-1 is expressed by cortical neural stem cells from E14 mouse embryos and inhibition of LINGO-1 during the first days of neural stem cell differentiation results in decreased neuronal maturation. Compared to neurons in control cultures, which after 6 days of differentiation have long extending neurites, neurons in cultures treated with anti-LINGO-1 antibodies retain an immature, round phenotype with only very short processes. Furthermore, neutralization of LINGO-1 results in a threefold increase in βIII tubulin-positive cells compared to untreated control cultures. By using BrdU incorporation assays we show that the immature neurons in LINGO-1 neutralized cultures are dividing neuroblasts. In contrast to control cultures, in which no cells were double positive for βIII tubulin and BrdU, 36% of the neurons in cultures treated with anti-LINGO-1 antibodies were proliferating after three days of differentiation. TUNEL assays revealed that the amount of cells going through apoptosis during the early phase of differentiation was significantly decreased in cultures treated with anti-LINGO-1 antibodies compared to untreated control cultures. Taken together, our results demonstrate a novel role for LINGO-1 in neural stem cell differentiation to neurons and suggest a possibility to use LINGO-1 inhibitors to compensate for neuronal cell loss in the injured brain.

  1. Inhibition of Sirt1 promotes neural progenitors toward motoneuron differentiation from human embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yun; Wang, Jing [Department of Neurology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Chen, Guian [Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Reproductive Medical Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Fan, Dongsheng, E-mail: dsfan@yahoo.cn [Department of Neurology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Deng, Min, E-mail: dengmin1706@yahoo.com.cn [Department of Neurology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China)

    2011-01-14

    Research highlights: {yields} Nicotinamide inhibit Sirt1. {yields} MASH1 and Ngn2 activation. {yields} Increase the expression of HB9. {yields} Motoneurons formation increases significantly. -- Abstract: Several protocols direct human embryonic stem cells (hESCs) toward differentiation into functional motoneurons, but the efficiency of motoneuron generation varies based on the human ESC line used. We aimed to develop a novel protocol to increase the formation of motoneurons from human ESCs. In this study, we tested a nuclear histone deacetylase protein, Sirt1, to promote neural precursor cell (NPC) development during differentiation of human ESCs into motoneurons. A specific inhibitor of Sirt1, nicotinamide, dramatically increased motoneuron formation. We found that about 60% of the cells from the total NPCs expressed HB9 and {beta}III-tubulin, commonly used motoneuronal markers found in neurons derived from ESCs following nicotinamide treatment. Motoneurons derived from ESC expressed choline acetyltransferase (ChAT), a positive marker of mature motoneuron. Moreover, we also examined the transcript levels of Mash1, Ngn2, and HB9 mRNA in the differentiated NPCs treated with the Sirt1 activator resveratrol (50 {mu}M) or inhibitor nicotinamide (100 {mu}M). The levels of Mash1, Ngn2, and HB9 mRNA were significantly increased after nicotinamide treatment compared with control groups, which used the traditional protocol. These results suggested that increasing Mash1 and Ngn2 levels by inhibiting Sirt1 could elevate HB9 expression, which promotes motoneuron differentiation. This study provides an alternative method for the production of transplantable motoneurons, a key requirement in the development of hESC-based cell therapy in motoneuron disease.

  2. Inhibition of Sirt1 promotes neural progenitors toward motoneuron differentiation from human embryonic stem cells

    International Nuclear Information System (INIS)

    Zhang, Yun; Wang, Jing; Chen, Guian; Fan, Dongsheng; Deng, Min

    2011-01-01

    Research highlights: → Nicotinamide inhibit Sirt1. → MASH1 and Ngn2 activation. → Increase the expression of HB9. → Motoneurons formation increases significantly. -- Abstract: Several protocols direct human embryonic stem cells (hESCs) toward differentiation into functional motoneurons, but the efficiency of motoneuron generation varies based on the human ESC line used. We aimed to develop a novel protocol to increase the formation of motoneurons from human ESCs. In this study, we tested a nuclear histone deacetylase protein, Sirt1, to promote neural precursor cell (NPC) development during differentiation of human ESCs into motoneurons. A specific inhibitor of Sirt1, nicotinamide, dramatically increased motoneuron formation. We found that about 60% of the cells from the total NPCs expressed HB9 and βIII-tubulin, commonly used motoneuronal markers found in neurons derived from ESCs following nicotinamide treatment. Motoneurons derived from ESC expressed choline acetyltransferase (ChAT), a positive marker of mature motoneuron. Moreover, we also examined the transcript levels of Mash1, Ngn2, and HB9 mRNA in the differentiated NPCs treated with the Sirt1 activator resveratrol (50 μM) or inhibitor nicotinamide (100 μM). The levels of Mash1, Ngn2, and HB9 mRNA were significantly increased after nicotinamide treatment compared with control groups, which used the traditional protocol. These results suggested that increasing Mash1 and Ngn2 levels by inhibiting Sirt1 could elevate HB9 expression, which promotes motoneuron differentiation. This study provides an alternative method for the production of transplantable motoneurons, a key requirement in the development of hESC-based cell therapy in motoneuron disease.

  3. Zika virus infection dysregulates human neural stem cell growth and inhibits differentiation into neuroprogenitor cells.

    Science.gov (United States)

    Devhare, Pradip; Meyer, Keith; Steele, Robert; Ray, Ratna B; Ray, Ranjit

    2017-10-12

    The current outbreak of Zika virus-associated diseases in South America and its threat to spread to other parts of the world has emerged as a global health emergency. A strong link between Zika virus and microcephaly exists, and the potential mechanisms associated with microcephaly are under intense investigation. In this study, we evaluated the effect of Zika virus infection of Asian and African lineages (PRVABC59 and MR766) in human neural stem cells (hNSCs). These two Zika virus strains displayed distinct infection pattern and growth rates in hNSCs. Zika virus MR766 strain increased serine 139 phosphorylation of histone H2AX (γH2AX), a known early cellular response proteins to DNA damage. On the other hand, PRVABC59 strain upregulated serine 15 phosphorylation of p53, p21 and PUMA expression. MR766-infected cells displayed poly (ADP-ribose) polymerase (PARP) and caspase-3 cleavage. Interestingly, infection of hNSCs by both strains of Zika virus for 24 h, followed by incubation in astrocyte differentiation medium, induced rounding and cell death. However, astrocytes generated from hNSCs by incubation in differentiation medium when infected with Zika virus displayed minimal cytopathic effect at an early time point. Infected hNSCs incubated in astrocyte differentiating medium displayed PARP cleavage within 24-36 h. Together, these results showed that two distinct strains of Zika virus potentiate hNSC growth inhibition by different mechanisms, but both viruses strongly induce death in early differentiating neuroprogenitor cells even at a very low multiplicity of infection. Our observations demonstrate further mechanistic insights for impaired neuronal homeostasis during active Zika virus infection.

  4. Zika virus infection dysregulates human neural stem cell growth and inhibits differentiation into neuroprogenitor cells

    Science.gov (United States)

    Devhare, Pradip; Meyer, Keith; Steele, Robert; Ray, Ratna B; Ray, Ranjit

    2017-01-01

    The current outbreak of Zika virus-associated diseases in South America and its threat to spread to other parts of the world has emerged as a global health emergency. A strong link between Zika virus and microcephaly exists, and the potential mechanisms associated with microcephaly are under intense investigation. In this study, we evaluated the effect of Zika virus infection of Asian and African lineages (PRVABC59 and MR766) in human neural stem cells (hNSCs). These two Zika virus strains displayed distinct infection pattern and growth rates in hNSCs. Zika virus MR766 strain increased serine 139 phosphorylation of histone H2AX (γH2AX), a known early cellular response proteins to DNA damage. On the other hand, PRVABC59 strain upregulated serine 15 phosphorylation of p53, p21 and PUMA expression. MR766-infected cells displayed poly (ADP-ribose) polymerase (PARP) and caspase-3 cleavage. Interestingly, infection of hNSCs by both strains of Zika virus for 24 h, followed by incubation in astrocyte differentiation medium, induced rounding and cell death. However, astrocytes generated from hNSCs by incubation in differentiation medium when infected with Zika virus displayed minimal cytopathic effect at an early time point. Infected hNSCs incubated in astrocyte differentiating medium displayed PARP cleavage within 24–36 h. Together, these results showed that two distinct strains of Zika virus potentiate hNSC growth inhibition by different mechanisms, but both viruses strongly induce death in early differentiating neuroprogenitor cells even at a very low multiplicity of infection. Our observations demonstrate further mechanistic insights for impaired neuronal homeostasis during active Zika virus infection. PMID:29022904

  5. Enhanced differentiation of neural stem cells to neurons and promotion of neurite outgrowth by oxygen-glucose deprivation.

    Science.gov (United States)

    Wang, Qin; Yang, Lin; Wang, Yaping

    2015-06-01

    Stroke has become the leading cause of mortality worldwide. Hypoxic or ischemic insults are crucial factors mediating the neural damage in the brain tissue of stroke patients. Neural stem cells (NSCs) have been recognized as a promising tool for the treatment of ischemic stroke and other neurodegenerative diseases due to their inducible pluripotency. In this study, we aim to mimick the cerebral hypoxic-ischemic injury in vitro using oxygen-glucose deprivation (OGD) strategy, and evaluate the effects of OGD on the NSC's neural differentiation, as well as the differentiated neurite outgrowth. Our data showed that NSCs under the short-term 2h OGD treatment are able to maintain cell viability and the capability to form neurospheres. Importantly, this moderate OGD treatment promotes NSC differentiation to neurons and enhances the performance of the mature neuronal networks, accompanying increased neurite outgrowth of differentiated neurons. However, long-term 6h and 8h OGD exposures in NSCs lead to decreased cell survival, reduced differentiation and diminished NSC-derived neurite outgrowth. The expressions of neuron-specific microtubule-associated protein 2 (MAP-2) and growth associated protein 43 (GAP-43) are increased by short-term OGD treatments but suppressed by long-term OGD. Overall, our results demonstrate that short-term OGD exposure in vitro induces differentiation of NSCs while maintaining their proliferation and survival, providing valuable insights of adopting NSC-based therapy for ischemic stroke and other neurodegenerative disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Effects of the Post-Spinal Cord Injury Microenvironment on the Differentiation Capacity of Human Neural Stem Cells Derived from Induced Pluripotent Stem Cells.

    Science.gov (United States)

    López-Serrano, Clara; Torres-Espín, Abel; Hernández, Joaquim; Alvarez-Palomo, Ana B; Requena, Jordi; Gasull, Xavier; Edel, Michael J; Navarro, Xavier

    2016-10-01

    Spinal cord injury (SCI) causes loss of neural functions below the level of the lesion due to interruption of spinal pathways and secondary neurodegenerative processes. The transplant of neural stem cells (NSCs) is a promising approach for the repair of SCI. Reprogramming of adult somatic cells into induced pluripotent stem cells (iPSCs) is expected to provide an autologous source of iPSC-derived NSCs, avoiding the immune response as well as ethical issues. However, there is still limited information on the behavior and differentiation pattern of transplanted iPSC-derived NSCs within the damaged spinal cord. We transplanted iPSC-derived NSCs, obtained from adult human somatic cells, into rats at 0 or 7 days after SCI, and evaluated motor-evoked potentials and locomotion of the animals. We histologically analyzed engraftment, proliferation, and differentiation of the iPSC-derived NSCs and the spared tissue in the spinal cords at 7, 21, and 63 days posttransplant. Both transplanted groups showed a late decline in functional recovery compared to vehicle-injected groups. Histological analysis showed proliferation of transplanted cells within the tissue and that cells formed a mass. At the final time point, most grafted cells differentiated to neural and astroglial lineages, but not into oligodendrocytes, while some grafted cells remained undifferentiated and proliferative. The proinflammatory tissue microenviroment of the injured spinal cord induced proliferation of the grafted cells and, therefore, there are possible risks associated with iPSC-derived NSC transplantation. New approaches are needed to promote and guide cell differentiation, as well as reduce their tumorigenicity once the cells are transplanted at the lesion site.

  7. The Postischemic Environment Differentially Impacts Teratoma or Tumor Formation After Transplantation of Human Embryonic Stem Cell-Derived Neural Progenitors

    Czech Academy of Sciences Publication Activity Database

    Seminatore, CH.; Polentes, J.; Ellman, D.; Kozubenko, Nataliya; Itier, V.; Tine, S.; Tritschler, L.; Brenot, M.; Guidou, E.; Blondeau, J.; Lhuillier, M.; Bugi, A.; Aubry, L.; Jendelová, Pavla; Syková, Eva; Perrier, A. L.; Finsen, B.; Onteniente, B.

    2010-01-01

    Roč. 41, č. 1 (2010), s. 153-159 ISSN 0039-2499 Institutional research plan: CEZ:AV0Z50390703 Keywords : brain transplantation * human embryonic stem cells * neural differentiation Subject RIV: FH - Neurology Impact factor: 5.756, year: 2010

  8. GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3

    Energy Technology Data Exchange (ETDEWEB)

    Boku, Shuken, E-mail: shuboku@med.hokudai.ac.jp [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Nakagawa, Shin [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Takamura, Naoki [Pharmaceutical Laboratories, Dainippon Sumitomo Pharma Co. Ltd., Osaka (Japan); Kato, Akiko [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Takebayashi, Minoru [Department of Psychiatry, National Hospital Organization Kure Medical Center, Kure (Japan); Hisaoka-Nakashima, Kazue [Department of Pharmacology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima (Japan); Omiya, Yuki; Inoue, Takeshi; Kusumi, Ichiro [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan)

    2013-05-17

    Highlights: •GDNF has no effect on ADP proliferation and apoptosis. •GDNF increases ADP differentiation into astrocyte. •A specific inhibitor of STAT3 decreases the astrogliogenic effect of GDNF. •STAT3 knockdown by lentiviral shRNA vector also decreases the astrogliogenic effect of GDNF. •GDNF increases the phosphorylation of STAT3. -- Abstract: While the pro-neurogenic actions of antidepressants in the adult hippocampal dentate gyrus (DG) are thought to be one of the mechanisms through which antidepressants exert their therapeutic actions, antidepressants do not increase proliferation of neural precursor cells derived from the adult DG. Because previous studies showed that antidepressants increase the expression and secretion of glial cell line-derived neurotrophic factor (GDNF) in C6 glioma cells derived from rat astrocytes and GDNF increases neurogenesis in adult DG in vivo, we investigated the effects of GDNF on the proliferation, differentiation and apoptosis of cultured neural precursor cells derived from the adult DG. Data showed that GDNF facilitated the differentiation of neural precursor cells into astrocytes but had no effect on their proliferation or apoptosis. Moreover, GDNF increased the phosphorylation of STAT3, and both a specific inhibitor of STAT3 and lentiviral shRNA for STAT3 decreased their differentiation into astrocytes. Taken together, our findings suggest that GDNF facilitates astrogliogenesis from neural precursor cells in adult DG through activating STAT3 and that this action might indirectly affect neurogenesis.

  9. GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3

    International Nuclear Information System (INIS)

    Boku, Shuken; Nakagawa, Shin; Takamura, Naoki; Kato, Akiko; Takebayashi, Minoru; Hisaoka-Nakashima, Kazue; Omiya, Yuki; Inoue, Takeshi; Kusumi, Ichiro

    2013-01-01

    Highlights: •GDNF has no effect on ADP proliferation and apoptosis. •GDNF increases ADP differentiation into astrocyte. •A specific inhibitor of STAT3 decreases the astrogliogenic effect of GDNF. •STAT3 knockdown by lentiviral shRNA vector also decreases the astrogliogenic effect of GDNF. •GDNF increases the phosphorylation of STAT3. -- Abstract: While the pro-neurogenic actions of antidepressants in the adult hippocampal dentate gyrus (DG) are thought to be one of the mechanisms through which antidepressants exert their therapeutic actions, antidepressants do not increase proliferation of neural precursor cells derived from the adult DG. Because previous studies showed that antidepressants increase the expression and secretion of glial cell line-derived neurotrophic factor (GDNF) in C6 glioma cells derived from rat astrocytes and GDNF increases neurogenesis in adult DG in vivo, we investigated the effects of GDNF on the proliferation, differentiation and apoptosis of cultured neural precursor cells derived from the adult DG. Data showed that GDNF facilitated the differentiation of neural precursor cells into astrocytes but had no effect on their proliferation or apoptosis. Moreover, GDNF increased the phosphorylation of STAT3, and both a specific inhibitor of STAT3 and lentiviral shRNA for STAT3 decreased their differentiation into astrocytes. Taken together, our findings suggest that GDNF facilitates astrogliogenesis from neural precursor cells in adult DG through activating STAT3 and that this action might indirectly affect neurogenesis

  10. Overexpressed Calponin3 by Subsonic Vibration Induces Neural Differentiation of hUC-MSCs by Regulating the Ionotropic Glutamate Receptor.

    Science.gov (United States)

    Kim, Hyun-Jung; Kim, Jin-Hee; Song, Yeo-Ju; Seo, Young-Kwon; Park, Jung-Keug; Kim, Chan-Wha

    2015-09-01

    In this study, we used proteomics to investigate the effects of sonic vibration (SV) on mesenchymal stem cells derived from human umbilical cords (hUC-MSCs) during neural differentiation to understand how SV enhances neural differentiation of hUC-MSCs. We investigated the levels of gene and protein related to neural differentiation after 3 or 5 days in a group treated with 40-Hz SV. In addition, protein expression patterns were compared between the control and the 40-Hz SV-treated hUC-MSC groups via a proteomic approach. Among these proteins, calponin3 (CNN3) was confirmed to have 299 % higher expression in the 40-Hz SV stimulated hUC-MSCs group than that in the control by Western blotting. Notably, overexpression of CNN3-GFP in Chinese hamster ovary (CHO)-K1 cells had positive effects on the stability and reorganization of F-actin compared with that in GFP-transfected cells. Moreover, CNN3 changed the morphology of the cells by making a neurite-like form. After being subjected to SV, messenger RNA (mRNA) levels of glutamate receptors such as PSD95, GluR1, and NR1 as well as intracellular calcium levels were upregulated. These results suggest that the activity of glutamate receptors increased because of CNN3 characteristics. Taken together, these results demonstrate that overexpressed CNN3 during SV increases expression of glutamate receptors and promotes functional neural differentiation of hUC-MSCs.

  11. A new avenue to the synthesis of GAG-mimicking polymers highly promoting neural differentiation of embryonic stem cells.

    Science.gov (United States)

    Wang, Mengmeng; Lyu, Zhonglin; Chen, Gaojian; Wang, Hongwei; Yuan, Yuqi; Ding, Kaiguo; Yu, Qian; Yuan, Lin; Chen, Hong

    2015-10-28

    A new strategy for the fabrication of glycosaminoglycan (GAG) analogs was proposed by copolymerizing the sulfonated unit and the glyco unit, 'splitted' from the sulfated saccharide building blocks of GAGs. The synthetic polymers can promote cell proliferation and neural differentiation of embryonic stem cells with the effects even better than those of heparin.

  12. Possible promotion of neuronal differentiation in fetal rat brain neural progenitor cells after sustained exposure to static magnetism.

    Science.gov (United States)

    Nakamichi, Noritaka; Ishioka, Yukichi; Hirai, Takao; Ozawa, Shusuke; Tachibana, Masaki; Nakamura, Nobuhiro; Takarada, Takeshi; Yoneda, Yukio

    2009-08-15

    We have previously shown significant potentiation of Ca(2+) influx mediated by N-methyl-D-aspartate receptors, along with decreased microtubules-associated protein-2 (MAP2) expression, in hippocampal neurons cultured under static magnetism without cell death. In this study, we investigated the effects of static magnetism on the functionality of neural progenitor cells endowed to proliferate for self-replication and differentiate into neuronal, astroglial, and oligodendroglial lineages. Neural progenitor cells were isolated from embryonic rat neocortex and hippocampus, followed by culture under static magnetism at 100 mT and subsequent determination of the number of cells immunoreactive for a marker protein of particular progeny lineages. Static magnetism not only significantly decreased proliferation of neural progenitor cells without affecting cell viability, but also promoted differentiation into cells immunoreactive for MAP2 with a concomitant decrease in that for an astroglial marker, irrespective of the presence of differentiation inducers. In neural progenitors cultured under static magnetism, a significant increase was seen in mRNA expression of several activator-type proneural genes, such as Mash1, Math1, and Math3, together with decreased mRNA expression of the repressor type Hes5. These results suggest that sustained static magnetism could suppress proliferation for self-renewal and facilitate differentiation into neurons through promoted expression of activator-type proneural genes by progenitor cells in fetal rat brain.

  13. Synaptic plasticity in a recurrent neural network for versatile and adaptive behaviors of a walking robot

    Directory of Open Access Journals (Sweden)

    Eduard eGrinke

    2015-10-01

    Full Text Available Walking animals, like insects, with little neural computing can effectively perform complex behaviors. They can walk around their environment, escape from corners/deadlocks, and avoid or climb over obstacles. While performing all these behaviors, they can also adapt their movements to deal with an unknown situation. As a consequence, they successfully navigate through their complex environment. The versatile and adaptive abilities are the result of an integration of several ingredients embedded in their sensorimotor loop. Biological studies reveal that the ingredients include neural dynamics, plasticity, sensory feedback, and biomechanics. Generating such versatile and adaptive behaviors for a walking robot is a challenging task. In this study, we present a bio-inspired approach to solve this task. Specifically, the approach combines neural mechanisms with plasticity, sensory feedback, and biomechanics. The neural mechanisms consist of adaptive neural sensory processing and modular neural locomotion control. The sensory processing is based on a small recurrent network consisting of two fully connected neurons. Online correlation-based learning with synaptic scaling is applied to adequately change the connections of the network. By doing so, we can effectively exploit neural dynamics (i.e., hysteresis effects and single attractors in the network to generate different turning angles with short-term memory for a biomechanical walking robot. The turning information is transmitted as descending steering signals to the locomotion control which translates the signals into motor actions. As a result, the robot can walk around and adapt its turning angle for avoiding obstacles in different situations as well as escaping from sharp corners or deadlocks. Using backbone joint control embedded in the locomotion control allows the robot to climb over small obstacles. Consequently, it can successfully explore and navigate in complex environments.

  14. miR-342-5p Regulates Neural Stem Cell Proliferation and Differentiation Downstream to Notch Signaling in Mice

    Directory of Open Access Journals (Sweden)

    Fang Gao

    2017-04-01

    Full Text Available Summary: Notch signaling is critically involved in neural development, but the downstream effectors remain incompletely understood. In this study, we cultured neurospheres from Nestin-Cre-mediated conditional Rbp-j knockout (Rbp-j cKO and control embryos and compared their miRNA expression profiles using microarray. Among differentially expressed miRNAs, miR-342-5p showed upregulated expression as Notch signaling was genetically or pharmaceutically interrupted. Consistently, the promoter of the miR-342-5p host gene, the Ena-vasodilator stimulated phosphoprotein-like (Evl, was negatively regulated by Notch signaling, probably through HES5. Transfection of miR-342-5p promoted the differentiation of neural stem cells (NSCs into intermediate neural progenitors (INPs in vitro and reduced the stemness of NSCs in vivo. Furthermore, miR-342-5p inhibited the differentiation of neural stem/intermediate progenitor cells into astrocytes, likely mediated by targeting GFAP directly. Our results indicated that miR-342-5p could function as a downstream effector of Notch signaling to regulate the differentiation of NSCs into INPs and astrocytes commitment. : In this article, Han and colleagues show that miR-342-5p acts as a downstream effector of Notch signaling in the mouse CNS. Notch signal inhibits miR-342-5p expression by regulating its host gene Evl. And with attenuated Notch signal in NSCs, miR-342-5p is upregulated to promote NSCs transition into INPs, and to inhibit astrocyte commitment by targeting GFAP. Keywords: neural stem cells, intermediate neural progenitors, Notch, RBP-J, neuron, glia, miR-342-5p

  15. Homology and homoplasy of swimming behaviors and neural circuits in the Nudipleura (Mollusca, Gastropoda, Opisthobranchia)

    Science.gov (United States)

    Newcomb, James M.; Sakurai, Akira; Lillvis, Joshua L.; Gunaratne, Charuni A.; Katz, Paul S.

    2012-01-01

    How neural circuit evolution relates to behavioral evolution is not well understood. Here the relationship between neural circuits and behavior is explored with respect to the swimming behaviors of the Nudipleura (Mollusca, Gastropoda, Opithobranchia). Nudipleura is a diverse monophyletic clade of sea slugs among which only a small percentage of species can swim. Swimming falls into a limited number of categories, the most prevalent of which are rhythmic left–right body flexions (LR) and rhythmic dorsal–ventral body flexions (DV). The phylogenetic distribution of these behaviors suggests a high degree of homoplasy. The central pattern generator (CPG) underlying DV swimming has been well characterized in Tritonia diomedea and in Pleurobranchaea californica. The CPG for LR swimming has been elucidated in Melibe leonina and Dendronotus iris, which are more closely related. The CPGs for the categorically distinct DV and LR swimming behaviors consist of nonoverlapping sets of homologous identified neurons, whereas the categorically similar behaviors share some homologous identified neurons, although the exact composition of neurons and synapses in the neural circuits differ. The roles played by homologous identified neurons in categorically distinct behaviors differ. However, homologous identified neurons also play different roles even in the swim CPGs of the two LR swimming species. Individual neurons can be multifunctional within a species. Some of those functions are shared across species, whereas others are not. The pattern of use and reuse of homologous neurons in various forms of swimming and other behaviors further demonstrates that the composition of neural circuits influences the evolution of behaviors. PMID:22723353

  16. Single- and Multiple-Objective Optimization with Differential Evolution and Neural Networks

    Science.gov (United States)

    Rai, Man Mohan

    2006-01-01

    Genetic and evolutionary algorithms have been applied to solve numerous problems in engineering design where they have been used primarily as optimization procedures. These methods have an advantage over conventional gradient-based search procedures became they are capable of finding global optima of multi-modal functions and searching design spaces with disjoint feasible regions. They are also robust in the presence of noisy data. Another desirable feature of these methods is that they can efficiently use distributed and parallel computing resources since multiple function evaluations (flow simulations in aerodynamics design) can be performed simultaneously and independently on ultiple processors. For these reasons genetic and evolutionary algorithms are being used more frequently in design optimization. Examples include airfoil and wing design and compressor and turbine airfoil design. They are also finding increasing use in multiple-objective and multidisciplinary optimization. This lecture will focus on an evolutionary method that is a relatively new member to the general class of evolutionary methods called differential evolution (DE). This method is easy to use and program and it requires relatively few user-specified constants. These constants are easily determined for a wide class of problems. Fine-tuning the constants will off course yield the solution to the optimization problem at hand more rapidly. DE can be efficiently implemented on parallel computers and can be used for continuous, discrete and mixed discrete/continuous optimization problems. It does not require the objective function to be continuous and is noise tolerant. DE and applications to single and multiple-objective optimization will be included in the presentation and lecture notes. A method for aerodynamic design optimization that is based on neural networks will also be included as a part of this lecture. The method offers advantages over traditional optimization methods. It is more

  17. Neural response to pictorial health warning labels can predict smoking behavioral change.

    Science.gov (United States)

    Riddle, Philip J; Newman-Norlund, Roger D; Baer, Jessica; Thrasher, James F

    2016-11-01

    In order to improve our understanding of how pictorial health warning labels (HWLs) influence smoking behavior, we examined whether brain activity helps to explain smoking behavior above and beyond self-reported effectiveness of HWLs. We measured the neural response in the ventromedial prefrontal cortex (vmPFC) and the amygdala while adult smokers viewed HWLs. Two weeks later, participants' self-reported smoking behavior and biomarkers of smoking behavior were reassessed. We compared multiple models predicting change in self-reported smoking behavior (cigarettes per day [CPD]) and change in a biomarkers of smoke exposure (expired carbon monoxide [CO]). Brain activity in the vmPFC and amygdala not only predicted changes in CO, but also accounted for outcome variance above and beyond self-report data. Neural data were most useful in predicting behavioral change as quantified by the objective biomarker (CO). This pattern of activity was significantly modulated by individuals' intention to quit. The finding that both cognitive (vmPFC) and affective (amygdala) brain areas contributed to these models supports the idea that smokers respond to HWLs in a cognitive-affective manner. Based on our findings, researchers may wish to consider using neural data from both cognitive and affective networks when attempting to predict behavioral change in certain populations (e.g. cigarette smokers). © The Author (2016). Published by Oxford University Press.

  18. Expression of polysialylated neural cell adhesion molecules on adult stem cells after neuronal differentiation of inner ear spiral ganglion neurons

    Energy Technology Data Exchange (ETDEWEB)

    Park, Kyoung Ho [Department of Otolaryngology Head and Neck Surgery, College of Medicine, Catholic University, Seoul (Korea, Republic of); Yeo, Sang Won, E-mail: swyeo@catholic.ac.kr [Department of Otolaryngology Head and Neck Surgery, College of Medicine, Catholic University, Seoul (Korea, Republic of); Troy, Frederic A., E-mail: fatroy@ucdavis.edu [Department of Biochemistry and Molecular Medicine, University of California, School of Medicine, Davis, CA 95616 (United States); Xiamen University, School of Medicine, Xiamen City (China)

    2014-10-17

    Highlights: • PolySia expressed on neurons primarily during early stages of neuronal development. • PolySia–NCAM is expressed on neural stem cells from adult guinea pig spiral ganglion. • PolySia is a biomarker that modulates neuronal differentiation in inner ear stem cells. - Abstract: During brain development, polysialylated (polySia) neural cell adhesion molecules (polySia–NCAMs) modulate cell–cell adhesive interactions involved in synaptogenesis, neural plasticity, myelination, and neural stem cell (NSC) proliferation and differentiation. Our findings show that polySia–NCAM is expressed on NSC isolated from adult guinea pig spiral ganglion (GPSG), and in neurons and Schwann cells after differentiation of the NSC with epidermal, glia, fibroblast growth factors (GFs) and neurotrophins. These differentiated cells were immunoreactive with mAb’s to polySia, NCAM, β-III tubulin, nestin, S-100 and stained with BrdU. NSC could regenerate and be differentiated into neurons and Schwann cells. We conclude: (1) polySia is expressed on NSC isolated from adult GPSG and on neurons and Schwann cells differentiated from these NSC; (2) polySia is expressed on neurons primarily during the early stage of neuronal development and is expressed on Schwann cells at points of cell–cell contact; (3) polySia is a functional biomarker that modulates neuronal differentiation in inner ear stem cells. These new findings suggest that replacement of defective cells in the inner ear of hearing impaired patients using adult spiral ganglion neurons may offer potential hope to improve the quality of life for patients with auditory dysfunction and impaired hearing disorders.

  19. Expression of polysialylated neural cell adhesion molecules on adult stem cells after neuronal differentiation of inner ear spiral ganglion neurons

    International Nuclear Information System (INIS)

    Park, Kyoung Ho; Yeo, Sang Won; Troy, Frederic A.

    2014-01-01

    Highlights: • PolySia expressed on neurons primarily during early stages of neuronal development. • PolySia–NCAM is expressed on neural stem cells from adult guinea pig spiral ganglion. • PolySia is a biomarker that modulates neuronal differentiation in inner ear stem cells. - Abstract: During brain development, polysialylated (polySia) neural cell adhesion molecules (polySia–NCAMs) modulate cell–cell adhesive interactions involved in synaptogenesis, neural plasticity, myelination, and neural stem cell (NSC) proliferation and differentiation. Our findings show that polySia–NCAM is expressed on NSC isolated from adult guinea pig spiral ganglion (GPSG), and in neurons and Schwann cells after differentiation of the NSC with epidermal, glia, fibroblast growth factors (GFs) and neurotrophins. These differentiated cells were immunoreactive with mAb’s to polySia, NCAM, β-III tubulin, nestin, S-100 and stained with BrdU. NSC could regenerate and be differentiated into neurons and Schwann cells. We conclude: (1) polySia is expressed on NSC isolated from adult GPSG and on neurons and Schwann cells differentiated from these NSC; (2) polySia is expressed on neurons primarily during the early stage of neuronal development and is expressed on Schwann cells at points of cell–cell contact; (3) polySia is a functional biomarker that modulates neuronal differentiation in inner ear stem cells. These new findings suggest that replacement of defective cells in the inner ear of hearing impaired patients using adult spiral ganglion neurons may offer potential hope to improve the quality of life for patients with auditory dysfunction and impaired hearing disorders

  20. Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection

    Directory of Open Access Journals (Sweden)

    Erica L. McGrath

    2017-03-01

    Full Text Available Zika virus (ZIKV infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7, to infect primary human neural stem cells (hNSCs originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection.

  1. The effect of interferon-{beta} on mouse neural progenitor cell survival and differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Hirsch, Marek [Neurology Department, University of Vermont College of Medicine, Burlington, VT (United States); Knight, Julia [Neuroscience Department, University of Vermont College of Medicine, Burlington, VT (United States); Tobita, Mari; Soltys, John; Panitch, Hillel [Neurology Department, University of Vermont College of Medicine, Burlington, VT (United States); Mao-Draayer, Yang, E-mail: yang.mao-draayer@vtmednet.org [Neurology Department, University of Vermont College of Medicine, Burlington, VT (United States)

    2009-10-16

    Interferon-{beta} (IFN-{beta}) is a mainstay therapy for relapse-remitting multiple sclerosis (MS). However, the direct effects of IFN-{beta} on the central nervous system (CNS) are not well understood. To determine whether IFN-{beta} has direct neuroprotective effects on CNS cells, we treated adult mouse neural progenitor cells (NPCs) in vitro with IFN-{beta} and examined the effects on proliferation, apoptosis, and differentiation. We found that mouse NPCs express high levels of IFN{alpha}/{beta} receptor (IFNAR). In response to IFN-{beta} treatment, no effect was observed on differentiation or proliferation. However, IFN-{beta} treated mouse NPCs demonstrated decreased apoptosis upon growth factor withdrawal. Pathway-specific polymerase chain reaction (PCR) arrays demonstrated that IFN-{beta} treatment upregulated the STAT 1 and 2 signaling pathway, as well as GFRA2, NOD1, Caspases 1 and 12, and TNFSF10. These results suggest that IFN-{beta} can directly affect NPC survival, possibly playing a neuroprotective role in the CNS by modulating neurotrophic factors.

  2. Expandable and Rapidly Differentiating Human Induced Neural Stem Cell Lines for Multiple Tissue Engineering Applications

    Directory of Open Access Journals (Sweden)

    Dana M. Cairns

    2016-09-01

    Full Text Available Limited availability of human neurons poses a significant barrier to progress in biological and preclinical studies of the human nervous system. Current stem cell-based approaches of neuron generation are still hindered by prolonged culture requirements, protocol complexity, and variability in neuronal differentiation. Here we establish stable human induced neural stem cell (hiNSC lines through the direct reprogramming of neonatal fibroblasts and adult adipose-derived stem cells. These hiNSCs can be passaged indefinitely and cryopreserved as colonies. Independently of media composition, hiNSCs robustly differentiate into TUJ1-positive neurons within 4 days, making them ideal for innervated co-cultures. In vivo, hiNSCs migrate, engraft, and contribute to both central and peripheral nervous systems. Lastly, we demonstrate utility of hiNSCs in a 3D human brain model. This method provides a valuable interdisciplinary tool that could be used to develop drug screening applications as well as patient-specific disease models related to disorders of innervation and the brain.

  3. The effect of interferon-β on mouse neural progenitor cell survival and differentiation

    International Nuclear Information System (INIS)

    Hirsch, Marek; Knight, Julia; Tobita, Mari; Soltys, John; Panitch, Hillel; Mao-Draayer, Yang

    2009-01-01

    Interferon-β (IFN-β) is a mainstay therapy for relapse-remitting multiple sclerosis (MS). However, the direct effects of IFN-β on the central nervous system (CNS) are not well understood. To determine whether IFN-β has direct neuroprotective effects on CNS cells, we treated adult mouse neural progenitor cells (NPCs) in vitro with IFN-β and examined the effects on proliferation, apoptosis, and differentiation. We found that mouse NPCs express high levels of IFNα/β receptor (IFNAR). In response to IFN-β treatment, no effect was observed on differentiation or proliferation. However, IFN-β treated mouse NPCs demonstrated decreased apoptosis upon growth factor withdrawal. Pathway-specific polymerase chain reaction (PCR) arrays demonstrated that IFN-β treatment upregulated the STAT 1 and 2 signaling pathway, as well as GFRA2, NOD1, Caspases 1 and 12, and TNFSF10. These results suggest that IFN-β can directly affect NPC survival, possibly playing a neuroprotective role in the CNS by modulating neurotrophic factors.

  4. Neural cell adhesion molecule (NCAM) marks adult myogenic cells committed to differentiation

    International Nuclear Information System (INIS)

    Capkovic, Katie L.; Stevenson, Severin; Johnson, Marc C.; Thelen, Jay J.; Cornelison, D.D.W.

    2008-01-01

    Although recent advances in broad-scale gene expression analysis have dramatically increased our knowledge of the repertoire of mRNAs present in multiple cell types, it has become increasingly clear that examination of the expression, localization, and associations of the encoded proteins will be critical for determining their functional significance. In particular, many signaling receptors, transducers, and effectors have been proposed to act in higher-order complexes associated with physically distinct areas of the plasma membrane. Adult muscle stem cells (satellite cells) must, upon injury, respond appropriately to a wide range of extracellular stimuli: the role of such signaling scaffolds is therefore a potentially important area of inquiry. To address this question, we first isolated detergent-resistant membrane fractions from primary satellite cells, then analyzed their component proteins using liquid chromatography-tandem mass spectrometry. Transmembrane and juxtamembrane components of adhesion-mediated signaling pathways made up the largest group of identified proteins; in particular, neural cell adhesion molecule (NCAM), a multifunctional cell-surface protein that has previously been associated with muscle regeneration, was significant. Immunohistochemical analysis revealed that not only is NCAM localized to discrete areas of the plasma membrane, it is also a very early marker of commitment to terminal differentiation. Using flow cytometry, we have sorted physically homogeneous myogenic cultures into proliferating and differentiating fractions based solely upon NCAM expression

  5. Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection.

    Science.gov (United States)

    McGrath, Erica L; Rossi, Shannan L; Gao, Junling; Widen, Steven G; Grant, Auston C; Dunn, Tiffany J; Azar, Sasha R; Roundy, Christopher M; Xiong, Ying; Prusak, Deborah J; Loucas, Bradford D; Wood, Thomas G; Yu, Yongjia; Fernández-Salas, Ildefonso; Weaver, Scott C; Vasilakis, Nikos; Wu, Ping

    2017-03-14

    Zika virus (ZIKV) infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7), to infect primary human neural stem cells (hNSCs) originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Neural stem cells was induced to differentiate into cholinergic neurons in vitro

    International Nuclear Information System (INIS)

    Chang Yan; Xu Yilong; Pan Jingkun; Tian Lei; Gao Yuhong; Guo Shuilong

    2004-01-01

    The cholinergic-inducing effect of BMP4 on isolated and cultivated rat's cerebral neural stem cells (NSCs) was examined. NSCs which were isolated from two month's old rat's brain region like hippocampus and striatum were cultivated in a medium containing EGF and bFGF, and were identified with morphological character by microscope and nestin immunocytochemistry test. After 24 hours, half NSCs were cultivated with a BMP4-added medium as a experimental group instead of the primary medium, while the an other half NSCs being cultivated with the primary medium as a control group. After 8 days the expression of choline acetyltransferase (ChAT) of the cultivated cells was observated by indirect immunofluorescence test. Results showed that more positive cells were found in the experimental group, and the fluorescence intensity were stronger; while less positive cells were found in the control group, and the fluorescence intensity was weaker. The differentiational efficiency of the NSCs was examined by FITC-labelled Flow Cytometry. The results showed that about 16% cells of the experimental group appeared ChAT-positive, while that of control group only 7%. So BMP4 may have the function of inducing NSCs to differentiate into neurons with cholinergic characteristic. (authors)

  7. Regionally-specified second trimester fetal neural stem cells reveals differential neurogenic programming.

    Directory of Open Access Journals (Sweden)

    Yiping Fan

    Full Text Available Neural stem/progenitor cells (NSC have the potential for treatment of a wide range of neurological diseases such as Parkinson Disease and multiple sclerosis. Currently, NSC have been isolated only from hippocampus and subventricular zone (SVZ of the adult brain. It is not known whether NSC can be found in all parts of the developing mid-trimester central nervous system (CNS when the brain undergoes massive transformation and growth. Multipotent NSC from the mid-trimester cerebra, thalamus, SVZ, hippocampus, thalamus, cerebellum, brain stem and spinal cord can be derived and propagated as clonal neurospheres with increasing frequencies with increasing gestations. These NSC can undergo multi-lineage differentiation both in vitro and in vivo, and engraft in a developmental murine model. Regionally-derived NSC are phenotypically distinct, with hippocampal NSC having a significantly higher neurogenic potential (53.6% over other sources (range of 0%-27.5%, p<0.004. Whole genome expression analysis showed differential gene expression between these regionally-derived NSC, which involved the Notch, epidermal growth factor as well as interleukin pathways. We have shown the presence of phenotypically-distinct regionally-derived NSC from the mid-trimester CNS, which may reflect the ontological differences occurring within the CNS. Aside from informing on the role of such cells during fetal growth, they may be useful for different cellular therapy applications.

  8. Distinct regulatory functions of calpain 1 and 2 during neural stem cell self-renewal and differentiation.

    Directory of Open Access Journals (Sweden)

    Daniela M Santos

    Full Text Available Calpains are calcium regulated cysteine proteases that have been described in a wide range of cellular processes, including apoptosis, migration and cell cycle regulation. In addition, calpains have been implicated in differentiation, but their impact on neural differentiation requires further investigation. Here, we addressed the role of calpain 1 and calpain 2 in neural stem cell (NSC self-renewal and differentiation. We found that calpain inhibition using either the chemical inhibitor calpeptin or the endogenous calpain inhibitor calpastatin favored differentiation of NSCs. This effect was associated with significant changes in cell cycle-related proteins and may be regulated by calcium. Interestingly, calpain 1 and calpain 2 were found to play distinct roles in NSC fate decision. Calpain 1 expression levels were higher in self-renewing NSC and decreased with differentiation, while calpain 2 increased throughout differentiation. In addition, calpain 1 silencing resulted in increased levels of both neuronal and glial markers, β-III Tubulin and glial fibrillary acidic protein (GFAP. Calpain 2 silencing elicited decreased levels of GFAP. These results support a role for calpain 1 in repressing differentiation, thus maintaining a proliferative NSC pool, and suggest that calpain 2 is involved in glial differentiation.

  9. Reactive Neural Control for Phototaxis and Obstacle Avoidance Behavior of Walking Machines

    DEFF Research Database (Denmark)

    Manoonpong, Poramate; Pasemann, Frank; Wörgötter, Florentin

    2007-01-01

    as a sensory fusion unit. It filters sensory noise and shapes sensory data to drive the corresponding reactive behavior. On the other hand, modular neural control based on a central pattern generator is applied for locomotion of walking machines. It coordinates leg movements and can generate omnidirectional...

  10. Dynamical Behaviors of Stochastic Reaction-Diffusion Cohen-Grossberg Neural Networks with Delays

    Directory of Open Access Journals (Sweden)

    Li Wan

    2012-01-01

    Full Text Available This paper investigates dynamical behaviors of stochastic Cohen-Grossberg neural network with delays and reaction diffusion. By employing Lyapunov method, Poincaré inequality and matrix technique, some sufficient criteria on ultimate boundedness, weak attractor, and asymptotic stability are obtained. Finally, a numerical example is given to illustrate the correctness and effectiveness of our theoretical results.

  11. Artificial Neural Networks: A New Approach for Predicting Application Behavior. AIR 2001 Annual Forum Paper.

    Science.gov (United States)

    Gonzalez, Julie M. Byers; DesJardins, Stephen L.

    This paper examines how predictive modeling can be used to study application behavior. A relatively new technique, artificial neural networks (ANNs), was applied to help predict which students were likely to get into a large Research I university. Data were obtained from a university in Iowa. Two cohorts were used, each containing approximately…

  12. Behavioral and Physiological Neural Network Analyses: A Common Pathway toward Pattern Recognition and Prediction

    Science.gov (United States)

    Ninness, Chris; Lauter, Judy L.; Coffee, Michael; Clary, Logan; Kelly, Elizabeth; Rumph, Marilyn; Rumph, Robin; Kyle, Betty; Ninness, Sharon K.

    2012-01-01

    Using 3 diversified datasets, we explored the pattern-recognition ability of the Self-Organizing Map (SOM) artificial neural network as applied to diversified nonlinear data distributions in the areas of behavioral and physiological research. Experiment 1 employed a dataset obtained from the UCI Machine Learning Repository. Data for this study…

  13. Neural Network modeling of forward and inverse behavior of rotary MR damper

    DEFF Research Database (Denmark)

    Bhowmik, Subrata; Høgsberg, Jan Becker; Weber, Felix

    2010-01-01

    of nonlinear problems. The present paper concerns the nonparametric neural network modeling of the dynamic behavior of a rotary MR damper. A rotary type MR damper consists of a rotating disk which is enclosed in a metallic housing filled with the MR fluid which is operated in shear mode. The dissipative torque...

  14. Behavior and neural basis of near-optimal visual search

    Science.gov (United States)

    Ma, Wei Ji; Navalpakkam, Vidhya; Beck, Jeffrey M; van den Berg, Ronald; Pouget, Alexandre

    2013-01-01

    The ability to search efficiently for a target in a cluttered environment is one of the most remarkable functions of the nervous system. This task is difficult under natural circumstances, as the reliability of sensory information can vary greatly across space and time and is typically a priori unknown to the observer. In contrast, visual-search experiments commonly use stimuli of equal and known reliability. In a target detection task, we randomly assigned high or low reliability to each item on a trial-by-trial basis. An optimal observer would weight the observations by their trial-to-trial reliability and combine them using a specific nonlinear integration rule. We found that humans were near-optimal, regardless of whether distractors were homogeneous or heterogeneous and whether reliability was manipulated through contrast or shape. We present a neural-network implementation of near-optimal visual search based on probabilistic population coding. The network matched human performance. PMID:21552276

  15. Decreased neural precursor cell pool in NADPH oxidase 2-deficiency: From mouse brain to neural differentiation of patient derived iPSC

    Directory of Open Access Journals (Sweden)

    Zeynab Nayernia

    2017-10-01

    Full Text Available There is emerging evidence for the involvement of reactive oxygen species (ROS in the regulation of stem cells and cellular differentiation. Absence of the ROS-generating NADPH oxidase NOX2 in chronic granulomatous disease (CGD patients, predominantly manifests as immune deficiency, but has also been associated with decreased cognition. Here, we investigate the role of NOX enzymes in neuronal homeostasis in adult mouse brain and in neural cells derived from human induced pluripotent stem cells (iPSC. High levels of NOX2 were found in mouse adult neurogenic regions. In NOX2-deficient mice, neurogenic regions showed diminished redox modifications, as well as decrease in neuroprecursor numbers and in expression of genes involved in neural differentiation including NES, BDNF and OTX2. iPSC from healthy subjects and patients with CGD were used to study the role of NOX2 in human in vitro neuronal development. Expression of NOX2 was low in undifferentiated iPSC, upregulated upon neural induction, and disappeared during neuronal differentiation. In human neurospheres, NOX2 protein and ROS generation were polarized within the inner cell layer of rosette structures. NOX2 deficiency in CGD-iPSCs resulted in an abnormal neural induction in vitro, as revealed by a reduced expression of neuroprogenitor markers (NES, BDNF, OTX2, NRSF/REST, and a decreased generation of mature neurons. Vector-mediated NOX2 expression in NOX2-deficient iPSCs rescued neurogenesis. Taken together, our study provides novel evidence for a regulatory role of NOX2 during early stages of neurogenesis in mouse and human.

  16. Histone Methylation and microRNA-dependent Regulation of Epigenetic Activities in Neural Progenitor Self-Renewal and Differentiation.

    Science.gov (United States)

    Cacci, Emanuele; Negri, Rodolfo; Biagioni, Stefano; Lupo, Giuseppe

    2017-01-01

    Neural stem/progenitor cell (NSPC) self-renewal and differentiation in the developing and the adult brain are controlled by extra-cellular signals and by the inherent competence of NSPCs to produce appropriate responses. Stage-dependent responsiveness of NSPCs to extrinsic cues is orchestrated at the epigenetic level. Epigenetic mechanisms such as DNA methylation, histone modifications and non-coding RNA-mediated regulation control crucial aspects of NSPC development and function, and are also implicated in pathological conditions. While their roles in the regulation of stem cell fate have been largely explored in pluripotent stem cell models, the epigenetic signature of NSPCs is also key to determine their multipotency as well as their progressive bias towards specific differentiation outcomes. Here we review recent developments in this field, focusing on the roles of histone methylation marks and the protein complexes controlling their deposition in NSPCs of the developing cerebral cortex and the adult subventricular zone. In this context, we describe how bivalent promoters, carrying antagonistic epigenetic modifications, feature during multiple steps of neural development, from neural lineage specification to neuronal differentiation. Furthermore, we discuss the emerging cross-talk between epigenetic regulators and microRNAs, and how the interplay between these different layers of regulation can finely tune the expression of genes controlling NSPC maintenance and differentiation. In particular, we highlight recent advances in the identification of astrocyte-enriched microRNAs and their function in cell fate choices of NSPCs differentiating towards glial lineages.

  17. What the laboratory rat has taught us about social play behavior: role in behavioral development and neural mechanisms.

    Science.gov (United States)

    Vanderschuren, Louk J M J; Trezza, Viviana

    2014-01-01

    Social play behavior is the most vigorous and characteristic form of social interaction displayed by developing mammals. The laboratory rat is an ideal species to study this behavior, since it shows ample social play that can be easily recognized and quantified. In this chapter, we will first briefly describe the structure of social play behavior in rats. Next, we will discuss studies that used social isolation rearing during the period in life when social play is most abundant to investigate the developmental functions of social play behavior in rats, focusing on the consequences of play deprivation on social, cognitive, emotional, and sensorimotor development. Last, we will discuss the neural substrates of social play behavior in rats, with emphasis on the limbic corticostriatal circuits that underlie emotions and their influence on behavior.

  18. Sex differences in neural and behavioral signatures of cooperation revealed by fNIRS hyperscanning

    Science.gov (United States)

    Baker, Joseph M.; Liu, Ning; Cui, Xu; Vrticka, Pascal; Saggar, Manish; Hosseini, S. M. Hadi; Reiss, Allan L.

    2016-01-01

    Researchers from multiple fields have sought to understand how sex moderates human social behavior. While over 50 years of research has revealed differences in cooperation behavior of males and females, the underlying neural correlates of these sex differences have not been explained. A missing and fundamental element of this puzzle is an understanding of how the sex composition of an interacting dyad influences the brain and behavior during cooperation. Using fNIRS-based hyperscanning in 111 same- and mixed-sex dyads, we identified significant behavioral and neural sex-related differences in association with a computer-based cooperation task. Dyads containing at least one male demonstrated significantly higher behavioral performance than female/female dyads. Individual males and females showed significant activation in the right frontopolar and right inferior prefrontal cortices, although this activation was greater in females compared to males. Female/female dyad’s exhibited significant inter-brain coherence within the right temporal cortex, while significant coherence in male/male dyads occurred in the right inferior prefrontal cortex. Significant coherence was not observed in mixed-sex dyads. Finally, for same-sex dyads only, task-related inter-brain coherence was positively correlated with cooperation task performance. Our results highlight multiple important and previously undetected influences of sex on concurrent neural and behavioral signatures of cooperation. PMID:27270754

  19. Large-scale generation of human iPSC-derived neural stem cells/early neural progenitor cells and their neuronal differentiation.

    Science.gov (United States)

    D'Aiuto, Leonardo; Zhi, Yun; Kumar Das, Dhanjit; Wilcox, Madeleine R; Johnson, Jon W; McClain, Lora; MacDonald, Matthew L; Di Maio, Roberto; Schurdak, Mark E; Piazza, Paolo; Viggiano, Luigi; Sweet, Robert; Kinchington, Paul R; Bhattacharjee, Ayantika G; Yolken, Robert; Nimgaonka, Vishwajit L; Nimgaonkar, Vishwajit L

    2014-01-01

    Induced pluripotent stem cell (iPSC)-based technologies offer an unprecedented opportunity to perform high-throughput screening of novel drugs for neurological and neurodegenerative diseases. Such screenings require a robust and scalable method for generating large numbers of mature, differentiated neuronal cells. Currently available methods based on differentiation of embryoid bodies (EBs) or directed differentiation of adherent culture systems are either expensive or are not scalable. We developed a protocol for large-scale generation of neuronal stem cells (NSCs)/early neural progenitor cells (eNPCs) and their differentiation into neurons. Our scalable protocol allows robust and cost-effective generation of NSCs/eNPCs from iPSCs. Following culture in neurobasal medium supplemented with B27 and BDNF, NSCs/eNPCs differentiate predominantly into vesicular glutamate transporter 1 (VGLUT1) positive neurons. Targeted mass spectrometry analysis demonstrates that iPSC-derived neurons express ligand-gated channels and other synaptic proteins and whole-cell patch-clamp experiments indicate that these channels are functional. The robust and cost-effective differentiation protocol described here for large-scale generation of NSCs/eNPCs and their differentiation into neurons paves the way for automated high-throughput screening of drugs for neurological and neurodegenerative diseases.

  20. Estimating the behavior of RC beams strengthened with NSM system using artificial neural networks

    Directory of Open Access Journals (Sweden)

    Seyed Rohollah Hosseini Vaez

    2017-12-01

    Full Text Available In the last decade, conventional materials such as steel and concrete are being replaced by fiber reinforced polymer (FRP materials for the strengthening of concrete structures. Among the strengthening techniques based on Fiber Reinforced Polymer composites, the use of near-surface mounted (NSM FRP rods is emerging as a promising technology for increasing flexural and shear strength of deficient concrete, masonry and timber members. An artificial neural network is an information processing tool that is inspired by the way biological nervous systems (such as the brain process the information. The key element of this tool is the novel structure of the information processing system. In engineering applications, a neural network can be a vector mapper which maps an input vector to an output one. In the present study, a new approach is developed to predict the behavior of strengthened concrete beam using a large number of experimental data by applying artificial neural networks. Having parameters used as input nodes in ANN modeling such as elastic modulus of the FRP reinforcement, the ratio of the steel longitudinal reinforcement, dimensions of the beam section, the ratio of the NSM-FRP reinforcement and characteristics of concrete, the output node was the flexural strength of beams. The idealized neural network was employed to generate empirical charts and equations to be used in design. The aim of this study is to investigate the behavior of strengthened RC beam using artificial neural networks.

  1. An optimally evolved connective ratio of neural networks that maximizes the occurrence of synchronized bursting behavior

    Science.gov (United States)

    2012-01-01

    Background Synchronized bursting activity (SBA) is a remarkable dynamical behavior in both ex vivo and in vivo neural networks. Investigations of the underlying structural characteristics associated with SBA are crucial to understanding the system-level regulatory mechanism of neural network behaviors. Results In this study, artificial pulsed neural networks were established using spike response models to capture fundamental dynamics of large scale ex vivo cortical networks. Network simulations with synaptic parameter perturbations showed the following two findings. (i) In a network with an excitatory ratio (ER) of 80-90%, its connective ratio (CR) was within a range of 10-30% when the occurrence of SBA reached the highest expectation. This result was consistent with the experimental observation in ex vivo neuronal networks, which were reported to possess a matured inhibitory synaptic ratio of 10-20% and a CR of 10-30%. (ii) No SBA occurred when a network does not contain any all-positive-interaction feedback loop (APFL) motif. In a neural network containing APFLs, the number of APFLs presented an optimal range corresponding to the maximal occurrence of SBA, which was very similar to the optimal CR. Conclusions In a neural network, the evolutionarily selected CR (10-30%) optimizes the occurrence of SBA, and APFL serves a pivotal network motif required to maximize the occurrence of SBA. PMID:22462685

  2. Neural basis of three dimensions of agitated behaviors in patients with Alzheimer disease

    Directory of Open Access Journals (Sweden)

    Banno K

    2014-02-01

    Full Text Available Koichi Banno,1 Shutaro Nakaaki,2 Junko Sato,1 Katsuyoshi Torii,1 Jin Narumoto,3 Jun Miyata,4 Nobutsugu Hirono,5 Toshi A Furukawa,6 Masaru Mimura,2 Tatsuo Akechi1 1Department of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; 2Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; 3Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 4Department of Neuropsychiatry, Graduate School of Medicine, Kyoto University, Kyoto, Japan; 5Department of Psychology, Kobe Gakuin University; Hyogo, Japan; 6Departments of Health Promotion and Human Behavior and of Clinical Epidemiology, Graduate School of Medicine/School of Public Health, Kyoto University, Kyoto, Japan Background: Agitated behaviors are frequently observed in patients with Alzheimer disease (AD. The neural substrate underlying the agitated behaviors in dementia is unclear. We hypothesized that different dimensions of agitated behaviors are mediated by distinct neural systems. Methods: All the patients (n=32 underwent single photon emission computed tomography (SPECT. Using the Agitated Behavior in Dementia scale, we identified the relationships between regional cerebral blood flow (rCBF patterns and the presence of each of three dimensions of agitated behavior (physically agitated behavior, verbally agitated behavior, and psychosis symptoms in AD patients. Statistical parametric mapping (SPM software was used to explore these neural correlations. Results: Physically agitated behavior was significantly correlated with lower rCBF values in the right superior temporal gyrus (Brodmann 22 and the right inferior frontal gyrus (Brodmann 47. Verbally agitated behavior was significantly associated with lower rCBF values in the left inferior frontal gyrus (Brodmann 46, 44 and the left insula (Brodmann 13. The psychosis symptoms were significantly correlated

  3. Synaptic plasticity in a recurrent neural network for versatile and adaptive behaviors of a walking robot.

    Science.gov (United States)

    Grinke, Eduard; Tetzlaff, Christian; Wörgötter, Florentin; Manoonpong, Poramate

    2015-01-01

    Walking animals, like insects, with little neural computing can effectively perform complex behaviors. For example, they can walk around their environment, escape from corners/deadlocks, and avoid or climb over obstacles. While performing all these behaviors, they can also adapt their movements to deal with an unknown situation. As a consequence, they successfully navigate through their complex environment. The versatile and adaptive abilities are the result of an integration of several ingredients embedded in their sensorimotor loop. Biological studies reveal that the ingredients include neural dynamics, plasticity, sensory feedback, and biomechanics. Generating such versatile and adaptive behaviors for a many degrees-of-freedom (DOFs) walking robot is a challenging task. Thus, in this study, we present a bio-inspired approach to solve this task. Specifically, the approach combines neural mechanisms with plasticity, exteroceptive sensory feedback, and biomechanics. The neural mechanisms consist of adaptive neural sensory processing and modular neural locomotion control. The sensory processing is based on a small recurrent neural network consisting of two fully connected neurons. Online correlation-based learning with synaptic scaling is applied to adequately change the connections of the network. By doing so, we can effectively exploit neural dynamics (i.e., hysteresis effects and single attractors) in the network to generate different turning angles with short-term memory for a walking robot. The turning information is transmitted as descending steering signals to the neural locomotion control which translates the signals into motor actions. As a result, the robot can walk around and adapt its turning angle for avoiding obstacles in different situations. The adaptation also enables the robot to effectively escape from sharp corners or deadlocks. Using backbone joint control embedded in the the locomotion control allows the robot to climb over small obstacles

  4. Predicting behavior change from persuasive messages using neural representational similarity and social network analyses.

    Science.gov (United States)

    Pegors, Teresa K; Tompson, Steven; O'Donnell, Matthew Brook; Falk, Emily B

    2017-08-15

    Neural activity in medial prefrontal cortex (MPFC), identified as engaging in self-related processing, predicts later health behavior change. However, it is unknown to what extent individual differences in neural representation of content and lived experience influence this brain-behavior relationship. We examined whether the strength of content-specific representations during persuasive messaging relates to later behavior change, and whether these relationships change as a function of individuals' social network composition. In our study, smokers viewed anti-smoking messages while undergoing fMRI and we measured changes in their smoking behavior one month later. Using representational similarity analyses, we found that the degree to which message content (i.e. health, social, or valence information) was represented in a self-related processing MPFC region was associated with later smoking behavior, with increased representations of negatively valenced (risk) information corresponding to greater message-consistent behavior change. Furthermore, the relationship between representations and behavior change depended on social network composition: smokers who had proportionally fewer smokers in their network showed increases in smoking behavior when social or health content was strongly represented in MPFC, whereas message-consistent behavior (i.e., less smoking) was more likely for those with proportionally more smokers in their social network who represented social or health consequences more strongly. These results highlight the dynamic relationship between representations in MPFC and key outcomes such as health behavior change; a complete understanding of the role of MPFC in motivation and action should take into account individual differences in neural representation of stimulus attributes and social context variables such as social network composition. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. The hippocampus and exploration: dynamically evolving behavior and neural representations

    Directory of Open Access Journals (Sweden)

    Adam eJohnson

    2012-07-01

    Full Text Available We develop a normative statistical approach to exploratory behavior called information foraging. Information foraging highlights the specific processes that contribute to active, rather than passive, exploration and learning. We hypothesize that the hippocampus plays a critical role in active exploration through directed information foraging by supporting a set of processes that allow an individual to determine where to sample. By examining these processes, we show how information directed information foraging provides a formal theoretical explanation for the common hippocampal substrates of constructive memory, vicarious trial and error behavior, schema-based facilitation of memory performance, and memory consolidation.

  6. The hippocampus and exploration: dynamically evolving behavior and neural representations

    Science.gov (United States)

    Johnson, Adam; Varberg, Zachary; Benhardus, James; Maahs, Anthony; Schrater, Paul

    2012-01-01

    We develop a normative statistical approach to exploratory behavior called information foraging. Information foraging highlights the specific processes that contribute to active, rather than passive, exploration and learning. We hypothesize that the hippocampus plays a critical role in active exploration through directed information foraging by supporting a set of processes that allow an individual to determine where to sample. By examining these processes, we show how information directed information foraging provides a formal theoretical explanation for the common hippocampal substrates of constructive memory, vicarious trial and error behavior, schema-based facilitation of memory performance, and memory consolidation. PMID:22848196

  7. Different requirements of functional telomeres in neural stem cells and terminally differentiated neurons.

    Science.gov (United States)

    Lobanova, Anastasia; She, Robert; Pieraut, Simon; Clapp, Charlie; Maximov, Anton; Denchi, Eros Lazzerini

    2017-04-01

    Telomeres have been studied extensively in peripheral tissues, but their relevance in the nervous system remains poorly understood. Here, we examine the roles of telomeres at distinct stages of murine brain development by using lineage-specific genetic ablation of TRF2, an essential component of the shelterin complex that protects chromosome ends from the DNA damage response machinery. We found that functional telomeres are required for embryonic and adult neurogenesis, but their uncapping has surprisingly no detectable consequences on terminally differentiated neurons. Conditional knockout of TRF2 in post-mitotic immature neurons had virtually no detectable effect on circuit assembly, neuronal gene expression, and the behavior of adult animals despite triggering massive end-to-end chromosome fusions across the brain. These results suggest that telomeres are dispensable in terminally differentiated neurons and provide mechanistic insight into cognitive abnormalities associated with aberrant telomere length in humans. © 2017 Lobanova et al.; Published by Cold Spring Harbor Laboratory Press.

  8. Behavior learning in differential games and reorientation maneuvers

    Science.gov (United States)

    Satak, Neha

    method is the Direct Approximation of Value Function (DAVF) method. In this method, unlike the CSR method, the player formulates an objective function for the opponent but does not formulates a strategy directly; rather, indirectly the player assumes that the opponent is playing optimally. Thus, a value function satisfying the HJB equation corresponding to the opponent's cost function exists. The DAVF method finds an approximate solution for the value function based on previous observations of the opponent's control. The approximate solution to the value function is then used to predict the opponent's future behavior. Game examples in which only a single player is learning its opponent's behavior are simulated. Subsequently, examples in which both players in a two-player game are learning each other's behavior are simulated. In the second part of this research, a reorientation control maneuver for a spinning spacecraft will be developed. This will aid the application of behavior learning and differential games concepts to the specific scenario involving multiple spinning spacecraft. An impulsive reorientation maneuver with coasting will be analytically designed to reorient the spin axis of the spacecraft using a single body fixed thruster. Cooperative maneuvers of multiple spacecraft optimizing fuel and relative orientation will be designed. Pareto optimality concepts will be used to arrive at mutually agreeable reorientation maneuvers for the cooperating spinning spacecraft.

  9. Diminished behavioral and neural sensitivity to sound modulation is associated with moderate developmental hearing loss.

    Directory of Open Access Journals (Sweden)

    Merri J Rosen

    Full Text Available The acoustic rearing environment can alter central auditory coding properties, yet altered neural coding is seldom linked with specific deficits to adult perceptual skills. To test whether developmental hearing loss resulted in comparable changes to perception and sensory coding, we examined behavioral and neural detection thresholds for sinusoidally amplitude modulated (sAM stimuli. Behavioral sAM detection thresholds for slow (5 Hz modulations were significantly worse for animals reared with bilateral conductive hearing loss (CHL, as compared to controls. This difference could not be attributed to hearing thresholds, proficiency at the task, or proxies for attention. Detection thresholds across the groups did not differ for fast (100 Hz modulations, a result paralleling that seen in humans. Neural responses to sAM stimuli were recorded in single auditory cortex neurons from separate groups of awake animals. Neurometric analyses indicated equivalent thresholds for the most sensitive neurons, but a significantly poorer detection threshold for slow modulations across the population of CHL neurons as compared to controls. The magnitude of the neural deficit matched that of the behavioral differences, suggesting that a reduction of sensory information can account for limitations to perceptual skills.

  10. Neural correlates of dynamically evolving interpersonal ties predict prosocial behavior

    NARCIS (Netherlands)

    J.J. Fahrenfort (Johannes J.); F.A.A.M. Winden, van (Frans); B. Pelloux (Benjamin); M. Stallen (Mirre); K.R. Ridderinkhof (Richard)

    2012-01-01

    textabstractThere is a growing interest for the determinants of human choice behavior in social settings. Upon initial contact, investment choices in social settings can be inherently risky, as the degree to which the other person will reciprocate is unknown. Nevertheless, people have been shown to

  11. Neural correlates of dynamically evolving interpersonal ties predict prosocial behavior

    NARCIS (Netherlands)

    Fahrenfort, J.J.; van Winden, F.A.A.M.; Pelloux, B.; Stallen, M.; Ridderinkhof, K.R.

    2012-01-01

    There is a growing interest for the determinants of human choice behavior in social settings. Upon initial contact, investment choices in social settings can be inherently risky, as the degree to which the other person will reciprocate is unknown. Nevertheless, people have been shown to exhibit

  12. Addiction: Pulling at the Neural Threads of Social Behaviors

    International Nuclear Information System (INIS)

    Volkow, N.D.; Goldstein, R.; Baler, R.D.; Goldstein, R.Z.

    2011-01-01

    Addiction coopts the brain's neuronal circuits necessary for insight, reward, motivation, and social behaviors. This functional overlap results in addicted individuals making poor choices despite awareness of the negative consequences; it explains why previously rewarding life situations and the threat of judicial punishment cannot stop drug taking and why a medical rather than a criminal approach is more effective in curtailing addiction.

  13. Artificial neural networks in prediction of mechanical behavior of concrete at high temperature

    International Nuclear Information System (INIS)

    Mukherjee, A.; Nag Biswas, S.

    1997-01-01

    The behavior of concrete structures that are exposed to extreme thermo-mechanical loading is an issue of great importance in nuclear engineering. The mechanical behavior of concrete at high temperature is non-linear. The properties that regulate its response are highly temperature dependent and extremely complex. In addition, the constituent materials, e.g. aggregates, influence the response significantly. Attempts have been made to trace the stress-strain curve through mathematical models and rheological models. However, it has been difficult to include all the contributing factors in the mathematical model. This paper examines a new programming paradigm, artificial neural networks, for the problem. Implementing a feedforward network and backpropagation algorithm the stress-strain relationship of the material is captured. The neural networks for the prediction of uniaxial behavior of concrete at high temperature has been presented here. The results of the present investigation are very encouraging. (orig.)

  14. Behavioral and neural concordance in parent-child dyadic sleep patterns.

    Science.gov (United States)

    Lee, Tae-Ho; Miernicki, Michelle E; Telzer, Eva H

    2017-08-01

    Sleep habits developed in adolescence shape long-term trajectories of psychological, educational, and physiological well-being. Adolescents' sleep behaviors are shaped by their parents' sleep at both the behavioral and biological levels. In the current study, we sought to examine how neural concordance in resting-state functional connectivity between parent-child dyads is associated with dyadic concordance in sleep duration and adolescents' sleep quality. To this end, we scanned both parents and their child (N=28 parent-child dyads; parent M age =42.8years; adolescent M age =14.9years; 14.3% father; 46.4% female adolescent) as they each underwent a resting-state scan. Using daily diaries, we also assessed dyadic concordance in sleep duration across two weeks. Our results show that greater daily concordance in sleep behavior is associated with greater neural concordance in default-mode network connectivity between parents and children. Moreover, greater neural and behavioral concordances in sleep is associated with more optimal sleep quality in adolescents. The current findings expand our understanding of dyadic concordance by providing a neurobiological mechanism by which parents and children share daily sleep behaviors. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Neural substrates of sexual desire in individuals with problematic hypersexual behavior

    Directory of Open Access Journals (Sweden)

    Ji-Woo eSeok

    2015-11-01

    Full Text Available Studies on the characteristics of individuals with hypersexual disorder have been accumulating due to increasing concerns about problematic hypersexual behavior (PHB. Currently, relatively little is known about the underlying behavioral and neural mechanisms of sexual desire. Our study aimed to investigate the neural correlates of sexual desire with event-related functional magnetic resonance imaging (fMRI. Twenty-three individuals with PHB and 22 age-matched healthy controls were scanned while they passively viewed sexual and nonsexual stimuli. The subjects’ levels of sexual desire were assessed in response to each sexual stimulus. Relative to controls, individuals with PHB experienced more frequent and enhanced sexual desire during exposure to sexual stimuli. Greater activation was observed in the caudate nucleus, inferior parietal lobe, dorsal anterior cingulate gyrus, thalamus, and dorsolateral prefrontal cortex in the PHB group than in the control group. In addition, the hemodynamic patterns in the activated areas differed between the groups. Consistent with the findings of brain imaging studies of substance and behavior addiction, individuals with the behavioral characteristics of PHB and enhanced desire exhibited altered activation in the prefrontal cortex and subcortical regions. In conclusion, our results will help to characterize the behaviors and associated neural mechanisms of individuals with PHB.

  16. Effects of light emitting diode irradiation on neural differentiation of human umbilical cord-derived mesenchymal cells.

    Science.gov (United States)

    Dehghani-Soltani, Samereh; Shojaee, Mohammad; Jalalkamali, Mahshid; Babaee, Abdolreza; Nematollahi-Mahani, Seyed Noureddin

    2017-08-30

    Recently, light emitting diodes (LEDs) have been introduced as a potential physical factor for proliferation and differentiation of various stem cells. Among the mesenchymal stem cells human umbilical cord matrix-derived mesenchymal (hUCM) cells are easily propagated in the laboratory and their low immunogenicity make them more appropriate for regenerative medicine procedures. We aimed at this study to evaluate the effect of red and green light emitted from LED on the neural lineage differentiation of hUCM cells in the presence or absence of retinoic acid (RA). Harvested hUCM cells exhibited mesenchymal and stemness properties. Irradiation of these cells by green and red LED with or without RA pre-treatment successfully differentiated them into neural lineage when the morphology of the induced cells, gene expression pattern (nestin, β-tubulin III and Olig2) and protein synthesis (anti-nestin, anti-β-tubulin III, anti-GFAP and anti-O4 antibodies) was evaluated. These data point for the first time to the fact that LED irradiation and optogenetic technology may be applied for neural differentiation and neuronal repair in regenerative medicine.

  17. Deciphering the Role of Sulfonated Unit in Heparin-Mimicking Polymer to Promote Neural Differentiation of Embryonic Stem Cells.

    Science.gov (United States)

    Lei, Jiehua; Yuan, Yuqi; Lyu, Zhonglin; Wang, Mengmeng; Liu, Qi; Wang, Hongwei; Yuan, Lin; Chen, Hong

    2017-08-30

    Glycosaminoglycans (GAGs), especially heparin and heparan sulfate (HS), hold great potential for inducing the neural differentiation of embryonic stem cells (ESCs) and have brought new hope for the treatment of neurological diseases. However, the disadvantages of natural heparin/HS, such as difficulty in isolating them with a sufficient amount, highly heterogeneous structure, and the risk of immune responses, have limited their further therapeutic applications. Thus, there is a great demand for stable, controllable, and well-defined synthetic alternatives of heparin/HS with more effective biological functions. In this study, based upon a previously proposed unit-recombination strategy, several heparin-mimicking polymers were synthesized by integrating glucosamine-like 2-methacrylamido glucopyranose monomers (MAG) with three sulfonated units in different structural forms, and their effects on cell proliferation, the pluripotency, and the differentiation of ESCs were carefully studied. The results showed that all the copolymers had good cytocompatibility and displayed much better bioactivity in promoting the neural differentiation of ESCs as compared to natural heparin; copolymers with different sulfonated units exhibited different levels of promoting ability; among them, copolymer with 3-sulfopropyl acrylate (SPA) as a sulfonated unit was the most potent in promoting the neural differentiation of ESCs; the promoting effect is dependent on the molecular weight and concentration of P(MAG-co-SPA), with the highest levels occurring at the intermediate molecular weight and concentration. These results clearly demonstrated that the sulfonated unit in the copolymers played an important role in determining the promoting effect on ESCs' neural differentiation; SPA was identified as the most potent sulfonated unit for copolymer with the strongest promoting ability. The possible reason for sulfonated unit structure as a vital factor influencing the ability of the copolymers

  18. Sex differences in the neural and behavioral response to intranasal oxytocin and vasopressin during human social interaction.

    Science.gov (United States)

    Rilling, James K; Demarco, Ashley C; Hackett, Patrick D; Chen, Xu; Gautam, Pritam; Stair, Sabrina; Haroon, Ebrahim; Thompson, Richmond; Ditzen, Beate; Patel, Rajan; Pagnoni, Giuseppe

    2014-01-01

    Both oxytocin (OT) and vasopressin (AVP) are known to modulate social behavior, and dysfunction in both systems has been postulated as a potential cause of certain psychiatric disorders that involve social behavioral deficits. In particular, there is growing interest in intranasal OT as a potential treatment for certain psychiatric disorders, and preliminary pre-clinical and clinical studies suggest efficacy in alleviating some of the associated symptoms. However, the vast majority of research participants in these studies have been male, and there is evidence for sexually differentiated effects of nonapeptides in both humans and non-human animals. To date, no study has investigated the effect of intranasal OT on brain function in human males and females within the same paradigm. Previously, in a randomized, placebo-controlled, double-blind fMRI study, we reported effects of intranasal OT and AVP on behavior and brain activity of human males as they played an interactive social game known as the Prisoner's Dilemma Game. Here, we present findings from an identical study in human females, and compare these with our findings from males. Overall, we find that both behavioral and neural responses to intranasal OT and AVP are highly sexually differentiated. In women, AVP increased conciliatory behavior, and both OT and AVP caused women to treat computer partners more like humans. In men, AVP increased reciprocation of cooperation from both human and computer partners. However, no specific drug effects on behavior were shared between men and women. During cooperative interactions, both OT and AVP increased brain activity in men within areas rich in OT and AVP receptors and in areas playing a key role in reward, social bonding, arousal and memory (e.g., the striatum, basal forebrain, insula, amygdala and hippocampus), whereas OT and AVP either had no effect or in some cases actually decreased brain activity in these regions in women. OT treatment rendered neural responses

  19. Addiction: Pulling at the Neural Threads of Social Behaviors

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Goldstein, R.; Volkow, N.D.; Baler, R.D.; Goldstein, R.Z.

    2011-01-27

    Addiction coopts the brain's neuronal circuits necessary for insight, reward, motivation, and social behaviors. This functional overlap results in addicted individuals making poor choices despite awareness of the negative consequences; it explains why previously rewarding life situations and the threat of judicial punishment cannot stop drug taking and why a medical rather than a criminal approach is more effective in curtailing addiction.

  20. NEURAL NETWORK INTERACTIONS AND INGESTIVE BEHAVIOR CONTROL DURING ANOREXIA

    Science.gov (United States)

    Watts, Alan G.; Salter, Dawna S.; Neuner, Christina M.

    2007-01-01

    Many models have been proposed over the years to explain how motivated feeding behavior is controlled. One of the most compelling is based on the original concepts of Eliot Stellar whereby sets of interosensory and exterosensory inputs converge on a hypothalamic control network that can either stimulate or inhibit feeding. These inputs arise from information originating in the blood, the viscera, and the telencephalon. In this manner the relative strengths of the hypothalamic stimulatory and inhibitory networks at a particular time dictates how an animal feeds. Anorexia occurs when the balance within the networks consistently favors the restraint of feeding. This article discusses experimental evidence supporting a model whereby the increases in plasma osmolality that result from drinking hypertonic saline activate pathways projecting to neurons in the paraventricular nucleus of the hypothalamus (PVH) and lateral hypothalamic area (LHA). These neurons constitute the hypothalamic controller for ingestive behavior, and receive a set of afferent inputs from regions of the brain that process sensory information that is critical for different aspects of feeding. Important sets of inputs arise in the arcuate nucleus, the hindbrain, and in the telencephalon. Anorexia is generated in dehydrated animals by way of osmosensitive projections to the behavior control neurons in the PVH and LHA, rather than by actions on their afferent inputs. PMID:17531275

  1. Workplace injuries, safety climate and behaviors: application of an artificial neural network.

    Science.gov (United States)

    Abubakar, A Mohammed; Karadal, Himmet; Bayighomog, Steven W; Merdan, Ethem

    2018-05-09

    This article proposes and tests a model for the interaction effect of the organizational safety climate and behaviors on workplace injuries. Using artificial neural network and survey data from 306 metal casting industry employees in central Anatolia, we found that an organizational safety climate mitigates workplace injuries, and safety behaviors enforce the strength of the negative impact of the safety climate on workplace injuries. The results suggest a complex relationship between the organizational safety climate, safety behavior and workplace injuries. Theoretical and practical implications are discussed in light of decreasing workplace injuries in the Anatolian metal casting industry.

  2. A comparative transcriptomic analysis of astrocytes differentiation from human neural progenitor cells.

    Science.gov (United States)

    Magistri, Marco; Khoury, Nathalie; Mazza, Emilia Maria Cristina; Velmeshev, Dmitry; Lee, Jae K; Bicciato, Silvio; Tsoulfas, Pantelis; Faghihi, Mohammad Ali

    2016-11-01

    Astrocytes are a morphologically and functionally heterogeneous population of cells that play critical roles in neurodevelopment and in the regulation of central nervous system homeostasis. Studies of human astrocytes have been hampered by the lack of specific molecular markers and by the difficulties associated with purifying and culturing astrocytes from adult human brains. Human neural progenitor cells (NPCs) with self-renewal and multipotent properties represent an appealing model system to gain insight into the developmental genetics and function of human astrocytes, but a comprehensive molecular characterization that confirms the validity of this cellular system is still missing. Here we used an unbiased transcriptomic analysis to characterize in vitro culture of human NPCs and to define the gene expression programs activated during the differentiation of these cells into astrocytes using FBS or the combination of CNTF and BMP4. Our results demonstrate that in vitro cultures of human NPCs isolated during the gliogenic phase of neurodevelopment mainly consist of radial glial cells (RGCs) and glia-restricted progenitor cells. In these cells the combination of CNTF and BMP4 activates the JAK/STAT and SMAD signaling cascades, leading to the inhibition of oligodendrocytes lineage commitment and activation of astrocytes differentiation. On the other hand, FBS-derived astrocytes have properties of reactive astrocytes. Our work suggests that in vitro culture of human NPCs represents a valuable cellular system to study human disorders characterized by impairment of astrocytes development and function. Our datasets represent an important resource for researchers studying human astrocytes development and might set the basis for the discovery of novel human-specific astrocyte markers. © 2016 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  3. GDNF/GFRα1 Complex Abrogates Self-Renewing Activity of Cortical Neural Precursors Inducing Their Differentiation

    Directory of Open Access Journals (Sweden)

    Antonela Bonafina

    2018-03-01

    Full Text Available Summary: The balance between factors leading to proliferation and differentiation of cortical neural precursors (CNPs determines the correct cortical development. In this work, we show that GDNF and its receptor GFRα1 are expressed in the neocortex during the period of cortical neurogenesis. We show that the GDNF/GFRα1 complex inhibits the self-renewal capacity of mouse CNP cells induced by fibroblast growth factor 2 (FGF2, promoting neuronal differentiation. While GDNF leads to decreased proliferation of cultured cortical precursor cells, ablation of GFRα1 in glutamatergic cortical precursors enhances its proliferation. We show that GDNF treatment of CNPs promoted morphological differentiation even in the presence of the self-renewal-promoting factor, FGF2. Analysis of GFRα1-deficient mice shows an increase in the number of cycling cells during cortical development and a reduction in dendrite development of cortical GFRα1-expressing neurons. Together, these results indicate that GDNF/GFRα1 signaling plays an essential role in regulating the proliferative condition and the differentiation of cortical progenitors. : In this article, Ledda and colleagues show that GDNF acting through its receptor GFRα1 plays a critical role in the maturation of cortical progenitors by counteracting FGF2 self-renewal activity on neural stem cells and promoting neuronal differentiation. Keywords: GDNF, GFRα1, cortical precursors, proliferation, postmitotic neurons, neuronal differentiation

  4. The changing brain--insights into the mechanisms of neural and behavioral adaptation to the environment

    DEFF Research Database (Denmark)

    Bergersen, L H; Bramham, C R; Hugdahl, K

    2013-01-01

    level and behavior. Thus a single amino acid change in a transcriptional repressor can disrupt gene regulation through neural activity (Greenberg). Deep sequencing analysis of the neuropil transcriptome indicates that a large fraction of the synaptic proteome is synthesized in situ in axons...... and dendrites, permitting local regulation (Schuman). The nature of the 'reset' function that makes animals dependent of sleep is being revealed (Cirelli). Maternal behavior can cause changes in gene expression that stably modify behavior in the offspring (Meaney). Removal of a single sensory channel protein...... in the vomero-nasal organ can switch off male-specific and switch on female-specific innate behavior of mice in response to environmental stimulation (Dulac). Innate behaviors can be stably transmitted from parent to offspring through generations even when those behaviors cannot be expressed, as illustrated...

  5. When problem size matters: differential effects of brain stimulation on arithmetic problem solving and neural oscillations.

    Directory of Open Access Journals (Sweden)

    Bruno Rütsche

    Full Text Available The problem size effect is a well-established finding in arithmetic problem solving and is characterized by worse performance in problems with larger compared to smaller operand size. Solving small and large arithmetic problems has also been shown to involve different cognitive processes and distinct electroencephalography (EEG oscillations over the left posterior parietal cortex (LPPC. In this study, we aimed to provide further evidence for these dissociations by using transcranial direct current stimulation (tDCS. Participants underwent anodal (30min, 1.5 mA, LPPC and sham tDCS. After the stimulation, we recorded their neural activity using EEG while the participants solved small and large arithmetic problems. We found that the tDCS effects on performance and oscillatory activity critically depended on the problem size. While anodal tDCS improved response latencies in large arithmetic problems, it decreased solution rates in small arithmetic problems. Likewise, the lower-alpha desynchronization in large problems increased, whereas the theta synchronization in small problems decreased. These findings reveal that the LPPC is differentially involved in solving small and large arithmetic problems and demonstrate that the effects of brain stimulation strikingly differ depending on the involved neuro-cognitive processes.

  6. Neural differentiation of choroid plexus epithelial cells: role of human traumatic cerebrospinal fluid

    Directory of Open Access Journals (Sweden)

    Elham Hashemi

    2017-01-01

    Full Text Available As the key producer of cerebrospinal fluid (CSF, the choroid plexus (CP provides a unique protective system in the central nervous system. CSF components are not invariable and they can change based on the pathological conditions of the central nervous system. The purpose of the present study was to assess the effects of non-traumatic and traumatic CSF on the differentiation of multipotent stem-like cells of CP into the neural and/or glial cells. CP epithelial cells were isolated from adult male rats and treated with human non-traumatic and traumatic CSF. Alterations in mRNA expression of Nestin and microtubule-associated protein (MAP2, as the specific markers of neurogenesis, and astrocyte marker glial fibrillary acidic protein (GFAP in cultured CP epithelial cells were evaluated using quantitative real-time PCR. The data revealed that treatment with CSF (non-traumatic and traumatic led to increase in mRNA expression levels of MAP2 and GFAP. Moreover, the expression of Nestin decreased in CP epithelial cells treated with non-traumatic CSF, while treatment with traumatic CSF significantly increased its mRNA level compared to the cells cultured only in DMEM/F12 as control. It seems that CP epithelial cells contain multipotent stem-like cells which are inducible under pathological conditions including exposure to traumatic CSF because of its compositions.

  7. A universal concept based on cellular neural networks for ultrafast and flexible solving of differential equations.

    Science.gov (United States)

    Chedjou, Jean Chamberlain; Kyamakya, Kyandoghere

    2015-04-01

    This paper develops and validates a comprehensive and universally applicable computational concept for solving nonlinear differential equations (NDEs) through a neurocomputing concept based on cellular neural networks (CNNs). High-precision, stability, convergence, and lowest-possible memory requirements are ensured by the CNN processor architecture. A significant challenge solved in this paper is that all these cited computing features are ensured in all system-states (regular or chaotic ones) and in all bifurcation conditions that may be experienced by NDEs.One particular quintessence of this paper is to develop and demonstrate a solver concept that shows and ensures that CNN processors (realized either in hardware or in software) are universal solvers of NDE models. The solving logic or algorithm of given NDEs (possible examples are: Duffing, Mathieu, Van der Pol, Jerk, Chua, Rössler, Lorenz, Burgers, and the transport equations) through a CNN processor system is provided by a set of templates that are computed by our comprehensive templates calculation technique that we call nonlinear adaptive optimization. This paper is therefore a significant contribution and represents a cutting-edge real-time computational engineering approach, especially while considering the various scientific and engineering applications of this ultrafast, energy-and-memory-efficient, and high-precise NDE solver concept. For illustration purposes, three NDE models are demonstratively solved, and related CNN templates are derived and used: the periodically excited Duffing equation, the Mathieu equation, and the transport equation.

  8. Quantitative differentiation of multiple virus in blood using nanoporous silicon oxide immunosensor and artificial neural network.

    Science.gov (United States)

    Chakraborty, W; Ray, R; Samanta, N; RoyChaudhuri, C

    2017-12-15

    In spite of the rapid developments in various nanosensor technologies, it still remains challenging to realize a reliable ultrasensitive electrical biosensing platform which will be able to detect multiple viruses in blood simultaneously with a fairly high reproducibility without using secondary labels. In this paper, we have reported quantitative differentiation of Hep-B and Hep-C viruses in blood using nanoporous silicon oxide immunosensor array and artificial neural network (ANN). The peak frequency output (f p ) from the steady state sensitivity characteristics and the first cut off frequency (f c ) from the transient characteristics have been considered as inputs to the multilayer ANN. Implementation of several classifier blocks in the ANN architecture and coupling them with both the sensor chips, functionalized with Hep-B and Hep-C antibodies have enabled the quantification of the viruses with an accuracy of around 95% in the range of 0.04fM-1pM and with an accuracy of around 90% beyond 1pM and within 25nM in blood serum. This is the most sensitive report on multiple virus quantification using label free method. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. A method for medulloblastoma tumor differentiation based on convolutional neural networks and transfer learning

    Science.gov (United States)

    Cruz-Roa, Angel; Arévalo, John; Judkins, Alexander; Madabhushi, Anant; González, Fabio

    2015-12-01

    Convolutional neural networks (CNN) have been very successful at addressing different computer vision tasks thanks to their ability to learn image representations directly from large amounts of labeled data. Features learned from a dataset can be used to represent images from a different dataset via an approach called transfer learning. In this paper we apply transfer learning to the challenging task of medulloblastoma tumor differentiation. We compare two different CNN models which were previously trained in two different domains (natural and histopathology images). The first CNN is a state-of-the-art approach in computer vision, a large and deep CNN with 16-layers, Visual Geometry Group (VGG) CNN. The second (IBCa-CNN) is a 2-layer CNN trained for invasive breast cancer tumor classification. Both CNNs are used as visual feature extractors of histopathology image regions of anaplastic and non-anaplastic medulloblastoma tumor from digitized whole-slide images. The features from the two models are used, separately, to train a softmax classifier to discriminate between anaplastic and non-anaplastic medulloblastoma image regions. Experimental results show that the transfer learning approach produce competitive results in comparison with the state of the art approaches for IBCa detection. Results also show that features extracted from the IBCa-CNN have better performance in comparison with features extracted from the VGG-CNN. The former obtains 89.8% while the latter obtains 76.6% in terms of average accuracy.

  10. Differential receptive field organizations give rise to nearly identical neural correlations across three parallel sensory maps in weakly electric fish.

    Science.gov (United States)

    Hofmann, Volker; Chacron, Maurice J

    2017-09-01

    Understanding how neural populations encode sensory information thereby leading to perception and behavior (i.e., the neural code) remains an important problem in neuroscience. When investigating the neural code, one must take into account the fact that neural activities are not independent but are actually correlated with one another. Such correlations are seen ubiquitously and have a strong impact on neural coding. Here we investigated how differences in the antagonistic center-surround receptive field (RF) organization across three parallel sensory maps influence correlations between the activities of electrosensory pyramidal neurons. Using a model based on known anatomical differences in receptive field center size and overlap, we initially predicted large differences in correlated activity across the maps. However, in vivo electrophysiological recordings showed that, contrary to modeling predictions, electrosensory pyramidal neurons across all three segments displayed nearly identical correlations. To explain this surprising result, we incorporated the effects of RF surround in our model. By systematically varying both the RF surround gain and size relative to that of the RF center, we found that multiple RF structures gave rise to similar levels of correlation. In particular, incorporating known physiological differences in RF structure between the three maps in our model gave rise to similar levels of correlation. Our results show that RF center overlap alone does not determine correlations which has important implications for understanding how RF structure influences correlated neural activity.

  11. Functional cross-talk between the cellular prion protein and the neural cell adhesion molecule is critical for neuronal differentiation of neural stem/precursor cells.

    Science.gov (United States)

    Prodromidou, Kanella; Papastefanaki, Florentia; Sklaviadis, Theodoros; Matsas, Rebecca

    2014-06-01

    Cellular prion protein (PrP) is prominently expressed in brain, in differentiated neurons but also in neural stem/precursor cells (NPCs). The misfolding of PrP is a central event in prion diseases, yet the physiological function of PrP is insufficiently understood. Although PrP has been reported to associate with the neural cell adhesion molecule (NCAM), the consequences of concerted PrP-NCAM action in NPC physiology are unknown. Here, we generated NPCs from the subventricular zone (SVZ) of postnatal day 5 wild-type and PrP null (-/-) mice and observed that PrP is essential for proper NPC proliferation and neuronal differentiation. Moreover, we found that PrP is required for the NPC response to NCAM-induced neuronal differentiation. In the absence of PrP, NCAM not only fails to promote neuronal differentiation but also induces an accumulation of doublecortin-positive neuronal progenitors at the proliferation stage. In agreement, we noted an increase in cycling neuronal progenitors in the SVZ of PrP-/- mice compared with PrP+/+ mice, as evidenced by double labeling for the proliferation marker Ki67 and doublecortin as well as by 5-bromo-2'-deoxyuridine incorporation experiments. Additionally, fewer newly born neurons were detected in the rostral migratory stream of PrP-/- mice. Analysis of the migration of SVZ cells in microexplant cultures from wild-type and PrP-/- mice revealed no differences between genotypes or a role for NCAM in this process. Our data demonstrate that PrP plays a critical role in neuronal differentiation of NPCs and suggest that this function is, at least in part, NCAM-dependent. © 2014 AlphaMed Press.

  12. Olfactory LOVER: Behavioral and neural correlates of autobiographical odor memory

    Directory of Open Access Journals (Sweden)

    Maria eLarsson

    2014-04-01

    Full Text Available Autobiographical memories (AMs are personally experienced events that may be localized in time and space. In the present work we present an overview targeting memories evoked by the sense of smell. Overall, research indicates that autobiographical odor memory is different than memories evoked by our primary sensory systems; sight and hearing. Here, observed differences from a behavioral and neuroanatomical perspective are presented. The key features of an olfactory evoked AM may be referred to the LOVER acronym - Limbic, Old, Vivid, Emotional, and Rare.

  13. MicroRNA-378 regulates neural stem cell proliferation and differentiation in vitro by modulating Tailless expression

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Yanxia [Department of Psychology and Psychiatry, The Second Affiliated Hospital of Xi' an Jiaotong University, Xi' an 710004 (China); Department of Rehabilitation, Xi' an Children' s Hospital, Xi' an 710003 (China); Liu, Xiaoguai [The 3rd Department of Infectious Diseases, Xi' an Children' s Hospital, Xi' an 710003 (China); Wang, Yaping, E-mail: yapwangyy@163.com [Department of Psychology and Psychiatry, The Second Affiliated Hospital of Xi' an Jiaotong University, Xi' an 710004 (China)

    2015-10-16

    Previous studies have suggested that microRNAs (miRNAs) play an important role in regulating neural stem cell (NSC) proliferation and differentiation. However, the precise role of miRNAs in NSC remains largely unexplored. In this study, we showed that miR-378 can target Tailless (TLX), a critical regulator of NSC, to regulate NSC proliferation and differentiation. By bioinformatic algorithms, miR-378 was found to have a predicted target site in the 3′-untranslated region of TLX, which was verified by a dual-luciferase reporter assay. The expression of miR-378 was increased during NSC differentiation and inversely correlated with TLX expression. qPCR and Western blot analysis also showed that miR-378 negatively regulated TLX mRNA and protein expression in neural stem cells (NSCs). Intriguingly, overexpression of miR-378 increased NSC differentiation and reduced NSC proliferation, whereas suppression of miR-378 led to decreased NSC differentiation and increased NSC proliferation. Moreover, the downstream targets of TLX, including p21, PTEN and Wnt/β-catenin were also found to be regulated by miR-378. Additionally, overexpression of TLX rescued the NSC proliferation deficiency induced by miR-378 overexpression and abolished miR-378-promoted NSC differentiation. Taken together, our data suggest that miR-378 is a novel miRNA that regulates NSC proliferation and differentiation via targeting TLX. Therefore, manipulating miR-378 in NSCs could be a novel strategy to develop novel interventions for the treatment of relevant neurological disorders. - Highlights: • miR-378 targeted and regulated TLX. • miR-378 was increased during NSC differentiation. • miR-378 regulated NSC proliferation and differentiation. • miR-378 regulated NSC self-renew through TLX.

  14. MicroRNA-378 regulates neural stem cell proliferation and differentiation in vitro by modulating Tailless expression

    International Nuclear Information System (INIS)

    Huang, Yanxia; Liu, Xiaoguai; Wang, Yaping

    2015-01-01

    Previous studies have suggested that microRNAs (miRNAs) play an important role in regulating neural stem cell (NSC) proliferation and differentiation. However, the precise role of miRNAs in NSC remains largely unexplored. In this study, we showed that miR-378 can target Tailless (TLX), a critical regulator of NSC, to regulate NSC proliferation and differentiation. By bioinformatic algorithms, miR-378 was found to have a predicted target site in the 3′-untranslated region of TLX, which was verified by a dual-luciferase reporter assay. The expression of miR-378 was increased during NSC differentiation and inversely correlated with TLX expression. qPCR and Western blot analysis also showed that miR-378 negatively regulated TLX mRNA and protein expression in neural stem cells (NSCs). Intriguingly, overexpression of miR-378 increased NSC differentiation and reduced NSC proliferation, whereas suppression of miR-378 led to decreased NSC differentiation and increased NSC proliferation. Moreover, the downstream targets of TLX, including p21, PTEN and Wnt/β-catenin were also found to be regulated by miR-378. Additionally, overexpression of TLX rescued the NSC proliferation deficiency induced by miR-378 overexpression and abolished miR-378-promoted NSC differentiation. Taken together, our data suggest that miR-378 is a novel miRNA that regulates NSC proliferation and differentiation via targeting TLX. Therefore, manipulating miR-378 in NSCs could be a novel strategy to develop novel interventions for the treatment of relevant neurological disorders. - Highlights: • miR-378 targeted and regulated TLX. • miR-378 was increased during NSC differentiation. • miR-378 regulated NSC proliferation and differentiation. • miR-378 regulated NSC self-renew through TLX.

  15. Anesthesia, brain changes, and behavior: Insights from neural systems biology.

    Science.gov (United States)

    Colon, Elisabeth; Bittner, Edward A; Kussman, Barry; McCann, Mary Ellen; Soriano, Sulpicio; Borsook, David

    2017-06-01

    Long-term consequences of anesthetic exposure in humans are not well understood. It is possible that alterations in brain function occur beyond the initial anesthetic administration. Research in children and adults has reported cognitive and/or behavioral changes after surgery and general anesthesia that may be short lived in some patients, while in others, such changes may persist. The changes observed in humans are corroborated by a large body of evidence from animal studies that support a role for alterations in neuronal survival (neuroapoptosis) or structure (altered dendritic and glial morphology) and later behavioral deficits at older age after exposure to various anesthetic agents during fetal or early life. The potential of anesthetics to induce long-term alterations in brain function, particularly in vulnerable populations, warrants investigation. In this review, we critically evaluate the available preclinical and clinical data on the developing and aging brain, and in known vulnerable populations to provide insights into potential changes that may affect the general population of patients in a more, subtle manner. In addition this review summarizes underlying processes of how general anesthetics produce changes in the brain at the cellular and systems level and the current understanding underlying mechanisms of anesthetics agents on brain systems. Finally, we present how neuroimaging techniques currently emerge as promising approaches to evaluate and define changes in brain function resulting from anesthesia, both in the short and the long-term. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. A model for integrating elementary neural functions into delayed-response behavior.

    Directory of Open Access Journals (Sweden)

    Thomas Gisiger

    2006-04-01

    Full Text Available It is well established that various cortical regions can implement a wide array of neural processes, yet the mechanisms which integrate these processes into behavior-producing, brain-scale activity remain elusive. We propose that an important role in this respect might be played by executive structures controlling the traffic of information between the cortical regions involved. To illustrate this hypothesis, we present a neural network model comprising a set of interconnected structures harboring stimulus-related activity (visual representation, working memory, and planning, and a group of executive units with task-related activity patterns that manage the information flowing between them. The resulting dynamics allows the network to perform the dual task of either retaining an image during a delay (delayed-matching to sample task, or recalling from this image another one that has been associated with it during training (delayed-pair association task. The model reproduces behavioral and electrophysiological data gathered on the inferior temporal and prefrontal cortices of primates performing these same tasks. It also makes predictions on how neural activity coding for the recall of the image associated with the sample emerges and becomes prospective during the training phase. The network dynamics proves to be very stable against perturbations, and it exhibits signs of scale-invariant organization and cooperativity. The present network represents a possible neural implementation for active, top-down, prospective memory retrieval in primates. The model suggests that brain activity leading to performance of cognitive tasks might be organized in modular fashion, simple neural functions becoming integrated into more complex behavior by executive structures harbored in prefrontal cortex and/or basal ganglia.

  17. A model for integrating elementary neural functions into delayed-response behavior.

    Science.gov (United States)

    Gisiger, Thomas; Kerszberg, Michel

    2006-04-01

    It is well established that various cortical regions can implement a wide array of neural processes, yet the mechanisms which integrate these processes into behavior-producing, brain-scale activity remain elusive. We propose that an important role in this respect might be played by executive structures controlling the traffic of information between the cortical regions involved. To illustrate this hypothesis, we present a neural network model comprising a set of interconnected structures harboring stimulus-related activity (visual representation, working memory, and planning), and a group of executive units with task-related activity patterns that manage the information flowing between them. The resulting dynamics allows the network to perform the dual task of either retaining an image during a delay (delayed-matching to sample task), or recalling from this image another one that has been associated with it during training (delayed-pair association task). The model reproduces behavioral and electrophysiological data gathered on the inferior temporal and prefrontal cortices of primates performing these same tasks. It also makes predictions on how neural activity coding for the recall of the image associated with the sample emerges and becomes prospective during the training phase. The network dynamics proves to be very stable against perturbations, and it exhibits signs of scale-invariant organization and cooperativity. The present network represents a possible neural implementation for active, top-down, prospective memory retrieval in primates. The model suggests that brain activity leading to performance of cognitive tasks might be organized in modular fashion, simple neural functions becoming integrated into more complex behavior by executive structures harbored in prefrontal cortex and/or basal ganglia.

  18. Musicians' Enhanced Neural Differentiation of Speech Sounds Arises Early in Life: Developmental Evidence from Ages 3 to 30

    Science.gov (United States)

    Strait, Dana L.; O'Connell, Samantha; Parbery-Clark, Alexandra; Kraus, Nina

    2014-01-01

    The perception and neural representation of acoustically similar speech sounds underlie language development. Music training hones the perception of minute acoustic differences that distinguish sounds; this training may generalize to speech processing given that adult musicians have enhanced neural differentiation of similar speech syllables compared with nonmusicians. Here, we asked whether this neural advantage in musicians is present early in life by assessing musically trained and untrained children as young as age 3. We assessed auditory brainstem responses to the speech syllables /ba/ and /ga/ as well as auditory and visual cognitive abilities in musicians and nonmusicians across 3 developmental time-points: preschoolers, school-aged children, and adults. Cross-phase analyses objectively measured the degree to which subcortical responses differed to these speech syllables in musicians and nonmusicians for each age group. Results reveal that musicians exhibit enhanced neural differentiation of stop consonants early in life and with as little as a few years of training. Furthermore, the extent of subcortical stop consonant distinction correlates with auditory-specific cognitive abilities (i.e., auditory working memory and attention). Results are interpreted according to a corticofugal framework for auditory learning in which subcortical processing enhancements are engendered by strengthened cognitive control over auditory function in musicians. PMID:23599166

  19. Neurogenesis and Increase in Differentiated Neural Cell Survival via Phosphorylation of Akt1 after Fluoxetine Treatment of Stem Cells

    Directory of Open Access Journals (Sweden)

    Anahita Rahmani

    2013-01-01

    Full Text Available Fluoxetine (FLX is a selective serotonin reuptake inhibitor (SSRI. Its action is possibly through an increase in neural cell survival. The mechanism of improved survival rate of neurons by FLX may relate to the overexpression of some kinases such as Akt protein. Akt1 (a serine/threonine kinase plays a key role in the modulation of cell proliferation and survival. Our study evaluated the effects of FLX on mesenchymal stem cell (MSC fate and Akt1 phosphorylation levels in MSCs. Evaluation tests included reverse transcriptase polymerase chain reaction, western blot, and immunocytochemistry assays. Nestin, MAP-2, and β-tubulin were detected after neurogenesis as neural markers. Ten μM of FLX upregulated phosphorylation of Akt1 protein in induced hEnSC significantly. Also FLX did increase viability of these MSCs. Continuous FLX treatment after neurogenesis elevated the survival rate of differentiated neural cells probably by enhanced induction of Akt1 phosphorylation. This study addresses a novel role of FLX in neurogenesis and differentiated neural cell survival that may contribute to explaining the therapeutic action of fluoxetine in regenerative pharmacology.

  20. White matter hyperintensity and stroke lesion segmentation and differentiation using convolutional neural networks

    Directory of Open Access Journals (Sweden)

    R. Guerrero

    2018-01-01

    Full Text Available White matter hyperintensities (WMH are a feature of sporadic small vessel disease also frequently observed in magnetic resonance images (MRI of healthy elderly subjects. The accurate assessment of WMH burden is of crucial importance for epidemiological studies to determine association between WMHs, cognitive and clinical data; their causes, and the effects of new treatments in randomized trials. The manual delineation of WMHs is a very tedious, costly and time consuming process, that needs to be carried out by an expert annotator (e.g. a trained image analyst or radiologist. The problem of WMH delineation is further complicated by the fact that other pathological features (i.e. stroke lesions often also appear as hyperintense regions. Recently, several automated methods aiming to tackle the challenges of WMH segmentation have been proposed. Most of these methods have been specifically developed to segment WMH in MRI but cannot differentiate between WMHs and strokes. Other methods, capable of distinguishing between different pathologies in brain MRI, are not designed with simultaneous WMH and stroke segmentation in mind. Therefore, a task specific, reliable, fully automated method that can segment and differentiate between these two pathological manifestations on MRI has not yet been fully identified. In this work we propose to use a convolutional neural network (CNN that is able to segment hyperintensities and differentiate between WMHs and stroke lesions. Specifically, we aim to distinguish between WMH pathologies from those caused by stroke lesions due to either cortical, large or small subcortical infarcts. The proposed fully convolutional CNN architecture, called uResNet, that comprised an analysis path, that gradually learns low and high level features, followed by a synthesis path, that gradually combines and up-samples the low and high level features into a class likelihood semantic segmentation. Quantitatively, the proposed CNN

  1. Enhanced dopaminergic differentiation of human neural stem cells by synergistic effect of Bcl-xL and reduced oxygen tension

    DEFF Research Database (Denmark)

    Krabbe, Christina; Courtois, Elise; Jensen, Pia

    2009-01-01

    Neural stem cells constitute a promising source of cells for transplantation in Parkinson's disease, but a protocol for controlled dopaminergic differentiation is not yet available. Here we investigated the effect of the anti-apoptotic protein Bcl-x(L) and oxygen tension on dopaminergic different......Neural stem cells constitute a promising source of cells for transplantation in Parkinson's disease, but a protocol for controlled dopaminergic differentiation is not yet available. Here we investigated the effect of the anti-apoptotic protein Bcl-x(L) and oxygen tension on dopaminergic...... days at 20% oxygen, hVMbcl-x(L) cultures contained proportionally more tyrosine hydroxylase(TH)-positive cells than hVM1 control cultures. This difference was significantly potentiated from 11 +/- 0.8% to 17.2 +/- 0.2% of total cells when the oxygen tension was lowered to 3%. Immunocytochemistry and Q...

  2. OSCILLATION BEHAVIOR OF SOLUTIONS FOR EVEN ORDER NEUTRAL FUNCTIONAL DIFFERENTIAL EQUATIONS

    Institute of Scientific and Technical Information of China (English)

    T.Candan

    2006-01-01

    Even order neutral functional differential equations are considered. Sufficient conditions for the oscillation behavior of solutions for this differential equation are presented. The new results are presented and some examples are also given.

  3. Identification of Noncanonical Wnt Receptors Required for Wnt-3a-Induced Early Differentiation of Human Neural Stem Cells.

    Science.gov (United States)

    Bengoa-Vergniory, Nora; Gorroño-Etxebarria, Irantzu; López-Sánchez, Inmaculada; Marra, Michele; Di Chiaro, Pierluigi; Kypta, Robert

    2017-10-01

    Wnt proteins preferentially activate either β-catenin-dependent or β-catenin-independent signals, but the activity of a particular Wnt also depends on cellular context and receptor availability. We previously reported that Wnt-3a induces neural differentiation of human embryonic stem cell-derived neural stem cells (NSCs) in a β-catenin-independent manner by activating a signal involving JNK and the AP-1 family member ATF-2. Here, we report the results of a gene silencing approach to identify the Wnt receptors that mediate this response to Wnt-3a. Silencing of ROR2 increased neuronal differentiation, as measured by expression of the genes DCX, NEUROD1, and NGN1, suggesting ROR2 signals normally prevent differentiation. Silencing of the other Wnt receptors singly did not affect Wnt-3a-induced neuronal differentiation. However, pairwise silencing of ROR1 and FZD4 or FZD5 and of LRP6 and FZD4 or FZD5 inhibited neuronal differentiation, as detected by reductions in the expression of neuronal genes and immunocytochemical detection of DCX, NEUROD1 and DCX. Ectopic expression of these receptors in HEK 293 cells increased ATF2-dependent transcription. In addition, ROR1 coimmunoprecipitated with FZD4 and LRP6 in transfected HEK 293 cells and colocalized with FZD4 and with LRP6 at the cell surface of transfected L cells. Wnt-3a did not appear to affect these interactions but did alter the interactions between LRP6 and FZD4/5. Together, these observations highlight roles for ROR1, LRP6, FZD4, and FZD5 in neural stem cell differentiation and provide support for a model in which dynamic interactions among these receptors mediate Wnt-3a activation of ATF2 signaling.

  4. Resting-state functional magnetic resonance imaging investigation of the neural correlates of cognitive-behavioral therapy for externalizing behavior problems in adolescent bullies.

    Science.gov (United States)

    Kim, Johanna Inhyang; Kang, Yun-Hyong; Lee, Jong-Min; Cha, Jungho; Park, Yeong-Hun; Kweon, Kuk-Ju; Kim, Bung-Nyun

    2018-06-06

    The purpose of this study was to investigate the neural correlates of cognitive-behavioral therapy (CBT) for externalizing behavior problems in perpetrators of school bullying using assessments of brain activity and behavior. Twenty-five adolescent bullies participated in an 8-session intervention. Prior to and after participation, 24 adolescents were evaluated using the Child Behavior Checklist (CBCL) and 23 completed resting-state functional magnetic resonance imaging. Changes in the fractional amplitude of low-frequency fluctuations (fALFF) and scores on the CBCL were analyzed. We also compared the identified changes into 2 groups (low and high delinquency) differentiated by a cutoff of 65 points on the delinquency subscale of the CBCL. Following the intervention, participants exhibited improvement in the subscores of the CBCL and decreases in the fALFF of the inferior parietal lobule, lingual, interior frontal and middle occipital gyrus. A positive correlation was observed between changes in the CBCL externalizing behavior scores and fALFF of the inferior frontal gyrus. The high delinquency group showed a greater decrease in delinquency and externalizing CBCL subscores across time than did the low delinquency group. The high delinquency group had more areas that showed change in fALFF post-intervention than did the low delinquency group. A positive correlation was observed between changes in the CBCL delinquency scores and fALFF of the precentral gyrus in the high delinquency group. The results indicate that this CBT for externalizing behavior problems in bullies had more positive effects on delinquent behavior in adolescents with high levels of delinquency, and these changes were associated with functional changes in brain activity. ClinicalTrials.gov identifier: NCT02670876. Copyright © 2018. Published by Elsevier Inc.

  5. Neural and behavioral associations of manipulated determination facial expressions.

    Science.gov (United States)

    Price, Tom F; Hortensius, Ruud; Harmon-Jones, Eddie

    2013-09-01

    Past research associated relative left frontal cortical activity with positive affect and approach motivation, or the urge to move toward a stimulus. Less work has examined relative left frontal activity and positive emotions ranging from low to high approach motivation, to test whether positive affects that differ in approach motivational intensity influence relative left frontal cortical activity. Participants in the present experiment adopted determination (high approach positive), satisfaction (low approach positive), or neutral facial expressions while electroencephalographic (EEG) activity was recorded. Next, participants completed a task measuring motivational persistence behavior and then they completed self-report emotion questionnaires. Determination compared to satisfaction and neutral facial expressions caused greater relative left frontal activity relative to baseline EEG recordings. Facial expressions did not directly influence task persistence. However, relative left frontal activity correlated positively with persistence on insolvable tasks in the determination condition. These results extend embodiment theories and motivational interpretations of relative left frontal activity. Published by Elsevier B.V.

  6. Effects of prenatal ionizing irradiation on neural function and behavior

    International Nuclear Information System (INIS)

    Brizzee, K.R.; Ordy, J.M.; Pennwalt Corp., Rochester, NY

    1986-01-01

    Behavioral studies in the past decade on postnatal effects of prenatal ionizing irradiation (125-R) revealed alterations in circadian locomotor activity and modifications of duration, frequency and sequences of certain behavioral acts in irradiated rats. Other studies have shown that the effect of irradiation (150-R) and enriched environment were both significant in initial, repetitive and total error scores while at 200-R enrichment was less effective. Rats irradiated on the 13th, 14th and 15th day of gestation were born with a hopping gait, paired hind and forelimbs moving in unison. Thoracic cord section led to crossed extention hind-limb reflexes in control rats and simultaneus withdrawal of hind limbs in hopping rats, in response to pinprick. In 90 day old squirrel monkeys the percent of correct response in visual orientation, discrimination and reversal learning in 50- and 100-R offspring (Co 60 irradiation at 89-90 days gestation) were significantly lower than those of controls, and differences in reversal learning persisted undiminished at 2 years of age. Time required for body righting, head-up orientation and climbing at 45 0 incline was significantly greater in irradiated (mainly 100-R) than control animals at from 2 to 28 days of age. Visual acuity levels of 50- and 100-R 30 day old infants were significantly lower than in control infants. Stabilimeter activity in the dark was significantly higher in 50- and 100-R 30 day old infants than in controls. In the squirrel monkey studies effects of Co 60 irradiation (100-R) on postnatal development of the brain and behaviour can be identified at statistically significant levels of confidence independent of offspring nursery rearing effects. (orig.)

  7. New bioactive motifs and their use in functionalized self-assembling peptides for NSC differentiation and neural tissue engineering

    Science.gov (United States)

    Gelain, F.; Cigognini, D.; Caprini, A.; Silva, D.; Colleoni, B.; Donegá, M.; Antonini, S.; Cohen, B. E.; Vescovi, A.

    2012-04-01

    Developing functionalized biomaterials for enhancing transplanted cell engraftment in vivo and stimulating the regeneration of injured tissues requires a multi-disciplinary approach customized for the tissue to be regenerated. In particular, nervous tissue engineering may take a great advantage from the discovery of novel functional motifs fostering transplanted stem cell engraftment and nervous fiber regeneration. Using phage display technology we have discovered new peptide sequences that bind to murine neural stem cell (NSC)-derived neural precursor cells (NPCs), and promote their viability and differentiation in vitro when linked to LDLK12 self-assembling peptide (SAPeptide). We characterized the newly functionalized LDLK12 SAPeptides via atomic force microscopy, circular dichroism and rheology, obtaining nanostructured hydrogels that support human and murine NSC proliferation and differentiation in vitro. One functionalized SAPeptide (Ac-FAQ), showing the highest stem cell viability and neural differentiation in vitro, was finally tested in acute contusive spinal cord injury in rats, where it fostered nervous tissue regrowth and improved locomotor recovery. Interestingly, animals treated with the non-functionalized LDLK12 had an axon sprouting/regeneration intermediate between Ac-FAQ-treated animals and controls. These results suggest that hydrogels functionalized with phage-derived peptides may constitute promising biomimetic scaffolds for in vitro NSC differentiation, as well as regenerative therapy of the injured nervous system. Moreover, this multi-disciplinary approach can be used to customize SAPeptides for other specific tissue engineering applications.Developing functionalized biomaterials for enhancing transplanted cell engraftment in vivo and stimulating the regeneration of injured tissues requires a multi-disciplinary approach customized for the tissue to be regenerated. In particular, nervous tissue engineering may take a great advantage from the

  8. Differentiation defect in neural crest-derived smooth muscle cells in patients with aortopathy associated with bicuspid aortic valves

    Directory of Open Access Journals (Sweden)

    Jiao Jiao

    2016-08-01

    Full Text Available Individuals with bicuspid aortic valves (BAV are at a higher risk of developing thoracic aortic aneurysms (TAA than patients with trileaflet aortic valves (TAV. The aneurysms associated with BAV most commonly involve the ascending aorta and spare the descending aorta. Smooth muscle cells (SMCs in the ascending and descending aorta arise from neural crest (NC and paraxial mesoderm (PM, respectively. We hypothesized defective differentiation of the neural crest stem cells (NCSCs-derived SMCs but not paraxial mesoderm cells (PMCs-derived SMCs contributes to the aortopathy associated with BAV. When induced pluripotent stem cells (iPSCs from BAV/TAA patients were differentiated into NCSC-derived SMCs, these cells demonstrated significantly decreased expression of marker of SMC differentiation (MYH11 and impaired contraction compared to normal control. In contrast, the PMC-derived SMCs were similar to control cells in these aspects. The NCSC-SMCs from the BAV/TAA also showed decreased TGF-β signaling based on phosphorylation of SMAD2, and increased mTOR signaling. Inhibition of mTOR pathway using rapamycin rescued the aberrant differentiation. Our data demonstrates that decreased differentiation and contraction of patient's NCSC-derived SMCs may contribute to that aortopathy associated with BAV.

  9. Vitamin E isomer δ-tocopherol enhances the efficiency of neural stem cell differentiation via L-type calcium channel.

    Science.gov (United States)

    Deng, Sihao; Hou, Guoqiang; Xue, Zhiqin; Zhang, Longmei; Zhou, Yuye; Liu, Chao; Liu, Yanqing; Li, Zhiyuan

    2015-01-12

    The effects of the vitamin E isomer δ-tocopherol on neural stem cell (NSC) differentiation have not been investigated until now. Here we investigated the effects of δ-tocopherol on NSC neural differentiation, maturation and its possible mechanisms. Neonatal rat NSCs were grown in suspended neurosphere cultures, and were identified by their expression of nestin protein and their capacity for self-renewal. Treatment with a low concentration of δ-tocopherol induced a significant increase in the percentage of β-III-tubulin-positive cells. δ-Tocopherol also stimulated morphological maturation of neurons in culture. We further observed that δ-tocopherol stimulation increased the expression of voltage-dependent Ca(2+) channels. Moreover, a L-type specific Ca(2+) channel blocker verapamil reduced the percentage of differentiated neurons after δ-tocopherol treatment, and blocked the effects of δ-tocopherol on NSC differentiation into neurons. Together, our study demonstrates that δ-tocopherol may act through elevation of L-type calcium channel activity to increase neuronal differentiation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Musical aptitude and second language pronunciation skills in school-aged children: neural and behavioral evidence.

    Science.gov (United States)

    Milovanov, Riia; Huotilainen, Minna; Välimäki, Vesa; Esquef, Paulo A A; Tervaniemi, Mari

    2008-02-15

    The main focus of this study was to examine the relationship between musical aptitude and second language pronunciation skills. We investigated whether children with superior performance in foreign language production represent musical sound features more readily in the preattentive level of neural processing compared with children with less-advanced production skills. Sound processing accuracy was examined in elementary school children by means of event-related potential (ERP) recordings and behavioral measures. Children with good linguistic skills had better musical skills as measured by the Seashore musicality test than children with less accurate linguistic skills. The ERP data accompany the results of the behavioral tests: children with good linguistic skills showed more pronounced sound-change evoked activation with the music stimuli than children with less accurate linguistic skills. Taken together, the results imply that musical and linguistic skills could partly be based on shared neural mechanisms.

  11. Arm injury produces long-term behavioral and neural hypersensitivity in octopus.

    Science.gov (United States)

    Alupay, Jean S; Hadjisolomou, Stavros P; Crook, Robyn J

    2014-01-13

    Cephalopod molluscs are the most neurally and behaviorally complex invertebrates, with brains rivaling those of some vertebrates in size and complexity. This has fostered the opinion that cephalopods, particularly octopuses, may experience vertebrate-like pain when injured. However, it is not known whether octopuses possess nociceptors or if their somatic sensory neurons exhibit sensitization after injury. Here we show that the octopus Abdopus aculeatus expresses nocifensive behaviors including arm autotomy, and displays marked neural hyperexcitability both in injured and uninjured arms for at least 24h after injury. These findings do not demonstrate that octopuses experience pain-like states; instead they add to the minimal existing literature on how cephalopods receive, process, and integrate noxious sensory information, potentially informing and refining regulations governing use of cephalopods in scientific research. Published by Elsevier Ireland Ltd.

  12. The neural basis of sex differences in sexual behavior: A quantitative meta-analysis

    Science.gov (United States)

    Poeppl, Timm B.; Langguth, Berthold; Rupprecht, Rainer; Safron, Adam; Bzdok, Danilo; Laird, Angela R.; Eickhoff, Simon B.

    2016-01-01

    Sexuality as to its etymology presupposes the duality of sexes. Using quantitative neuroimaging meta-analyses, we demonstrate robust sex differences in the neural processing of sexual stimuli in thalamus, hypothalamus, and basal ganglia. In a narrative review, we show how these relate to the well-established sex differences on the behavioral level. More specifically, we describe the neural bases of known poor agreement between self-reported and genital measures of female sexual arousal, of previously proposed male proneness to affective sexual conditioning, as well as hints of unconscious activation of bonding mechanisms during sexual stimulation in women. In summary, our meta-analytic review demonstrates that neurofunctional sex differences during sexual stimulation can account for well-established sex differences in sexual behavior. PMID:27742561

  13. Efficient and Fast Differentiation of Human Neural Stem Cells from Human Embryonic Stem Cells for Cell Therapy

    Directory of Open Access Journals (Sweden)

    Xinxin Han

    2017-01-01

    Full Text Available Stem cell-based therapies have been used for repairing damaged brain tissue and helping functional recovery after brain injury. Aberrance neurogenesis is related with brain injury, and multipotential neural stem cells from human embryonic stem (hES cells provide a great promise for cell replacement therapies. Optimized protocols for neural differentiation are necessary to produce functional human neural stem cells (hNSCs for cell therapy. However, the qualified procedure is scarce and detailed features of hNSCs originated from hES cells are still unclear. In this study, we developed a method to obtain hNSCs from hES cells, by which we could harvest abundant hNSCs in a relatively short time. Then, we examined the expression of pluripotent and multipotent marker genes through immunostaining and confirmed differentiation potential of the differentiated hNSCs. Furthermore, we analyzed the mitotic activity of these hNSCs. In this report, we provided comprehensive features of hNSCs and delivered the knowledge about how to obtain more high-quality hNSCs from hES cells which may help to accelerate the NSC-based therapies in brain injury treatment.

  14. Neural Based Orthogonal Data Fitting The EXIN Neural Networks

    CERN Document Server

    Cirrincione, Giansalvo

    2008-01-01

    Written by three leaders in the field of neural based algorithms, Neural Based Orthogonal Data Fitting proposes several neural networks, all endowed with a complete theory which not only explains their behavior, but also compares them with the existing neural and traditional algorithms. The algorithms are studied from different points of view, including: as a differential geometry problem, as a dynamic problem, as a stochastic problem, and as a numerical problem. All algorithms have also been analyzed on real time problems (large dimensional data matrices) and have shown accurate solutions. Wh

  15. A Neural Network Classifier Model for Forecasting Safety Behavior at Workplaces

    Directory of Open Access Journals (Sweden)

    Fakhradin Ghasemi

    2017-07-01

    Full Text Available The construction industry is notorious for having an unacceptable rate of fatal accidents. Unsafe behavior has been recognized as the main cause of most accidents occurring at workplaces, particularly construction sites. Having a predictive model of safety behavior can be helpful in preventing construction accidents. The aim of the present study was to build a predictive model of unsafe behavior using the Artificial Neural Network approach. A brief literature review was conducted on factors affecting safe behavior at workplaces and nine factors were selected to be included in the study. Data were gathered using a validated questionnaire from several construction sites. Multilayer perceptron approach was utilized for constructing the desired neural network. Several models with various architectures were tested to find the best one. Sensitivity analysis was conducted to find the most influential factors. The model with one hidden layer containing fourteen hidden neurons demonstrated the best performance (Sum of Squared Errors=6.73. The error rate of the model was approximately 21 percent. The results of sensitivity analysis showed that safety attitude, safety knowledge, supportive environment, and management commitment had the highest effects on safety behavior, while the effects from resource allocation and perceived work pressure were identified to be lower than those of others. The complex nature of human behavior at workplaces and the presence of many influential factors make it difficult to achieve a model with perfect performance.

  16. Ageing differentially affects neural processing of different conflict types – an fMRI study

    Directory of Open Access Journals (Sweden)

    Margarethe eKorsch

    2014-04-01

    Full Text Available Interference control and conflict resolution is affected by ageing. There is increasing evidence that ageing does not compromise interference control in general but rather shows distinctive effects on different components of interference control. Different conflict types, (e.g. stimulus-stimulus (S-S or stimulus-response (S-R conflicts trigger different cognitive processes and thus activate different neural networks. In the present functional magnetic resonance imaging (fMRI study, we used a combined Flanker and Stimulus Response Conflict (SRC task to investigate the effect of ageing on S-S and S-R conflicts. Behavioral data analysis revealed larger SRC effects in elderly. fMRI Results show that both age groups recruited similar regions (caudate nucleus, cingulate gyrus and middle occipital gyrus during Flanker conflict processing. Furthermore, elderly show an additional activation pattern in parietal and frontal areas. In contrast, no common activation of both age groups was found in response to the SRC. These data suggest that ageing has distinctive effects on S-S and S-R conflicts.

  17. Ageing differentially affects neural processing of different conflict types-an fMRI study.

    Science.gov (United States)

    Korsch, Margarethe; Frühholz, Sascha; Herrmann, Manfred

    2014-01-01

    Interference control and conflict resolution is affected by ageing. There is increasing evidence that ageing does not compromise interference control in general but rather shows distinctive effects on different components of interference control. Different conflict types, [e.g., stimulus-stimulus (S-S) or stimulus-response (S-R) conflicts] trigger different cognitive processes and thus activate different neural networks. In the present functional magnetic resonance imaging (fMRI) study, we used a combined Flanker and Stimulus Response Conflict (SRC) task to investigate the effect of ageing on S-S and S-R conflicts. Behavioral data analysis revealed larger SRC effects in elderly. fMRI Results show that both age groups recruited similar regions [caudate nucleus, cingulate gyrus and middle occipital gyrus (MOG)] during Flanker conflict processing. Furthermore, elderly show an additional activation pattern in parietal and frontal areas. In contrast, no common activation of both age groups was found in response to the SRC. These data suggest that ageing has distinctive effects on S-S and S-R conflicts.

  18. A neural network to predict reactor core behaviors

    International Nuclear Information System (INIS)

    Juan Jose Ortiz-Servin; Jose Alejandro Castillo; Pelta, David A.

    2014-01-01

    The global fuel management problem in BWRs (Boiling Water Reactors) can be understood as a very complex optimization problem, where the variables represent design decisions and the quality assessment of each solution is done through a complex and computational expensive simulation. This last aspect is the major impediment to perform an extensive exploration of the design space, mainly due to the time lost evaluating non promising solutions. In this work, we show how we can train a Multi-Layer Perceptron (MLP) to predict the reactor behavior for a given configuration. The trained MLP is able to evaluate the configurations immediately, thus allowing performing an exhaustive evaluation of the possible configurations derived from a stock of fuel lattices, fuel reload patterns and control rods patterns. For our particular problem, the number of configurations is approximately 7.7 x 10 10 ; the evaluation with the core simulator would need above 200 years, while only 100 hours were required with our approach to discern between bad and good configurations. The later were then evaluated by the simulator and we confirm the MLP usefulness. The good core configurations reached the energy requirements, satisfied the safety parameter constrains and they could reduce uranium enrichment costs. (authors)

  19. Differential gene expression associated with honey bee grooming behavior in response to varroa mites

    Science.gov (United States)

    Honey bee (Apis mellifera) grooming behavior is an important mechanism of resistance against the parasitic mite Varroa destructor. This research was conducted to study associations between grooming behavior and the expression of selected immune, neural, detoxification, developmental and health-relat...

  20. Adolescence and Reward: Making Sense of Neural and Behavioral Changes Amid the Chaos.

    Science.gov (United States)

    Walker, Deena M; Bell, Margaret R; Flores, Cecilia; Gulley, Joshua M; Willing, Jari; Paul, Matthew J

    2017-11-08

    Adolescence is a time of significant neural and behavioral change with remarkable development in social, emotional, and cognitive skills. It is also a time of increased exploration and risk-taking (e.g., drug use). Many of these changes are thought to be the result of increased reward-value coupled with an underdeveloped inhibitory control, and thus a hypersensitivity to reward. Perturbations during adolescence can alter the developmental trajectory of the brain, resulting in long-term alterations in reward-associated behaviors. This review highlights recent developments in our understanding of how neural circuits, pubertal hormones, and environmental factors contribute to adolescent-typical reward-associated behaviors with a particular focus on sex differences, the medial prefrontal cortex, social reward, social isolation, and drug use. We then introduce a new approach that makes use of natural adaptations of seasonally breeding species to investigate the role of pubertal hormones in adolescent development. This research has only begun to parse out contributions of the many neural, endocrine, and environmental changes to the heightened reward sensitivity and increased vulnerability to mental health disorders that characterize this life stage. Copyright © 2017 the authors 0270-6474/17/3710855-12$15.00/0.

  1. The Elementary Nature of Purposive Behavior: Evolving Minimal Neural Structures that Display Intrinsic Intentionality

    Directory of Open Access Journals (Sweden)

    John S. Watson

    2005-01-01

    Full Text Available A study of the evolution of agency in artificial life was designed to access the potential emergence of purposiveness and intentionality as these attributes of behavior have been defined in psychology and philosophy. The study involved Darwinian evolution of mobile neural nets (autonomous agents in terms of their adaptive weight patterning and structure (number of sensory, hidden, and memory units that controlled movement. An agent was embedded in a 10 × 10 toroidal matrix along with “containers” that held benefit or harm if entered. Sensory exposure to content of a container was only briefly available at a distance so that adaptive response to a nearby container required use of relevant memory. The best 20% of each generation of agents, based on net benefit consumed during limited lifetime, were selected to parent the following generation. Purposiveness emerged for all selected agents by 300 generations. By 4000 generations, 90% passed a test of purposive intentionality based on Piaget's criteria for Stage IV object permanence in human infants. An additional test of these agents confirmed that the behavior of 67% of them was consistent with the philosophical criterion of intention being “about” the container's contents. Given that the evolved neural structure of more than half of the successful agents had only 1 hidden and 1 memory node, it is argued that, contrary to common assumption, purposive and intentional aspects of adaptive behavior require an evolution of minimal complexity of supportive neural structure.

  2. Suppression of anomalous synchronization and nonstationary behavior of neural network under small-world topology

    Science.gov (United States)

    Boaretto, B. R. R.; Budzinski, R. C.; Prado, T. L.; Kurths, J.; Lopes, S. R.

    2018-05-01

    It is known that neural networks under small-world topology can present anomalous synchronization and nonstationary behavior for weak coupling regimes. Here, we propose methods to suppress the anomalous synchronization and also to diminish the nonstationary behavior occurring in weakly coupled neural network under small-world topology. We consider a network of 2000 thermally sensitive identical neurons, based on the model of Hodgkin-Huxley in a small-world topology, with the probability of adding non local connection equal to p = 0 . 001. Based on experimental protocols to suppress anomalous synchronization, as well as nonstationary behavior of the neural network dynamics, we make use of (i) external stimulus (pulsed current); (ii) biologic parameters changing (neuron membrane conductance changes); and (iii) body temperature changes. Quantification analysis to evaluate phase synchronization makes use of the Kuramoto's order parameter, while recurrence quantification analysis, particularly the determinism, computed over the easily accessible mean field of network, the local field potential (LFP), is used to evaluate nonstationary states. We show that the methods proposed can control the anomalous synchronization and nonstationarity occurring for weak coupling parameter without any effect on the individual neuron dynamics, neither in the expected asymptotic synchronized states occurring for large values of the coupling parameter.

  3. Using Neural Data to Test A Theory of Investor Behavior: An Application to Realization Utility.

    Science.gov (United States)

    Frydman, Cary; Barberis, Nicholas; Camerer, Colin; Bossaerts, Peter; Rangel, Antonio

    2014-04-01

    We use measures of neural activity provided by functional magnetic resonance imaging (fMRI) to test the "realization utility" theory of investor behavior, which posits that people derive utility directly from the act of realizing gains and losses. Subjects traded stocks in an experimental market while we measured their brain activity. We find that all subjects exhibit a strong disposition effect in their trading, even though it is suboptimal. Consistent with the realization utility explanation for this behavior, we find that activity in the ventromedial prefrontal cortex, an area known to encode the value of options during choices, correlates with the capital gains of potential trades; that the neural measures of realization utility correlate across subjects with their individual tendency to exhibit a disposition effect; and that activity in the ventral striatum, an area known to encode information about changes in the present value of experienced utility, exhibits a positive response when subjects realize capital gains. These results provide support for the realization utility model and, more generally, demonstrate how neural data can be helpful in testing models of investor behavior.

  4. Age differences in behavioral and neural correlates of proactive interference: Disentangling the role of overall working memory performance.

    Science.gov (United States)

    Loosli, Sandra V; Rahm, Benjamin; Unterrainer, Josef M; Mader, Irina; Weiller, Cornelius; Kaller, Christoph P

    2016-02-15

    Reliable performance in working memory (WM) critically depends on the ability to resist proactive interference (PI) from previously relevant WM contents. Both WM performance and PI susceptibility are subject to cognitive decline at older adult age. However, the behavioral and neural processes underlying these co-evolving developmental changes and their potential interdependencies are not yet understood. Here, we investigated PI using a recent-probes WM paradigm and functional MRI in a cross-sectional sample of younger (n=18, 10 female, 23.4 ± 2.7 years) and older adults (n=18, 10 female, 70.2 ± 2.7 years). As expected, older adults showed lower WM performance and higher PI susceptibility than younger adults. Resolution of PI activated a mainly bilateral frontal network across all participants. Significant interactions with age indicated reduced neural activation in older adults for PI resolution. A second analysis in a selection of younger and older adults (n=12 each) with matched WM performance also revealed significant differences in PI between both age groups and - on a descriptive level - again a hypo-activation of the older adults' PI network. But the differential effect of age on the neural PI effects did not reach significance in this smaller sample most likely to the reduced statistical power. However, given the highly similar patterns in both the overall and the WM-matched samples, we propose that the hypo-activation of the PI network in the older adults may not be attributable to age-related differences in overall WM performance, hence suggesting that higher PI susceptibility in older adult age does not directly depend on their lower WM performance. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. A neural population model incorporating dopaminergic neurotransmission during complex voluntary behaviors.

    Directory of Open Access Journals (Sweden)

    Stefan Fürtinger

    2014-11-01

    Full Text Available Assessing brain activity during complex voluntary motor behaviors that require the recruitment of multiple neural sites is a field of active research. Our current knowledge is primarily based on human brain imaging studies that have clear limitations in terms of temporal and spatial resolution. We developed a physiologically informed non-linear multi-compartment stochastic neural model to simulate functional brain activity coupled with neurotransmitter release during complex voluntary behavior, such as speech production. Due to its state-dependent modulation of neural firing, dopaminergic neurotransmission plays a key role in the organization of functional brain circuits controlling speech and language and thus has been incorporated in our neural population model. A rigorous mathematical proof establishing existence and uniqueness of solutions to the proposed model as well as a computationally efficient strategy to numerically approximate these solutions are presented. Simulated brain activity during the resting state and sentence production was analyzed using functional network connectivity, and graph theoretical techniques were employed to highlight differences between the two conditions. We demonstrate that our model successfully reproduces characteristic changes seen in empirical data between the resting state and speech production, and dopaminergic neurotransmission evokes pronounced changes in modeled functional connectivity by acting on the underlying biological stochastic neural model. Specifically, model and data networks in both speech and rest conditions share task-specific network features: both the simulated and empirical functional connectivity networks show an increase in nodal influence and segregation in speech over the resting state. These commonalities confirm that dopamine is a key neuromodulator of the functional connectome of speech control. Based on reproducible characteristic aspects of empirical data, we suggest a number

  6. Supervised learning methods for pathological arterial pulse wave differentiation: A SVM and neural networks approach.

    Science.gov (United States)

    Paiva, Joana S; Cardoso, João; Pereira, Tânia

    2018-01-01

    The main goal of this study was to develop an automatic method based on supervised learning methods, able to distinguish healthy from pathologic arterial pulse wave (APW), and those two from noisy waveforms (non-relevant segments of the signal), from the data acquired during a clinical examination with a novel optical system. The APW dataset analysed was composed by signals acquired in a clinical environment from a total of 213 subjects, including healthy volunteers and non-healthy patients. The signals were parameterised by means of 39pulse features: morphologic, time domain statistics, cross-correlation features, wavelet features. Multiclass Support Vector Machine Recursive Feature Elimination (SVM RFE) method was used to select the most relevant features. A comparative study was performed in order to evaluate the performance of the two classifiers: Support Vector Machine (SVM) and Artificial Neural Network (ANN). SVM achieved a statistically significant better performance for this problem with an average accuracy of 0.9917±0.0024 and a F-Measure of 0.9925±0.0019, in comparison with ANN, which reached the values of 0.9847±0.0032 and 0.9852±0.0031 for Accuracy and F-Measure, respectively. A significant difference was observed between the performances obtained with SVM classifier using a different number of features from the original set available. The comparison between SVM and NN allowed reassert the higher performance of SVM. The results obtained in this study showed the potential of the proposed method to differentiate those three important signal outcomes (healthy, pathologic and noise) and to reduce bias associated with clinical diagnosis of cardiovascular disease using APW. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Differential Response of Neural Cells to Trauma-Induced Swelling In Vitro.

    Science.gov (United States)

    Jayakumar, A R; Taherian, M; Panickar, K S; Shamaladevi, N; Rodriguez, M E; Price, B G; Norenberg, M D

    2018-02-01

    Brain edema and the associated increase in intracranial pressure are major consequences of traumatic brain injury (TBI) that accounts for most early deaths after TBI. We recently showed that acute severe trauma to cultured astrocytes results in cell swelling. We further examined whether trauma induces cell swelling in neurons and microglia. We found that severe trauma also caused cell swelling in cultured neurons, whereas no swelling was observed in microglia. While severe trauma caused cell swelling in both astrocytes and neurons, mild trauma to astrocytes, neurons, and microglia failed to cell swelling. Since extracellular levels of glutamate are increased in brain post-TBI and microglia are known to release cytokine, and direct exposure of astrocytes to these molecules are known to stimulate cell swelling, we examined whether glutamate or cytokines have any additive effect on trauma-induced cell swelling. Exposure of cultured astrocytes to trauma caused cell swelling, and such swelling was potentiated by the exposure of traumatized astrocytes to glutamate and cytokines. Conditioned medium (CM) from traumatized astrocytes had no effect on neuronal swelling post-trauma, while CM from traumatized neurons and microglia potentiated the effect of trauma on astrocyte swelling. Further, trauma significantly increased the Na-K-Cl co-transporter (NKCC) activity in neurons, and that inhibition of NKCC activity diminished the trauma-induced neuronal swelling. Our results indicate that a differential sensitivity to trauma-induced cell swelling exists in neural cells and that neurons and microglia are likely to be involved in the potentiation of the astrocyte swelling post-trauma.

  8. Subtypes of trait impulsivity differentially correlate with neural responses to food choices

    NARCIS (Netherlands)

    van der Laan, Laura N.; Barendse, Marjolein E. A.; Viergever, Max A.; Smeets, Paul A. M.

    2016-01-01

    Impulsivity is a personality trait that is linked to unhealthy eating and overweight. A few studies assessed how impulsivity relates to neural responses to anticipating and tasting food, but it is unknown how impulsivity relates to neural responses during food choice. Although impulsivity is a

  9. Nonassociative learning as gated neural integrator and differentiator in stimulus-response pathways

    Directory of Open Access Journals (Sweden)

    Young Daniel L

    2006-08-01

    Full Text Available Abstract Nonassociative learning is a basic neuroadaptive behavior exhibited across animal phyla and sensory modalities but its role in brain intelligence is unclear. Current literature on habituation and sensitization, the classic "dual process" of nonassociative learning, gives highly incongruous accounts between varying experimental paradigms. Here we propose a general theory of nonassociative learning featuring four base modes: habituation/primary sensitization in primary stimulus-response pathways, and desensitization/secondary sensitization in secondary stimulus-response pathways. Primary and secondary modes of nonassociative learning are distinguished by corresponding activity-dependent recall, or nonassociative gating, of neurotransmission memory. From the perspective of brain computation, nonassociative learning is a form of integral-differential calculus whereas nonassociative gating is a form of Boolean logic operator – both dynamically transforming the stimulus-response relationship. From the perspective of sensory integration, nonassociative gating provides temporal filtering whereas nonassociative learning affords low-pass, high-pass or band-pass/band-stop frequency filtering – effectively creating an intelligent sensory firewall that screens all stimuli for attention and resultant internal model adaptation and reaction. This unified framework ties together many salient characteristics of nonassociative learning and nonassociative gating and suggests a common kernel that correlates with a wide variety of sensorimotor integration behaviors such as central resetting and self-organization of sensory inputs, fail-safe sensorimotor compensation, integral-differential and gated modulation of sensorimotor feedbacks, alarm reaction, novelty detection and selective attention, as well as a variety of mental and neurological disorders such as sensorimotor instability, attention deficit hyperactivity, sensory defensiveness, autism

  10. The missing link: Mothers’ neural response to infant cry related to infant attachment behaviors

    Science.gov (United States)

    Laurent, Heidemarie K.; Ablow, Jennifer C.

    2012-01-01

    This study addresses a gap in the attachment literature by investigating maternal neural response to cry related to infant attachment classifications and behaviors. Twenty-two primiparous mothers and their 18-month old infants completed the Strange Situation Procedure (SS) to elicit attachment behaviors. During a separate functional MRI session, mothers were exposed to their own infant’s cry sound, as well as an unfamiliar infant’s cry and control sound. Maternal neural response to own infant cry related to both overall attachment security and specific infant behaviors. Mothers of less secure infants maintained greater activation to their cry in left parahippocampal and amygdala regions and the right posterior insula. consistent with a negative schematic response bias. Mothers of infants exhibiting more avoidant or contact maintaining behaviors during the SS showed diminished response across left prefrontal, parietal, and cerebellar areas involved in attentional processing and cognitive control. Mothers of infants exhibiting more disorganized behavior showed reduced response in bilateral temporal and subcallosal areas relevant to social cognition and emotion regulation. No differences by attachment classification were found. Implications for attachment transmission models are discussed. PMID:22982277

  11. The missing link: mothers' neural response to infant cry related to infant attachment behaviors.

    Science.gov (United States)

    Laurent, Heidemarie K; Ablow, Jennifer C

    2012-12-01

    This study addresses a gap in the attachment literature by investigating maternal neural response to cry related to infant attachment classifications and behaviors. Twenty-two primiparous mothers and their 18-month old infants completed the Strange Situation (SS) procedure to elicit attachment behaviors. During a separate functional MRI session, mothers were exposed to their own infant's cry sound, as well as an unfamiliar infant's cry and control sound. Maternal neural response to own infant cry related to both overall attachment security and specific infant behaviors. Mothers of less secure infants maintained greater activation to their cry in left parahippocampal and amygdala regions and the right posterior insula consistent with a negative schematic response bias. Mothers of infants exhibiting more avoidant or contact maintaining behaviors during the SS showed diminished response across left prefrontal, parietal, and cerebellar areas involved in attentional processing and cognitive control. Mothers of infants exhibiting more disorganized behavior showed reduced response in bilateral temporal and subcallosal areas relevant to social cognition and emotion regulation. No differences by attachment classification were found. Implications for attachment transmission models are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. On the Control of Social Approach-Avoidance Behavior: Neural and Endocrine Mechanisms.

    Science.gov (United States)

    Kaldewaij, Reinoud; Koch, Saskia B J; Volman, Inge; Toni, Ivan; Roelofs, Karin

    The ability to control our automatic action tendencies is crucial for adequate social interactions. Emotional events trigger automatic approach and avoidance tendencies. Although these actions may be generally adaptive, the capacity to override these emotional reactions may be key to flexible behavior during social interaction. The present chapter provides a review of the neuroendocrine mechanisms underlying this ability and their relation to social psychopathologies. Aberrant social behavior, such as observed in social anxiety or psychopathy, is marked by abnormalities in approach-avoidance tendencies and the ability to control them. Key neural regions involved in the regulation of approach-avoidance behavior are the amygdala, widely implicated in automatic emotional processing, and the anterior prefrontal cortex, which exerts control over the amygdala. Hormones, especially testosterone and cortisol, have been shown to affect approach-avoidance behavior and the associated neural mechanisms. The present chapter also discusses ways to directly influence social approach and avoidance behavior and will end with a research agenda to further advance this important research field. Control over approach-avoidance tendencies may serve as an exemplar of emotional action regulation and might have a great value in understanding the underlying mechanisms of the development of affective disorders.

  13. MicroRNA-378 regulates neural stem cell proliferation and differentiation in vitro by modulating Tailless expression.

    Science.gov (United States)

    Huang, Yanxia; Liu, Xiaoguai; Wang, Yaping

    2015-10-16

    Previous studies have suggested that microRNAs (miRNAs) play an important role in regulating neural stem cell (NSC) proliferation and differentiation. However, the precise role of miRNAs in NSC remains largely unexplored. In this study, we showed that miR-378 can target Tailless (TLX), a critical regulator of NSC, to regulate NSC proliferation and differentiation. By bioinformatic algorithms, miR-378 was found to have a predicted target site in the 3'-untranslated region of TLX, which was verified by a dual-luciferase reporter assay. The expression of miR-378 was increased during NSC differentiation and inversely correlated with TLX expression. qPCR and Western blot analysis also showed that miR-378 negatively regulated TLX mRNA and protein expression in neural stem cells (NSCs). Intriguingly, overexpression of miR-378 increased NSC differentiation and reduced NSC proliferation, whereas suppression of miR-378 led to decreased NSC differentiation and increased NSC proliferation. Moreover, the downstream targets of TLX, including p21, PTEN and Wnt/β-catenin were also found to be regulated by miR-378. Additionally, overexpression of TLX rescued the NSC proliferation deficiency induced by miR-378 overexpression and abolished miR-378-promoted NSC differentiation. Taken together, our data suggest that miR-378 is a novel miRNA that regulates NSC proliferation and differentiation via targeting TLX. Therefore, manipulating miR-378 in NSCs could be a novel strategy to develop novel interventions for the treatment of relevant neurological disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. A chemically defined substrate for the expansion and neuronal differentiation of human pluripotent stem cell-derived neural progenitor cells

    Directory of Open Access Journals (Sweden)

    Yihuan Tsai

    2015-07-01

    Full Text Available Due to the limitation of current pharmacological therapeutic strategies, stem cell therapies have emerged as a viable option for treating many incurable neurological disorders. Specifically, human pluripotent stem cell (hPSC-derived neural progenitor cells (hNPCs, a multipotent cell population that is capable of near indefinite expansion and subsequent differentiation into the various cell types that comprise the central nervous system (CNS, could provide an unlimited source of cells for such cell-based therapies. However the clinical application of these cells will require (i defined, xeno-free conditions for their expansion and neuronal differentiation and (ii scalable culture systems that enable their expansion and neuronal differentiation in numbers sufficient for regenerative medicine and drug screening purposes. Current extracellular matrix protein (ECMP-based substrates for the culture of hNPCs are expensive, difficult to isolate, subject to batch-to-batch variations, and, therefore, unsuitable for clinical application of hNPCs. Using a high-throughput array-based screening approach, we identified a synthetic polymer, poly(4-vinyl phenol (P4VP, that supported the long-term proliferation and self-renewal of hNPCs. The hNPCs cultured on P4VP maintained their characteristic morphology, expressed high levels of markers of multipotency, and retained their ability to differentiate into neurons. Such chemically defined substrates will eliminate critical roadblocks for the utilization of hNPCs for human neural regenerative repair, disease modeling, and drug discovery.

  15. Effects of radiofrequency exposure emitted from a GSM mobile phone on proliferation, differentiation, and apoptosis of neural stem cells

    Science.gov (United States)

    Eghlidospour, Mahsa; Ghanbari, Amir

    2017-01-01

    Due to the importance of neural stem cells (NSCs) in plasticity of the nervous system and treating neurodegenerative diseases, the main goal of this study was to evaluate the effects of radiofrequency radiation emitted from a GSM 900-MHz mobile phone with different exposure duration on proliferation, differentiation and apoptosis of adult murine NSCs in vitro. We used neurosphere assay to evaluate NSCs proliferation, and immunofluorescence assay of neural cell markers to examine NSCs differentiation. We also employed alamarBlue and caspase 3 apoptosis assays to assess harmful effects of mobile phone on NSCs. Our results showed that the number and size of resulting neurospheres and also the percentage of cells differentiated into neurons decreased significantly with increasing exposure duration to GSM 900-MHz radiofrequency (RF)-electromagnetic field (EMF). In contrast, exposure to GSM 900-MHz RF-EMF at different durations did not influence cell viability and apoptosis of NSCs and also their astrocytic differentiation. It is concluded that accumulating dose of GSM 900-MHz RF-EMF might have devastating effects on NSCs proliferation and neurogenesis requiring more causations in terms of using mobile devices. PMID:28713615

  16. Optimization behavior of brainstem respiratory neurons. A cerebral neural network model.

    Science.gov (United States)

    Poon, C S

    1991-01-01

    A recent model of respiratory control suggested that the steady-state respiratory responses to CO2 and exercise may be governed by an optimal control law in the brainstem respiratory neurons. It was not certain, however, whether such complex optimization behavior could be accomplished by a realistic biological neural network. To test this hypothesis, we developed a hybrid computer-neural model in which the dynamics of the lung, brain and other tissue compartments were simulated on a digital computer. Mimicking the "controller" was a human subject who pedalled on a bicycle with varying speed (analog of ventilatory output) with a view to minimize an analog signal of the total cost of breathing (chemical and mechanical) which was computed interactively and displayed on an oscilloscope. In this manner, the visuomotor cortex served as a proxy (homolog) of the brainstem respiratory neurons in the model. Results in 4 subjects showed a linear steady-state ventilatory CO2 response to arterial PCO2 during simulated CO2 inhalation and a nearly isocapnic steady-state response during simulated exercise. Thus, neural optimization is a plausible mechanism for respiratory control during exercise and can be achieved by a neural network with cognitive computational ability without the need for an exercise stimulus.

  17. Malware Classification Based on the Behavior Analysis and Back Propagation Neural Network

    Directory of Open Access Journals (Sweden)

    Pan Zhi-Peng

    2016-01-01

    Full Text Available With the development of the Internet, malwares have also been expanded on the network systems rapidly. In order to deal with the diversity and amount of the variants, a number of automated behavior analysis tools have emerged as the time requires. Yet these tools produce detailed behavior reports of the malwares, it still needs to specify its category and judge its criticality manually. In this paper, we propose an automated malware classification approach based on the behavior analysis. We firstly perform dynamic analyses to obtain the detailed behavior profiles of the malwares, which are then used to abstract the main features of the malwares and serve as the inputs of the Back Propagation (BP Neural Network model.The experimental results demonstrate that our classification technique is able to classify the malware variants effectively and detect malware accurately.

  18. Preschool externalizing behavior predicts gender-specific variation in adolescent neural structure.

    Directory of Open Access Journals (Sweden)

    Jessica Z K Caldwell

    Full Text Available Dysfunction in the prefrontal cortex, amygdala, and hippocampus is believed to underlie the development of much psychopathology. However, to date only limited longitudinal data relate early behavior with neural structure later in life. Our objective was to examine the relationship of early life externalizing behavior with adolescent brain structure. We report here the first longitudinal study linking externalizing behavior during preschool to brain structure during adolescence. We examined the relationship of preschool externalizing behavior with amygdala, hippocampus, and prefrontal cortex volumes at age 15 years in a community sample of 76 adolescents followed longitudinally since their mothers' pregnancy. A significant gender by externalizing behavior interaction revealed that males-but not females-with greater early childhood externalizing behavior had smaller amygdala volumes at adolescence (t = 2.33, p = .023. No significant results were found for the hippocampus or the prefrontal cortex. Greater early externalizing behavior also related to smaller volume of a cluster including the angular gyrus and tempoparietal junction across genders. Results were not attributable to the impact of preschool anxiety, preschool maternal stress, school-age internalizing or externalizing behaviors, or adolescent substance use. These findings demonstrate a novel, gender-specific relationship between early-childhood externalizing behavior and adolescent amygdala volume, as well as a cross-gender result for the angular gyrus and tempoparietal junction.

  19. Behavioral and neural Darwinism: selectionist function and mechanism in adaptive behavior dynamics.

    Science.gov (United States)

    McDowell, J J

    2010-05-01

    An evolutionary theory of behavior dynamics and a theory of neuronal group selection share a common selectionist framework. The theory of behavior dynamics instantiates abstractly the idea that behavior is selected by its consequences. It implements Darwinian principles of selection, reproduction, and mutation to generate adaptive behavior in virtual organisms. The behavior generated by the theory has been shown to be quantitatively indistinguishable from that of live organisms. The theory of neuronal group selection suggests a mechanism whereby the abstract principles of the evolutionary theory may be implemented in the nervous systems of biological organisms. According to this theory, groups of neurons subserving behavior may be selected by synaptic modifications that occur when the consequences of behavior activate value systems in the brain. Together, these theories constitute a framework for a comprehensive account of adaptive behavior that extends from brain function to the behavior of whole organisms in quantitative detail. Copyright (c) 2009 Elsevier B.V. All rights reserved.

  20. Promoted neuronal differentiation after activation of alpha4/beta2 nicotinic acetylcholine receptors in undifferentiated neural progenitors.

    Directory of Open Access Journals (Sweden)

    Takeshi Takarada

    Full Text Available BACKGROUND: Neural progenitor is a generic term used for undifferentiated cell populations of neural stem, neuronal progenitor and glial progenitor cells with abilities for proliferation and differentiation. We have shown functional expression of ionotropic N-methyl-D-aspartate (NMDA and gamma-aminobutyrate type-A receptors endowed to positively and negatively regulate subsequent neuronal differentiation in undifferentiated neural progenitors, respectively. In this study, we attempted to evaluate the possible functional expression of nicotinic acetylcholine receptor (nAChR by undifferentiated neural progenitors prepared from neocortex of embryonic rodent brains. METHODOLOGY/PRINCIPAL FINDINGS: Reverse transcription polymerase chain reaction analysis revealed mRNA expression of particular nAChR subunits in undifferentiated rat and mouse progenitors prepared before and after the culture with epidermal growth factor under floating conditions. Sustained exposure to nicotine significantly inhibited the formation of neurospheres composed of clustered proliferating cells and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide reduction activity at a concentration range of 1 µM to 1 mM without affecting cell survival. In these rodent progenitors previously exposed to nicotine, marked promotion was invariably seen for subsequent differentiation into cells immunoreactive for a neuronal marker protein following the culture of dispersed cells under adherent conditions. Both effects of nicotine were significantly prevented by the heteromeric α4β2 nAChR subtype antagonists dihydro-β-erythroidine and 4-(5-ethoxy-3-pyridinyl-N-methyl-(3E-3-buten-1-amine, but not by the homomeric α7 nAChR subtype antagonist methyllycaconitine, in murine progenitors. Sustained exposure to nicotine preferentially increased the expression of Math1 among different basic helix-loop-helix proneural genes examined. In undifferentiated progenitors from embryonic mice

  1. γ-Secretase modulators reduce endogenous amyloid β42 levels in human neural progenitor cells without altering neuronal differentiation

    Science.gov (United States)

    D’Avanzo, Carla; Sliwinski, Christopher; Wagner, Steven L.; Tanzi, Rudolph E.; Kim, Doo Yeon; Kovacs, Dora M.

    2015-01-01

    Soluble γ-secretase modulators (SGSMs) selectively decrease toxic amyloid β (Aβ) peptides (Aβ42). However, their effect on the physiologic functions of γ-secretase has not been tested in human model systems. γ-Secretase regulates fate determination of neural progenitor cells. Thus, we studied the impact of SGSMs on the neuronal differentiation of ReNcell VM (ReN) human neural progenitor cells (hNPCs). Quantitative PCR analysis showed that treatment of neurosphere-like ReN cell aggregate cultures with γ-secretase inhibitors (GSIs), but not SGSMs, induced a 2- to 4-fold increase in the expression of the neuronal markers Tuj1 and doublecortin. GSI treatment also induced neuronal marker protein expression, as shown by Western blot analysis. In the same conditions, SGSM treatment selectively reduced endogenous Aβ42 levels by ∼80%. Mechanistically, we found that Notch target gene expressions were selectively inhibited by a GSI, not by SGSM treatment. We can assert, for the first time, that SGSMs do not affect the neuronal differentiation of hNPCs while selectively decreasing endogenous Aβ42 levels in the same conditions. Our results suggest that our hNPC differentiation system can serve as a useful model to test the impact of GSIs and SGSMs on both endogenous Aβ levels and γ-secretase physiologic functions including endogenous Notch signaling.—D’Avanzo, C., Sliwinski, C., Wagner, S. L., Tanzi, R. E., Kim, D. Y., Kovacs, D. M. γ-Secretase modulators reduce endogenous amyloid β42 levels in human neural progenitor cells without altering neuronal differentiation. PMID:25903103

  2. Neurotrophin-3 promotes proliferation and cholinergic neuronal differentiation of bone marrow- derived neural stem cells via notch signaling pathway.

    Science.gov (United States)

    Yan, Yu-Hui; Li, Shao-Heng; Gao, Zhong; Zou, Sa-Feng; Li, Hong-Yan; Tao, Zhen-Yu; Song, Jie; Yang, Jing-Xian

    2016-12-01

    Recently, the potential for neural stem cells (NSCs) to be used in the treatment of Alzheimer's disease (AD) has been reported; however, the therapeutic effects are modest by virtue of the low neural differentiation rate. In our study, we transfected bone marrow-derived NSCs (BM-NSCs) with Neurotrophin-3 (NT-3), a superactive neurotrophic factor that promotes neuronal survival, differentiation, and migration of neuronal cells, to investigate the effects of NT-3 gene overexpression on the proliferation and differentiation into cholinergic neuron of BM-NSCs in vitro and its possible molecular mechanism. BM-NSCs were generated from BM mesenchymal cells of adult C57BL/6 mice and cultured in vitro. After transfected with NT-3 gene, immunofluorescence and RT-PCR method were used to determine the ability of BM-NSCs on proliferation and differentiation into cholinergic neuron; Acetylcholine Assay Kit was used for acetylcholine (Ach). RT-PCR and WB analysis were used to characterize mRNA and protein level related to the Notch signaling pathway. We found that NT-3 can promote the proliferation and differentiation of BM-NSCs into cholinergic neurons and elevate the levels of acetylcholine (ACh) in the supernatant. Furthermore, NT-3 gene overexpression increase the expression of Hes1, decreased the expression of Mash1 and Ngn1 during proliferation of BM-NSCs. Whereas, the expression of Hes1 was down-regulated, and Mash1 and Ngn1 expression were up-regulated during differentiation of BM-NSCs. Our findings support the prospect of using NT-3-transduced BM-NSCs in developing therapies for AD due to their equivalent therapeutic potential as subventricular zone-derived NSCs (SVZ-NSCs), greater accessibility, and autogenous attributes. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. The motivation and pleasure dimension of negative symptoms: neural substrates and behavioral outputs.

    Science.gov (United States)

    Kring, Ann M; Barch, Deanna M

    2014-05-01

    A range of emotional and motivation impairments have long been clinically documented in people with schizophrenia, and there has been a resurgence of interest in understanding the psychological and neural mechanisms of the so-called "negative symptoms" in schizophrenia, given their lack of treatment responsiveness and their role in constraining function and life satisfaction in this illness. Negative symptoms comprise two domains, with the first covering diminished motivation and pleasure across a range of life domains and the second covering diminished verbal and non-verbal expression and communicative output. In this review, we focus on four aspects of the motivation/pleasure domain, providing a brief review of the behavioral and neural underpinnings of this domain. First, we cover liking or in-the-moment pleasure: immediate responses to pleasurable stimuli. Second, we cover anticipatory pleasure or wanting, which involves prediction of a forthcoming enjoyable outcome (reward) and feeling pleasure in anticipation of that outcome. Third, we address motivation, which comprises effort computation, which involves figuring out how much effort is needed to achieve a desired outcome, planning, and behavioral response. Finally, we cover the maintenance emotional states and behavioral responses. Throughout, we consider the behavioral manifestations and brain representations of these four aspects of motivation/pleasure deficits in schizophrenia. We conclude with directions for future research as well as implications for treatment. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

  4. Spared behavioral repetition effects in Alzheimer's disease linked to an altered neural mechanism at posterior cortex.

    Science.gov (United States)

    Broster, Lucas S; Li, Juan; Wagner, Benjamin; Smith, Charles D; Jicha, Gregory A; Schmitt, Frederick A; Munro, Nancy; Haney, Ryan H; Jiang, Yang

    2018-02-20

    Individuals with dementia of the Alzheimer type (AD) classically show disproportionate impairment in measures of working memory, but repetition learning effects are relatively preserved. As AD affects brain regions implicated in both working memory and repetition effects, the neural basis of this discrepancy is poorly understood. We hypothesized that the posterior repetition effect could account for this discrepancy due to the milder effects of AD at visual cortex. Participants with early AD, amnestic mild cognitive impairment (MCI), and healthy controls performed a working memory task with superimposed repetition effects while electroencephalography was collected to identify possible neural mechanisms of preserved repetition effects. Participants with AD showed preserved behavioral repetition effects and a change in the posterior repetition effect. Visual cortex may play a role in maintained repetition effects in persons with early AD.

  5. Taurine Protected Against the Impairments of Neural Stem Cell Differentiated Neurons Induced by Oxygen-Glucose Deprivation.

    Science.gov (United States)

    Xiao, Bo; Liu, Huazhen; Gu, Zeyun; Liu, Sining; Ji, Cheng

    2015-11-01

    Cell transplantation of neural stem cells (NSCs) is a promising approach for neurological recovery both structurally and functionally. However, one big obstacle is to promote differentiation of NSCs into neurons and the followed maturation. In the present study, we aimed to investigate the protective effect of taurine on the differentiation of NSCs and subsequent maturation of their neuronal lineage, when exposed to oxygen-glucose deprivation (OGD). The results suggested that taurine (5-20 mM) promoted the viability and proliferation of NSCs, and it protected against 8 h of OGD induced impairments. Furthermore, 20 mM taurine promoted NSCs to differentiate into neurons after 7 days of culture, and it also protected against the suppressive impairments of 8 h of OGD. Consistently, taurine (20 mM) promoted the neurite sprouting and outgrowth of the NSC differentiated neurons after 14 days of differentiation, which were significantly inhibited by OGD (8 h). At D21, the mushroom spines and spine density were promoted or restored by 20 mM taurine. Taken together, the enhanced viability and proliferation of NSCs, more differentiated neurons and the promoted maturation of neurons by 20 mM taurine support its therapeutic application during stem cell therapy to enhance neurological recovery. Moreover, it protected against the impairments induced by OGD, which may highlight its role for a more direct therapeutic application especially in an ischemic stroke environment.

  6. Neural correlates of distraction in borderline personality disorder before and after dialectical behavior therapy.

    Science.gov (United States)

    Winter, Dorina; Niedtfeld, Inga; Schmitt, Ruth; Bohus, Martin; Schmahl, Christian; Herpertz, Sabine C

    2017-02-01

    Neural underpinnings of emotion dysregulation in borderline personality disorder (BPD) are characterized by limbic hyperactivity and disturbed prefrontal activity. It is unknown whether neural correlates of emotion regulation change after a psychotherapy which has the goal to improve emotion dysregulation in BPD, such as dialectical behavioral therapy (DBT). We investigated distraction as a main emotion regulation strategy before and after DBT in female patients with BPD. Thirty-one BPD patients were instructed to either passively view or memorize letters before being confronted with negative or neutral pictures in a distraction task during functional magnetic resonance imaging. This paradigm was applied before and after a 12-week residential DBT-based treatment program. We compared the DBT group to 15 BPD control patients, who continued their usual, non-DBT-based treatment or did not have any treatment, and 22 healthy participants. Behaviorally, BPD groups and healthy participants did not differ significantly with respect to alterations over time. On the neural level, BPD patients who received DBT-based treatment showed an activity decrease in the right inferior parietal lobe/supramarginal gyrus during distraction from negative rather than neutral stimuli when compared to both control groups. This decrease was correlated with improvement in self-reported borderline symptom severity. DBT responders exhibited decreased right perigenual anterior cingulate activity when viewing negative (rather than neutral) pictures. In conclusion, our findings reveal changes in neural activity associated with distraction during emotion processing after DBT in patients with BPD. These changes point to lower emotional susceptibility during distraction after BPD symptom improvement.

  7. Endogenous neural stem cells in central canal of adult rats acquired limited ability to differentiate into neurons following mild spinal cord injury

    Science.gov (United States)

    Liu, Yuan; Tan, Botao; Wang, Li; Long, Zaiyun; Li, Yingyu; Liao, Weihong; Wu, Yamin

    2015-01-01

    Endogenous neural stem cells in central canal of adult mammalian spinal cord exhibit stem cell properties following injury. In the present study, the endogenous neural stem cells were labeled with Dil to track the differentiation of cells after mild spinal cord injury (SCI). Compared with 1 and 14 days post mild injury, the number of endogenous neural stem cells significantly increased at the injured site of spinal cord on 3 and 7 days post-injury. Dil-labeled βIII-tublin and GFAP expressing cells could be detected on 7 days post-injury, which indicated that the endogenous neural stem cells in central canal of spinal cord differentiated into different type of neural cells, but there were more differentiated astrocytes than the neurons after injury. Furthermore, after injury the expression of inhibitory Notch1 and Hes1 mRNA began to increase at 6 hours and was evident at 12 and 24 hours, which maintained high levels up to 7 days post-injury. These results indicated that a mild SCI in rat is sufficient to induce endogenous neural stem cells proliferation and differentiation. However, the ability to differentiate into neurons is limited, which may be, at least in part, due to high expression of inhibitory Notch1 and Hes1 genes after injury. PMID:26097566

  8. Alternating current electric fields of varying frequencies: effects on proliferation and differentiation of porcine neural progenitor cells.

    Science.gov (United States)

    Lim, Ji-Hey; McCullen, Seth D; Piedrahita, Jorge A; Loboa, Elizabeth G; Olby, Natasha J

    2013-10-01

    Application of sinusoidal electric fields (EFs) has been observed to affect cellular processes, including alignment, proliferation, and differentiation. In the present study, we applied low-frequency alternating current (AC) EFs to porcine neural progenitor cells (pNPCs) and investigated the effects on cell patterning, proliferation, and differentiation. pNPCs were grown directly on interdigitated electrodes (IDEs) localizing the EFs to a region accessible visually for fluorescence-based assays. Cultures of pNPCs were exposed to EFs (1 V/cm) of 1 Hz, 10 Hz, and 50 Hz for 3, 7, and 14 days and compared to control cultures. Immunocytochemistry was performed to evaluate the expression of neural markers. pNPCs grew uniformly with no evidence of alignment to the EFs and no change in cell numbers when compared with controls. Nestin expression was shown in all groups at 3 and 7 days, but not at 14 days. NG2 expression was low in all groups. Co-expression of glial fibrillary acidic protein (GFAP) and TUJ1 was significantly higher in the cultures exposed to 10- and 50-Hz EFs than the controls. In summary, sinusoidal AC EFs via IDEs did not alter the alignment and proliferation of pNPCs, but higher frequency stimulation appeared to delay differentiation into mature astrocytes.

  9. Induction of apoptotic death and retardation of neuronal differentiation of human neural stem cells by sodium arsenite treatment

    International Nuclear Information System (INIS)

    Ivanov, Vladimir N.; Hei, Tom K.

    2013-01-01

    Chronic arsenic toxicity is a global health problem that affects more than 100 million people worldwide. Long-term health effects of inorganic sodium arsenite in drinking water may result in skin, lung and liver cancers and in severe neurological abnormalities. We investigated in the present study whether sodium arsenite affects signaling pathways that control cell survival, proliferation and neuronal differentiation of human neural stem cells (NSC). We demonstrated that the critical signaling pathway, which was suppressed by sodium arsenite in NSC, was the protective PI3K–AKT pathway. Sodium arsenite (2–4 μM) also caused down-regulation of Nanog, one of the key transcription factors that control pluripotency and self-renewal of stem cells. Mitochondrial damage and cytochrome-c release induced by sodium arsenite exposure was followed by initiation of the mitochondrial apoptotic pathway in NSC. Beside caspase-9 and caspase-3 inhibitors, suppression of JNK activity decreased levels of arsenite-induced apoptosis in NSC. Neuronal differentiation of NSC was substantially inhibited by sodium arsenite exposure. Overactivation of JNK1 and ERK1/2 and down-regulation of PI3K–AKT activity induced by sodium arsenite were critical factors that strongly affected neuronal differentiation. In conclusion, sodium arsenite exposure of human NSC induces the mitochondrial apoptotic pathway, which is substantially accelerated due to the simultaneous suppression of PI3K–AKT. Sodium arsenite also negatively affects neuronal differentiation of NSC through overactivation of MEK–ERK and suppression of PI3K–AKT. - Highlights: ► Arsenite induces the mitochondrial apoptotic pathway in human neural stem cells. ► Arsenite-induced apoptosis is strongly upregulated by suppression of PI3K–AKT. ► Arsenite-induced apoptosis is strongly down-regulated by inhibition of JNK–cJun. ► Arsenite negatively affects neuronal differentiation by inhibition of PI3K–AKT

  10. Induction of apoptotic death and retardation of neuronal differentiation of human neural stem cells by sodium arsenite treatment

    Energy Technology Data Exchange (ETDEWEB)

    Ivanov, Vladimir N., E-mail: vni3@columbia.edu [Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, NY 10032 (United States); Hei, Tom K. [Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, NY 10032 (United States)

    2013-04-01

    Chronic arsenic toxicity is a global health problem that affects more than 100 million people worldwide. Long-term health effects of inorganic sodium arsenite in drinking water may result in skin, lung and liver cancers and in severe neurological abnormalities. We investigated in the present study whether sodium arsenite affects signaling pathways that control cell survival, proliferation and neuronal differentiation of human neural stem cells (NSC). We demonstrated that the critical signaling pathway, which was suppressed by sodium arsenite in NSC, was the protective PI3K–AKT pathway. Sodium arsenite (2–4 μM) also caused down-regulation of Nanog, one of the key transcription factors that control pluripotency and self-renewal of stem cells. Mitochondrial damage and cytochrome-c release induced by sodium arsenite exposure was followed by initiation of the mitochondrial apoptotic pathway in NSC. Beside caspase-9 and caspase-3 inhibitors, suppression of JNK activity decreased levels of arsenite-induced apoptosis in NSC. Neuronal differentiation of NSC was substantially inhibited by sodium arsenite exposure. Overactivation of JNK1 and ERK1/2 and down-regulation of PI3K–AKT activity induced by sodium arsenite were critical factors that strongly affected neuronal differentiation. In conclusion, sodium arsenite exposure of human NSC induces the mitochondrial apoptotic pathway, which is substantially accelerated due to the simultaneous suppression of PI3K–AKT. Sodium arsenite also negatively affects neuronal differentiation of NSC through overactivation of MEK–ERK and suppression of PI3K–AKT. - Highlights: ► Arsenite induces the mitochondrial apoptotic pathway in human neural stem cells. ► Arsenite-induced apoptosis is strongly upregulated by suppression of PI3K–AKT. ► Arsenite-induced apoptosis is strongly down-regulated by inhibition of JNK–cJun. ► Arsenite negatively affects neuronal differentiation by inhibition of PI3K–AKT.

  11. Pyrolysed 3D-Carbon Scaffolds Induce Spontaneous Differentiation of Human Neural Stem Cells and Facilitate Real-Time Dopamine Detection

    DEFF Research Database (Denmark)

    Amato, Letizia; Heiskanen, Arto; Caviglia, Claudia

    2014-01-01

    Structurally patterned pyrolysed three-dimensional carbon scaffolds (p3Dcarbon) are fabricated and applied for differentiation of human neural stem cells (hNSCs) developed for cell replacement therapy and sensing of released dopamine. In the absence of differentiation factors (DF) the pyrolysed c...

  12. Development of social skills in children: neural and behavioral evidence for the elaboration of cognitive models

    Science.gov (United States)

    Soto-Icaza, Patricia; Aboitiz, Francisco; Billeke, Pablo

    2015-01-01

    Social skills refer to a wide group of abilities that allow us to interact and communicate with others. Children learn how to solve social situations by predicting and understanding other's behaviors. The way in which humans learn to interact successfully with others encompasses a complex interaction between neural, behavioral, and environmental elements. These have a role in the accomplishment of positive developmental outcomes, including peer acceptance, academic achievement, and mental health. All these social abilities depend on widespread brain networks that are recently being studied by neuroscience. In this paper, we will first review the studies on this topic, aiming to clarify the behavioral and neural mechanisms related to the acquisition of social skills during infancy and their appearance in time. Second, we will briefly describe how developmental diseases like Autism Spectrum Disorders (ASD) can inform about the neurobiological mechanisms of social skills. We finally sketch a general framework for the elaboration of cognitive models in order to facilitate the comprehension of human social development. PMID:26483621

  13. Behavioral and neural responses to infant and adult tears: The impact of maternal love withdrawal.

    Science.gov (United States)

    Riem, Madelon M E; van IJzendoorn, Marinus H; De Carli, Pietro; Vingerhoets, Ad J J M; Bakermans-Kranenburg, Marian J

    2017-09-01

    The current study examined behavioral and neural responses to infant and adult tears, taking into account childhood experiences with parental love-withdrawal. With functional MRI (fMRI), we measured neural reactivity to pictures of infants and adults with and without tears on their faces in nulliparous women with varying childhood experiences of maternal use of love withdrawal. Behavioral responses to infant and adult tears were measured with an approach-avoidance task. We found that individuals with experiences of love withdrawal showed less amygdala and insula reactivity to adult tears, but love withdrawal did not affect amygdala and insula reactivity to infant tears. During the approach-avoidance task, individuals responded faster to adult tears in the approach condition compared with the avoidance condition, indicating that adult tears facilitate approach behavior. Individuals responded faster to infant tears than to adult tears, regardless of approach or avoidance condition. Our findings suggest that infant tears are highly salient and may, therefore, overrule the effects of contextual and personal characteristics that influence the perception of adult crying. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  14. The effect of magnetic nanoparticles on neuronal differentiation of induced pluripotent stem cell-derived neural precursors

    Czech Academy of Sciences Publication Activity Database

    Jiráková, Klára; Šeneklová, Monika; Jirák, D.; Turnovcová, Karolína; Vosmanská, M.; Babič, Michal; Horák, Daniel; Veverka, Pavel; Jendelová, Pavla

    2016-01-01

    Roč. 11, č. 2016 (2016), s. 6267-6281 E-ISSN 1178-2013 R&D Projects: GA MŠk(CZ) LQ1604; GA MŠk(CZ) ED1.1.00/02.0109; GA MŠk(CZ) 7F14057 Institutional support: RVO:68378041 ; RVO:61389013 ; RVO:68378271 Keywords : neural precursors * magnetic resonance imaging * cell differentiation Subject RIV: FH - Neurology; EB - Genetics ; Molecular Biology (FGU-C); CD - Macromolecular Chemistry (UMCH-V) Impact factor: 4.300, year: 2016

  15. [Neural Mechanisms That Facilitate Adaptive Behavior Based on Acquired Stimulus-Outcome Information].

    Science.gov (United States)

    Ogawa, Masaaki

    2017-11-01

    In response to changing internal and external situations, we always need to adapt our behavior based on previous experiences, particularly, acquired stimulus-outcome information. The orbitofrontal cortex (OFC), a prefrontal cortical region, is critical for this type of decision-making. The current understanding of the fundamental functions of the OFC has been reviewed by introducing, as an example, how the OFC contributes to the processing of uncertain rewards. Furthermore, the importance of revealing context and temporally specific causal roles of neural circuits including the OFC in decision-making, as well as the techniques to achieve the goal, have been discussed.

  16. Overexpression of miR‑21 promotes neural stem cell proliferation and neural differentiation via the Wnt/β‑catenin signaling pathway in vitro.

    Science.gov (United States)

    Zhang, Wei-Min; Zhang, Zhi-Ren; Yang, Xi-Tao; Zhang, Yong-Gang; Gao, Yan-Sheng

    2018-01-01

    The primary aim of the present study was to examine the effects of microRNA‑21 (miR‑21) on the proliferation and differentiation of rat primary neural stem cells (NSCs) in vitro. miR‑21 was overexpressed in NSCs by transfection with a miR‑21 mimic. The effects of miR‑21 overexpression on NSC proliferation were revealed by Cell Counting kit 8 and 5‑ethynyl‑2'‑deoxyuridine incorporation assay, and miR‑21 overexpression was revealed to increase NSC proliferation. miR‑21 overexpression was confirmed using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). mRNA and protein expression levels of key molecules (β‑catenin, cyclin D1, p21 and miR‑21) in the Wnt/β‑catenin signaling pathway were studied by RT‑qPCR and western blot analysis. RT‑qPCR and western blot analyses revealed that miR‑21 overexpression increased β‑catenin and cyclin D1 expression, and decreased p21 expression. These results suggested that miR‑21‑induced increase in proliferation was mediated by activation of the Wnt/β‑catenin signaling pathway, since overexpression of miR‑21 increased β‑catenin and cyclin D1 expression and reduced p21 expression. Furthermore, inhibition of the Wnt/β‑catenin pathway with FH535 attenuated the influence of miR‑21 overexpression on NSC proliferation, indicating that the factors activated by miR‑21 overexpression were inhibited by FH535 treatment. Furthermore, overexpression of miR‑21 enhanced the differentiation of NSCs into neurons and inhibited their differentiation into astrocytes. The present study indicated that in primary rat NSCs, overexpression of miR‑21 may promote proliferation and differentiation into neurons via the Wnt/β‑catenin signaling pathway in vitro.

  17. Differentiated human midbrain-derived neural progenitor cells express excitatory strychnine-sensitive glycine receptors containing α2β subunits.

    Directory of Open Access Journals (Sweden)

    Florian Wegner

    Full Text Available BACKGROUND: Human fetal midbrain-derived neural progenitor cells (NPCs may deliver a tissue source for drug screening and regenerative cell therapy to treat Parkinson's disease. While glutamate and GABA(A receptors play an important role in neurogenesis, the involvement of glycine receptors during human neurogenesis and dopaminergic differentiation as well as their molecular and functional characteristics in NPCs are largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigated NPCs in respect to their glycine receptor function and subunit expression using electrophysiology, calcium imaging, immunocytochemistry, and quantitative real-time PCR. Whole-cell recordings demonstrate the ability of NPCs to express functional strychnine-sensitive glycine receptors after differentiation for 3 weeks in vitro. Pharmacological and molecular analyses indicate a predominance of glycine receptor heteromers containing α2β subunits. Intracellular calcium measurements of differentiated NPCs suggest that glycine evokes depolarisations mediated by strychnine-sensitive glycine receptors and not by D-serine-sensitive excitatory glycine receptors. Culturing NPCs with additional glycine, the glycine-receptor antagonist strychnine, or the Na(+-K(+-Cl(- co-transporter 1 (NKCC1-inhibitor bumetanide did not significantly influence cell proliferation and differentiation in vitro. CONCLUSIONS/SIGNIFICANCE: These data indicate that NPCs derived from human fetal midbrain tissue acquire essential glycine receptor properties during neuronal maturation. However, glycine receptors seem to have a limited functional impact on neurogenesis and dopaminergic differentiation of NPCs in vitro.

  18. Stimulation of neural differentiation in human bone marrow mesenchymal stem cells by extremely low-frequency electromagnetic fields incorporated with MNPs.

    Science.gov (United States)

    Choi, Yun-Kyong; Lee, Dong Heon; Seo, Young-Kwon; Jung, Hyun; Park, Jung-Keug; Cho, Hyunjin

    2014-10-01

    Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) have been investigated as a new cell-therapeutic solution due to their capacity that could differentiate into neural-like cells. Extremely low-frequency electromagnetic fields (ELF-EMFs) therapy has emerged as a novel technique, using mechanical stimulus to differentiate hBM-MSCs and significantly enhance neuronal differentiation to affect cellular and molecular reactions. Magnetic iron oxide (Fe3O4) nanoparticles (MNPs) have recently achieved widespread use for biomedical applications and polyethylene glycol (PEG)-labeled nanoparticles are used to increase their circulation time, aqueous solubility, biocompatibility, and nonspecific cellular uptake as well as to decrease immunogenicity. Many studies have used MNP-labeled cells for differentiation, but there have been no reports of MNP-labeled neural differentiation combined with EMFs. In this study, synthesized PEG-phospholipid encapsulated magnetite (Fe3O4) nanoparticles are used on hBM-MSCs to improve their intracellular uptake. The PEGylated nanoparticles were exposed to the cells under 50 Hz of EMFs to improve neural differentiation. First, we measured cell viability and intracellular iron content in hBM-MSCs after treatment with MNPs. Analysis was conducted by RT-PCR, and immunohistological analysis using neural cell type-specific genes and antibodies after exposure to 50 Hz electromagnetic fields. These results suggest that electromagnetic fields enhance neural differentiation in hBM-MSCs incorporated with MNPs and would be an effective method for differentiating neural cells.

  19. Nanoparticle-mediated transcriptional modification enhances neuronal differentiation of human neural stem cells following transplantation in rat brain.

    Science.gov (United States)

    Li, Xiaowei; Tzeng, Stephany Y; Liu, Xiaoyan; Tammia, Markus; Cheng, Yu-Hao; Rolfe, Andrew; Sun, Dong; Zhang, Ning; Green, Jordan J; Wen, Xuejun; Mao, Hai-Quan

    2016-04-01

    Strategies to enhance survival and direct the differentiation of stem cells in vivo following transplantation in tissue repair site are critical to realizing the potential of stem cell-based therapies. Here we demonstrated an effective approach to promote neuronal differentiation and maturation of human fetal tissue-derived neural stem cells (hNSCs) in a brain lesion site of a rat traumatic brain injury model using biodegradable nanoparticle-mediated transfection method to deliver key transcriptional factor neurogenin-2 to hNSCs when transplanted with a tailored hyaluronic acid (HA) hydrogel, generating larger number of more mature neurons engrafted to the host brain tissue than non-transfected cells. The nanoparticle-mediated transcription activation method together with an HA hydrogel delivery matrix provides a translatable approach for stem cell-based regenerative therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. The Effect of Agmatine on Expression of IL-1β and TLX Which Promotes Neuronal Differentiation in Lipopolysaccharide-Treated Neural Progenitors.

    Science.gov (United States)

    Song, Juhyun; Kumar, Bokara Kiran; Kang, Somang; Park, Kyung Ah; Lee, Won Taek; Lee, Jong Eun

    2013-12-01

    Differentiation of neural progenitor cells (NPCs) is important for protecting neural cells and brain tissue during inflammation. Interleukin-1 beta (IL-1β) is the most common pro- inflammatory cytokine in brain inflammation, and increased IL-1β levels can decrease the proliferation of NPCs. We aimed to investigate whether agmatine (Agm), a primary polyamine that protects neural cells, could trigger differentiation of NPCs by activating IL-1β in vitro. The cortex of ICR mouse embryos (E14) was dissociated to culture NPCs. NPCs were stimulated by lipopolysaccharide (LPS). After 6 days, protein expression of stem cell markers and differentiation signal factors was confirmed by using western blot analysis. Also, immunocytochemistry was used to confirm the cell fate. Agm treatment activated NPC differentiation significantly more than in the control group, which was evident by the increased expression of a neuronal marker, MAP2, in the LPS-induced, Agm-treated group. Differentiation of LPS-induced, Agm-treated NPCs was regulated by the MAPK pathway and is thought to be related to IL-1β activation and decreased expression of TLX, a transcription factor that regulates NPC differentiation. Our results reveal that Agm can promote NPC differentiation to neural stem cells by modulating IL-1β expression under inflammatory condition, and they suggest that Agm may be a novel therapeutic strategy for neuroinflammatory diseases.

  1. Teacher Implementation of Trial-Based Functional Analysis and Differential Reinforcement of Alternative Behavior for Students with Challenging Behavior

    Science.gov (United States)

    Flynn, Susan D.; Lo, Ya-yu

    2016-01-01

    The purpose of this study was to examine the effects of a training package on three middle school special education teachers' accurate implementation of trial-based functional analysis (TBFA) and differential reinforcement of alternative behavior (DRA) with their students with autism spectrum disorders or emotional and behavioral disorders in the…

  2. A chemically defined substrate for the expansion and neuronal differentiation of human pluripotent stem cell-derived neural progenitor cells.

    Science.gov (United States)

    Tsai, Yihuan; Cutts, Josh; Kimura, Azuma; Varun, Divya; Brafman, David A

    2015-07-01

    Due to the limitation of current pharmacological therapeutic strategies, stem cell therapies have emerged as a viable option for treating many incurable neurological disorders. Specifically, human pluripotent stem cell (hPSC)-derived neural progenitor cells (hNPCs), a multipotent cell population that is capable of near indefinite expansion and subsequent differentiation into the various cell types that comprise the central nervous system (CNS), could provide an unlimited source of cells for such cell-based therapies. However the clinical application of these cells will require (i) defined, xeno-free conditions for their expansion and neuronal differentiation and (ii) scalable culture systems that enable their expansion and neuronal differentiation in numbers sufficient for regenerative medicine and drug screening purposes. Current extracellular matrix protein (ECMP)-based substrates for the culture of hNPCs are expensive, difficult to isolate, subject to batch-to-batch variations, and, therefore, unsuitable for clinical application of hNPCs. Using a high-throughput array-based screening approach, we identified a synthetic polymer, poly(4-vinyl phenol) (P4VP), that supported the long-term proliferation and self-renewal of hNPCs. The hNPCs cultured on P4VP maintained their characteristic morphology, expressed high levels of markers of multipotency, and retained their ability to differentiate into neurons. Such chemically defined substrates will eliminate critical roadblocks for the utilization of hNPCs for human neural regenerative repair, disease modeling, and drug discovery. Copyright © 2015. Published by Elsevier B.V.

  3. Neural and Behavioral Evidence for an Online Resetting Process in Visual Working Memory.

    Science.gov (United States)

    Balaban, Halely; Luria, Roy

    2017-02-01

    Visual working memory (VWM) guides behavior by holding a set of active representations and modifying them according to changes in the environment. This updating process relies on a unique mapping between each VWM representation and an actual object in the environment. Here, we destroyed this mapping by either presenting a coherent object but then breaking it into independent parts or presenting an object but then abruptly replacing it with a different object. This allowed us to introduce the neural marker and behavioral consequence of an online resetting process in humans' VWM. Across seven experiments, we demonstrate that this resetting process involves abandoning the old VWM contents because they no longer correspond to the objects in the environment. Then, VWM encodes the novel information and reestablishes the correspondence between the new representations and the objects. The resetting process was marked by a unique neural signature: a sharp drop in the amplitude of the electrophysiological index of VWM contents (the contralateral delay activity), presumably indicating the loss of the existent object-to-representation mappings. This marker was missing when an updating process occurred. Moreover, when tracking moving items, VWM failed to detect salient changes in the object's shape when these changes occurred during the resetting process. This happened despite the object being fully visible, presumably because the mapping between the object and a VWM representation was lost. Importantly, we show that resetting, its neural marker, and the behavioral cost it entails, are specific to situations that involve a destruction of the objects-to-representations correspondence. Visual working memory (VWM) maintains task-relevant information in an online state. Previous studies showed that VWM representations are accessed and modified after changes in the environment. Here, we show that this updating process critically depends on an ongoing mapping between the

  4. Examining overlap in behavioral and neural representations of morals, facts, and preferences.

    Science.gov (United States)

    Theriault, Jordan; Waytz, Adam; Heiphetz, Larisa; Young, Liane

    2017-11-01

    Metaethical judgments refer to judgments about the information expressed by moral claims. Moral objectivists generally believe that moral claims are akin to facts, whereas moral subjectivists generally believe that moral claims are more akin to preferences. Evidence from developmental and social psychology has generally favored an objectivist view; however, this work has typically relied on few examples, and analyses have disallowed statistical generalizations beyond these few stimuli. The present work addresses whether morals are represented as fact-like or preference-like, using behavioral and neuroimaging methods, in combination with statistical techniques that can (a) generalize beyond our sample stimuli, and (b) test whether particular item features are associated with neural activity. Behaviorally, and contrary to prior work, morals were perceived as more preference-like than fact-like. Neurally, morals and preferences elicited common magnitudes and spatial patterns of activity, particularly within the dorsal-medial prefrontal cortex (DMPFC), a critical region for social cognition. This common DMPFC activity for morals and preferences was present across whole-brain conjunctions, and in individually localized functional regions of interest (targeting the theory of mind network). By contrast, morals and facts did not elicit any neural activity in common. Follow-up item analyses suggested that the activity elicited in common by morals and preferences was explained by their shared tendency to evoke representations of mental states. We conclude that morals are represented as far more subjective than prior work has suggested. This conclusion is consistent with recent theoretical research, which has argued that morality is fundamentally about regulating social relationships. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  5. Neural changes associated with semantic processing in healthy aging despite intact behavioral performance.

    Science.gov (United States)

    Lacombe, Jacinthe; Jolicoeur, Pierre; Grimault, Stephan; Pineault, Jessica; Joubert, Sven

    2015-10-01

    Semantic memory recruits an extensive neural network including the left inferior prefrontal cortex (IPC) and the left temporoparietal region, which are involved in semantic control processes, as well as the anterior temporal lobe region (ATL) which is considered to be involved in processing semantic information at a central level. However, little is known about the underlying neuronal integrity of the semantic network in normal aging. Young and older healthy adults carried out a semantic judgment task while their cortical activity was recorded using magnetoencephalography (MEG). Despite equivalent behavioral performance, young adults activated the left IPC to a greater extent than older adults, while the latter group recruited the temporoparietal region bilaterally and the left ATL to a greater extent than younger adults. Results indicate that significant neuronal changes occur in normal aging, mainly in regions underlying semantic control processes, despite an apparent stability in performance at the behavioral level. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Gender effects and sexual-orientation impact on androstadienone-evoked behavior and neural processing

    Directory of Open Access Journals (Sweden)

    Jacqueline eKrajnik

    2014-07-01

    Full Text Available In humans, the most established and investigated substance acting as a chemosignal, i.e., a substance that is excreted from the body, is 4,16-androstadien-3-one (AND. AND, which is found in sweat and saliva, is known to be responsible for influencing several variables, such as psychophysiological status, behavior, as well as cortical processing. The aim of the present review is to give insight into the variety of AND effects, with special regard to specific cross-sexual characteristics of this putative human chemosignal, emphasizing the neural activation patterns and factors such as contextual conditions. This review highlights the importance of including those contributing factors into the analysis of behavioral as well as brain-related studies.

  7. Bridging the Gap: Towards a Cell-Type Specific Understanding of Neural Circuits Underlying Fear Behaviors

    Science.gov (United States)

    McCullough, KM; Morrison, FG; Ressler, KJ

    2016-01-01

    Fear and anxiety-related disorders are remarkably common and debilitating, and are often characterized by dysregulated fear responses. Rodent models of fear learning and memory have taken great strides towards elucidating the specific neuronal circuitries underlying the learning of fear responses. The present review addresses recent research utilizing optogenetic approaches to parse circuitries underlying fear behaviors. It also highlights the powerful advances made when optogenetic techniques are utilized in a genetically defined, cell-type specific, manner. The application of next-generation genetic and sequencing approaches in a cell-type specific context will be essential for a mechanistic understanding of the neural circuitry underlying fear behavior and for the rational design of targeted, circuit specific, pharmacologic interventions for the treatment and prevention of fear-related disorders. PMID:27470092

  8. Modeling the behavioral substrates of associate learning and memory - Adaptive neural models

    Science.gov (United States)

    Lee, Chuen-Chien

    1991-01-01

    Three adaptive single-neuron models based on neural analogies of behavior modification episodes are proposed, which attempt to bridge the gap between psychology and neurophysiology. The proposed models capture the predictive nature of Pavlovian conditioning, which is essential to the theory of adaptive/learning systems. The models learn to anticipate the occurrence of a conditioned response before the presence of a reinforcing stimulus when training is complete. Furthermore, each model can find the most nonredundant and earliest predictor of reinforcement. The behavior of the models accounts for several aspects of basic animal learning phenomena in Pavlovian conditioning beyond previous related models. Computer simulations show how well the models fit empirical data from various animal learning paradigms.

  9. Directed differentiation of porcine epiblast-derived neural progenitor cells into neurons and glia

    DEFF Research Database (Denmark)

    Rasmussen, Mikkel Aabech; Hall, Vanessa Jane; Carter, T.F.

    2011-01-01

    Neural progenitor cells (NPCs) are promising candidates for cell-based therapy of neurodegenerative diseases; however, safety concerns must be addressed through transplantation studies in large animal models, such as the pig. The aim of this study was to derive NPCs from porcine blastocysts...

  10. Characterization of calcium responses and electrical activity in differentiating mouse neural progenitor cells in vitro

    NARCIS (Netherlands)

    de Groot, Martje W G D M; Dingemans, Milou M L; Rus, Katinka H; de Groot, Aart; Westerink, Remco H S

    In vitro methods for developmental neurotoxicity (DNT) testing have the potential to reduce animal use and increase insight into cellular and molecular mechanisms underlying chemical-induced alterations in the development of functional neuronal networks. Mouse neural progenitor cells (mNPCs)

  11. Application of the differential neural network observer to the kinetic parameters identification of the anthracene degradation in contaminated model soil

    Energy Technology Data Exchange (ETDEWEB)

    Poznyak, Tatyana [Superior School of Chemical Engineering, National Polytechnic Institute of Mexico (ESIQIE-IPN), Edif. 7, UPALM, C.P. 07738, Mexico D.F. (Mexico)]. E-mail: tpoznyak@ipn.mx; Garcia, Alejandro [Department of Automatic Control, CINVESTAV-IPN, Av. Instituto Politecnico Nacional, Col. San Pedro Zacatenco, C.P. 07360, Mexico D.F. (Mexico); Chairez, Isaac [Department of Automatic Control, CINVESTAV-IPN, Av. Instituto Politecnico Nacional, Col. San Pedro Zacatenco, C.P. 07360, Mexico D.F. (Mexico); Gomez, Miriam [Superior School of Chemical Engineering, National Polytechnic Institute of Mexico (ESIQIE-IPN), Edif. 7, UPALM, C.P. 07738, Mexico D.F. (Mexico); Poznyak, Alexander [Department of Automatic Control, CINVESTAV-IPN, Av. Instituto Politecnico Nacional, Col. San Pedro Zacatenco, C.P. 07360, Mexico D.F. (Mexico)]. E-mail: apoznyak@ctrl.cinvestav.mx

    2007-07-31

    In this work a new technique dealing with differential neural network observer (DNNO), which is related with differential neural networks (DNN) approach, is applied to estimate the anthracene dynamics decomposition and to identify the kinetic parameters in a contaminated model soil treatment by simple ozonation. To obtain the experimental data set, the model soil (sand) is combined with an initial anthracene concentration of 3.24 mg/g and treated by ozone (with the ozone initial concentration 16 mg/L) during 90 min in a reactor by the 'fluid bed' principle. The anthracene degradation degree was controlled by UV-vis spectrophotometry and HPLC techniques. Based on the HPLC data, the obtained results confirm that anthracene may be decomposed completely in the solid phase by simple ozonation during 20 min and by-products of ozonation are started to be destroyed after 30 min of treatment. In the ozonation process the ozone concentration in the gas phase at the reactor outlet is registered by an ozone detector. The variation of this parameter is used to obtain the summary characteristic curve of the anthracene ozonation (ozonogram). Then, using the experimental decomposition dynamics of anthracene and the ozonogram, the proposed DNNO is trained to reconstruct the anthracene decomposition and to estimate the anthracene ozonation constant using the DNN technique and a modified Least Square method.

  12. Neural Differentiation in HDAC1-Depleted Cells Is Accompanied by Coilin Downregulation and the Accumulation of Cajal Bodies in Nucleoli.

    Science.gov (United States)

    Krejčí, Jana; Legartová, Soňa; Bártová, Eva

    2017-01-01

    Cajal bodies (CBs) are important compartments containing accumulated proteins that preferentially regulate RNA-related nuclear events, including splicing. Here, we studied the nuclear distribution pattern of CBs in neurogenesis. In adult brains, coilin was present at a high density, but CB formation was absent in the nuclei of the choroid plexus of the lateral ventricles. Cells of the adult hippocampus were characterized by a crescent-like morphology of coilin protein. We additionally observed a 70 kDa splice variant of coilin in adult mouse brains, which was different to embryonic brains and mouse pluripotent embryonic stem cells (mESCs), characterized by the 80 kDa standard variant of coilin. Here, we also showed that depletion of coilin is induced during neural differentiation and HDAC1 deficiency in mESCs caused coilin accumulation inside the fibrillarin-positive region of the nucleoli. A similar distribution pattern was observed in adult brain hippocampi, characterized by lower levels of both coilin and HDAC1. In summary, we observed that neural differentiation and HDAC1 deficiency lead to coilin depletion and coilin accumulation in body-like structures inside the nucleoli.

  13. Application of the differential neural network observer to the kinetic parameters identification of the anthracene degradation in contaminated model soil

    International Nuclear Information System (INIS)

    Poznyak, Tatyana; Garcia, Alejandro; Chairez, Isaac; Gomez, Miriam; Poznyak, Alexander

    2007-01-01

    In this work a new technique dealing with differential neural network observer (DNNO), which is related with differential neural networks (DNN) approach, is applied to estimate the anthracene dynamics decomposition and to identify the kinetic parameters in a contaminated model soil treatment by simple ozonation. To obtain the experimental data set, the model soil (sand) is combined with an initial anthracene concentration of 3.24 mg/g and treated by ozone (with the ozone initial concentration 16 mg/L) during 90 min in a reactor by the 'fluid bed' principle. The anthracene degradation degree was controlled by UV-vis spectrophotometry and HPLC techniques. Based on the HPLC data, the obtained results confirm that anthracene may be decomposed completely in the solid phase by simple ozonation during 20 min and by-products of ozonation are started to be destroyed after 30 min of treatment. In the ozonation process the ozone concentration in the gas phase at the reactor outlet is registered by an ozone detector. The variation of this parameter is used to obtain the summary characteristic curve of the anthracene ozonation (ozonogram). Then, using the experimental decomposition dynamics of anthracene and the ozonogram, the proposed DNNO is trained to reconstruct the anthracene decomposition and to estimate the anthracene ozonation constant using the DNN technique and a modified Least Square method

  14. Strategies for memory-based decision making: Modeling behavioral and neural signatures within a cognitive architecture.

    Science.gov (United States)

    Fechner, Hanna B; Pachur, Thorsten; Schooler, Lael J; Mehlhorn, Katja; Battal, Ceren; Volz, Kirsten G; Borst, Jelmer P

    2016-12-01

    How do people use memories to make inferences about real-world objects? We tested three strategies based on predicted patterns of response times and blood-oxygen-level-dependent (BOLD) responses: one strategy that relies solely on recognition memory, a second that retrieves additional knowledge, and a third, lexicographic (i.e., sequential) strategy, that considers knowledge conditionally on the evidence obtained from recognition memory. We implemented the strategies as computational models within the Adaptive Control of Thought-Rational (ACT-R) cognitive architecture, which allowed us to derive behavioral and neural predictions that we then compared to the results of a functional magnetic resonance imaging (fMRI) study in which participants inferred which of two cities is larger. Overall, versions of the lexicographic strategy, according to which knowledge about many but not all alternatives is searched, provided the best account of the joint patterns of response times and BOLD responses. These results provide insights into the interplay between recognition and additional knowledge in memory, hinting at an adaptive use of these two sources of information in decision making. The results highlight the usefulness of implementing models of decision making within a cognitive architecture to derive predictions on the behavioral and neural level. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Neural substrates and behavioral profiles of romantic jealousy and its temporal dynamics.

    Science.gov (United States)

    Sun, Yan; Yu, Hongbo; Chen, Jie; Liang, Jie; Lu, Lin; Zhou, Xiaolin; Shi, Jie

    2016-06-07

    Jealousy is not only a way of experiencing love but also a stabilizer of romantic relationships, although morbid romantic jealousy is maladaptive. Being engaged in a formal romantic relationship can tune one's romantic jealousy towards a specific target. Little is known about how the human brain processes romantic jealousy by now. Here, by combining scenario-based imagination and functional MRI, we investigated the behavioral and neural correlates of romantic jealousy and their development across stages (before vs. after being in a formal relationship). Romantic jealousy scenarios elicited activations primarily in the basal ganglia (BG) across stages, and were significantly higher after the relationship was established in both the behavioral rating and BG activation. The intensity of romantic jealousy was related to the intensity of romantic happiness, which mainly correlated with ventral medial prefrontal cortex activation. The increase in jealousy across stages was associated with the tendency for interpersonal aggression. These results bridge the gap between the theoretical conceptualization of romantic jealousy and its neural correlates and shed light on the dynamic changes in jealousy.

  16. The porous boundaries between explicit and implicit memory: behavioral and neural evidence.

    Science.gov (United States)

    Dew, Ilana T Z; Cabeza, Roberto

    2011-04-01

    Explicit memory refers to the conscious retrieval of past information or experiences, whereas implicit memory refers to an unintentional or nonconscious form of retrieval. Much of the literature in cognitive psychology and cognitive neuroscience has focused on differences between explicit and implicit memory, and the traditional view is that they rely on distinct brain systems. However, the potential interplay between implicit and explicit memory is not always clear. This review draws from behavioral and functional neuroimaging evidence to evaluate three areas in which implicit and explicit memory may be interrelated. First, we discuss views of familiarity-based recognition in terms of its relationship with implicit memory. Second, we review the challenges of distinguishing between implicit memory and involuntary aware memory, at both behavioral and neural levels. Finally, we examine evidence indicating that implicit and explicit retrieval of relational information may rely on a common neural mechanism. Taken together, these areas indicate that, under certain circumstances, there may be an important and influential relationship between conscious and nonconscious expressions of memory. © 2011 New York Academy of Sciences.

  17. Cognitive control in adolescence: neural underpinnings and relation to self-report behaviors.

    Directory of Open Access Journals (Sweden)

    Jessica R Andrews-Hanna

    Full Text Available Adolescence is commonly characterized by impulsivity, poor decision-making, and lack of foresight. However, the developmental neural underpinnings of these characteristics are not well established.To test the hypothesis that these adolescent behaviors are linked to under-developed proactive control mechanisms, the present study employed a hybrid block/event-related functional Magnetic Resonance Imaging (fMRI Stroop paradigm combined with self-report questionnaires in a large sample of adolescents and adults, ranging in age from 14 to 25. Compared to adults, adolescents under-activated a set of brain regions implicated in proactive top-down control across task blocks comprised of difficult and easy trials. Moreover, the magnitude of lateral prefrontal activity in adolescents predicted self-report measures of impulse control, foresight, and resistance to peer pressure. Consistent with reactive compensatory mechanisms to reduced proactive control, older adolescents exhibited elevated transient activity in regions implicated in response-related interference resolution.Collectively, these results suggest that maturation of cognitive control may be partly mediated by earlier development of neural systems supporting reactive control and delayed development of systems supporting proactive control. Importantly, the development of these mechanisms is associated with cognitive control in real-life behaviors.

  18. Neural substrates underlying effort, time, and risk-based decision making in motivated behavior.

    Science.gov (United States)

    Bailey, Matthew R; Simpson, Eleanor H; Balsam, Peter D

    2016-09-01

    All mobile organisms rely on adaptive motivated behavior to overcome the challenges of living in an environment in which essential resources may be limited. A variety of influences ranging from an organism's environment, experiential history, and physiological state all influence a cost-benefit analysis which allows motivation to energize behavior and direct it toward specific goals. Here we review the substantial amount of research aimed at discovering the interconnected neural circuits which allow organisms to carry-out the cost-benefit computations which allow them to behave in adaptive ways. We specifically focus on how the brain deals with different types of costs, including effort requirements, delays to reward and payoff riskiness. An examination of this broad literature highlights the importance of the extended neural circuits which enable organisms to make decisions about these different types of costs. This involves Cortical Structures, including the Anterior Cingulate Cortex (ACC), the Orbital Frontal Cortex (OFC), the Infralimbic Cortex (IL), and prelimbic Cortex (PL), as well as the Baso-Lateral Amygdala (BLA), the Nucleus Accumbens (NAcc), the Ventral Pallidal (VP), the Sub Thalamic Nucleus (STN) among others. Some regions are involved in multiple aspects of cost-benefit computations while the involvement of other regions is restricted to information relating to specific types of costs. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Behavioral and neural correlates of loss aversion and risk avoidance in adolescents and adults.

    Science.gov (United States)

    Barkley-Levenson, Emily E; Van Leijenhorst, Linda; Galván, Adriana

    2013-01-01

    Individuals are frequently faced with risky decisions involving the potential for both gain and loss. Exploring the role of both potential gains and potential losses in predicting risk taking is critical to understanding how adolescents and adults make the choice to engage in or avoid a real-life risk. This study aimed to examine the impact of potential losses as well as gains on adolescent decisions during risky choice in a laboratory task. Adolescent (n=18) and adult (n=16) participants underwent functional magnetic resonance imaging (fMRI) during a mixed gambles task, and completed questionnaires measuring real-world risk-taking behaviors. While potential loss had a significantly greater effect on choice than potential gain in both adolescents and adults and there were no behavioral group differences on the task, adolescents recruited significantly more frontostriatal circuitry than adults when choosing to reject a gamble. During risk-seeking behavior, adolescent activation in medial prefrontal cortex (mPFC) was negatively correlated with self-reported likelihood of risk taking. During risk-avoidant behavior, mPFC activation of in adults was negatively correlated with self-reported benefits of risk-taking. Taken together, these findings reflect different neural patterns during risk-taking and risk-avoidant behaviors in adolescents and adults. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Discovering Multimodal Behavior in Ms. Pac-Man through Evolution of Modular Neural Networks.

    Science.gov (United States)

    Schrum, Jacob; Miikkulainen, Risto

    2016-03-12

    Ms. Pac-Man is a challenging video game in which multiple modes of behavior are required: Ms. Pac-Man must escape ghosts when they are threats and catch them when they are edible, in addition to eating all pills in each level. Past approaches to learning behavior in Ms. Pac-Man have treated the game as a single task to be learned using monolithic policy representations. In contrast, this paper uses a framework called Modular Multi-objective NEAT (MM-NEAT) to evolve modular neural networks. Each module defines a separate behavior. The modules are used at different times according to a policy that can be human-designed (i.e. Multitask) or discovered automatically by evolution. The appropriate number of modules can be fixed or discovered using a genetic operator called Module Mutation. Several versions of Module Mutation are evaluated in this paper. Both fixed modular networks and Module Mutation networks outperform monolithic networks and Multitask networks. Interestingly, the best networks dedicate modules to critical behaviors (such as escaping when surrounded after luring ghosts near a power pill) that do not follow the customary division of the game into chasing edible and escaping threat ghosts. The results demonstrate that MM-NEAT can discover interesting and effective behavior for agents in challenging games.

  1. Behavioral and neural plasticity caused by early social experiences: the case of the honeybee

    Directory of Open Access Journals (Sweden)

    Andrés eArenas

    2013-08-01

    Full Text Available Cognitive experiences during the early stages of life play an important role in shaping future behavior. Behavioral and neural long-term changes after early sensory and associative experiences have been recently reported in the honeybee. This invertebrate is an excellent model for assessing the role of precocious experiences on later behavior due to its extraordinarily tuned division of labor based on age polyethism. These studies are mainly focused on the role and importance of experiences occurred during the first days of the adult lifespan, their impact on foraging decisions and their contribution to coordinate food gathering. Odor-rewarded experiences during the first days of honeybee adulthood alter the responsiveness to sucrose, making young hive bees more sensitive to assess gustatory features about the nectar brought back to the hive and affecting the dynamic of the food transfers and the propagation of food-related information within the colony as well. Early olfactory experiences lead to stable and long-term associative memories that can be successfully recalled after many days, even at foraging ages. Also they improve memorizing of new associative learning events later in life. The establishment of early memories promotes stable reorganization of the olfactory circuits inducing structural and functional changes in the antennal lobe. Early rewarded experiences have relevant consequences at the social level too, biasing dance and trophallaxis partner choice and affecting recruitment. Here, we revised recent results in bees´ physiology, behavior and sociobiology to depict how the early experiences affect their cognition abilities and neural-related circuits.

  2. Seeing Jesus in toast: neural and behavioral correlates of face pareidolia.

    Science.gov (United States)

    Liu, Jiangang; Li, Jun; Feng, Lu; Li, Ling; Tian, Jie; Lee, Kang

    2014-04-01

    Face pareidolia is the illusory perception of non-existent faces. The present study, for the first time, contrasted behavioral and neural responses of face pareidolia with those of letter pareidolia to explore face-specific behavioral and neural responses during illusory face processing. Participants were shown pure-noise images but were led to believe that 50% of them contained either faces or letters; they reported seeing faces or letters illusorily 34% and 38% of the time, respectively. The right fusiform face area (rFFA) showed a specific response when participants "saw" faces as opposed to letters in the pure-noise images. Behavioral responses during face pareidolia produced a classification image (CI) that resembled a face, whereas those during letter pareidolia produced a CI that was letter-like. Further, the extent to which such behavioral CIs resembled faces was directly related to the level of face-specific activations in the rFFA. This finding suggests that the rFFA plays a specific role not only in processing of real faces but also in illusory face perception, perhaps serving to facilitate the interaction between bottom-up information from the primary visual cortex and top-down signals from the prefrontal cortex (PFC). Whole brain analyses revealed a network specialized in face pareidolia, including both the frontal and occipitotemporal regions. Our findings suggest that human face processing has a strong top-down component whereby sensory input with even the slightest suggestion of a face can result in the interpretation of a face. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Dynamical Integration of Language and Behavior in a Recurrent Neural Network for Human--Robot Interaction

    Directory of Open Access Journals (Sweden)

    Tatsuro Yamada

    2016-07-01

    Full Text Available To work cooperatively with humans by using language, robots must not only acquire a mapping between language and their behavior but also autonomously utilize the mapping in appropriate contexts of interactive tasks online. To this end, we propose a novel learning method linking language to robot behavior by means of a recurrent neural network. In this method, the network learns from correct examples of the imposed task that are given not as explicitly separated sets of language and behavior but as sequential data constructed from the actual temporal flow of the task. By doing this, the internal dynamics of the network models both language--behavior relationships and the temporal patterns of interaction. Here, ``internal dynamics'' refers to the time development of the system defined on the fixed-dimensional space of the internal states of the context layer. Thus, in the execution phase, by constantly representing where in the interaction context it is as its current state, the network autonomously switches between recognition and generation phases without any explicit signs and utilizes the acquired mapping in appropriate contexts. To evaluate our method, we conducted an experiment in which a robot generates appropriate behavior responding to a human's linguistic instruction. After learning, the network actually formed the attractor structure representing both language--behavior relationships and the task's temporal pattern in its internal dynamics. In the dynamics, language--behavior mapping was achieved by the branching structure. Repetition of human's instruction and robot's behavioral response was represented as the cyclic structure, and besides, waiting to a subsequent instruction was represented as the fixed-point attractor. Thanks to this structure, the robot was able to interact online with a human concerning the given task by autonomously switching phases.

  4. Dynamical Integration of Language and Behavior in a Recurrent Neural Network for Human-Robot Interaction.

    Science.gov (United States)

    Yamada, Tatsuro; Murata, Shingo; Arie, Hiroaki; Ogata, Tetsuya

    2016-01-01

    To work cooperatively with humans by using language, robots must not only acquire a mapping between language and their behavior but also autonomously utilize the mapping in appropriate contexts of interactive tasks online. To this end, we propose a novel learning method linking language to robot behavior by means of a recurrent neural network. In this method, the network learns from correct examples of the imposed task that are given not as explicitly separated sets of language and behavior but as sequential data constructed from the actual temporal flow of the task. By doing this, the internal dynamics of the network models both language-behavior relationships and the temporal patterns of interaction. Here, "internal dynamics" refers to the time development of the system defined on the fixed-dimensional space of the internal states of the context layer. Thus, in the execution phase, by constantly representing where in the interaction context it is as its current state, the network autonomously switches between recognition and generation phases without any explicit signs and utilizes the acquired mapping in appropriate contexts. To evaluate our method, we conducted an experiment in which a robot generates appropriate behavior responding to a human's linguistic instruction. After learning, the network actually formed the attractor structure representing both language-behavior relationships and the task's temporal pattern in its internal dynamics. In the dynamics, language-behavior mapping was achieved by the branching structure. Repetition of human's instruction and robot's behavioral response was represented as the cyclic structure, and besides, waiting to a subsequent instruction was represented as the fixed-point attractor. Thanks to this structure, the robot was able to interact online with a human concerning the given task by autonomously switching phases.

  5. Ferulic acid promotes survival and differentiation of neural stem cells to prevent gentamicin-induced neuronal hearing loss.

    Science.gov (United States)

    Gu, Lintao; Cui, Xinhua; Wei, Wei; Yang, Jia; Li, Xuezhong

    2017-11-15

    Neural stem cells (NSCs) have exhibited promising potential in therapies against neuronal hearing loss. Ferulic acid (FA) has been widely reported to enhance neurogenic differentiation of different stem cells. We investigated the role of FA in promoting NSC transplant therapy to prevent gentamicin-induced neuronal hearing loss. NSCs were isolated from mouse cochlear tissues to establish in vitro culture, which were then treated with FA. The survival and differentiation of NSCs were evaluated. Subsequently, neurite outgrowth and excitability of the in vitro neuronal network were assessed. Gentamicin was used to induce neuronal hearing loss in mice, in the presence and absence of FA, followed by assessments of auditory brainstem response (ABR) and distortion product optoacoustic emissions (DPOAE) amplitude. FA promoted survival, neurosphere formation and differentiation of NSCs, as well as neurite outgrowth and excitability of in vitro neuronal network. Furthermore, FA restored ABR threshold shifts and DPOAE in gentamicin-induced neuronal hearing loss mouse model in vivo. Our data, for the first time, support potential therapeutic efficacy of FA in promoting survival and differentiation of NSCs to prevent gentamicin-induced neuronal hearing loss. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Who can you trust? Behavioral and neural differences between perceptual and memory-based influences

    Directory of Open Access Journals (Sweden)

    John D Rudoy

    2009-08-01

    Full Text Available Decisions about whether to trust someone can be influenced by competing sources of information, such as analysis of facial features versus remembering specific information about the person. We hypothesized that such sources can differentially influence trustworthiness judgments depending on the circumstances in which judgments are made. In our experiments, subjects first learned face-word associations. Stimuli were trustworthy and untrustworthy faces selected on the basis of consensus judgments and personality attributes that carried either the same valence (consistent with face or the opposite valence (inconsistent with face. Subsequently, subjects rated the trustworthiness of each face. Both learned and perceptual information influenced ratings, but learned information was less influential under speeded than under non-speeded conditions. EEG data further revealed neural evidence of the processing of these two competing sources. Perceptual influences were apparent earlier than memory influences, substantiating the conclusion that time pressure can selectively disrupt memory retrieval relevant to trustworthiness attributions.

  7. The predator and prey behaviors of crabs: from ecology to neural adaptations.

    Science.gov (United States)

    Tomsic, Daniel; Sztarker, Julieta; Berón de Astrada, Martín; Oliva, Damián; Lanza, Estela

    2017-07-01

    Predator avoidance and prey capture are among the most vital of animal behaviors. They require fast reactions controlled by comparatively straightforward neural circuits often containing giant neurons, which facilitates their study with electrophysiological techniques. Naturally occurring avoidance behaviors, in particular, can be easily and reliably evoked in the laboratory, enabling their neurophysiological investigation. Studies in the laboratory alone, however, can lead to a biased interpretation of an animal's behavior in its natural environment. In this Review, we describe current knowledge - acquired through both laboratory and field studies - on the visually guided escape behavior of the crab Neohelice granulata Analyses of the behavioral responses to visual stimuli in the laboratory have revealed the main characteristics of the crab's performance, such as the continuous regulation of the speed and direction of the escape run, or the enduring changes in the strength of escape induced by learning and memory. This work, in combination with neuroanatomical and electrophysiological studies, has allowed the identification of various giant neurons, the activity of which reflects most essential aspects of the crabs' avoidance performance. In addition, behavioral analyses performed in the natural environment reveal a more complex picture: crabs make use of much more information than is usually available in laboratory studies. Moreover, field studies have led to the discovery of a robust visually guided chasing behavior in Neohelice Here, we describe similarities and differences in the results obtained between the field and the laboratory, discuss the sources of any differences and highlight the importance of combining the two approaches. © 2017. Published by The Company of Biologists Ltd.

  8. Functional Roles of Neural Preparatory Processes in a Cued Stroop Task Revealed by Linking Electrophysiology with Behavioral Performance.

    Science.gov (United States)

    Wang, Chao; Ding, Mingzhou; Kluger, Benzi M

    2015-01-01

    It is well established that cuing facilitates behavioral performance and that different aspects of instructional cues evoke specific neural preparatory processes in cued task-switching paradigms. To deduce the functional role of these neural preparatory processes the majority of studies vary aspects of the experimental paradigm and describe how these variations alter markers of neural preparatory processes. Although these studies provide important insights, they also have notable limitations, particularly in terms of understanding the causal or functional relationship of neural markers to cognitive and behavioral processes. In this study, we sought to address these limitations and uncover the functional roles of neural processes by examining how variability in the amplitude of neural preparatory processes predicts behavioral performance to subsequent stimuli. To achieve this objective 16 young adults were recruited to perform a cued Stroop task while their brain activity was measured using high-density electroencephalography. Four temporally overlapping but functionally and topographically distinct cue-triggered event related potentials (ERPs) were identified: 1) A left-frontotemporal negativity (250-700 ms) that was positively associated with word-reading performance; 2) a midline-frontal negativity (450-800 ms) that was positively associated with color-naming and incongruent performance; 3) a left-frontal negativity (450-800 ms) that was positively associated with switch trial performance; and 4) a centroparietal positivity (450-800 ms) that was positively associated with performance for almost all trial types. These results suggest that at least four dissociable cognitive processes are evoked by instructional cues in the present task, including: 1) domain-specific task facilitation; 2) switch-specific task-set reconfiguration; 3) preparation for response conflict; and 4) proactive attentional control. Examining the relationship between ERPs and behavioral

  9. Functional Roles of Neural Preparatory Processes in a Cued Stroop Task Revealed by Linking Electrophysiology with Behavioral Performance.

    Directory of Open Access Journals (Sweden)

    Chao Wang

    Full Text Available It is well established that cuing facilitates behavioral performance and that different aspects of instructional cues evoke specific neural preparatory processes in cued task-switching paradigms. To deduce the functional role of these neural preparatory processes the majority of studies vary aspects of the experimental paradigm and describe how these variations alter markers of neural preparatory processes. Although these studies provide important insights, they also have notable limitations, particularly in terms of understanding the causal or functional relationship of neural markers to cognitive and behavioral processes. In this study, we sought to address these limitations and uncover the functional roles of neural processes by examining how variability in the amplitude of neural preparatory processes predicts behavioral performance to subsequent stimuli. To achieve this objective 16 young adults were recruited to perform a cued Stroop task while their brain activity was measured using high-density electroencephalography. Four temporally overlapping but functionally and topographically distinct cue-triggered event related potentials (ERPs were identified: 1 A left-frontotemporal negativity (250-700 ms that was positively associated with word-reading performance; 2 a midline-frontal negativity (450-800 ms that was positively associated with color-naming and incongruent performance; 3 a left-frontal negativity (450-800 ms that was positively associated with switch trial performance; and 4 a centroparietal positivity (450-800 ms that was positively associated with performance for almost all trial types. These results suggest that at least four dissociable cognitive processes are evoked by instructional cues in the present task, including: 1 domain-specific task facilitation; 2 switch-specific task-set reconfiguration; 3 preparation for response conflict; and 4 proactive attentional control. Examining the relationship between ERPs and behavioral

  10. Asymptotic behavior of solutions of linear multi-order fractional differential equation systems

    OpenAIRE

    Diethelm, Kai; Siegmund, Stefan; Tuan, H. T.

    2017-01-01

    In this paper, we investigate some aspects of the qualitative theory for multi-order fractional differential equation systems. First, we obtain a fundamental result on the existence and uniqueness for multi-order fractional differential equation systems. Next, a representation of solutions of homogeneous linear multi-order fractional differential equation systems in series form is provided. Finally, we give characteristics regarding the asymptotic behavior of solutions to some classes of line...

  11. Differential expression of the neural cell adhesion molecule NCAM 140 in human pituitary tumors

    OpenAIRE

    Aletsee-Ufrecht, M. C.; Langley, O. K.; Gratzl, O.; Gratzl, Manfred

    1990-01-01

    We have analyzed the expression of the intracellular marker protein neuron specific enolase (NSE), synaptophysin (SYN) and of the cell surface marker NCAM (neural cell adhesion molecule) in both normal human hypophysis and in pituitary adenomas in order to explore their potential use as diagnostic tools. All adenomas (4 prolactinomas, 3 growth hormone (GH) producing adenomas and 4 inactive adenomas) showed SYN and NSE immunoreactivity on tissue sections and this was confirmed by immunoblots. ...

  12. High glucose suppresses embryonic stem cell differentiation into neural lineage cells

    OpenAIRE

    Yang, Penghua; Shen, Wei-bin; Reece, E. Albert; Chen, Xi; Yang, Peixin

    2016-01-01

    Abnormal neurogenesis occurs during embryonic development in human diabetic pregnancies and in animal models of diabetic embryopathy. Our previous studies in a mouse model of diabetic embryopathy have implicated that high glucose of maternal diabetes delays neurogenesis in the developing neuroepithelium leading to neural tube defects. However, the underlying process in high glucose-impaired neurogenesis is uncharacterized. Neurogenesis from embryonic stem (ES) cells provides a valuable model ...

  13. Linear-quadratic control and quadratic differential forms for multidimensional behaviors

    NARCIS (Netherlands)

    Napp, D.; Trentelman, H.L.

    2011-01-01

    This paper deals with systems described by constant coefficient linear partial differential equations (nD-systems) from a behavioral point of view. In this context we treat the linear-quadratic control problem where the performance functional is the integral of a quadratic differential form. We look

  14. Asymptotic behavior and stability of second order neutral delay differential equations

    NARCIS (Netherlands)

    Chen, G.L.; van Gaans, O.W.; Verduyn Lunel, Sjoerd

    2014-01-01

    We study the asymptotic behavior of a class of second order neutral delay differential equations by both a spectral projection method and an ordinary differential equation method approach. We discuss the relation of these two methods and illustrate some features using examples. Furthermore, a fixed

  15. Impact of adolescent social experiences on behavior and neural circuits implicated in mental illnesses.

    Science.gov (United States)

    Burke, Andrew R; McCormick, Cheryl M; Pellis, Sergio M; Lukkes, Jodi L

    2017-05-01

    Negative social experiences during adolescence are central features for several stress-related mental illnesses. Social play fighting behavior in rats peaks during early adolescence and is essential for the final maturation of brain and behavior. Manipulation of the rat adolescent social experience alters many neurobehavioral measurements implicated in anxiety, depression, and substance abuse. In this review, we will highlight the importance of social play and the use of three separate social stress models (isolation-rearing, social defeat, and social instability stress) to disrupt the acquisition of this adaptive behavior. Social stress during adolescence leads to the development of anxiety and depressive behavior as well as escalated drug use in adulthood. Furthermore, sex- and age-dependent effects on the hormonal stress response following adolescent social stress are also observed. Finally, manipulation of the social experience during adolescence alters stress-related neural circuits and monoaminergic systems. Overall, positive social experiences among age-matched conspecifics during rat adolescence are critical for healthy neurobehavioral maturation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Chaotic Behavior of a Generalized Sprott E Differential System

    Science.gov (United States)

    Oliveira, Regilene; Valls, Claudia

    A chaotic system with only one equilibrium, a stable node-focus, was introduced by Wang and Chen [2012]. This system was found by adding a nonzero constant b to the Sprott E system [Sprott, 1994]. The coexistence of three types of attractors in this autonomous system was also considered by Braga and Mello [2013]. Adding a second parameter to the Sprott E differential system, we get the autonomous system ẋ = ayz + b,ẏ = x2 - y,ż = 1 - 4x, where a,b ∈ ℝ are parameters and a≠0. In this paper, we consider theoretically some global dynamical aspects of this system called here the generalized Sprott E differential system. This polynomial differential system is relevant because it is the first polynomial differential system in ℝ3 with two parameters exhibiting, besides the point attractor and chaotic attractor, coexisting stable limit cycles, demonstrating that this system is truly complicated and interesting. More precisely, we show that for b sufficiently small this system can exhibit two limit cycles emerging from the classical Hopf bifurcation at the equilibrium point p = (1/4, 1/16, 0). We also give a complete description of its dynamics on the Poincaré sphere at infinity by using the Poincaré compactification of a polynomial vector field in ℝ3, and we show that it has no first integrals in the class of Darboux functions.

  17. Asymptotic behavior of solutions of forced fractional differential equations

    Directory of Open Access Journals (Sweden)

    Said Grace

    2016-09-01

    where $y(t=\\left( a(tx^{\\prime }(t\\right ^{\\prime }$, $c_{0}=\\frac{y(c}{\\Gamma (1}=y(c$, and $c_{0}$ is a real constant. The technique used in obtaining their results will apply to related fractional differential equations with Caputo derivatives of any order. Examples illustrate the results obtained in this paper.

  18. Sensorimotor learning biases choice behavior: a learning neural field model for decision making.

    Directory of Open Access Journals (Sweden)

    Christian Klaes

    Full Text Available According to a prominent view of sensorimotor processing in primates, selection and specification of possible actions are not sequential operations. Rather, a decision for an action emerges from competition between different movement plans, which are specified and selected in parallel. For action choices which are based on ambiguous sensory input, the frontoparietal sensorimotor areas are considered part of the common underlying neural substrate for selection and specification of action. These areas have been shown capable of encoding alternative spatial motor goals in parallel during movement planning, and show signatures of competitive value-based selection among these goals. Since the same network is also involved in learning sensorimotor associations, competitive action selection (decision making should not only be driven by the sensory evidence and expected reward in favor of either action, but also by the subject's learning history of different sensorimotor associations. Previous computational models of competitive neural decision making used predefined associations between sensory input and corresponding motor output. Such hard-wiring does not allow modeling of how decisions are influenced by sensorimotor learning or by changing reward contingencies. We present a dynamic neural field model which learns arbitrary sensorimotor associations with a reward-driven Hebbian learning algorithm. We show that the model accurately simulates the dynamics of action selection with different reward contingencies, as observed in monkey cortical recordings, and that it correctly predicted the pattern of choice errors in a control experiment. With our adaptive model we demonstrate how network plasticity, which is required for association learning and adaptation to new reward contingencies, can influence choice behavior. The field model provides an integrated and dynamic account for the operations of sensorimotor integration, working memory and action

  19. Mindfulness training applied to addiction therapy: insights into the neural mechanisms of positive behavioral change

    Directory of Open Access Journals (Sweden)

    Garl

    2016-07-01

    Full Text Available Eric L Garland,1,2 Matthew O Howard,3 Sarah E Priddy,1 Patrick A McConnell,4 Michael R Riquino,1 Brett Froeliger4 1College of Social Work, 2Hunstsman Cancer Institute, University of Utah, Salt Lake City, UT, USA; 3School of Social Work, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 4Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA Abstract: Dual-process models from neuroscience suggest that addiction is driven by dysregulated interactions between bottom-up neural processes underpinning reward learning and top-down neural functions subserving executive function. Over time, drug use causes atrophy in prefrontally mediated cognitive control networks and hijacks striatal circuits devoted to processing natural rewards in service of compulsive seeking of drug-related reward. In essence, mindfulness-based interventions (MBIs can be conceptualized as mental training programs for exercising, strengthening, and remediating these functional brain networks. This review describes how MBIs may remediate addiction by regulating frontostriatal circuits, thereby restoring an adaptive balance between these top-down and bottom-up processes. Empirical evidence is presented suggesting that MBIs facilitate cognitive control over drug-related automaticity, attentional bias, and drug cue reactivity, while enhancing responsiveness to natural rewards. Findings from the literature are incorporated into an integrative account of the neural mechanisms of mindfulness-based therapies for effecting positive behavior change in the context of addiction recovery. Implications of our theoretical framework are presented with respect to how these insights can inform the addiction therapy process. Keywords: mindfulness, frontostriatal, savoring, cue reactivity, hedonic dysregulation, reward, addiction

  20. White blood cell differential count of maturation stages in bone marrow smear using dual-stage convolutional neural networks.

    Science.gov (United States)

    Choi, Jin Woo; Ku, Yunseo; Yoo, Byeong Wook; Kim, Jung-Ah; Lee, Dong Soon; Chai, Young Jun; Kong, Hyoun-Joong; Kim, Hee Chan

    2017-01-01

    The white blood cell differential count of the bone marrow provides information concerning the distribution of immature and mature cells within maturation stages. The results of such examinations are important for the diagnosis of various diseases and for follow-up care after chemotherapy. However, manual, labor-intensive methods to determine the differential count lead to inter- and intra-variations among the results obtained by hematologists. Therefore, an automated system to conduct the white blood cell differential count is highly desirable, but several difficulties hinder progress. There are variations in the white blood cells of each maturation stage, small inter-class differences within each stage, and variations in images because of the different acquisition and staining processes. Moreover, a large number of classes need to be classified for bone marrow smear analysis, and the high density of touching cells in bone marrow smears renders difficult the segmentation of single cells, which is crucial to traditional image processing and machine learning. Few studies have attempted to discriminate bone marrow cells, and even these have either discriminated only a few classes or yielded insufficient performance. In this study, we propose an automated white blood cell differential counting system from bone marrow smear images using a dual-stage convolutional neural network (CNN). A total of 2,174 patch images were collected for training and testing. The dual-stage CNN classified images into 10 classes of the myeloid and erythroid maturation series, and achieved an accuracy of 97.06%, a precision of 97.13%, a recall of 97.06%, and an F-1 score of 97.1%. The proposed method not only showed high classification performance, but also successfully classified raw images without single cell segmentation and manual feature extraction by implementing CNN. Moreover, it demonstrated rotation and location invariance. These results highlight the promise of the proposed method

  1. White blood cell differential count of maturation stages in bone marrow smear using dual-stage convolutional neural networks

    Science.gov (United States)

    Choi, Jin Woo; Ku, Yunseo; Yoo, Byeong Wook; Kim, Jung-Ah; Lee, Dong Soon; Chai, Young Jun; Kong, Hyoun-Joong

    2017-01-01

    The white blood cell differential count of the bone marrow provides information concerning the distribution of immature and mature cells within maturation stages. The results of such examinations are important for the diagnosis of various diseases and for follow-up care after chemotherapy. However, manual, labor-intensive methods to determine the differential count lead to inter- and intra-variations among the results obtained by hematologists. Therefore, an automated system to conduct the white blood cell differential count is highly desirable, but several difficulties hinder progress. There are variations in the white blood cells of each maturation stage, small inter-class differences within each stage, and variations in images because of the different acquisition and staining processes. Moreover, a large number of classes need to be classified for bone marrow smear analysis, and the high density of touching cells in bone marrow smears renders difficult the segmentation of single cells, which is crucial to traditional image processing and machine learning. Few studies have attempted to discriminate bone marrow cells, and even these have either discriminated only a few classes or yielded insufficient performance. In this study, we propose an automated white blood cell differential counting system from bone marrow smear images using a dual-stage convolutional neural network (CNN). A total of 2,174 patch images were collected for training and testing. The dual-stage CNN classified images into 10 classes of the myeloid and erythroid maturation series, and achieved an accuracy of 97.06%, a precision of 97.13%, a recall of 97.06%, and an F-1 score of 97.1%. The proposed method not only showed high classification performance, but also successfully classified raw images without single cell segmentation and manual feature extraction by implementing CNN. Moreover, it demonstrated rotation and location invariance. These results highlight the promise of the proposed method

  2. White blood cell differential count of maturation stages in bone marrow smear using dual-stage convolutional neural networks.

    Directory of Open Access Journals (Sweden)

    Jin Woo Choi

    Full Text Available The white blood cell differential count of the bone marrow provides information concerning the distribution of immature and mature cells within maturation stages. The results of such examinations are important for the diagnosis of various diseases and for follow-up care after chemotherapy. However, manual, labor-intensive methods to determine the differential count lead to inter- and intra-variations among the results obtained by hematologists. Therefore, an automated system to conduct the white blood cell differential count is highly desirable, but several difficulties hinder progress. There are variations in the white blood cells of each maturation stage, small inter-class differences within each stage, and variations in images because of the different acquisition and staining processes. Moreover, a large number of classes need to be classified for bone marrow smear analysis, and the high density of touching cells in bone marrow smears renders difficult the segmentation of single cells, which is crucial to traditional image processing and machine learning. Few studies have attempted to discriminate bone marrow cells, and even these have either discriminated only a few classes or yielded insufficient performance. In this study, we propose an automated white blood cell differential counting system from bone marrow smear images using a dual-stage convolutional neural network (CNN. A total of 2,174 patch images were collected for training and testing. The dual-stage CNN classified images into 10 classes of the myeloid and erythroid maturation series, and achieved an accuracy of 97.06%, a precision of 97.13%, a recall of 97.06%, and an F-1 score of 97.1%. The proposed method not only showed high classification performance, but also successfully classified raw images without single cell segmentation and manual feature extraction by implementing CNN. Moreover, it demonstrated rotation and location invariance. These results highlight the promise of

  3. Deep Learning with Convolutional Neural Network for Differentiation of Liver Masses at Dynamic Contrast-enhanced CT: A Preliminary Study.

    Science.gov (United States)

    Yasaka, Koichiro; Akai, Hiroyuki; Abe, Osamu; Kiryu, Shigeru

    2018-03-01

    Purpose To investigate diagnostic performance by using a deep learning method with a convolutional neural network (CNN) for the differentiation of liver masses at dynamic contrast agent-enhanced computed tomography (CT). Materials and Methods This clinical retrospective study used CT image sets of liver masses over three phases (noncontrast-agent enhanced, arterial, and delayed). Masses were diagnosed according to five categories (category A, classic hepatocellular carcinomas [HCCs]; category B, malignant liver tumors other than classic and early HCCs; category C, indeterminate masses or mass-like lesions [including early HCCs and dysplastic nodules] and rare benign liver masses other than hemangiomas and cysts; category D, hemangiomas; and category E, cysts). Supervised training was performed by using 55 536 image sets obtained in 2013 (from 460 patients, 1068 sets were obtained and they were augmented by a factor of 52 [rotated, parallel-shifted, strongly enlarged, and noise-added images were generated from the original images]). The CNN was composed of six convolutional, three maximum pooling, and three fully connected layers. The CNN was tested with 100 liver mass image sets obtained in 2016 (74 men and 26 women; mean age, 66.4 years ± 10.6 [standard deviation]; mean mass size, 26.9 mm ± 25.9; 21, nine, 35, 20, and 15 liver masses for categories A, B, C, D, and E, respectively). Training and testing were performed five times. Accuracy for categorizing liver masses with CNN model and the area under receiver operating characteristic curve for differentiating categories A-B versus categories C-E were calculated. Results Median accuracy of differential diagnosis of liver masses for test data were 0.84. Median area under the receiver operating characteristic curve for differentiating categories A-B from C-E was 0.92. Conclusion Deep learning with CNN showed high diagnostic performance in differentiation of liver masses at dynamic CT. © RSNA, 2017 Online

  4. Distal C terminus of CaV1.2 channels plays a crucial role in the neural differentiation of dental pulp stem cells.

    Directory of Open Access Journals (Sweden)

    Jianping Ge

    Full Text Available L-type voltage-dependent CaV1.2 channels play an important role in the maintenance of intracellular calcium homeostasis, and influence multiple cellular processes. C-terminal cleavage of CaV1.2 channels was reported in several types of excitable cells, but its expression and possible roles in non-excitable cells is still not clear. The aim of this study was to determine whether distal C-terminal fragment of CaV1.2 channels is present in rat dental pulp stem cells and its possible role in the neural differentiation of rat dental pulp stem cells. We generated stable CaV1.2 knockdown cells via short hairpin RNA (shRNA. Rat dental pulp stem cells with deleted distal C-terminal of CaV1.2 channels lost the potential of differentiation to neural cells. Re-expression of distal C-terminal of CaV1.2 rescued the effect of knocking down the endogenous CaV1.2 on the neural differentiation of rat dental pulp stem cells, indicating that the distal C-terminal of CaV1.2 is required for neural differentiation of rat dental pulp stem cells. These results provide new insights into the role of voltage-gated Ca(2+ channels in stem cells during differentiation.

  5. Cocaine- and amphetamine-regulated transcript promotes the differentiation of mouse bone marrow-derived mesenchymal stem cells into neural cells

    Directory of Open Access Journals (Sweden)

    Jin Jiali

    2011-07-01

    Full Text Available Abstract Background Neural tissue has limited potential to self-renew after neurological damage. Cell therapy using BM-MSCs (bone marrow mesenchymal stromal cells seems like a promising approach for the treatment of neurological diseases. However, the neural differentiation of stem cells influenced by massive factors and interactions is not well studied at present. Results In this work, we isolated and identified MSCs from mouse bone marrow. Co-cultured with CART (0.4 nM for six days, BM-MSCs were differentiated into neuron-like cells by the observation of optical microscopy. Immunofluorescence demonstrated that the differentiated BM-MSCs expressed neural specific markers including MAP-2, Nestin, NeuN and GFAP. In addition, NeuN positive cells could co-localize with TH or ChAT by double-labled immunofluorescence and Nissl bodies were found in several differentiated cells by Nissl stain. Furthermore, BDNF and NGF were increased by CART using RT-PCR. Conclusion This study demonstrated that CART could promote the differentiation of BM-MSCs into neural cells through increasing neurofactors, including BNDF and NGF. Combined application of CART and BM-MSCs may be a promising cell-based therapy for neurological diseases.

  6. Neural-differentiated mesenchymal stem cells incorporated into muscle stuffed vein scaffold forms a stable living nerve conduit.

    Science.gov (United States)

    Hassan, Nur Hidayah; Sulong, Ahmad Fadzli; Ng, Min-Hwei; Htwe, Ohnmar; Idrus, Ruszymah B H; Roohi, Sharifah; Naicker, Amaramalar S; Abdullah, Shalimar

    2012-10-01

    Autologous nerve grafts to bridge nerve gaps have donor site morbidity and possible neuroma formation resulting in development of various methods of bridging nerve gaps without using autologous nerve grafts. We have fabricated an acellular muscle stuffed vein seeded with differentiated mesenchymal stem cells (MSCs) as a substitute for nerve autografts. Human vein and muscle were both decellularized by liquid nitrogen immersion with subsequent hydrolysis in hydrochloric acid. Human MSCs were subjected to a series of treatments with a reducing agent, retinoic acid, and a combination of trophic factors. The differentiated MSCs were seeded on the surface of acellular muscle tissue and then stuffed into the vein. Our study showed that 35-75% of the cells expressed neural markers such as S100b, glial fibrillary acidic protein (GFAP), p75 NGF receptor, and Nestin after differentiation. Histological and ultra structural analyses of muscle stuffed veins showed attachment of cells onto the surface of the acellular muscle and penetration of the cells into the hydrolyzed fraction of muscle fibers. We implanted these muscle stuffed veins into athymic mice and at 8 weeks post-implantation, the acellular muscle tissue had fully degraded and replaced with new matrix produced by the seeded cells. The vein was still intact and no inflammatory reactions were observed proving the biocompatibility and biodegradability of the conduit. In conclusion, we have successfully formed a stable living nerve conduit which may serve as a substitute for autologous nerves. Copyright © 2012 Orthopaedic Research Society.

  7. Classification of C2C12 cells at differentiation by convolutional neural network of deep learning using phase contrast images.

    Science.gov (United States)

    Niioka, Hirohiko; Asatani, Satoshi; Yoshimura, Aina; Ohigashi, Hironori; Tagawa, Seiichi; Miyake, Jun

    2018-01-01

    In the field of regenerative medicine, tremendous numbers of cells are necessary for tissue/organ regeneration. Today automatic cell-culturing system has been developed. The next step is constructing a non-invasive method to monitor the conditions of cells automatically. As an image analysis method, convolutional neural network (CNN), one of the deep learning method, is approaching human recognition level. We constructed and applied the CNN algorithm for automatic cellular differentiation recognition of myogenic C2C12 cell line. Phase-contrast images of cultured C2C12 are prepared as input dataset. In differentiation process from myoblasts to myotubes, cellular morphology changes from round shape to elongated tubular shape due to fusion of the cells. CNN abstract the features of the shape of the cells and classify the cells depending on the culturing days from when differentiation is induced. Changes in cellular shape depending on the number of days of culture (Day 0, Day 3, Day 6) are classified with 91.3% accuracy. Image analysis with CNN has a potential to realize regenerative medicine industry.

  8. Tumour necrosis factor-alpha impairs neuronal differentiation but not proliferation of hippocampal neural precursor cells: Role of Hes1.

    Science.gov (United States)

    Keohane, Aoife; Ryan, Sinead; Maloney, Eimer; Sullivan, Aideen M; Nolan, Yvonne M

    2010-01-01

    Tumour necrosis factor-alpha (TNFalpha) is a pro-inflammatory cytokine, which influences neuronal survival and function yet there is limited information available on its effects on hippocampal neural precursor cells (NPCs). We show that TNFalpha treatment during proliferation had no effect on the percentage of proliferating cells prepared from embryonic rat hippocampal neurosphere cultures, nor did it affect cell fate towards either an astrocytic or neuronal lineage when cells were then allowed to differentiate. However, when cells were differentiated in the presence of TNFalpha, significantly reduced percentages of newly born and post-mitotic neurons, significantly increased percentages of astrocytes and increased expression of TNFalpha receptors, TNF-R1 and TNF-R2, as well as expression of the anti-neurogenic Hes1 gene, were observed. These data indicate that exposure of hippocampal NPCs to TNFalpha when they are undergoing differentiation but not proliferation has a detrimental effect on their neuronal lineage fate, which may be mediated through increased expression of Hes1. Copyright 2009 Elsevier Inc. All rights reserved.

  9. Using neural networks to understand the information that guides behavior: a case study in visual navigation.

    Science.gov (United States)

    Philippides, Andrew; Graham, Paul; Baddeley, Bart; Husbands, Philip

    2015-01-01

    To behave in a robust and adaptive way, animals must extract task-relevant sensory information efficiently. One way to understand how they achieve this is to explore regularities within the information animals perceive during natural behavior. In this chapter, we describe how we have used artificial neural networks (ANNs) to explore efficiencies in vision and memory that might underpin visually guided route navigation in complex worlds. Specifically, we use three types of neural network to learn the regularities within a series of views encountered during a single route traversal (the training route), in such a way that the networks output the familiarity of novel views presented to them. The problem of navigation is then reframed in terms of a search for familiar views, that is, views similar to those associated with the route. This approach has two major benefits. First, the ANN provides a compact holistic representation of the data and is thus an efficient way to encode a large set of views. Second, as we do not store the training views, we are not limited in the number of training views we use and the agent does not need to decide which views to learn.

  10. Gender Differences in Behavioral and Neural Responses to Unfairness Under Social Pressure.

    Science.gov (United States)

    Zheng, Li; Ning, Reipeng; Li, Lin; Wei, Chunli; Cheng, Xuemei; Zhou, Chu; Guo, Xiuyan

    2017-10-18

    Numerous studies have revealed the key role of social pressure on individuals' decision-making processes. However, the impact of social pressure on unfairness-related decision-making processes remains unclear. In the present study, we investigated how social pressure modulated men's and women's responses in an ultimatum game. Twenty women and eighteen men played the ultimatum game as responders in the scanner, where fair and unfair offers were tendered by proposers acting alone (low pressure) or by proposers endorsed by three supporters (high pressure). Results showed that men rejected more, whereas women accepted more unfair offers in the high versus low pressure context. Neurally, pregenual anterior cingulate cortex activation in women positively predicted their acceptance rate difference between contexts. In men, stronger right anterior insula activation and increased connectivity between right anterior insula and dorsal anterior cingulate cortex were observed when they receiving unfair offers in the high than low pressure context. Furthermore, more bilateral anterior insula and left dorsolateral prefrontal cortex activations were found when men rejected (relative to accepted) unfair offers in the high than low pressure context. These findings highlighted gender differences in the modulation of behavioral and neural responses to unfairness by social pressure.

  11. Single-Cell Memory Regulates a Neural Circuit for Sensory Behavior.

    Science.gov (United States)

    Kobayashi, Kyogo; Nakano, Shunji; Amano, Mutsuki; Tsuboi, Daisuke; Nishioka, Tomoki; Ikeda, Shingo; Yokoyama, Genta; Kaibuchi, Kozo; Mori, Ikue

    2016-01-05

    Unveiling the molecular and cellular mechanisms underlying memory has been a challenge for the past few decades. Although synaptic plasticity is proven to be essential for memory formation, the significance of "single-cell memory" still remains elusive. Here, we exploited a primary culture system for the analysis of C. elegans neurons and show that a single thermosensory neuron has an ability to form, retain, and reset a temperature memory. Genetic and proteomic analyses found that the expression of the single-cell memory exhibits inter-individual variability, which is controlled by the evolutionarily conserved CaMKI/IV and Raf pathway. The variable responses of a sensory neuron influenced the neural activity of downstream interneurons, suggesting that modulation of the sensory neurons ultimately determines the behavioral output in C. elegans. Our results provide proof of single-cell memory and suggest that the individual differences in neural responses at the single-cell level can confer individuality. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  12. A theory of how active behavior stabilises neural activity: Neural gain modulation by closed-loop environmental feedback.

    Directory of Open Access Journals (Sweden)

    Christopher L Buckley

    2018-01-01

    Full Text Available During active behaviours like running, swimming, whisking or sniffing, motor actions shape sensory input and sensory percepts guide future motor commands. Ongoing cycles of sensory and motor processing constitute a closed-loop feedback system which is central to motor control and, it has been argued, for perceptual processes. This closed-loop feedback is mediated by brainwide neural circuits but how the presence of feedback signals impacts on the dynamics and function of neurons is not well understood. Here we present a simple theory suggesting that closed-loop feedback between the brain/body/environment can modulate neural gain and, consequently, change endogenous neural fluctuations and responses to sensory input. We support this theory with modeling and data analysis in two vertebrate systems. First, in a model of rodent whisking we show that negative feedback mediated by whisking vibrissa can suppress coherent neural fluctuations and neural responses to sensory input in the barrel cortex. We argue this suppression provides an appealing account of a brain state transition (a marked change in global brain activity coincident with the onset of whisking in rodents. Moreover, this mechanism suggests a novel signal detection mechanism that selectively accentuates active, rather than passive, whisker touch signals. This mechanism is consistent with a predictive coding strategy that is sensitive to the consequences of motor actions rather than the difference between the predicted and actual sensory input. We further support the theory by re-analysing previously published two-photon data recorded in zebrafish larvae performing closed-loop optomotor behaviour in a virtual swim simulator. We show, as predicted by this theory, that the degree to which each cell contributes in linking sensory and motor signals well explains how much its neural fluctuations are suppressed by closed-loop optomotor behaviour. More generally we argue that our results

  13. A theory of how active behavior stabilises neural activity: Neural gain modulation by closed-loop environmental feedback.

    Science.gov (United States)

    Buckley, Christopher L; Toyoizumi, Taro

    2018-01-01

    During active behaviours like running, swimming, whisking or sniffing, motor actions shape sensory input and sensory percepts guide future motor commands. Ongoing cycles of sensory and motor processing constitute a closed-loop feedback system which is central to motor control and, it has been argued, for perceptual processes. This closed-loop feedback is mediated by brainwide neural circuits but how the presence of feedback signals impacts on the dynamics and function of neurons is not well understood. Here we present a simple theory suggesting that closed-loop feedback between the brain/body/environment can modulate neural gain and, consequently, change endogenous neural fluctuations and responses to sensory input. We support this theory with modeling and data analysis in two vertebrate systems. First, in a model of rodent whisking we show that negative feedback mediated by whisking vibrissa can suppress coherent neural fluctuations and neural responses to sensory input in the barrel cortex. We argue this suppression provides an appealing account of a brain state transition (a marked change in global brain activity) coincident with the onset of whisking in rodents. Moreover, this mechanism suggests a novel signal detection mechanism that selectively accentuates active, rather than passive, whisker touch signals. This mechanism is consistent with a predictive coding strategy that is sensitive to the consequences of motor actions rather than the difference between the predicted and actual sensory input. We further support the theory by re-analysing previously published two-photon data recorded in zebrafish larvae performing closed-loop optomotor behaviour in a virtual swim simulator. We show, as predicted by this theory, that the degree to which each cell contributes in linking sensory and motor signals well explains how much its neural fluctuations are suppressed by closed-loop optomotor behaviour. More generally we argue that our results demonstrate the dependence

  14. Shaping vulnerability to addiction - the contribution of behavior, neural circuits and molecular mechanisms.

    Science.gov (United States)

    Egervari, Gabor; Ciccocioppo, Roberto; Jentsch, J David; Hurd, Yasmin L

    2018-02-01

    Substance use disorders continue to impose increasing medical, financial and emotional burdens on society in the form of morbidity and overdose, family disintegration, loss of employment and crime, while advances in prevention and treatment options remain limited. Importantly, not all individuals exposed to abused substances effectively develop the disease. Genetic factors play a significant role in determining addiction vulnerability and interactions between innate predisposition, environmental factors and personal experiences are also critical. Thus, understanding individual differences that contribute to the initiation of substance use as well as on long-term maladaptations driving compulsive drug use and relapse propensity is of critical importance to reduce this devastating disorder. In this paper, we discuss current topics in the field of addiction regarding individual vulnerability related to behavioral endophenotypes, neural circuits, as well as genetics and epigenetic mechanisms. Expanded knowledge of these factors is of importance to improve and personalize prevention and treatment interventions in the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. The simplest maximum entropy model for collective behavior in a neural network

    International Nuclear Information System (INIS)

    Tkačik, Gašper; Marre, Olivier; Mora, Thierry; Amodei, Dario; Bialek, William; Berry II, Michael J

    2013-01-01

    Recent work emphasizes that the maximum entropy principle provides a bridge between statistical mechanics models for collective behavior in neural networks and experiments on networks of real neurons. Most of this work has focused on capturing the measured correlations among pairs of neurons. Here we suggest an alternative, constructing models that are consistent with the distribution of global network activity, i.e. the probability that K out of N cells in the network generate action potentials in the same small time bin. The inverse problem that we need to solve in constructing the model is analytically tractable, and provides a natural ‘thermodynamics’ for the network in the limit of large N. We analyze the responses of neurons in a small patch of the retina to naturalistic stimuli, and find that the implied thermodynamics is very close to an unusual critical point, in which the entropy (in proper units) is exactly equal to the energy. (paper)

  16. Behavioral and neural reactions to emotions of others in the distribution of resources.

    Science.gov (United States)

    Lelieveld, Gert-Jan; Van Dijk, Eric; Güroğlu, Berna; Van Beest, Ilja; Van Kleef, Gerben A; Rombouts, Serge A R B; Crone, Eveline A

    2013-01-01

    This study investigated the neural mechanisms involved in the interpersonal effects of emotions--i.e., how people are influenced by other people's emotions. Participants were allocators in a version of the dictator game and made a choice between two offers after receiving written emotional expressions of the recipients. The results showed that participants more often made a self-serving offer when dealing with an angry recipient than when dealing with a happy or disappointed recipient. Compared to disappointment, expressions of anger increased activation in regions associated with self-referential thinking (anterior medial prefrontal cortex, aMPFC) and (emotional) conflict (anterior cingulate cortex). We found increased activation in temporoparietal junction for receiving happy reactions in comparison with receiving angry or disappointed reactions. This study thus emphasizes that distinct emotions have distinct effects on people in terms of behavior and underlying neurological mechanisms.

  17. Altered behavior and neural activity in conspecific cagemates co-housed with mouse models of brain disorders.

    Science.gov (United States)

    Yang, Hyunwoo; Jung, Seungmoon; Seo, Jinsoo; Khalid, Arshi; Yoo, Jung-Seok; Park, Jihyun; Kim, Soyun; Moon, Jangsup; Lee, Soon-Tae; Jung, Keun-Hwa; Chu, Kon; Lee, Sang Kun; Jeon, Daejong

    2016-09-01

    The psychosocial environment is one of the major contributors of social stress. Family members or caregivers who consistently communicate with individuals with brain disorders are considered at risk for physical and mental health deterioration, possibly leading to mental disorders. However, the underlying neural mechanisms of this phenomenon remain poorly understood. To address this, we developed a social stress paradigm in which a mouse model of epilepsy or depression was housed long-term (>4weeks) with normal conspecifics. We characterized the behavioral phenotypes and electrophysiologically investigated the neural activity of conspecific cagemate mice. The cagemates exhibited deficits in behavioral tasks assessing anxiety, locomotion, learning/memory, and depression-like behavior. Furthermore, they showed severe social impairment in social behavioral tasks involving social interaction or aggression. Strikingly, behavioral dysfunction remained in the cagemates 4weeks following co-housing cessation with the mouse models. In an electrophysiological study, the cagemates showed an increased number of spikes in medial prefrontal cortex (mPFC) neurons. Our results demonstrate that conspecifics co-housed with mouse models of brain disorders develop chronic behavioral dysfunctions, and suggest a possible association between abnormal mPFC neural activity and their behavioral pathogenesis. These findings contribute to the understanding of the psychosocial and psychiatric symptoms frequently present in families or caregivers of patients with brain disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. The Human Factor: Behavioral and Neural Correlates of Humanized Perception in Moral Decision Making

    Science.gov (United States)

    Majdandžić, Jasminka; Bauer, Herbert; Windischberger, Christian; Moser, Ewald; Engl, Elisabeth; Lamm, Claus

    2012-01-01

    The extent to which people regard others as full-blown individuals with mental states (“humanization”) seems crucial for their prosocial motivation towards them. Previous research has shown that decisions about moral dilemmas in which one person can be sacrificed to save multiple others do not consistently follow utilitarian principles. We hypothesized that this behavior can be explained by the potential victim’s perceived humanness and an ensuing increase in vicarious emotions and emotional conflict during decision making. Using fMRI, we assessed neural activity underlying moral decisions that affected fictitious persons that had or had not been experimentally humanized. In implicit priming trials, participants either engaged in mentalizing about these persons (Humanized condition) or not (Neutral condition). In subsequent moral dilemmas, participants had to decide about sacrificing these persons’ lives in order to save the lives of numerous others. Humanized persons were sacrificed less often, and the activation pattern during decisions about them indicated increased negative affect, emotional conflict, vicarious emotions, and behavioral control (pgACC/mOFC, anterior insula/IFG, aMCC and precuneus/PCC). Besides, we found enhanced effective connectivity between aMCC and anterior insula, which suggests increased emotion regulation during decisions affecting humanized victims. These findings highlight the importance of others’ perceived humanness for prosocial behavior - with aversive affect and other-related concern when imagining harming more “human-like” persons acting against purely utilitarian decisions. PMID:23082194

  19. Behavioral and Neural Correlates of Executive Function: Interplay between Inhibition and Updating Processes.

    Science.gov (United States)

    Kim, Na Young; Wittenberg, Ellen; Nam, Chang S

    2017-01-01

    This study investigated the interaction between two executive function processes, inhibition and updating, through analyses of behavioral, neurophysiological, and effective connectivity metrics. Although, many studies have focused on behavioral effects of executive function processes individually, few studies have examined the dynamic causal interactions between these two functions. A total of twenty participants from a local university performed a dual task combing flanker and n-back experimental paradigms, and completed the Operation Span Task designed to measure working memory capacity. We found that both behavioral (accuracy and reaction time) and neurophysiological (P300 amplitude and alpha band power) metrics on the inhibition task (i.e., flanker task) were influenced by the updating load (n-back level) and modulated by working memory capacity. Using independent component analysis, source localization (DIPFIT), and Granger Causality analysis of the EEG time-series data, the present study demonstrated that manipulation of cognitive demand in a dual executive function task influenced the causal neural network. We compared connectivity across three updating loads (n-back levels) and found that experimental manipulation of working memory load enhanced causal connectivity of a large-scale neurocognitive network. This network contains the prefrontal and parietal cortices, which are associated with inhibition and updating executive function processes. This study has potential applications in human performance modeling and assessment of mental workload, such as the design of training materials and interfaces for those performing complex multitasking under stress.

  20. Adolescent transformations of behavioral and neural processes as potential targets for prevention.

    Science.gov (United States)

    Eldreth, Dana; Hardin, Michael G; Pavletic, Nevia; Ernst, Monique

    2013-06-01

    Adolescence is a transitional period in development that is marked by a distinct, typical behavioral profile of high rates of exploration, novelty-seeking, and emotional lability. While these behaviors generally assist the adolescent transition to independence, they can also confer vulnerability for excessive risk-taking and psychopathology, particularly in the context of specific environmental or genetic influences. As prevention research depends on the identification of targets of vulnerability, the following review will discuss the interplay among motivational systems including reward-related, avoidance-related, and regulatory processes in typical and atypical adolescent development. Each set of processes will be discussed in relation to their underlying neural correlates and distinct developmental trajectories. Evidence suggests that typical adolescent behavior and the risk for atypical development are mediated by heightened adolescent responsiveness of reward-related and avoidance-related systems under specific conditions, concurrent with poor modulation by immature regulatory processes. Finally, we will propose strategies to exploit heightened reward processing to reinforce inhibitory control, which is an essential component of regulatory processes in prevention interventions.

  1. Neural correlates underlying naloxone-induced amelioration of sexual behavior deterioration due to an alarm pheromone

    Directory of Open Access Journals (Sweden)

    Tatsuya eKobayashi

    2015-02-01

    Full Text Available Sexual behavior is suppressed by various types of stressors. We previously demonstrated that an alarm pheromone released by stressed male Wistar rats is a stressor to other rats, increases the number of mounts needed for ejaculation, and decreases the hit rate (described as the number of intromissions/sum of the mounts and intromissions. This deterioration in sexual behavior was ameliorated by pretreatment with the opioid receptor antagonist naloxone. However, the neural mechanism underlying this remains to be elucidated. Here, we examined Fos expression in 31 brain regions of pheromone-exposed rats and naloxone-pretreated pheromone-exposed rats 60 min after 10 intromissions. As previously reported, the alarm pheromone increased the number of mounts and decreased the hit rate. In addition, Fos expression was increases in the anterior medial division, anterior lateral division and posterior division of the bed nucleus of the stria terminalis, parvocellular part of the paraventricular nucleus of the hypothalamus, arcuate nucleus, dorsolateral and ventrolateral periaqueductal gray, and nucleus paragigantocellularis. Fos expression decreased in the magnocellular part of the paraventricular nucleus of the hypothalamus. Pretreatment with naloxone blocked the pheromone-induced changes in Fos expression in the magnocellular part of the paraventricular nucleus of the hypothalamus, ventrolateral periaqueductal gray, and nucleus paragigantocellularis. Based on these results, we hypothesize that the alarm pheromone deteriorated sexual behavior by activating the ventrolateral periaqueductal gray-nucleus paragigantocellularis cluster and suppressing the magnocellular part of the paraventricular nucleus of the hypothalamus via the opioidergic pathway.

  2. The human factor: behavioral and neural correlates of humanized perception in moral decision making.

    Science.gov (United States)

    Majdandžić, Jasminka; Bauer, Herbert; Windischberger, Christian; Moser, Ewald; Engl, Elisabeth; Lamm, Claus

    2012-01-01

    The extent to which people regard others as full-blown individuals with mental states ("humanization") seems crucial for their prosocial motivation towards them. Previous research has shown that decisions about moral dilemmas in which one person can be sacrificed to save multiple others do not consistently follow utilitarian principles. We hypothesized that this behavior can be explained by the potential victim's perceived humanness and an ensuing increase in vicarious emotions and emotional conflict during decision making. Using fMRI, we assessed neural activity underlying moral decisions that affected fictitious persons that had or had not been experimentally humanized. In implicit priming trials, participants either engaged in mentalizing about these persons (Humanized condition) or not (Neutral condition). In subsequent moral dilemmas, participants had to decide about sacrificing these persons' lives in order to save the lives of numerous others. Humanized persons were sacrificed less often, and the activation pattern during decisions about them indicated increased negative affect, emotional conflict, vicarious emotions, and behavioral control (pgACC/mOFC, anterior insula/IFG, aMCC and precuneus/PCC). Besides, we found enhanced effective connectivity between aMCC and anterior insula, which suggests increased emotion regulation during decisions affecting humanized victims. These findings highlight the importance of others' perceived humanness for prosocial behavior - with aversive affect and other-related concern when imagining harming more "human-like" persons acting against purely utilitarian decisions.

  3. The human factor: behavioral and neural correlates of humanized perception in moral decision making.

    Directory of Open Access Journals (Sweden)

    Jasminka Majdandžić

    Full Text Available The extent to which people regard others as full-blown individuals with mental states ("humanization" seems crucial for their prosocial motivation towards them. Previous research has shown that decisions about moral dilemmas in which one person can be sacrificed to save multiple others do not consistently follow utilitarian principles. We hypothesized that this behavior can be explained by the potential victim's perceived humanness and an ensuing increase in vicarious emotions and emotional conflict during decision making. Using fMRI, we assessed neural activity underlying moral decisions that affected fictitious persons that had or had not been experimentally humanized. In implicit priming trials, participants either engaged in mentalizing about these persons (Humanized condition or not (Neutral condition. In subsequent moral dilemmas, participants had to decide about sacrificing these persons' lives in order to save the lives of numerous others. Humanized persons were sacrificed less often, and the activation pattern during decisions about them indicated increased negative affect, emotional conflict, vicarious emotions, and behavioral control (pgACC/mOFC, anterior insula/IFG, aMCC and precuneus/PCC. Besides, we found enhanced effective connectivity between aMCC and anterior insula, which suggests increased emotion regulation during decisions affecting humanized victims. These findings highlight the importance of others' perceived humanness for prosocial behavior - with aversive affect and other-related concern when imagining harming more "human-like" persons acting against purely utilitarian decisions.

  4. Behavioral and Neural Correlates of Executive Function: Interplay between Inhibition and Updating Processes

    Directory of Open Access Journals (Sweden)

    Na Young Kim

    2017-06-01

    Full Text Available This study investigated the interaction between two executive function processes, inhibition and updating, through analyses of behavioral, neurophysiological, and effective connectivity metrics. Although, many studies have focused on behavioral effects of executive function processes individually, few studies have examined the dynamic causal interactions between these two functions. A total of twenty participants from a local university performed a dual task combing flanker and n-back experimental paradigms, and completed the Operation Span Task designed to measure working memory capacity. We found that both behavioral (accuracy and reaction time and neurophysiological (P300 amplitude and alpha band power metrics on the inhibition task (i.e., flanker task were influenced by the updating load (n-back level and modulated by working memory capacity. Using independent component analysis, source localization (DIPFIT, and Granger Causality analysis of the EEG time-series data, the present study demonstrated that manipulation of cognitive demand in a dual executive function task influenced the causal neural network. We compared connectivity across three updating loads (n-back levels and found that experimental manipulation of working memory load enhanced causal connectivity of a large-scale neurocognitive network. This network contains the prefrontal and parietal cortices, which are associated with inhibition and updating executive function processes. This study has potential applications in human performance modeling and assessment of mental workload, such as the design of training materials and interfaces for those performing complex multitasking under stress.

  5. Financial Incentives Differentially Regulate Neural Processing of Positive and Negative Emotions during Value-Based Decision-Making

    Directory of Open Access Journals (Sweden)

    Anne M. Farrell

    2018-02-01

    Full Text Available Emotional and economic incentives often conflict in decision environments. To make economically desirable decisions then, deliberative neural processes must be engaged to regulate automatic emotional reactions. In this functional magnetic resonance imaging (fMRI study, we evaluated how fixed wage (FW incentives and performance-based (PB financial incentives, in which pay is proportional to outcome, differentially regulate positive and negative emotional reactions to hypothetical colleagues that conflicted with the economics of available alternatives. Neural activity from FW to PB incentive contexts decreased for positive emotional stimuli but increased for negative stimuli in middle temporal, insula, and medial prefrontal regions. In addition, PB incentives further induced greater responses to negative than positive emotional decisions in the frontal and anterior cingulate regions involved in emotion regulation. Greater response to positive than negative emotional features in these regions also correlated with lower frequencies of economically desirable choices. Our findings suggest that whereas positive emotion regulation involves a reduction of responses in valence representation regions, negative emotion regulation additionally engages brain regions for deliberative processing and signaling of incongruous events.

  6. Financial Incentives Differentially Regulate Neural Processing of Positive and Negative Emotions during Value-Based Decision-Making.

    Science.gov (United States)

    Farrell, Anne M; Goh, Joshua O S; White, Brian J

    2018-01-01

    Emotional and economic incentives often conflict in decision environments. To make economically desirable decisions then, deliberative neural processes must be engaged to regulate automatic emotional reactions. In this functional magnetic resonance imaging (fMRI) study, we evaluated how fixed wage (FW) incentives and performance-based (PB) financial incentives, in which pay is proportional to outcome, differentially regulate positive and negative emotional reactions to hypothetical colleagues that conflicted with the economics of available alternatives. Neural activity from FW to PB incentive contexts decreased for positive emotional stimuli but increased for negative stimuli in middle temporal, insula, and medial prefrontal regions. In addition, PB incentives further induced greater responses to negative than positive emotional decisions in the frontal and anterior cingulate regions involved in emotion regulation. Greater response to positive than negative emotional features in these regions also correlated with lower frequencies of economically desirable choices. Our findings suggest that whereas positive emotion regulation involves a reduction of responses in valence representation regions, negative emotion regulation additionally engages brain regions for deliberative processing and signaling of incongruous events.

  7. MicroRNA-130b targets Fmr1 and regulates embryonic neural progenitor cell proliferation and differentiation

    International Nuclear Information System (INIS)

    Gong, Xi; Zhang, Kunshan; Wang, Yanlu; Wang, Junbang; Cui, Yaru; Li, Siguang; Luo, Yuping

    2013-01-01

    Highlights: •We found that the 3′ UTR of the Fmr1 mRNA is a target of miR-130b. •MiR-130b suppresses the expression of Fmr1 in mouse embryonic stem cell. •MiR-130b alters the proliferation of mouse embryonic stem cell. •MiR-130b alters fate specification of mouse embryonic stem cell. -- Abstract: Fragile X syndrome, one of the most common forms of inherited mental retardation, is caused by expansion of the CGG repeat in the 5′-untranslated region of the X-linked Fmr1 gene, which results in transcriptional silencing and loss of expression of its encoded protein FMRP. The loss of FMRP increases proliferation and alters fate specification in adult neural progenitor cells (aNPCs). However, little is known about Fmr1 mRNA regulation at the transcriptional and post-transcriptional levels. In the present study, we report that miR-130b regulated Fmr1 expression by directly targeting its 3′-untranslated region (3′ UTR). Up-regulation of miR-130b in mouse embryonic neural progenitor cells (eNPCs) decreased Fmr1 expression, markedly increased eNPC proliferation and altered the differentiation tendency of eNPCs, suggesting that antagonizing miR-130b may be a new therapeutic entry point for treating Fragile X syndrome

  8. MicroRNA-130b targets Fmr1 and regulates embryonic neural progenitor cell proliferation and differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Gong, Xi [State Key Laboratory of Food Science and Technology, College of Life Sciences and Food Engineering, Nanchang University, Nanchang 330047 (China); Zhang, Kunshan [Department of Regenerative Medicine, Stem Cell Center, Tongji University School of Medicine, Shanghai 200092 (China); Wang, Yanlu; Wang, Junbang; Cui, Yaru [State Key Laboratory of Food Science and Technology, College of Life Sciences and Food Engineering, Nanchang University, Nanchang 330047 (China); Li, Siguang, E-mail: siguangli@163.com [Department of Regenerative Medicine, Stem Cell Center, Tongji University School of Medicine, Shanghai 200092 (China); Luo, Yuping, E-mail: luoyuping@163.com [State Key Laboratory of Food Science and Technology, College of Life Sciences and Food Engineering, Nanchang University, Nanchang 330047 (China)

    2013-10-04

    Highlights: •We found that the 3′ UTR of the Fmr1 mRNA is a target of miR-130b. •MiR-130b suppresses the expression of Fmr1 in mouse embryonic stem cell. •MiR-130b alters the proliferation of mouse embryonic stem cell. •MiR-130b alters fate specification of mouse embryonic stem cell. -- Abstract: Fragile X syndrome, one of the most common forms of inherited mental retardation, is caused by expansion of the CGG repeat in the 5′-untranslated region of the X-linked Fmr1 gene, which results in transcriptional silencing and loss of expression of its encoded protein FMRP. The loss of FMRP increases proliferation and alters fate specification in adult neural progenitor cells (aNPCs). However, little is known about Fmr1 mRNA regulation at the transcriptional and post-transcriptional levels. In the present study, we report that miR-130b regulated Fmr1 expression by directly targeting its 3′-untranslated region (3′ UTR). Up-regulation of miR-130b in mouse embryonic neural progenitor cells (eNPCs) decreased Fmr1 expression, markedly increased eNPC proliferation and altered the differentiation tendency of eNPCs, suggesting that antagonizing miR-130b may be a new therapeutic entry point for treating Fragile X syndrome.

  9. Navigating Monogamy: Nonapeptide Sensitivity in a Memory Neural Circuit May Shape Social Behavior and Mating Decisions

    Directory of Open Access Journals (Sweden)

    Alexander G. Ophir

    2017-07-01

    Full Text Available The role of memory in mating systems is often neglected despite the fact that most mating systems are defined in part by how animals use space. Monogamy, for example, is usually characterized by affiliative (e.g., pairbonding and defensive (e.g., mate guarding behaviors, but a high degree of spatial overlap in home range use is the easiest defining feature of monogamous animals in the wild. The nonapeptides vasopressin and oxytocin have been the focus of much attention for their importance in modulating social behavior, however this work has largely overshadowed their roles in learning and memory. To date, the understanding of memory systems and mechanisms governing social behavior have progressed relatively independently. Bridging these two areas will provide a deeper appreciation for understanding behavior, and in particular the mechanisms that mediate reproductive decision-making. Here, I argue that the ability to mate effectively as monogamous individuals is linked to the ability to track conspecifics in space. I discuss the connectivity across some well-known social and spatial memory nuclei, and propose that the nonapeptide receptors within these structures form a putative “socio-spatial memory neural circuit.” This purported circuit may function to integrate social and spatial information to shape mating decisions in a context-dependent fashion. The lateral septum and/or the nucleus accumbens, and neuromodulation therein, may act as an intermediary to relate socio-spatial information with social behavior. Identifying mechanisms responsible for relating information about the social world with mechanisms mediating mating tactics is crucial to fully appreciate the suite of factors driving reproductive decisions and social decision-making.

  10. Navigating Monogamy: Nonapeptide Sensitivity in a Memory Neural Circuit May Shape Social Behavior and Mating Decisions

    Science.gov (United States)

    Ophir, Alexander G.

    2017-01-01

    The role of memory in mating systems is often neglected despite the fact that most mating systems are defined in part by how animals use space. Monogamy, for example, is usually characterized by affiliative (e.g., pairbonding) and defensive (e.g., mate guarding) behaviors, but a high degree of spatial overlap in home range use is the easiest defining feature of monogamous animals in the wild. The nonapeptides vasopressin and oxytocin have been the focus of much attention for their importance in modulating social behavior, however this work has largely overshadowed their roles in learning and memory. To date, the understanding of memory systems and mechanisms governing social behavior have progressed relatively independently. Bridging these two areas will provide a deeper appreciation for understanding behavior, and in particular the mechanisms that mediate reproductive decision-making. Here, I argue that the ability to mate effectively as monogamous individuals is linked to the ability to track conspecifics in space. I discuss the connectivity across some well-known social and spatial memory nuclei, and propose that the nonapeptide receptors within these structures form a putative “socio-spatial memory neural circuit.” This purported circuit may function to integrate social and spatial information to shape mating decisions in a context-dependent fashion. The lateral septum and/or the nucleus accumbens, and neuromodulation therein, may act as an intermediary to relate socio-spatial information with social behavior. Identifying mechanisms responsible for relating information about the social world with mechanisms mediating mating tactics is crucial to fully appreciate the suite of factors driving reproductive decisions and social decision-making. PMID:28744194

  11. Systematic Review of Differential Reinforcement of Alternative Behavior Without Extinction for Individuals With Autism.

    Science.gov (United States)

    MacNaul, Hannah L; Neely, Leslie C

    2018-05-01

    The purpose of this article is to review the literature on differential reinforcement of alternative behavior procedures without extinction for individuals with autism. Using predetermined inclusion criteria, a total of 10 studies were included and summarized in terms of the following: (a) participant characteristics (e.g., sex, age, and diagnosis), (b) treatment setting, (c) problem behavior, (d) function, (e) alternative behavior, (f) intervention, (g) outcomes, and (h) conclusiveness of evidence. Of the 10 studies, nine demonstrated positive effects and one mixed effects. Five studies successfully reduced problem behavior by manipulating different reinforcement parameters (magnitude, immediacy, and quality) and four manipulated the schedule of reinforcement. One study had mixed results with two of the three participants requiring extinction. The findings of this review suggest that variations of differential reinforcement of alternative behavior interventions without an extinction component may be considered promising practices for the treatment of challenging behavior in individuals with autism.

  12. CSK negatively regulates nerve growth factor induced neural differentiation and augments AKT kinase activity

    International Nuclear Information System (INIS)

    Dey, Nandini; Howell, Brian W.; De, Pradip K.; Durden, Donald L.

    2005-01-01

    Src family kinases are involved in transducing growth factor signals for cellular differentiation and proliferation in a variety of cell types. The activity of all Src family kinases (SFKs) is controlled by phosphorylation at their C-terminal 527-tyrosine residue by C-terminal SRC kinase, CSK. There is a paucity of information regarding the role of CSK and/or specific Src family kinases in neuronal differentiation. Pretreatment of PC12 cells with the Src family kinase inhibitor, PP1, blocked NGF-induced activation of SFKs and obliterated neurite outgrowth. To confirm a role for CSK and specific isoforms of SFKs in neuronal differentiation, we overexpressed active and catalytically dead CSK in the rat pheochromocytoma cell line, PC12. CSK overexpression caused a profound inhibition of NGF-induced activation of FYN, YES, RAS, and ERK and inhibited neurite outgrowth, NGF-stimulated integrin-directed migration and blocked the NGF-induced conversion of GDP-RAC to its GTP-bound active state. CSK overexpression markedly augmented the activation state of AKT following NGF stimulation. In contrast, kinase-dead CSK augmented the activation of FYN, RAS, and ERK and increased neurite outgrowth. These data suggest a distinct requirement for CSK in the regulation of NGF/TrkA activation of RAS, RAC, ERK, and AKT via the differential control of SFKs in the orchestration of neuronal differentiation

  13. Origin-Dependent Neural Cell Identities in Differentiated Human iPSCs In Vitro and after Transplantation into the Mouse Brain

    Directory of Open Access Journals (Sweden)

    Gunnar Hargus

    2014-09-01

    Full Text Available The differentiation capability of induced pluripotent stem cells (iPSCs toward certain cell types for disease modeling and drug screening assays might be influenced by their somatic cell of origin. Here, we have compared the neural induction of human iPSCs generated from fetal neural stem cells (fNSCs, dermal fibroblasts, or cord blood CD34+ hematopoietic progenitor cells. Neural progenitor cells (NPCs and neurons could be generated at similar efficiencies from all iPSCs. Transcriptomics analysis of the whole genome and of neural genes revealed a separation of neuroectoderm-derived iPSC-NPCs from mesoderm-derived iPSC-NPCs. Furthermore, we found genes that were similarly expressed in fNSCs and neuroectoderm, but not in mesoderm-derived iPSC-NPCs. Notably, these neural signatures were retained after transplantation into the cortex of mice and paralleled with increased survival of neuroectoderm-derived cells in vivo. These results indicate distinct origin-dependent neural cell identities in differentiated human iPSCs both in vitro and in vivo.

  14. Differential neural substrates of working memory and cognitive skill learning in healthy young volunteers

    International Nuclear Information System (INIS)

    Cho, Sang Soo; Lee, Eun Ju; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun

    2005-01-01

    It is known that different neural circuits are involved in working memory and cognitive skill learning that represent explicit and implicit memory functions, respectively. In the present study, we investigated the metabolic correlates of working memory and cognitive skill learning with correlation analysis of FDG PET images. Fourteen right-handed healthy subjects (age, 24 ± 2 yr; 5 males and 9 females) underwent brain FDG PET and neuropsychological testing. Two-back task and weather prediction task were used for the evaluation of working memory and cognitive skill learning, respectively, Correlation between regional glucose metabolism and cognitive task performance was examined using SPM99. A significant positive correlation between 2-back task performance and regional glucose metabolism was found in the prefrontal regions and superior temporal gyri bilaterally. In the first term of weather prediction task the task performance correlated positively with glucose metabolism in the bilateral prefrontal areas, left middle temporal and posterior cingulate gyri, and left thalamus. In the second and third terms of the task, the correlation found in the prefrontal areas, superior temporal and anterior cingulate gyri bilaterally, right insula, left parahippocampal gyrus, and right caudate nucleus. We identified the neural substrates that are related with performance of working memory and cognitive skill learning. These results indicate that brain regions associated with the explicit memory system are recruited in early periods of cognitive skill learning, but additional brain regions including caudate nucleus are involved in late periods of cognitive skill learning

  15. Differential neural substrates of working memory and cognitive skill learning in healthy young volunteers

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sang Soo; Lee, Eun Ju; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2005-07-01

    It is known that different neural circuits are involved in working memory and cognitive skill learning that represent explicit and implicit memory functions, respectively. In the present study, we investigated the metabolic correlates of working memory and cognitive skill learning with correlation analysis of FDG PET images. Fourteen right-handed healthy subjects (age, 24 {+-} 2 yr; 5 males and 9 females) underwent brain FDG PET and neuropsychological testing. Two-back task and weather prediction task were used for the evaluation of working memory and cognitive skill learning, respectively, Correlation between regional glucose metabolism and cognitive task performance was examined using SPM99. A significant positive correlation between 2-back task performance and regional glucose metabolism was found in the prefrontal regions and superior temporal gyri bilaterally. In the first term of weather prediction task the task performance correlated positively with glucose metabolism in the bilateral prefrontal areas, left middle temporal and posterior cingulate gyri, and left thalamus. In the second and third terms of the task, the correlation found in the prefrontal areas, superior temporal and anterior cingulate gyri bilaterally, right insula, left parahippocampal gyrus, and right caudate nucleus. We identified the neural substrates that are related with performance of working memory and cognitive skill learning. These results indicate that brain regions associated with the explicit memory system are recruited in early periods of cognitive skill learning, but additional brain regions including caudate nucleus are involved in late periods of cognitive skill learning.

  16. Distinct contributions of functional and deep neural network features to representational similarity of scenes in human brain and behavior.

    Science.gov (United States)

    Groen, Iris Ia; Greene, Michelle R; Baldassano, Christopher; Fei-Fei, Li; Beck, Diane M; Baker, Chris I

    2018-03-07

    Inherent correlations between visual and semantic features in real-world scenes make it difficult to determine how different scene properties contribute to neural representations. Here, we assessed the contributions of multiple properties to scene representation by partitioning the variance explained in human behavioral and brain measurements by three feature models whose inter-correlations were minimized a priori through stimulus preselection. Behavioral assessments of scene similarity reflected unique contributions from a functional feature model indicating potential actions in scenes as well as high-level visual features from a deep neural network (DNN). In contrast, similarity of cortical responses in scene-selective areas was uniquely explained by mid- and high-level DNN features only, while an object label model did not contribute uniquely to either domain. The striking dissociation between functional and DNN features in their contribution to behavioral and brain representations of scenes indicates that scene-selective cortex represents only a subset of behaviorally relevant scene information.

  17. Organic cation transporter-mediated ergothioneine uptake in mouse neural progenitor cells suppresses proliferation and promotes differentiation into neurons.

    Directory of Open Access Journals (Sweden)

    Takahiro Ishimoto

    Full Text Available The aim of the present study is to clarify the functional expression and physiological role in neural progenitor cells (NPCs of carnitine/organic cation transporter OCTN1/SLC22A4, which accepts the naturally occurring food-derived antioxidant ergothioneine (ERGO as a substrate in vivo. Real-time PCR analysis revealed that mRNA expression of OCTN1 was much higher than that of other organic cation transporters in mouse cultured cortical NPCs. Immunocytochemical analysis showed colocalization of OCTN1 with the NPC marker nestin in cultured NPCs and mouse embryonic carcinoma P19 cells differentiated into neural progenitor-like cells (P19-NPCs. These cells