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Sample records for neural differentiation behavior

  1. In search for the neural mechanisms of individual development: behavior-driven differential Hebbian learning

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    Ralf eDer

    2016-01-01

    Full Text Available When Donald Hebb published his 1949 book ``The Organization of Behavior'' he opened a new way of thinking in theoretical neuroscience which, in retrospective, is very close to contemporary ideas in self-organization. His metaphor of ``wiring'' together what ``fires together'' matches very closely the commonparadigm that global organization can derive from simple local rules. While ingenious at his time and inspiring the research over decades, the results still fall short of the expectations. For instance,unsupervised as they are, such neural mechanisms should be able to explain and realize the self-organizedacquisition of sensorimotor competencies. This paper proposes a new synaptic law which replaces Hebb's original metaphor by that of ``chaining together'' what ``changes together''. Starting from differential Hebbian learning,the new rule grounds the behavior of the agent directly in the internal synaptic dynamics.Therefore, one may call this a behavior-driven synaptic plasticity.Neurorobotics is an ideal testing ground for this new, unsupervised learning rule. This paper focuses on the close coupling between body, control, and environmentin challenging physical settings. The examples demonstrate how the new synaptic mechanism induces a self-determined ``search and converge'' strategy in behavior space, generating spontaneously a variety of sensorimotor competencies. The emerging behavior patterns are qualified by involving body and environment inan irreducible conjunction with the internal mechanism.The results may not only be of immediate interest for the further development of embodied intelligence.They also offer a new view on the role of self-learning processes in natural evolutionand in the brain.Videos and further details may be found under url{http://robot.informatik.uni-leipzig.de/research/supplementary/NeuroAutonomy/}.

  2. Functional differential inclusions and dynamic behaviors for memristor-based BAM neural networks with time-varying delays

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    Cai, Zuowei; Huang, Lihong

    2014-05-01

    In this paper, we formulate and investigate a class of memristor-based BAM neural networks with time-varying delays. Under the framework of Filippov solutions, the viability and dissipativity of solutions for functional differential inclusions and memristive BAM neural networks can be guaranteed by the matrix measure approach and generalized Halanay inequalities. Then, a new method involving the application of set-valued version of Krasnoselskii' fixed point theorem in a cone is successfully employed to derive the existence of the positive periodic solution. The dynamic analysis in this paper utilizes the theory of set-valued maps and functional differential equations with discontinuous right-hand sides of Filippov type. The obtained results extend and improve some previous works on conventional BAM neural networks. Finally, numerical examples are given to demonstrate the theoretical results via computer simulations.

  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. Differential effects of unnatural sialic acids on the polysialylation of the neural cell adhesion molecule and neuronal behavior.

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    Charter, Neil W; Mahal, Lara K; Koshland, Daniel E; Bertozzi, Carolyn R

    2002-03-15

    In this study we have examined how unnatural sialic acids can alter polysialic acid expression and influence the adhesive properties of the neural cell adhesion molecule (NCAM). Unnatural sialic acids are generated by metabolic conversion of synthetic N-acyl mannosamines and are typically incorporated into cell-surface glycoconjugates. However, N-butanoylmannosamine and N-pentanoylmannosamine are effective inhibitors of polysialic acid (PSA) synthesis in stably transfected HeLa cells expressing NCAM and the polysialyltransferase STX. These cells were used as substrates to examine the effect of inhibiting PSA synthesis on the development of neurons derived from the chick dorsal root ganglion. N-butanoylmannosamine blocked polysialylation of NCAM and significantly reduced neurite outgrowth comparable with enzymatic removal of PSA by endoneuraminidases. As a result, neurite outgrowth was similar to that observed for non-polysialylated NCAM. In contrast, previous studies have shown that N-propanoyl sialic acid (SiaProp), generated from N-propanoylmannosamine, is readily accepted by polysialyltransferases and permits the extension of poly(SiaProp) on NCAM. Despite being immunologically distinct, poly(SiaProp) can promote neurite outgrowth similarly to natural polysialic acid. Thus, subtle structural differences in PSA resulting from the incorporation of SiaProp residues do not alter the antiadhesive properties of polysialylated NCAM.

  5. Patterns of neural differentiation in melanomas

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    Singh Avantika V

    2010-11-01

    Full Text Available Abstract Background Melanomas, highly malignant tumors arise from the melanocytes which originate as multipotent neural crest cells during neural tube genesis. The purpose of this study is to assess the pattern of neural differentiation in relation to angiogenesis in VGP melanomas using the tumor as a three dimensional system. Methods Tumor-vascular complexes [TVC] are formed at the tumor-stroma interphase, by tumor cells ensheathing angiogenic vessels to proliferate into a mantle of 5 to 6 layers [L1 to L5] forming a perivascular mantle zone [PMZ]. The pattern of neural differentiation is assessed by immunopositivity for HMB45, GFAP, NFP and synaptophysin has been compared in: [a] the general tumor [b] tumor-vascular complexes and [c] perimantle zone [PC] on serial frozen and paraffin sections. Statistical Analysis: ANOVA: Kruskal-Wallis One Way Analysis of Variance; All Pairwise Multiple Comparison Procedures [Tukey Test]. Results The cells abutting on the basement membrane acquire GFAP positivity and extend processes. New layers of tumor cells show a transition between L2 to L3 followed by NFP and Syn positivity in L4&L5. The level of GFAP+vity in L1&L2 directly proportionate to the percentage of NFP/Syn+vity in L4&L5, on comparing pigmented PMZ with poorly pigmented PMZ. Tumor cells in the perimantle zone show high NFP [65%] and Syn [35.4%] positivity with very low GFAP [6.9%] correlating with the positivity in the outer layers. Discussion From this study it is seen that melanoma cells revert to the embryonic pattern of differentiation, with radial glial like cells [GFAP+ve] which further differentiate into neuronal positive cells [NFP&Syn+ve] during angiogenic tumor-vascular interaction, as seen during neurogenesis, to populate the tumor substance.

  6. miR-381 Regulates Neural Stem Cell Proliferation and Differentiation via Regulating Hes1 Expression.

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    Xiaodong Shi

    Full Text Available Neural stem cells are self-renewing, multipotent and undifferentiated precursors that retain the capacity for differentiation into both glial (astrocytes and oligodendrocytes and neuronal lineages. Neural stem cells offer cell-based therapies for neurological disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease and spinal cord injuries. However, their cellular behavior is poorly understood. MicroRNAs (miRNAs are a class of small noncoding RNAs involved in cell development, proliferation and differentiation through regulating gene expression at post-transcriptional level. The role of miR-381 in the development of neural stem cells remains unknown. In this study, we showed that overexpression of miR-381 promoted neural stem cells proliferation. It induced the neural stem cells differentiation to neurons and inhibited their differentiation to astrocytes. Furthermore, we identified HES1 as a direct target of miR-381 in neural stem cells. Moreover, re-expression of HES1 impaired miR-381-induced promotion of neural stem cells proliferation and induce neural stem cells differentiation to neurons. In conclusion, miR-381 played important role in neural stem cells proliferation and differentiation.

  7. Developmental plasticity in neural circuits for a learned behavior.

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    Bottjer, S W; Arnold, A P

    1997-01-01

    The neural substrate underlying learned vocal behavior in songbirds provides a textbook illustration of anatomical localization of function for a complex learned behavior in vertebrates. The song-control system has become an important model for studying neural systems related to learning, behavior, and development. The song system of zebra finches is characterized by a heightened capacity for both neural and behavioral change during development and has taught us valuable information regarding sensitive periods, rearrangement of synaptic connections, topographic specificity, cell death and neurogenesis, experience-dependent neural plasticity, and sexual differentiation. The song system differs in some interesting ways from some well-studied mammalian model systems and thus offers fresh perspectives on specific theoretical issues. In this highly selective review, we concentrate on two major questions: What are the developmental changes in the song system responsible for song learning and the restriction of learning to a sensitive period, and what factors explain the highly sexually dimorphic development of this system? We discuss the important role of sex steroid hormones and of neurotrophins in creating a male-typical neural song circuit (which can learn to produce complex vocalizations) instead of a reduced, female-typical song circuit that does not produce learned song.

  8. 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.

  9. Antagonistic Neural Networks Underlying Differentiated Leadership Roles

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    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.

  10. 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

  11. Mir-29b Mediates the Neural Tube versus Neural Crest Fate Decision during Embryonic Stem Cell Neural Differentiation.

    Science.gov (United States)

    Xi, Jiajie; Wu, Yukang; Li, Guoping; Ma, Li; Feng, Ke; Guo, Xudong; Jia, Wenwen; Wang, Guiying; Yang, Guang; Li, Ping; Kang, Jiuhong

    2017-08-08

    During gastrulation, the neuroectoderm cells form the neural tube and neural crest. The nervous system contains significantly more microRNAs than other tissues, but the role of microRNAs in controlling the differentiation of neuroectodermal cells into neural tube epithelial (NTE) cells and neural crest cells (NCCs) remains unknown. Using embryonic stem cell (ESC) neural differentiation systems, we found that miR-29b was upregulated in NTE cells and downregulated in NCCs. MiR-29b promoted the differentiation of ESCs into NTE cells and inhibited their differentiation into NCCs. Accordingly, the inhibition of miR-29b significantly inhibited the differentiation of NTE cells. A mechanistic study revealed that miR-29b targets DNA methyltransferase 3a (Dnmt3a) to regulate neural differentiation. Moreover, miR-29b mediated the function of Pou3f1, a critical neural transcription factor. Therefore, our study showed that the Pou3f1-miR-29b-Dnmt3a regulatory axis was active at the initial stage of neural differentiation and regulated the determination of cell fate. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Neural and Behavioral Correlates of Song Prosody

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

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    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…

  14. Differentiation state determines neural effects on microvascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Muffley, Lara A., E-mail: muffley@u.washington.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Pan, Shin-Chen, E-mail: pansc@mail.ncku.edu.tw [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Smith, Andria N., E-mail: gnaunderwater@gmail.com [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Ga, Maricar, E-mail: marga16@uw.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Hocking, Anne M., E-mail: ahocking@u.washington.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Gibran, Nicole S., E-mail: nicoleg@u.washington.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States)

    2012-10-01

    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: Black-Right-Pointing-Pointer Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell proliferation. Black-Right-Pointing-Pointer Neural progenitor cells, not dorsal root ganglion neurons, regulate microvascular endothelial cell migration. Black-Right-Pointing-Pointer Neural progenitor cells and dorsal root ganglion neurons do not effect microvascular endothelial tube formation. Black-Right-Pointing-Pointer Dorsal root ganglion neurons, not neural progenitor cells, regulate

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

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    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.

  16. Behavioral, Cognitive and Neural Markers of Asperger Syndrome.

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    Faridi, Farnaz; Khosrowabadi, Reza

    2017-01-01

    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.

  17. 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. 

  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

    following a constriction injury of the sciatic nerve. RESULTS: Ectopic Runx1a expression in cultured NCSCs resulted in predominantly glial differentiation. Offsprings in which Runx1a had been activated showed retarded growth and displayed megacolon, pigment defects, and dystrophic dorsal root ganglia...

  19. Neural and behavioral investigations into timbre perception

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    Stephen Michael Town

    2013-11-01

    Full Text Available Timbre is the attribute that distinguishes sounds of equal pitch, loudness and duration. It contributes to our perception and discrimination of different vowels and consonants in speech, instruments in music and environmental sounds. Here we begin by reviewing human timbre perception and the spectral and temporal acoustic features that give rise to timbre in speech, musical and environmental sounds. We also consider the perception of timbre by animals, both in the case of human vowels and non-human vocalizations. We then explore the neural representation of timbre, first within the peripheral auditory system and later at the level of the auditory cortex. We examine the neural networks that are implicated in timbre perception and the computations that may be performed in auditory cortex to enable listeners to extract information about timbre. We consider whether single neurons in auditory cortex are capable of representing spectral timbre independently of changes in other perceptual attributes and the mechanisms that may shape neural sensitivity to timbre. Finally, we conclude by outlining some of the questions that remain about the role of neural mechanisms in behavior and consider some potentially fruitful avenues for future research.

  20. Antagonistic neural networks underlying differentiated leadership roles

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    Richard Eleftherios Boyatzis; Kylie eRochford; Anthony Ian Jack

    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 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 ...

  1. Natural neural projection dynamics underlying social behavior.

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    Gunaydin, Lisa A; Grosenick, Logan; Finkelstein, Joel C; Kauvar, Isaac V; Fenno, Lief E; Adhikari, Avishek; Lammel, Stephan; Mirzabekov, Julie J; Airan, Raag D; Zalocusky, Kelly A; Tye, Kay M; Anikeeva, Polina; Malenka, Robert C; Deisseroth, Karl

    2014-06-19

    Social interaction is a complex behavior essential for many species and is impaired in major neuropsychiatric disorders. Pharmacological studies have implicated certain neurotransmitter systems in social behavior, but circuit-level understanding of endogenous neural activity during social interaction is lacking. We therefore developed and applied a new methodology, termed fiber photometry, to optically record natural neural activity in genetically and connectivity-defined projections to elucidate the real-time role of specified pathways in mammalian behavior. Fiber photometry revealed that activity dynamics of a ventral tegmental area (VTA)-to-nucleus accumbens (NAc) projection could encode and predict key features of social, but not novel object, interaction. Consistent with this observation, optogenetic control of cells specifically contributing to this projection was sufficient to modulate social behavior, which was mediated by type 1 dopamine receptor signaling downstream in the NAc. Direct observation of deep projection-specific activity in this way captures a fundamental and previously inaccessible dimension of mammalian circuit dynamics. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Toward a Neural Basis for Social Behavior

    OpenAIRE

    Stanley, Damian A.; Adolphs, Ralph

    2013-01-01

    Nearly 25 years ago, the shared interests of psychologists and biologists in understanding the neural basis of social behavior led to the inception of social neuroscience. In the past decade, this field has exploded, in large part due to the infusion of studies that use fMRI. At the same time, tensions have arisen about how to prioritize a diverse range of questions and about the authority of neurobiological data in answering them. The field is now poised to tackle some of the most interestin...

  3. Neural progestin receptors and female sexual behavior

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    Mani, Shaila K.; Blaustein, Jeffrey D.

    2012-01-01

    The steroid hormone, progesterone, modulates neuroendocrine functions in the central nervous system resulting in integration of reproduction and reproductive behaviors in female mammals. Although it is widely recognized that progesterone’s effects on female sex behavior are mediated by the classical neural progestin receptors (PRs) functioning as “ligand-dependent” transcription factors to regulate genes and genomic networks, additional mechanisms of PR activation also contribute to the behavioral response. Cellular and molecular evidence indicates that PRs can be activated in a ligand-independent manner by neurotransmitters, growth factors, cyclic nucleotides, progestin metabolites and mating stimuli. The rapid responses of progesterone may be mediated by a variety of PR types, including membrane-associated PRs or extra-nuclear PRs. Furthermore, these rapid, non-classical progesterone actions involving cytoplasmic kinase signaling and/or extra-nuclear PRs also converge with classical PR-mediated, transcription dependent pathway to regulate reproductive behaviors. In this review, we summarize some of the history of the study of the role of PRs in reproductive behaviors, and update the status of PR-mediated mechanisms involved in the facilitation of female sex behavior. We present an integrative model of PR activation via crosstalk and convergence of multiple signaling pathways. PMID:22538437

  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. 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.

  6. Toward a neural basis for social behavior.

    Science.gov (United States)

    Stanley, Damian A; Adolphs, Ralph

    2013-10-30

    Nearly 25 years ago, the shared interests of psychologists and biologists in understanding the neural basis of social behavior led to the inception of social neuroscience. In the past decade, this field has exploded, in large part due to the infusion of studies that use fMRI. At the same time, tensions have arisen about how to prioritize a diverse range of questions and about the authority of neurobiological data in answering them. The field is now poised to tackle some of the most interesting and important questions about human and animal behavior but at the same time faces uncertainty about how to achieve focus in its research and cohesion among the scientists who tackle it. The next 25 years offer the opportunity to alleviate some of these growing pains, as well as the challenge of answering large questions that encompass the nature and bounds of diverse social interactions (in humans, including interactions through the internet); how to characterize, and treat, social dysfunction in psychiatric illness; and how to compare social cognition in humans with that in other animals. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Neural basis of economic bubble behavior.

    Science.gov (United States)

    Ogawa, A; Onozaki, T; Mizuno, T; Asamizuya, T; Ueno, K; Cheng, K; Iriki, A

    2014-04-18

    Throughout human history, economic bubbles have formed and burst. As a bubble grows, microeconomic behavior ceases to be constrained by realistic predictions. This contradicts the basic assumption of economics that agents have rational expectations. To examine the neural basis of behavior during bubbles, we performed functional magnetic resonance imaging while participants traded shares in a virtual stock exchange with two non-bubble stocks and one bubble stock. The price was largely deflected from the fair price in one of the non-bubble stocks, but not in the other. Their fair prices were specified. The price of the bubble stock showed a large increase and battering, as based on a real stock-market bust. The imaging results revealed modulation of the brain circuits that regulate trade behavior under different market conditions. The premotor cortex was activated only under a market condition in which the price was largely deflected from the fair price specified. During the bubble, brain regions associated with the cognitive processing that supports order decisions were identified. The asset preference that might bias the decision was associated with the ventrolateral prefrontal cortex and the dorsolateral prefrontal cortex (DLPFC). The activity of the inferior parietal lobule (IPL) was correlated with the score of future time perspective, which would bias the estimation of future price. These regions were deemed to form a distinctive network during the bubble. A functional connectivity analysis showed that the connectivity between the DLPFC and the IPL was predominant compared with other connectivities only during the bubble. These findings indicate that uncertain and unstable market conditions changed brain modes in traders. These brain mechanisms might lead to a loss of control caused by wishful thinking, and to microeconomic bubbles that expand, on the macroscopic scale, toward bust. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. The versatility of RhoA activities in neural differentiation.

    Science.gov (United States)

    Horowitz, Arie; Yang, Junning; Cai, Jingli; Iacovitti, Lorraine

    2017-01-26

    In this commentary we discuss a paper we published recently on the activities of the GTPase RhoA during neural differentiation of murine embryonic stem cells, and relate our findings to previous studies. We narrate how we found that RhoA impedes neural differentiation by inhibiting the production as well as the secretion of noggin, a soluble factor that antagonizes bone morphogenetic protein. We discuss how the questions we tried to address shaped the study, and how embryonic stem cells isolated from a genetically modified mouse model devoid of Syx, a RhoA-specific guanine exchange factor, were used to address them. We detail several signaling pathways downstream of RhoA that are hindered by the absence of Syx, and obstructed by retinoic acid, resulting in an increase of noggin production; we explain how the lower RhoA activity and, consequently, the sparser peri-junctional stress fibers in Syx -/- cells facilitated noggin secretion; and we report unpublished results showing that pharmacological inhibition of RhoA accelerates the neuronal differentiation of human embryonic stem cells. Finally, we identify signaling mechanisms in our recent study that warrant further study, and speculate on the possibility of manipulating RhoA signaling in combination with other pathways to drive the differentiation of neuronal subtypes.

  9. Differentiating neural reward responsiveness in autism versus ADHD

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    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.

  10. 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.

  11. A Bayesian framework for simultaneously modeling neural and behavioral data.

    Science.gov (United States)

    Turner, Brandon M; Forstmann, Birte U; Wagenmakers, Eric-Jan; Brown, Scott D; Sederberg, Per B; Steyvers, Mark

    2013-05-15

    Scientists who study cognition infer underlying processes either by observing behavior (e.g., response times, percentage correct) or by observing neural activity (e.g., the BOLD response). These two types of observations have traditionally supported two separate lines of study. The first is led by cognitive modelers, who rely on behavior alone to support their computational theories. The second is led by cognitive neuroimagers, who rely on statistical models to link patterns of neural activity to experimental manipulations, often without any attempt to make a direct connection to an explicit computational theory. Here we present a flexible Bayesian framework for combining neural and cognitive models. Joining neuroimaging and computational modeling in a single hierarchical framework allows the neural data to influence the parameters of the cognitive model and allows behavioral data, even in the absence of neural data, to constrain the neural model. Critically, our Bayesian approach can reveal interactions between behavioral and neural parameters, and hence between neural activity and cognitive mechanisms. We demonstrate the utility of our approach with applications to simulated fMRI data with a recognition model and to diffusion-weighted imaging data with a response time model of perceptual choice. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. A Bayesian framework for simultaneously modeling neural and behavioral data✩

    Science.gov (United States)

    Turner, Brandon M.; Forstmann, Birte U.; Wagenmakers, Eric-Jan; Brown, Scott D.; Sederberg, Per B.; Steyvers, Mark

    2013-01-01

    Scientists who study cognition infer underlying processes either by observing behavior (e.g., response times, percentage correct) or by observing neural activity (e.g., the BOLD response). These two types of observations have traditionally supported two separate lines of study. The first is led by cognitive modelers, who rely on behavior alone to support their computational theories. The second is led by cognitive neuroimagers, who rely on statistical models to link patterns of neural activity to experimental manipulations, often without any attempt to make a direct connection to an explicit computational theory. Here we present a flexible Bayesian framework for combining neural and cognitive models. Joining neuroimaging and computational modeling in a single hierarchical framework allows the neural data to influence the parameters of the cognitive model and allows behavioral data, even in the absence of neural data, to constrain the neural model. Critically, our Bayesian approach can reveal interactions between behavioral and neural parameters, and hence between neural activity and cognitive mechanisms. We demonstrate the utility of our approach with applications to simulated fMRI data with a recognition model and to diffusion-weighted imaging data with a response time model of perceptual choice. PMID:23370060

  13. Lack of Motor Neuron Differentiation is an Intrinsic Property of the Mouse Secondary Neural Tube

    Science.gov (United States)

    Shum, Alisa S.W.; Tang, Louisa S.C.; Copp, Andrew J.; Roelink, Henk

    2016-01-01

    The cranial part of the amniote neural tube is formed by folding and fusion of the ectoderm-derived neural plate (primary neurulation). After posterior neuropore closure, however, the caudal neural tube is formed by cavitation of tail bud mesenchyme (secondary neurulation). In mouse embryos, the secondary neural tube expresses several genes important in early patterning and induction, in restricted domains similar to the primary neural tube, yet it does not undergo neuronal differentiation, but subsequently degenerates. Although the secondary neural tube, isolated from surrounding tissues, is responsive to exogenous Sonic Hedgehog proteins in vitro, motor neuron differentiation is never observed. This cannot be attributed to the properties of the secondary notochord, since it is able to induce motor neuron differentiation in naïve chick neural plate explants. Taken together, these results support that the lack of motor neuron differentiation is an intrinsic property of the mouse secondary neural tube. PMID:20960561

  14. 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

  15. Radiation Behavior of Analog Neural Network Chip

    Science.gov (United States)

    Langenbacher, H.; Zee, F.; Daud, T.; Thakoor, A.

    1996-01-01

    A neural network experiment conducted for the Space Technology Research Vehicle (STRV-1) 1-b launched in June 1994. Identical sets of analog feed-forward neural network chips was used to study and compare the effects of space and ground radiation on the chips. Three failure mechanisms are noted.

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

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    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.

  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. Epigenetic landscaping during hESC differentiation to neural cells.

    Science.gov (United States)

    Golebiewska, Anna; Atkinson, Stuart P; Lako, Majlinda; Armstrong, Lyle

    2009-06-01

    The molecular mechanisms underlying pluripotency and lineage specification from embryonic stem cells (ESCs) are still largely unclear. To address the role of chromatin structure in maintenance of pluripotency in human ESCs (hESCs) and establishment of lineage commitment, we analyzed a panel of histone modifications at promoter sequences of genes involved in maintenance of pluripotency, self-renewal, and in early stages of differentiation. To understand the changes occurring at lineage-specific gene regulatory sequences, we have established an efficient purification system that permits the examination of two distinct populations of lineage committed cells; fluorescence activated cell sorted CD133(+) CD45(-)CD34(-) neural stem cells and beta-III-tubulin(+) putative neurons. Here we report the importance of other permissive marks supporting trimethylation of Lysine 4 H3 at the active stem cell promoters as well as poised bivalent and nonbivalent lineage-specific gene promoters in hESCs. Methylation of lysine 9 H3 was found to play a role in repression of pluripotency-associated and lineage-specific genes on differentiation. Moreover, presence of newly formed bivalent domains was observed at the neural progenitor stage. However, they differ significantly from the bivalent domains observed in hESCs, with a possible role of dimethylation of lysine 9 H3 in repressing the poised genes.

  19. 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.

  20. 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.

  1. Neural differentiation of transplanted neural stem cells in a rat model of striatal lacunar infarction: light and electron microscopic observations

    Science.gov (United States)

    Muñetón-Gómez, Vilma C.; Doncel-Pérez, Ernesto; Fernandez, Ana P.; Serrano, Julia; Pozo-Rodrigálvarez, Andrea; Vellosillo-Huerta, Lara; Taylor, Julian S.; Cardona-Gómez, Gloria P.; Nieto-Sampedro, Manuel; Martínez-Murillo, Ricardo

    2012-01-01

    The increased risk and prevalence of lacunar stroke and Parkinson's disease (PD) makes the search for better experimental models an important requirement for translational research. In this study we assess ischemic damage of the nigrostriatal pathway in a model of lacunar stroke evoked by damaging the perforating arteries in the territory of the substantia nigra (SN) of the rat after stereotaxic administration of endothelin-1 (ET-1), a potent vasoconstrictor peptide. We hypothesized that transplantation of neural stem cells (NSCs) with the capacity of differentiating into diverse cell types such as neurons and glia, but with limited proliferation potential, would constitute an alternative and/or adjuvant therapy for lacunar stroke. These cells showed neuritogenic activity in vitro and a high potential for neural differentiation. Light and electron microscopy immunocytochemistry was used to characterize GFP-positive neurons derived from the transplants. 48 h after ET-1 injection, we characterized an area of selective degeneration of dopaminergic neurons within the nigrostriatal pathway characterized with tissue necrosis and glial scar formation, with subsequent behavioral signs of Parkinsonism. Light microscopy showed that grafted cells within the striatal infarction zone differentiated with a high yield into mature glial cells (GFAP-positive) and neuron types present in the normal striatum. Electron microscopy revealed that NSCs-derived neurons integrated into the host circuitry establishing synaptic contacts, mostly of the asymmetric type. Astrocytes were closely associated with normal small-sized blood vessels in the area of infarct, suggesting a possible role in the regulation of the blood brain barrier and angiogenesis. Our results encourage the use of NSCs as a cell-replacement therapy for the treatment of human vascular Parkinsonism. PMID:22876219

  2. Differential neural activity patterns for spatial relations in humans: a MEG study.

    Science.gov (United States)

    Scott, Nicole M; Leuthold, Arthur; Sera, Maria D; Georgopoulos, Apostolos P

    2016-02-01

    Children learn the words for above-below relations earlier than for left-right relations, despite treating these equally well in a simple visual categorization task. Even as adults--conflicts in congruency, such as when a stimulus is depicted in a spatially incongruent manner with respect to salient global cues--can be challenging. Here we investigated the neural correlates of encoding and maintaining in working memory above-below and left-right relational planes in 12 adults using magnetoencephalography in order to discover whether above-below relations are represented by the brain differently than left-right relations. Adults performed perfectly on the task behaviorally, so any differences in neural activity were attributed to the stimuli's cognitive attributes. In comparing above-below to left-right relations during stimulus encoding, we found the greatest differences in neural activity in areas associated with space and movement. In comparing congruent to incongruent trials, we found the greatest differential activity in premotor areas. For both contrasts, brain areas involved in the encoding phase were also involved in the maintenance phase, which provides evidence that those brain areas are particularly important in representing the relational planes or congruency types throughout the trial. When comparing neural activity associated with the relational planes during working memory, additional right posterior areas were implicated, whereas the congruent-incongruent contrast implicated additional bilateral frontal and temporal areas. These findings are consistent with the hypothesis left-right relations are represented differently than above-below relations.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Japanese studies on neural circuits and behavior of Caenorhabditis elegans

    Science.gov (United States)

    Sasakura, Hiroyuki; Tsukada, Yuki; Takagi, Shin; Mori, Ikue

    2013-01-01

    The nematode Caenorhabditis elegans is an ideal organism for studying neural plasticity and animal behaviors. A total of 302 neurons of a C. elegans hermaphrodite have been classified into 118 neuronal groups. This simple neural circuit provides a solid basis for understanding the mechanisms of the brains of higher animals, including humans. Recent studies that employ modern imaging and manipulation techniques enable researchers to study the dynamic properties of nervous systems with great precision. Behavioral and molecular genetic analyses of this tiny animal have contributed greatly to the advancement of neural circuit research. Here, we will review the recent studies on the neural circuits of C. elegans that have been conducted in Japan. Several laboratories have established unique and clever methods to study the underlying neuronal substrates of behavioral regulation in C. elegans. The technological advances applied to studies of C. elegans have allowed new approaches for the studies of complex neural systems. Through reviewing the studies on the neuronal circuits of C. elegans in Japan, we will analyze and discuss the directions of neural circuit studies. PMID:24348340

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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).

  10. 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.

  11. A Bayesian framework for simultaneously modeling neural and behavioral data

    NARCIS (Netherlands)

    Turner, B.M.; Forstmann, B.U.; Wagenmakers, E.-J.; Brown, S.D.; Sederberg, P.B.; Steyvers, M.

    2013-01-01

    Scientists who study cognition infer underlying processes either by observing behavior (e.g., response times, percentage correct) or by observing neural activity (e.g., the BOLD response). These two types of observations have traditionally supported two separate lines of study. The first is led by

  12. Artificial Neural Networks: A New Approach to Predicting Application Behavior.

    Science.gov (United States)

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

    2002-01-01

    Applied the technique of artificial neural networks to predict which students were likely to apply to one research university. Compared the results to the traditional analysis tool, logistic regression modeling. Found that the addition of artificial intelligence models was a useful new tool for predicting student application behavior. (EV)

  13. Pig Induced Pluripotent Stem Cell-Derived Neural Rosettes Developmentally Mimic Human Pluripotent Stem Cell Neural Differentiation.

    Science.gov (United States)

    Gallegos-Cárdenas, Amalia; Webb, Robin; Jordan, Erin; West, Rachel; West, Franklin D; Yang, Jeong-Yeh; Wang, Kai; Stice, Steven L

    2015-08-15

    For diseases of the brain, the pig (Sus scrofa) is increasingly being used as a model organism that shares many anatomical and biological similarities with humans. We report that pig induced pluripotent stem cells (iPSC) can recapitulate events in early mammalian neural development. Pig iPSC line (POU5F1(high)/SSEA4(low)) had a higher potential to form neural rosettes (NR) containing neuroepithelial cells than either POU5F1(low)/SSEA4(low) or POU5F1(low)/SSEA4(high) lines. Thus, POU5F1 and SSEA4 pluripotency marker profiles in starting porcine iPSC populations can predict their propensity to form more robust NR populations in culture. The NR were isolated and expanded in vitro, retaining their NR morphology and neuroepithelial molecular properties. These cells expressed anterior central nervous system fate markers OTX2 and GBX2 through at least seven passages, and responded to retinoic acid, promoting a more posterior fate (HOXB4+, OTX2-, and GBX2-). These findings offer insight into pig iPSC development, which parallels the human iPSC in both anterior and posterior neural cell fates. These in vitro similarities in early neural differentiation processes support the use of pig iPSC and differentiated neural cells as a cell therapy in allogeneic porcine neural injury and degeneration models, providing relevant translational data for eventual human neural cell therapies.

  14. Dynamic behaviors of the non-neural ectoderm during mammalian cranial neural tube closure.

    Science.gov (United States)

    Ray, Heather J; Niswander, Lee A

    2016-08-15

    The embryonic brain and spinal cord initially form through the process of neural tube closure (NTC). NTC is thought to be highly similar between rodents and humans, and studies of mouse genetic mutants have greatly increased our understanding of the molecular basis of NTC with relevance for human neural tube defects. In addition, studies using amphibian and chick embryos have shed light into the cellular and tissue dynamics underlying NTC. However, the dynamics of mammalian NTC has been difficult to study due to in utero development until recently when advances in mouse embryo ex vivo culture techniques along with confocal microscopy have allowed for imaging of mouse NTC in real time. Here, we have performed live imaging of mouse embryos with a particular focus on the non-neural ectoderm (NNE). Previous studies in multiple model systems have found that the NNE is important for proper NTC, but little is known about the behavior of these cells during mammalian NTC. Here we utilized a NNE-specific genetic labeling system to assess NNE dynamics during murine NTC and identified different NNE cell behaviors as the cranial region undergoes NTC. These results bring valuable new insight into regional differences in cellular behavior during NTC that may be driven by different molecular regulators and which may underlie the various positional disruptions of NTC observed in humans with neural tube defects. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Fahrenfort, Johannes J; van Winden, Frans; Pelloux, Benjamin; Stallen, Mirre; Ridderinkhof, K Richard

    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 prosocial behavior even in one-shot laboratory settings where all interaction has been taken away. A logical step has been to link such behavior to trait empathy-related neurobiological networks. However, as a social interaction unfolds, the degree of uncertainty with respect to the expected payoff of choice behavior may change as a function of the interaction. Here we attempt to capture this factor. We show that the interpersonal tie one develops with another person during interaction - rather than trait empathy - motivates investment in a public good that is shared with an anonymous interaction partner. We examined how individual differences in trait empathy and interpersonal ties modulate neural responses to imposed monetary sharing. After, but not before interaction in a public good game, sharing prompted activation of neural systems associated with reward (striatum), empathy (anterior insular cortex and anterior cingulate cortex) as well as altruism, and social significance [posterior superior temporal sulcus (pSTS)]. Although these activations could be linked to both empathy and interpersonal ties, only tie-related pSTS activation predicted prosocial behavior during subsequent interaction, suggesting a neural substrate for keeping track of social relevance.

  16. Neural Correlates of Dynamically Evolving Interpersonal Ties Predict Prosocial Behavior

    Science.gov (United States)

    Fahrenfort, Johannes J.; van Winden, Frans; Pelloux, Benjamin; Stallen, Mirre; Ridderinkhof, K. Richard

    2011-01-01

    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 prosocial behavior even in one-shot laboratory settings where all interaction has been taken away. A logical step has been to link such behavior to trait empathy-related neurobiological networks. However, as a social interaction unfolds, the degree of uncertainty with respect to the expected payoff of choice behavior may change as a function of the interaction. Here we attempt to capture this factor. We show that the interpersonal tie one develops with another person during interaction – rather than trait empathy – motivates investment in a public good that is shared with an anonymous interaction partner. We examined how individual differences in trait empathy and interpersonal ties modulate neural responses to imposed monetary sharing. After, but not before interaction in a public good game, sharing prompted activation of neural systems associated with reward (striatum), empathy (anterior insular cortex and anterior cingulate cortex) as well as altruism, and social significance [posterior superior temporal sulcus (pSTS)]. Although these activations could be linked to both empathy and interpersonal ties, only tie-related pSTS activation predicted prosocial behavior during subsequent interaction, suggesting a neural substrate for keeping track of social relevance. PMID:22403524

  17. 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.

  18. Distinct neural bases of disruptive behavior and autism symptom severity in boys with autism spectrum disorder.

    Science.gov (United States)

    Yang, Y J Daniel; Sukhodolsky, Denis G; Lei, Jiedi; Dayan, Eran; Pelphrey, Kevin A; Ventola, Pamela

    2017-01-01

    primarily in ACC. In boys with ASD, disruptive behavior has a neural basis in reduced DMN deactivation, which is distinct and separable from that of core ASD symptoms, with the latter characterized by hypoactivation in the social perception circuitry. These differential neurobiological markers may potentially serve as neural targets or predictors for interventions when treating disruptive behavior vs. core symptoms in ASD.

  19. Role of ciliary neurotrophic factor in the proliferation and differentiation of neural stem cells.

    Science.gov (United States)

    Ding, Jun; He, Zhili; Ruan, Juan; Ma, Zilong; Liu, Ying; Gong, Chengxin; Iqbal, Khalid; Sun, Shenggang; Chen, Honghui

    2013-01-01

    Ciliary neurotrophic factor (CNTF) is a pleiotropic cytokine that has been fully studied for its structure, receptor, and signaling pathways and its multiplex effects on neural system, skeletal muscle, and weight control. Recent research demonstrates that CNTF also plays an important role in neurogenesis and the differentiation of neural stem cells. In this article, we summarize the general characteristics of CNTF and its function on neural stem cells, which could be a valuable therapeutic strategy in treating neurological disorders.

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

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    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.

  1. Blueprints for behavior: genetic specification of neural circuitry for innate behaviors.

    Science.gov (United States)

    Manoli, Devanand S; Meissner, Geoffrey W; Baker, Bruce S

    2006-08-01

    Innate behaviors offer a unique opportunity to use genetic analysis to dissect and characterize the neural substrates of complex behavioral programs. Courtship in Drosophila involves a complex series of stereotyped behaviors that include numerous exchanges of multimodal sensory information over time. As we will discuss in this review, recent work has demonstrated that male-specific expression of Fruitless transcription factors (Fru(M) proteins) is necessary and sufficient to confer the potential for male courtship behaviors. Fru(M) factors program neurons of the male central and peripheral nervous systems whose function is dedicated to sexual behaviors. This circuitry seems to integrate sensory information to define behavioral states and regulate conserved neural elements for sex-specific behavioral output. The principles that govern the circuitry specified by Fru(M) expression might also operate in subcortical networks that govern innate behaviors in mammals.

  2. Umbilical cord blood cells CD133+/CD133- cultivation in neural proliferation media differentiates towards neural cell lineages.

    Science.gov (United States)

    Slovinska, Lucia; Novotna, Ivana; Kubes, Miroslav; Radonak, Jozef; Jergova, Stanislava; Cigankova, Viera; Rosocha, Jan; Cizkova, Dasa

    2011-10-01

    Umbilical cord blood (UCB) has been identified as a good source of hematopoietic and nonhematopoietic stem cells that can be easily isolated. In the present study we investigated the possibility of whether stem cells in mononuclear UCB grown under defined conditions can produce progeny with neural phenotype. A combination of antigen-driven magnetic cell sorting (MACs) method and defined culture conditions specific for cells of neural lineages were used for isolation, expansion and differentiation of CD133+/- cells from UCB. Both UCB-derived fractions were expanded by exposure to growth factors (EGF, bFGF). Differentiation was induced by replacing them with fetal bovine serum. Using immunocytochemistry, the cell markers for neural (MAP2, GFAP, RIP) and non-neural lineages (S-100, von Willebrand factor) were detected. The analysis revealed occurrence of fully mature neural and non-neural lineages, which showed qualitative and quantitative differences between population of CD133+ and CD133- cells. The expression levels of MAP2 and RIP in CD133+ were significantly higher than in CD133-, more GFAP positive cells were found in the CD133-. At the same time, S-100 was expressed by 32.47 ± 6.24% of CD133- cells and 29.42 ± 1.32% of CD133- cell expressed a von Willebrand factor antigen. Our results indicate that stem cells derived from umbilical cord blood are easy to obtain, proliferate and are able to differentiate towards the cells of neural lineages, which represents a promising way for their utilization in cell-based therapies for CNS injuries and diseases. Copyright © 2011 IMSS. Published by Elsevier Inc. All rights reserved.

  3. Owl's behavior and neural representation predicted by Bayesian inference.

    Science.gov (United States)

    Fischer, Brian J; Peña, José Luis

    2011-07-03

    The owl captures prey using sound localization. In the classical model, the owl infers sound direction from the position of greatest activity in a brain map of auditory space. However, this model fails to describe the actual behavior. Although owls accurately localize sources near the center of gaze, they systematically underestimate peripheral source directions. We found that this behavior is predicted by statistical inference, formulated as a Bayesian model that emphasizes central directions. We propose that there is a bias in the neural coding of auditory space, which, at the expense of inducing errors in the periphery, achieves high behavioral accuracy at the ethologically relevant range. We found that the owl's map of auditory space decoded by a population vector is consistent with the behavioral model. Thus, a probabilistic model describes both how the map of auditory space supports behavior and why this representation is optimal.

  4. Three-dimensional extracellular matrix-mediated neural stem cell differentiation in a microfluidic device.

    Science.gov (United States)

    Han, Sewoon; Yang, Kisuk; Shin, Yoojin; Lee, Jung Seung; Kamm, Roger D; Chung, Seok; Cho, Seung-Woo

    2012-07-07

    Here, we report a unique method to quantify the effects of in vivo-like extracellular matrix (ECM) for guiding differentiation of neural stem cells (NSCs) in three-dimensional (3D) microenvironments using quantitative real-time polymerase chain reaction (qRT-PCR). We successfully monitored and quantified differentiation of NSCs in small volume ECMs and found that differentiation of NSCs, especially those differentiating towards neuronal and oligodendrocytic lineages, is significantly enhanced by 3D microenvironments reconstituted in the microfluidic channels.

  5. 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

  6. Abnormal differentiation of Sandhoff disease model mouse-derived multipotent stem cells toward a neural lineage.

    Directory of Open Access Journals (Sweden)

    Yasuhiro Ogawa

    Full Text Available In Sandhoff disease (SD, the activity of the lysosomal hydrolytic enzyme, β-hexosaminidase (Hex, is lost due to a Hexb gene defect, which results in the abnormal accumulation of the substrate, GM2 ganglioside (GM2, in neuronal cells, causing neuronal loss, microglial activation, and astrogliosis. We established induced pluripotent stem cells from the cells of SD mice (SD-iPSCs. In the present study, we investigated the occurrence of abnormal differentiation and development of a neural lineage in the asymptomatic phase of SD in vitro using SD mouse fetus-derived neural stem cells (NSCs and SD-iPSCs. It was assumed that the number of SD mouse fetal brain-derived NSCs was reduced and differentiation was promoted, resulting in the inhibition of differentiation into neurons and enhancement of differentiation into astrocytes. The number of SD-iPSC-derived NSCs was also reduced, suggesting that the differentiation of NSCs was promoted, resulting in the inhibition of differentiation into neurons and enhancement of that into astrocytes. This abnormal differentiation of SD-iPSCs toward a neural lineage was reduced by the glucosylceramide synthase inhibitor, miglustat. Furthermore, abnormal differentiation toward a neural lineage was reduced in SD-iPSCs with Hexb gene transfection. Therefore, differentiation ability along the time axis appears to be altered in SD mice in which the differentiation ability of NSCs is promoted and differentiation into neurons is completed earlier, while the timing of differentiation into astrocytes is accelerated. These results clarified that the abnormal differentiation of SD-iPSCs toward a neural lineage in vitro was shown to reflect the pathology of SD.

  7. 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.

  8. Inhibition of DNA methyltransferases and histone deacetylases induces astrocytic differentiation of neural progenitors.

    Science.gov (United States)

    Majumder, Anirban; Dhara, Sujoy K; Swetenburg, Raymond; Mithani, Miloni; Cao, Kaixiang; Medrzycki, Magdalena; Fan, Yuhong; Stice, Steven L

    2013-07-01

    Understanding how to specify rapid differentiation of human neural progenitor towards enriched non-transformed human astrocyte progenitors will provide a critical cell source to further our understanding of how astrocytes play a pivotal role in neural function and development. Human neural progenitors derived from pluripotent embryonic stem cells and propagated in adherent serum-free cultures provide a fate restricted renewable source for quick production of neural cells; however, such cells are highly refractive to astrocytogenesis and show a strong neurogenic bias, similar to neural progenitors from the early embryonic central nervous system (CNS). We found that several astrocytic genes are hypermethylated in such progenitors potentially preventing generation of astrocytes and leading to the proneuronal fate of these progenitors. However, epigenetic modification by Azacytidine (Aza-C) and Trichostatin A (TSA), with concomitant signaling from BMP2 and LIF in neural progenitor cultures shifts this bias, leading to expression of astrocytic markers as early as 5days of differentiation, with near complete suppression of neuronal differentiation. The resultant cells express major astrocytic markers, are amenable to co-culture with neurons, can be propagated as astrocyte progenitors and are cryopreservable. Although previous reports have generated astrocytes from pluripotent cells, the differentiation required extensive culture or selection based on cell surface antigens. The development of a label free and rapid differentiation process will expedite future derivation of astrocytes from various sources pluripotent cells including, but not limited to, human astrocytes associated with various neurological diseases. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Neural circuits mediating olfactory-driven behavior in fish

    Science.gov (United States)

    Kermen, Florence; Franco, Luis M.; Wyatt, Cameron; Yaksi, Emre

    2013-01-01

    The fish olfactory system processes odor signals and mediates behaviors that are crucial for survival such as foraging, courtship, and alarm response. Although the upstream olfactory brain areas (olfactory epithelium and olfactory bulb) are well-studied, less is known about their target brain areas and the role they play in generating odor-driven behaviors. Here we review a broad range of literature on the anatomy, physiology, and behavioral output of the olfactory system and its target areas in a wide range of teleost fish. Additionally, we discuss how applying recent technological advancements to the zebrafish (Danio rerio) could help in understanding the function of these target areas. We hope to provide a framework for elucidating the neural circuit computations underlying the odor-driven behaviors in this small, transparent, and genetically amenable vertebrate. PMID:23596397

  10. Neural correlates of behavioral preference for culturally familiar drinks.

    Science.gov (United States)

    McClure, Samuel M; Li, Jian; Tomlin, Damon; Cypert, Kim S; Montague, Latané M; Montague, P Read

    2004-10-14

    Coca-Cola (Coke) and Pepsi are nearly identical in chemical composition, yet humans routinely display strong subjective preferences for one or the other. This simple observation raises the important question of how cultural messages combine with content to shape our perceptions; even to the point of modifying behavioral preferences for a primary reward like a sugared drink. We delivered Coke and Pepsi to human subjects in behavioral taste tests and also in passive experiments carried out during functional magnetic resonance imaging (fMRI). Two conditions were examined: (1) anonymous delivery of Coke and Pepsi and (2) brand-cued delivery of Coke and Pepsi. For the anonymous task, we report a consistent neural response in the ventromedial prefrontal cortex that correlated with subjects' behavioral preferences for these beverages. In the brand-cued experiment, brand knowledge for one of the drinks had a dramatic influence on expressed behavioral preferences and on the measured brain responses.

  11. Jarid1b targets genes regulating development and is involved in neural differentiation

    DEFF Research Database (Denmark)

    Schmitz, Sandra U; Albert, Mareike; Malatesta, Martina

    2011-01-01

    -renewal and differentiation is just starting to emerge. Here, we show that the H3K4me2/3 histone demethylase Jarid1b (Kdm5b/Plu1) is dispensable for ESC self-renewal, but essential for ESC differentiation along the neural lineage. By genome-wide location analysis, we demonstrate that Jarid1b localizes predominantly...

  12. 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

    2018-01-10

    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.

  13. 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

    Cerebral ischemia activates endogenous reparative processes, such as increased proliferation of neural stem cells (NSCs) in the subventricular zone (SVZ) and migration of neural progenitor cells (NPCs) toward the ischemic area. However, this reparative process is limited because most of the NPCs...

  14. 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.

  15. 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.

  16. Combined effect of pulsed electromagnetic field and sound wave on In vitro and In vivo neural differentiation of human mesenchymal stem cells.

    Science.gov (United States)

    Choi, Yun-Kyong; Urnukhsaikhan, Enerelt; Yoon, Hee-Hoon; Seo, Young-Kwon; Cho, Hyunjin; Jeong, Jong-Seob; Kim, Soo-Chan; Park, Jung-Keug

    2017-01-01

    Biophysical wave stimulus has been used as an effective tool to promote cellular maturation and differentiation in the construction of engineered tissue. Pulsed electromagnetic fields (PEMFs) and sound waves have been selected as effective stimuli that can promote neural differentiation. The aim of this study was to investigate the synergistic effect of PEMFs and sound waves on the neural differentiation potential in vitro and in vivo using human bone marrow mesenchymal stem cells (hBM-MSCs). In vitro, neural-related genes in hBM-MSCs were accelerated by the combined exposure to both waves more than by individual exposure to PEMFs or sound waves. The combined wave also up-regulated the expression of neural and synaptic-related proteins in a three-dimensional (3-D) culture system through the phosphorylation of extracellular signal-related kinase. In a mouse model of photochemically induced ischemia, exposure to the combined wave reduced the infarction volume and improved post-injury behavioral activity. These results indicate that a combined stimulus of biophysical waves, PEMFs and sound can enhance and possibly affect the differentiation of MSCs into neural cells. Our study is meaningful for highlighting the potential of combined wave for neurogenic effects and providing new therapeutic approaches for neural cell therapy. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:201-211, 2017. © 2016 American Institute of Chemical Engineers.

  17. Models of Acetylcholine and Dopamine Signals Differentially Improve Neural Representations

    Science.gov (United States)

    Holca-Lamarre, Raphaël; Lücke, Jörg; Obermayer, Klaus

    2017-01-01

    Biological and artificial neural networks (ANNs) represent input signals as patterns of neural activity. In biology, neuromodulators can trigger important reorganizations of these neural representations. For instance, pairing a stimulus with the release of either acetylcholine (ACh) or dopamine (DA) evokes long lasting increases in the responses of neurons to the paired stimulus. The functional roles of ACh and DA in rearranging representations remain largely unknown. Here, we address this question using a Hebbian-learning neural network model. Our aim is both to gain a functional understanding of ACh and DA transmission in shaping biological representations and to explore neuromodulator-inspired learning rules for ANNs. We model the effects of ACh and DA on synaptic plasticity and confirm that stimuli coinciding with greater neuromodulator activation are over represented in the network. We then simulate the physiological release schedules of ACh and DA. We measure the impact of neuromodulator release on the network's representation and on its performance on a classification task. We find that ACh and DA trigger distinct changes in neural representations that both improve performance. The putative ACh signal redistributes neural preferences so that more neurons encode stimulus classes that are challenging for the network. The putative DA signal adapts synaptic weights so that they better match the classes of the task at hand. Our model thus offers a functional explanation for the effects of ACh and DA on cortical representations. Additionally, our learning algorithm yields performances comparable to those of state-of-the-art optimisation methods in multi-layer perceptrons while requiring weaker supervision signals and interacting with synaptically-local weight updates. PMID:28690509

  18. SSEA4-positive pig induced pluripotent stem cells are primed for differentiation into neural cells.

    Science.gov (United States)

    Yang, Jeong-Yeh; Mumaw, Jennifer L; Liu, Yubing; Stice, Steve L; West, Franklin D

    2013-01-01

    Neural cells derived from induced pluripotent stem cells (iPSCs) have the potential for autologous cell therapies in treating patients with severe neurological disorders or injury. However, further study of efficacy and safety are needed in large animal preclinical models that have similar neural anatomy and physiology to humans such as the pig. The pig model for pluripotent stem cell therapy has been made possible for the first time with the development of pig iPSCs (piPSCs) capable of in vitro and in vivo differentiation into tissues of all three germ layers. Still, the question remains if piPSCs are capable of undergoing robust neural differentiation using a system similar to those being used with human iPSCs. In this study, we generated a new line of piPSCs from fibroblast cells that expressed pluripotency markers and were capable of embryoid body differentiation into all three germ layers. piPSCs demonstrated robust neural differentiation forming βIII-TUB/MAP2+ neurons, GFAP+ astrocytes, and O4+ oligodendrocytes and demonstrated strong upregulation of neural cell genes representative of all three major neural lineages of the central nervous system. In the presence of motor neuron signaling factors, piPSC-derived neurons showed expression of transcription factors associated with motor neuron differentiation (HB9 and ISLET1). Our findings demonstrate that SSEA4 expression is required for piPSCs to differentiate into neurons, astrocytes, and oligodendrocytes and furthermore develop specific neuronal subtypes. This indicates that the pigs can fill the need for a powerful model to study autologous neural iPSC therapies in a system similar to humans.

  19. Elastic modulus affects the growth and differentiation of neural stem cells

    Directory of Open Access Journals (Sweden)

    Xian-feng Jiang

    2015-01-01

    Full Text Available It remains poorly understood if carrier hardness, elastic modulus, and contact area affect neural stem cell growth and differentiation. Tensile tests show that the elastic moduli of Tiansu and SMI silicone membranes are lower than that of an ordinary dish, while the elastic modulus of SMI silicone membrane is lower than that of Tiansu silicone membrane. Neural stem cells from the cerebral cortex of embryonic day 16 Sprague-Dawley rats were seeded onto ordinary dishes as well as Tiansu silicone membrane and SMI silicone membrane. Light microscopy showed that neural stem cells on all three carriers show improved adherence. After 7 days of differentiation, neuron specific enolase, glial fibrillary acidic protein, and myelin basic protein expression was detected by immunofluorescence. Moreover, flow cytometry revealed a higher rate of neural stem cell differentiation into astrocytes on Tiansu and SMI silicone membranes than on the ordinary dish, which was also higher on the SMI than the Tiansu silicone membrane. These findings confirm that all three cell carrier types have good biocompatibility, while SMI and Tiansu silicone membranes exhibit good mechanical homogenization. Thus, elastic modulus affects neural stem cell differentiation into various nerve cells. Within a certain range, a smaller elastic modulus results in a more obvious trend of cell differentiation into astrocytes.

  20. 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.

  1. Shaping embodied neural networks for adaptive goal-directed behavior.

    Directory of Open Access Journals (Sweden)

    Zenas C Chao

    2008-03-01

    Full Text Available The acts of learning and memory are thought to emerge from the modifications of synaptic connections between neurons, as guided by sensory feedback during behavior. However, much is unknown about how such synaptic processes can sculpt and are sculpted by neuronal population dynamics and an interaction with the environment. Here, we embodied a simulated network, inspired by dissociated cortical neuronal cultures, with an artificial animal (an animat through a sensory-motor loop consisting of structured stimuli, detailed activity metrics incorporating spatial information, and an adaptive training algorithm that takes advantage of spike timing dependent plasticity. By using our design, we demonstrated that the network was capable of learning associations between multiple sensory inputs and motor outputs, and the animat was able to adapt to a new sensory mapping to restore its goal behavior: move toward and stay within a user-defined area. We further showed that successful learning required proper selections of stimuli to encode sensory inputs and a variety of training stimuli with adaptive selection contingent on the animat's behavior. We also found that an individual network had the flexibility to achieve different multi-task goals, and the same goal behavior could be exhibited with different sets of network synaptic strengths. While lacking the characteristic layered structure of in vivo cortical tissue, the biologically inspired simulated networks could tune their activity in behaviorally relevant manners, demonstrating that leaky integrate-and-fire neural networks have an innate ability to process information. This closed-loop hybrid system is a useful tool to study the network properties intermediating synaptic plasticity and behavioral adaptation. The training algorithm provides a stepping stone towards designing future control systems, whether with artificial neural networks or biological animats themselves.

  2. Cognition: Differential-geometrical view on neural networks

    Directory of Open Access Journals (Sweden)

    S. A. Buffalov

    1999-01-01

    Full Text Available A neural network taken as a model of a trainable system appears to be nothing but a dynamical system evolving on a tangent bundle with changeable metrics. In other words to learn means to change metrics of a definite manifold.

  3. 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.

  4. Differentiation of reprogrammed human adipose mesenchymal stem cells toward neural cells with defined transcription factors.

    Science.gov (United States)

    Qu, Xinjian; Liu, Tianqing; Song, Kedong; Li, Xiangqin; Ge, Dan

    2013-10-04

    Somatic cell reprogramming may become a powerful approach to generate specific human cell types for cell-fate determination studies and potential transplantation therapies of neurological diseases. Here we report a reprogramming methodology with which human adipose stem cells (hADSCs) can be differentiated into neural cells. After being reprogrammed with polycistronic plasmid carrying defined factor OCT3/4, SOX2, KLF4 and c-MYC, and further treated with neural induce medium, the hADSCs switched to differentiate toward neural cell lineages. The generated cells had normal karyotypes and exogenous vector sequences were not inserted in the genomes. Therefore, this cell lineage conversion methodology bypasses the risk of mutation and gene instability, and provides a novel strategy to obtain patient-specific neural cells for basic research and therapeutic application. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Cell density-dependent differential proliferation of neural stem cells on omnidirectional nanopore-arrayed surface.

    Science.gov (United States)

    Cha, Kyoung Je; Kong, Sun-Young; Lee, Ji Soo; Kim, Hyung Woo; Shin, Jae-Yeon; La, Moonwoo; Han, Byung Woo; Kim, Dong Sung; Kim, Hyun-Jung

    2017-10-12

    Recently, the importance of surface nanotopography in the determination of stem cell fate and behavior has been revealed. In the current study, we generated polystyrene cell-culture dishes with an omnidirectional nanopore arrayed surface (ONAS) (diameter: 200 nm, depth: 500 nm, center-to-center distance: 500 nm) and investigated the effects of nanotopography on rat neural stem cells (NSCs). NSCs cultured on ONAS proliferated better than those on the flat surface when cell density was low and showed less spontaneous differentiation during proliferation in the presence of mitogens. Interestingly, NSCs cultured on ONAS at clonal density demonstrated a propensity to generate neurospheres, whereas those on the flat surface migrated out, proliferated as individuals, and spread out to attach to the surface. However, the differential patterns of proliferation were cell density-dependent since the distinct phenomena were lost when cell density was increased. ONAS modulated cytoskeletal reorganization and inhibited formation of focal adhesion, which is generally observed in NSCs grown on flat surfaces. ONAS appeared to reinforce NSC-NSC interaction, restricted individual cell migration and prohibited NSC attachment to the nanopore surface. These data demonstrate that ONAS maintains NSCs as undifferentiated while retaining multipotency and is a better topography for culturing low density NSCs.

  6. Differential diagnosis of dumbbell lesions associated with spinal neural foraminal widening: Imaging features

    Energy Technology Data Exchange (ETDEWEB)

    Kivrak, Ali Sami [Selcuk University, Meram Medical Faculty, Department of Radiology, 42080 Konya (Turkey)], E-mail: alisamikivrak@hotmail.com; Koc, Osman; Emlik, Dilek; Kiresi, Demet; Odev, Kemal [Selcuk University, Meram Medical Faculty, Department of Radiology, 42080 Konya (Turkey); Kalkan, Erdal [Selcuk University, Meram Medical Faculty, Department of Neurosurgery, Konya (Turkey)

    2009-07-15

    Computed tomography (CT) and magnetic resonance imaging (MRI) reliably demonstrate typical features of schwannomas or neurofibromas in the vast majority of dumbbell lesions responsible for neural foraminal widening. However, a large variety of unusual lesions which are causes of neural foraminal widening can also be encountered in the spinal neural foramen. Radiologic findings can be helpful in differential diagnosis of lesions of spinal neural foramen including neoplastic lesions such as benign/malign peripheral nerve sheath tumors (PNSTs), solitary bone plasmacytoma (SBP), chondroid chordoma, superior sulcus tumor, metastasis and non-neoplastic lesions such as infectious process (tuberculosis, hydatid cyst), aneurysmal bone cyst (ABC), synovial cyst, traumatic pseudomeningocele, arachnoid cyst, vertebral artery tortuosity. In this article, we discuss CT and MRI findings of dumbbell lesions which are causes of neural foraminal widening.

  7. 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

  8. The Effects of Topographical Patterns and Sizes on Neural Stem Cell Behavior

    Science.gov (United States)

    Qi, Lin; Li, Ning; Huang, Rong; Song, Qin; Wang, Long; Zhang, Qi; Su, Ruigong; Kong, Tao; Tang, Mingliang; Cheng, Guosheng

    2013-01-01

    Engineered topographical manipulation, a paralleling approach with conventional biochemical cues, has recently attracted the growing interests in utilizations to control stem cell fate. In this study, effects of topological parameters, pattern and size are emphasized on the proliferation and differentiation of adult neural stem cells (ANSCs). We fabricate micro-scale topographical Si wafers with two different feature sizes. These topographical patterns present linear micro-pattern (LMP), circular micro-pattern (CMP) and dot micro-pattern (DMP). The results show that the three topography substrates are suitable for ANSC growth, while they all depress ANSC proliferation when compared to non-patterned substrates (control). Meanwhile, LMP and CMP with two feature sizes can both significantly enhance ANSC differentiation to neurons compared to control. The smaller the feature size is, the better upregulation applies to ANSC for the differentiated neurons. The underlying mechanisms of topography-enhanced neuronal differentiation are further revealed by directing suppression of mitogen-activated protein kinase/extracellular signaling-regulated kinase (MAPK/Erk) signaling pathway in ANSC using U0126, known to inhibit the activation of Erk. The statistical results suggest MAPK/Erk pathway is partially involved in topography-induced differentiation. These observations provide a better understanding on the different roles of topographical cues on stem cell behavior, especially on the selective differentiation, and facilitate to advance the field of stem cell therapy. PMID:23527077

  9. Genome-wide copy number profiling of mouse neural stem cells during differentiation

    Directory of Open Access Journals (Sweden)

    U. Fischer

    2015-09-01

    Full Text Available There is growing evidence that gene amplifications were present in neural stem and progenitor cells during differentiation. We used array-CGH to discover copy number changes including gene amplifications and deletions during differentiation of mouse neural stem cells using TGF-ß and FCS for differentiation induction. Array data were deposited in GEO (Gene Expression Omnibus, NCBI under accession number GSE35523. Here, we describe in detail the cell culture features and our TaqMan qPCR-experiments to validate the array-CGH analysis. Interpretation of array-CGH experiments regarding gene amplifications in mouse and further detailed analysis of amplified chromosome regions associated with these experiments were published by Fischer and colleagues in Oncotarget (Fischer et al., 2015. We provide additional information on deleted chromosome regions during differentiation and give an impressive overview on copy number changes during differentiation induction at a time line.

  10. Nano-Biosensor for Monitoring the Neural Differentiation of Stem Cells

    Directory of Open Access Journals (Sweden)

    Jin-Ho Lee

    2016-11-01

    Full Text Available In tissue engineering and regenerative medicine, monitoring the status of stem cell differentiation is crucial to verify therapeutic efficacy and optimize treatment procedures. However, traditional methods, such as cell staining and sorting, are labor-intensive and may damage the cells. Therefore, the development of noninvasive methods to monitor the differentiation status in situ is highly desirable and can be of great benefit to stem cell-based therapies. Toward this end, nanotechnology has been applied to develop highly-sensitive biosensors to noninvasively monitor the neural differentiation of stem cells. Herein, this article reviews the development of noninvasive nano-biosensor systems to monitor the neural differentiation of stem cells, mainly focusing on optical (plasmonic and eletrochemical methods. The findings in this review suggest that novel nano-biosensors capable of monitoring stem cell differentiation are a promising type of technology that can accelerate the development of stem cell therapies, including regenerative medicine.

  11. Knockdown of tissue nonspecific alkaline phosphatase impairs neural stem cell proliferation and differentiation.

    Science.gov (United States)

    Kermer, Vanessa; Ritter, Mathias; Albuquerque, Boris; Leib, Christoph; Stanke, Matthias; Zimmermann, Herbert

    2010-11-26

    In the adult mammalian brain the subependymal layer of the lateral ventricles houses neural stem cells giving rise to young neurons migrating towards the olfactory bulb. The molecular cues controlling essential functions within the neurogenesis pathway such as proliferation, short and long distance migration, differentiation and functional integration are poorly understood. Neural progenitors in situ express the tissue nonspecific form of alkaline phosphatase (TNAP), a cell surface-located nonspecific phosphomonoesterase capable of hydrolyzing extracellular nucleotides. To gain insight into the functional role of TNAP in cultured multipotent neural stem cells we applied a knockdown protocol using RNA interference with shRNA and retroviral infection. We show that TNAP knockdown reduces cell proliferation and differentiation into neurons or oligodendrocytes. This effect is abrogated by addition of alkaline phosphatase to the culture medium. Our results suggest that TNAP is essential for NSC proliferation and differentiation in vitro and possibly also in vivo. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  12. Oxytocin modulation of neural circuits for social behavior.

    Science.gov (United States)

    Marlin, Bianca J; Froemke, Robert C

    2017-02-01

    Oxytocin is a hypothalamic neuropeptide that has gained attention for the effects on social behavior. Recent findings shed new light on the mechanisms of oxytocin in synaptic plasticity and adaptively modifying neural circuits for social interactions such as conspecific recognition, pair bonding, and maternal care. Here, we review several of these newer studies on oxytocin in the context of previous findings, with an emphasis on social behavior and circuit plasticity in various brain regions shown to be enriched for oxytocin receptors. We provide a framework that highlights current circuit-level mechanisms underlying the widespread action of oxytocin. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 169-189, 2017. © 2016 Wiley Periodicals, Inc.

  13. Anticipation in Object Manipulation: Behavioral and Neural Correlates.

    Science.gov (United States)

    Schneider, Thomas; Hermsdörfer, Joachim

    2016-01-01

    One way to foster the understanding of the impressively skilled fine motor control of human object manipulation is to investigate the rules of the underlying fundamental mechanisms. Examining the action of grasping and lifting objects of various characteristics reveals that one vital step to handle objects in a skilled and fluent way is to predict their properties and plan motor actions accordingly. A large number of behavioral studies have extracted the factors on which we rely when we interact with objects in an anticipatory mode of action. At the same time, considerable effort was taken to elucidate the neuroanatomical areas and networks involved and crucial for anticipatory behavior by conducting functional imaging and stimulation studies and examining the deficits of patients with localized brain damage. This chapter gives an overview of these studies and tries to reconcile their findings, in order to provide an insight into the basic principles of anticipatory motor control and their underlying neural substrates.

  14. Neural correlates of choice behavior related to impulsivity and venturesomeness.

    Science.gov (United States)

    Hinvest, Neal S; Elliott, R; McKie, S; Anderson, Ian M

    2011-07-01

    Impulsivity has been associated with several psychiatric disorders including drug addiction and gambling. Impulsive subjects typically have a preference for short-term over long-term rewards and make risky choices. This study used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of self-rated impulsivity and venturesomeness during tasks involving delayed and risky choice. A broader sampling approach was taken by recruiting participants with behaviors that have been linked to impulsivity (gambling N=15, and recreational drug use N=10) and those without these behaviors (N=9). Selection between delayed or probabilistic rewards was associated with activation in fronto-parietal regions in line with previous research. When selecting between delayed rewards, activity within the pregenual anterior cingulate cortex and ventrolateral prefrontal cortex correlated positively with impulsivity scores while activity within the orbitofrontal cortex, subgenual anterior cingulate cortex and caudate correlated positively with venturesomeness scores. Selection between probabilistic rewards revealed no correlation between scores and regional activations. The results from this study provide targets for future research investigating the neural substrates of impulsivity. They also provide targets for the further investigation into the pathophysiology of addiction and impulse-control disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. 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.

  16. 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

  17. Sexual differentiation of brain and behavior: the zebra finch is not just a flying rat.

    Science.gov (United States)

    Arnold, A P; Schlinger, B A

    1993-01-01

    In rats and other mammals, sex differences in the brain and behavior result from differential secretions of gonadal steroid hormones during early critical periods of neural development. We review the experimental results that support current ideas about the mechanisms of sexual differentiation in mammals, and then apply the same experimental analysis to the study of sexual differentiation of the neural song circuit in the zebra finch (Poephila guttata), a passerine song bird. Administration of estrogen to young female zebra finches causes the female to develop a more masculine song system and to sing as an adult. This estrogenic masculinization is similar to that found for copulatory behavior in mammals. However, striking differences emerge in other aspects of the sexual differentiation process. Experiments that use endocrine agents to block the masculine development in genetic males have so far failed. Moreover, the brain of zebra finches has an unusually high expression of aromatase (estrogen synthetase) in the telencephalon, and estrogen synthesized in the brain from androgen is released into the general circulation. These results suggest that the brain is the primary source of estrogen in the body. If so, then a further understanding of sexual differentiation requires more information on the factors that regulate the cerebral synthesis of estrogen.

  18. The Development of Animal Behavior: From Lorenz to Neural Nets

    Science.gov (United States)

    Bolhuis, Johan J.

    In the study of behavioral development both causal and functional approaches have been used, and they often overlap. The concept of ontogenetic adaptations suggests that each developmental phase involves unique adaptations to the environment of the developing animal. The functional concept of optimal outbreeding has led to further experimental evidence and theoretical models concerning the role of sexual imprinting in the evolutionary process of sexual selection. From a causal perspective it has been proposed that behavioral ontogeny involves the development of various kinds of perceptual, motor, and central mechanisms and the formation of connections among them. This framework has been tested for a number of complex behavior systems such as hunger and dustbathing. Imprinting is often seen as a model system for behavioral development in general. Recent advances in imprinting research have been the result of an interdisciplinary effort involving ethology, neuroscience, and experimental psychology, with a continual interplay between these approaches. The imprinting results are consistent with Lorenz' early intuitive suggestions and are also reflected in the architecture of recent neural net models.

  19. 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

  20. 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......-culture, large numbers of tyrosine hydroxylase (TH)-immunoreactive, catecholaminergic cells could be found underneath individual striatal slices. Cell counting revealed that up to 25.3% (average 16.1%) of the total number of cells in these areas were TH-positive, contrasting a few TH-positive cells (

  1. 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.

  2. 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.

  3. Transient expression of Olig1 initiates the differentiation of neural stem cells into oligodendrocyte progenitor cells

    NARCIS (Netherlands)

    Balasubramaniyan, [No Value; Timmer, N; Kust, B; Boddeke, E; Copray, S

    2004-01-01

    In order to develop an efficient strategy to induce the in vitro differentiation of neural stem cells (NSCs) into oligodendrocyte progenitor cells (OPCs), NSCs were isolated from E14 mice and grown in medium containing epidermal growth factor and fibroblast growth factor (FGF). Besides supplementing

  4. Differentiation of Neural Stem Cells into Oligodendrocytes : Involvement of the Polycomb Group Protein Ezh2

    NARCIS (Netherlands)

    Sher, Falak; Rossler, Reinhard; Brouwer, Nieske; Balasubramaniyan, Veerakumar; Boddeke, Erik; Copray, Sjef

    2008-01-01

    The mechanisms underlying the regulation of neural stem cell (NSC) renewal and maintenance of their multipotency are still not completely understood. Self-renewal of stem cells in general implies repression of genes that encode for cell lineage differentiation. Enhancer of zeste homolog 2 (Ezh2) is

  5. Neural tracking of attended versus ignored speech is differentially affected by hearing loss.

    Science.gov (United States)

    Petersen, Eline Borch; Wöstmann, Malte; Obleser, Jonas; Lunner, Thomas

    2017-01-01

    Hearing loss manifests as a reduced ability to understand speech, particularly in multitalker situations. In these situations, younger normal-hearing listeners' brains are known to track attended speech through phase-locking of neural activity to the slow-varying envelope of the speech. This study investigates how hearing loss, compensated by hearing aids, affects the neural tracking of the speech-onset envelope in elderly participants with varying degree of hearing loss (n = 27, 62-86 yr; hearing thresholds 11-73 dB hearing level). In an active listening task, a to-be-attended audiobook (signal) was presented either in quiet or against a competing to-be-ignored audiobook (noise) presented at three individualized signal-to-noise ratios (SNRs). The neural tracking of the to-be-attended and to-be-ignored speech was quantified through the cross-correlation of the electroencephalogram (EEG) and the temporal envelope of speech. We primarily investigated the effects of hearing loss and SNR on the neural envelope tracking. First, we found that elderly hearing-impaired listeners' neural responses reliably track the envelope of to-be-attended speech more than to-be-ignored speech. Second, hearing loss relates to the neural tracking of to-be-ignored speech, resulting in a weaker differential neural tracking of to-be-attended vs. to-be-ignored speech in listeners with worse hearing. Third, neural tracking of to-be-attended speech increased with decreasing background noise. Critically, the beneficial effect of reduced noise on neural speech tracking decreased with stronger hearing loss. In sum, our results show that a common sensorineural processing deficit, i.e., hearing loss, interacts with central attention mechanisms and reduces the differential tracking of attended and ignored speech. The present study investigates the effect of hearing loss in older listeners on the neural tracking of competing speech. Interestingly, we observed that whereas internal degradation (hearing

  6. Neural tracking of attended versus ignored speech is differentially affected by hearing loss

    Science.gov (United States)

    Wöstmann, Malte; Lunner, Thomas

    2016-01-01

    Hearing loss manifests as a reduced ability to understand speech, particularly in multitalker situations. In these situations, younger normal-hearing listeners' brains are known to track attended speech through phase-locking of neural activity to the slow-varying envelope of the speech. This study investigates how hearing loss, compensated by hearing aids, affects the neural tracking of the speech-onset envelope in elderly participants with varying degree of hearing loss (n = 27, 62–86 yr; hearing thresholds 11–73 dB hearing level). In an active listening task, a to-be-attended audiobook (signal) was presented either in quiet or against a competing to-be-ignored audiobook (noise) presented at three individualized signal-to-noise ratios (SNRs). The neural tracking of the to-be-attended and to-be-ignored speech was quantified through the cross-correlation of the electroencephalogram (EEG) and the temporal envelope of speech. We primarily investigated the effects of hearing loss and SNR on the neural envelope tracking. First, we found that elderly hearing-impaired listeners' neural responses reliably track the envelope of to-be-attended speech more than to-be-ignored speech. Second, hearing loss relates to the neural tracking of to-be-ignored speech, resulting in a weaker differential neural tracking of to-be-attended vs. to-be-ignored speech in listeners with worse hearing. Third, neural tracking of to-be-attended speech increased with decreasing background noise. Critically, the beneficial effect of reduced noise on neural speech tracking decreased with stronger hearing loss. In sum, our results show that a common sensorineural processing deficit, i.e., hearing loss, interacts with central attention mechanisms and reduces the differential tracking of attended and ignored speech. NEW & NOTEWORTHY The present study investigates the effect of hearing loss in older listeners on the neural tracking of competing speech. Interestingly, we observed that whereas internal

  7. Glycogen synthase kinase-3beta regulates differentiation-induced apoptosis of human neural progenitor cells.

    Science.gov (United States)

    Jaeger, Alexandra; Baake, Jana; Weiss, Dieter G; Kriehuber, Ralf

    2013-02-01

    Glycogen synthase kinase-3beta is a multifunctional key regulator enzyme in neural developmental processes and a main component of the canonical Wnt signaling pathway. It is already known that the Wnt-driven differentiation of neural progenitor cells is accompanied by an increase of apoptosis at which the pro-apoptotic function of GSK-3beta is still discussed. The aim of the present study was to investigate whether the phosphorylation level of GSK-3beta at serine 9 is the primary regulatory mechanism of differentiation-induced apoptosis. Differentiating human neural ReNcell VM progenitor cells were treated with the specific GSK-3beta inhibitor SB216763 (10 μM) and analyzed in respect to the intrinsic apoptosis pathway regulation using microscopy and protein expression analysis. Differentiation of ReNcell VM cells was accompanied by cell morphological changes, cytoskeleton rearrangement and apoptosis increase. Treatment of differentiating cells with SB216763 induced a significant dephosphorylation of GSK-3beta at serine 9 accompanied by a significant decrease of apoptosis of about 0.7±0.03% and reduced activation of caspase-3 as well as BAX and PARP cleavage during the first 12h of differentiation compared to untreated, differentiating cells. Dephosphorylation of GSK-3beta at serine 9 appears not solely to be responsible for its pro-apoptotic function, because we observed a decrease of intrinsic apoptosis after treatment of the cells with the specific GSK-3beta inhibitor SB216763. We assume that GSK-3beta drives neural progenitor cell apoptosis by direct interaction with pro-apoptotic BAX or by indirect influence on the canonical Wnt/beta-catenin target gene transcription. Copyright © 2012 ISDN. Published by Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Neuromodulatory connectivity defines the structure of a behavioral neural network.

    Science.gov (United States)

    Diao, Feici; Elliott, Amicia D; Diao, Fengqiu; Shah, Sarav; White, Benjamin H

    2017-11-22

    Neural networks are typically defined by their synaptic connectivity, yet synaptic wiring diagrams often provide limited insight into network function. This is due partly to the importance of non-synaptic communication by neuromodulators, which can dynamically reconfigure circuit activity to alter its output. Here, we systematically map the patterns of neuromodulatory connectivity in a network that governs a developmentally critical behavioral sequence in Drosophila. This sequence, which mediates pupal ecdysis, is governed by the serial release of several key factors, which act both somatically as hormones and within the brain as neuromodulators. By identifying and characterizing the functions of the neuronal targets of these factors, we find that they define hierarchically organized layers of the network controlling the pupal ecdysis sequence: a modular input layer, an intermediate central pattern generating layer, and a motor output layer. Mapping neuromodulatory connections in this system thus defines the functional architecture of the network.

  10. Behavioral and neural correlates of visual preference decision

    Science.gov (United States)

    Shimojo, Shinsuke

    2009-02-01

    Three sets of findings are reported here, all related to behavioral and neural correlates of preference decision. First, when one is engaged in a preference decision task with free observation, one's gaze is biased towards the to-be-chosen stimulus (eg. face) long before (s)he is consciously aware of the decision ("gaze cascade effect"). Second, an fMRI study suggested that implicit activity in a subcortical structure (the Nucleus Accumbens) precedes cognitive and conscious decision of preference. Finally, both novelty and familiarity causally contribute to attractiveness, but differently across object categories (such as faces and natural scenes). Taken together, these results point to dynamical and implicit processes both in short- and long-term, towards conscious preference decision. Finally, some discussion will be given on aesthetic decision (i.e. "beauty").

  11. 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

  12. Habit learning and memory in mammals: behavioral and neural characteristics.

    Science.gov (United States)

    Gasbarri, Antonella; Pompili, Assunta; Packard, Mark G; Tomaz, Carlos

    2014-10-01

    Goal-direct behavior and habit learning represent two forms of instrumental learning; whereas the former is rapidly acquired and regulated by its outcome, the latter is reflexive, elicited by antecedent stimuli rather than their consequences. Habit learning can be generally defined as the acquisition of associations between stimuli and responses. Habits are acquired via experience-dependent plasticity, occurring repeatedly over the course of days or years and becoming remarkably fixed. The distinction between habit learning, as a product of a procedural learning brain system, and a declarative learning system for encoding facts and episodes is based on the hypothesis that memory is composed of multiple systems that have distinct neuroanatomy and operating principles. Here we review recent research analyzing the main behavioral and neural characteristics of habit learning. In particular, we focus on the distinction between goal-directed and habitual behavior, and describe the brain areas and neurotransmitters systems involved in habit learning. The emotional modulation of habit learning in rodents and primates is reviewed, and the implications of habit learning in psychopathology are briefly described. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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    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.

  14. 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.

  15. 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.

  16. The role of microRNAs in human neural stem cells, neuronal differentiation and subtype specification.

    Science.gov (United States)

    Stappert, Laura; Roese-Koerner, Beate; Brüstle, Oliver

    2015-01-01

    The impressive neuronal diversity found within the nervous system emerges from a limited pool of neural progenitor cells that proceed through different gene expression programs to acquire distinct cell fates. Here, we review recent evidence indicating that microRNAs (miRNAs) are critically involved in conferring neural cell identities during neural induction, neuronal differentiation and subtype specification. Several studies have shown that miRNAs act in concert with other gene regulatory factors and genetic switches to regulate the spatial and temporal expression profiles of important cell fate determinants. So far, most studies addressing the role of miRNAs during neurogenesis were conducted using animal models. With the advent of human pluripotent stem cells and the possibility to differentiate these into neural stem cells, we now have the opportunity to study miRNAs in a human context. More insight into the impact of miRNA-based regulation during neural fate choice could in the end be exploited to develop new strategies for the generation of distinct human neuronal cell types.

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

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jinqiao, E-mail: jinqiao1977@163.com [Institute of Pediatrics, Children' s Hospital of Fudan University (China); Sha, Bin [Department of Neonatology, Children' s Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102 (China); Zhou, Wenhao, E-mail: zhou_wenhao@yahoo.com.cn [Department of Neonatology, Children' s Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102 (China); Yang, Yi [Institute of Pediatrics, Children' s Hospital of Fudan University (China)

    2010-03-26

    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.

  18. Genome-wide gene amplification during differentiation of neural progenitor cells in vitro.

    Directory of Open Access Journals (Sweden)

    Ulrike Fischer

    Full Text Available DNA sequence amplification is a phenomenon that occurs predictably at defined stages during normal development in some organisms. Developmental gene amplification was first described in amphibians during gametogenesis and has not yet been described in humans. To date gene amplification in humans is a hallmark of many tumors. We used array-CGH (comparative genomic hybridization and FISH (fluorescence in situ hybridization to discover gene amplifications during in vitro differentiation of human neural progenitor cells. Here we report a complex gene amplification pattern two and five days after induction of differentiation of human neural progenitor cells. We identified several amplified genes in neural progenitor cells that are known to be amplified in malignant tumors. There is also a striking overlap of amplified chromosomal regions between differentiating neural progenitor cells and malignant tumor cells derived from astrocytes. Gene amplifications in normal human cells as physiological process has not been reported yet and may bear resemblance to developmental gene amplifications in amphibians and insects.

  19. Crosslinking of extracellular matrix scaffolds derived from pluripotent stem cell aggregates modulates neural differentiation.

    Science.gov (United States)

    Sart, Sébastien; Yan, Yuanwei; Li, Yan; Lochner, Eric; Zeng, Changchun; Ma, Teng; Li, Yan

    2016-01-01

    At various developmental stages, pluripotent stem cells (PSCs) and their progeny secrete a large amount of extracellular matrices (ECMs) which could interact with regulatory growth factors to modulate stem cell lineage commitment. ECMs derived from PSC can be used as unique scaffolds that provide broad signaling capacities to mediate cellular differentiation. However, the rapid degradation of ECMs can impact their applications as the scaffolds for in vitro cell expansion and in vivo transplantation. To address this issue, this study investigated the effects of crosslinking on the ECMs derived from embryonic stem cells (ESCs) and the regulatory capacity of the crosslinked ECMs on the proliferation and differentiation of reseeded ESC-derived neural progenitor cells (NPCs). To create different biological cues, undifferentiated aggregates, spontaneous embryoid bodies, and ESC-derived NPC aggregates were decellularized. The derived ECMs were crosslinked using genipin or glutaraldehyde to enhance the scaffold stability. ESC-derived NPC aggregates were reseeded on different ECM scaffolds and differential cellular compositions of neural progenitors, neurons, and glial cells were observed. The results indicate that ESC-derived ECM scaffolds affect neural differentiation through intrinsic biological cues and biophysical properties. These scaffolds have potential for in vitro cell culture and in vivo tissue regeneration study. Dynamic interactions of acellular extracellular matrices and stem cells are critical for lineage-specific commitment and tissue regeneration. Understanding the synergistic effects of biochemical, biological, and biophysical properties of acellular matrices would facilitate scaffold design and the functional regulation of stem cells. The present study assessed the influence of crosslinked embryonic stem cell-derived extracellular matrix on neural differentiation and revealed the synergistic interactions of various matrix properties. While embryonic stem

  20. Behavioral and neural bases of extinction learning in Hermissenda

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    Joel S. Cavallo

    2014-08-01

    Full Text Available Extinction of classical conditioning is thought to produce new learning that masks or interferes with the original memory. However, research in the nudibranch Hermissenda crassicornis (H.c. has challenged this view, and instead suggested that extinction erased the original associative memory. We have re-examined extinction in H.c. to test whether extinguished associative memories can be detected on the behavioral and cellular levels, and to characterize the temporal variables involved. Associative conditioning using pairings of light (CS and rotation (US produced characteristic suppression of H.c. phototactic behavior. A single session of extinction training (repeated light-alone presentations reversed suppressed behavior back to pre-training levels when administered 15 min after associative conditioning. This effect was abolished if extinction was delayed by 23 hr, and yet was recovered using extended extinction training (three consecutive daily extinction sessions. Extinguished phototactic suppression did not spontaneously recover at any retention interval tested (2-, 24-, 48-, 72-hr, or after additional US presentations (no observed reinstatement. Extinction training (single session, 15 min interval also reversed the pairing-produced increases in light-evoked spike frequencies of Type B photoreceptors, an identified site of associative memory storage that is causally related to phototactic suppression. These results suggest that the behavioral effects of extinction training are not due to temporary suppression of associative memories, but instead represent a reversal of the underlying cellular changes necessary for the expression of learning. In the companion article, we further elucidate mechanisms responsible for extinction-produced reversal of memory-related neural plasticity in Type B photoreceptors.

  1. Behavioral and neural bases of extinction learning in Hermissenda

    Science.gov (United States)

    Cavallo, Joel S.; Hamilton, Brittany N.; Farley, Joseph

    2014-01-01

    Extinction of classical conditioning is thought to produce new learning that masks or interferes with the original memory. However, research in the nudibranch Hermissenda crassicornis (H.c.) has challenged this view, and instead suggested that extinction erased the original associative memory. We have re-examined extinction in H.c. to test whether extinguished associative memories can be detected on the behavioral and cellular levels, and to characterize the temporal variables involved. Associative conditioning using pairings of light (CS) and rotation (US) produced characteristic suppression of H.c. phototactic behavior. A single session of extinction training (repeated light-alone presentations) reversed suppressed behavior back to pre-training levels when administered 15 min after associative conditioning. This effect was abolished if extinction was delayed by 23 h, and yet was recovered using extended extinction training (three consecutive daily extinction sessions). Extinguished phototactic suppression did not spontaneously recover at any retention interval (RI) tested (2-, 24-, 48-, 72-h), or after additional US presentations (no observed reinstatement). Extinction training (single session, 15 min interval) also reversed the pairing-produced increases in light-evoked spike frequencies of Type B photoreceptors, an identified site of associative memory storage that is causally related to phototactic suppression. These results suggest that the behavioral effects of extinction training are not due to temporary suppression of associative memories, but instead represent a reversal of the underlying cellular changes necessary for the expression of learning. In the companion article, we further elucidate mechanisms responsible for extinction-produced reversal of memory-related neural plasticity in Type B photoreceptors. PMID:25191236

  2. Development of a sexually differentiated behavior and its underlying CNS arousal functions.

    Science.gov (United States)

    Kow, Lee-Ming; Florea, Cristina; Schwanzel-Fukuda, Marlene; Devidze, Nino; Kami Kia, Hosein; Lee, Anna; Zhou, Jin; Maclaughlin, David; Donahoe, Patricia; Pfaff, Donald

    2007-01-01

    This chapter addresses questions regarding lordosis behavior, the most extremely sexually differentiated behavior that has been analyzed for its neural and molecular mechanisms. Analysis of this behavior has proved for the first time that specific biochemical reactions in specific nerve cell groups in the brain determine a mammalian behavior. Lordosis is done by the female but not by the male. How did the process of sexual differentiation occur? A large literature implicates high levels of testosterone during a critical period during development as being responsible for the defeminization of the brain. A new idea, however, offers the possibility of direct genetic influences independent of testosterone levels themselves. We propose here that Mullerian Inhibiting Substance (MIS) and its receptors could constitute an example of a nonandrogenic genetic influence. Further, specific sexual behaviors depend on underlying arousal states in the central nervous system (CNS). We have proposed the concept of generalized CNS arousal and provide information as to how generalized arousal forces interact with specifically sexual influences, thus to facilitate sexually differentiated mating behaviors.

  3. 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.

  4. Gallium nitride induces neuronal differentiation markers in neural stem/precursor cells derived from rat cerebral cortex.

    Science.gov (United States)

    Chen, Chi-Ruei; Li, Yi-Chen; Young, Tai-Horng

    2009-09-01

    In the present study, gallium nitride (GaN) was used as a substrate to culture neural stem/precursor cells (NSPCs), isolated from embryonic rat cerebral cortex, to examine the effect of GaN on the behavior of NSPCs in the presence of basic fibroblast growth factor (bFGF) in serum-free medium. Morphological studies showed that neurospheres maintained their initial shape and formed many long and thick processes with the fasciculate feature on GaN. Immunocytochemical characterization showed that GaN could induce the differentiation of NSPCs into neurons and astrocytes. Compared to poly-d-lysine (PDL), the most common substrate used for culturing neurons, there was considerable expression of synapsin I for differentiated neurons on GaN, suggesting GaN could induce the differentiation of NSPCs towards the mature differentiated neurons. Western blot analysis showed that the suppression of glycogen synthase kinase-3beta (GSK-3beta) activity was one of the effects of GaN-promoted NSPC differentiation into neurons. Finally, compared to PDL, GaN could significantly improve cell survival to reduce cell death after long-term culture. These results suggest that GaN potentially has a combination of electric characteristics suitable for developing neuron and/or NSPC chip systems.

  5. 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

    , neurological disease as well as contributing to clinical research. The neural differentiation process is associated with changes at protein and their post-translational modifications (PTMs). PTMs are important regulators of proteins physicochemical properties, function, activity, and interaction with other...... 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...

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

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    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.

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

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    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.

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

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    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

  9. Behavior and neural correlates of empathy in adolescents.

    Science.gov (United States)

    Overgaauw, Sandy; Güroğlu, Berna; Rieffe, Carolien; Crone, Eveline A

    2014-01-01

    This study examined neural correlates of empathy in adolescence while observing harmful acts. A total of 32 participants (aged 12-19 years) viewed pictures depicting negative (offenders inflicting intentional harm) and positive (friends socializing) social situations. After viewing each picture, participants could allocate hypothetical points to either the offender or the victim in a dictator game. Behaviorally, participants of all ages acted prosocially towards victims, fairly towards positive individuals and punishingly towards offenders. Brain imaging analyses showed that viewing negative situations was associated with more activation in the bilateral intraparietal lobule and the superior temporal sulcus (STS), whereas viewing positive situations was associated with more medial prefrontal cortex and left temporal parietal junction activity. Analyses testing for associations between brain activity and self-reported empathy showed that the STS was correlated negatively with reports of understanding others' distress and the willingness to help others. Together, the findings suggest that adolescents show similar prosocial behavior, as previously reported in adults with greater STS activity, when observing negative social acts that is modulated by an individual's empathy for others. © 2014 S. Karger AG, Basel.

  10. Integrin-associated protein promotes neuronal differentiation of neural stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Kazuhiko Fujimura

    Full Text Available Neural stem/progenitor cells (NSPCs proliferate and differentiate depending on their intrinsic properties and local environment. During the development of the mammalian nervous system, NSPCs generate neurons and glia sequentially. However, little is known about the mechanism that determines the timing of switch from neurogenesis to gliogenesis. In this study, we established a culture system in which the neurogenic potential of NSPCs is decreased in a time-dependent manner, so that short-term-cultured NSPCs differentiate into more neurons compared with long-term-cultured NSPCs. We found that short-term-cultured NSPCs express high levels of integrin-associated protein form 2 (IAP2; so-called CD47 mRNA using differential display analysis. Moreover, IAP2 overexpression in NSPCs induced neuronal differentiation of NSPCs. These findings reveal a novel mechanism by which IAP2 induces neuronal differentiation of NSPCs.

  11. A novel method linking neural connectivity to behavioral fluctuations: Behavior-regressed connectivity.

    Science.gov (United States)

    Passaro, Antony D; Vettel, Jean M; McDaniel, Jonathan; Lawhern, Vernon; Franaszczuk, Piotr J; Gordon, Stephen M

    2017-03-01

    During an experimental session, behavioral performance fluctuates, yet most neuroimaging analyses of functional connectivity derive a single connectivity pattern. These conventional connectivity approaches assume that since the underlying behavior of the task remains constant, the connectivity pattern is also constant. We introduce a novel method, behavior-regressed connectivity (BRC), to directly examine behavioral fluctuations within an experimental session and capture their relationship to changes in functional connectivity. This method employs the weighted phase lag index (WPLI) applied to a window of trials with a weighting function. Using two datasets, the BRC results are compared to conventional connectivity results during two time windows: the one second before stimulus onset to identify predictive relationships, and the one second after onset to capture task-dependent relationships. In both tasks, we replicate the expected results for the conventional connectivity analysis, and extend our understanding of the brain-behavior relationship using the BRC analysis, demonstrating subject-specific BRC maps that correspond to both positive and negative relationships with behavior. Comparison with Existing Method(s): Conventional connectivity analyses assume a consistent relationship between behaviors and functional connectivity, but the BRC method examines performance variability within an experimental session to understand dynamic connectivity and transient behavior. The BRC approach examines connectivity as it covaries with behavior to complement the knowledge of underlying neural activity derived from conventional connectivity analyses. Within this framework, BRC may be implemented for the purpose of understanding performance variability both within and between participants. Published by Elsevier B.V.

  12. A Neural Substrate for Rapid Timbre Recognition? Neural and Behavioral Discrimination of Very Brief Acoustic Vowels.

    Science.gov (United States)

    Occelli, F; Suied, C; Pressnitzer, D; Edeline, J-M; Gourévitch, B

    2016-06-01

    The timbre of a sound plays an important role in our ability to discriminate between behaviorally relevant auditory categories, such as different vowels in speech. Here, we investigated, in the primary auditory cortex (A1) of anesthetized guinea pigs, the neural representation of vowels with impoverished timbre cues. Five different vowels were presented with durations ranging from 2 to 128 ms. A psychophysical experiment involving human listeners showed that identification performance was near ceiling for the longer durations and degraded close to chance level for the shortest durations. This was likely due to spectral splatter, which reduced the contrast between the spectral profiles of the vowels at short durations. Effects of vowel duration on cortical responses were well predicted by the linear frequency responses of A1 neurons. Using mutual information, we found that auditory cortical neurons in the guinea pig could be used to reliably identify several vowels for all durations. Information carried by each cortical site was low on average, but the population code was accurate even for durations where human behavioral performance was poor. These results suggest that a place population code is available at the level of A1 to encode spectral profile cues for even very short sounds. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. 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.

  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. Extensive neuronal differentiation of human neural stem cell grafts in adult rat spinal cord.

    Directory of Open Access Journals (Sweden)

    Jun Yan

    2007-02-01

    Full Text Available Effective treatments for degenerative and traumatic diseases of the nervous system are not currently available. The support or replacement of injured neurons with neural grafts, already an established approach in experimental therapeutics, has been recently invigorated with the addition of neural and embryonic stem-derived precursors as inexhaustible, self-propagating alternatives to fetal tissues. The adult spinal cord, i.e., the site of common devastating injuries and motor neuron disease, has been an especially challenging target for stem cell therapies. In most cases, neural stem cell (NSC transplants have shown either poor differentiation or a preferential choice of glial lineages.In the present investigation, we grafted NSCs from human fetal spinal cord grown in monolayer into the lumbar cord of normal or injured adult nude rats and observed large-scale differentiation of these cells into neurons that formed axons and synapses and established extensive contacts with host motor neurons. Spinal cord microenvironment appeared to influence fate choice, with centrally located cells taking on a predominant neuronal path, and cells located under the pia membrane persisting as NSCs or presenting with astrocytic phenotypes. Slightly fewer than one-tenth of grafted neurons differentiated into oligodendrocytes. The presence of lesions increased the frequency of astrocytic phenotypes in the white matter.NSC grafts can show substantial neuronal differentiation in the normal and injured adult spinal cord with good potential of integration into host neural circuits. In view of recent similar findings from other laboratories, the extent of neuronal differentiation observed here disputes the notion of a spinal cord that is constitutively unfavorable to neuronal repair. Restoration of spinal cord circuitry in traumatic and degenerative diseases may be more realistic than previously thought, although major challenges remain, especially with respect to the

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

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    Manoj Tripathy

    2012-01-01

    Full Text Available 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 discriminate between internal faults from inrush and overexcitation conditions. This algorithm has been developed by considering optimal number of neurons in hidden layer and optimal number of neurons at output layer. The proposed algorithm makes use of ratio of voltage to frequency and amplitude of differential current for transformer operating condition detection. This paper presents a comparative study of power transformer differential protection algorithms based on harmonic restraint method, NNPCA, feed forward back propagation neural network (FFBPNN, space vector analysis of the differential signal, and their time characteristic shapes in Park’s plane. The algorithms are compared as to their speed of response, computational burden, and the capability to distinguish between a magnetizing inrush and power transformer internal fault. The mathematical basis for each algorithm is briefly described. All the algorithms are evaluated using simulation performed with PSCAD/EMTDC and MATLAB.

  17. Hormonal influences on sexually differentiated behavior in nonhuman primates.

    Science.gov (United States)

    Wallen, Kim

    2005-04-01

    Sexually dimorphic behavior in nonhuman primates results from behavioral predispositions organized by prenatal androgens. The rhesus monkey has been the primary primate model for understanding the hormonal organization of sexually dimorphic behavior. Historically, female fetuses have received high prenatal androgen doses to investigate the masculinizing and defeminizing effects of androgens. Such treatments masculinized juvenile and adult copulatory behavior and defeminized female-typical sexual initiation to adult estrogen treatment. Testosterone and the nonaromatizable androgen, 5alpha-dihydrotestosterone, produced similar effects suggesting that estrogenic metabolites of androgens are not critical for masculinization and defeminization in rhesus monkeys. Long duration androgen treatments masculinized both behavior and genitalia suggesting that socializing responses to the females' male-like appearance may have produced the behavioral changes. Treatments limited to 35 days early or late in gestation differentially affected behavioral and genital masculinization demonstrating direct organizing actions of prenatal androgens. Recent studies exposed fetal females to smaller doses of androgens and interfered with endogenous androgens using the anti-androgen flutamide. Low dose androgen treatment only significantly masculinized infant vocalizations and produced no behavioral defeminization. Females receiving late gestation flutamide showed masculinized infant vocalizations and defeminized interest in infants. Both late androgen and flutamide treatment hypermasculinized some male juvenile behaviors. Early flutamide treatment blocked full male genital masculinization, but did not alter their juvenile or adult behavior. The role of neuroendocrine feedback mechanisms in the flutamide effects is discussed. Sexually differentiated behavior ultimately reflects both hormonally organized behavioral predispositions and the social experience that converts these predispositions

  18. 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.

  19. Distinct intracellular Ca(2+) dynamics regulate apical constriction and differentially contribute to neural tube closure.

    Science.gov (United States)

    Suzuki, Makoto; Sato, Masanao; Koyama, Hiroshi; Hara, Yusuke; Hayashi, Kentaro; Yasue, Naoko; Imamura, Hiromi; Fujimori, Toshihiko; Nagai, Takeharu; Campbell, Robert E; Ueno, Naoto

    2017-04-01

    Early in the development of the central nervous system, progenitor cells undergo a shape change, called apical constriction, that triggers the neural plate to form a tubular structure. How apical constriction in the neural plate is controlled and how it contributes to tissue morphogenesis are not fully understood. In this study, we show that intracellular calcium ions (Ca(2+)) are required for Xenopus neural tube formation and that there are two types of Ca(2+)-concentration changes, a single-cell and a multicellular wave-like fluctuation, in the developing neural plate. Quantitative imaging analyses revealed that transient increases in Ca(2+) concentration induced cortical F-actin remodeling, apical constriction and accelerations of the closing movement of the neural plate. We also show that extracellular ATP and N-cadherin (cdh2) participate in the Ca(2+)-induced apical constriction. Furthermore, our mathematical model suggests that the effect of Ca(2+) fluctuations on tissue morphogenesis is independent of fluctuation frequency and that fluctuations affecting individual cells are more efficient than those at the multicellular level. We propose that distinct Ca(2+) signaling patterns differentially modulate apical constriction for efficient epithelial folding and that this mechanism has a broad range of physiological outcomes. © 2017. Published by The Company of Biologists Ltd.

  20. Three dimensional cellular microarray platform for human neural stem cell differentiation and toxicology

    Directory of Open Access Journals (Sweden)

    Luciana Meli

    2014-07-01

    Full Text Available We developed a three-dimensional (3D cellular microarray platform for the high-throughput (HT analysis of human neural stem cell (hNSC growth and differentiation. The growth of an immortalized hNSC line, ReNcell VM, was evaluated on a miniaturized cell culture chip consisting of 60 nl spots of cells encapsulated in alginate, and compared to standard 2D well plate culture conditions. Using a live/dead cell viability assay, we demonstrated that the hNSCs are able to expand on-chip, albeit with lower proliferation rates and viabilities than in conventional 2D culture platforms. Using an in-cell, on-chip immunofluorescence assay, which provides quantitative information on cellular levels of proteins involved in neural fate, we demonstrated that ReNcell VM can preserve its multipotent state during on-chip expansion. Moreover, differentiation of the hNSCs into glial progeny was achieved both off- and on-chip six days after growth factor removal, accompanied by a decrease in the neural progenitor markers. The versatility of the platform was further demonstrated by complementing the cell culture chip with a chamber system that allowed us to screen for differential toxicity of small molecules to hNSCs. Using this approach, we showed differential toxicity when evaluating three neurotoxic compounds and one antiproliferative compound, and the null effect of a non-toxic compound at relevant concentrations. Thus, our 3D high-throughput microarray platform may help predict, in vitro, which compounds pose an increased threat to neural development and should therefore be prioritized for further screening and evaluation.

  1. Three dimensional cellular microarray platform for human neural stem cell differentiation and toxicology.

    Science.gov (United States)

    Meli, Luciana; Barbosa, Hélder S C; Hickey, Anne Marie; Gasimli, Leyla; Nierode, Gregory; Diogo, Maria Margarida; Linhardt, Robert J; Cabral, Joaquim M S; Dordick, Jonathan S

    2014-07-01

    We developed a three-dimensional (3D) cellular microarray platform for the high-throughput (HT) analysis of human neural stem cell (hNSC) growth and differentiation. The growth of an immortalized hNSC line, ReNcell VM, was evaluated on a miniaturized cell culture chip consisting of 60nl spots of cells encapsulated in alginate, and compared to standard 2D well plate culture conditions. Using a live/dead cell viability assay, we demonstrated that the hNSCs are able to expand on-chip, albeit with lower proliferation rates and viabilities than in conventional 2D culture platforms. Using an in-cell, on-chip immunofluorescence assay, which provides quantitative information on cellular levels of proteins involved in neural fate, we demonstrated that ReNcell VM can preserve its multipotent state during on-chip expansion. Moreover, differentiation of the hNSCs into glial progeny was achieved both off- and on-chip six days after growth factor removal, accompanied by a decrease in the neural progenitor markers. The versatility of the platform was further demonstrated by complementing the cell culture chip with a chamber system that allowed us to screen for differential toxicity of small molecules to hNSCs. Using this approach, we showed differential toxicity when evaluating three neurotoxic compounds and one antiproliferative compound, and the null effect of a non-toxic compound at relevant concentrations. Thus, our 3D high-throughput microarray platform may help predict, in vitro, which compounds pose an increased threat to neural development and should therefore be prioritized for further screening and evaluation. Copyright © 2014. Published by Elsevier B.V.

  2. Neural Stem Cell Differentiation Is Dictated by Distinct Actions of Nuclear Receptor Corepressors and Histone Deacetylases

    Directory of Open Access Journals (Sweden)

    Gonçalo Castelo-Branco

    2014-09-01

    Full Text Available Signaling factors including retinoic acid (RA and thyroid hormone (T3 promote neuronal, oligodendrocyte, and astrocyte differentiation of cortical neural stem cells (NSCs. However, the functional specificity of transcriptional repressor checkpoints controlling these differentiation programs remains unclear. Here, we show by genome-wide analysis that histone deacetylase (HDAC2 and HDAC3 show overlapping and distinct promoter occupancy at neuronal and oligodendrocyte-related genes in NSCs. The absence of HDAC3, but not HDAC2, initiated a neuronal differentiation pathway in NSCs. The ablation of the corepressor NCOR or HDAC2, in conjunction with T3 treatment, resulted in increased expression of oligodendrocyte genes, revealing a direct HDAC2-mediated repression of Sox8 and Sox10 expression. Interestingly, Sox10 was required also for maintaining the more differentiated state by repression of stem cell programming factors such as Sox2 and Sox9. Distinct and nonredundant actions of NCORs and HDACs are thus critical for control of lineage progression and differentiation programs in neural progenitors.

  3. [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.

  4. Classification of behavior using unsupervised temporal neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Adair, K.L. [Florida State Univ., Tallahassee, FL (United States). Dept. of Computer Science; Argo, P. [Los Alamos National Lab., NM (United States)

    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.

  5. Differentiation of Human Embryonic Stem Cells to Regional Specific Neural Precursors in Chemically Defined Medium Conditions

    Science.gov (United States)

    Erceg, Slaven; Laínez, Sergio; Ronaghi, Mohammad; Stojkovic, Petra; Pérez-Aragó, Maria Amparo; Moreno-Manzano, Victoria; Moreno-Palanques, Rubén; Planells-Cases, Rosa; Stojkovic, Miodrag

    2008-01-01

    Background Human embryonic stem cells (hESC) provide a unique model to study early events in human development. The hESC-derived cells can potentially be used to replace or restore different tissues including neuronal that have been damaged by disease or injury. Methodology and Principal Findings The cells of two different hESC lines were converted to neural rosettes using adherent and chemically defined conditions. The progenitor cells were exposed to retinoic acid (RA) or to human recombinant basic fibroblast growth factor (bFGF) in the late phase of the rosette formation. Exposing the progenitor cells to RA suppressed differentiation to rostral forebrain dopamine neural lineage and promoted that of spinal neural tissue including motor neurons. The functional characteristics of these differentiated neuronal precursors under both, rostral (bFGF) and caudalizing (RA) signals were confirmed by patch clamp analysis. Conclusions/Significance These findings suggest that our differentiation protocol has the capacity to generate region-specific and electrophysiologically active neurons under in vitro conditions without embryoid body formation, co-culture with stromal cells and without presence of cells of mesodermal or endodermal lineages. PMID:18461168

  6. Differentiation of human embryonic stem cells to regional specific neural precursors in chemically defined medium conditions.

    Directory of Open Access Journals (Sweden)

    Slaven Erceg

    Full Text Available BACKGROUND: Human embryonic stem cells (hESC provide a unique model to study early events in human development. The hESC-derived cells can potentially be used to replace or restore different tissues including neuronal that have been damaged by disease or injury. METHODOLOGY AND PRINCIPAL FINDINGS: The cells of two different hESC lines were converted to neural rosettes using adherent and chemically defined conditions. The progenitor cells were exposed to retinoic acid (RA or to human recombinant basic fibroblast growth factor (bFGF in the late phase of the rosette formation. Exposing the progenitor cells to RA suppressed differentiation to rostral forebrain dopamine neural lineage and promoted that of spinal neural tissue including motor neurons. The functional characteristics of these differentiated neuronal precursors under both, rostral (bFGF and caudalizing (RA signals were confirmed by patch clamp analysis. CONCLUSIONS/SIGNIFICANCE: These findings suggest that our differentiation protocol has the capacity to generate region-specific and electrophysiologically active neurons under in vitro conditions without embryoid body formation, co-culture with stromal cells and without presence of cells of mesodermal or endodermal lineages.

  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. Behavioral and neural properties of social reinforcement learning.

    Science.gov (United States)

    Jones, Rebecca M; Somerville, Leah H; Li, Jian; Ruberry, Erika J; Libby, Victoria; Glover, Gary; Voss, Henning U; Ballon, Douglas J; Casey, B J

    2011-09-14

    Social learning is critical for engaging in complex interactions with other individuals. Learning from positive social exchanges, such as acceptance from peers, may be similar to basic reinforcement learning. We formally test this hypothesis by developing a novel paradigm that is based on work in nonhuman primates and human imaging studies of reinforcement learning. The probability of receiving positive social reinforcement from three distinct peers was parametrically manipulated while brain activity was recorded in healthy adults using event-related functional magnetic resonance imaging. Over the course of the experiment, participants responded more quickly to faces of peers who provided more frequent positive social reinforcement, and rated them as more likeable. Modeling trial-by-trial learning showed ventral striatum and orbital frontal cortex activity correlated positively with forming expectations about receiving social reinforcement. Rostral anterior cingulate cortex activity tracked positively with modulations of expected value of the cues (peers). Together, the findings across three levels of analysis--social preferences, response latencies, and modeling neural responses--are consistent with reinforcement learning theory and nonhuman primate electrophysiological studies of reward. This work highlights the fundamental influence of acceptance by one's peers in altering subsequent behavior.

  9. 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

  10. Behavioral and neural properties of social reinforcement learning

    Science.gov (United States)

    Jones, Rebecca M.; Somerville, Leah H.; Li, Jian; Ruberry, Erika J.; Libby, Victoria; Glover, Gary; Voss, Henning U.; Ballon, Douglas J.; Casey, BJ

    2011-01-01

    Social learning is critical for engaging in complex interactions with other individuals. Learning from positive social exchanges, such as acceptance from peers, may be similar to basic reinforcement learning. We formally test this hypothesis by developing a novel paradigm that is based upon work in non-human primates and human imaging studies of reinforcement learning. The probability of receiving positive social reinforcement from three distinct peers was parametrically manipulated while brain activity was recorded in healthy adults using event-related functional magnetic resonance imaging (fMRI). Over the course of the experiment, participants responded more quickly to faces of peers who provided more frequent positive social reinforcement, and rated them as more likeable. Modeling trial-by-trial learning showed ventral striatum and orbital frontal cortex activity correlated positively with forming expectations about receiving social reinforcement. Rostral anterior cingulate cortex activity tracked positively with modulations of expected value of the cues (peers). Together, the findings across three levels of analysis - social preferences, response latencies and modeling neural responses – are consistent with reinforcement learning theory and non-human primate electrophysiological studies of reward. This work highlights the fundamental influence of acceptance by one’s peers in altering subsequent behavior. PMID:21917787

  11. 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.

  12. Altered neural correlates of affective processing after internet-delivered cognitive behavior therapy for social anxiety disorder.

    Science.gov (United States)

    Månsson, Kristoffer N T; Carlbring, Per; Frick, Andreas; Engman, Jonas; Olsson, Carl-Johan; Bodlund, Owe; Furmark, Tomas; Andersson, Gerhard

    2013-12-30

    Randomized controlled trials have yielded promising results for internet-delivered cognitive behavior therapy (iCBT) for patients with social anxiety disorder (SAD). The present study investigated anxiety-related neural changes after iCBT for SAD. The amygdala is a critical hub in the neural fear network, receptive to change using emotion regulation strategies and a putative target for iCBT. Twenty-two subjects were included in pre- and post-treatment functional magnetic resonance imaging at 3T assessing neural changes during an affective face processing task. Treatment outcome was assessed using social anxiety self-reports and the Clinical Global Impression-Improvement (CGI-I) scale. ICBT yielded better outcome than ABM (66% vs. 25% CGI-I responders). A significant differential activation of the left amygdala was found with relatively decreased reactivity after iCBT. Changes in the amygdala were related to a behavioral measure of social anxiety. Functional connectivity analysis in the iCBT group showed that the amygdala attenuation was associated with increased activity in the medial orbitofrontal cortex and decreased activity in the right ventrolateral and dorsolateral (dlPFC) cortices. Treatment-induced neural changes with iCBT were consistent with previously reported studies on regular CBT and emotion regulation in general. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

    NARCIS (Netherlands)

    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

  14. Lingo-1 shRNA and Notch signaling inhibitor DAPT promote differentiation of neural stem/progenitor cells into neurons.

    Science.gov (United States)

    Wang, Jue; Ye, Zhizhong; Zheng, Shuhui; Chen, Luming; Wan, Yong; Deng, Yubin; Yang, Ruirui

    2016-03-01

    Determination of the exogenous factors that regulate differentiation of neural stem/progenitor cells into neurons, oligodendrocytes and astrocytes is an important step in the clinical therapy of spinal cord injury (SCI). The Notch pathway inhibits the differentiation of neural stem/progenitor cells and Lingo-1 is a strong negative regulator for myelination and axon growth. While Lingo-1 shRNA and N-[N-(3, 5-difluorophenacetyl)-1-alanyl]-S-Phenylglycinet-butylester (DAPT), a Notch pathway inhibitor, have been used separately to help repair SCI, the results have been unsatisfactory. Here we investigated and elucidated the preliminary mechanism for the effect of Lingo-1 shRNA and DAPT on neural stem/progenitor cells differentiation. We found that neural stem/progenitor cells from E14 rat embryos expressed Nestin, Sox-2 and Lingo-1, and we optimized the transduction of neural stem/progenitor cells using lentiviral vectors encoding Lingo-1 shRNA. The addition of DAPT decreased the expression of Notch intracellular domain (NICD) as well as the downstream genes Hes1 and Hes5. Expression of NeuN, CNPase and GFAP in DAPT treated cells and expression of NeuN in Lingo-1 shRNA treated cells confirmed differentiation of neural stem/progenitor cells into neurons, oligodendrocytes and astrocytes. These results revealed that while Lingo-1 shRNA and Notch signaling inhibitor DAPT both promoted differentiation of neural stem cells into neurons, only DAPT was capable of driving neural stem/progenitor cells differentiation into oligodendrocytes and astrocytes. Since we were able to show that both Lingo-1 shRNA and DAPT could drive neural stem/progenitor cells differentiation, our data might aid the development of more effective SCI therapies using Lingo-1 shRNA and DAPT. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Differentiation of human neural progenitor cell-derived spiral ganglion-like neurons: a time-lapse video study.

    Science.gov (United States)

    Edin, Fredrik; Liu, Wei; Boström, Marja; Magnusson, Peetra U; Rask-Andersen, Helge

    2014-05-01

    Human neural progenitor cells can differentiate into spiral ganglion-like cells when exposed to inner ear-associated growth factors. The phenotype bears resemblance to human sphere-derived neurons. To establish an in vitro model for the human auditory nerve to replace and complement in vivo animal experiments and ultimately human in vivo transplantation. Human neural progenitors were differentiated under conditions developed for in vitro survival of human primary spiral ganglion culture with media containing growth factors associated with inner ear development. Differentiation was documented using time-lapse video microscopy. Time-dependent marker expression was evaluated using immunocytochemistry with fluorescence and laser confocal microscopy. Within 14 days of differentiation, neural progenitors adopted neural phenotype and expressed spiral ganglion-associated markers.

  16. 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.

  17. STAT3 modulation to enhance motor neuron differentiation in human neural stem cells.

    Directory of Open Access Journals (Sweden)

    Rajalaxmi Natarajan

    Full Text Available Spinal cord injury or amyotrophic lateral sclerosis damages spinal motor neurons and forms a glial scar, which prevents neural regeneration. Signal transducer and activator of transcription 3 (STAT3 plays a critical role in astrogliogenesis and scar formation, and thus a fine modulation of STAT3 signaling may help to control the excessive gliogenic environment and enhance neural repair. The objective of this study was to determine the effect of STAT3 inhibition on human neural stem cells (hNSCs. In vitro hNSCs primed with fibroblast growth factor 2 (FGF2 exhibited a lower level of phosphorylated STAT3 than cells primed by epidermal growth factor (EGF, which correlated with a higher number of motor neurons differentiated from FGF2-primed hNSCs. Treatment with STAT3 inhibitors, Stattic and Niclosamide, enhanced motor neuron differentiation only in FGF2-primed hNSCs, as shown by increased homeobox gene Hb9 mRNA levels as well as HB9+ and microtubule-associated protein 2 (MAP2+ co-labeled cells. The increased motor neuron differentiation was accompanied by a decrease in the number of glial fibrillary acidic protein (GFAP-positive astrocytes. Interestingly, Stattic and Niclosamide did not affect the level of STAT3 phosphorylation; rather, they perturbed the nuclear translocation of phosphorylated STAT3. In summary, we demonstrate that FGF2 is required for motor neuron differentiation from hNSCs and that inhibition of STAT3 further increases motor neuron differentiation at the expense of astrogliogenesis. Our study thus suggests a potential benefit of targeting the STAT3 pathway for neurotrauma or neurodegenerative diseases.

  18. 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…

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

    Science.gov (United States)

    Marotta, Mario; Fernández-Martín, Alejandra; Oria, Marc; Fontecha, Cesar G; Giné, Carles; Martínez-Ibáñez, Vicente; Carreras, Elena; Belfort, Michael A; Pelizzo, Gloria; Peiró, Jose L

    2017-07-01

    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 26weeks 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. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  20. 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.

  1. Enrichment and Schwann Cell Differentiation of Neural Crest-derived Dental Pulp Stem Cells.

    Science.gov (United States)

    Al-Zer, Heba; Apel, Christian; Heiland, Max; Friedrich, Reinhard E; Jung, Ole; Kroeger, Nadja; Eichhorn, Wolfgang; Smeets, Ralf

    2015-01-01

    As already described in previous studies, neural crest stem cells (NCSCs) can be found in adult human dental pulp. The present study investigated the methodology for enrichment and differentiation-induction of the above mentioned cells. Dental pulp was extracted from human wisdom teeth of four patients and subsequently cultured as explants on fibronectin-coated plates in neurobasal medium supplemented with B27, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin, l-glutamine and neuregulin-β1. The cells were then characterized by immunofluorescence, while their differentiation-potential was tested by the attempt to induce cells into different lineages, i.e. osteogenic, melanocytic and glial. The enriched cell population expressed nestin, CD271 and SOX10, which are well-known markers for NCSCs. Consequently, the cells were successfully induced to differentiate into osteoblasts, melanocytes and Schwann cells, expressing the corresponding differentiation markers. Human adult dental pulp contains a population of stem cells with neural crest ontogeny, which can thus be recruited for multiple regenerative therapies. Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  2. Monitoring neural stem cell differentiation using PEDOT-PSS based MEA.

    Science.gov (United States)

    Furukawa, Yuriko; Shimada, Akiyoshi; Kato, Koichi; Iwata, Hiroo; Torimitsu, Keiichi

    2013-09-01

    Transplantation is one potential clinical application of neural stem cells (NSCs). However, it is very difficult to monitor/control NSCs after transplantation and so provide effective treatment. Electrical measurement using a poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) modified microelectrode array (MEA) is a biocompatible, non-invasive, non-destructive approach to understanding cell conditions. This property makes continuous monitoring available for the evaluation/assessment of the development of cells such as NSCs. A PEDOT-PSS modified MEA was used to monitor electrical signals during NSC development in a culture derived from rat embryo striatum in order to understand the NSC differentiation conditions. Electrical data indicated that NSCs with nerve growth factor (NGF) generate a cultured cortical neuron-like burst pattern while a random noise pattern was measured with epidermal growth factor (EGF) at 4days in vitro (DIV) and a burst pattern was observed in both cases at 11 DIV indicating the successful monitoring of differentiation differences and developmental changes. The electrical analysis of cell activity using a PEDOT-PSS modified MEA could indicate neural network formation by differentiated neurons. Changes in NSC differentiation could be monitored. The method is based on non-invasive continuous measurement and so could prove a useful tool for the primary/preliminary evaluation of a pharmaceutical analysis. This article is part of a Special Issue entitled Organic Bioelectronics-Novel Applications in Biomedicine. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Differential Effects of a Tier Two Behavior Intervention Based on Function of Problem Behavior

    Science.gov (United States)

    McIntosh, Kent; Campbell, Amy L.; Carter, Deborah Russell; Dickey, Celeste Rossetto

    2009-01-01

    The purpose of this study was to investigate the effectiveness of a tier two daily behavior card intervention and differential effects based on function of problem behavior. The participants were 36 elementary school students nominated for additional intervention beyond universal School-Wide Positive Behavior Support. Measures included…

  4. 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.

  5. 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

    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...

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

    Directory of Open Access Journals (Sweden)

    Samantha J Brooks

    Full Text Available 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.

  7. Differential effects of perturbation direction and magnitude on the neural processing of voice pitch feedback.

    Science.gov (United States)

    Liu, Hanjun; Meshman, Michelle; Behroozmand, Roozbeh; Larson, Charles R

    2011-05-01

    The present study examined the differential effects of voice auditory feedback perturbation direction and magnitude on voice fundamental frequency (F(0)) responses and event-related potentials (ERPs) from EEG electrodes on the scalp. The voice F(0) responses and N1 and P2 components of ERPs were examined from 12 right-handed speakers when they sustained a vowel phonation and their mid-utterance voice pitch feedback was shifted ±100, ±200, and ±500 cents with 200 ms duration. Downward voice pitch feedback perturbations led to larger voice F(0) responses than upward perturbations. The amplitudes of N1 and P2 components were larger for downward compared with upward pitch-shifts for 200 and 500 cents stimulus magnitudes. Shorter N1 and P2 latencies were also associated with larger magnitudes of pitch feedback perturbations. Corresponding changes in vocal and neural responses to upward and downward voice pitch feedback perturbations suggest that the N1 and P2 components of ERPs reflect neural concomitants of the vocal responses. The findings of interactive effects between the magnitude and direction of voice feedback pitch perturbation on N1 and P2 ERP components indicate that the neural mechanisms underlying error detection and correction in voice pitch auditory feedback are differentially sensitive to both the magnitude and direction of pitch perturbations. Copyright © 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  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

    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

  9. Functional evaluation of neural stem cell differentiation by single cell calcium imaging.

    Science.gov (United States)

    Eiriz, Maria Francisca; Grade, Sofia; Rosa, Alexandra; Xapelli, Sara; Bernardino, Liliana; Agasse, Fabienne; Malva, João O

    2011-09-01

    Neurogenesis in the adult mammalian brain occurs in two specific brain areas, the subventricular zone (SVZ) bordering the lateral ventricles and the subgranular zone (SGZ) of the hippocampus. Although these regions are prone to produce new neurons, cultured cells from these neurogenic niches tend to be mixed cultures, containing both neurons and glial cells. Several reports highlight the potential of the self-healing capacity of the brain following injury. Even though much knowledge has been produced on the neurogenesis itself, brain repairing strategies are still far away from patients cure. Here we review general concepts in the neurogenesis field, also addressing the methods available to study neural stem cell differentiation. A major problem faced by research groups and companies dedicated to brain regenerative medicine resides on the lack of good methods to functionally identify neural stem cell differentiation and novel drug targets. To address this issue, we developed a unique single cell calcium imaging-based method to functionally discriminate different cell types derived from SVZ neural stem cell cultures. The unique functional profile of each SVZ cell type was correlated at the single cell level with the immunodetection of specific phenotypic markers. This platform was raised on the basis of the functional response of neurons, oligodendrocytes and immature cells to depolarising agents, to thrombin and to histamine, respectively. We also outline key studies in which our new platform was extremely relevant in the context of drug discovery and development in the area of brain regenerative medicine.

  10. Coseeded Schwann cells myelinate neurites from differentiated neural stem cells in neurotrophin-3-loaded PLGA carriers

    Science.gov (United States)

    Xiong, Yi; Zhu, Ji-Xiang; Fang, Zheng-Yu; Zeng, Cheng-Guang; Zhang, Chao; Qi, Guo-Long; Li, Man-Hui; Zhang, Wei; Quan, Da-Ping; Wan, Jun

    2012-01-01

    Biomaterials and neurotrophic factors represent promising guidance for neural repair. In this study, we combined poly-(lactic acid-co-glycolic acid) (PLGA) conduits and neurotrophin-3 (NT-3) to generate NT-3-loaded PLGA carriers in vitro. Bioactive NT-3 was released stably and constantly from PLGA conduits for up to 4 weeks. Neural stem cells (NSCs) and Schwann cells (SCs) were coseeded into an NT-releasing scaffold system and cultured for 14 days. Immunoreactivity against Map2 showed that most of the grafted cells (>80%) were differentiated toward neurons. Double-immunostaining for synaptogenesis and myelination revealed the formation of synaptic structures and myelin sheaths in the coculture, which was also observed under electron microscope. Furthermore, under depolarizing conditions, these synapses were excitable and capable of releasing synaptic vesicles labeled with FM1-43 or FM4-64. Taken together, coseeding NSCs and SCs into NT-3-loaded PLGA carriers increased the differentiation of NSCs into neurons, developed synaptic connections, exhibited synaptic activities, and myelination of neurites by the accompanying SCs. These results provide an experimental basis that supports transplantation of functional neural construction in spinal cord injury. PMID:22619535

  11. 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.

  12. Static stretch affects neural stem cell differentiation in an extracellular matrix-dependent manner.

    Science.gov (United States)

    Arulmoli, Janahan; Pathak, Medha M; McDonnell, Lisa P; Nourse, Jamison L; Tombola, Francesco; Earthman, James C; Flanagan, Lisa A

    2015-02-17

    Neural stem and progenitor cell (NSPC) fate is strongly influenced by mechanotransduction as modulation of substrate stiffness affects lineage choice. Other types of mechanical stimuli, such as stretch (tensile strain), occur during CNS development and trauma, but their consequences for NSPC differentiation have not been reported. We delivered a 10% static equibiaxial stretch to NSPCs and examined effects on differentiation. We found static stretch specifically impacts NSPC differentiation into oligodendrocytes, but not neurons or astrocytes, and this effect is dependent on particular extracellular matrix (ECM)-integrin linkages. Generation of oligodendrocytes from NSPCs was reduced on laminin, an outcome likely mediated by the α6 laminin-binding integrin, whereas similar effects were not observed for NSPCs on fibronectin. Our data demonstrate a direct role for tensile strain in dictating the lineage choice of NSPCs and indicate the dependence of this phenomenon on specific substrate materials, which should be taken into account for the design of biomaterials for NSPC transplantation.

  13. Neural stem cells differentiated from iPS cells spontaneously regain pluripotency.

    Science.gov (United States)

    Choi, Hyun Woo; Kim, Jong Soo; Choi, Sol; Hong, Yean Ju; Kim, Min Jung; Seo, Han Geuk; Do, Jeong Tae

    2014-10-01

    Differentiated somatic cells can be reprogrammed into pluripotent stem cells by transduction of exogenous reprogramming factors. After induced pluripotent stem (iPS) cells are established, exogenous genes are silenced. In the pluripotent state, retroviral genes integrated in the host genome are kept inactive through epigenetic transcriptional regulation. In this study, we tried to determine whether exogenous genes remain silenced or are reactivated upon loss of pluripotency or on differentiation using an in vitro system. We induced differentiation of iPS cells into neural stem cells (NSCs) in vitro; the NSCs appeared morphologically indistinguishable from brain-derived NSCs and stained positive for the NSC markers Nestin and Sox2. These iPS cell-derived NSCs (iPS-NSCs) were also capable of differentiating into all three neural subtypes. Interestingly, iPS-NSCs spontaneously formed aggregates on long-term culture and showed reactivation of the Oct4-GFP marker, which was followed by the formation of embryonic stem cell-like colonies. The spontaneously reverted green fluorescent protein (GFP)-positive (iPS-NSC-GFP(+) ) cells expressed high levels of pluripotency markers (Oct4 and Nanog) and formed germline chimeras, indicating that iPS-NSC-GFP(+) cells had the same pluripotency as the original iPS cells. The reactivation of silenced exogenous genes was tightly correlated with the downregulation of DNA methyltransferases (Dnmts) during differentiation of iPS cells. This phenomenon was not observed in doxycycline-inducible iPS cells, where the reactivation of exogenous genes could be induced only by doxycycline treatment. These results indicate that pluripotency can be regained through reactivation of exogenous genes, which is associated with dynamic change of Dnmt levels during differentiation of iPS cells. © 2014 AlphaMed Press.

  14. Significance of red cell distribution width in the differential diagnosis between neurally mediated syncope and arrhythmic syncope in children.

    Science.gov (United States)

    Zhang, Qingyou; Li, Yaqi; Liao, Ying; Du, Junbao

    2017-05-01

    The aim of the present study was to explore the predictive value of red cell distribution width as a means to differentiate between neurally mediated syncope and arrhythmic syncope in children. Patients were divided into a neurally mediated syncope group (n=72) and an arrhythmic syncope group (n=21) on the basis of clinical history, results of the head-up tilt test, electrocardiography, and 24-hour ambulatory electrocardiography. As controls, we recruited 55 healthy children. Red cell distribution width was determined for children in all groups. A receiver operating characteristic curve was drawn to study the predictive effect of red cell distribution width to differentiate between neurally mediated syncope and arrhythmic syncope. Red cell distribution width was significantly higher in children with neurally mediated syncope than in children with arrhythmic syncope and the control group. A receiver operating characteristic curve on the predictive value of red cell distribution width in differentiating neurally mediated syncope from arrhythmic syncope showed that the area under the curve was 0.841 (95% confidence interval: 0.737-0.945, pred cell distribution width value of 12.8% as the cut-off value yielded a sensitivity of 80.6% and a specificity of 76.2% in discriminating between patients with neurally mediated syncope and arrhythmic syncope. Red cell distribution width value of ⩾12.8% might be a useful adjunct for primary-care physicians to differentiate neurally mediated syncope from arrhythmic syncope in children.

  15. 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.

  16. 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.

  17. Dynamic mass redistribution assay decodes differentiation of a neural progenitor stem cell.

    Science.gov (United States)

    Pai, Sadashiva; Verrier, Florence; Sun, Haiyan; Hu, Haibei; Ferrie, Ann M; Eshraghi, Azita; Fang, Ye

    2012-10-01

    Stem cells hold great potential in drug discovery and development. However, challenges remain to quantitatively measure the functions of stem cells and their differentiated products. Here, we applied fluorescent imaging, quantitative real-time PCR, and label-free dynamic mass redistribution (DMR) assays to characterize the differentiation process of the ReNcell VM human neural progenitor stem cell. Immunofluorescence imaging showed that after growth factor withdrawal, the neuroprogenitor stem cell was differentiated into dopaminergic neurons, astrocytes, and oligodendrocytes, thus creating a neuronal cell system. High-performance liquid chromatography analysis showed that the differentiated cell system released dopamine upon depolarization with KCl. In conjunction with quantitative real-time PCR, DMR assays using a G-protein-coupled receptor agonist library revealed that a subset of receptors, including dopamine D(1) and D(4) receptors, underwent marked alterations in both receptor expression and signaling pathway during the differentiation process. These findings suggest that DMR assays can decode the differentiation process of stem cells at the cell system level.

  18. 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.

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Highly efficient differentiation of neural precursors from human embryonic stem cells and benefits of transplantation after ischemic stroke in mice.

    Science.gov (United States)

    Drury-Stewart, Danielle; Song, Mingke; Mohamad, Osama; Guo, Ying; Gu, Xiaohuan; Chen, Dongdong; Wei, Ling

    2013-08-08

    Ischemic stroke is a leading cause of death and disability, but treatment options are severely limited. Cell therapy offers an attractive strategy for regenerating lost tissues and enhancing the endogenous healing process. In this study, we investigated the use of human embryonic stem cell-derived neural precursors as a cell therapy in a murine stroke model. Neural precursors were derived from human embryonic stem cells by using a fully adherent SMAD inhibition protocol employing small molecules. The efficiency of neural induction and the ability of these cells to further differentiate into neurons were assessed by using immunocytochemistry. Whole-cell patch-clamp recording was used to demonstrate the electrophysiological activity of human embryonic stem cell-derived neurons. Neural precursors were transplanted into the core and penumbra regions of a focal ischemic stroke in the barrel cortex of mice. Animals received injections of bromodeoxyuridine to track regeneration. Neural differentiation of the transplanted cells and regenerative markers were measured by using immunohistochemistry. The adhesive removal test was used to determine functional improvement after stroke and intervention. After 11 days of neural induction by using the small-molecule protocol, over 95% of human embryonic stem-derived cells expressed at least one neural marker. Further in vitro differentiation yielded cells that stained for mature neuronal markers and exhibited high-amplitude, repetitive action potentials in response to depolarization. Neuronal differentiation also occurred after transplantation into the ischemic cortex. A greater level of bromodeoxyuridine co-localization with neurons was observed in the penumbra region of animals receiving cell transplantation. Transplantation also improved sensory recovery in transplant animals over that in control animals. Human embryonic stem cell-derived neural precursors derived by using a highly efficient small-molecule SMAD inhibition

  2. 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

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

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    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.

  4. Neural integration of speech and gesture in schizophrenia: evidence for differential processing of metaphoric gestures.

    Science.gov (United States)

    Straube, Benjamin; Green, Antonia; Sass, Katharina; Kirner-Veselinovic, André; Kircher, Tilo

    2013-07-01

    Gestures are an important component of interpersonal communication. Especially, complex multimodal communication is assumed to be disrupted in patients with schizophrenia. In healthy subjects, differential neural integration processes for gestures in the context of concrete [iconic (IC) gestures] and abstract sentence contents [metaphoric (MP) gestures] had been demonstrated. With this study we wanted to investigate neural integration processes for both gesture types in patients with schizophrenia. During functional magnetic resonance imaging-data acquisition, 16 patients with schizophrenia (P) and a healthy control group (C) were shown videos of an actor performing IC and MP gestures and associated sentences. An isolated gesture (G) and isolated sentence condition (S) were included to separate unimodal from bimodal effects at the neural level. During IC conditions (IC > G ∩ IC > S) we found increased activity in the left posterior middle temporal gyrus (pMTG) in both groups. Whereas in the control group the left pMTG and the inferior frontal gyrus (IFG) were activated for the MP conditions (MP > G ∩ MP > S), no significant activation was found for the identical contrast in patients. The interaction of group (P/C) and gesture condition (MP/IC) revealed activation in the bilateral hippocampus, the left middle/superior temporal and IFG. Activation of the pMTG for the IC condition in both groups indicates intact neural integration of IC gestures in schizophrenia. However, failure to activate the left pMTG and IFG for MP co-verbal gestures suggests a disturbed integration of gestures embedded in an abstract sentence context. This study provides new insight into the neural integration of co-verbal gestures in patients with schizophrenia. Copyright © 2012 Wiley Periodicals, Inc.

  5. Differentiating Behaviors among Spillane's Forms of Distributed Leadership

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    Zirkle, Laura

    2012-01-01

    The purpose of this study was to identify what leadership behaviors are associated with each of Spillane's (2006) three conceptually distinct forms of distributed leadership, and to determine whether specific influence tactics (Yukl, Seifert & Chavez, 2008) are differentially associated with each form. A two-phased, mixed methods design was…

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  7. Three dimensional cellular microarray platform for human neural stem cell differentiation and toxicology

    OpenAIRE

    Luciana Meli; Hélder S.C. Barbosa; Anne Marie Hickey; Leyla Gasimli; Gregory Nierode; Maria Margarida Diogo; Linhardt, Robert J.; Joaquim M S Cabral; Dordick, Jonathan S.

    2014-01-01

    We developed a three-dimensional (3D) cellular microarray platform for the high-throughput (HT) analysis of human neural stem cell (hNSC) growth and differentiation. The growth of an immortalized hNSC line, ReNcell VM, was evaluated on a miniaturized cell culture chip consisting of 60 nl spots of cells encapsulated in alginate, and compared to standard 2D well plate culture conditions. Using a live/dead cell viability assay, we demonstrated that the hNSCs are able to expand on-chip, albeit wi...

  8. Three Dimensional Cellular Microarray Platform for Human Neural Stem Cell Differentiation and Toxicology

    OpenAIRE

    Meli, Luciana; Hélder S.C. Barbosa; Hickey, Anne Marie; Gasimli, Leyla; Nierode, Gregory; Diogo, Maria Margarida; Linhardt, Robert J.; Joaquim M S Cabral; Dordick, Jonathan S.

    2014-01-01

    We developed a three-dimensional (3D) cellular microarray platform for the high-throughput (HT) analysis of human neural stem cell (hNSC) growth and differentiation. The growth of an immortalized hNSC line, ReNcell VM, was evaluated on a miniaturized cell culture chip consisting of 60 nl spots of cells encapsulated in alginate, and compared to standard 2D well plate culture conditions. Using a live/dead cell viability assay, we demonstrated that the hNSCs are able to expand on-chip, albeit wi...

  9. Prenatal Diagnosis, Fetal Surgery, Recurrence Risk and Differential Diagnosis of Neural Tube Defects

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2008-09-01

    Full Text Available Prenatal screening with α-fetoprotein (AFP and ultrasonography have allowed the prenatal diagnosis of neural tube defects (NTDs in current obstetric care, and open spina bifida has been considered a potential candidate for in utero treatment in modern pediatric surgery. This article provides an overview of maternal serum AFP screening, amniotic fluid AFP assays, amniotic fluid acetylcholinesterase immunoassays and level II ultrasound for NTDs, prenatal repair of fetal myelomeningocele, recurrence risk of NTDs, and differential diagnosis of NTDs on prenatal ultrasound.

  10. Regulation of neural stem cell differentiation by transcription factors HNF4-1 and MAZ-1.

    Science.gov (United States)

    Wang, Jiao; Cheng, Hua; Li, Xiao; Lu, Wei; Wang, Kai; Wen, Tieqiao

    2013-02-01

    Neural stem cells (NSCs) are promising candidates for a variety of neurological diseases due to their ability to differentiate into neurons, astrocytes, and oligodentrocytes. During this process, Rho GTPases are heavily involved in neuritogenesis, axon formation and dendritic development, due to their effects on the cytoskeleton through downstream effectors. The activities of Rho GTPases are controlled by Rho-GDP dissociation inhibitors (Rho-GDIs). As shown in our previous study, these are also involved in the differentiation of NSCs; however, little is known about the underlying regulatory mechanism. Here, we describe how the transcription factors hepatic nuclear factor (HNF4-1) and myc-associated zinc finger protein (MAZ-1) regulate the expression of Rho-GDIγ in the stimulation of NSC differentiation. Using a transfection of cis-element double-stranded oligodeoxynucleotides (ODNs) strategy, referred to as "decoy" ODNs, we examined the effects of HNF4-1 and MAZ-1 on NSC differentiation in the NSC line C17.2. Our results show that HNF4-1 and MAZ-1 decoy ODNs significantly knock down Rho-GDIγ gene transcription, leading to NSC differentiation towards neurons. We observed that HNF4-1 and MAZ-1 decoy ODNs are able enter to the cell nucleolus and specifically bind to their target transcription factors. Furthermore, the expression of Rho-GDIγ-mediated genes was identified, suggesting that the regulatory mechanism for the differentiation of NSCs is triggered by the transcription factors MAZ-1 and HNF4-1. These findings indicate that HNF4-1 and MAZ-1 regulate the expression of Rho-GDIγ and contribute to the differentiation of NSCs. Our findings provide a new perspective within regulatory mechanism research during differentiation of NSCs, especially the clinical application of transcription factor decoys in vivo, suggesting potential therapeutic strategies for neurodegenerative disease.

  11. Differential neural contributions to native- and foreign-language talker identification.

    Science.gov (United States)

    Perrachione, Tyler K; Pierrehumbert, Janet B; Wong, Patrick C M

    2009-12-01

    Humans are remarkably adept at identifying individuals by the sound of their voice, a behavior supported by the nervous system's ability to integrate information from voice and speech perception. Talker-identification abilities are significantly impaired when listeners are unfamiliar with the language being spoken. Recent behavioral studies describing the language-familiarity effect implicate functionally integrated neural systems for speech and voice perception, yet specific neuroscientific evidence demonstrating the basis for such integration has not yet been shown. Listeners in the present study learned to identify voices speaking a familiar (native) or unfamiliar (foreign) language. The talker-identification performance of neural circuitry in each cerebral hemisphere was assessed using dichotic listening. To determine the relative contribution of circuitry in each hemisphere to ecological (binaural) talker identification abilities, we compared the predictive capacity of dichotic performance on binaural performance across languages. Listeners' right-ear (left hemisphere) performance was a better predictor of binaural accuracy in their native language than a foreign one. This enhanced role of the classically language-dominant left hemisphere in listeners' native language demonstrates functionally integrated neural systems for speech and voice perception during talker identification.

  12. Overexpression of Wnt3a facilitates the proliferation and neural differentiation of neural stem cells in vitro and after transplantation into an injured rat retina.

    Science.gov (United States)

    Yang, Xi-Tao; Bi, Yong-Yan; Chen, Er-Tao; Feng, Dong-Fu

    2014-02-01

    Neural stem cell-based therapy is a promising option for repair after injury. However, poor stem cell proliferation and insufficient differentiation of the stem cells into neurons are still difficult problems. The present study investigated whether transplantation of neural stem cells (NSCs) genetically modified to express Wnt3a is a promising approach to overcome these difficulties. We explored the possibility that Wnt3a might contribute to the therapeutic effect of NSC transplantation in retinal repair. The relative promotion of proliferation and neural differentiation by modified NSCs was investigated in a rat model of optic nerve crush. A recombinant lentivirus (Lenti-Wnt3a) was engineered to express Wnt3a. NSCs infected with control lentivirus (Lenti-GFP) or Lenti-Wnt3a were transplanted into the subretinal space immediately after the optic nerve crush. The proliferation and neural differentiation activity of the NSCs were assessed in vitro and in vivo. Overexpression of Wnt3a in NSCs induced activation of Wnt signaling, promoted proliferation, and directed the differentiation of the NSCs into neurons both in vitro and in vivo. Our study suggests that Wnt3a can potentiate the therapeutic benefits of NSC-based therapy in the injured retina. Copyright © 2013 Wiley Periodicals, Inc.

  13. The neural stem cell fate determinant TRIM32 regulates complex behavioral traits

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    Anna-Lena eHillje

    2015-03-01

    Full Text Available In mammals, new neurons are generated throughout the entire lifespan in two restricted areas of the brain, the dentate gyrus (DG of the hippocampus and the subventricular zone (SVZ – olfactory bulb (OB system. In both regions newborn neurons display unique properties that clearly distinguish them from mature neurons. Enhanced excitability and increased synaptic plasticity enables them to add specific properties to information processing by modulating the existing local circuitry of already established mature neurons. Hippocampal neurogenesis has been suggested to play a role in spatial-navigation learning, spatial memory and spatial pattern separation. Cumulative evidences implicate that adult-born OB neurons contribute to learning processes and odor memory. We recently demonstrated that the cell fate determinant TRIM32 is upregulated in differentiating neuroblasts of the SVZ-OB system in the adult mouse brain. The absence of TRIM32 leads to increased progenitor cell proliferation and less cell death. Both effects accumulate in an overproduction of adult-generated OB neurons. Here, we present novel data from behavioral studies showing that such an enhancement of OB neurogenesis not necessarily leads to increased olfactory performance but in contrast even results in impaired olfactory capabilities. In addition, we show at the cellular level that TRIM32 protein levels increase during differentiation of neural stem cells. At the molecular level, several metabolic intermediates that are connected to glycolysis, glycine or cysteine metabolism are deregulated in TRIM32 knockout mice brain tissue. These metabolomics pathways are directly or indirectly linked to anxiety or depression like behavior. In summary, our study provides comprehensive data on how the impairment of neurogenesis caused by the loss of the cell fate determinant TRIM32 causes a decrease of olfactory performance as well as a deregulation of metabolomic pathways that are linked to

  14. Confidence as Bayesian Probability: From Neural Origins to Behavior.

    Science.gov (United States)

    Meyniel, Florent; Sigman, Mariano; Mainen, Zachary F

    2015-10-07

    Research on confidence spreads across several sub-fields of psychology and neuroscience. Here, we explore how a definition of confidence as Bayesian probability can unify these viewpoints. This computational view entails that there are distinct forms in which confidence is represented and used in the brain, including distributional confidence, pertaining to neural representations of probability distributions, and summary confidence, pertaining to scalar summaries of those distributions. Summary confidence is, normatively, derived or "read out" from distributional confidence. Neural implementations of readout will trade off optimality versus flexibility of routing across brain systems, allowing confidence to serve diverse cognitive functions. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Temporal Modeling of Neural Net Input/Output Behaviors: The Case of XOR

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    Bernard P. Zeigler

    2017-01-01

    Full Text Available In the context of the modeling and simulation of neural nets, we formulate definitions for the behavioral realization of memoryless functions. The definitions of realization are substantively different for deterministic and stochastic systems constructed of neuron-inspired components. In contrast to earlier generations of neural net models, third generation spiking neural nets exhibit important temporal and dynamic properties, and random neural nets provide alternative probabilistic approaches. Our definitions of realization are based on the Discrete Event System Specification (DEVS formalism that fundamentally include temporal and probabilistic characteristics of neuron system inputs, state, and outputs. The realizations that we construct—in particular for the Exclusive Or (XOR logic gate—provide insight into the temporal and probabilistic characteristics that real neural systems might display. Our results provide a solid system-theoretical foundation and simulation modeling framework for the high-performance computational support of such applications.

  16. Comparison of Artificial Neural Network Architecture in Solving Ordinary Differential Equations

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    Susmita Mall

    2013-01-01

    Full Text Available This paper investigates the solution of Ordinary Differential Equations (ODEs with initial conditions using Regression Based Algorithm (RBA and compares the results with arbitrary- and regression-based initial weights for different numbers of nodes in hidden layer. Here, we have used feed forward neural network and error back propagation method for minimizing the error function and for the modification of the parameters (weights and biases. Initial weights are taken as combination of random as well as by the proposed regression based model. We present the method for solving a variety of problems and the results are compared. Here, the number of nodes in hidden layer has been fixed according to the degree of polynomial in the regression fitting. For this, the input and output data are fitted first with various degree polynomials using regression analysis and the coefficients involved are taken as initial weights to start with the neural training. Fixing of the hidden nodes depends upon the degree of the polynomial. For the example problems, the analytical results have been compared with neural results with arbitrary and regression based weights with four, five, and six nodes in hidden layer and are found to be in good agreement.

  17. Differential neural activation when voluntarily regulating emotions in service members with chronic mild traumatic brain injury.

    Science.gov (United States)

    Dretsch, Michael N; Daniel, Thomas A; Goodman, Adam M; Katz, Jeffrey S; Denney, Thomas; Deshpande, Gopikrishna; Robinson, Jennifer L

    2017-09-19

    The objective of this study was to characterize the functional activation of the neural correlates of voluntary regulation of emotion in soldiers both with and without chronic mild traumatic brain injury (mTBI). Using functional magnetic resonance imaging (fMRI) and a battery of cognitive and psychological health measures, we assessed differences between active-duty U.S. soldiers with chronic mTBI (n = 37) and without (Controls, n = 35). Participants were instructed to maintain (passively view), enhance, and suppress emotions associated with negative and neutral visual stimuli. The mTBI group showed significantly greater clinical symptoms, but only a mild decrement in attention. Group contrasts, while controlling for posttraumatic stress disorder (PTSD) symptoms, revealed a differential neural activation pattern compared to controls, but only during the enhance condition. Specifically, the mTBI group showed greater activation in the precentral gyrus, postcentral gyrus, inferior parietal lobe, insula, and superior temporal gyrus. Finally, the effect of PTSD symptoms during the enhance condition was associated with accentuated activation of the frontal and limbic regions implicated in both emotion regulation and PTSD. Hyperactivation of neural regions in the mTBI group during the enhance condition may reflect vigilance towards negative contextual stimuli and/or poor strategy that might result in suboptimal allocation of resources to regulate emotions.

  18. 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.

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

    Science.gov (United States)

    Dreyer-Andersen, Nanna; Almeida, Ana Sofia; Jensen, Pia; Kamand, Morad; Okarmus, Justyna; Rosenberg, Tine; Friis, Stig Düring; Martínez Serrano, Alberto; Blaabjerg, Morten; Kristensen, Bjarne Winther; Skrydstrup, Troels; Gramsbergen, Jan Bert; Vieira, Helena L. A.

    2018-01-01

    Exploratory studies using human fetal tissue have suggested that intrastriatal transplantation of dopaminergic neurons may become a future treatment for patients with Parkinson’s disease. However, the use of human fetal tissue is compromised by ethical, regulatory and practical concerns. Human stem 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 (Caspase3) was reduced, whereas the expression of a cell proliferation marker (Ki67) was left unchanged. Increased expression of hypoxia inducible factor-1α and production of reactive oxygen species (ROS) in cultures exposed to CO may suggest a mechanism involving mitochondrial alterations and generation of ROS. In conclusion, the present procedure using controlled, short-term CO exposure allows efficient dopaminergic differentiation of human neural stem cells at low cost and may as such be useful for derivation of cells for experimental studies and future development of donor cells for transplantation in Parkinson’s disease. PMID:29338033

  20. Genome Stability by DNA Polymerase β in Neural Progenitors Contributes to Neuronal Differentiation in Cortical Development.

    Science.gov (United States)

    Onishi, Kohei; Uyeda, Akiko; Shida, Mitsuhiro; Hirayama, Teruyoshi; Yagi, Takeshi; Yamamoto, Nobuhiko; Sugo, Noriyuki

    2017-08-30

    DNA repair is crucial for genome stability in the developing cortex, as somatic de novo mutations cause neurological disorders. However, how DNA repair contributes to neuronal development is largely unknown. To address this issue, we studied the spatiotemporal roles of DNA polymerase β (Polβ), a key enzyme in DNA base excision repair pathway, in the developing cortex using distinct forebrain-specific conditional knock-out mice, Emx1-Cre/Polβ (fl/fl) and Nex-Cre/Polβ (fl/fl) mice. Polβ expression was absent in both neural progenitors and postmitotic neurons in Emx1-Cre/Polβ (fl/fl) mice, whereas only postmitotic neurons lacked Polβ expression in Nex-Cre/Polβ (fl/fl) mice. We found that DNA double-strand breaks (DSBs) were frequently detected during replication in cortical progenitors of Emx1-Cre/Polβ (fl/fl) mice. Increased DSBs remained in postmitotic cells, which resulted in p53-mediated neuronal apoptosis. This neuronal apoptosis caused thinning of the cortical plate, although laminar structure was normal. In addition, accumulated DSBs also affected growth of corticofugal axons but not commissural axons. These phenotypes were not observed in Nex-Cre/Polβ (fl/fl) mice. Moreover, cultured Polβ-deficient neural progenitors exhibited higher sensitivity to the base-damaging agent methylmethanesulfonate, resulting in enhanced DSB formation. Similar damage was found by vitamin C treatment, which induces TET1-mediated DNA demethylation via 5-hydroxymethylcytosine. Together, genome stability mediated by Polβ-dependent base excision repair is crucial for the competence of neural progenitors, thereby contributing to neuronal differentiation in cortical development.SIGNIFICANCE STATEMENT DNA repair is crucial for development of the nervous system. However, how DNA polymerase β (Polβ)-dependent DNA base excision repair pathway contributes to the process is still unknown. We found that loss of Polβ in cortical progenitors rather than postmitotic neurons led to

  1. Radiation-induced glioblastoma signaling cascade regulates viability, apoptosis and differentiation of neural stem cells (NSC).

    Science.gov (United States)

    Ivanov, Vladimir N; Hei, Tom K

    2014-12-01

    Ionizing radiation alone or in combination with chemotherapy is the main treatment modality for brain tumors including glioblastoma. Adult neurons and astrocytes demonstrate substantial radioresistance; in contrast, human neural stem cells (NSC) are highly sensitive to radiation via induction of apoptosis. Irradiation of tumor cells has the potential risk of affecting the viability and function of NSC. In this study, we have evaluated the effects of irradiated glioblastoma cells on viability, proliferation and differentiation potential of non-irradiated (bystander) NSC through radiation-induced signaling cascades. Using media transfer experiments, we demonstrated significant effects of the U87MG glioblastoma secretome after gamma-irradiation on apoptosis in non-irradiated NSC. Addition of anti-TRAIL antibody to the transferred media partially suppressed apoptosis in NSC. Furthermore, we observed a dramatic increase in the production and secretion of IL8, TGFβ1 and IL6 by irradiated glioblastoma cells, which could promote glioblastoma cell survival and modify the effects of death factors in bystander NSC. While differentiation of NSC into neurons and astrocytes occurred efficiently with the corresponding differentiation media, pretreatment of NSC for 8 h with medium from irradiated glioblastoma cells selectively suppressed the differentiation of NSC into neurons, but not into astrocytes. Exogenous IL8 and TGFβ1 increased NSC/NPC survival, but also suppressed neuronal differentiation. On the other hand, IL6 was known to positively affect survival and differentiation of astrocyte progenitors. We established a U87MG neurosphere culture that was substantially enriched by SOX2(+) and CD133(+) glioma stem-like cells (GSC). Gamma-irradiation up-regulated apoptotic death in GSC via the FasL/Fas pathway. Media transfer experiments from irradiated GSC to non-targeted NSC again demonstrated induction of apoptosis and suppression of neuronal differentiation of NSC. In

  2. 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

  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. Neural and Behavioral Correlates of Alcohol-Induced Aggression Under Provocation

    OpenAIRE

    Gan, Gabriela; Sterzer, Philipp; Marxen, Michael; Zimmermann, Ulrich S.; Smolka, Michael N.

    2015-01-01

    Although alcohol consumption is linked to increased aggression, its neural correlates have not directly been studied in humans so far. Based on a comprehensive neurobiological model of alcohol-induced aggression, we hypothesized that alcohol-induced aggression would go along with increased amygdala and ventral striatum reactivity and impaired functioning of the prefrontal cortex (PFC) under alcohol. We measured neural and behavioral correlates of alcohol-induced aggression in a provoking vs n...

  5. Behavior Emergence in Autonomous Robot Control by Means of Evolutionary Neural Networks

    Science.gov (United States)

    Neruda, Roman; Slušný, Stanislav; Vidnerová, Petra

    We study the emergence of intelligent behavior of a simple mobile robot. Robot control system is realized by mechanisms based on neural networks and evolutionary algorithms. The evolutionary algorithm is responsible for the adaptation of a neural network parameters based on the robot's performance in a simulated environment. In experiments, we demonstrate the performance of evolutionary algorithm on selected problems, namely maze exploration and discrimination of walls and cylinders. A comparison of different networks architectures is presented and discussed.

  6. Convergence behavior of delayed discrete cellular neural network without periodic coefficients.

    Science.gov (United States)

    Wang, Jinling; Jiang, Haijun; Hu, Cheng; Ma, Tianlong

    2014-05-01

    In this paper, we study convergence behaviors of delayed discrete cellular neural networks without periodic coefficients. Some sufficient conditions are derived to ensure all solutions of delayed discrete cellular neural network without periodic coefficients converge to a periodic function, by applying mathematical analysis techniques and the properties of inequalities. Finally, some examples showing the effectiveness of the provided criterion are given. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Neural and Behavioral Correlates of Alcohol-Induced Aggression Under Provocation.

    Science.gov (United States)

    Gan, Gabriela; Sterzer, Philipp; Marxen, Michael; Zimmermann, Ulrich S; Smolka, Michael N

    2015-12-01

    Although alcohol consumption is linked to increased aggression, its neural correlates have not directly been studied in humans so far. Based on a comprehensive neurobiological model of alcohol-induced aggression, we hypothesized that alcohol-induced aggression would go along with increased amygdala and ventral striatum reactivity and impaired functioning of the prefrontal cortex (PFC) under alcohol. We measured neural and behavioral correlates of alcohol-induced aggression in a provoking vs non-provoking condition with a variant of the Taylor aggression paradigm (TAP) allowing to differentiate between reactive (provoked) and proactive (unprovoked) aggression. In a placebo-controlled cross-over design with moderate alcohol intoxication (~0.6 g/kg), 35 young healthy adults performed the TAP during functional magnetic resonance imaging (fMRI). Analyses revealed that provoking vs non-provoking conditions and alcohol vs placebo increased aggression and decreased brain responses in the anterior cingulate cortex/dorso-medial PFC (provokingalcoholalcohol specifically increased proactive (unprovoked) but not reactive (provoked) aggression (alcohol × provocation interaction). However, investigation of inter-individual differences revealed (1) that pronounced alcohol-induced proactive aggression was linked to higher levels of aggression under placebo, and (2) that pronounced alcohol-induced reactive aggression was related to increased amygdala and ventral striatum reactivity under alcohol, providing evidence for their role in human alcohol-induced reactive aggression. Our findings suggest that in healthy young adults a liability for alcohol-induced aggression in a non-provoking context might depend on overall high levels of aggression, but on alcohol-induced increased striatal and amygdala reactivity when triggered by provocation.

  8. Neural and Behavioral Correlates of Alcohol-Induced Aggression Under Provocation

    Science.gov (United States)

    Gan, Gabriela; Sterzer, Philipp; Marxen, Michael; Zimmermann, Ulrich S; Smolka, Michael N

    2015-01-01

    Although alcohol consumption is linked to increased aggression, its neural correlates have not directly been studied in humans so far. Based on a comprehensive neurobiological model of alcohol-induced aggression, we hypothesized that alcohol-induced aggression would go along with increased amygdala and ventral striatum reactivity and impaired functioning of the prefrontal cortex (PFC) under alcohol. We measured neural and behavioral correlates of alcohol-induced aggression in a provoking vs non-provoking condition with a variant of the Taylor aggression paradigm (TAP) allowing to differentiate between reactive (provoked) and proactive (unprovoked) aggression. In a placebo-controlled cross-over design with moderate alcohol intoxication (~0.6 g/kg), 35 young healthy adults performed the TAP during functional magnetic resonance imaging (fMRI). Analyses revealed that provoking vs non-provoking conditions and alcohol vs placebo increased aggression and decreased brain responses in the anterior cingulate cortex/dorso-medial PFC (provokingalcoholalcohol specifically increased proactive (unprovoked) but not reactive (provoked) aggression (alcohol × provocation interaction). However, investigation of inter-individual differences revealed (1) that pronounced alcohol-induced proactive aggression was linked to higher levels of aggression under placebo, and (2) that pronounced alcohol-induced reactive aggression was related to increased amygdala and ventral striatum reactivity under alcohol, providing evidence for their role in human alcohol-induced reactive aggression. Our findings suggest that in healthy young adults a liability for alcohol-induced aggression in a non-provoking context might depend on overall high levels of aggression, but on alcohol-induced increased striatal and amygdala reactivity when triggered by provocation. PMID:25971590

  9. Differentiation of human neural progenitor cells regulated by Wnt-3a.

    Science.gov (United States)

    Hübner, Rayk; Schmöle, Anne-Caroline; Liedmann, Andrea; Frech, Moritz J; Rolfs, Arndt; Luo, Jiankai

    2010-09-24

    Wnt ligands play pivotal roles in the control of cell growth and differentiation during central nervous system development via the Wnt signaling pathway. In this study, we investigated the effects of Wnt-3a and β-catenin on the differentiation of ReNcell VM human neural progenitor cells. After overexpression of Wnt-3a or mutant-stabilized β-catenin in ReNcell VM cells, their effects on TCF-mediated transcription, Wnt target gene expression and differentiation into neuronal and glial cells were investigated. Our results show that activation of Wnt/β-catenin signaling increases TCF-mediated transcription and the expression of the Wnt target genes Axin2, LEF1 and CyclinD1 in ReNcell VM cells. In contrast to mutant-stabilized β-catenin, Wnt-3a increases neurogenesis during the differentiation of ReNcell VM cells. Thus, our data suggest that neurogenesis induced by Wnt-3a is independent of the transcriptional activity of Wnt/β-catenin pathway in ReNcell VM cells. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. 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.

  11. Effects of radiofrequency exposure emitted from a GSM mobile phone on proliferation, differentiation, and apoptosis of neural stem cells

    OpenAIRE

    Eghlidospour, Mahsa; Ghanbari, Amir; Mortazavi, Seyyed Mohammad Javad; Azari, Hassan

    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 differen...

  12. Neural activity in human primary motor cortex areas 4a and 4p is modulated differentially by attention to action

    OpenAIRE

    Binkofski, F.; Fink, Gereon R.; Geyer, Stefan; Buccino, G.; Gruber, Oliver; Shah, N. Jon; Taylor, John G.; Seitz, Rüdiger J.; Zilles, Karl; Freund, Hans-Joachim

    2002-01-01

    The mechanisms underlying attention to action are poorly understood. Although distracted by something else, we often maintain the accuracy of a movement, which suggests that differential neural mechanisms for the control of attended and nonattended action exist. Using functional magnetic resonance imaging (fMRI) in normal volunteers and probabilistic cytoarchitectonic maps, we observed that neural activity in subarea 4p (posterior) within the primary motor cortex was modulated by attention to...

  13. 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.

  14. Effects of Nerve Growth Factor and Basic Fibroblast Growth Factor Promote Human Dental Pulp Stem Cells to Neural Differentiation.

    Science.gov (United States)

    Zhang, Jinlong; Lian, Min; Cao, Peipei; Bao, Guofeng; Xu, Guanhua; Sun, Yuyu; Wang, Lingling; Chen, Jiajia; Wang, Yi; Feng, Guijuan; Cui, Zhiming

    2017-04-01

    Dental pulp stem cells (DPSCs) were the most widely used seed cells in the field of neural regeneration and bone tissue engineering, due to their easily isolation, lack of ethical controversy, low immunogenicity and low rates of transplantation rejection. The purpose of this study was to investigate the role of basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) on neural differentiation of DPSCs in vitro. DPSCs were cultured in neural differentiation medium containing NGF and bFGF alone or combination for 7 days. Then neural genes and protein markers were analyzed using western blot and RT-PCR. Our study revealed that bFGF and NGF increased neural differentiation of DPSCs synergistically, compared with bFGF and NGF alone. The levels of Nestin, MAP-2, βIII-tubulin and GFAP were the most highest in the DPSCs + bFGF + NGF group. Our results suggested that bFGF and NGF signifiantly up-regulated the levels of Sirt1. After treatment with Sirt1 inhibitor, western blot, RT-PCR and immunofluorescence staining showed that neural genes and protein markers had markedly decreased. Additionally, the ERK and AKT signaling pathway played a key role in the neural differentiation of DPSCs stimulated with bFGF + NGF. These results suggested that manipulation of the ERK and AKT signaling pathway may be associated with the differentiation of bFGF and NGF treated DPSCs. Our date provided theoretical basis for DPSCs to treat neurological diseases and repair neuronal damage.

  15. 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

  16. 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.

  17. 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.

  18. Prenatal exposure of ethanol induces increased glutamatergic neuronal differentiation of neural progenitor cells

    Directory of Open Access Journals (Sweden)

    Han Seol-Heui

    2010-11-01

    Full Text Available Abstract Background Prenatal ethanol exposure during pregnancy induces a spectrum of mental and physical disorders called fetal alcohol spectrum disorder (FASD. The central nervous system is the main organ influenced by FASD, and neurological symptoms include mental retardation, learning abnormalities, hyperactivity and seizure susceptibility in childhood along with the microcephaly. In this study, we examined whether ethanol exposure adversely affects the proliferation of NPC and de-regulates the normal ratio between glutamatergic and GABAergic neuronal differentiation using primary neural progenitor culture (NPC and in vivo FASD models. Methods Neural progenitor cells were cultured from E14 embryo brain of Sprague-Dawley rat. Pregnant mice and rats were treated with ethanol (2 or 4 g/kg/day diluted with normal saline from E7 to E16 for in vivo FASD animal models. Expression level of proteins was investigated by western blot analysis and immunocytochemical assays. MTT was used for cell viability. Proliferative activity of NPCs was identified by BrdU incorporation, immunocytochemistry and FACS analysis. Results Reduced proliferation of NPCs by ethanol was demonstrated using BrdU incorporation, immunocytochemistry and FACS analysis. In addition, ethanol induced the imbalance between glutamatergic and GABAergic neuronal differentiation via transient increase in the expression of Pax6, Ngn2 and NeuroD with concomitant decrease in the expression of Mash1. Similar pattern of expression of those transcription factors was observed using an in vivo model of FASD as well as the increased expression of PSD-95 and decreased expression of GAD67. Conclusions These results suggest that ethanol induces hyper-differentiation of glutamatergic neuron through Pax6 pathway, which may underlie the hyper-excitability phenotype such as hyperactivity or seizure susceptibility in FASD patients.

  19. Demonstration of a neural circuit critical for imprinting behavior in chicks.

    Science.gov (United States)

    Nakamori, Tomoharu; Sato, Katsushige; Atoji, Yasuro; Kanamatsu, Tomoyuki; Tanaka, Kohichi; Ohki-Hamazaki, Hiroko

    2010-03-24

    Imprinting behavior in birds is elicited by visual and/or auditory cues. It has been demonstrated previously that visual cues are recognized and processed in the visual Wulst (VW), and imprinting memory is stored in the intermediate medial mesopallium (IMM) of the telencephalon. Alteration of neural responses in these two regions according to imprinting has been reported, yet direct evidence of the neural circuit linking these two regions is lacking. Thus, it remains unclear how memory is formed and expressed in this circuit. Here, we present anatomical as well as physiological evidence of the neural circuit connecting the VW and IMM and show that imprinting training during the critical period strengthens and refines this circuit. A functional connection established by imprint training resulted in an imprinting behavior. After the closure of the critical period, training could not activate this circuit nor induce the imprinting behavior. Glutamatergic neurons in the ventroposterior region of the VW, the core region of the hyperpallium densocellulare (HDCo), sent their axons to the periventricular part of the HD, just dorsal and afferent to the IMM. We found that the HDCo is important in imprinting behavior. The refinement and/or enhancement of this neural circuit are attributed to increased activity of HDCo cells, and the activity depended on NR2B-containing NMDA receptors. These findings show a neural connection in the telencephalon in Aves and demonstrate that NR2B function is indispensable for the plasticity of HDCo cells, which are key mediators of imprinting.

  20. Metformin Acts on Two Different Molecular Pathways to Enhance Adult Neural Precursor Proliferation/Self-Renewal and Differentiation

    Directory of Open Access Journals (Sweden)

    Michael Fatt

    2015-12-01

    Full Text Available The recruitment of endogenous adult neural stem cells for brain repair is a promising regenerative therapeutic strategy. This strategy involves stimulation of multiple stages of adult neural stem cell development, including proliferation, self-renewal, and differentiation. Currently, there is a lack of a single therapeutic approach that can act on these multiple stages of adult neural stem cell development to enhance neural regeneration. Here we show that metformin, an FDA-approved diabetes drug, promotes proliferation, self-renewal, and differentiation of adult neural precursors (NPCs. Specifically, we show that metformin enhances adult NPC proliferation and self-renewal dependent upon the p53 family member and transcription factor TAp73, while it promotes neuronal differentiation of these cells by activating the AMPK-aPKC-CBP pathway. Thus, metformin represents an optimal candidate neuro-regenerative agent that is capable of not only expanding the adult NPC population but also subsequently driving them toward neuronal differentiation by activating two distinct molecular pathways.

  1. Differential development of neuronal physiological responsiveness in two human neural stem cell lines.

    Science.gov (United States)

    Donato, Roberta; Miljan, Erik A; Hines, Susan J; Aouabdi, Sihem; Pollock, Kenneth; Patel, Sara; Edwards, Frances A; Sinden, John D

    2007-05-25

    Neural stem cells (NSCs) are powerful research tools for the design and discovery of new approaches to neurodegenerative disease. Overexpression of the myc family transcription factors in human primary cells from developing cortex and mesencephalon has produced two stable multipotential NSC lines (ReNcell VM and CX) that can be continuously expanded in monolayer culture. In the undifferentiated state, both ReNcell VM and CX are nestin positive and have resting membrane potentials of around -60 mV but do not display any voltage-activated conductances. As initially hypothesized, using standard methods (stdD) for differentiation, both cell lines can form neurons, astrocytes and oligodendrocytes according to immunohistological characteristics. However it became clear that this was not true for electrophysiological features which designate neurons, such as the firing of action potentials. We have thus developed a new differentiation protocol, designated 'pre-aggregation differentiation' (preD) which appears to favor development of electrophysiologically functional neurons and to lead to an increase in dopaminergic neurons in the ReNcell VM line. In contrast, the protocol used had little effect on the differentiation of ReNcell CX in which dopaminergic differentiation was not observed. Moreover, after a week of differentiation with the preD protocol, 100% of ReNcell VM featured TTX-sensitive Na+-channels and fired action potentials, compared to 25% after stdD. Currents via other voltage-gated channels did not appear to depend on the differentiation protocol. ReNcell CX did not display the same electrophysiological properties as the VM line, generating voltage-dependant K+ currents but no Na+ currents or action potentials under either stdD or preD differentiation. These data demonstrate that overexpression of myc in NSCs can be used to generate electrophysiologically active neurons in culture. Development of a functional neuronal phenotype may be dependent on parameters

  2. Differential development of neuronal physiological responsiveness in two human neural stem cell lines

    Directory of Open Access Journals (Sweden)

    Patel Sara

    2007-05-01

    Full Text Available Abstract Background Neural stem cells (NSCs are powerful research tools for the design and discovery of new approaches to neurodegenerative disease. Overexpression of the myc family transcription factors in human primary cells from developing cortex and mesencephalon has produced two stable multipotential NSC lines (ReNcell VM and CX that can be continuously expanded in monolayer culture. Results In the undifferentiated state, both ReNcell VM and CX are nestin positive and have resting membrane potentials of around -60 mV but do not display any voltage-activated conductances. As initially hypothesized, using standard methods (stdD for differentiation, both cell lines can form neurons, astrocytes and oligodendrocytes according to immunohistological characteristics. However it became clear that this was not true for electrophysiological features which designate neurons, such as the firing of action potentials. We have thus developed a new differentiation protocol, designated 'pre-aggregation differentiation' (preD which appears to favor development of electrophysiologically functional neurons and to lead to an increase in dopaminergic neurons in the ReNcell VM line. In contrast, the protocol used had little effect on the differentiation of ReNcell CX in which dopaminergic differentiation was not observed. Moreover, after a week of differentiation with the preD protocol, 100% of ReNcell VM featured TTX-sensitive Na+-channels and fired action potentials, compared to 25% after stdD. Currents via other voltage-gated channels did not appear to depend on the differentiation protocol. ReNcell CX did not display the same electrophysiological properties as the VM line, generating voltage-dependant K+ currents but no Na+ currents or action potentials under either stdD or preD differentiation. Conclusion These data demonstrate that overexpression of myc in NSCs can be used to generate electrophysiologically active neurons in culture. Development of a

  3. 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, BJ

    2014-01-01

    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 current 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 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 towards 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 suggests possible explanations for how peers may motivate adolescent behavior. PMID:24550063

  4. 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.

  5. 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.

  6. Donepezil promotes differentiation of neural stem cells into mature oligodendrocytes at the expense of astrogenesis.

    Science.gov (United States)

    Imamura, Osamu; Arai, Masaaki; Dateki, Minori; Takishima, Kunio

    2017-01-01

    Oligodendrocytes are the myelin-forming cells of the central nervous system. Oligodendrocyte loss and failure of myelin development result in serious human disorders, including multiple sclerosis. Previously, using oligodendrocyte progenitor cells, we have shown that donepezil, which is an acetylcholinesterase inhibitor developed for the treatment of Alzheimer's disease, stimulates myelin gene expression and oligodendrocyte differentiation. Here, we aimed to analyze the effects of donepezil on primary mouse embryonic neural stem cells (NSCs). Donepezil treatment led to impaired self-renewal ability and increased apoptosis. These effects appeared to be mediated through the Akt/Bad signaling pathway. Using neurosphere differentiation analysis, we observed that donepezil leads to reduced numbers of astrocytes and increased numbers of oligodendrocytes and neurons. Consistent with this finding, mRNA and protein levels for the oligodendrocyte markers myelin-associated glycoprotein, 2', 3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase), and myelin basic protein, as well as the neuronal marker β-tubulin type III (Tuj1) were up-regulated. In contrast, the expression of the astrocyte marker glial fibrillary acidic protein (GFAP) was down-regulated by donepezil in a dose- and time-dependent manner. Moreover, donepezil increased oligodendrocyte differentiation, resulting in a reduction in the differentiation of NSCs into astrocytes, by suppressing the activation of signal transducer and activator of transcription 3 (STAT3), SMAD1/5/9, and the downstream target gene GFAP, even under astrocyte-inducing conditions. These results suggest that efficient differentiation of NSCs into oligodendrocytes by donepezil may indicate a novel therapeutic role for this drug in promoting repair in demyelinated lesions in addition to its role in preventing astrogenesis. © 2016 International Society for Neurochemistry.

  7. Transient muscarinic and glutamatergic stimulation of neural stem cells triggers acute and persistent changes in differentiation.

    Science.gov (United States)

    Samarasinghe, Ranmal A; Kanuparthi, Prasad S; Timothy Greenamyre, J; DeFranco, Donald B; Di Maio, Roberto

    2014-10-01

    While aberrant cell proliferation and differentiation may contribute to epileptogenesis, the mechanisms linking an initial epileptic insult to subsequent changes in cell fate remain elusive. Using both mouse and human iPSC-derived neural progenitor/stem cells (NPSCs), we found that a combined transient muscarinic and mGluR1 stimulation inhibited overall neurogenesis but enhanced NPSC differentiation into immature GABAergic cells. If treated NPSCs were further passaged, they retained a nearly identical phenotype upon differentiation. A similar profusion of immature GABAergic cells was seen in rats with pilocarpine-induced chronic epilepsy. Furthermore, live cell imaging revealed abnormal de-synchrony of Ca(++) transients and altered gap junction intercellular communication following combined muscarinic/glutamatergic stimulation, which was associated with either acute site-specific dephosphorylation of connexin 43 or a long-term enhancement of its degradation. Therefore, epileptogenic stimuli can trigger acute and persistent changes in cell fate by altering distinct mechanisms that function to maintain appropriate intercellular communication between coupled NPSCs. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. 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.

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

    Science.gov (United States)

    Milosevic, Javorina; Schwarz, Sigrid C; Ogunlade, Vera; Meyer, Anne K; Storch, Alexander; Schwarz, Johannes

    2009-06-15

    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.

  10. 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.

  11. 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.

  12. Directed differentiation of porcine epiblast-derived neural progenitor cells into neurons and glia.

    Science.gov (United States)

    Rasmussen, M A; Hall, V J; Carter, T F; Hyttel, P

    2011-09-01

    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 and evaluate their in-vitro differentiation potential. Epiblasts were manually isolated from expanded hatched blastocysts and cultured on MEF feeder cells. Outgrowth colonies were passaged to MS5 cells and rosettes were further passaged to Matrigel-coated dishes containing bFGF and EGF. Three NPC lines were established which showed expression of SOX2, NESTIN and VIMENTIN. One line was characterised in more detail, retaining a normal karyotype and proliferating for more than three months in culture. Following differentiation, TUJI was significantly up-regulated in protocol 2 (RA and SHH; 58% positive cells) as were NF and TH. In contrast, MBP was significantly up-regulated in protocol 3 (FGF8 and SHH; 63% positive cells), whereas, GFAP was significantly up-regulated in protocols 1-4 (33%, 25%, 43% and 22%). The present study provides the first report of a porcine blastocyst-derived NPC line capable of differentiating into both neurons and glia, which may be of paramount importance for future transplantation studies in large animal models of neurodegenerative diseases. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Every child is different : differential parental treatment and adolescent problem behavior

    NARCIS (Netherlands)

    Tamrouti-Makkink, Ilse Diana

    2006-01-01

    This dissertation is an important contribution to the research on differential parental treatment and adolescent problem behavior. First, it extends earlier studies by exploring possible moderating factors explaining the level of differential parental treatment and the link between differential

  14. 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.

  15. 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.

  16. 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.

  17. Neural networks and differential evolution algorithm applied for modelling the depollution process of some gaseous streams.

    Science.gov (United States)

    Curteanu, Silvia; Suditu, Gabriel Dan; Buburuzan, Adela Marina; Dragoi, Elena Niculina

    2014-11-01

    The depollution of some gaseous streams containing n-hexane is studied by adsorption in a fixed bed column, under dynamic conditions, using granular activated carbon and two types of non-functionalized hypercross-linked polymeric resins. In order to model the process, a new neuro-evolutionary approach is proposed. It is a combination of a modified differential evolution (DE) with neural networks (NNs) and two local search algorithms, the global and local optimizers, working together to determine the optimal NN model. The main elements that characterize the applied variant of DE consist in using an opposition-based learning initialization, a simple self-adaptive procedure for the control parameters, and a modified mutation principle based on the fitness function as a criterion for reorganization. The results obtained prove that the proposed algorithm is able to determine a good model of the considered process, its performance being better than those of an available phenomenological model.

  18. 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.

  19. 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.

  20. Geminin loss causes neural tube defects through disrupted progenitor specification and neuronal differentiation

    Science.gov (United States)

    ES, Patterson; LE, Waller; KL, Kroll

    2014-01-01

    Geminin is a nucleoprotein that can directly bind chromatin regulatory complexes to modulate gene expression during development. Geminin knockout mouse embryos are preimplantation lethal by the 32-cell stage, precluding in vivo study of Geminin's role in neural development. Therefore, here we used a conditional Geminin allele in combination with several Cre-driver lines to define an essential role for Geminin during mammalian neural tube (NT) formation and patterning. Geminin was required in the NT within a critical developmental time window (embryonic day 8.5–10.5), when NT patterning and closure occurs. Geminin excision at these stages resulted in strongly diminished expression of genes that mark and promote dorsal NT identities and decreased differentiation of ventral motor neurons, resulting in completely penetrant NT defects, while excision after embryonic day 10.5 did not result in NT defects. When Geminin was deleted specifically in the spinal NT, both NT defects and axial skeleton defects were observed, but neither defect occurred when Geminin was excised in paraxial mesenchyme, indicating a tissue autonomous requirement for Geminin in developing neuroectoderm. Despite a potential role for Geminin in cell cycle control, we found no evidence of proliferation defects or altered apoptosis. Comparisons of gene expression in the NT of Geminin mutant versus wild-type siblings at embryonic day 10.5 revealed decreased expression of key regulators of neurogenesis, including neurogenic bHLH transcription factors and dorsal interneuron progenitor markers. Together, these data demonstrate a requirement for Geminin for NT patterning and neuronal differentiation during mammalian neurulation in vivo. PMID:24995796

  1. 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

  2. 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.

  3. Appetitive traits from infancy to adolescence: using behavioral and neural measures to investigate obesity risk.

    Science.gov (United States)

    Carnell, Susan; Benson, Leora; Pryor, Katherine; Driggin, Elissa

    2013-09-10

    We come into the world with enduring predispositions towards food, which interact with environmental factors to influence our eating behaviors and weight trajectories. But our fates are not sealed - by learning more about this process we can identify ways to intervene. To advance this goal this we need to be able to assess appetitive traits such as food cue responsiveness and satiety sensitivity at different developmental stages. Assessment methods might include behavioral measures (e.g. eating behavior tests, psychometric questionnaires), but also biomarkers such as brain responses to food cues measured using fMRI. Evidence from infants, children and adolescents suggests that these indices of appetite differ not only with body weight, but also with familial obesity risk as assessed by parent weight, which reflects both genetic and environmental influences, and may provide a useful predictor of obesity development. Behavioral and neural approaches have great potential to inform each other: examining eating behavior can help us identify meaningful appetitive endophenotypes whose neural bases can be probed, while increasing knowledge of the shared neurobiology underlying appetite, obesity, and related behaviors and disorders may ultimately lead to innovative generalized interventions. Another challenge will be to combine comprehensive behavioral and neural assessments of appetitive traits with measures of relevant genetic and environmental factors within long-term prospective studies. This approach may help to identify the biobehavioral precursors of obesity, and lay the foundations for targeted neurobehavioral interventions that can interrupt the pathway to excess weight. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. 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....

  5. 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

    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...... 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...

  6. 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.

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

    Science.gov (United States)

    Lööv, Camilla; Fernqvist, Maria; Walmsley, Adrian; Marklund, Niklas; Erlandsson, Anna

    2012-01-01

    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.

  8. 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

  9. Estrogen Stimulates Proliferation and Differentiation of Neural Stem/Progenitor Cells through Different Signal Transduction Pathways

    Directory of Open Access Journals (Sweden)

    Makiko Okada

    2010-10-01

    Full Text Available Our previous study indicated that both 17β-estradiol (E2, known to be an endogenous estrogen, and bisphenol A (BPA, known to be a xenoestrogen, could positively influence the proliferation or differentiation of neural stem/progenitor cells (NS/PCs. The aim of the present study was to identify the signal transduction pathways for estrogenic activities promoting proliferation and differentiation of NS/PCs via well known nuclear estrogen receptors (ERs or putative membrane-associated ERs. NS/PCs were cultured from the telencephalon of 15-day-old rat embryos. In order to confirm the involvement of nuclear ERs for estrogenic activities, their specific antagonist, ICI-182,780, was used. The presence of putative membrane-associated ER was functionally examined as to whether E2 can activate rapid intracellular signaling mechanism. In order to confirm the involvement of membrane-associated ERs for estrogenic activities, a cell-impermeable E2, bovine serum albumin-conjugated E2 (E2-BSA was used. We showed that E2 could rapidly activate extracellular signal-regulated kinases 1/2 (ERK 1/2, which was not inhibited by ICI-182,780. ICI-182,780 abrogated the stimulatory effect of these estrogens (E2 and BPA on the proliferation of NS/PCs, but not their effect on the differentiation of the NS/PCs into oligodendroglia. Furthermore, E2-BSA mimicked the activity of differentiation from NS/PCs into oligodendroglia, but not the activity of proliferation. Our study suggests that (1 the estrogen induced proliferation of NS/PCs is mediated via nuclear ERs; (2 the oligodendroglial generation from NS/PCs is likely to be stimulated via putative membrane‑associated ERs.

  10. 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.

  11. Differential Reinforcement of Low Rate Schedules Reduce Severe Problem Behavior.

    Science.gov (United States)

    Bonner, Andrew C; Borrero, John C

    2017-09-01

    Differential-reinforcement-of-low-rate (DRL) schedules are reinforcement contingencies designed to reduce response rates. A common variation of the DRL arrangement is known as full-session DRL ( f-DRL), in which a reinforcer is presented at the end of an interval if the response rate during that interval is below a predetermined criterion. Prior human operant research involving arbitrary mouse clicks has shown that the f-DRL is likely to reduce target responding to near zero rates. Similarly, applied research has shown that the f-DRL is likely to reduce minimally disruptive classroom behavior. There are, however, relatively few successful applications of the f-DRL to severe forms of problem behavior (e.g., self-injurious behavior). Thus, the purpose of this study was to examine the effects of f-DRL on the severe problem behavior of individuals with intellectual and developmental disabilities. For four participants, the f-DRL reduced severe problem behavior by clinically significant levels. Furthermore, results of a contingency strength analysis showed a strong negative contingency strength between target responding and reinforcer delivery for all participants.

  12. Characterization of Apoptosis Signaling Cascades During the Differentiation Process of Human Neural ReNcell VM Progenitor Cells In Vitro.

    Science.gov (United States)

    Jaeger, Alexandra; Fröhlich, Michael; Klum, Susanne; Lantow, Margareta; Viergutz, Torsten; Weiss, Dieter G; Kriehuber, Ralf

    2015-11-01

    Apoptosis is an essential physiological process accompanying the development of the central nervous system and human neurogenesis. However, the time scale and the underlying molecular mechanisms are yet poorly understood. Due to this fact, we investigated the functionality and general inducibility of apoptosis in the human neural ReNcell VM progenitor cell line during differentiation and also after exposure to staurosporine (STS) and ultraviolet B (UVB) irradiation. Transmission light microscopy, flow cytometry, and Western-/Immunoblot analysis were performed to compare proliferating and differentiating, in addition to STS- and UVB-treated cells. In particular, from 24 to 72 h post-initiation of differentiation, G0/G1 cell cycle arrest, increased loss of apoptotic cells, activation of pro-apoptotic BAX, Caspase-3, and cleavage of its substrate PARP were observed during cell differentiation and, to a higher extent, after treatment with STS and UVB. We conclude that redundant or defective cells are eliminated by apoptosis, while otherwise fully differentiated cells were less responsive to apoptosis induction by STS than proliferating cells, likely as a result of reduced APAF-1 expression, and increased levels of BCL-2. These data provide the evidence that apoptotic mechanisms in the neural ReNcell VM progenitor cell line are not only functional, but also inducible by external stimuli like growth factor withdrawal or treatment with STS and UVB, which marks this cell line as a suitable model to investigate apoptosis signaling pathways in respect to the differentiation processes of human neural progenitor cells in vitro.

  13. Quantitative and kinetic profile of Wnt/β-catenin signaling components during human neural progenitor cell differentiation.

    Science.gov (United States)

    Mazemondet, Orianne; Hubner, Rayk; Frahm, Jana; Koczan, Dirk; Bader, Benjamin M; Weiss, Dieter G; Uhrmacher, Adelinde M; Frech, Moritz J; Rolfs, Arndt; Luo, Jiankai

    2011-12-01

    ReNcell VM is an immortalized human neural progenitor cell line with the ability to differentiate in vitro into astrocytes and neurons, in which the Wnt/β-catenin pathway is known to be involved. However, little is known about kinetic changes of this pathway in human neural progenitor cell differentiation. In the present study, we provide a quantitative profile of Wnt/β-catenin pathway dynamics showing its spatio-temporal regulation during ReNcell VM cell differentiation. We show first that T-cell factor dependent transcription can be activated by stabilized β-catenin. Furthermore, endogenous Wnt ligands, pathway receptors and signaling molecules are temporally controlled, demonstrating changes related to differentiation stages. During the first three hours of differentiation the signaling molecules LRP6, Dvl2 and β-catenin are spatio-temporally regulated between distinct cellular compartments. From 24 h onward, components of the Wnt/β-catenin pathway are strongly activated and regulated as shown by mRNA up-regulation of Wnt ligands (Wnt5a and Wnt7a), receptors including Frizzled-2, -3, -6, -7, and -9, and co-receptors, and target genes including Axin2. This detailed temporal profile of the Wnt/β-catenin pathway is a first step to understand, control and to orientate, in vitro, human neural progenitor cell differentiation.

  14. 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…

  15. Oscillatory Behavior on a Three-Node Neural Network Model with Discrete and Distributed Delays

    Directory of Open Access Journals (Sweden)

    Chunhua Feng

    2014-01-01

    Full Text Available This paper investigates the oscillatory behavior of the solutions for a three-node neural network with discrete and distributed delays. Two theorems are provided to determine the conditions for oscillating solutions of the model. The criteria for selecting the parameters in this network are derived. Some simulation examples are presented to illustrate the effectiveness of the results.

  16. 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…

  17. 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...

  18. 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.

  19. Electromagnetic fields induce neural differentiation of human bone marrow derived mesenchymal stem cells via ROS mediated EGFR activation.

    Science.gov (United States)

    Park, Jeong-Eun; Seo, Young-Kwon; Yoon, Hee-Hoon; Kim, Chan-Wha; Park, Jung-Keug; Jeon, Songhee

    2013-03-01

    Even though the inducing effect of electromagnetic fields (EMF) on the neural differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) is a distinctive, the underlying mechanism of differentiation remains unclear. To find out the signaling pathways involved in the neural differentiation of BM-MSCs by EMF, we examined the CREB phosphorylation and Akt or ERK activation as an upstream of CREB. In hBM-MSCs treated with ELF-EMF (50 Hz, 1 mT), the expression of neural markers such as NF-L, MAP2, and NeuroD1 increased at 6 days and phosphorylation of Akt and CREB but not ERK increased at 90 min in BM-MSCs. Moreover, EMF increased phosphorylation of epidermal growth factor receptor (EGFR) as an upstream receptor tyrosine kinase of PI3K/Akt at 90 min. It has been well documented that ELF-MF exposure may alter cellular processes by increasing intracellular reactive oxygen species (ROS) concentrations. Thus, we examined EMF-induced ROS production in BM-MSCs. Moreover, pretreatment with a ROS scavenger, N-acetylcystein, and an EGFR inhibitor, AG-1478, prevented the phosphorylation of EGFR and downstream molecules. These results suggest that EMF induce neural differentiation through activation of EGFR signaling and mild generation of ROS. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. 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.

  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...

  2. Culture, characterization and differentiation of neural precursors from the central nervous system of guinea pigs (Cavia porcellus Linnaeus, 1758

    Directory of Open Access Journals (Sweden)

    Erika Toledo da Fonseca

    Full Text Available Abstract: Potentially neurogenic areas were initially identified by incorporation of bromodeoxyuridine (BrdU in cells underlying the subventricular zone (SVZ of the lateral ventricles wall, hippocampus and olfactory bulbs of newborn guinea pigs. Neural precursors from the SVZ were cultured in suspension, generating neurospheres (NSFs, which, upon dissociation were able to generate new NSFs. Upon culture in the absence of growth factors, cells dissociated from NSFs displayed evidence for neural differentiation, giving rise to cells from neural lineage. Flow cytometry analysis for of NSFs-derived cells after differentiation revealed approximately 13.3% nestin positive, 5.5% Beta-III-tubulin positive, 9% GFAP positive and 7.8% mGalC positive. Functional assays by measurement of calcium influx upon gamma butiric amino acid (GABA and glutamate stimuli, revealed stimulation in differentiated cells, an indicator of neuronal differentiation. The ability of guinea pig SVZ cells to originate functional neurons in vitro is promising for research and towards a future use of neural stem cells in the therapy of neurological disorders.

  3. Neural Correlates of Impulsive Aggressive Behavior in Subjects With a History of Alcohol Dependence

    OpenAIRE

    Kose,Samet; Steinberg, Joel L.; Moeller, F. Gerard; Gowin, Joshua L.; Zuniga, Edward; Kamdar, Zahra N.; Schmitz, Joy M.; Scott D. Lane

    2015-01-01

    Alcohol-related aggression is a complex and problematic phenomenon with profound public health consequences. We examined neural correlates potentially moderating the relationship between human aggressive behavior and chronic alcohol use. Thirteen subjects meeting DSM–IV criteria for past alcohol-dependence in remission (AD) and 13 matched healthy controls (CONT) participated in an fMRI study adapted from a laboratory model of human aggressive behavior (Point Subtraction Aggression Paradigm, o...

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. Alcohol-induced epigenetic alterations to developmentally crucial genes regulating neural stemness and differentiation.

    Science.gov (United States)

    Veazey, Kylee J; Carnahan, Mindy N; Muller, Daria; Miranda, Rajesh C; Golding, Michael C

    2013-07-01

    From studies using a diverse range of model organisms, we now acknowledge that epigenetic changes to chromatin structure provide a plausible link between environmental teratogens and alterations in gene expression leading to disease. Observations from a number of independent laboratories indicate that ethanol (EtOH) has the capacity to act as a powerful epigenetic disruptor and potentially derail the coordinated processes of cellular differentiation. In this study, we sought to examine whether primary neurospheres cultured under conditions maintaining stemness were susceptible to alcohol-induced alterations in the histone code. We focused our studies on trimethylated histone 3 lysine 4 and trimethylated histone 3 lysine 27, as these are 2 of the most prominent posttranslational histone modifications regulating stem cell maintenance and neural differentiation. Primary neurosphere cultures were maintained under conditions promoting the stem cell state and treated with EtOH for 5 days. Control and EtOH-treated cellular extracts were examined using a combination of quantitative RT-PCR and chromatin immunoprecipitation techniques. We find that the regulatory regions of genes controlling both neural precursor cell identity and processes of differentiation exhibited significant declines in the enrichment of the chromatin marks examined. Despite these widespread changes in chromatin structure, only a small subset of genes including Dlx2, Fabp7, Nestin, Olig2, and Pax6 displayed EtOH-induced alterations in transcription. Unexpectedly, the majority of chromatin-modifying enzymes examined including members of the Polycomb Repressive Complex displayed minimal changes in expression and localization. Only transcripts encoding Dnmt1, Uhrf1, Ehmt1, Ash2 l, Wdr5, and Kdm1b exhibited significant differences. Our results indicate that primary neurospheres maintained as stem cells in vitro are susceptible to alcohol-induced perturbation of the histone code and errors in the epigenetic

  15. Differentiation and Cell-Cell Interactions of Neural Progenitor Cells Transplanted into Intact Adult Brain.

    Science.gov (United States)

    Sukhinich, K K; Kosykh, A V; Aleksandrova, M A

    2015-11-01

    We studied the behavior and cell-cell interactions of embryonic brain cell from GFP-reporter mice after their transplantation into the intact adult brain. Fragments or cell suspensions of fetal neocortical cells at different stages of development were transplanted into the neocortex and striatum of adult recipients. Even in intact brain, the processes of transplanted neurons formed extensive networks in the striatum and neocortical layers I and V-VI. Processes of transplanted cells at different stages of development attained the rostral areas of the frontal cortex and some of them reached the internal capsule. However, the cells transplanted in suspension had lower process growth potency than cells from tissue fragments. Tyrosine hydroxylase fibers penetrated from the recipient brain into grafts at both early and late stages of development. Our experiments demonstrated the formation of extensive reciprocal networks between the transplanted fetal neural cells and recipient brain neurons even in intact brain.

  16. The regulation of social recognition, social communication and aggression: vasopressin in the social behavior neural network.

    Science.gov (United States)

    Albers, H Elliott

    2012-03-01

    Neuropeptides in the arginine vasotocin/arginine vasopressin (AVT/AVP) family play a major role in the regulation of social behavior by their actions in the brain. In mammals, AVP is found within a circuit of recriprocally connected limbic structures that form the social behavior neural network. This review examines the role played by AVP within this network in controlling social processes that are critical for the formation and maintenance of social relationships: social recognition, social communication and aggression. Studies in a number of mammalian species indicate that AVP and AVP V1a receptors are ideally suited to regulate the expression of social processes because of their plasticity in response to factors that influence social behavior. The pattern of AVP innervation and V1a receptors across the social behavior neural network may determine the potential range and intensity of social responses that individuals display in different social situations. Although fundamental information on how social behavior is wired in the brain is still lacking, it is clear that different social behaviors can be influenced by the actions of AVP in the same region of the network and that AVP can act within multiple regions of this network to regulate the expression of individual social behaviors. The existing data suggest that AVP can influence social behavior by modulating the interpretation of sensory information, by influencing decision making and by triggering complex motor outputs. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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.

  5. Inhibition and impulsivity: behavioral and neural basis of response control.

    Science.gov (United States)

    Bari, Andrea; Robbins, Trevor W

    2013-09-01

    In many circumstances alternative courses of action and thoughts have to be inhibited to allow the emergence of goal-directed behavior. However, this has not been the accepted view in the past and only recently has inhibition earned its own place in the neurosciences as a fundamental cognitive function. In this review we first introduce the concept of inhibition from early psychological speculations based on philosophical theories of the human mind. The broad construct of inhibition is then reduced to its most readily observable component which necessarily is its behavioral manifestation. The study of 'response inhibition' has the advantage of dealing with a relatively simple and straightforward process, the overriding of a planned or already initiated action. Deficient inhibitory processes profoundly affect everyday life, causing impulsive conduct which is generally detrimental for the individual. Impulsivity has been consistently linked to several types of addiction, attention deficit/hyperactivity disorder, mania and other psychiatric conditions. Our discussion of the behavioral assessment of impulsivity will focus on objective laboratory tasks of response inhibition that have been implemented in parallel for humans and other species with relatively few qualitative differences. The translational potential of these measures has greatly improved our knowledge of the neurobiological basis of behavioral inhibition and impulsivity. We will then review the current models of behavioral inhibition along with their expression via underlying brain regions, including those involved in the activation of the brain's emergency 'brake' operation, those engaged in more controlled and sustained inhibitory processes and other ancillary executive functions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. 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.

  7. Female Songbirds: The unsung drivers of courtship behavior and its neural substrates.

    Science.gov (United States)

    Perkes, Ammon; White, David; Wild, J Martin; Schmidt, Marc

    2017-12-10

    Songbirds hold a prominent role in the fields of neurobiology, evolution, and social behavior. Many of these fields have assumed that females lacked the ability to produce song and have therefore treated song as a male-specific behavior. Consequently, much of our understanding regarding the evolution and neural control of song behavior has been driven by these assumptions. Here we review literature from diverse fields to provide a broader perspective of the role of females in vocal communication and courtship. Recent evidence indicates that song evolved in both males and females and instances of female song are still common. The specialized neural circuit known as the "song system," which is necessary for singing in males, is also present in females, including those that do not sing, implying broader functions that include evaluating male song and controlling courtship behavior. In addition to having flexible, individualized preferences, females actively shape their social network through their interactions with males, females, and juveniles. We suggest that by developing more accurate hypotheses concerning the role of females we may better understand the evolution and neural mechanisms of song production and courtship behavior. Copyright © 2017. Published by Elsevier B.V.

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

    Directory of Open Access Journals (Sweden)

    Tae-Ho Lee

    2017-08-01

    Full Text Available 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 Mage = 42.8 years; adolescent Mage = 14.9 years; 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.

  9. The role of histone acetylation in cocaine-induced neural plasticity and behavior.

    Science.gov (United States)

    Rogge, George A; Wood, Marcelo A

    2013-01-01

    How do drugs of abuse, such as cocaine, cause stable changes in neural plasticity that in turn drive long-term changes in behavior? What kind of mechanism can underlie such stable changes in neural plasticity? One prime candidate mechanism is epigenetic mechanisms of chromatin regulation. Chromatin regulation has been shown to generate short-term and long-term molecular memory within an individual cell. They have also been shown to underlie cell fate decisions (or cellular memory). Now, there is accumulating evidence that in the CNS, these same mechanisms may be pivotal for drug-induced changes in gene expression and ultimately long-term behavioral changes. As these mechanisms are also being found to be fundamental for learning and memory, an exciting new possibility is the extinction of drug-seeking behavior by manipulation of epigenetic mechanisms. In this review, we critically discuss the evidence demonstrating a key role for chromatin regulation via histone acetylation in cocaine action.

  10. Motivation and cognitive control: from behavior to neural mechanism.

    Science.gov (United States)

    Botvinick, Matthew; Braver, Todd

    2015-01-03

    Research on cognitive control and executive function has long recognized the relevance of motivational factors. Recently, however, the topic has come increasingly to center stage, with a surge of new studies examining the interface of motivation and cognitive control. In the present article we survey research situated at this interface, considering work from cognitive and social psychology and behavioral economics, but with a particular focus on neuroscience research. We organize existing findings into three core areas, considering them in the light of currently vying theoretical perspectives. Based on the accumulated evidence, we advocate for a view of control function that treats it as a domain of reward-based decision making. More broadly, we argue that neuroscientific evidence plays a critical role in understanding the mechanisms by which motivation and cognitive control interact. Opportunities for further cross-fertilization between behavioral and neuroscientific research are highlighted.

  11. Neural and Behavioral Correlates of PTSD and Alcohol Use

    Science.gov (United States)

    2014-12-01

    and Ventrolateral Prefrontal Cortex Activation to Masked Angry Faces in Children and Adolescents with Generalized Anxiety Disorder. Arch Gen...Modulation by Early Maternal Separation. Stress. 12, 362-369. 906308344 [pii] 10.1080/10253890802506391. [93] Vinkers CH, Bijlsma EY, Houtepen LC...Summavielle T (2006) MDMA in Adolescent Male Rats: Decreased Serotonin in the Amygdala and Behavioral Effects in the Elevated Plus-Maze Test. Ann N Y

  12. 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.

  13. 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

  14. γ-Secretase modulators reduce endogenous amyloid β42 levels in human neural progenitor cells without altering neuronal differentiation

    OpenAIRE

    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 cultu...

  15. TRF2-mediated stabilization of hREST4 is critical for the differentiation and maintenance of neural progenitors.

    Science.gov (United States)

    Ovando-Roche, Patrick; Yu, Jason S L; Testori, Sarah; Ho, Chloe; Cui, Wei

    2014-08-01

    Telomere repeat binding factor 2 (TRF2) is a component of the shelterin complex that is known to bind and protect telomeric DNA, yet the detection of TRF2 in extra-telomeric regions of chromosomes suggests other roles for TRF2 besides telomere protection. Here, we demonstrate that TRF2 plays a critical role in antagonizing the repressive function of neuron-restrictive silencer factor, also known as repressor element-1 silencing transcription factor (REST), during the neural differentiation of human embryonic stem cells (hESCs) by enhancing the expression of a truncated REST splice isoform we term human REST4 (hREST4) due to its similarity to rodent REST4. We show that TRF2 is specifically upregulated during hESC neural differentiation concordantly with an increase in the expression of hREST4 and that both proteins are highly expressed in NPCs. Overexpression of TRF2 in hESCs increases hREST4 levels and induces their neural differentiation, whereas TRF2 knockdown in hESCs and NPCs reduces hREST4 expression, hindering their ability to differentiate to the neural lineage. Concurrently, we show that TRF2 directly interacts with the C-terminal of hREST4 through its TRF2 core binding motif [F/Y]xL, protecting hREST4 from ubiquitin-mediated proteasomal degradation and consequently furthering neural induction. Thus, the TRF2-mediated counterbalance between hREST4 and REST is vital for both the generation and maintenance of NPCs, suggesting an important role for TRF2 in both neurogenesis and function of the central nervous system. © 2014 AlphaMed Press.

  16. In vitro induction and differentiation of newborn guinea pig hippocampus neural stem cells into cells resembling inner hair cells, using artificial perilymph.

    Science.gov (United States)

    Wang, Y; Dong, M-M

    2011-08-01

    To investigate whether artificial perilymph can induce neural stem cells, derived from the hippocampus of newborn guinea pigs, to differentiate into inner ear hair cells, in vitro. Primary neural stem cells derived from the hippocampus of newborn guinea pigs were incubated in medium containing either 10 per cent fetal bovine serum or 5, 10 or 15 per cent artificial perilymph, for three weeks. Differentiated cells were identified using immunofluorescence, Western blot and scanning electron microscopy. Both fetal bovine serum and artificial perilymph induced the neural stem cells to differentiate into cells with hair-cell-specific antibodies. Neural stem cells can survive in both fetal bovine serum and artificial perilymph, and within these media can differentiate into cells with hair-cell-specific antibodies. This provides an experimental basis for transplantation of neural stem cells into the inner ear.

  17. The Differential Role of Smell and Taste For Eating Behavior.

    Science.gov (United States)

    Boesveldt, Sanne; de Graaf, Kees

    2017-01-01

    Food choice and food intake are guided by both sensory and metabolic processes. The senses of taste and smell play a key role in the sensory effects on choice and intake. This article provides a comprehensive overview of, and will argue for, the differential role of smell and taste for eating behavior by focusing on appetite, choice, intake, and satiation. The sense of smell mainly plays a priming role in eating behavior. It has been demonstrated that (orthonasal) odor exposure induces appetite specifically for the cued food. However, the influence of odors on food choice and intake is less clear, and may also depend on awareness or intensity of the odors, or personality traits of the participants. Taste on the other hand, has a clear role as a (macro)nutrient sensing system, during consumption. Together with texture, taste is responsible for eating rate, and thus in determining the oral exposure duration of food in the mouth, thereby contributing to satiation. Results from these experimental studies should be taken to real-life situations, to assess longer-term effects on energy intake. With this knowledge, it will be possible to steer people's eating behavior, as well as food product development, toward a less obesogenic society.

  18. Antagonistic Serotonergic and Octopaminergic Neural Circuits Mediate Food-Dependent Locomotory Behavior in Caenorhabditis elegans.

    Science.gov (United States)

    Churgin, Matthew A; McCloskey, Richard J; Peters, Emily; Fang-Yen, Christopher

    2017-08-16

    Biogenic amines are conserved signaling molecules that link food cues to behavior and metabolism in a wide variety of organisms. In the nematode Caenorhabditis elegans, the biogenic amines serotonin (5-HT) and octopamine regulate a number of food-related behaviors. Using a novel method for long-term quantitative behavioral imaging, we show that 5-HT and octopamine jointly influence locomotor activity and quiescence in feeding and fasting hermaphrodites, and we define the neural circuits through which this modulation occurs. We show that 5-HT produced by the ADF neurons acts via the SER-5 receptor in muscles and neurons to suppress quiescent behavior and promote roaming in fasting worms, whereas 5-HT produced by the NSM neurons acts on the MOD-1 receptor in AIY neurons to promote low-amplitude locomotor behavior characteristic of well fed animals. Octopamine, produced by the RIC neurons, acts via SER-3 and SER-6 receptors in SIA neurons to promote roaming behaviors characteristic of fasting animals. We find that 5-HT signaling is required for animals to assume food-appropriate behavior, whereas octopamine signaling is required for animals to assume fasting-appropriate behavior. The requirement for both neurotransmitters in both the feeding and fasting states enables increased behavioral adaptability. Our results define the molecular and neural pathways through which parallel biogenic amine signaling tunes behavior appropriately to nutrient conditions.SIGNIFICANCE STATEMENT Animals adjust behavior in response to environmental changes, such as fluctuations in food abundance, to maximize survival and reproduction. Biogenic amines, such as like serotonin, are conserved neurotransmitters that regulate behavior and metabolism in relation to energy status. Disruptions of biogenic amine signaling contribute to human neurological diseases of mood, appetite, and movement. In this study, we investigated the roles of the biogenic amines serotonin and octopamine in regulating

  19. Antipsychotic dose modulates behavioral and neural responses to feedback during reinforcement learning in schizophrenia.

    Science.gov (United States)

    Insel, Catherine; Reinen, Jenna; Weber, Jochen; Wager, Tor D; Jarskog, L Fredrik; Shohamy, Daphna; Smith, Edward E

    2014-03-01

    Schizophrenia is characterized by an abnormal dopamine system, and dopamine blockade is the primary mechanism of antipsychotic treatment. Consistent with the known role of dopamine in reward processing, prior research has demonstrated that patients with schizophrenia exhibit impairments in reward-based learning. However, it remains unknown how treatment with antipsychotic medication impacts the behavioral and neural signatures of reinforcement learning in schizophrenia. The goal of this study was to examine whether antipsychotic medication modulates behavioral and neural responses to prediction error coding during reinforcement learning. Patients with schizophrenia completed a reinforcement learning task while undergoing functional magnetic resonance imaging. The task consisted of two separate conditions in which participants accumulated monetary gain or avoided monetary loss. Behavioral results indicated that antipsychotic medication dose was associated with altered behavioral approaches to learning, such that patients taking higher doses of medication showed increased sensitivity to negative reinforcement. Higher doses of antipsychotic medication were also associated with higher learning rates (LRs), suggesting that medication enhanced sensitivity to trial-by-trial feedback. Neuroimaging data demonstrated that antipsychotic dose was related to differences in neural signatures of feedback prediction error during the loss condition. Specifically, patients taking higher doses of medication showed attenuated prediction error responses in the striatum and the medial prefrontal cortex. These findings indicate that antipsychotic medication treatment may influence motivational processes in patients with schizophrenia.

  20. Asymmetries in behavioral and neural responses to spectral cues demonstrate the generality of auditory looming bias

    Science.gov (United States)

    Reed, Darrin K.; Tóth, Brigitta; Best, Virginia; Majdak, Piotr; Colburn, H. Steven; Shinn-Cunningham, Barbara

    2017-01-01

    Studies of auditory looming bias have shown that sources increasing in intensity are more salient than sources decreasing in intensity. Researchers have argued that listeners are more sensitive to approaching sounds compared with receding sounds, reflecting an evolutionary pressure. However, these studies only manipulated overall sound intensity; therefore, it is unclear whether looming bias is truly a perceptual bias for changes in source distance, or only in sound intensity. Here we demonstrate both behavioral and neural correlates of looming bias without manipulating overall sound intensity. In natural environments, the pinnae induce spectral cues that give rise to a sense of externalization; when spectral cues are unnatural, sounds are perceived as closer to the listener. We manipulated the contrast of individually tailored spectral cues to create sounds of similar intensity but different naturalness. We confirmed that sounds were perceived as approaching when spectral contrast decreased, and perceived as receding when spectral contrast increased. We measured behavior and electroencephalography while listeners judged motion direction. Behavioral responses showed a looming bias in that responses were more consistent for sounds perceived as approaching than for sounds perceived as receding. In a control experiment, looming bias disappeared when spectral contrast changes were discontinuous, suggesting that perceived motion in distance and not distance itself was driving the bias. Neurally, looming bias was reflected in an asymmetry of late event-related potentials associated with motion evaluation. Hence, both our behavioral and neural findings support a generalization of the auditory looming bias, representing a perceptual preference for approaching auditory objects. PMID:28827336

  1. Asymmetries in behavioral and neural responses to spectral cues demonstrate the generality of auditory looming bias.

    Science.gov (United States)

    Baumgartner, Robert; Reed, Darrin K; Tóth, Brigitta; Best, Virginia; Majdak, Piotr; Colburn, H Steven; Shinn-Cunningham, Barbara

    2017-09-05

    Studies of auditory looming bias have shown that sources increasing in intensity are more salient than sources decreasing in intensity. Researchers have argued that listeners are more sensitive to approaching sounds compared with receding sounds, reflecting an evolutionary pressure. However, these studies only manipulated overall sound intensity; therefore, it is unclear whether looming bias is truly a perceptual bias for changes in source distance, or only in sound intensity. Here we demonstrate both behavioral and neural correlates of looming bias without manipulating overall sound intensity. In natural environments, the pinnae induce spectral cues that give rise to a sense of externalization; when spectral cues are unnatural, sounds are perceived as closer to the listener. We manipulated the contrast of individually tailored spectral cues to create sounds of similar intensity but different naturalness. We confirmed that sounds were perceived as approaching when spectral contrast decreased, and perceived as receding when spectral contrast increased. We measured behavior and electroencephalography while listeners judged motion direction. Behavioral responses showed a looming bias in that responses were more consistent for sounds perceived as approaching than for sounds perceived as receding. In a control experiment, looming bias disappeared when spectral contrast changes were discontinuous, suggesting that perceived motion in distance and not distance itself was driving the bias. Neurally, looming bias was reflected in an asymmetry of late event-related potentials associated with motion evaluation. Hence, both our behavioral and neural findings support a generalization of the auditory looming bias, representing a perceptual preference for approaching auditory objects.

  2. Interrelationships between Hormones, Behavior, and Affect during Adolescence: Complex Relationships Exist between Reproductive Hormones, Stress‐Related Hormones, and the Activity of Neural Systems That Regulate Behavioral Affect. Comments on Part III

    National Research Council Canada - National Science Library

    CAMERON, JUDY L

    2004-01-01

    ..., and changes in behavioral affect regulation. The interactions between activity in the reproductive axis, the neural systems that regulate stress, hormones produced in response to stress, and neural systems governing behavioral affect regulation...

  3. An "as soon as possible" effect in human intertemporal decision making: behavioral evidence and neural mechanisms.

    Science.gov (United States)

    Kable, Joseph W; Glimcher, Paul W

    2010-05-01

    Many decisions involve a trade-off between the quality of an outcome and the time at which that outcome is received. In psychology and behavioral economics, the most widely studied models hypothesize that the values of future gains decline as a roughly hyperbolic function of delay from the present. Recently, it has been proposed that this hyperbolic-like decline in value arises from the interaction of two separate neural systems: one specialized to value immediate rewards and the other specialized to value delayed rewards. Here we report behavioral and functional magnetic resonance imaging results that are inconsistent with both the standard behavioral models of discounting and the hypothesis that separate neural systems value immediate and delayed rewards. Behaviorally, we find that human subjects do not necessarily make the impulsive preference reversals predicted by hyperbolic-like discounting. We also find that blood oxygenation level dependent activity in ventral striatum, medial prefrontal, and posterior cingulate cortex does not track whether an immediate reward was present, as proposed by the separate neural systems hypothesis. Activity in these regions was correlated with the subjective value of both immediate and delayed rewards. Rather than encoding only the relative value of one reward compared with another, these values are represented on a more absolute scale. These data support an alternative behavioral-neural model (which we call "ASAP"), in which subjective value declines hyperbolically relative to the soonest currently available reward and a small number of valuation areas serve as a final common pathway through which these subjective values guide choice.

  4. 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.

  5. β1-Integrin and integrin linked kinase regulate astrocytic differentiation of neural stem cells.

    Directory of Open Access Journals (Sweden)

    Liuliu Pan

    Full Text Available Astrogliosis with glial scar formation after damage to the nervous system is a major impediment to axonal regeneration and functional recovery. The present study examined the role of β1-integrin signaling in regulating astrocytic differentiation of neural stem cells. In the adult spinal cord β1-integrin is expressed predominantly in the ependymal region where ependymal stem cells (ESCs reside. β1-integrin signaling suppressed astrocytic differentiation of both cultured ESCs and subventricular zone (SVZ progenitor cells. Conditional knockout of β1-integrin enhanced astrogliogenesis both by cultured ESCs and by SVZ progenitor cells. Previous studies have shown that injection into the injured spinal cord of a self-assembling peptide amphiphile that displays an IKVAV epitope (IKVAV-PA limits glial scar formation and enhances functional recovery. Here we find that injection of IKVAV-PA induced high levels of β1-integrin in ESCs in vivo, and that conditional knockout of β1-integrin abolished the astroglial suppressive effects of IKVAV-PA in vitro. Injection into an injured spinal cord of PAs expressing two other epitopes known to interact with β1-integrin, a Tenascin C epitope and the fibronectin epitope RGD, improved functional recovery comparable to the effects of IKVAV-PA. Finally we found that the effects of β1-integrin signaling on astrogliosis are mediated by integrin linked kinase (ILK. These observations demonstrate an important role for β1-integrin/ILK signaling in regulating astrogliosis from ESCs and suggest ILK as a potential target for limiting glial scar formation after nervous system injury.

  6. Comprehensive Behavioral Analysis of Cluster of Differentiation 47 Knockout Mice

    Science.gov (United States)

    Koshimizu, Hisatsugu; Takao, Keizo; Matozaki, Takashi; Ohnishi, Hiroshi; Miyakawa, Tsuyoshi

    2014-01-01

    Cluster of differentiation 47 (CD47) is a member of the immunoglobulin superfamily which functions as a ligand for the extracellular region of signal regulatory protein α (SIRPα), a protein which is abundantly expressed in the brain. Previous studies, including ours, have demonstrated that both CD47 and SIRPα fulfill various functions in the central nervous system (CNS), such as the modulation of synaptic transmission and neuronal cell survival. We previously reported that CD47 is involved in the regulation of depression-like behavior of mice in the forced swim test through its modulation of tyrosine phosphorylation of SIRPα. However, other potential behavioral functions of CD47 remain largely unknown. In this study, in an effort to further investigate functional roles of CD47 in the CNS, CD47 knockout (KO) mice and their wild-type littermates were subjected to a battery of behavioral tests. CD47 KO mice displayed decreased prepulse inhibition, while the startle response did not differ between genotypes. The mutants exhibited slightly but significantly decreased sociability and social novelty preference in Crawley’s three-chamber social approach test, whereas in social interaction tests in which experimental and stimulus mice have direct contact with each other in a freely moving setting in a novel environment or home cage, there were no significant differences between the genotypes. While previous studies suggested that CD47 regulates fear memory in the inhibitory avoidance test in rodents, our CD47 KO mice exhibited normal fear and spatial memory in the fear conditioning and the Barnes maze tests, respectively. These findings suggest that CD47 is potentially involved in the regulation of sensorimotor gating and social behavior in mice. PMID:24586890

  7. Comprehensive behavioral analysis of cluster of differentiation 47 knockout mice.

    Directory of Open Access Journals (Sweden)

    Hisatsugu Koshimizu

    Full Text Available Cluster of differentiation 47 (CD47 is a member of the immunoglobulin superfamily which functions as a ligand for the extracellular region of signal regulatory protein α (SIRPα, a protein which is abundantly expressed in the brain. Previous studies, including ours, have demonstrated that both CD47 and SIRPα fulfill various functions in the central nervous system (CNS, such as the modulation of synaptic transmission and neuronal cell survival. We previously reported that CD47 is involved in the regulation of depression-like behavior of mice in the forced swim test through its modulation of tyrosine phosphorylation of SIRPα. However, other potential behavioral functions of CD47 remain largely unknown. In this study, in an effort to further investigate functional roles of CD47 in the CNS, CD47 knockout (KO mice and their wild-type littermates were subjected to a battery of behavioral tests. CD47 KO mice displayed decreased prepulse inhibition, while the startle response did not differ between genotypes. The mutants exhibited slightly but significantly decreased sociability and social novelty preference in Crawley's three-chamber social approach test, whereas in social interaction tests in which experimental and stimulus mice have direct contact with each other in a freely moving setting in a novel environment or home cage, there were no significant differences between the genotypes. While previous studies suggested that CD47 regulates fear memory in the inhibitory avoidance test in rodents, our CD47 KO mice exhibited normal fear and spatial memory in the fear conditioning and the Barnes maze tests, respectively. These findings suggest that CD47 is potentially involved in the regulation of sensorimotor gating and social behavior in mice.

  8. Prediction of Phase Behavior in Microemulsion Systems Using Artificial Neural Networks

    Science.gov (United States)

    Richardson; Mbanefo; Aboofazeli; Lawrence; Barlow

    1997-03-15

    Preliminary investigations have been conducted to assess the potential for using (back-propagation, feed-forward) artificial neural networks to predict the phase behavior of quaternary microemulsion-forming systems, with a view to employing this type of methodology in the evaluation of novel cosurfactants for the formulation of pharmaceutically acceptable drug-delivery systems. The data employed in training the neural networks related to microemulsion systems containing lecithin, isopropyl myristate, and water, together with different types of cosurfactants, including short- and medium-chain alcohols, amines, acids, and ethylene glycol monoalkyl ethers. Previously unpublished phase diagrams are presented for four systems involving the cosurfactants 2-methyl-2-butanol, 2-methyl-1-propanol, 2-methyl-1-butanol, and isopropanol, which, along with eight other published sets of data, are used to test the predictive ability of the trained networks. The pseudo-ternary phase diagrams for these systems are predicted using only four computed physicochemical properties for the cosurfactants involved. The artificial neural networks are shown to be highly successful in predicting phase behavior for these systems, achieving mean success rates of 96.7 and 91.6% for training and test data, respectively. The conclusion is reached that artificial neural networks can provide useful tools for the development of microemulsion-based drug-delivery systems.

  9. A Comparison of Response Cost and Differential Reinforcement of Other Behavior to Reduce Disruptive Behavior in a Preschool Classroom

    Science.gov (United States)

    Conyers, Carole; Miltenberger, Raymond; Maki, Amber; Barenz, Rebecca; Jurgens, Mandy; Sailer, Angela; Haugen, Meredith; Kopp, Brandon

    2004-01-01

    This study investigated the effectiveness of response cost and differential reinforcement of other behavior (DRO) in reducing the disruptive behaviors of 25 children in a preschool classroom. Using an alternating treatments design, disruptive behavior was reduced when the participants earned tokens for the absence of disruptive behavior (DRO) or…

  10. Learning about stress: neural, endocrine and behavioral adaptations.

    Science.gov (United States)

    McCarty, Richard

    2016-09-01

    In this review, nonassociative learning is advanced as an organizing principle to draw together findings from both sympathetic-adrenal medullary and hypothalamic-pituitary-adrenocortical (HPA) axis responses to chronic intermittent exposure to a variety of stressors. Studies of habituation, facilitation and sensitization of stress effector systems are reviewed and linked to an animal's prior experience with a given stressor, the intensity of the stressor and the appraisal by the animal of its ability to mobilize physiological systems to adapt to the stressor. Brain pathways that regulate physiological and behavioral responses to stress are discussed, especially in light of their regulation of nonassociative processes in chronic intermittent stress. These findings may have special relevance to various psychiatric diseases, including depression and post-traumatic stress disorder (PTSD).

  11. Behavioral, Neural, and Computational Principles of Bodily Self-Consciousness.

    Science.gov (United States)

    Blanke, Olaf; Slater, Mel; Serino, Andrea

    2015-10-07

    Recent work in human cognitive neuroscience has linked self-consciousness to the processing of multisensory bodily signals (bodily self-consciousness [BSC]) in fronto-parietal cortex and more posterior temporo-parietal regions. We highlight the behavioral, neurophysiological, neuroimaging, and computational laws that subtend BSC in humans and non-human primates. We propose that BSC includes body-centered perception (hand, face, and trunk), based on the integration of proprioceptive, vestibular, and visual bodily inputs, and involves spatio-temporal mechanisms integrating multisensory bodily stimuli within peripersonal space (PPS). We develop four major constraints of BSC (proprioception, body-related visual information, PPS, and embodiment) and argue that the fronto-parietal and temporo-parietal processing of trunk-centered multisensory signals in PPS is of particular relevance for theoretical models and simulations of BSC and eventually of self-consciousness. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Artificial neural network to aid differentiation of malignant and benign breast masses by ultrasound imaging

    Science.gov (United States)

    Song, Jae H.; Venkatesh, Santosh S.; Conant, Emily F.; Cary, Ted W.; Arger, Peter H.; Sehgal, Chandra M.

    2005-04-01

    The goal of this study is to evaluate an Artificial Neural Network (ANN) for differentiating benign and malignant breast masses on ultrasound scans. The ANN was designed with three layers (input, hidden and output layer), where a sigmoidal (hyperbolic tangent) response function is used as an activation function at each unit. Data from 54 patients with biopsy-proven malignant (N=20) and benign (N=34) masses were used to evaluate the diagnostic performance of the ANN. Of the seven quantitative features extracted from ultrasound images, only four showed statistically significant difference between the two categories. These features were margin sharpness, margin echogenicity, angular continuity, and age of patients. The diagnostic performance was evaluated by round-robin substitution to negate bias due to small sample size. All the input features were standardized to zero-mean and unit-variance to prevent non-uniform learning, which can generate unwanted error. The outputs of the network were analyzed by Receiver Operating Characteristics (ROC). The resulting area under the ROC curve Az was 0.856 +/- 0.058 with 95% confidence limit from 0.734 to 0.936, providing 76.5% specificity at 95% sensitivity. The performance of the ANN was comparable to the performance by logistic regression analysis reported by our group earlier. These results suggest that an ANN when combined with sonography can effectively classify malignant and benign breast lesions.

  13. 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.

  14. 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 (fp) from the steady state sensitivity characteristics and the first cut off frequency (fc) 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.

  15. 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.

  16. 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.

  17. Differential neural network of checking versus washing symptoms in obsessive-compulsive disorder.

    Science.gov (United States)

    Murayama, Keitaro; Nakao, Tomohiro; Sanematsu, Hirokuni; Okada, Kayo; Yoshiura, Takashi; Tomita, Mayumi; Masuda, Yusuke; Isomura, Kayoko; Nakagawa, Akiko; Kanba, Shigenobu

    2013-01-10

    Obsessive-compulsive disorder (OCD) is clinically heterogeneous. The aim of this study was to investigate differential neural responses to a symptom provocation task in drug-free patients who have predominantly aggression/checking symptoms (Checkers) and patients with contamination/washing symptoms (Washers). We compared the Checkers (n=10) and the Washers (n=12) separately to normal controls during the symptom provocation tasks using fMRI (functional magnetic resonance imaging). Moreover, we performed correlative analysis in each OCD group between brain activation and symptom severity. The Checkers showed hypoactivation in the left caudate and left anterior cingulate cortex (ACC) compared to the normal controls and a positive correlation between activated brain areas and symptom severity in the left ACC. The Washers showed hyperactivation in several bilateral cortico-cerebellar regions and a positive correlation between symptom severity and the bilateral fronto-temporal gyrus. We suggest that the caudate and ACC are associated with checking rituals and that large cortical brain regions are related to washing rituals. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Behavioral activation can normalize neural hypoactivation in subthreshold depression during a monetary incentive delay task.

    Science.gov (United States)

    Mori, Asako; Okamoto, Yasumasa; Okada, Go; Takagaki, Koki; Jinnin, Ran; Takamura, Masahiro; Kobayakawa, Makoto; Yamawaki, Shigeto

    2016-01-01

    Late adolescents are under increased risk of developing depressive symptoms. Behavioral activation is an effective treatment for subthreshold depression, which can prevent the development of subthreshold depression into a major depressive disorder. However, the neural mechanisms underlying the efficacy of behavioral activation have not been clearly understood. We investigated neural responses during reward processing by individuals with subthreshold depression to clarify the neural mechanisms of behavioral activation. Late adolescent university students with subthreshold depression (n=15, age 18-19 years) as indicated by a high score on the Beck's Depression Inventory-ll (BDI-ll) and 15 age-matched controls with a low BDI-ll score participated in functional magnetic resonance imaging scanning conducted during a monetary incentive delay task on two occasions. The Individuals in the subthreshold depression group received five, weekly behavioral activation sessions between the two scanning sessions. Moreover, they did not receive any medication until the study was completed. Behavioral activation significantly reduced depressive symptoms. Moreover, compared to the changes in brain functions in the control group, the behavioral activation group showed functional changes during loss anticipation in brain structures that mediates cognitive and emotional regulation, including the left ventrolateral prefrontal cortex and angular gyrus. Replication of the study with a larger sample size is required to increase the generalizability of these results. Behavioral activation results in improved functioning of the fronto-parietal region during loss anticipation. These results increase our understanding of the mechanisms underlying specific psychotherapies. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. A Comparison of Function-Based Differential Reinforcement Interventions for Children Engaging in Disruptive Classroom Behavior

    Science.gov (United States)

    LeGray, Matthew W.; Dufrene, Brad A.; Sterling-Turner, Heather; Olmi, D. Joe; Bellone, Katherine

    2010-01-01

    This study provides a direct comparison of differential reinforcement of other behavior (DRO) and differential reinforcement of alternative behavior (DRA). Participants included three children in center-based classrooms referred for functional assessments due to disruptive classroom behavior. Functional assessments included interviews and brief…

  20. 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.

  1. 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.

  2. 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

    Magneto-rheological (MR) dampers have received considerable attention within the last decades, mainly because of their design simplicity, low power requirements, large force range and robustness. The most common models to describe the dynamic MR damper behavior are the Bouc-Wen model, the Lu...... 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...... produced is transformed into a translational force through the crank shaft mechanism. A feed-forward back propagation neural network is used to model both the forward and the inverse dynamics of the MR damper. The forward model output is the estimated force and therefore can be used later as observer...

  3. Task-dependent neural and behavioral effects of verb argument structure features.

    Science.gov (United States)

    Malyutina, Svetlana; den Ouden, Dirk-Bart

    2017-05-01

    Understanding which verb argument structure (VAS) features (if any) are part of verbs' lexical entries and under which conditions they are accessed provides information on the nature of lexical representations and sentence construction. We investigated neural and behavioral effects of three understudied VAS characteristics (number of subcategorization options, number of thematic options and overall number of valency frames) in lexical decision and sentence well-formedness judgment in healthy adults. VAS effects showed strong dependency on processing conditions. As reflected by behavioral performance and neural recruitment patterns, increased VAS complexity in terms of subcategorization options and thematic options had a detrimental effect on sentence processing, but facilitated lexical access to single words, possibly by providing more lexico-semantic associations and access routes (facilitation through complexity). Effects of the number of valency frames are equivocal. We suggest that VAS effects may be mediated semantically rather than by a dedicated VAS module in verbs' representations. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. 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.

  5. 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.

  6. 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.

  7. 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

    2014-09-01

    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. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Resonant Dynamics of Grounded Cognition: Explanation of Behavioral and Neuroimaging Data Using the ART Neural Network

    OpenAIRE

    Domijan, Dražen; Šetić, Mia

    2016-01-01

    Research on grounded cognition suggests that the processing of a word or concept reactivates the perceptual representations that are associated with the referent object. The objective of this work is to demonstrate how behavioral and functional neuroimaging data on grounded cognition can be understood as different manifestations of the same cortical circuit designed to achieve stable category learning, as proposed by the adaptive resonance theory (ART). We showed that the ART neural network p...

  9. 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

  10. The matrix metalloproteinase inhibitor marimastat promotes neural progenitor cell differentiation into neurons by gelatinase-independent TIMP-2-dependent mechanisms.

    Science.gov (United States)

    Sinno, Maddalena; Biagioni, Stefano; Ajmone-Cat, Maria Antonietta; Pafumi, Irene; Caramanica, Pasquale; Medda, Virginia; Tonti, Gaetana; Minghetti, Luisa; Mannello, Ferdinando; Cacci, Emanuele

    2013-02-01

    Metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs), produced in the brain by cells of non-neural and neural origin, including neural progenitors (NPs), are emerging as regulators of nervous system development and adult brain functions. In the present study, we explored whether MMP-2, MMP-9, and TIMP-2, abundantly produced in the brain, modulate NP developmental properties. We found that treatment of NPs, isolated from the murine fetal cerebral cortex or adult subventricular zone, with the clinically tested broad-spectrum MMP inhibitor Marimastat profoundly affected the NP differentiation fate. Marimastat treatment allowed for an enrichment of our cultures in neuronal cells, inducing NPs to generate higher percentage of neurons and a lower percentage of astrocytes, possibly affecting NP commitment. Consistently with its proneurogenic effect, Marimastat early downregulated the expression of Notch target genes, such as Hes1 and Hes5. MMP-2 and MMP-9 profiling on proliferating and differentiating NPs revealed that MMP-9 was not expressed under these conditions, whereas MMP-2 increased in the medium as pro-MMP-2 (72 kDa) during differentiation; its active form (62 kDa) was not detectable by gel zymography. MMP-2 silencing or administration of recombinant active MMP-2 demonstrated that MMP-2 does not affect NP neuronal differentiation, nor it is involved in the Marimastat proneurogenic effect. We also found that TIMP-2 is expressed in NPs and increases during late differentiation, mainly as a consequence of astrocyte generation. Endogenous TIMP-2 did not modulate NP neurogenic potential; however, the proneurogenic action of Marimastat was mediated by TIMP-2, as demonstrated by silencing experiments. In conclusion, our data exclude a major involvement of MMP-2 and MMP-9 in the regulation of basal NP differentiation, but highlight the ability of TIMP-2 to act as key effector of the proneurogenic response to an inducing stimulus such as Marimastat.

  11. 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.

  12. 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.

  13. 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

  14. Learning by experience? Visceral pain-related neural and behavioral responses in a classical conditioning paradigm.

    Science.gov (United States)

    Icenhour, A; Labrenz, F; Ritter, C; Theysohn, N; Forsting, M; Bingel, U; Elsenbruch, S

    2017-06-01

    Studies investigating mechanisms underlying nocebo responses in pain have mainly focused on negative expectations induced by verbal suggestions. Herein, we addressed neural and behavioral correlates of nocebo responses induced by classical conditioning in a visceral pain model. In two independent studies, a total of 40 healthy volunteers underwent classical conditioning, consisting of repeated pairings of one visual cue (CS High ) with rectal distensions of high intensity, while a second cue (CS Low ) was always followed by low-intensity distensions. During subsequent test, only low-intensity distensions were delivered, preceded by either CS High or CS Low . Distension intensity ratings were assessed in both samples and functional magnetic resonance imaging data were available from one study (N=16). As a consequence of conditioning, we hypothesized CS High -cued distensions to be perceived as more intense and expected enhanced cue- and distension-related neural responses in regions encoding sensory and affective dimensions of pain and in structures associated with pain-related fear memory. During test, distension intensity ratings did not differ depending on preceding cue. Greater distension-induced neural activation was observed in somatosensory, prefrontal, and cingulate cortices and caudate when preceded by CS High . Analysis of cue-related responses revealed strikingly similar activation patterns. We report changes in neural activation patterns during anticipation and visceral stimulation induced by prior conditioning. In the absence of behavioral effects, markedly altered neural responses may indicate conditioning with visceral signals to induce hypervigilance rather than hyperalgesia, involving altered attention, reappraisal, and perceptual acuity as processes contributing to the pathophysiology of visceral pain. © 2017 John Wiley & Sons Ltd.

  15. 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

  16. 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.

  17. 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.

  18. Differential effects of neural inactivation of the dorsolateral striatum on response and latent extinction.

    Science.gov (United States)

    Goodman, Jarid; Gabriele, Amanda; Packard, Mark G

    2017-04-01

    The present study examined the role of the dorsolateral striatum (DLS) in extinction behavior. Male Long-Evans rats were initially trained on the straight alley maze, in which they were reinforced to traverse a straight runway and retrieve food reward at the opposite end of the maze. After initial acquisition, animals were given extinction training using 1 of 2 distinct protocols: response extinction or latent extinction. For response extinction, the animal was released from the same starting position and had the opportunity to perform the originally reinforced approach response to the goal end of the maze, which no longer contained food. For latent extinction, the animal was confined to the original goal location without food, allowing the animal to form a new cognitive expectation (i.e., that the goal location is no longer reinforced). Immediately before response or latent extinction training, animals received bilateral intra-DLS administration of the sodium channel blocker bupivacaine or control injections of physiological saline. Results indicated that neural inactivation of the DLS with bupivacaine impaired response extinction, but did not influence latent extinction. The dissociation observed indicates that the DLS selectively mediates extinction mechanisms involving suppression of the original response, as opposed to cognitive mechanisms involving a change in expectation. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  19. 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.

  20. 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...

  1. 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.

  2. Neural differentiation of human embryonic stem cells induced by the transgene-mediated overexpression of single transcription factors.

    Science.gov (United States)

    Matsushita, Misako; Nakatake, Yuhki; Arai, Itaru; Ibata, Keiji; Kohda, Kazuhisa; Goparaju, Sravan K; Murakami, Miyako; Sakota, Miki; Chikazawa-Nohtomi, Nana; Ko, Shigeru B H; Kanai, Takanori; Yuzaki, Michisuke; Ko, Minoru S H

    2017-08-19

    Pluripotent human embryonic stem cells (hESCs) can differentiate into multiple cell lineages, thus, providing one of the best platforms to study molecular mechanisms during cell differentiation. Recently, we have reported rapid and efficient differentiation of hESCs into functional neurons by introducing a cocktail of synthetic mRNAs encoding five transcription factors (TFs): NEUROG1, NEUROG2, NEUROG3, NEUROD1, and NEUROD2. Here we further tested a possibility that even single transcription factors, when expressed ectopically, can differentiate hESCs into neurons. To this end, we established hESC lines in which each of these TFs can be overexpressed by the doxycycline-inducible piggyBac vector. The overexpression of any of these five TFs indeed caused a rapid and rather uniform differentiation of hESCs, which were identified as neurons based on their morphologies, qRT-PCR, and immunohistochemistry. Furthermore, calcium-imaging analyses and patch clamp recordings demonstrated that these differentiated cells are electrophysiologically functional. Interestingly, neural differentiations occurred despite the cell culture conditions that rather promote the maintenance of the undifferentiated state. These results indicate that over-expression of each of these five TFs can override the pluripotency-specific gene network and force hESCs to differentiate into neurons. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. 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.

  4. 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.

  5. 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.

  6. A comparison of response cost and differential reinforcement of other behavior to reduce disruptive behavior in a preschool classroom.

    OpenAIRE

    Conyers, Carole; Miltenberger, Raymond; Maki, Amber; Barenz, Rebecca; Jurgens, Mandy; Sailer, Angela; Haugen, Meredith; Kopp, Brandon

    2004-01-01

    This study investigated the effectiveness of response cost and differential reinforcement of other behavior (DRO) in reducing the disruptive behaviors of 25 children in a preschool classroom. Using an alternating treatments design, disruptive behavior was reduced when the participants earned tokens for the absence of disruptive behavior (DRO) or lost tokens for the occurrence of disruptive behavior (response cost). Initially, DRO was more successful in reducing the number of disruptive behavi...

  7. Genetic and neural predictors of behavioral weight loss treatment: A preliminary study.

    Science.gov (United States)

    Chen, Eunice Y; Olino, Thomas M; Conklin, Chris J; Mohamed, Feroze B; Hoge, W Scott; Foster, Gary D; Arlt, Jean M; Eneva, Kalina; Kidd, Judy R; Kidd, Kenneth R; Lent, Michelle R; Murray, Susan; Newberg, Andrew; Tewksbury, Colleen; VanderVeur, Stephanie S; Yiu, Angelina

    2017-01-01

    To examine neural mechanisms of action in behavioral weight loss treatment (BWL) and explore neural and genetic predictors of BWL. Neural activation to milkshake receipt and genetics were compared in 17 women with obesity who received 12 weeks of BWL and 17 women who received no intervention. Participants were scanned twice using functional magnetic resonance imaging at baseline and 12 weeks. Weight was assessed at baseline, 12, 36, and 60 weeks. BWL participants lost more weight than controls at 12 weeks (-4.82% versus -0.70%). After 12 weeks, BWL had greater reduction in right caudate activation response to milk shake receipt than did controls. Among BWL participants, baseline to 12-week reduction in frontostriatal activation to milk shake predicted greater weight loss at 12, 36, and 60 weeks. Possessing the A/A or T/A genotype of the fat mass and obesity-associated (FTO) variant rs9939609 predicted greater weight loss at 12 and 36 weeks. These preliminary data reveal that reduction in right caudate activation may be a neural mechanism of weight loss in BWL, and baseline FTO variant and reduction in frontostriatal activation during BWL predict short- and long-term weight loss. These findings require replication in larger samples. © 2016 The Obesity Society.

  8. Factors influencing the differentiation of dopaminergic traits in transplanted neural stem cells.

    Science.gov (United States)

    Yang, Ming; Donaldson, Angela E; Jiang, Yubao; Iacovitti, Lorraine

    2003-10-01

    1. Our previous studies demonstrated that when neural stem cells (NSCs) of the C17.2 clonal line are transplanted into the intact or 6-hydroxydopamine (6-OHDA) lesioned rat striatum, in most, but not all grafts, cells spontaneously express the dopamine (DA) biosynthetic enzymes, tyrosine hydroxylase (TH), and aromatic L-amino acid decarboxylase (Yang, M., Stull, N. D., Snyder. E. Y., Berk, M. A., and Iacovitti, L. (2002). Exp. Neurol.). 2. These results suggested that there were certain conditions which were more conducive to the development of DA traits in NSCs and possibly other neurotransmitter phenotypes. 3. In the present study, we modified a number of variables in vitro (i.e. passage number, confluence) and/or in vivo (degree, type, and site of injury) before assessing the survival, migration. and differentiation of engrafted NSCs. 4. We found that low confluence cultures were comprised exclusively of flattened polygonal cells, which when transplanted, migrated widely in the brain but did not express TH. 5. In contrast, high confluence cultures contained both polygonal cells and an overlying bed of fusiform cells. 6. When these NSCs were maintained for 12-20 passages and then transplanted, virtually all engrafted cells in 65% of the grafts expressed TH but not markers of other neurotransmitter systems. 7. Importantly, all TH+ grafts were accompanied by significant physical damage to the brain while TH- grafts were not, suggesting that local injury-related factors were also important. 8. Of no apparent influence on TH expression, regardless of how cells were grown prior to implantation, was the site of transplantation (cortex or striatum) or the degree of chemical lesion (intact, partial or full). 9. We conclude that transplanted NSCs can express traits specifically associated with DA neurons but only when cells are grown under certain conditions in vitro and then transplanted in proximity to injury-induced factors present in vivo.

  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. Nonassociative learning as gated neural integrator and differentiator in stimulus-response pathways.

    Science.gov (United States)

    Poon, Chi-Sang; Young, Daniel L

    2006-08-08

    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, nonassociative fear and anxiety

  11. 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

  12. 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.

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

    Science.gov (United States)

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

    2016-08-01

    Individuals with developmental prosopagnosia (DP) exhibit severe difficulties in recognizing faces and to a lesser extent, also exhibit difficulties in recognizing non-face objects. We used fMRI to investigate whether these behavioral deficits could be accounted for by altered spontaneous neural activity. Two aspects of spontaneous neural activity were measured: the intensity of neural activity in a voxel indexed by the fractional amplitude of spontaneous low-frequency fluctuations (fALFF), and the connectivity of a voxel to neighboring voxels indexed by regional homogeneity (ReHo). Compared with normal adults, both the fALFF and ReHo values within the right occipital face area (rOFA) were significantly reduced in DP subjects. Follow-up studies on the normal adults revealed that these two measures indicated further functional division of labor within the rOFA. The fALFF in the rOFA was positively correlated with behavioral performance in recognition of non-face objects, whereas ReHo in the rOFA was positively correlated with processing of faces. When considered together, the altered fALFF and ReHo within the same region (rOFA) may account for the comorbid deficits in both face and object recognition in DPs, whereas the functional division of labor in these two measures helps to explain the relative independency of deficits in face recognition and object recognition in DP. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Differential Reinforcement of Alternative Behavior in Center-Based Classrooms: Evaluation of Pre-Teaching the Alternative Behavior

    Science.gov (United States)

    LeGray, Matthew W.; Dufrene, Brad A.; Mercer, Sterett; Olmi, D. Joe; Sterling, Heather

    2013-01-01

    This study investigated the effectiveness of a differential reinforcement of alternative behavior procedure in decreasing disruptive behavior while simultaneously increasing the appropriate behavior of four children of typical development between the ages of 4 and 6 in center-based classrooms. We began with brief functional analyses for each…

  15. Behavioral and neural plasticity caused by early social experiences: the case of the honeybee.

    Science.gov (United States)

    Arenas, Andrés; Ramírez, Gabriela P; Balbuena, María Sol; Farina, Walter M

    2013-01-01

    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. 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 (AL). 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.

  16. 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.

  17. The effect of magnetic nanoparticles on neuronal differentiation of induced pluripotent stem cell-derived neural precursors

    Science.gov (United States)

    Jiráková, Klára; Šeneklová, Monika; Jirák, Daniel; Turnovcová, Karolína; Vosmanská, Magda; Babič, Michal; Horák, Daniel; Veverka, Pavel; Jendelová, Pavla

    2016-01-01

    Introduction Magnetic resonance (MR) imaging is suitable for noninvasive long-term tracking. We labeled human induced pluripotent stem cell-derived neural precursors (iPSC-NPs) with two types of iron-based nanoparticles, silica-coated cobalt zinc ferrite nanoparticles (CZF) and poly-l-lysine-coated iron oxide superparamagnetic nanoparticles (PLL-coated γ-Fe2O3) and studied their effect on proliferation and neuronal differentiation. Materials and methods We investigated the effect of these two contrast agents on neural precursor cell proliferation and differentiation capability. We further defined the intracellular localization and labeling efficiency and analyzed labeled cells by MR. Results Cell proliferation was not affected by PLL-coated γ-Fe2O3 but was slowed down in cells labeled with CZF. Labeling efficiency, iron content and relaxation rates measured by MR were lower in cells labeled with CZF when compared to PLL-coated γ-Fe2O3. Cytoplasmic localization of both types of nanoparticles was confirmed by transmission electron microscopy. Flow cytometry and immunocytochemical analysis of specific markers expressed during neuronal differentiation did not show any significant differences between unlabeled cells or cells labeled with both magnetic nanoparticles. Conclusion Our results show that cells labeled with PLL-coated γ-Fe2O3 are suitable for MR detection, did not affect the differentiation potential of iPSC-NPs and are suitable for in vivo cell therapies in experimental models of central nervous system disorders. PMID:27920532

  18. 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; Mortazavi, Seyyed Mohammad Javad; Azari, Hassan

    2017-06-01

    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.

  19. Morin hydrate promotes inner ear neural stem cell survival and differentiation and protects cochlea against neuronal hearing loss.

    Science.gov (United States)

    He, Qiang; Jia, Zhanwei; Zhang, Ying; Ren, Xiumin

    2017-03-01

    We aimed to investigate the effect of morin hydrate on neural stem cells (NSCs) isolated from mouse inner ear and its potential in protecting neuronal hearing loss. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and bromodeoxyuridine incorporation assays were employed to assess the effect of morin hydrate on the viability and proliferation of in vitro NSC culture. The NSCs were then differentiated into neurons, in which neurosphere formation and differentiation were evaluated, followed by neurite outgrowth and neural excitability measurements in the subsequent in vitro neuronal network. Mechanotransduction of cochlea ex vivo culture and auditory brainstem responses threshold and distortion product optoacoustic emissions amplitude in mouse ototoxicity model were also measured following gentamicin treatment to investigate the protective role of morin hydrate against neuronal hearing loss. Morin hydrate improved viability and proliferation, neurosphere formation and neuronal differentiation of inner ear NSCs, and promoted in vitro neuronal network functions. In both ex vivo and in vivo ototoxicity models, morin hydrate prevented gentamicin-induced neuronal hearing loss. Morin hydrate exhibited potent properties in promoting growth and differentiation of inner ear NSCs into functional neurons and protecting from gentamicin ototoxicity. Our study supports its clinical potential in treating neuronal hearing loss. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  20. Differentiated cell behavior: a multiscale approach using measure theory.

    Science.gov (United States)

    Colombi, Annachiara; Scianna, Marco; Tosin, Andrea

    2015-11-01

    This paper deals with the derivation of a collective model of cell populations out of an individual-based description of the underlying physical particle system. By looking at the spatial distribution of cells in terms of time-evolving measures, rather than at individual cell paths, we obtain an ensemble representation stemming from the phenomenological behavior of the single component cells. In particular, as a key advantage of our approach, the scale of representation of the system, i.e., microscopic/discrete vs. macroscopic/continuous, can be chosen a posteriori according only to the spatial structure given to the aforesaid measures. The paper focuses in particular on the use of different scales based on the specific functions performed by cells. A two-population hybrid system is considered, where cells with a specialized/differentiated phenotype are treated as a discrete population of point masses while unspecialized/undifferentiated cell aggregates are represented by a continuous approximation. Numerical simulations and analytical investigations emphasize the role of some biologically relevant parameters in determining the specific evolution of such a hybrid cell system.

  1. AAV-mediated Anterograde Transsynaptic Tagging: Mapping Input-Defined Functional Neural Pathways for Defense Behavior

    Science.gov (United States)

    Zingg, Brian; Chou, Xiao-lin; Zhang, Zheng-gang; Mesik, Lukas; Liang, Feixue; Tao, Huizhong Whit; Zhang, Li I.

    2017-01-01

    To decipher neural circuits underlying brain functions, viral tracers are widely applied to map input and output connectivity of specific neuronal populations. Despite the successful application of retrograde transsynaptic viruses for identifying presynaptic neurons of transduced neurons, analogous anterograde transsynaptic tools for tagging postsynaptically targeted neurons remain under development. Here, we report that adeno-associated virus (AAV1 and AAV9) exhibit anterograde transsynaptic spread properties. AAV1-Cre from transduced presynaptic neurons effectively and specifically drove Cre-dependent transgene expression in selected postsynaptic neuronal targets, and thus allowed the tracing and functional manipulation of axonal projections from the latter input-defined neuronal population. Application of this tool in superior colliculus (SC) revealed that SC neuron subpopulations receiving corticocollicular projections from auditory and visual cortex specifically drove flight and freezing, two different types of defense behavior, respectively. Such anterograde transsynaptic tagging is thus useful for forward screening of distinct functional neural pathways embedded in complex brain circuits. PMID:27989459

  2. Neural stem cell differentiation by electrical stimulation using a cross-linked PEDOT substrate: Expanding the use of biocompatible conjugated conductive polymers for neural tissue engineering.

    Science.gov (United States)

    Pires, Filipa; Ferreira, Quirina; Rodrigues, Carlos A V; Morgado, Jorge; Ferreira, Frederico Castelo

    2015-06-01

    The use of conjugated polymers allows versatile interactions between cells and flexible processable materials, while providing a platform for electrical stimulation, which is particularly relevant when targeting differentiation of neural stem cells and further application for therapy or drug screening. Materials were tested for cytotoxicity following the ISO10993-5. PSS was cross-linked. ReNcellVM neural stem cells (NSC) were seeded in laminin coated surfaces, cultured for 4 days in the presence of EGF (20 ng/mL), FGF-2 (20 ng/mL) and B27 (20 μg/mL) and differentiated over eight additional days in the absence of those factors under 100Hz pulsed DC electrical stimulation, 1V with 10 ms pulses. NSC and neuron elongation aspect ratio as well as neurite length were assessed using ImageJ. Cells were immune-stained for Tuj1 and GFAP. F8T2, MEH-PPV, P3HT and cross-linked PSS (x PSS) were assessed as non-cytotoxic. L929 fibroblast population was 1.3 higher for x PSS than for glass control, while F8T2 presents moderate proliferation. The population of neurons (Tuj1) was 1.6 times higher with longer neurites (73 vs 108 μm) for cells cultured under electrical stimulus, with cultured NSC. Such stimulus led also to longer neurons. x PSS was, for the first time, used to elongate human NSC through the application of pulsed current, impacting on their differentiation towards neurons and contributing to longer neurites. The range of conductive conjugated polymers known as non-cytotoxic was expanded. x PSS was introduced as a stable material, easily processed from solution, to interface with biological systems, in particular NSC, without the need of in-situ polymerization. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. 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.

  4. 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

  5. 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).

  6. 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.

  7. Development of social skills in children: neural and behavioral evidence for the elaboration of cognitive models

    Directory of Open Access Journals (Sweden)

    Patricia eSoto-Icaza

    2015-09-01

    Full Text Available 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 only 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 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.

  8. Evolutionarily conserved role for SoxC genes in neural crest specification and neuronal differentiation.

    Science.gov (United States)

    Uy, Benjamin R; Simoes-Costa, Marcos; Koo, Daniel E S; Sauka-Spengler, Tatjana; Bronner, Marianne E

    2015-01-15

    Members of the Sox family of transcription factors play a variety of critical developmental roles in both vertebrates and invertebrates. Whereas SoxBs and SoxEs are involved in neural and neural crest development, respectively, far less is known about members of the SoxC subfamily. To address this from an evolutionary perspective, we compare expression and function of SoxC genes in neural crest cells and their derivatives in lamprey (Petromyzon marinus), a basal vertebrate, to frog (Xenopus laevis). Analysis of transcript distribution reveals conservation of lamprey and X. laevis SoxC expression in premigratory neural crest, branchial arches, and cranial ganglia. Moreover, morpholino-mediated loss-of-function of selected SoxC family members demonstrates essential roles in aspects of neural crest development in both organisms. The results suggest important and conserved functions of SoxC genes during vertebrate evolution and a particularly critical, previously unrecognized role in early neural crest specification. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. 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

    2015-08-01

    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. © FASEB.

  10. Preventive Healthcare: A Neural Network Analysis of Behavioral Habits and Chronic Diseases.

    Science.gov (United States)

    Raghupathi, Viju; Raghupathi, Wullianallur

    2017-02-06

    The research aims to explore the association between behavioral habits and chronic diseases, and to identify a portfolio of risk factors for preventive healthcare. The data is taken from the Behavioral Risk Factor Surveillance System (BRFSS) database of the Centers for Disease Control and Prevention, for the year 2012. Using SPSS Modeler, we deploy neural networks to identify strong positive and negative associations between certain chronic diseases and behavioral habits. The data for 475,687 records from BRFS database included behavioral habit variables of consumption of soda and fruits/vegetables, alcohol, smoking, weekly working hours, and exercise; chronic disease variables of heart attack, stroke, asthma, and diabetes; and demographic variables of marital status, income, and age. Our findings indicate that with chronic conditions, behavioral habits of physical activity and fruit and vegetable consumption are negatively associated; soda, alcohol, and smoking are positively associated; and income and age are positively associated. We contribute to individual and national preventive healthcare by offering a portfolio of significant behavioral risk factors that enable individuals to make lifestyle changes and governments to frame campaigns and policies countering chronic conditions and promoting public health.

  11. NEURAL REACTIVITY TO REWARD AS A PREDICTOR OF COGNITIVE BEHAVIORAL THERAPY RESPONSE IN ANXIETY AND DEPRESSION.

    Science.gov (United States)

    Burkhouse, Katie L; Kujawa, Autumn; Kennedy, Amy E; Shankman, Stewart A; Langenecker, Scott A; Phan, K Luan; Klumpp, Heide

    2016-04-01

    Cognitive behavioral therapy (CBT) is a well-established treatment for anxiety and depression; however, response to CBT is heterogeneous across patients and many remain symptomatic after therapy, raising the need to identify prospective predictors for treatment planning. Altered neural processing of reward has been implicated in both depression and anxiety, and improving hedonic capacity is a goal of CBT. However, little is known about how neural response to reward relates to CBT outcomes in depression and anxiety. The current study used the reward positivity (RewP) event-related potential (ERP) component to examine whether neural reactivity to reward would predict CBT response in a sample of patients with anxiety without depression (n = 30) and comorbid anxiety and depression (CAD, n = 22). Participants completed a guessing reward ERP paradigm before completing 12 weeks of standard CBT. The majority of the sample (68%; 35 out of 52 patients) responded to treatment, and those with a reduced RewP at baseline were more likely to respond to treatment. A reduced RewP was also associated with a greater pre-to-post CBT reduction in depressive symptoms among individuals with CAD, but not among individuals with pure anxiety. CBT may be most beneficial in reducing depressive symptoms for individuals who demonstrate decreased reward reactivity prior to treatment. CBT may target reward brain function, leading to greater improvement in symptoms. These effects may be strongest, and therefore most meaningful, for individuals with reward-processing deficits prior to treatment. © 2016 Wiley Periodicals, Inc.

  12. Behavioral dynamics and neural grounding of a dynamic field theory of multi-object tracking.

    Science.gov (United States)

    Spencer, J P; Barich, K; Goldberg, J; Perone, S

    2012-09-01

    The ability to dynamically track moving objects in the environment is crucial for efficient interaction with the local surrounds. Here, we examined this ability in the context of the multi-object tracking (MOT) task. Several theories have been proposed to explain how people track moving objects; however, only one of these previous theories is implemented in a real-time process model, and there has been no direct contact between theories of object tracking and the growing neural literature using ERPs and fMRI. Here, we present a neural process model of object tracking that builds from a Dynamic Field Theory of spatial cognition. Simulations reveal that our dynamic field model captures recent behavioral data examining the impact of speed and tracking duration on MOT performance. Moreover, we show that the same model with the same trajectories and parameters can shed light on recent ERP results probing how people distribute attentional resources to targets vs. distractors. We conclude by comparing this new theory of object tracking to other recent accounts, and discuss how the neural grounding of the theory might be effectively explored in future work.

  13. Degraded neural and behavioral processing of speech sounds in a rat model of Rett syndrome.

    Science.gov (United States)

    Engineer, Crystal T; Rahebi, Kimiya C; Borland, Michael S; Buell, Elizabeth P; Centanni, Tracy M; Fink, Melyssa K; Im, Kwok W; Wilson, Linda G; Kilgard, Michael P

    2015-11-01

    Individuals with Rett syndrome have greatly impaired speech and language abilities. Auditory brainstem responses to sounds are normal, but cortical responses are highly abnormal. In this study, we used the novel rat Mecp2 knockout model of Rett syndrome to document the neural and behavioral processing of speech sounds. We hypothesized that both speech discrimination ability and the neural response to speech sounds would be impaired in Mecp2 rats. We expected that extensive speech training would improve speech discrimination ability and the cortical response to speech sounds. Our results reveal that speech responses across all four auditory cortex fields of Mecp2 rats were hyperexcitable, responded slower, and were less able to follow rapidly presented sounds. While Mecp2 rats could accurately perform consonant and vowel discrimination tasks in quiet, they were significantly impaired at speech sound discrimination in background noise. Extensive speech training improved discrimination ability. Training shifted cortical responses in both Mecp2 and control rats to favor the onset of speech sounds. While training increased the response to low frequency sounds in control rats, the opposite occurred in Mecp2 rats. Although neural coding and plasticity are abnormal in the rat model of Rett syndrome, extensive therapy appears to be effective. These findings may help to explain some aspects of communication deficits in Rett syndrome and suggest that extensive rehabilitation therapy might prove beneficial. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. 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...

  15. p53 interaction with JMJD3 results in its nuclear distribution during mouse neural stem cell differentiation.

    Directory of Open Access Journals (Sweden)

    Susana Solá

    2011-03-01

    Full Text Available Conserved elements of apoptosis are also integral components of cellular differentiation. In this regard, p53 is involved in neurogenesis, being required for neurite outgrowth in primary neurons and for axonal regeneration in mice. Interestingly, demethylases regulate p53 activity and its interaction with co-activators by acting on non-histone proteins. In addition, the histone H3 lysine 27-specific demethylase JMJD3 induces ARF expression, thereby stabilizing p53 in mouse embryonic fibroblasts. We hypothesized that p53 interacts with key regulators of neurogenesis to redirect stem cells to differentiation, as an alternative to cell death. Specifically, we investigated the potential cross-talk between p53 and JMJD3 during mouse neural stem cell (NSC differentiation. Our results demonstrated that JMJD3 mRNA and protein levels were increased early in mouse NSC differentiation, when JMJD3 activity was readily detected. Importantly, modulation of JMJD3 in NSCs resulted in changes of total p53 protein, coincident with increased ARF mRNA and protein expression. ChIP analysis revealed that JMJD3 was present at the promoter and exon 1 regions of ARF during neural differentiation, although without changes in H3K27me3. Immunoprecipitation assays demonstrated a direct interaction between p53 and JMJD3, independent of the C-terminal region of JMJD3, and modulation of p53 methylation by JMJD3-demethylase activity. Finally, transfection of mutant JMJD3 showed that the demethylase activity of JMJD3 was crucial in regulating p53 cellular distribution and function. In conclusion, JMJD3 induces p53 stabilization in mouse NSCs through ARF-dependent mechanisms, directly interacts with p53 and, importantly, causes nuclear accumulation of p53. This suggests that JMJD3 and p53 act in a common pathway during neurogenesis.

  16. Epigenetic marks define the lineage and differentiation potential of two distinct neural crest-derived intermediate odontogenic progenitor populations.

    Science.gov (United States)

    Gopinathan, Gokul; Kolokythas, Antonia; Luan, Xianghong; Diekwisch, Thomas G H

    2013-06-15

    Epigenetic mechanisms, such as histone modifications, play an active role in the differentiation and lineage commitment of mesenchymal stem cells. In the present study, epigenetic states and differentiation profiles of two odontogenic neural crest-derived intermediate progenitor populations were compared: dental pulp (DP) and dental follicle (DF). ChIP on chip assays revealed substantial H3K27me3-mediated repression of odontoblast lineage genes DSPP and dentin matrix protein 1 (DMP1) in DF cells, but not in DP cells. Mineralization inductive conditions caused steep increases of mineralization and patterning gene expression levels in DP cells when compared to DF cells. In contrast, mineralization induction resulted in a highly dynamic histone modification response in DF cells, while there was only a subdued effect in DP cells. Both DF and DP progenitors featured H3K4me3-active marks on the promoters of early mineralization genes RUNX2, MSX2, and DLX5, while OSX, IBSP, and BGLAP promoters were enriched for H3K9me3 or H3K27me3. Compared to DF cells, DP cells expressed higher levels of three pluripotency-associated genes, OCT4, NANOG, and SOX2. Finally, gene ontology comparison of bivalent marks unique for DP and DF cells highlighted cell-cell attachment genes in DP cells and neurogenesis genes in DF cells. In conclusion, the present study indicates that the DF intermediate odontogenic neural crest lineage is distinguished from its DP counterpart by epigenetic repression of DSPP and DMP1 genes and through dynamic histone enrichment responses to mineralization induction. Findings presented here highlight the crucial role of epigenetic regulatory mechanisms in the terminal differentiation of odontogenic neural crest lineages.

  17. Distribution and localization of fibroblast growth factor-8 in rat brain and nerve cells during neural stem/progenitor cell differentiation.

    Science.gov (United States)

    Lu, Jiang; Li, Dongsheng; Lu, Kehuan

    2012-07-05

    The present study explored the distribution and localization of fibroblast growth factor-8 and its potential receptor, fibroblast growth factor receptor-3, in adult rat brain in vivo and in nerve cells during differentiation of neural stem/progenitor cells in vitro. Immunohistochemistry was used to examine the distribution of fibroblast growth factor-8 in adult rat brain in vivo. Localization of fibroblast growth factor-8 and fibroblast growth factor receptor-3 in cells during neural stem/progenitor cell differentiation in vitro was detected by immunofluorescence. Flow cytometry and immunofluorescence were used to evaluate the effect of an anti-fibroblast growth factor-8 antibody on neural stem/progenitor cell differentiation and expansion in vitro. Results from this study confirmed that fibroblast growth factor-8 was mainly distributed in adult midbrain, namely the substantia nigra, compact part, dorsal tier, substantia nigra and reticular part, but was not detected in the forebrain comprising the caudate putamen and striatum. Unusual results were obtained in retrosplenial locations of adult rat brain. We found that fibroblast growth factor-8 and fibroblast growth factor receptor-3 were distributed on the cell membrane and in the cytoplasm of nerve cells using immunohistochemistry and immunofluorescence analyses. We considered that the distribution of fibroblast growth factor-8 and fibroblast growth factor receptor-3 in neural cells corresponded to the characteristics of fibroblast growth factor-8, a secretory factor. Addition of an anti-fibroblast growth factor-8 antibody to cultures significantly affected the rate of expansion and differentiation of neural stem/progenitor cells. In contrast, addition of recombinant fibroblast growth factor-8 to differentiation medium promoted neural stem/progenitor cell differentiation and increased the final yields of dopaminergic neurons and total neurons. Our study may help delineate the important roles of fibroblast growth

  18. Robot manipulator identification based on adaptive multiple-input and multiple-output neural model optimized by advanced differential evolution algorithm

    Directory of Open Access Journals (Sweden)

    Nguyen Ngoc Son

    2016-12-01

    Full Text Available This article proposes a novel advanced differential evolution method which combines the differential evolution with the modified back-propagation algorithm. This new proposed approach is applied to train an adaptive enhanced neural model for approximating the inverse model of the industrial robot arm. Experimental results demonstrate that the proposed modeling procedure using the new identification approach obtains better convergence and more precision than the traditional back-propagation method or the lonely differential evolution approach. Furthermore, the inverse model of the industrial robot arm using the adaptive enhanced neural model performs outstanding results.

  19. 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

  20. Vesicular glutamate transporters play a role in neuronal differentiation of cultured SVZ-derived neural precursor cells.

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    Eduardo H Sánchez-Mendoza

    Full Text Available The role of glutamate in the regulation of neurogenesis is well-established, but the role of vesicular glutamate transporters (VGLUTs and excitatory amino acid transporters (EAATs in controlling adult neurogenesis is unknown. Here we investigated the implication of VGLUTs in the differentiation of subventricular zone (SVZ-derived neural precursor cells (NPCs. Our results show that NPCs express VGLUT1-3 and EAAT1-3 both at the mRNA and protein level. Their expression increases during differentiation closely associated with the expression of marker genes. In expression analyses we show that VGLUT1 and VGLUT2 are preferentially expressed by cultured SVZ-derived doublecortin+ neuroblasts, while VGLUT3 is found on GFAP+ glial cells. In cultured NPCs, inhibition of VGLUT by Evans Blue increased the mRNA level of neuronal markers doublecortin, B3T and MAP2, elevated the number of NPCs expressing doublecortin protein and promoted the number of cells with morphological appearance of branched neurons, suggesting that VGLUT function prevents neuronal differentiation of NPCs. This survival- and differentiation-promoting effect of Evans blue was corroborated by increased AKT phosphorylation and reduced MAPK phosphorylation. Thus, under physiological conditions, VGLUT1-3 inhibition, and thus decreased glutamate exocytosis, may promote neuronal differentiation of NPCs.

  1. Phasor fluorescence lifetime microscopy of free and protein-bound NADH reveals neural stem cell differentiation potential.

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    Chiara Stringari

    Full Text Available In the stem cell field there is a lack of non invasive and fast methods to identify stem cell's metabolic state, differentiation state and cell-lineage commitment. Here we describe a label-free method that uses NADH as an intrinsic biomarker and the Phasor approach to Fluorescence Lifetime microscopy to measure the metabolic fingerprint of cells. We show that different metabolic states are related to different cell differentiation stages and to stem cell bias to neuronal and glial fate, prior the expression of lineage markers. Our data demonstrate that the NADH FLIM signature distinguishes non-invasively neurons from undifferentiated neural progenitor and stem cells (NPSCs at two different developmental stages (E12 and E16. NPSCs follow a metabolic trajectory from a glycolytic phenotype to an oxidative phosphorylation phenotype through different stages of differentiation. NSPCs are characterized by high free/bound NADH ratio, while differentiated neurons are characterized by low free/bound NADH ratio. We demonstrate that the metabolic signature of NPSCs correlates with their differentiation potential, showing that neuronal progenitors and glial progenitors have a different free/bound NADH ratio. Reducing conditions in NPSCs correlates with their neurogenic potential, while oxidative conditions correlate with glial potential. For the first time we show that FLIM NADH metabolic fingerprint provides a novel, and quantitative measure of stem cell potential and a label-free and non-invasive means to identify neuron- or glial- biased progenitors.

  2. Differentiated human midbrain-derived neural progenitor cells express excitatory strychnine-sensitive glycine receptors containing α2β subunits.

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    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.

  3. 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.

  4. Transport and metabolism behavior of brazilein during its entrance into neural cells.

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    Shuang Zhao

    Full Text Available Brazilein, a natural small molecule, shows a variety of pharmacological activities, especially on nervous system and immune system. As a potential multifunctional drug, we studied the distribution and the transport behavior and metabolic behavior of brazilein in vivo and in vitro. Brazilein was found to be able to distribute in the mouse brain and transport into neural cells. A metabolite was found in the brain and in the cells. Positive and negative mode-MS/MS and Q-TOF were used to identify the metabolite. MS/MS fragmentation mechanisms showed the methylation occurred at the 10-hydroxyl of brazilein (10-O-methylbrazilein. Further, catechol-O- methyltransferase (COMT was confirmed as a crucial enzyme correlated with the methylated metabolite generation by molecular docking and pharmacological experiment.

  5. Neural substrates of treatment response to cognitive-behavioral therapy in panic disorder with agoraphobia.

    Science.gov (United States)

    Lueken, Ulrike; Straube, Benjamin; Konrad, Carsten; Wittchen, Hans-Ulrich; Ströhle, Andreas; Wittmann, André; Pfleiderer, Bettina; Uhlmann, Christina; Arolt, Volker; Jansen, Andreas; Kircher, Tilo

    2013-11-01

    Although exposure-based cognitive-behavioral therapy (CBT) is an effective treatment option for panic disorder with agoraphobia, the neural substrates of treatment response remain unknown. Evidence suggests that panic disorder with agoraphobia is characterized by dysfunctional safety signal processing. Using fear conditioning as a neurofunctional probe, the authors investigated neural baseline characteristics and neuroplastic changes after CBT that were associated with treatment outcome in patients with panic disorder with agoraphobia. Neural correlates of fear conditioning and extinction were measured using functional MRI before and after a manualized CBT program focusing on behavioral exposure in 49 medication-free patients with a primary diagnosis of panic disorder with agoraphobia. Treatment response was defined as a reduction exceeding 50% in Hamilton Anxiety Rating Scale scores. At baseline, nonresponders exhibited enhanced activation in the right pregenual anterior cingulate cortex, the hippocampus, and the amygdala in response to a safety signal. While this activation pattern partly resolved in nonresponders after CBT, successful treatment was characterized by increased right hippocampal activation when processing stimulus contingencies. Treatment response was associated with an inhibitory functional coupling between the anterior cingulate cortex and the amygdala that did not change over time. This study identified brain activation patterns associated with treatment response in patients with panic disorder with agoraphobia. Altered safety signal processing and anterior cingulate cortex-amygdala coupling may indicate individual differences among these patients that determine the effectiveness of exposure-based CBT and associated neuroplastic changes. Findings point to brain networks by which successful CBT in this patient population is mediated.

  6. 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).

  7. 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.

  8. 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 BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

  9. Resonant Dynamics of Grounded Cognition: Explanation of Behavioral and Neuroimaging Data Using the ART Neural Network.

    Science.gov (United States)

    Domijan, Dražen; Šetić, Mia

    2016-01-01

    Research on grounded cognition suggests that the processing of a word or concept reactivates the perceptual representations that are associated with the referent object. The objective of this work is to demonstrate how behavioral and functional neuroimaging data on grounded cognition can be understood as different manifestations of the same cortical circuit designed to achieve stable category learning, as proposed by the adaptive resonance theory (ART). We showed that the ART neural network provides a mechanistic explanation of why reaction times in behavioral studies depend on the expectation or attentional priming created by the word meaning (Richter and Zwaan, 2009). A mismatch between top-down expectation and bottom-up sensory data activates an orienting subsystem that slows execution of the current task. Furthermore, we simulated the data from functional neuroimaging studies of color knowledge retrieval that showed anterior shift (Chao and Martin, 1999; Thompson-Schill, 2003) and an overlap effect (Simmons et al., 2007; Hsu et al., 2011) in the left fusiform gyrus. We explain the anterior effect as a result of the partial activation of different components of the same ART circuit in the condition of passive viewing. Conversely, a demanding perceptual task requires activation of the whole ART circuit. This condition is reflected in the fMRI image as an overlap between cortical activation during perceptual and conceptual processing. We conclude that the ART neural network is able to explain how the brain grounds symbols in perception via perceptual simulation.

  10. Resonant Dynamics of Grounded Cognition: Explanation of Behavioral and Neuroimaging Data Using the ART Neural Network

    Directory of Open Access Journals (Sweden)

    Dražen eDomijan

    2016-02-01

    Full Text Available Research on grounded cognition suggests that the processing of a word or concept reactivates the perceptual representations that are associated with the referent object. The objective of this work is to demonstrate how behavioral and functional neuroimaging data on grounded cognition can be understood as different manifestations of the same cortical circuit designed to achieve stable category learning, as proposed by the adaptive resonance theory (ART. We showed that the ART neural network provides a mechanistic explanation of why reaction times in behavioral studies depend on the expectation or attentional priming created by the word meaning (Richter & Zwaan, 2009. A mismatch between top-down expectation and bottom-up sensory data activates an orienting subsystem that slows execution of the current task. Furthermore, we simulated the data from functional neuroimaging studies of color knowledge retrieval that showed anterior shift (Chao & Martin, 1999; Thompson-Schill, 2003 and an overlap effect (Hsu et al., 2011; Simmons et al., 2007 in the left fusiform gyrus. We explain the anterior effect as a result of the partial activation of different components of the same ART circuit in the condition of passive viewing. Conversely, a demanding perceptual task requires activation of the whole ART circuit. This condition is reflected in the fMRI image as an overlap between cortical activation during perceptual and conceptual processing. We conclude that the ART neural network is able to explain how the brain grounds symbols in perception via perceptual simulation.

  11. 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.

  12. Neural correlates of impulsive aggressive behavior in subjects with a history of alcohol dependence.

    Science.gov (United States)

    Kose, Samet; Steinberg, Joel L; Moeller, F Gerard; Gowin, Joshua L; Zuniga, Edward; Kamdar, Zahra N; Schmitz, Joy M; Lane, Scott D

    2015-04-01

    Alcohol-related aggression is a complex and problematic phenomenon with profound public health consequences. We examined neural correlates potentially moderating the relationship between human aggressive behavior and chronic alcohol use. Thirteen subjects meeting DSM-IV criteria for past alcohol-dependence in remission (AD) and 13 matched healthy controls (CONT) participated in an fMRI study adapted from a laboratory model of human aggressive behavior (Point Subtraction Aggression Paradigm, or PSAP). Blood oxygen level dependent (BOLD) activation was measured during bouts of operationally defined aggressive behavior, during postprovocation periods, and during monetary-reinforced behavior. Whole brain voxelwise random-effects analyses found group differences in brain regions relevant to chronic alcohol use and aggressive behavior (e.g., emotional and behavioral control). Behaviorally, AD subjects responded on both the aggressive response and monetary response options at significantly higher rates than CONT. Whole brain voxelwise random-effects analyses revealed significant group differences in response to provocation (monetary subtractions), with CONT subjects showing greater activation in frontal and prefrontal cortex, thalamus, and hippocampus. Collapsing data across all subjects, regression analyses of postprovocation brain activation on aggressive response rate revealed significant positive regression slopes in precentral gyrus and parietal cortex; and significant negative regression slopes in orbitofrontal cortex, prefrontal cortex, caudate, thalamus, and middle temporal gyrus. In these collapsed analyses, response to provocation and aggressive behavior were associated with activation in brain regions subserving inhibitory and emotional control, sensorimotor integration, and goal directed motor activity. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  13. 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. PMID:27471463

  14. 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.

  15. The Differential Role of Verbal and Spatial Working Memory in the Neural Basis of Arithmetic

    Science.gov (United States)

    Demir, Özlem Ece; Prado, Jérôme; Booth, James R.

    2014-01-01

    We examine the relations of verbal and spatial WM ability to the neural bases of arithmetic in school-age children. We independently localize brain regions subserving verbal versus spatial representations. For multiplication, higher verbal WM ability is associated with greater recruitment of the left temporal cortex, identified by the verbal localizer. For multiplication and subtraction, higher spatial WM ability is associated with greater recruitment of right parietal cortex, identified by the spatial localizer. Depending on their WM ability, children engage different neural systems that manipulate different representations to solve arithmetic problems. PMID:25144257

  16. Denoising by coupled partial differential equations and extracting phase by backpropagation neural networks for electronic speckle pattern interferometry.

    Science.gov (United States)

    Tang, Chen; Lu, Wenjing; Chen, Song; Zhang, Zhen; Li, Botao; Wang, Wenping; Han, Lin

    2007-10-20

    We extend and refine previous work [Appl. Opt. 46, 2907 (2007)]. Combining the coupled nonlinear partial differential equations (PDEs) denoising model with the ordinary differential equations enhancement method, we propose the new denoising and enhancing model for electronic speckle pattern interferometry (ESPI) fringe patterns. Meanwhile, we propose the backpropagation neural networks (BPNN) method to obtain unwrapped phase values based on a skeleton map instead of traditional interpolations. We test the introduced methods on the computer-simulated speckle ESPI fringe patterns and experimentally obtained fringe pattern, respectively. The experimental results show that the coupled nonlinear PDEs denoising model is capable of effectively removing noise, and the unwrapped phase values obtained by the BPNN method are much more accurate than those obtained by the well-known traditional interpolation. In addition, the accuracy of the BPNN method is adjustable by changing the parameters of networks such as the number of neurons.

  17. Differential regulation of observational fear and neural oscillations by serotonin and dopamine in the mouse anterior cingulate cortex.

    Science.gov (United States)

    Kim, Byung Sun; Lee, Junghee; Bang, Minji; Seo, Bo Am; Khalid, Arshi; Jung, Min Whan; Jeon, Daejong

    2014-11-01

    The aberrant regulation of serotonin (5-HT) and dopamine (DA) in the brain has been implicated in neuropsychiatric disorders associated with marked impairments in empathy, such as schizophrenia and autism. Many psychiatric drugs bind to both types of receptors, and the anterior cingulate cortex (ACC) is known to be centrally involved with empathy. However, the relationship between the 5-HT/DA system in the ACC and empathic behavior is not yet well known. We investigated the role of 5-HT/DA in empathy-like behavior and in the regulation of ACC neural activity. An observational fear learning task was conducted following microinjections of 5-HT, DA, 5-HT and DA, methysergide (5-HT receptor antagonist), SCH-23390 (DA D1 receptor antagonist), or haloperidol (DA D2 receptor antagonist) into the mouse ACC. The ACC neural activity influenced by 5-HT and DA was electrophysiologically characterized in vitro and in vivo. The microinjection of haloperidol, but not methysergide or SCH-23390, decreased the fear response of observing mice. The administration of 5-HT and 5-HT and DA together, but not DA alone, reduced the freezing response of observing mice. 5-HT enhanced delta-band activity and reduced alpha- and gamma-band activities in the ACC, whereas DA reduced only alpha-band activity. Based on entropy, reduced complexity of ACC neural activity was observed with 5-HT treatment. The current results demonstrated that DA D2 receptors in the ACC are required for observational fear learning, whereas increased 5-HT levels disrupt observational fear and alter the regularity of ACC neural oscillations.

  18. Akhirin regulates the proliferation and differentiation of neural stem cells in intact and injured mouse spinal cord.

    Science.gov (United States)

    Abdulhaleem, Felemban Athary M; Song, Xiaohong; Kawano, Rie; Uezono, Naohiro; Ito, Ayako; Ahmed, Giasuddin; Hossain, Mahmud; Nakashima, Kinichi; Tanaka, Hideaki; Ohta, Kunimasa

    2015-05-01

    Although the central nervous system is considered a comparatively static tissue with limited cell turnover, cells with stem cell properties have been isolated from most neural tissues. The spinal cord ependymal cells show neural stem cell potential in vitro and in vivo in injured spinal cord. However, very little is known regarding the ependymal niche in the mouse spinal cord. We previously reported that a secreted factor, chick Akhirin, is expressed in the ciliary marginal zone of the eye, where it works as a heterophilic cell-adhesion molecule. Here, we describe a new crucial function for mouse Akhirin (M-AKH) in regulating the proliferation and differentiation of progenitors in the mouse spinal cord. During embryonic spinal cord development, M-AKH is transiently expressed in the central canal ependymal cells, which possess latent neural stem cell properties. Targeted inactivation of the AKH gene in mice causes a reduction in the size of the spinal cord and decreases BrdU incorporation in the spinal cord. Remarkably, the expression patterns of ependymal niche molecules in AKH knockout (AKH-/-) mice are different from those of AKH+/+, both in vitro and in vivo. Furthermore, we provide evidence that AKH expression in the central canal is rapidly upregulated in the injured spinal cord. Taken together, these results indicate that M-AKH plays a crucial role in mouse spinal cord formation by regulating the ependymal niche in the central canal. © 2014 Wiley Periodicals, Inc.

  19. The role of hSCs in promoting neural differentiation of hUC-MSCs in spinal cord injury

    Directory of Open Access Journals (Sweden)

    Wu QL

    2013-11-01

    Full Text Available Qiuli Wu,1,* You Chen,1,* Guangzhi Ning,1 Shiqing Feng,1 Junling Han,2 Qiang Wu,1 Yulin LI,1 Hong Wu,1 Hongyu Shi1 1Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, People's Republic of China; 2Tianjin Union Stem Cell and Gene Engineering Co., Ltd, Tianjin, People's Republic of China * These authors contributed equally to this paper Abstract: Cell therapy is a promising approach to treating spinal cord injury (SCI. Previous studies demonstrated that co-transplantation of human umbilical cord mesenchymal stem cells (hUC-MSCs and human Schwann cells (hSCs was an effective strategy by which to promote the regeneration of corticospinal fibers and locomotor recovery after SCI in rats. However, the neural differentiation potential of hUC-MSCs was not fully understood. In the present study, we examined the influence of hSCs on the survival and differentiation of hUC-MSCs in SCI rats. Four groups of rats were implanted with Dulbecco's Modified Eagle's Medium (DMEM, hSCs, hUC-MSCs, or a combination of hSCs and hUC-MSCs, respectively. Our results demonstrated that MAB1281 immunopositive cells appeared in the injured site of the transplanted cell groups, while myelin basic protein and high-molecular-weight neurofilament immunopositive cells were detected only in the co-transplantation group under the positive background of MAB1281. Furthermore, polymerase chain reaction (PCR and Western blot showed significantly higher expression of myelin basic protein and high-molecular-weight neurofilament and lower expression of glial fibrillary acidic protein in the co-transplantation group (P < 0.05, which correlated strongly with immunofluorescence findings. These results suggest that hSCs could induce hUC-MSC differentiation into neurons and oligodendrocytes and inhibit the formation of glial scarring after SCI. The neural differentiation of hUC-MSCs is likely induced by soluble factors provided by hSCs. Keywords: spinal cord injury

  20. The ciliary proteins Meckelin and Jouberin are required for retinoic acid-dependent neural differentiation of mouse embryonic stem cells.

    Science.gov (United States)

    Romani, Sveva; Illi, Barbara; De Mori, Roberta; Savino, Mauro; Gleeson, Joseph G; Valente, Enza Maria

    2014-01-01

    The dysfunction of the primary cilium, a complex, evolutionarily conserved, organelle playing an important role in sensing and transducing cell signals, is the unifying pathogenetic mechanism of a growing number of diseases collectively termed "ciliopathies", typically characterized by multiorgan involvement. Developmental defects of the central nervous system (CNS) characterize a subset of ciliopathies showing clinical and genetic overlap, such as Joubert syndrome (JS) and Meckel syndrome (MS). Although several knock-out mice lacking a variety of ciliary proteins have shown the importance of primary cilia in the development of the brain and CNS-derived structures, developmental in vitro studies, extremely useful to unravel the role of primary cilia along the course of neural differentiation, are still missing. Mouse embryonic stem cells (mESCs) have been recently proven to mimic brain development, giving the unique opportunity to dissect the CNS differentiation process along its sequential steps. In the present study we show that mESCs express the ciliary proteins Meckelin and Jouberin in a developmentally-regulated manner, and that these proteins co-localize with acetylated tubulin labeled cilia located at the outer embryonic layer. Further, mESCs differentiating along the neuronal lineage activate the cilia-dependent sonic hedgehog signaling machinery, which is impaired in Meckelin knock-out cells but results unaffected in Jouberin-deficient mESCs. However, both lose the ability to acquire a neuronal phenotype. Altogether, these results demonstrate a pivotal role of Meckelin and Jouberin during embryonic neural specification and indicate mESCs as a suitable tool to investigate the developmental impact of ciliary proteins dysfunction. Copyright © 2014 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  1. Propofol at Clinically Relevant Concentrations Increases Neuronal Differentiation but Is Not Toxic to Hippocampal Neural Precursor Cells In Vitro

    Science.gov (United States)

    Sall, Jeffrey W.; Stratmann, Greg; Leong, Jason; Woodward, Elliott; Bickler, Philip E.

    2012-01-01

    Background Propofol in the early postnatal period has been shown to cause brain cell death. One proposed mechanism for cognitive dysfunction after anesthesia is alteration of neural stem cell function and neurogenesis. We examined the effect of propofol on neural precursor or stem cells (NPCs) grown in vitro. Methods Hippocampal derived NPCs from postnatal day 2 rats were exposed to propofol or to Diprivan. NPCs were then analyzed for bromodeoxyuridine incorporation to measure proliferation. Cell death was measured by lactate dehydrogenase release. Immunocytochemistry was used to evaluate the expression of neuronal and glial markers in differentiating NPCs exposed to propofol. Results Propofol dose dependently increases the release of lactate dehydrogenase from NPCs under both proliferating and differentiating conditions at supraclinical concentrations (> 7.1μM). Both Diprivan and propofol had the same effect on NPCs. Propofol mediated release of lactate dehydrogenase is not inhibited by blocking the γ-aminobutyric acid type A receptor or extracellular calcium influx and is not mediated by caspase-3/7. Direct γ-aminobutyric acid type A receptor activation did not have the same effect. In differentiating NPCs 6 h of propofol at 2.1 μM increased the number neurons but not glial cells 4 days later. Increased neuronal differentiation was not blocked by Bicuculline. Conclusions Only supraclinical concentrations of propofol or Diprivan kill NPCs in culture by a non-γ-aminobutyric acid type A, noncaspase 3 mechanism. Clinically relevant doses of propofol increase neuronal fate choice by a non-γ-aminobutyric acid type A mechanism. PMID:23001052

  2. 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...

  3. Differential expression of neural cell adhesion molecule and cadherins in pancreatic islets, glucagonomas, and insulinomas

    DEFF Research Database (Denmark)

    Møller, C J; Christgau, S; Williamson, M R

    1992-01-01

    in a process where cell adhesion molecules are involved. In this study we have analyzed the expression of neural cell adhesion molecule (NCAM) and cadherin molecules in neonatal, young, and adult rat islet cells as well as in glucagonomas and insulinomas derived from a pluripotent rat islet cell tumor. Whereas...

  4. Folic acid and homocysteine affect neural crest and neuroepithelial cell outgrowth and differentiation in vitro.

    NARCIS (Netherlands)

    Boot, M.J.; Steegers-Theunissen, R.P.M.; Poelmann, R.E.; Iperen, L. van; Lindemans, J.; Groot, A. de

    2003-01-01

    The beneficial effect of additional folic acid in the periconceptional period to prevent neural tube defects, orofacial clefts, and conotruncal heart defects in the offspring has been shown. Folate shortage results in homocysteine accumulation. Elevated levels of homocysteine have been related to

  5. Functionally deficient neuronal differentiation of mouse embryonic neural stem cells in vitro

    NARCIS (Netherlands)

    Balasubramaniyan, [No Value; de Haas, AH; Bakels, R; Koper, A; Boddeke, HWGM; Copray, JM

    Embryonic mouse neural stem cells (NSCs) were isolated from E14 mice, multiplied in medium containing epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) and plated in laminin-coated wells in basic serum-free neurobasal medium. After 7 days in vitro, approximately 20% of the

  6. The ROCK/GGTase Pathway Are Essential to the Proliferation and Differentiation of Neural Stem Cells Mediated by Simvastatin.

    Science.gov (United States)

    Zhang, Chan; Wu, Jian-Min; Liao, Min; Wang, Jun-Ling; Xu, Chao-Jin

    2016-12-01

    Simvastatin, a lipophilic and fermentation-derived natural statin, is reported to treat neurological disorders, such as traumatic brain injury, Parkinson's disease (PD), Alzheimer disease (AD), etc. Recently, research also indicated that simvastatin could promote regeneration in the dentate gyrus of adult mice by Wnt/β-catenin signaling (Robin et al. in Stem Cell Reports 2:9-17, 2014). However, the effect and mechanisms by which simvastatin may affect the neural stem cells (NSCs; from the embryonic day 14.5 (E14.5) SD rat brain) are not fully understood. Here, we investigated the effects of different doses of simvastatin on the survival, proliferation, differentiation, migration, and cell cycle of NSCs as well as underlying intracellular signaling pathways. The results showed that simvastatin not only inhibits the proliferation of NSCs but also enhances the βIII-tubulin(+) neuron differentiation rate. Additionally, we find that simvastatin could also promote NSC migration and induce cell cycle arrest at M2 phrase. All these effects of simvastatin on NSCs were mimicked with an inhibitor of Rho kinase (ROCK) and a specific inhibitor of geranylgeranyl transferase (GGTase). In conclusion, these data indicate that simvastatin could promote neurogenesis of neural stem cells, and these effects were mediated through the ROCK/GGTase pathway.

  7. 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

  8. 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.

  9. Analyzing animal behavior via classifying each video frame using convolutional neural networks

    Science.gov (United States)

    Stern, Ulrich; He, Ruo; Yang, Chung-Hui

    2015-01-01

    High-throughput analysis of animal behavior requires software to analyze videos. Such software analyzes each frame individually, detecting animals’ body parts. But the image analysis rarely attempts to recognize “behavioral states”—e.g., actions or facial expressions—directly from the image instead of using the detected body parts. Here, we show that convolutional neural networks (CNNs)—a machine learning approach that recently became the leading technique for object recognition, human pose estimation, and human action recognition—were able to recognize directly from images whether Drosophila were “on” (standing or walking) or “off” (not in physical contact with) egg-laying substrates for each frame of our videos. We used multiple nets and image transformations to optimize accuracy for our classification task, achieving a surprisingly low error rate of just 0.072%. Classifying one of our 8 h videos took less than 3 h using a fast GPU. The approach enabled uncovering a novel egg-laying-induced behavior modification in Drosophila. Furthermore, it should be readily applicable to other behavior analysis tasks. PMID:26394695

  10. 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.

  11. Extremely low-frequency electromagnetic fields affect transcript levels of neuronal differentiation-related genes in embryonic neural stem cells.

    Science.gov (United States)

    Ma, Qinlong; Deng, Ping; Zhu, Gang; Liu, Chuan; Zhang, Lei; Zhou, Zhou; Luo, Xue; Li, Min; Zhong, Min; Yu, Zhengping; Chen, Chunhai; Zhang, Yanwen

    2014-01-01

    Previous studies have reported that extremely low-frequency electromagnetic fields (ELF-EMF) can affect the processes of brain development, but the underlying mechanism is largely unknown. The proliferation and differentiation of embryonic neural stem cells (eNSCs) is essential for brain development during the gestation period. To date, there is no report about the effects of ELF-EMF on eNSCs. In this paper, we studied the effects of ELF-EMF on the proliferation and differentiation of eNSCs. Primary cultured eNSCs were treated with 50 Hz ELF-EMF; various magnetic intensities and exposure times were applied. Our data showed that there was no significant change in cell proliferation, which was evaluated by cell viability (CCK-8 assay), DNA synthesis (Edu incorporation), average diameter of neurospheres, cell cycle distribution (flow cytometry) and transcript levels of cell cycle related genes (P53, P21 and GADD45 detected by real-time PCR). When eNSCs were induced to differentiation, real-time PCR results showed a down-regulation of Sox2 and up-regulation of Math1, Math3, Ngn1 and Tuj1 mRNA levels after 50 Hz ELF-EMF exposure (2 mT for 3 days), but the percentages of neurons (Tuj1 positive cells) and astrocytes (GFAP positive cells) were not altered when detected by immunofluorescence assay. Although cell proliferation and the percentages of neurons and astrocytes differentiated from eNSCs were not affected by 50 Hz ELF-EMF, the expression of genes regulating neuronal differentiation was altered. In conclusion, our results support that 50 Hz ELF-EMF induce molecular changes during eNSCs differentiation, which might be compensated by post-transcriptional mechanisms to support cellular homeostasis.

  12. Extremely low-frequency electromagnetic fields affect transcript levels of neuronal differentiation-related genes in embryonic neural stem cells.

    Directory of Open Access Journals (Sweden)

    Qinlong Ma

    Full Text Available Previous studies have reported that extremely low-frequency electromagnetic fields (ELF-EMF can affect the processes of brain development, but the underlying mechanism is largely unknown. The proliferation and differentiation of embryonic neural stem cells (eNSCs is essential for brain development during the gestation period. To date, there is no report about the effects of ELF-EMF on eNSCs. In this paper, we studied the effects of ELF-EMF on the proliferation and differentiation of eNSCs. Primary cultured eNSCs were treated with 50 Hz ELF-EMF; various magnetic intensities and exposure times were applied. Our data showed that there was no significant change in cell proliferation, which was evaluated by cell viability (CCK-8 assay, DNA synthesis (Edu incorporation, average diameter of neurospheres, cell cycle distribution (flow cytometry and transcript levels of cell cycle related genes (P53, P21 and GADD45 detected by real-time PCR. When eNSCs were induced to differentiation, real-time PCR results showed a down-regulation of Sox2 and up-regulation of Math1, Math3, Ngn1 and Tuj1 mRNA levels after 50 Hz ELF-EMF exposure (2 mT for 3 days, but the percentages of neurons (Tuj1 positive cells and astrocytes (GFAP positive cells were not altered when detected by immunofluorescence assay. Although cell proliferation and the percentages of neurons and astrocytes differentiated from eNSCs were not affected by 50 Hz ELF-EMF, the expression of genes regulating neuronal differentiation was altered. In conclusion, our results support that 50 Hz ELF-EMF induce molecular changes during eNSCs differentiation, which might be compensated by post-transcriptional mechanisms to support cellular homeostasis.

  13. 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

  14. 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

  15. Role for estradiol in female-typical brain and behavioral sexual differentiation

    OpenAIRE

    Bakker, Julie; Baum, M.J.

    2007-01-01

    The importance of estrogens in controlling brain and behavioral sexual differentiation in female rodents is an unresolved issue in the field of behavioral neuroendocrinology. Whereas, the current dogma states that the female brain develops independently of estradiol, many studies have hinted at possible roles of estrogen in female sexual differentiation. Accordingly, it has been proposed that alpha-fetoprotein, a fetal plasma protein that binds estrogens with high affinity, has more than a ne...

  16. Planarian Phototactic Assay Reveals Differential Behavioral Responses Based on Wavelength.

    Science.gov (United States)

    Paskin, Taylor R; Jellies, John; Bacher, Jessica; Beane, Wendy S

    2014-01-01

    Planarians are free-living aquatic flatworms that possess a well-documented photophobic response to light. With a true central nervous system and simple cerebral eyes (ocelli), planarians are an emerging model for regenerative eye research. However, comparatively little is known about the physiology of their photoreception or how their behavior is affected by various wavelengths. Most phototactic studies have examined planarian behavior using white light. Here, we describe a novel planarian behavioral assay to test responses to small ranges of visible wavelengths (red, blue, green), as well as ultraviolet (UV) and infrared (IR) which have not previously been examined. Our data show that planarians display behavioral responses across a range of wavelengths. These responses occur in a hierarchy, with the shortest wavelengths (UV) causing the most intense photophobic responses while longer wavelengths produce no effect (red) or an apparent attraction (IR). In addition, our data reveals that planarian photophobia is comprised of both a general photophobic response (that drives planarians to escape the light source regardless of wavelength) and wavelength-specific responses that encompass specific behavioral reactions to individual wavelengths. Our results serve to improve the understanding of planarian phototaxis and suggest that behavioral studies performed with white light mask a complex behavioral interaction with the environment.

  17. Planarian Phototactic Assay Reveals Differential Behavioral Responses Based on Wavelength.

    Directory of Open Access Journals (Sweden)

    Taylor R Paskin

    Full Text Available Planarians are free-living aquatic flatworms that possess a well-documented photophobic response to light. With a true central nervous system and simple cerebral eyes (ocelli, planarians are an emerging model for regenerative eye research. However, comparatively little is known about the physiology of their photoreception or how their behavior is affected by various wavelengths. Most phototactic studies have examined planarian behavior using white light. Here, we describe a novel planarian behavioral assay to test responses to small ranges of visible wavelengths (red, blue, green, as well as ultraviolet (UV and infrared (IR which have not previously been examined. Our data show that planarians display behavioral responses across a range of wavelengths. These responses occur in a hierarchy, with the shortest wavelengths (UV causing the most intense photophobic responses while longer wavelengths produce no effect (red or an apparent attraction (IR. In addition, our data reveals that planarian photophobia is comprised of both a general photophobic response (that drives planarians to escape the light source regardless of wavelength and wavelength-specific responses that encompass specific behavioral reactions to individual wavelengths. Our results serve to improve the understanding of planarian phototaxis and suggest that behavioral studies performed with white light mask a complex behavioral interaction with the environment.

  18. Chondroitinase and growth factors enhance activation and oligodendrocyte differentiation of endogenous neural precursor cells after spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Soheila Karimi-Abdolrezaee

    Full Text Available The adult spinal cord harbours a population of multipotent neural precursor cells (NPCs with the ability to replace oligodendrocytes. However, despite this capacity, proliferation and endogenous remyelination is severely limited after spinal cord injury (SCI. In the post-traumatic microenvironment following SCI, endogenous spinal NPCs mainly differentiate into astrocytes which could contribute to astrogliosis that exacerbate the outcomes of SCI. These findings emphasize a key role for the post-SCI niche in modulating the behaviour of spinal NPCs after SCI. We recently reported that chondroitin sulphate proteoglycans (CSPGs in the glial scar restrict the outcomes of NPC transplantation in SCI by reducing the survival, migration and integration of engrafted NPCs within the injured spinal cord. These inhibitory effects were attenuated by administration of chondroitinase (ChABC prior to NPC transplantation. Here, in a rat model of compressive SCI, we show that perturbing CSPGs by ChABC in combination with sustained infusion of growth factors (EGF, bFGF and PDGF-AA optimize the activation and oligodendroglial differentiation of spinal NPCs after injury. Four days following SCI, we intrathecally delivered ChABC and/or GFs for seven days. We performed BrdU incorporation to label proliferating cells during the treatment period after SCI. This strategy increased the proliferation of spinal NPCs, reduced the generation of new astrocytes and promoted their differentiation along an oligodendroglial lineage, a prerequisite for remyelination. Furthermore, ChABC and GF treatments enhanced the response of non-neural cells by increasing the generation of new vascular endothelial cells and decreasing the number of proliferating macrophages/microglia after SCI. In conclusions, our data strongly suggest that optimization of the behaviour of endogenous spinal NPCs after SCI is critical not only to promote endogenous oligodendrocyte replacement, but also to reverse

  19. Nanotubes impregnated human olfactory bulb neural stem cells promote neuronal differentiation in Trimethyltin-induced neurodegeneration rat model.

    Science.gov (United States)

    Marei, Hany E; Elnegiry, Ahmed A; Zaghloul, Adel; Althani, Asma; Afifi, Nahla; Abd-Elmaksoud, Ahmed; Farag, Amany; Lashen, Samah; Rezk, Shymaa; Shouman, Zeinab; Cenciarelli, Carlo; Hasan, Anwarul

    2017-12-01

    Neural stem cells (NSCs) are multipotent self-renewing cells that could be used in cellular-based therapy for a wide variety of neurodegenerative diseases including Alzheimer's diseases (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Being multipotent in nature, they are practically capable of giving rise to major cell types of the nervous tissue including neurons, astrocytes, and oligodendrocytes. This is in marked contrast to neural progenitor cells which are committed to a specific lineage fate. In previous studies, we have demonstrated the ability of NSCs isolated from human olfactory bulb (OB) to survive, proliferate, differentiate, and restore cognitive and motor deficits associated with AD, and PD rat models, respectively. The use of carbon nanotubes (CNTs) to enhance the survivability and differentiation potential of NSCs following their in vivo engraftment have been recently suggested. Here, in order to assess the ability of CNTs to enhance the therapeutic potential of human OBNSCs for restoring cognitive deficits and neurodegenerative lesions, we co-engrafted CNTs and human OBNSCs in TMT-neurodegeneration rat model. The present study revealed that engrafted human OBNSCS-CNTs restored cognitive deficits, and neurodegenerative changes associated with TMT-induced rat neurodegeneration model. Moreover, the CNTs seemed to provide a support for engrafted OBNSCs, with increasing their tendency to differentiate into neurons rather than into glia cells. The present study indicate the marked ability of CNTs to enhance the therapeutic potential of human OBNSCs which qualify this novel therapeutic paradigm as a promising candidate for cell-based therapy of different neurodegenerative diseases. © 2017 Wiley Periodicals, Inc.

  20. Studies on the differentiation of dopaminergic traits in human neural progenitor cells in vitro and in vivo.

    Science.gov (United States)

    Yang, Ming; Donaldson, Angela E; Marshall, Cheryl E; Shen, James; Iacovitti, Lorraine

    2004-01-01

    The development of cell replacement therapies for the treatment of neurodegenerative disorders such as Parkinson's disease (PD) may depend upon the successful differentiation of human neural stem/progenitor cells into dopamine (DA) neurons. We show here that primary human neural progenitors (HNPs) can be expanded and maintained in culture both as neurospheres (NSPs) and attached monolayers where they develop into neurons and glia. When transplanted into the 6-hydroxydopamine-lesioned rat striatum, undifferentiated NSPs survive longer (60% graft survival at 8-16 weeks vs. 30% graft survival at 8-13 weeks) and migrate farther than their attached counterparts. While both NSP and attached cells continue to express neuronal traits after transplantation, the spontaneous expression of differentiated transmitter-related traits is not observed in either cell type. However, following predifferentiation in culture using a previously described cocktail of reagents, approximately 25% of HNPs can permanently express the DA enzyme tyrosine hydroxylase (TH), even following replating and removal of the DA differentiation cocktail. When these predifferentiated HNPs are transplanted into the brain, however, TH staining is not observed, either because expression is lost or TH-expressing cells preferentially die. Consistent with the latter view is a decrease in total cell survival and migration, and an enhanced glial response in these grafts. In contrast, we found that the overall survival of HNPs is improved when cells engraft near blood vessels or CSF compartments or when they are placed into an intact unlesioned brain, suggesting that there are factors, as yet unidentified, that can better support the development of engrafted HNPs.

  1. Recovering Components of Variance from Differential Ratings of Behavior and Environment in Pairs of Relatives.

    Science.gov (United States)

    Eaves, Lindon J.; Carbonneau, Rene

    1998-01-01

    Illustrates contribution of genetic and environmental factors to differential ratings of within-family behavior and environmental differences. Maintains that, assuming differential ratings are a linear function of underlying trait differences, it is simple to recover within-family statistics, offering a more legitimate basis than comparing mean…

  2. 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

  3. The Relationship between Differentiated Instruction and Student Behavior in Georgia Middle School and High School Classrooms

    Science.gov (United States)

    Schuessler, Wesely

    2017-01-01

    The purpose of this study was to investigate the relationship between levels of implementation of Tomlinson's (2015) differentiated instruction and students' disruptive classroom behaviors. This is an area of research that has not been previously explored. Tomlinson's differentiated instruction is a process of teaching in which each student's…

  4. Homeodomain transcription factor Phox2a, via cyclic AMP-mediated activation, induces p27Kip1 transcription, coordinating neural progenitor cell cycle exit and differentiation.

    Science.gov (United States)

    Paris, Maryline; Wang, Wen-Horng; Shin, Min-Hwa; Franklin, David S; Andrisani, Ourania M

    2006-12-01

    Mechanisms coordinating neural progenitor cell cycle exit and differentiation are incompletely understood. The cyclin-dependent kinase inhibitor p27(Kip1) is transcriptionally induced, switching specific neural progenitors from proliferation to differentiation. However, neuronal differentiation-specific transcription factors mediating p27(Kip1) transcription have not been identified. We demonstrate the homeodomain transcription factor Phox2a, required for central nervous system (CNS)- and neural crest (NC)-derived noradrenergic neuron differentiation, coordinates cell cycle exit and differentiation by inducing p27(Kip1) transcription. Phox2a transcription and activation in the CNS-derived CAD cell line and primary NC cells is mediated by combined cyclic AMP (cAMP) and bone morphogenetic protein 2 (BMP2) signaling. In the CAD cellular model, cAMP and BMP2 signaling initially induces proliferation of the undifferentiated precursors, followed by p27(Kip1) transcription, G(1) arrest, and neuronal differentiation. Small interfering RNA silencing of either Phox2a or p27(Kip1) suppresses p27(Kip1) transcription and neuronal differentiation, suggesting a causal link between p27(Kip1) expression and differentiation. Conversely, ectopic Phox2a expression via the Tet-off expression system promotes accelerated CAD cell neuronal differentiation and p27(Kip1) transcription only in the presence of cAMP signaling. Importantly, endogenous or ectopically expressed Phox2a activated by cAMP signaling binds homeodomain cis-acting elements of the p27(Kip1) promoter in vivo and mediates p27(Kip1)-luciferase expression in CAD and NC cells. We conclude that developmental cues of cAMP signaling causally link Phox2a activation with p27(Kip1) transcription, thereby coordinating neural progenitor cell cycle exit and differentiation.

  5. Differential development of neuronal physiological responsiveness in two human neural stem cell lines

    OpenAIRE

    Patel Sara; Pollock Kenneth; Aouabdi Sihem; Hines Susan J; Miljan Erik A; Donato Roberta; Edwards Frances A; Sinden John D

    2007-01-01

    Abstract Background Neural stem cells (NSCs) are powerful research tools for the design and discovery of new approaches to neurodegenerative disease. Overexpression of the myc family transcription factors in human primary cells from developing cortex and mesencephalon has produced two stable multipotential NSC lines (ReNcell VM and CX) that can be continuously expanded in monolayer culture. Results In the undifferentiated state, both ReNcell VM and CX are nestin positive and have resting memb...

  6. Large-scale nanoelectrode arrays to monitor the dopaminergic differentiation of human neural stem cells

    OpenAIRE

    Kim, Tae-Hyung; Yea, Cheol-Heon; Chueng, Sy-Tsong Dean; Yin, Perry To-Tien; Conley, Brian; Dardir, Kholud; Pak, Yusin; Jung, Gun Young; Choi, Jeong-Woo; Lee, Ki-Bum

    2015-01-01

    A novel cell-based biosensing platform (Large-scale Homogeneous Nanoelectrode Arryas, LHONA) is developed using a combination of sequential laser interference lithography and electrochemical deposition methods. This enables the sensitive discrimination of dopaminergic cells from other types of neural cells in a completely non-destructive manner owing to its enhanced biocompatibility and excellent electrochemical properties. As such, this platform/detection strategy holds great potential as an...

  7. Large-Scale Nanoelectrode Arrays to Monitor the Dopaminergic Differentiation of Human Neural Stem Cells.

    Science.gov (United States)

    Kim, Tae-Hyung; Yea, Cheol-Heon; Chueng, Sy-Tsong Dean; Yin, Perry To-Tien; Conley, Brian; Dardir, Kholud; Pak, Yusin; Jung, Gun Young; Choi, Jeong-Woo; Lee, Ki-Bum

    2015-11-04

    A novel cell-based biosensing platform is developed using a combination of sequential laser interference lithography and electrochemical deposition methods. This enables the sensitive discrimination of dopaminergic cells from other types of neural cells in a completely nondestructive manner. This platform and detection strategy may become an effective noninvasive in situ monitoring tool that can be used to determine stem cell fate for various regenerative applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Factors Influencing the Differentiation of Dopaminergic Traits in Transplanted Neural Stem Cells

    OpenAIRE

    Yang, Ming; Donaldson, Angela E.; Jiang, Yubao; Iacovitti, Lorraine

    2003-01-01

    Our previous studies demonstrated that when neural stem cells (NSCs) of the C17.2 clonal line are transplanted into the intact or 6-hydroxydopamine (6-OHDA) lesioned rat striatum, in most, but not all grafts, cells spontaneously express the dopamine (DA) biosynthetic enzymes, tyrosine hydroxylase (TH), and aromatic l-amino acid decarboxylase (Yang, M., Stull, N. D., Snyder, E. Y., Berk, M. A., and Iacovitti, L. (2002). Exp. Neurol.).These results suggested that there were certain conditions w...

  9. Behavioral change and its neural correlates in visual agnosia after expertise training.

    Science.gov (United States)

    Behrmann, Marlene; Marotta, Jonathan; Gauthier, Isabel; Tarr, Michael J; McKeeff, Thomas J

    2005-04-01

    Agnosia, the impairment in object and face recognition despite intact vision and intelligence, is one of the most intriguing and debilitating neuropsychological deficits. The goal of this study was to determine whether S.M., an individual with longstanding visual agnosia and concomitant prosopagnosia, can be retrained to perform visual object recognition and, if so, what neural substrates mediate this reacquisition. Additionally, of interest is the extent to which training on one type of visual stimulus generalizes to other visual stimuli, as this informs our understanding of the organization of ventral visual cortex. Greebles were chosen as the stimuli for retraining given that, in neurologically normal individuals, these stimuli can engage the fusiform face area. Posttraining, S.M. showed significant improvement in recognizing Greebles, although he did not attain normal levels of performance. He was also able to recognize untrained Greebles and showed improvement in recognizing common objects. Surprisingly, his performance on face recognition, albeit poor initially, was even more impaired following training. A comparison of pre- and postintervention functional neuroimaging data mirrored the behavioral findings: Face-selective voxels in the fusiform gyrus prior to training were no longer so and were, in fact, more Greeble-selective. The findings indicate potential for experience-dependent dynamic reorganization in agnosia with the possibility that residual neural tissue, with limited capacity, will compete for representations.

  10. Learning to Associate Auditory and Visual Stimuli: Behavioral and Neural Mechanisms

    Science.gov (United States)

    Altieri, Nicholas; Stevenson, Ryan; Wallace, Mark T.; Wenger, Michael J.

    2014-01-01

    The ability to effectively combine sensory inputs across modalities is vital for acquiring a unified percept of events. For example, watching a hammer hit a nail while simultaneously identifying the sound as originating from the event requires the ability to identify spatio-temporal congruencies and statistical regularities. In this study, we applied a reaction time (RT) and hazard function measure known as capacity (e.g., Townsend and Ashby, 1978) to quantify the extent to which observers learn paired associations between simple auditory and visual patterns in a model theoretic manner. As expected, results showed that learning was associated with an increase in accuracy, but more significantly, an increase in capacity. The aim of this study was to associate capacity measures of multisensory learning, with neural based measures, namely mean Global Field Power (GFP). We observed a co-variation between an increase in capacity, and a decrease in GFP amplitude as learning occurred. This suggests that capacity constitutes a reliable behavioral index of efficient energy expenditure in the neural domain. PMID:24276220

  11. AAV-Mediated Anterograde Transsynaptic Tagging: Mapping Corticocollicular Input-Defined Neural Pathways for Defense Behaviors.

    Science.gov (United States)

    Zingg, Brian; Chou, Xiao-Lin; Zhang, Zheng-Gang; Mesik, Lukas; Liang, Feixue; Tao, Huizhong Whit; Zhang, Li I

    2017-01-04

    To decipher neural circuits underlying brain functions, viral tracers are widely applied to map input and output connectivity of neuronal populations. Despite the successful application of retrograde transsynaptic viruses for identifying presynaptic neurons of transduced neurons, analogous anterograde transsynaptic tools for tagging postsynaptically targeted neurons remain under development. Here, we discovered that adeno-associated viruses (AAV1 and AAV9) exhibit anterograde transsynaptic spread properties. AAV1-Cre from transduced presynaptic neurons effectively and specifically drives Cre-dependent transgene expression in selected postsynaptic neuronal targets, thus allowing axonal tracing and functional manipulations of the latter input-defined neuronal population. Its application in superior colliculus (SC) reveals that SC neuron subpopulations receiving corticocollicular projections from auditory and visual cortex specifically drive flight and freezing, two different types of defense behavior, respectively. Together with an intersectional approach, AAV-mediated anterograde transsynaptic tagging can categorize neurons by their inputs and molecular identity, and allow forward screening of distinct functional neural pathways embedded in complex brain circuits. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Differential neural correlates underlie judgment of learning and subsequent memory performance

    Directory of Open Access Journals (Sweden)

    Haiyan eYang

    2015-11-01

    Full Text Available Judgment of learning (JOL plays a pivotal role in self-regulated learning. Although the JOLs are in general accurate, important deviations from memory performance are often reported, especially when the JOLs are made immediately after learning. Nevertheless, existing studies have not clearly dissociated the neural processes underlying subjective JOL and objective memory. In the present study, participants were asked to study a list of words that would be tested one day later. Immediately after learning, participants predicted how likely they would remember that item. Critically, the JOL was performed on only half of the studied items to avoid its contamination on subsequent memory. We found that during encoding, compared to items later judged as will be forgotten, those judged as will be remembered showed stronger activities in the default-mode network, including the ventromedial prefrontal cortex (PFC and posterior cingulate cortex, as well as weaker functional connectivity between the left dorsolateral PFC and the visual cortex. The exact opposite pattern was found when comparing items that were actually remembered with that were later forgotten. These important neural dissociations between JOL and memory performance shed light on the neural mechanisms of human metamemory bias.

  13. The differential role of smell and taste for eating behavior

    NARCIS (Netherlands)

    Boesveldt, Sanne; Graaf, de Kees

    2017-01-01

    Food choice and food intake are guided by both sensory and metabolic processes. The senses of taste and smell play a key role in the sensory effects on choice and intake. This article provides a comprehensive overview of, and will argue for, the differential role of smell and taste for eating

  14. 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.

  15. Serotonin versus catecholamine deficiency: behavioral and neural effects of experimental depletion in remitted depression

    Science.gov (United States)

    Homan, P; Neumeister, A; Nugent, A C; Charney, D S; Drevets, W C; Hasler, G

    2015-01-01

    Despite immense efforts into development of new antidepressant drugs, the increases of serotoninergic and catecholaminergic neurotransmission have remained the two major pharmacodynamic principles of current drug treatments for depression. Consequently, psychopathological or biological markers that predict response to drugs that selectively increase serotonin and/or catecholamine neurotransmission hold the potential to optimize the prescriber's selection among currently available treatment options. The aim of this study was to elucidate the differential symptomatology and neurophysiology in response to reductions in serotonergic versus catecholaminergic neurotransmission in subjects at high risk of depression recurrence. Using identical neuroimaging procedures with [18F] fluorodeoxyglucose positron emission tomography after tryptophan depletion (TD) and catecholamine depletion (CD), subjects with remitted depression were compared with healthy controls in a double-blind, randomized, crossover design. Although TD induced significantly more depressed mood, sadness and hopelessness than CD, CD induced more inactivity, concentration difficulties, lassitude and somatic anxiety than TD. CD specifically increased glucose metabolism in the bilateral ventral striatum and decreased glucose metabolism in the bilateral orbitofrontal cortex, whereas TD specifically increased metabolism in the right prefrontal cortex and the posterior cingulate cortex. Although we found direct associations between changes in brain metabolism and induced depressive symptoms following CD, the relationship between neural activity and symptoms was less clear after TD. In conclusion, this study showed that serotonin and catecholamines have common and differential roles in the pathophysiology of depression. PMID:25781231

  16. Dynamical Behavior of Delayed Reaction-Diffusion Hopfield Neural Networks Driven by Infinite Dimensional Wiener Processes.

    Science.gov (United States)

    Liang, Xiao; Wang, Linshan; Wang, Yangfan; Wang, Ruili

    2016-09-01

    In this paper, we focus on the long time behavior of the mild solution to delayed reaction-diffusion Hopfield neural networks (DRDHNNs) driven by infinite dimensional Wiener processes. We analyze the existence, uniqueness, and stability of this system under the local Lipschitz function by constructing an appropriate Lyapunov-Krasovskii function and utilizing the semigroup theory. Some easy-to-test criteria affecting the well-posedness and stability of the networks, such as infinite dimensional noise and diffusion effect, are obtained. The criteria can be used as theoretic guidance to stabilize DRDHNNs in practical applications when infinite dimensional noise is taken into consideration. Meanwhile, considering the fact that the standard Brownian motion is a special case of infinite dimensional Wiener process, we undertake an analysis of the local Lipschitz condition, which has a wider range than the global Lipschitz condition. Two samples are given to examine the availability of the results in this paper. Simulations are also given using the MATLAB.

  17. Informing others is associated with behavioral and neural signatures of value.

    Science.gov (United States)

    Tamir, Diana I; Zaki, Jamil; Mitchell, Jason P

    2015-12-01

    One of the many proclivities of our species is the drive to share information with others. What drives this unusual proclivity for propagating knowledge? Here, we test a common prediction made by recent theories in this domain: that individuals value opportunities to inform others. Two sets of studies supported this hypothesis. Behaviorally, individuals gave up money to inform others, even in "minimalistic" settings under which informing neither improved participants' reputation nor provided material benefits to information recipients. Neurally, opportunities to inform others engaged brain regions associated with motivation and reward, including the nucleus accumbens and ventromedial prefrontal cortex. Together, these findings suggest that people place intrinsic value on sharing information with others. (c) 2015 APA, all rights reserved).

  18. 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.

  19. Coexisting Behaviors of Asymmetric Attractors in Hyperbolic-Type Memristor based Hopfield Neural Network

    Directory of Open Access Journals (Sweden)

    Bocheng Bao

    2017-08-01

    Full Text Available A new hyperbolic-type memristor emulator is presented and its frequency-dependent pinched hysteresis loops are analyzed by numerical simulations and confirmed by hardware experiments. Based on the emulator, a novel hyperbolic-type memristor based 3-neuron Hopfield neural network (HNN is proposed, which is achieved through substituting one coupling-connection weight with a memristive synaptic weight. It is numerically shown that the memristive HNN has a dynamical transition from chaotic, to periodic, and further to stable point behaviors with the variations of the memristor inner parameter, implying the stabilization effect of the hyperbolic-type memristor on the chaotic HNN. Of particular interest, it should be highly stressed that for different memristor inner parameters, different coexisting behaviors of asymmetric attractors are emerged under different initial conditions, leading to the existence of multistable oscillation states in the memristive HNN. Furthermore, by using commercial discrete components, a nonlinear circuit is designed and PSPICE circuit simulations and hardware experiments are performed. The results simulated and captured from the realization circuit are consistent with numerical simulations, which well verify the facticity of coexisting asymmetric attractors' behaviors.

  20. 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.

  1. 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.

  2. Neural substrates of contingency learning and executive control: dissociating physical, valuative, and behavioral changes

    Directory of Open Access Journals (Sweden)

    O'Dhaniel A Mullette-Gillman

    2009-09-01

    Full Text Available Contingency learning is fundamental to cognition. Knowledge about environmental contingencies allows behavioral flexibility, as executive control processes accommodate the demands of novel or changing environments. Studies of experiential learning have focused on the relationship between actions and the values of associated outcomes. However, outcome values have often been confounded with the physical changes in the outcomes themselves. Here, we dissociated contingency learning into valuative and non-valuative forms, using a novel version of the two-alternative choice task, while measuring the neural effects of contingency changes using functional magnetic resonance imaging (fMRI. Changes in value-relevant contingencies evoked activation in the lateral prefrontal cortex (LPFC, posterior parietal cortex (PPC, and dorsomedial prefrontal cortex (DMPFC consistent with prior results (e.g., reversal-learning paradigms. Changes in physical contingencies unrelated to value or to action produced similar activations within the LPFC, indicating that LPFC may engage in generalized contingency learning that is not specific to valuation. In contrast, contingency changes that required behavioral shifts evoked activation localized to the DMPFC, supplementary motor, and precentral cortices, suggesting that these regions play more specific roles within the executive control of behavior.

  3. 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.

  4. Neural Circuitry That Mediates Behavior Governing the Tradeoffs Between Survival and Reproduction in Caenorhabditis elegans.

    Science.gov (United States)

    Emmons, Scott W

    2017-12-01

    In all outcrossing sexual species there is a mechanism that brings two parents together. For animals, this reproductive requirement may at times conflict with other needs, such as foraging for food. This tension has been studied using the tiny (1 mm) nematode worm, Caenorhabditis elegans. In a trade off between certainty of survival and possibility of reproduction, the C. elegans male will abandon a food patch lacking mates and explore its environment to find one where mates are present. A quantitative behavioral assay has been used to study the behavioral mechanism of mate searching and nutritional, sexual, and neurohormonal pathways that influence the underlying drive state. Taking advantage of the known connectivity of the C. elegans nervous system, neural pathways have been identified that influence the male's behavior in the presence of food with and without mates. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  5. 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.

  6. 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.

  7. Goal-Directed Behavior and Instrumental Devaluation: A Neural System-Level Computational Model.

    Science.gov (United States)

    Mannella, Francesco; Mirolli, Marco; Baldassarre, Gianluca

    2016-01-01

    Devaluation is the key experimental paradigm used to demonstrate the presence of instrumental behaviors guided by goals in mammals. We propose a neural system-level computational model to address the question of which brain mechanisms allow the current value of rewards to control instrumental actions. The model pivots on and shows the computational soundness of the hypothesis for which the internal representation of instrumental manipulanda (e.g., levers) activate the representation of rewards (or "action-outcomes", e.g., foods) while attributing to them a value which depends on the current internal state of the animal (e.g., satiation for some but not all foods). The model also proposes an initial hypothesis of the integrated system of key brain components supporting this process and allowing the recalled outcomes to bias action selection: (a) the sub-system formed by the basolateral amygdala and insular cortex acquiring the manipulanda-outcomes associations and attributing the current value to the outcomes; (b) three basal ganglia-cortical loops selecting respectively goals, associative sensory representations, and actions; (c) the cortico-cortical and striato-nigro-striatal neural pathways supporting the selection, and selection learning, of actions based on habits and goals. The model reproduces and explains the results of several devaluation experiments carried out with control rats and rats with pre- and post-training lesions of the basolateral amygdala, the nucleus accumbens core, the prelimbic cortex, and the dorso-medial striatum. The results support the soundness of the hypotheses of the model and show its capacity to integrate, at the system-level, the operations of the key brain structures underlying devaluation. Based on its hypotheses and predictions, the model also represents an operational framework to support the design and analysis of new experiments on the motivational aspects of goal-directed behavior.

  8. Emotion regulation in social anxiety disorder: behavioral and neural responses to three socio-emotional tasks

    Science.gov (United States)

    2013-01-01

    Background Social anxiety disorder (SAD) is thought to involve deficits in emotion regulation, and more specifically, deficits in cognitive reappraisal. However, evidence for such deficits is mixed. Methods Using functional magnetic resonance imaging (fMRI) of blood oxygen-level dependent (BOLD) signal, we examined reappraisal-related behavioral and neural responses in 27 participants with generalized SAD and 27 healthy controls (HC) during three socio-emotional tasks: (1) looming harsh faces (Faces); (2) videotaped actors delivering social criticism (Criticism); and (3) written autobiographical negative self-beliefs (Beliefs). Results Behaviorally, compared to HC, participants with SAD had lesser reappraisal-related reduction in negative emotion in the Beliefs task. Neurally, compared to HC, participants with SAD had lesser BOLD responses in reappraisal-related brain regions when reappraising faces, in visual and attention related regions when reappraising criticism, and in the left superior temporal gyrus when reappraising beliefs. Examination of the temporal dynamics of BOLD responses revealed late reappraisal-related increased responses in HC, compared to SAD. In addition, the dorsomedial prefrontal cortex (DMPFC), which showed reappraisal-related increased activity in both groups, had similar temporal dynamics in SAD and HC during the Faces and Criticism tasks, but greater late response increases in HC, compared to SAD, during the Beliefs task. Reappraisal-related greater late DMPFC responses were associated with greater percent reduction in negative emotion ratings in SAD patients. Conclusions These results suggest a dysfunction of cognitive reappraisal in SAD patients, with overall reduced late brain responses in prefrontal regions, particularly when reappraising faces. Decreased late activity in the DMPFC might be associated with deficient reappraisal and greater negative reactivity. Trial registration ClinicalTrials.gov identifier: NCT00380731 PMID

  9. Spatial interactions in the superior colliculus predict saccade behavior in a neural field model.

    Science.gov (United States)

    Marino, Robert A; Trappenberg, Thomas P; Dorris, Michael; Munoz, Douglas P

    2012-02-01

    During natural vision, eye movements are dynamically controlled by the combinations of goal-related top-down (TD) and stimulus-related bottom-up (BU) neural signals that map onto objects or locations of interest in the visual world. In primates, both BU and TD signals converge in many areas of the brain, including the intermediate layers of the superior colliculus (SCi), a midbrain structure that contains a retinotopically coded map for saccades. How TD and BU signals combine or interact within the SCi map to influence saccades remains poorly understood and actively debated. It has been proposed that winner-take-all competition between these signals occurs dynamically within this map to determine the next location for gaze. Here, we examine how TD and BU signals interact spatially within an artificial two-dimensional dynamic winner-take-all neural field model of the SCi to influence saccadic RT (SRT). We measured point images (spatially organized population activity on the SC map) physiologically to inform the TD and BU model parameters. In this model, TD and BU signals interacted nonlinearly within the SCi map to influence SRT via changes to the (1) spatial size or extent of individual signals, (2) peak magnitude of individual signals, (3) total number of competing signals, and (4) the total spatial separation between signals in the visual field. This model reproduced previous behavioral studies of TD and BU influences on SRT and accounted for multiple inconsistencies between them. This is achieved by demonstrating how, under different experimental conditions, the spatial interactions of TD and BU signals can lead to either increases or decreases in SRT. Our results suggest that dynamic winner-take-all modeling with local excitation and distal inhibition in two dimensions accurately reflects both the physiological activity within the SCi map and the behavioral changes in SRT that result from BU and TD manipulations.

  10. Inhibitory control and trait aggression: neural and behavioral insights using the emotional stop signal task.

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    Pawliczek, Christina M; Derntl, Birgit; Kellermann, Thilo; Kohn, Nils; Gur, Ruben C; Habel, Ute

    2013-10-01

    Deficits in response inhibition and heightened impulsivity have been linked to psychiatric disorders and aggression. They have been investigated in clinical groups as well as individuals with trait characteristics, yielding insights into the underlying neural and behavioral mechanisms of response inhibition and impulsivity. The motor inhibition tasks employed in most studies, however, have lacked an emotional component, which is crucial given that both response inhibition and impulsivity attain salience within a socio-emotional context. For this fMRI study, we selected a group with high trait aggression (HA, n=17) and one with low trait aggression (LA, n=16) from 550 males who had completed an Aggression Questionnaire. Neural activation was compared to an emotional version (including angry and neutral faces) of the stop signal task. Behavioral results revealed impaired response inhibition in HA, associated with higher motor impulsivity. This was accompanied by attenuated activation in brain regions involved in response inhibition, including the pre-supplementary motor area (SMA) and motor cortex. Together, these findings offer evidence that a reduced inhibition capacity is present in HA. Notably, response inhibition improved during anger trials in both groups, suggesting a facilitation effect through heightened activation in the related brain regions. In both groups, inclusion of the anger stimuli enhanced the activation of the motor and somatosensory areas, which modulate executive control, and of limbic regions including the amygdala. In summary, the investigation of response inhibition in individuals with high and low trait characteristics affords useful insights into the underlying distinct processing mechanisms. It can contribute to the investigation of trait markers in a clinical context without having to deal with the complex mechanisms of a clinical disorder itself. In contrast, the mechanisms of emotional response inhibition did not differ between groups

  11. White blood cell differential count of maturation stages in bone marrow smear using dual-stage convolutional neural networks.

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    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

  12. 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

  13. Deep Learning with Convolutional Neural Network for Differentiation of Liver Masses at Dynamic Contrast-enhanced CT: A Preliminary Study.

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    Yasaka, Koichiro; Akai, Hiroyuki; Abe, Osamu; Kiryu, Shigeru

    2017-10-27

    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

  14. Distributed recurrent neural forward models with synaptic adaptation and CPG-based control for complex behaviors of walking robots.

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    Dasgupta, Sakyasingha; Goldschmidt, Dennis; Wörgötter, Florentin; Manoonpong, Poramate

    2015-01-01

    Walking animals, like stick insects, cockroaches or ants, demonstrate a fascinating range of locomotive abilities and complex behaviors. The locomotive behaviors can consist of a variety of walking patterns along with adaptation that allow the animals to deal with changes in environmental conditions, like uneven terrains, gaps, obstacles etc. Biological study has revealed that such complex behaviors are a result of a combination of biomechanics and neural mechanism thus representing the true nature of embodied interactions. While the biomechanics helps maintain flexibility and sustain a variety of movements, the neural mechanisms generate movements while making appropriate predictions crucial for achieving adaptation. Such predictions or planning ahead can be achieved by way of internal models that are grounded in the overall behavior of the animal. Inspired by these findings, we present here, an artificial bio-inspired walking system which effectively combines biomechanics (in terms of the body and leg structures) with the underlying neural mechanisms. The neural mechanisms consist of (1) central pattern generator based control for generating basic rhythmic patterns and coordinated movements, (2) distributed (at each leg) recurrent neural network based adaptive forward models with efference copies as internal models for sensory predictions and instantaneous state estimations, and (3) searching and elevation control for adapting the movement of an individual leg to deal with different environmental conditions. Using simulations we show that this bio-inspired approach with adaptive internal models allows the walking robot to perform complex locomotive behaviors as observed in insects, including walking on undulated terrains, crossing large gaps, leg damage adaptations, as well as climbing over high obstacles. Furthermore, we demonstrate that the newly developed recurrent network based approach to online forward models outperforms the adaptive neuron forward models

  15. Identification of neural biomarkers of altered sexual differentiation following gestational exposure###

    Science.gov (United States)

    Sexual differentiation of the brain occurs during late gestation through the early postnatal period. The development of the phenotypical male brain is dependent on the aromatization of circulating testosterone to estradiol. Exposure to endocrine disrupting chemicals (EDCs) duri...

  16. IDENTIFICATION OF NEURAL BIOMARKERS OF ALTERED SEXUAL DIFFERENTIATION FOLLOWING GESTATIONAL EXPOSURE***

    Science.gov (United States)

    Sexual differentiation of the brain occurs during late gestation through the early postnatal period. The development of the phenotypical male brain is dependent on the aromatization of circulati