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Une nouvelle procédure d'identification des paramètres de lois cohésives

OpenAIRE

Blaysat , Benoît; Hoefnagels , Johan ,; Lubineau , Gilles; Geers , Marc

2013-01-01

International audience; L'objectif est ici d'introduire un nouvel outil de caractérisation de lois cohésives, modèle le plus couramment utilisé pour décrire et simuler le phénomène de délaminage. Cet outil est basé sur une méthode de corrélation d'image globale, où la définition de l'espace de recherche cinématique est adéquatement choisie. Après avoir présenté le principe de cette méthode, on s'intéresse à sa validation, ainsi qu'à son comportement au bruit. Cette validation est réalisée num...

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Neuroprotective effects of ginsenoside Rg1-induced neural stem cell transplantation on hypoxic-ischemic encephalopathy

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Ying-bo Li

2015-01-01

Full Text Available Ginsenoside Rg1 is the major pharmacologically active component of ginseng, and is reported to have various therapeutic actions. To determine whether it induces the differentiation of neural stem cells, and whether neural stem cell transplantation after induction has therapeutic effects on hypoxic-ischemic encephalopathy, we cultured neural stem cells in 10-80 µM ginsenoside Rg1. Immunohistochemistry revealed that of the concentrations tested, 20 mM ginsenoside Rg1 had the greatest differentiation-inducing effect and was the concentration used for subsequent experiments. Whole-cell patch clamp showed that neural stem cells induced by 20 µM ginsenoside Rg1 were more mature than non-induced cells. We then established neonatal rat models of hypoxic-ischemic encephalopathy using the suture method, and ginsenoside Rg1-induced neural stem cells were transplanted via intracerebroventricular injection. These tests confirmed that neural stem cells induced by ginsenoside had fewer pathological lesions and had a significantly better behavioral capacity than model rats that received saline. Transplanted neural stem cells expressed neuron-specific enolase, and were mainly distributed in the hippocampus and cerebral cortex. The present data suggest that ginsenoside Rg1-induced neural stem cells can promote the partial recovery of complicated brain functions in models of hypoxic-ischemic encephalopathy.

NMDA Receptor Signaling Is Important for Neural Tube Formation and for Preventing Antiepileptic Drug-Induced Neural Tube Defects.

Science.gov (United States)

Sequerra, Eduardo B; Goyal, Raman; Castro, Patricio A; Levin, Jacqueline B; Borodinsky, Laura N

2018-05-16

Failure of neural tube closure leads to neural tube defects (NTDs), which can have serious neurological consequences or be lethal. Use of antiepileptic drugs (AEDs) during pregnancy increases the incidence of NTDs in offspring by unknown mechanisms. Here we show that during Xenopus laevis neural tube formation, neural plate cells exhibit spontaneous calcium dynamics that are partially mediated by glutamate signaling. We demonstrate that NMDA receptors are important for the formation of the neural tube and that the loss of their function induces an increase in neural plate cell proliferation and impairs neural cell migration, which result in NTDs. We present evidence that the AED valproic acid perturbs glutamate signaling, leading to NTDs that are rescued with varied efficacy by preventing DNA synthesis, activating NMDA receptors, or recruiting the NMDA receptor target ERK1/2. These findings may prompt mechanistic identification of AEDs that do not interfere with neural tube formation. SIGNIFICANCE STATEMENT Neural tube defects are one of the most common birth defects. Clinical investigations have determined that the use of antiepileptic drugs during pregnancy increases the incidence of these defects in the offspring by unknown mechanisms. This study discovers that glutamate signaling regulates neural plate cell proliferation and oriented migration and is necessary for neural tube formation. We demonstrate that the widely used antiepileptic drug valproic acid interferes with glutamate signaling and consequently induces neural tube defects, challenging the current hypotheses arguing that they are side effects of this antiepileptic drug that cause the increased incidence of these defects. Understanding the mechanisms of neurotransmitter signaling during neural tube formation may contribute to the identification and development of antiepileptic drugs that are safer during pregnancy. Copyright © 2018 the authors 0270-6474/18/384762-12$15.00/0.

Structural Analysis of Three-dimensional Human Neural Tissue derived from Induced Pluripotent Stem Cells

DEFF Research Database (Denmark)

Terrence Brooks, Patrick; Rasmussen, Mikkel Aabech; Hyttel, Poul

2016-01-01

Objective: The present study aimed at establishing a method for production of a three-dimensional (3D) human neural tissue derived from induced pluripotent stem cells (iPSCs) and analyzing the outcome by a combination of tissue ultrastructure and expression of neural markers. Methods: A two......-step cell culture procedure was implemented by subjecting human iPSCs to a 3D scaffoldbased neural differentiation protocol. First, neural fate-inducing small molecules were used to create a neuroepithelial monolayer. Second, the monolayer was trypsinized into single cells and seeded into a porous...... polystyrene scaffold and further cultured to produce a 3D neural tissue. The neural tissue was characterized by a combination of immunohistochemistry and transmission electron microscopy (TEM). Results: iPSCs developed into a 3D neural tissue expressing markers for neural progenitor cells, early neural...

Il De uno alla luce dell’Exemplum tractatus de iustitia universali, sive de fontibus iuris di Francis Bacon

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Romana Bassi

2016-11-01

Full Text Available [Reading “De uno” in light of Francis Bacon’s “Exemplum tractatus de iustitia universali, sive de fontibus iuris”]. Although Vico was admittedly disappointed by Bacon’s Exemplum tractatus, a parallel reading of this text and De uno can provide insights as to how Vico ended up having to confront a series of issues: how does the universal law project itself into history? Where does the law stem from? Is there a link between law, occasion, and utility? What are the sources and the scope of authority? How does violence affect the law? What role for religion and piety? How to devise a philology for the laws and ancient fables? Bacon’s scattered aphorisms offer glimpses into problems which find a solution in the all-encompassing order of De uno.

Comparison of 2D and 3D neural induction methods for the generation of neural progenitor cells from human induced pluripotent stem cells

DEFF Research Database (Denmark)

Chandrasekaran, Abinaya; Avci, Hasan; Ochalek, Anna

2017-01-01

Neural progenitor cells (NPCs) from human induced pluripotent stem cells (hiPSCs) are frequently induced using 3D culture methodologies however, it is unknown whether spheroid-based (3D) neural induction is actually superior to monolayer (2D) neural induction. Our aim was to compare the efficiency......), cortical layer (TBR1, CUX1) and glial markers (SOX9, GFAP, AQP4). Electron microscopy demonstrated that both methods resulted in morphologically similar neural rosettes. However, quantification of NPCs derived from 3D neural induction exhibited an increase in the number of PAX6/NESTIN double positive cells...... the electrophysiological properties between the two induction methods. In conclusion, 3D neural induction increases the yield of PAX6+/NESTIN+ cells and gives rise to neurons with longer neurites, which might be an advantage for the production of forebrain cortical neurons, highlighting the potential of 3D neural...

Inactivity-induced respiratory plasticity: Protecting the drive to breathe in disorders that reduce respiratory neural activity☆

Science.gov (United States)

Strey, K.A.; Baertsch, N.A.; Baker-Herman, T.L.

2013-01-01

Multiple forms of plasticity are activated following reduced respiratory neural activity. For example, in ventilated rats, a central neural apnea elicits a rebound increase in phrenic and hypoglossal burst amplitude upon resumption of respiratory neural activity, forms of plasticity called inactivity-induced phrenic and hypoglossal motor facilitation (iPMF and iHMF), respectively. Here, we provide a conceptual framework for plasticity following reduced respiratory neural activity to guide future investigations. We review mechanisms giving rise to iPMF and iHMF, present new data suggesting that inactivity-induced plasticity is observed in inspiratory intercostals (iIMF) and point out gaps in our knowledge. We then survey conditions relevant to human health characterized by reduced respiratory neural activity and discuss evidence that inactivity-induced plasticity is elicited during these conditions. Understanding the physiological impact and circumstances in which inactivity-induced respiratory plasticity is elicited may yield novel insights into the treatment of disorders characterized by reductions in respiratory neural activity. PMID:23816599

Wnt/Yes-Associated Protein Interactions During Neural Tissue Patterning of Human Induced Pluripotent Stem Cells.

Science.gov (United States)

Bejoy, Julie; Song, Liqing; Zhou, Yi; Li, Yan

2018-04-01

Human induced pluripotent stem cells (hiPSCs) have special ability to self-assemble into neural spheroids or mini-brain-like structures. During the self-assembly process, Wnt signaling plays an important role in regional patterning and establishing positional identity of hiPSC-derived neural progenitors. Recently, the role of Wnt signaling in regulating Yes-associated protein (YAP) expression (nuclear or cytoplasmic), the pivotal regulator during organ growth and tissue generation, has attracted increasing interests. However, the interactions between Wnt and YAP expression for neural lineage commitment of hiPSCs remain poorly explored. The objective of this study is to investigate the effects of Wnt signaling and YAP expression on the cellular population in three-dimensional (3D) neural spheroids derived from hiPSCs. In this study, Wnt signaling was activated using CHIR99021 for 3D neural spheroids derived from human iPSK3 cells through embryoid body formation. Our results indicate that Wnt activation induces nuclear localization of YAP and upregulates the expression of HOXB4, the marker for hindbrain/spinal cord. By contrast, the cells exhibit more rostral forebrain neural identity (expression of TBR1) without Wnt activation. Cytochalasin D was then used to induce cytoplasmic YAP and the results showed the decreased HOXB4 expression. In addition, the incorporation of microparticles in the neural spheroids was investigated for the perturbation of neural patterning. This study may indicate the bidirectional interactions of Wnt signaling and YAP expression during neural tissue patterning, which have the significance in neurological disease modeling, drug screening, and neural tissue regeneration.

dNTP deficiency induced by HU via inhibiting ribonucleotide reductase affects neural tube development

International Nuclear Information System (INIS)

Guan, Zhen; Wang, Xiuwei; Dong, Yanting; Xu, Lin; Zhu, Zhiqiang; Wang, Jianhua; Zhang, Ting; Niu, Bo

2015-01-01

Highlights: • Murine NTDs were successfully induced by means of hydroxyurea (HU). • The impairment of dNTP was induced via inhibition of ribonucleotide reductase. • dNTP deficiency induced by HU caused defective DNA synthesis and repair. • Abnormal apoptosis and proliferation induced by HU affected neural tube development. - Abstract: Exposure to environmental toxic chemicals in utero during the neural tube development period can cause developmental disorders. To evaluate the disruption of neural tube development programming, the murine neural tube defects (NTDs) model was induced by interrupting folate metabolism using methotrexate in our previous study. The present study aimed to examine the effects of dNTP deficiency induced by hydroxyurea (HU), a specific ribonucleotide reductase (RNR) inhibitor, during murine neural tube development. Pregnant C57BL/6J mice were intraperitoneally injected with various doses of HU on gestation day (GD) 7.5, and the embryos were checked on GD 11.5. RNR activity and deoxynucleoside triphosphate (dNTP) levels were measured in the optimal dose. Additionally, DNA damage was examined by comet analysis and terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling (TUNEL) assay. Cellular behaviors in NTDs embryos were evaluated with phosphorylation of histone H3 (PH-3) and caspase-3 using immunohistochemistry and western blot analysis. The results showed that NTDs were observed mostly with HU treatment at an optimal dose of 225 mg/kg b/w. RNR activity was inhibited and dNTP levels were decreased in HU-treated embryos with NTDs. Additionally, increased DNA damage, decreased proliferation, and increased caspase-3 were significant in NTDs embryos compared to the controls. Results indicated that HU induced murine NTDs model by disturbing dNTP metabolism and further led to the abnormal cell balance between proliferation and apoptosis

Neural stem cells induce bone-marrow-derived mesenchymal stem cells to generate neural stem-like cells via juxtacrine and paracrine interactions

International Nuclear Information System (INIS)

Alexanian, Arshak R.

2005-01-01

Several recent reports suggest that there is far more plasticity that previously believed in the developmental potential of bone-marrow-derived cells (BMCs) that can be induced by extracellular developmental signals of other lineages whose nature is still largely unknown. In this study, we demonstrate that bone-marrow-derived mesenchymal stem cells (MSCs) co-cultured with mouse proliferating or fixed (by paraformaldehyde or methanol) neural stem cells (NSCs) generate neural stem cell-like cells with a higher expression of Sox-2 and nestin when grown in NS-A medium supplemented with N2, NSC conditioned medium (NSCcm) and bFGF. These neurally induced MSCs eventually differentiate into β-III-tubulin and GFAP expressing cells with neuronal and glial morphology when grown an additional week in Neurobasal/B27 without bFGF. We conclude that juxtacrine interaction between NSCs and MSCs combined with soluble factors released from NSCs are important for generation of neural-like cells from bone-marrow-derived adherent MSCs

Progress of research on cytoskeleton and neural cell migration obstacle induced by ionizing radiation

International Nuclear Information System (INIS)

Qiu Jun; Wu Cuiping; Wang Mingming

2012-01-01

The dynamic changes of the microtubules and microfilaments provide the main force that drives the normal migration. Biological effects in tissues and cells induced by ionizing radiation are closely correlated with the changes happening to the cytoskeleton. It is that the ionizing radiation can induce the depolymeration of microfilaments and the assembly obstacles of microtubules, and make neural cell incapable of entering the model of migration or abnormally migrate. The effects of relevant changes of the cytoskeleton induced by irradiation on neural cell migration were discussed in this paper. (authors)

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.

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

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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.

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.

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.

Comparison of 2D and 3D neural induction methods for the generation of neural progenitor cells from human induced pluripotent stem cells.

Science.gov (United States)

Chandrasekaran, Abinaya; Avci, Hasan X; Ochalek, Anna; Rösingh, Lone N; Molnár, Kinga; László, Lajos; Bellák, Tamás; Téglási, Annamária; Pesti, Krisztina; Mike, Arpad; Phanthong, Phetcharat; Bíró, Orsolya; Hall, Vanessa; Kitiyanant, Narisorn; Krause, Karl-Heinz; Kobolák, Julianna; Dinnyés, András

2017-12-01

Neural progenitor cells (NPCs) from human induced pluripotent stem cells (hiPSCs) are frequently induced using 3D culture methodologies however, it is unknown whether spheroid-based (3D) neural induction is actually superior to monolayer (2D) neural induction. Our aim was to compare the efficiency of 2D induction with 3D induction method in their ability to generate NPCs, and subsequently neurons and astrocytes. Neural differentiation was analysed at the protein level qualitatively by immunocytochemistry and quantitatively by flow cytometry for NPC (SOX1, PAX6, NESTIN), neuronal (MAP2, TUBB3), cortical layer (TBR1, CUX1) and glial markers (SOX9, GFAP, AQP4). Electron microscopy demonstrated that both methods resulted in morphologically similar neural rosettes. However, quantification of NPCs derived from 3D neural induction exhibited an increase in the number of PAX6/NESTIN double positive cells and the derived neurons exhibited longer neurites. In contrast, 2D neural induction resulted in more SOX1 positive cells. While 2D monolayer induction resulted in slightly less mature neurons, at an early stage of differentiation, the patch clamp analysis failed to reveal any significant differences between the electrophysiological properties between the two induction methods. In conclusion, 3D neural induction increases the yield of PAX6 + /NESTIN + cells and gives rise to neurons with longer neurites, which might be an advantage for the production of forebrain cortical neurons, highlighting the potential of 3D neural induction, independent of iPSCs' genetic background. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Firing patterns transition and desynchronization induced by time delay in neural networks

Science.gov (United States)

Huang, Shoufang; Zhang, Jiqian; Wang, Maosheng; Hu, Chin-Kun

2018-06-01

We used the Hindmarsh-Rose (HR) model (Hindmarsh and Rose, 1984) to study the effect of time delay on the transition of firing behaviors and desynchronization in neural networks. As time delay is increased, neural networks exhibit diversity of firing behaviors, including regular spiking or bursting and firing patterns transitions (FPTs). Meanwhile, the desynchronization of firing and unstable bursting with decreasing amplitude in neural system, are also increasingly enhanced with the increase of time delay. Furthermore, we also studied the effect of coupling strength and network randomness on these phenomena. Our results imply that time delays can induce transition and desynchronization of firing behaviors in neural networks. These findings provide new insight into the role of time delay in the firing activities of neural networks, and can help to better understand the firing phenomena in complex systems of neural networks. A possible mechanism in brain that can cause the increase of time delay is discussed.

Intermittent reductions in respiratory neural activity elicit spinal TNF-α-independent, atypical PKC-dependent inactivity-induced phrenic motor facilitation.

Science.gov (United States)

Baertsch, Nathan A; Baker-Herman, Tracy L

2015-04-15

In many neural networks, mechanisms of compensatory plasticity respond to prolonged reductions in neural activity by increasing cellular excitability or synaptic strength. In the respiratory control system, a prolonged reduction in synaptic inputs to the phrenic motor pool elicits a TNF-α- and atypical PKC-dependent form of spinal plasticity known as inactivity-induced phrenic motor facilitation (iPMF). Although iPMF may be elicited by a prolonged reduction in respiratory neural activity, iPMF is more efficiently induced when reduced respiratory neural activity (neural apnea) occurs intermittently. Mechanisms giving rise to iPMF following intermittent neural apnea are unknown. The purpose of this study was to test the hypothesis that iPMF following intermittent reductions in respiratory neural activity requires spinal TNF-α and aPKC. Phrenic motor output was recorded in anesthetized and ventilated rats exposed to brief intermittent (5, ∼1.25 min), brief sustained (∼6.25 min), or prolonged sustained (30 min) neural apnea. iPMF was elicited following brief intermittent and prolonged sustained neural apnea, but not following brief sustained neural apnea. Unlike iPMF following prolonged neural apnea, spinal TNF-α was not required to initiate iPMF during intermittent neural apnea; however, aPKC was still required for its stabilization. These results suggest that different patterns of respiratory neural activity induce iPMF through distinct cellular mechanisms but ultimately converge on a similar downstream pathway. Understanding the diverse cellular mechanisms that give rise to inactivity-induced respiratory plasticity may lead to development of novel therapeutic strategies to treat devastating respiratory control disorders when endogenous compensatory mechanisms fail. Copyright © 2015 the American Physiological Society.

The meninges contribute to the conditioned taste avoidance induced by neural cooling in male rats.

Science.gov (United States)

Wang, Yuan; Chambers, Kathleen C

2002-08-21

After consumption of a novel sucrose solution, temporary cooling of neural areas that mediate conditioned taste avoidance can itself induce conditioned avoidance to the sucrose. It has been suggested that this effect is either a result of inactivation of neurons in these areas or of cooling the meninges. In a series of studies, we demonstrated that cooling the outer layer of the meninges, the dura mater, does not contribute to the conditioned taste avoidance induced by cooling any of these areas. The present experiments were designed to determine whether the inner layers of the meninges are involved. If they are involved, then one would expect that cooling locations in the brain that do not mediate conditioned taste avoidance, such as the caudate putamen (CP), would induce conditioned taste avoidance as long as the meninges were cooled as well. One also would expect that cooling neural tissue without cooling the meninges would reduce the strength of the conditioned taste avoidance. Experiment 1 established that the temperature of the neural tissue and meninges around the cold probes implanted in the CP were cooled to temperatures that have been shown to block synaptic transmission. Experiment 2 demonstrated that cooling the caudate putamen and overlying cortex and meninges induced conditioned taste avoidance. In experiment 3, a circle of meninges was cut away so that the caudate putamen and overlying cortex could be cooled without cooling the meninges. The strength of the conditioned taste avoidance was substantially reduced, but it was not entirely eliminated. These data support the hypothesis that cooling the meninges contributes to the conditioned taste avoidance induced by neural cooling. They also allow the possibility that neural inactivation produces physiological changes that can induce conditioned taste avoidance. Copyright 2002 Elsevier Science B.V.

Coherence Resonance and Noise-Induced Synchronization in Hindmarsh-Rose Neural Network with Different Topologies

International Nuclear Information System (INIS)

Wei Duqu; Luo Xiaoshu

2007-01-01

In this paper, we investigate coherence resonance (CR) and noise-induced synchronization in Hindmarsh-Rose (HR) neural network with three different types of topologies: regular, random, and small-world. It is found that the additive noise can induce CR in HR neural network with different topologies and its coherence is optimized by a proper noise level. It is also found that as coupling strength increases the plateau in the measure of coherence curve becomes broadened and the effects of network topology is more pronounced simultaneously. Moreover, we find that increasing the probability p of the network topology leads to an enhancement of noise-induced synchronization in HR neurons network.

Predicting musically induced emotions from physiological inputs: linear and neural network models.

Science.gov (United States)

Russo, Frank A; Vempala, Naresh N; Sandstrom, Gillian M

2013-01-01

Listening to music often leads to physiological responses. Do these physiological responses contain sufficient information to infer emotion induced in the listener? The current study explores this question by attempting to predict judgments of "felt" emotion from physiological responses alone using linear and neural network models. We measured five channels of peripheral physiology from 20 participants-heart rate (HR), respiration, galvanic skin response, and activity in corrugator supercilii and zygomaticus major facial muscles. Using valence and arousal (VA) dimensions, participants rated their felt emotion after listening to each of 12 classical music excerpts. After extracting features from the five channels, we examined their correlation with VA ratings, and then performed multiple linear regression to see if a linear relationship between the physiological responses could account for the ratings. Although linear models predicted a significant amount of variance in arousal ratings, they were unable to do so with valence ratings. We then used a neural network to provide a non-linear account of the ratings. The network was trained on the mean ratings of eight of the 12 excerpts and tested on the remainder. Performance of the neural network confirms that physiological responses alone can be used to predict musically induced emotion. The non-linear model derived from the neural network was more accurate than linear models derived from multiple linear regression, particularly along the valence dimension. A secondary analysis allowed us to quantify the relative contributions of inputs to the non-linear model. The study represents a novel approach to understanding the complex relationship between physiological responses and musically induced emotion.

Predicting musically induced emotions from physiological inputs: Linear and neural network models

Directory of Open Access Journals (Sweden)

Frank A. Russo

2013-08-01

Full Text Available Listening to music often leads to physiological responses. Do these physiological responses contain sufficient information to infer emotion induced in the listener? The current study explores this question by attempting to predict judgments of 'felt' emotion from physiological responses alone using linear and neural network models. We measured five channels of peripheral physiology from 20 participants – heart rate, respiration, galvanic skin response, and activity in corrugator supercilii and zygomaticus major facial muscles. Using valence and arousal (VA dimensions, participants rated their felt emotion after listening to each of 12 classical music excerpts. After extracting features from the five channels, we examined their correlation with VA ratings, and then performed multiple linear regression to see if a linear relationship between the physiological responses could account for the ratings. Although linear models predicted a significant amount of variance in arousal ratings, they were unable to do so with valence ratings. We then used a neural network to provide a nonlinear account of the ratings. The network was trained on the mean ratings of eight of the 12 excerpts and tested on the remainder. Performance of the neural network confirms that physiological responses alone can be used to predict musically induced emotion. The nonlinear model derived from the neural network was more accurate than linear models derived from multiple linear regression, particularly along the valence dimension. A secondary analysis allowed us to quantify the relative contributions of inputs to the nonlinear model. The study represents a novel approach to understanding the complex relationship between physiological responses and musically induced emotion.

Neural mechanisms underlying sound-induced visual motion perception: An fMRI study.

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Hidaka, Souta; Higuchi, Satomi; Teramoto, Wataru; Sugita, Yoichi

2017-07-01

Studies of crossmodal interactions in motion perception have reported activation in several brain areas, including those related to motion processing and/or sensory association, in response to multimodal (e.g., visual and auditory) stimuli that were both in motion. Recent studies have demonstrated that sounds can trigger illusory visual apparent motion to static visual stimuli (sound-induced visual motion: SIVM): A visual stimulus blinking at a fixed location is perceived to be moving laterally when an alternating left-right sound is also present. Here, we investigated brain activity related to the perception of SIVM using a 7T functional magnetic resonance imaging technique. Specifically, we focused on the patterns of neural activities in SIVM and visually induced visual apparent motion (VIVM). We observed shared activations in the middle occipital area (V5/hMT), which is thought to be involved in visual motion processing, for SIVM and VIVM. Moreover, as compared to VIVM, SIVM resulted in greater activation in the superior temporal area and dominant functional connectivity between the V5/hMT area and the areas related to auditory and crossmodal motion processing. These findings indicate that similar but partially different neural mechanisms could be involved in auditory-induced and visually-induced motion perception, and neural signals in auditory, visual, and, crossmodal motion processing areas closely and directly interact in the perception of SIVM. Copyright © 2017 Elsevier B.V. All rights reserved.

Generation of Oligodendrogenic Spinal Neural Progenitor Cells From Human Induced Pluripotent Stem Cells.

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Khazaei, Mohamad; Ahuja, Christopher S; Fehlings, Michael G

2017-08-14

This unit describes protocols for the efficient generation of oligodendrogenic neural progenitor cells (o-NPCs) from human induced pluripotent stem cells (hiPSCs). Specifically, detailed methods are provided for the maintenance and differentiation of hiPSCs, human induced pluripotent stem cell-derived neural progenitor cells (hiPS-NPCs), and human induced pluripotent stem cell-oligodendrogenic neural progenitor cells (hiPSC-o-NPCs) with the final products being suitable for in vitro experimentation or in vivo transplantation. Throughout, cell exposure to growth factors and patterning morphogens has been optimized for both concentration and timing, based on the literature and empirical experience, resulting in a robust and highly efficient protocol. Using this derivation procedure, it is possible to obtain millions of oligodendrogenic-NPCs within 40 days of initial cell plating which is substantially shorter than other protocols for similar cell types. This protocol has also been optimized to use translationally relevant human iPSCs as the parent cell line. The resultant cells have been extensively characterized both in vitro and in vivo and express key markers of an oligodendrogenic lineage. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley and Sons, Inc.

Rejuvenation of MPTP-induced human neural precursor cell senescence by activating autophagy

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Zhu, Liang [East Hospital, Tongji University School of Medicine, Shanghai (China); Dong, Chuanming [East Hospital, Tongji University School of Medicine, Shanghai (China); Department of Anatomy and Neurobiology, The Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong (China); Sun, Chenxi; Ma, Rongjie; Yang, Danjing [East Hospital, Tongji University School of Medicine, Shanghai (China); Zhu, Hongwen, E-mail: hongwen_zhu@hotmail.com [Tianjin Hospital, Tianjin Academy of Integrative Medicine, Tianjin (China); Xu, Jun, E-mail: xunymc2000@yahoo.com [East Hospital, Tongji University School of Medicine, Shanghai (China)

2015-08-21

Aging of neural stem cell, which can affect brain homeostasis, may be caused by many cellular mechanisms. Autophagy dysfunction was found in aged and neurodegenerative brains. However, little is known about the relationship between autophagy and human neural stem cell (hNSC) aging. The present study used 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) to treat neural precursor cells (NPCs) derived from human embryonic stem cell (hESC) line H9 and investigate related molecular mechanisms involved in this process. MPTP-treated NPCs were found to undergo premature senescence [determined by increased senescence-associated-β-galactosidase (SA-β-gal) activity, elevated intracellular reactive oxygen species level, and decreased proliferation] and were associated with impaired autophagy. Additionally, the cellular senescence phenotypes were manifested at the molecular level by a significant increase in p21 and p53 expression, a decrease in SOD2 expression, and a decrease in expression of some key autophagy-related genes such as Atg5, Atg7, Atg12, and Beclin 1. Furthermore, we found that the senescence-like phenotype of MPTP-treated hNPCs was rejuvenated through treatment with a well-known autophagy enhancer rapamycin, which was blocked by suppression of essential autophagy gene Beclin 1. Taken together, these findings reveal the critical role of autophagy in the process of hNSC aging, and this process can be reversed by activating autophagy. - Highlights: • We successfully establish hESC-derived neural precursor cells. • MPTP treatment induced senescence-like state in hESC-derived NPCs. • MPTP treatment induced impaired autophagy of hESC-derived NPCs. • MPTP-induced hESC-derived NPC senescence was rejuvenated by activating autophagy.

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

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

2016-01-01

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

Neural correlates of cognitive dissonance and choice-induced preference change.

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Izuma, Keise; Matsumoto, Madoka; Murayama, Kou; Samejima, Kazuyuki; Sadato, Norihiro; Matsumoto, Kenji

2010-12-21

According to many modern economic theories, actions simply reflect an individual's preferences, whereas a psychological phenomenon called "cognitive dissonance" claims that actions can also create preference. Cognitive dissonance theory states that after making a difficult choice between two equally preferred items, the act of rejecting a favorite item induces an uncomfortable feeling (cognitive dissonance), which in turn motivates individuals to change their preferences to match their prior decision (i.e., reducing preference for rejected items). Recently, however, Chen and Risen [Chen K, Risen J (2010) J Pers Soc Psychol 99:573-594] pointed out a serious methodological problem, which casts a doubt on the very existence of this choice-induced preference change as studied over the past 50 y. Here, using a proper control condition and two measures of preferences (self-report and brain activity), we found that the mere act of making a choice can change self-report preference as well as its neural representation (i.e., striatum activity), thus providing strong evidence for choice-induced preference change. Furthermore, our data indicate that the anterior cingulate cortex and dorsolateral prefrontal cortex tracked the degree of cognitive dissonance on a trial-by-trial basis. Our findings provide important insights into the neural basis of how actions can alter an individual's preferences.

Human induced pluripotent stem cell-derived models to investigate human cytomegalovirus infection in neural cells.

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Leonardo D'Aiuto

Full Text Available Human cytomegalovirus (HCMV infection is one of the leading prenatal causes of congenital mental retardation and deformities world-wide. Access to cultured human neuronal lineages, necessary to understand the species specific pathogenic effects of HCMV, has been limited by difficulties in sustaining primary human neuronal cultures. Human induced pluripotent stem (iPS cells now provide an opportunity for such research. We derived iPS cells from human adult fibroblasts and induced neural lineages to investigate their susceptibility to infection with HCMV strain Ad169. Analysis of iPS cells, iPS-derived neural stem cells (NSCs, neural progenitor cells (NPCs and neurons suggests that (i iPS cells are not permissive to HCMV infection, i.e., they do not permit a full viral replication cycle; (ii Neural stem cells have impaired differentiation when infected by HCMV; (iii NPCs are fully permissive for HCMV infection; altered expression of genes related to neural metabolism or neuronal differentiation is also observed; (iv most iPS-derived neurons are not permissive to HCMV infection; and (v infected neurons have impaired calcium influx in response to glutamate.

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

Science.gov (United States)

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

2016-11-01

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

Distinct steps of neural induction revealed by Asterix, Obelix and TrkC, genes induced by different signals from the organizer.

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Sonia Pinho

2011-04-01

Full Text Available The amniote organizer (Hensen's node can induce a complete nervous system when grafted into a peripheral region of a host embryo. Although BMP inhibition has been implicated in neural induction, non-neural cells cannot respond to BMP antagonists unless previously exposed to a node graft for at least 5 hours before BMP inhibitors. To define signals and responses during the first 5 hours of node signals, a differential screen was conducted. Here we describe three early response genes: two of them, Asterix and Obelix, encode previously undescribed proteins of unknown function but Obelix appears to be a nuclear RNA-binding protein. The third is TrkC, a neurotrophin receptor. All three genes are induced by a node graft within 4-5 hours but they differ in the extent to which they are inducible by FGF: FGF is both necessary and sufficient to induce Asterix, sufficient but not necessary to induce Obelix and neither sufficient nor necessary for induction of TrkC. These genes are also not induced by retinoic acid, Noggin, Chordin, Dkk1, Cerberus, HGF/SF, Somatostatin or ionomycin-mediated Calcium entry. Comparison of the expression and regulation of these genes with other early neural markers reveals three distinct "epochs", or temporal waves, of gene expression accompanying neural induction by a grafted organizer, which are mirrored by specific stages of normal neural plate development. The results are consistent with neural induction being a cascade of responses elicited by different signals, culminating in the formation of a patterned nervous system.

Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation through activating the NR2B subunits of NMDA receptors

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Shi, Wen-Zhu [Anesthesia and Operation Center, Hainan Branch of Chinese PLA General Hospital, Hainan 572013 (China); Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853 (China); Miao, Yu-Liang [Department of Anesthesiology, PLA No. 306 Hospital, Beijing 100101 (China); Guo, Wen-Zhi [Department of Anesthesiology, Beijing Military General Hospital of Chinese People’s Liberation Army, Beijing 100700 (China); Wu, Wei, E-mail: wwzwgk@163.com [Department of Head and Neck Surgery of Otolaryngology, PLA No. 306 Hospital, Beijing 100101 (China); Li, Bao-Wei [Department of Head and Neck Surgery of Otolaryngology, PLA No. 306 Hospital, Beijing 100101 (China); An, Li-Na [Department of Anesthesiology, Armed Police General Hospital, Beijing 100039 (China); Fang, Wei-Wu [Department of Anesthesiology, PLA No. 306 Hospital, Beijing 100101 (China); Mi, Wei-Dong, E-mail: elite2005gg@163.com [Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853 (China)

2014-04-25

Highlights: • Leptin promotes the proliferation of neural stem cells isolated from embryonic mouse hippocampus. • Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation. • The effects of leptin are partially mediated by upregulating NR2B subunits. - Abstract: Corticosterone inhibits the proliferation of hippocampal neural stem cells (NSCs). The removal of corticosterone-induced inhibition of NSCs proliferation has been reported to contribute to neural regeneration. Leptin has been shown to regulate brain development, improve angiogenesis, and promote neural regeneration; however, its effects on corticosterone-induced inhibition of NSCs proliferation remain unclear. Here we reported that leptin significantly promoted the proliferation of hippocampal NSCs in a concentration-dependent pattern. Also, leptin efficiently reversed the inhibition of NSCs proliferation induced by corticosterone. Interestingly, pre-treatment with non-specific NMDA antagonist MK-801, specific NR2B antagonist Ro 25-6981, or small interfering RNA (siRNA) targeting NR2B, significantly blocked the effect of leptin on corticosterone-induced inhibition of NSCs proliferation. Furthermore, corticosterone significantly reduced the protein expression of NR2B, whereas pre-treatment with leptin greatly reversed the attenuation of NR2B expression caused by corticosterone in cultured hippocampal NSCs. Our findings demonstrate that leptin reverses the corticosterone-induced inhibition of NSCs proliferation. This process is, at least partially mediated by increased expression of NR2B subunits of NMDA receptors.

Plasmid-based generation of induced neural stem cells from adult human fibroblasts

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Philipp Capetian

2016-10-01

Full Text Available Direct reprogramming from somatic to neural cell types has become an alternative to induced pluripotent stem cells. Most protocols employ viral expression systems, posing the risk of random genomic integration. Recent developments led to plasmid-based protocols, lowering this risk. However, these protocols either relied on continuous presence of a variety of small molecules or were only able to reprogram murine cells. We therefore established a reprogramming protocol based on vectors containing the Epstein-Barr virus (EBV-derived oriP/EBNA1 as well as the defined expression factors Oct3/4, Sox2, Klf4, L-myc, Lin28, and a small hairpin directed against p53. We employed a defined neural medium in combination with the neurotrophins bFGF, EGF and FGF4 for cultivation without the addition of small molecules. After reprogramming, cells demonstrated a temporary increase in the expression of endogenous Oct3/4. We obtained induced neural stem cells (iNSC 30 days after transfection. In contrast to previous results, plasmid vectors as well as a residual expression of reprogramming factors remained detectable in all cell lines. Cells showed a robust differentiation into neuronal (72% and glial cells (9% astrocytes, 6% oligodendrocytes. Despite the temporary increase of pluripotency-associated Oct3/4 expression during reprogramming, we did not detect pluripotent stem cells or non-neural cells in culture (except occasional residual fibroblasts. Neurons showed electrical activity and functional glutamatergic synapses. Our results demonstrate that reprogramming adult human fibroblasts to iNSC by plasmid vectors and basic neural medium without small molecules is possible and feasible. However, a full set of pluripotency-associated transcription factors may indeed result in the acquisition of a transient (at least partial pluripotent intermediate during reprogramming. In contrast to previous reports, the EBV-based plasmid system remained present and active inside

Recognition of edible oil by using BP neural network and laser induced fluorescence spectrum

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Mu, Tao-tao; Chen, Si-ying; Zhang, Yin-chao; Guo, Pan; Chen, He; Zhang, Hong-yan; Liu, Xiao-hua; Wang, Yuan; Bu, Zhi-chao

2013-09-01

In order to accomplish recognition of the different edible oil we set up a laser induced fluorescence spectrum system in the laboratory based on Laser induced fluorescence spectrum technology, and then collect the fluorescence spectrum of different edible oil by using that system. Based on this, we set up a fluorescence spectrum database of different cooking oil. It is clear that there are three main peak position of different edible oil from fluorescence spectrum chart. Although the peak positions of all cooking oil were almost the same, the relative intensity of different edible oils was totally different. So it could easily accomplish that oil recognition could take advantage of the difference of relative intensity. Feature invariants were extracted from the spectrum data, which were chosen from the fluorescence spectrum database randomly, before distinguishing different cooking oil. Then back propagation (BP) neural network was established and trained by the chosen data from the spectrum database. On that basis real experiment data was identified by BP neural network. It was found that the overall recognition rate could reach as high as 83.2%. Experiments showed that the laser induced fluorescence spectrum of different cooking oil was very different from each other, which could be used to accomplish the oil recognition. Laser induced fluorescence spectrum technology, combined BP neural network，was fast, high sensitivity, non-contact, and high recognition rate. It could become a new technique to accomplish the edible oil recognition and quality detection.

Coupling Strength and System Size Induce Firing Activity of Globally Coupled Neural Network

International Nuclear Information System (INIS)

Wei Duqu; Luo Xiaoshu; Zou Yanli

2008-01-01

We investigate how firing activity of globally coupled neural network depends on the coupling strength C and system size N. Network elements are described by space-clamped FitzHugh-Nagumo (SCFHN) neurons with the values of parameters at which no firing activity occurs. It is found that for a given appropriate coupling strength, there is an intermediate range of system size where the firing activity of globally coupled SCFHN neural network is induced and enhanced. On the other hand, for a given intermediate system size level, there exists an optimal value of coupling strength such that the intensity of firing activity reaches its maximum. These phenomena imply that the coupling strength and system size play a vital role in firing activity of neural network

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

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Hutt, Axel; Buhry, Laure

2014-12-01

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

Fatty acid-induced gut-brain signaling attenuates neural and behavioral effects of sad emotion in humans.

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Van Oudenhove, Lukas; McKie, Shane; Lassman, Daniel; Uddin, Bilal; Paine, Peter; Coen, Steven; Gregory, Lloyd; Tack, Jan; Aziz, Qasim

2011-08-01

Although a relationship between emotional state and feeding behavior is known to exist, the interactions between signaling initiated by stimuli in the gut and exteroceptively generated emotions remain incompletely understood. Here, we investigated the interaction between nutrient-induced gut-brain signaling and sad emotion induced by musical and visual cues at the behavioral and neural level in healthy nonobese subjects undergoing functional magnetic resonance imaging. Subjects received an intragastric infusion of fatty acid solution or saline during neutral or sad emotion induction and rated sensations of hunger, fullness, and mood. We found an interaction between fatty acid infusion and emotion induction both in the behavioral readouts (hunger, mood) and at the level of neural activity in multiple pre-hypothesized regions of interest. Specifically, the behavioral and neural responses to sad emotion induction were attenuated by fatty acid infusion. These findings increase our understanding of the interplay among emotions, hunger, food intake, and meal-induced sensations in health, which may have important implications for a wide range of disorders, including obesity, eating disorders, and depression.

Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins

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Hayato Fukusumi

2016-01-01

Full Text Available Human neural progenitor cells (hNPCs have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi. Our results showed that expandable hNPCs could be generated from hiPSC clones with diverse somatic tissue origins. The established hNPCs exhibited a mid/hindbrain-type neural identity and uniform expression of neural progenitor genes.

Inactivity-induced phrenic and hypoglossal motor facilitation are differentially expressed following intermittent vs. sustained neural apnea

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Baertsch, N. A.

2013-01-01

Reduced respiratory neural activity elicits a rebound increase in phrenic and hypoglossal motor output known as inactivity-induced phrenic and hypoglossal motor facilitation (iPMF and iHMF, respectively). We hypothesized that, similar to other forms of respiratory plasticity, iPMF and iHMF are pattern sensitive. Central respiratory neural activity was reversibly reduced in ventilated rats by hyperventilating below the CO2 apneic threshold to create brief intermittent neural apneas (5, ∼1.5 min each, separated by 5 min), a single brief massed neural apnea (7.5 min), or a single prolonged neural apnea (30 min). Upon restoration of respiratory neural activity, long-lasting (>60 min) iPMF was apparent following brief intermittent and prolonged, but not brief massed, neural apnea. Further, brief intermittent and prolonged neural apnea elicited an increase in the maximum phrenic response to high CO2, suggesting that iPMF is associated with an increase in phrenic dynamic range. By contrast, only prolonged neural apnea elicited iHMF, which was transient in duration (<15 min). Intermittent, massed, and prolonged neural apnea all elicited a modest transient facilitation of respiratory frequency. These results indicate that iPMF, but not iHMF, is pattern sensitive, and that the response to respiratory neural inactivity is motor pool specific. PMID:23493368

Increased respiratory neural drive and work of breathing in exercise-induced laryngeal obstruction.

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Walsted, Emil S; Faisal, Azmy; Jolley, Caroline J; Swanton, Laura L; Pavitt, Matthew J; Luo, Yuan-Ming; Backer, Vibeke; Polkey, Michael I; Hull, James H

2018-02-01

Exercise-induced laryngeal obstruction (EILO), a phenomenon in which the larynx closes inappropriately during physical activity, is a prevalent cause of exertional dyspnea in young individuals. The physiological ventilatory impact of EILO and its relationship to dyspnea are poorly understood. The objective of this study was to evaluate exercise-related changes in laryngeal aperture on ventilation, pulmonary mechanics, and respiratory neural drive. We prospectively evaluated 12 subjects (6 with EILO and 6 healthy age- and gender-matched controls). Subjects underwent baseline spirometry and a symptom-limited incremental exercise test with simultaneous and synchronized recording of endoscopic video and gastric, esophageal, and transdiaphragmatic pressures, diaphragm electromyography, and respiratory airflow. The EILO and control groups had similar peak work rates and minute ventilation (V̇e) (work rate: 227 ± 35 vs. 237 ± 35 W; V̇e: 103 ± 20 vs. 98 ± 23 l/min; P > 0.05). At submaximal work rates (140-240 W), subjects with EILO demonstrated increased work of breathing ( P respiratory neural drive ( P respiratory mechanics and diaphragm electromyography with endoscopic video, we demonstrate, for the first time, increased work of breathing and respiratory neural drive in association with the development of EILO. Future detailed investigations are now needed to understand the role of upper airway closure in causing exertional dyspnea and exercise limitation. NEW & NOTEWORTHY Exercise-induced laryngeal obstruction is a prevalent cause of exertional dyspnea in young individuals; yet, how laryngeal closure affects breathing is unknown. In this study we synchronized endoscopic video with respiratory physiological measurements, thus providing the first detailed commensurate assessment of respiratory mechanics and neural drive in relation to laryngeal closure. Laryngeal closure was associated with increased work of breathing and respiratory neural drive preceded by an

Long-Term Alterations in Neural and Endocrine Processes Induced by Motherhood

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Bridges, Robert S.

2015-01-01

The reproductive experience of pregnancy, lactation and motherhood can significantly remodel the female’s biological state, affecting endocrine, neuroendocrine, neural, and immunological processes. The brain, pituitary gland, liver, thymus, and mammary tissue are among the structures that are modified by reproductive experience. The present review that focuses on rodent research, but also includes pertinent studies in sheep and other species, identifies specific changes in these processes brought about by the biological states of pregnancy, parturition, and lactation and how the components of reproductive experience contribute to the remodeling of the maternal brain and organ systems. Findings indicate that prior parity alters key circulating hormone levels and neural receptor gene expression. Moreover, reproductive experience results in modifications in neural processes and glial support. The possible role of pregnancy-induced neurogenesis is considered in the context of neuroplasticity and behavior, and the effects of reproductive experience on maternal memory, i.e. the retention of maternal behavior, together with anxiety and learning are presented. Together, these sets of findings support the concept that the neural and biological state of the adult female is significantly and dramatically altered on a long-term basis by the experiences of parity and motherhood. Remodeling of the maternal brain and other biological systems is posited to help facilitate adaptations to environmental/ecological challenges as the female raises young and ages. PMID:26388065

Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain

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Kathrin Hemmer

2014-09-01

Full Text Available Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]. iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications.

The Neural Border: Induction, Specification and Maturation of the territory that generates Neural Crest cells.

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Pla, Patrick; Monsoro-Burq, Anne H

2018-05-28

The neural crest is induced at the edge between the neural plate and the nonneural ectoderm, in an area called the neural (plate) border, during gastrulation and neurulation. In recent years, many studies have explored how this domain is patterned, and how the neural crest is induced within this territory, that also participates to the prospective dorsal neural tube, the dorsalmost nonneural ectoderm, as well as placode derivatives in the anterior area. This review highlights the tissue interactions, the cell-cell signaling and the molecular mechanisms involved in this dynamic spatiotemporal patterning, resulting in the induction of the premigratory neural crest. Collectively, these studies allow building a complex neural border and early neural crest gene regulatory network, mostly composed by transcriptional regulations but also, more recently, including novel signaling interactions. Copyright © 2018. Published by Elsevier Inc.

ADAM13 Induces Cranial Neural Crest by Cleaving Class B Ephrins and Regulating Wnt Signaling

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Wei, Shuo; Xu, Guofeng; Bridges, Lance C.; Williams, Phoebe; White, Judith M.; DeSimone, Douglas W.

2010-01-01

The cranial neural crest (CNC) are multipotent embryonic cells that contribute to craniofacial structures and other cells and tissues of the vertebrate head. During embryogenesis, CNC is induced at the neural plate boundary through the interplay of several major signaling pathways. Here we report that the metalloproteinase activity of ADAM13 is required for early induction of CNC in Xenopus. In both cultured cells and X. tropicalis embryos, membrane-bound Ephrins (Efns) B1 and B2 were identif...

An artificial neural network approach to laser-induced breakdown spectroscopy quantitative analysis

International Nuclear Information System (INIS)

D’Andrea, Eleonora; Pagnotta, Stefano; Grifoni, Emanuela; Lorenzetti, Giulia; Legnaioli, Stefano; Palleschi, Vincenzo; Lazzerini, Beatrice

2014-01-01

The usual approach to laser-induced breakdown spectroscopy (LIBS) quantitative analysis is based on the use of calibration curves, suitably built using appropriate reference standards. More recently, statistical methods relying on the principles of artificial neural networks (ANN) are increasingly used. However, ANN analysis is often used as a ‘black box’ system and the peculiarities of the LIBS spectra are not exploited fully. An a priori exploration of the raw data contained in the LIBS spectra, carried out by a neural network to learn what are the significant areas of the spectrum to be used for a subsequent neural network delegated to the calibration, is able to throw light upon important information initially unknown, although already contained within the spectrum. This communication will demonstrate that an approach based on neural networks specially taylored for dealing with LIBS spectra would provide a viable, fast and robust method for LIBS quantitative analysis. This would allow the use of a relatively limited number of reference samples for the training of the network, with respect to the current approaches, and provide a fully automatizable approach for the analysis of a large number of samples. - Highlights: • A methodological approach to neural network analysis of LIBS spectra is proposed. • The architecture of the network and the number of inputs are optimized. • The method is tested on bronze samples already analyzed using a calibration-free LIBS approach. • The results are validated, compared and discussed

Neural basis of stereotype-induced shifts in women's mental rotation performance

OpenAIRE

Wraga, Maryjane; Helt, Molly; Jacobs, Emily; Sullivan, Kerry

2007-01-01

Recent negative focus on women's academic abilities has fueled disputes over gender disparities in the sciences. The controversy derives, in part, from women's relatively poorer performance in aptitude tests, many of which require skills of spatial reasoning. We used functional magnetic imaging to examine the neural structure underlying shifts in women's performance of a spatial reasoning task induced by positive and negative stereotypes. Three groups of participants performed a task involvin...

Neural mechanisms of reactivation-induced updating that enhance and distort memory

OpenAIRE

St. Jacques, Peggy L.; Olm, Christopher; Schacter, Daniel L.

2013-01-01

We remember a considerable number of personal experiences because we are frequently reminded of them, a process known as memory reactivation. Although memory reactivation helps to stabilize and update memories, reactivation may also introduce distortions if novel information becomes incorporated with memory. Here we used functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms mediating reactivation-induced updating in memory for events experienced during a museum tou...

Therapeutically engineered induced neural stem cells are tumour-homing and inhibit progression of glioblastoma

OpenAIRE

Bag?, Juli R.; Alfonso-Pecchio, Adolfo; Okolie, Onyi; Dumitru, Raluca; Rinkenbaugh, Amanda; Baldwin, Albert S.; Miller, C. Ryan; Magness, Scott T.; Hingtgen, Shawn D.

2016-01-01

Transdifferentiation (TD) is a recent advancement in somatic cell reprogramming. The direct conversion of TD eliminates the pluripotent intermediate state to create cells that are ideal for personalized cell therapy. Here we provide evidence that TD-derived induced neural stem cells (iNSCs) are an efficacious therapeutic strategy for brain cancer. We find that iNSCs genetically engineered with optical reporters and tumouricidal gene products retain the capacity to differentiate and induced ap...

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

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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

Experimental evaluation of neural probe’s insertion induced injury based on digital image correlation method

Energy Technology Data Exchange (ETDEWEB)

Zhang, Wenguang, E-mail: zhwg@sjtu.edu.cn; Ma, Yakun; Li, Zhengwei [State Key Laboratory of Mechanical System and Vibration, Shanghai Jiao Tong University, Shanghai 200240 (China)

2016-01-15

Purpose: The application of neural probes in clinic has been challenged by probes’ short lifetime when implanted into brain tissue. The primary goal is to develop an evaluation system for testing brain tissue injury induced by neural probe’s insertion using microscope based digital image correlation method. Methods: A brain tissue phantom made of silicone rubber with speckle pattern on its surface was fabricated. To obtain the optimal speckle pattern, mean intensity gradient parameter was used for quality assessment. The designed testing system consists of three modules: (a) load module for simulating neural electrode implantation process; (b) data acquisition module to capture micrographs of speckle pattern and to obtain reactive forces during the insertion of the probe; (c) postprocessing module for extracting tissue deformation information from the captured speckle patterns. On the basis of the evaluation system, the effects of probe wedge angle, insertion speed, and probe streamline on insertion induced tissue injury were investigated. Results: The optimal quality speckle pattern can be attained by the following fabrication parameters: spin coating rate—1000 r/min, silicone rubber component A: silicone rubber component B: softener: graphite = 5 ml: 5 ml: 2 ml: 0.6 g. The probe wedge angle has a significant effect on tissue injury. Compared to wedge angle 40° and 20°, maximum principal strain of 60° wedge angle was increased by 40.3% and 87.5%, respectively; compared with a relatively higher speed (500 μm/s), the maximum principle strain within the tissue induced by slow insertion speed (100 μm/s) was increased by 14.3%; insertion force required by probe with convex streamline was smaller than the force of traditional probe. Based on the experimental results, a novel neural probe that has a rounded tip covered by a biodegradable silk protein coating with convex streamline was proposed, which has both lower insertion and micromotion induced tissue

Chemically Induced Reprogramming of Somatic Cells to Pluripotent Stem Cells and Neural Cells.

Science.gov (United States)

Biswas, Dhruba; Jiang, Peng

2016-02-06

The ability to generate transplantable neural cells in a large quantity in the laboratory is a critical step in the field of developing stem cell regenerative medicine for neural repair. During the last few years, groundbreaking studies have shown that cell fate of adult somatic cells can be reprogrammed through lineage specific expression of transcription factors (TFs)-and defined culture conditions. This key concept has been used to identify a number of potent small molecules that could enhance the efficiency of reprogramming with TFs. Recently, a growing number of studies have shown that small molecules targeting specific epigenetic and signaling pathways can replace all of the reprogramming TFs. Here, we provide a detailed review of the studies reporting the generation of chemically induced pluripotent stem cells (ciPSCs), neural stem cells (ciNSCs), and neurons (ciN). We also discuss the main mechanisms of actions and the pathways that the small molecules regulate during chemical reprogramming.

Induced neural stem cells achieve long-term survival and functional integration in the adult mouse brain.

Science.gov (United States)

Hemmer, Kathrin; Zhang, Mingyue; van Wüllen, Thea; Sakalem, Marna; Tapia, Natalia; Baumuratov, Aidos; Kaltschmidt, Christian; Kaltschmidt, Barbara; Schöler, Hans R; Zhang, Weiqi; Schwamborn, Jens C

2014-09-09

Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]). iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC) technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins

OpenAIRE

Hayato Fukusumi; Tomoko Shofuda; Yohei Bamba; Atsuyo Yamamoto; Daisuke Kanematsu; Yukako Handa; Keisuke Okita; Masaya Nakamura; Shinya Yamanaka; Hideyuki Okano; Yonehiro Kanemura

2016-01-01

Human neural progenitor cells (hNPCs) have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC) clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB) formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi). Our results showed that expandable hNPCs could be generated from hiPS...

Neural mechanisms of reactivation-induced updating that enhance and distort memory.

Science.gov (United States)

St Jacques, Peggy L; Olm, Christopher; Schacter, Daniel L

2013-12-03

We remember a considerable number of personal experiences because we are frequently reminded of them, a process known as memory reactivation. Although memory reactivation helps to stabilize and update memories, reactivation may also introduce distortions if novel information becomes incorporated with memory. Here we used functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms mediating reactivation-induced updating in memory for events experienced during a museum tour. During scanning, participants were shown target photographs to reactivate memories from the museum tour followed by a novel lure photograph from an alternate tour. Later, participants were presented with target and lure photographs and asked to determine whether the photographs showed a stop they visited during the tour. We used a subsequent memory analysis to examine neural recruitment during reactivation that was associated with later true and false memories. We predicted that the quality of reactivation, as determined by online ratings of subjective recollection, would increase subsequent true memories but also facilitate incorporation of the lure photograph, thereby increasing subsequent false memories. The fMRI results revealed that the quality of reactivation modulated subsequent true and false memories via recruitment of left posterior parahippocampal, bilateral retrosplenial, and bilateral posterior inferior parietal cortices. However, the timing of neural recruitment and the way in which memories were reactivated contributed to differences in whether memory reactivation led to distortions or not. These data reveal the neural mechanisms recruited during memory reactivation that modify how memories will be subsequently retrieved, supporting the flexible and dynamic aspects of memory.

Suppressed neural complexity during ketamine- and propofol-induced unconsciousness.

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Wang, Jisung; Noh, Gyu-Jeong; Choi, Byung-Moon; Ku, Seung-Woo; Joo, Pangyu; Jung, Woo-Sung; Kim, Seunghwan; Lee, Heonsoo

2017-07-13

Ketamine and propofol have distinctively different molecular mechanisms of action and neurophysiological features, although both induce loss of consciousness. Therefore, identifying a common feature of ketamine- and propofol-induced unconsciousness would provide insight into the underlying mechanism of losing consciousness. In this study we search for a common feature by applying the concept of type-II complexity, and argue that neural complexity is essential for a brain to maintain consciousness. To test this hypothesis, we show that complexity is suppressed during loss of consciousness induced by ketamine or propofol. We analyzed the randomness (type-I complexity) and complexity (type-II complexity) of electroencephalogram (EEG) signals before and after bolus injection of ketamine or propofol. For the analysis, we use Mean Information Gain (MIG) and Fluctuation Complexity (FC), which are information-theory-based measures that quantify disorder and complexity of dynamics respectively. Both ketamine and propofol reduced the complexity of the EEG signal, but ketamine increased the randomness of the signal and propofol decreased it. The finding supports our claim and suggests EEG complexity as a candidate for a consciousness indicator. Copyright © 2017 Elsevier B.V. All rights reserved.

Earthquake-induced landslide-susceptibility mapping using an artificial neural network

Directory of Open Access Journals (Sweden)

S. Lee

2006-01-01

Full Text Available The purpose of this study was to apply and verify landslide-susceptibility analysis techniques using an artificial neural network and a Geographic Information System (GIS applied to Baguio City, Philippines. The 16 July 1990 earthquake-induced landslides were studied. Landslide locations were identified from interpretation of aerial photographs and field survey, and a spatial database was constructed from topographic maps, geology, land cover and terrain mapping units. Factors that influence landslide occurrence, such as slope, aspect, curvature and distance from drainage were calculated from the topographic database. Lithology and distance from faults were derived from the geology database. Land cover was identified from the topographic database. Terrain map units were interpreted from aerial photographs. These factors were used with an artificial neural network to analyze landslide susceptibility. Each factor weight was determined by a back-propagation exercise. Landslide-susceptibility indices were calculated using the back-propagation weights, and susceptibility maps were constructed from GIS data. The susceptibility map was compared with known landslide locations and verified. The demonstrated prediction accuracy was 93.20%.

Excitation of lateral habenula neurons as a neural mechanism underlying ethanol-induced conditioned taste aversion.

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Tandon, Shashank; Keefe, Kristen A; Taha, Sharif A

2017-02-15

The lateral habenula (LHb) has been implicated in regulation of drug-seeking behaviours through aversion-mediated learning. In this study, we recorded neuronal activity in the LHb of rats during an operant task before and after ethanol-induced conditioned taste aversion (CTA) to saccharin. Ethanol-induced CTA caused significantly higher baseline firing rates in LHb neurons, as well as elevated firing rates in response to cue presentation, lever press and saccharin taste. In a separate cohort of rats, we found that bilateral LHb lesions blocked ethanol-induced CTA. Our results strongly suggest that excitation of LHb neurons is required for ethanol-induced CTA, and point towards a mechanism through which LHb firing may regulate voluntary ethanol consumption. Ethanol, like other drugs of abuse, has both rewarding and aversive properties. Previous work suggests that sensitivity to ethanol's aversive effects negatively modulates voluntary alcohol intake and thus may be important in vulnerability to developing alcohol use disorders. We previously found that rats with lesions of the lateral habenula (LHb), which is implicated in aversion-mediated learning, show accelerated escalation of voluntary ethanol consumption. To understand neural encoding in the LHb contributing to ethanol-induced aversion, we recorded neural firing in the LHb of freely behaving, water-deprived rats before and after an ethanol-induced (1.5 g kg -1 20% ethanol, i.p.) conditioned taste aversion (CTA) to saccharin taste. Ethanol-induced CTA strongly decreased motivation for saccharin in an operant task to obtain the tastant. Comparison of LHb neural firing before and after CTA induction revealed four main differences in firing properties. First, baseline firing after CTA induction was significantly higher. Second, firing evoked by cues signalling saccharin availability shifted from a pattern of primarily inhibition before CTA to primarily excitation after CTA induction. Third, CTA induction reduced

Excitation of lateral habenula neurons as a neural mechanism underlying ethanol‐induced conditioned taste aversion

Science.gov (United States)

Keefe, Kristen A.; Taha, Sharif A.

2016-01-01

Key points The lateral habenula (LHb) has been implicated in regulation of drug‐seeking behaviours through aversion‐mediated learning.In this study, we recorded neuronal activity in the LHb of rats during an operant task before and after ethanol‐induced conditioned taste aversion (CTA) to saccharin.Ethanol‐induced CTA caused significantly higher baseline firing rates in LHb neurons, as well as elevated firing rates in response to cue presentation, lever press and saccharin taste.In a separate cohort of rats, we found that bilateral LHb lesions blocked ethanol‐induced CTA.Our results strongly suggest that excitation of LHb neurons is required for ethanol‐induced CTA, and point towards a mechanism through which LHb firing may regulate voluntary ethanol consumption. Abstract Ethanol, like other drugs of abuse, has both rewarding and aversive properties. Previous work suggests that sensitivity to ethanol's aversive effects negatively modulates voluntary alcohol intake and thus may be important in vulnerability to developing alcohol use disorders. We previously found that rats with lesions of the lateral habenula (LHb), which is implicated in aversion‐mediated learning, show accelerated escalation of voluntary ethanol consumption. To understand neural encoding in the LHb contributing to ethanol‐induced aversion, we recorded neural firing in the LHb of freely behaving, water‐deprived rats before and after an ethanol‐induced (1.5 g kg−1 20% ethanol, i.p.) conditioned taste aversion (CTA) to saccharin taste. Ethanol‐induced CTA strongly decreased motivation for saccharin in an operant task to obtain the tastant. Comparison of LHb neural firing before and after CTA induction revealed four main differences in firing properties. First, baseline firing after CTA induction was significantly higher. Second, firing evoked by cues signalling saccharin availability shifted from a pattern of primarily inhibition before CTA to primarily excitation after CTA

Diet-induced obesity and low testosterone increase neuroinflammation and impair neural function.

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Jayaraman, Anusha; Lent-Schochet, Daniella; Pike, Christian J

2014-09-16

Low testosterone and obesity are independent risk factors for dysfunction of the nervous system including neurodegenerative disorders such as Alzheimer's disease (AD). In this study, we investigate the independent and cooperative interactions of testosterone and diet-induced obesity on metabolic, inflammatory, and neural health indices in the central and peripheral nervous systems. Male C57B6/J mice were maintained on normal or high-fat diet under varying testosterone conditions for a four-month treatment period, after which metabolic indices were measured and RNA isolated from cerebral cortex and sciatic nerve. Cortices were used to generate mixed glial cultures, upon which embryonic cerebrocortical neurons were co-cultured for assessment of neuron survival and neurite outgrowth. Peripheral nerve damage was determined using paw-withdrawal assay, myelin sheath protein expression levels, and Na+,K+-ATPase activity levels. Our results demonstrate that detrimental effects on both metabolic (blood glucose, insulin sensitivity) and proinflammatory (cytokine expression) responses caused by diet-induced obesity are exacerbated by testosterone depletion. Mixed glial cultures generated from obese mice retain elevated cytokine expression, although low testosterone effects do not persist ex vivo. Primary neurons co-cultured with glial cultures generated from high-fat fed animals exhibit reduced survival and poorer neurite outgrowth. In addition, low testosterone and diet-induced obesity combine to increase inflammation and evidence of nerve damage in the peripheral nervous system. Testosterone and diet-induced obesity independently and cooperatively regulate neuroinflammation in central and peripheral nervous systems, which may contribute to observed impairments in neural health. Together, our findings suggest that low testosterone and obesity are interactive regulators of neuroinflammation that, in combination with adipose-derived inflammatory pathways and other factors

A scale out approach towards neural induction of human induced pluripotent stem cells for neurodevelopmental toxicity studies.

Science.gov (United States)

Miranda, Cláudia C; Fernandes, Tiago G; Pinto, Sandra N; Prieto, Manuel; Diogo, M Margarida; Cabral, Joaquim M S

2018-05-21

Stem cell's unique properties confer them a multitude of potential applications in the fields of cellular therapy, disease modelling and drug screening fields. In particular, the ability to differentiate neural progenitors (NP) from human induced pluripotent stem cells (hiPSCs) using chemically-defined conditions provides an opportunity to create a simple and straightforward culture platform for application in these fields. Here, we demonstrated that hiPSCs are capable of undergoing neural commitment inside microwells, forming characteristic neural structures resembling neural rosettes and further give rise to glial and neuronal cells. Furthermore, this platform can be applied towards the study of the effect of neurotoxic molecules that impair normal embryonic development. As a proof of concept, the neural teratogenic potential of the antiepileptic drug valproic acid (VPA) was analyzed. It was verified that exposure to VPA, close to typical dosage values (0.3 to 0.75 mM), led to a prevalence of NP structures over neuronal differentiation, as confirmed by analysis of the expression of neural cell adhesion molecule, as well as neural rosette number and morphology assessment. The methodology proposed herein for the generation and neural differentiation of hiPSC aggregates can potentially complement current toxicity tests such as the humanized embryonic stem cell test for the detection of teratogenic compounds that can interfere with normal embryonic development. Copyright © 2018 Elsevier B.V. All rights reserved.

Induced Pluripotent Stem Cell-Derived Neural Cells Survive and Mature in the Nonhuman Primate Brain

Directory of Open Access Journals (Sweden)

Marina E. Emborg

2013-03-01

Full Text Available The generation of induced pluripotent stem cells (iPSCs opens up the possibility for personalized cell therapy. Here, we show that transplanted autologous rhesus monkey iPSC-derived neural progenitors survive for up to 6 months and differentiate into neurons, astrocytes, and myelinating oligodendrocytes in the brains of MPTP-induced hemiparkinsonian rhesus monkeys with a minimal presence of inflammatory cells and reactive glia. This finding represents a significant step toward personalized regenerative therapies.

Mindful attention reduces neural and self-reported cue-induced craving in smokers

Science.gov (United States)

Creswell, John David; Tabibnia, Golnaz; Julson, Erica; Kober, Hedy; Tindle, Hilary A.

2013-01-01

An emerging body of research suggests that mindfulness-based interventions may be beneficial for smoking cessation and the treatment of other addictive disorders. One way that mindfulness may facilitate smoking cessation is through the reduction of craving to smoking cues. The present work considers whether mindful attention can reduce self-reported and neural markers of cue-induced craving in treatment seeking smokers. Forty-seven (n = 47) meditation-naïve treatment-seeking smokers (12-h abstinent from smoking) viewed and made ratings of smoking and neutral images while undergoing functional magnetic resonance imaging (fMRI). Participants were trained and instructed to view these images passively or with mindful attention. Results indicated that mindful attention reduced self-reported craving to smoking images, and reduced neural activity in a craving-related region of subgenual anterior cingulate cortex (sgACC). Moreover, a psychophysiological interaction analysis revealed that mindful attention reduced functional connectivity between sgACC and other craving-related regions compared to passively viewing smoking images, suggesting that mindfulness may decouple craving neurocircuitry when viewing smoking cues. These results provide an initial indication that mindful attention may describe a ‘bottom-up’ attention to one’s present moment experience in ways that can help reduce subjective and neural reactivity to smoking cues in smokers. PMID:22114078

Topological probability and connection strength induced activity in complex neural networks

International Nuclear Information System (INIS)

Du-Qu, Wei; Bo, Zhang; Dong-Yuan, Qiu; Xiao-Shu, Luo

2010-01-01

Recent experimental evidence suggests that some brain activities can be assigned to small-world networks. In this work, we investigate how the topological probability p and connection strength C affect the activities of discrete neural networks with small-world (SW) connections. Network elements are described by two-dimensional map neurons (2DMNs) with the values of parameters at which no activity occurs. It is found that when the value of p is smaller or larger, there are no active neurons in the network, no matter what the value of connection strength is; for a given appropriate connection strength, there is an intermediate range of topological probability where the activity of 2DMN network is induced and enhanced. On the other hand, for a given intermediate topological probability level, there exists an optimal value of connection strength such that the frequency of activity reaches its maximum. The possible mechanism behind the action of topological probability and connection strength is addressed based on the bifurcation method. Furthermore, the effects of noise and transmission delay on the activity of neural network are also studied. (general)

Induced pluripotent stem cell-derived neural cells survive and mature in the nonhuman primate brain.

Science.gov (United States)

Emborg, Marina E; Liu, Yan; Xi, Jiajie; Zhang, Xiaoqing; Yin, Yingnan; Lu, Jianfeng; Joers, Valerie; Swanson, Christine; Holden, James E; Zhang, Su-Chun

2013-03-28

The generation of induced pluripotent stem cells (iPSCs) opens up the possibility for personalized cell therapy. Here, we show that transplanted autologous rhesus monkey iPSC-derived neural progenitors survive for up to 6 months and differentiate into neurons, astrocytes, and myelinating oligodendrocytes in the brains of MPTP-induced hemiparkinsonian rhesus monkeys with a minimal presence of inflammatory cells and reactive glia. This finding represents a significant step toward personalized regenerative therapies. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

[A comparative study on inducing non-homologous mesenchymal stem cells to differentiate into neural stem cells using non-homologous cerebrospinal fluid].

Science.gov (United States)

Ren, Chao; Liu, Xiaoyun; Wan, Meirong; Geng, Deqin; Ge, Wei; Li, Jinmei; Zhang, Weiwei

2013-12-01

In order to set up a base for stem cells to be widely used in clinical medicine, we tried to optimize, in this study, the technique that induces human mesenchymal stem cells (hMSCs) to differentiate into neural stem cells by using cerebrospinal fluid (CSF) from the different groups. After the induction, presence of neural stem cells was confirmed with microscope observation, flow cytometry analysis, immunohistochemistry and fluorescent immunohistochemistry. At the same time, we also compared and analysed the data of the number of stem cells when it totally met the requirements for clinical treatment and the days required. At last, we confirmed that hMSCs could be induced to differentiate into neural stem cells, and that the number of cells totally met the requirements for clinical treatment. But there were some differences both in the number of cells and the days required. Among the groups, the group that marrow mesenchymal stem cells from patients own induced by CSF from healthy volunteers used the shortest time and the quantity of the cells was significantly higher than those of the others.

Purification of human induced pluripotent stem cell-derived neural precursors using magnetic activated cell sorting.

Science.gov (United States)

Rodrigues, Gonçalo M C; Fernandes, Tiago G; Rodrigues, Carlos A V; Cabral, Joaquim M S; Diogo, Maria Margarida

2015-01-01

Neural precursor (NP) cells derived from human induced pluripotent stem cells (hiPSCs), and their neuronal progeny, will play an important role in disease modeling, drug screening tests, central nervous system development studies, and may even become valuable for regenerative medicine treatments. Nonetheless, it is challenging to obtain homogeneous and synchronously differentiated NP populations from hiPSCs, and after neural commitment many pluripotent stem cells remain in the differentiated cultures. Here, we describe an efficient and simple protocol to differentiate hiPSC-derived NPs in 12 days, and we include a final purification stage where Tra-1-60+ pluripotent stem cells (PSCs) are removed using magnetic activated cell sorting (MACS), leaving the NP population nearly free of PSCs.

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

Science.gov (United States)

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

2017-01-01

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

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.

Synchrony-induced modes of oscillation of a neural field model

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Esnaola-Acebes, Jose M.; Roxin, Alex; Avitabile, Daniele; Montbrió, Ernest

2017-11-01

We investigate the modes of oscillation of heterogeneous ring networks of quadratic integrate-and-fire (QIF) neurons with nonlocal, space-dependent coupling. Perturbations of the equilibrium state with a particular wave number produce transient standing waves with a specific temporal frequency, analogously to those in a tense string. In the neuronal network, the equilibrium corresponds to a spatially homogeneous, asynchronous state. Perturbations of this state excite the network's oscillatory modes, which reflect the interplay of episodes of synchronous spiking with the excitatory-inhibitory spatial interactions. In the thermodynamic limit, an exact low-dimensional neural field model describing the macroscopic dynamics of the network is derived. This allows us to obtain formulas for the Turing eigenvalues of the spatially homogeneous state and hence to obtain its stability boundary. We find that the frequency of each Turing mode depends on the corresponding Fourier coefficient of the synaptic pattern of connectivity. The decay rate instead is identical for all oscillation modes as a consequence of the heterogeneity-induced desynchronization of the neurons. Finally, we numerically compute the spectrum of spatially inhomogeneous solutions branching from the Turing bifurcation, showing that similar oscillatory modes operate in neural bump states and are maintained away from onset.

A neural flow estimator

DEFF Research Database (Denmark)

Jørgensen, Ivan Harald Holger; Bogason, Gudmundur; Bruun, Erik

1995-01-01

This paper proposes a new way to estimate the flow in a micromechanical flow channel. A neural network is used to estimate the delay of random temperature fluctuations induced in a fluid. The design and implementation of a hardware efficient neural flow estimator is described. The system...... is implemented using switched-current technique and is capable of estimating flow in the μl/s range. The neural estimator is built around a multiplierless neural network, containing 96 synaptic weights which are updated using the LMS1-algorithm. An experimental chip has been designed that operates at 5 V...

Forecasting of Energy Expenditure of Induced Seismicity with Use of Artificial Neural Network

Science.gov (United States)

Cichy, Tomasz; Banka, Piotr

2017-12-01

Coal mining in many Polish mines in the Upper Silesian Coal Basin is accompanied by high levels of induced seismicity. In mining plants, the methods of shock monitoring are improved, allowing for more accurate localization of the occurring phenomena and determining their seismic energy. Equally important is the development of ways of forecasting seismic hazards that may occur while implementing mine design projects. These methods, depending on the length of time for which the forecasts are made, can be divided into: longterm, medium-term, short-term and so-called alarm. Long-term forecasts are particularly useful for the design of seam exploitations. The paper presents a method of predicting changes in energy expenditure of shock using a properly trained artificial neural network. This method allows to make long-term forecasts at the stage of the mine’s exploitation design, thus enabling the mining work plans to be reviewed to minimize the potential for tremors. The information given at the input of the neural network is indicative of the specific energy changes of the elastic deformation occurring in the selected, thick, resistant rock layers (tremor-prone layers). Energy changes, taking place in one or more tremor-prone layers are considered. These indicators describe only the specific energy changes of the elastic deformation accumulating in the rock as a consequence of the mining operation, but does not determine the amount of energy released during the destruction of a given volume of rock. In this process, the potential energy of elastic strain transforms into other, non-measurable energy types, including the seismic energy of recorded tremors. In this way, potential energy changes affect the observed induced seismicity. The parameters used are characterized by increases (declines) of specific energy with separation to occur before the hypothetical destruction of the rock and after it. Additional input information is an index characterizing the rate of

c-Myc Enhances Sonic Hedgehog-Induced Medulloblastoma Formation from Nestin-Expressing Neural Progenitors in Mice

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Ganesh Rao

2003-05-01

Full Text Available Medulloblastomas are malignant brain tumors that arise in the cerebella of children. The presumed cellsof-origin are undifferentiated precursors of granule neurons that occupy the external granule layer (EGL of the developing cerebellum. The overexpression of proteins that normally stimulate proliferation of neural progenitor cells may initiate medulloblastoma formation. Two known mitogens for neural progenitors are the c-Myc oncoprotein and Sonic hedgehog (Shh, a crucial determinant of embryonic pattern formation in the central nervous system. We modeled the ability of c-Myc and Shh to induce medulloblastoma in mice using the RCAS/tv-a system, which allows postnatal gene transfer and expression in a cell type-specific manner. We targeted the expression of Shh and c-Myc to nestin-expressing neural progenitor cells by injecting replication-competent ALV splice acceptor (RCAS vectors into the cerebella of newborn mice. Following injection with RCAS-Shh alone, 3/32 (9% mice developed medulloblastomas and 5/32 showed multifocal hyperproliferation of the EGL, possibly a precursor stage of medulloblastoma. Following injection with RCAS-Shh plus RCAS-Myc, 9/39 (23% mice developed medulloblastomas. We conclude that nestin-expressing neural progenitors, present in the cerebellum at birth, can act as the cells-of-origin for medulloblastoma, and that c-Myc cooperates with Shh to enhance tumorigenicity.

Anti-ghrelin Spiegelmer inhibits exogenous ghrelin-induced increases in food intake, hoarding, and neural activation, but not food deprivation-induced increases

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Teubner, Brett J. W.

2013-01-01

Circulating concentrations of the stomach-derived “hunger-peptide” ghrelin increase in direct proportion to the time since the last meal. Exogenous ghrelin also increases food intake in rodents and humans, suggesting ghrelin may increase post-fast ingestive behaviors. Food intake after food deprivation is increased by laboratory rats and mice, but not by humans (despite dogma to the contrary) or by Siberian hamsters; instead, humans and Siberian hamsters increase food hoarding, suggesting the latter as a model of fasting-induced changes in human ingestive behavior. Exogenous ghrelin markedly increases food hoarding by ad libitum-fed Siberian hamsters similarly to that after food deprivation, indicating sufficiency. Here, we tested the necessity of ghrelin to increase food foraging, food hoarding, and food intake, and neural activation [c-Fos immunoreactivity (c-Fos-ir)] using anti-ghrelin Spiegelmer NOX-B11–2 (SPM), an l-oligonucleotide that specifically binds active ghrelin, inhibiting peptide-receptor interaction. SPM blocked exogenous ghrelin-induced increases in food hoarding the first 2 days after injection, and foraging and food intake at 1–2 h and 2–4 h, respectively, and inhibited hypothalamic c-Fos-ir. SPM given every 24 h across 48-h food deprivation inconsistently inhibited food hoarding after refeeding and c-Fos-ir, similarly to inabilities to do so in laboratory rats and mice. These results suggest that ghrelin may not be necessary for food deprivation-induced foraging and hoarding and neural activation. A possible compensatory response, however, may underlie these findings because SPM treatment led to marked increases in circulating ghrelin concentrations. Collectively, these results show that SPM can block exogenous ghrelin-induced ingestive behaviors, but the necessity of ghrelin for food deprivation-induced ingestive behaviors remains unclear. PMID:23804279

Comparison of canny and V1 neural network based edge detectors applied to road extraction

CSIR Research Space (South Africa)

Hauptfleisch, AC

2006-11-01

Full Text Available and vertically, for succes- sive pixels p and q that satisfy the distance and gradient orien- tation conditions. The conditions can be summarised as follows (See Figure 3): • The gradient at p must be approximately equal to the gra- dient at q plus 180...

Neural basis of stereotype-induced shifts in women's mental rotation performance.

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Wraga, Maryjane; Helt, Molly; Jacobs, Emily; Sullivan, Kerry

2007-03-01

Recent negative focus on women's academic abilities has fueled disputes over gender disparities in the sciences. The controversy derives, in part, from women's relatively poorer performance in aptitude tests, many of which require skills of spatial reasoning. We used functional magnetic imaging to examine the neural structure underlying shifts in women's performance of a spatial reasoning task induced by positive and negative stereotypes. Three groups of participants performed a task involving imagined rotations of the self. Prior to scanning, the positive stereotype group was exposed to a false but plausible stereotype of women's superior perspective-taking abilities; the negative stereotype group was exposed to the pervasive stereotype that men outperform women on spatial tasks; and the control group received neutral information. The significantly poorer performance we found in the negative stereotype group corresponded to increased activation in brain regions associated with increased emotional load. In contrast, the significantly improved performance we found in the positive stereotype group was associated with increased activation in visual processing areas and, to a lesser degree, complex working memory processes. These findings suggest that stereotype messages affect the brain selectively, with positive messages producing relatively more efficient neural strategies than negative messages.

Effects of small-world connectivity on noise-induced temporal and spatial order in neural media

International Nuclear Information System (INIS)

Perc, Matjaz

2007-01-01

We present an overview of possible effects of small-world connectivity on noise-induced temporal and spatial order in a two-dimensional network of excitable neural media with FitzHugh-Nagumo local dynamics. Small-world networks are characterized by a given fraction of so-called long-range couplings or shortcut links that connect distant units of the system, while all other units are coupled in a diffusive-like manner. Interestingly, already a small fraction of these long-range couplings can have wide-ranging effects on the temporal as well as spatial noise-induced dynamics of the system. Here we present two main effects. First, we show that the temporal order, characterized by the autocorrelation of a firing-rate function, can be greatly enhanced by the introduction of small-world connectivity, whereby the effect increases with the increasing fraction of introduced shortcut links. Second, we show that the introduction of long-range couplings induces disorder of otherwise ordered, spiral-wave-like, noise-induced patterns that can be observed by exclusive diffusive connectivity of spatial units. Thereby, already a small fraction of shortcut links is sufficient to destroy coherent pattern formation in the media. Although the two results seem contradictive, we provide an explanation considering the inherent scale-free nature of small-world networks, which on one hand, facilitates signal transduction and thus temporal order in the system, whilst on the other hand, disrupts the internal spatial scale of the media thereby hindering the existence of coherent wave-like patterns. Additionally, the importance of spatially versus temporally ordered neural network functioning is discussed

High glucose-induced oxidative stress represses sirtuin deacetylase expression and increases histone acetylation leading to neural tube defects.

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Yu, Jingwen; Wu, Yanqing; Yang, Peixin

2016-05-01

Aberrant epigenetic modifications are implicated in maternal diabetes-induced neural tube defects (NTDs). Because cellular stress plays a causal role in diabetic embryopathy, we investigated the possible role of the stress-resistant sirtuin (SIRT) family histone deacetylases. Among the seven sirtuins (SIRT1-7), pre-gestational maternal diabetes in vivo or high glucose in vitro significantly reduced the expression of SIRT 2 and SIRT6 in the embryo or neural stem cells, respectively. The down-regulation of SIRT2 and SIRT6 was reversed by superoxide dismutase 1 (SOD1) over-expression in the in vivo mouse model of diabetic embryopathy and the SOD mimetic, tempol and cell permeable SOD, PEGSOD in neural stem cell cultures. 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), a superoxide generating agent, mimicked high glucose-suppressed SIRT2 and SIRT6 expression. The acetylation of histone 3 at lysine residues 56 (H3K56), H3K14, H3K9, and H3K27, putative substrates of SIRT2 and SIRT6, was increased by maternal diabetes in vivo or high glucose in vitro, and these increases were blocked by SOD1 over-expression or tempol treatment. SIRT2 or SIRT6 over-expression abrogated high glucose-suppressed SIRT2 or SIRT6 expression, and prevented the increase in acetylation of their histone substrates. The potent sirtuin activator (SRT1720) blocked high glucose-increased histone acetylation and NTD formation, whereas the combination of a pharmacological SIRT2 inhibitor and a pan SIRT inhibitor mimicked the effect of high glucose on increased histone acetylation and NTD induction. Thus, diabetes in vivo or high glucose in vitro suppresses SIRT2 and SIRT6 expression through oxidative stress, and sirtuin down-regulation-induced histone acetylation may be involved in diabetes-induced NTDs. The mechanism underlying pre-gestational diabetes-induced neural tube defects (NTDs) is still elusive. Our study unravels a new epigenetic mechanism in which maternal diabetes-induced oxidative stress represses

Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD-1 mice

Energy Technology Data Exchange (ETDEWEB)

Dawson, Jennifer E [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen' s University, Kingston, Ontario, K7L 3N6 (Canada); Raymond, Angela M [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen' s University, Kingston, Ontario, K7L 3N6 (Canada); Winn, Louise M [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen' s University, Kingston, Ontario, K7L 3N6 (Canada)

2006-03-01

In utero exposure to valproic acid (VPA) during pregnancy is associated with an increased risk of neural tube defects (NTDs). Although the mechanism by which VPA mediates these effects is unknown, VPA-initiated changes in embryonic protein levels have been implicated. The objectives of this study were to investigate the effect of in utero VPA exposure on embryonic protein levels of p53, NF-{kappa}B, Pim-1, c-Myb, Bax, and Bcl-2 in the CD-1 mouse. We also evaluated the protective effects of folic acid and pantothenic acid on VPA-induced NTDs and VPA-induced embryonic protein changes in this model. Pregnant CD-1 mice were administered a teratogenic dose of VPA prior to neural tube closure and embryonic protein levels were analyzed. In our study, VPA (400 mg/kg)-induced NTDs (24%) and VPA-exposed embryos with an NTD showed a 2-fold increase in p53, and 4-fold decreases in NF-{kappa}B, Pim-1, and c-Myb protein levels compared to their phenotypically normal littermates (P < 0.05). Additionally, VPA increased the ratio of embryonic Bax/Bcl-2 protein levels (P < 0.05). Pretreatment of pregnant dams with either folic acid or pantothenic acid prior to VPA significantly protected against VPA-induced NTDs (P < 0.05). Folic acid also reduced VPA-induced alterations in p53, NF-{kappa}B, Pim-1, c-Myb, and Bax/Bcl-2 protein levels, while pantothenic acid prevented VPA-induced alterations in NF-{kappa}B, Pim-1, and c-Myb. We hypothesize that folic acid and pantothenic acid protect CD-1 embryos from VPA-induced NTDs by independent, but not mutually exclusive mechanisms, both of which may be mediated by the prevention of VPA-induced alterations in proteins involved in neurulation.

Herpes simplex virus induces neural oxidative damage via microglial cell Toll-like receptor-2

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Little Morgan R

2010-06-01

Full Text Available Abstract Background Using a murine model of herpes simplex virus (HSV-1 encephalitis, our laboratory has determined that induction of proinflammatory mediators in response to viral infection is largely mediated through a Toll-like receptor-2 (TLR2-dependent mechanism. Published studies have shown that, like other inflammatory mediators, reactive oxygen species (ROS are generated during viral brain infection. It is increasingly clear that ROS are responsible for facilitating secondary tissue damage during central nervous system infection and may contribute to neurotoxicity associated with herpes encephalitis. Methods Purified microglial cell and mixed neural cell cultures were prepared from C57B/6 and TLR2-/- mice. Intracellular ROS production in cultured murine microglia was measured via 2', 7'-Dichlorofluorescin diacetate (DCFH-DA oxidation. An assay for 8-isoprostane, a marker of lipid peroxidation, was utilized to measure free radical-associated cellular damage. Mixed neural cultures obtained from β-actin promoter-luciferase transgenic mice were used to detect neurotoxicity induced by HSV-infected microglia. Results Stimulation with HSV-1 elevated intracellular ROS in wild-type microglial cell cultures, while TLR2-/- microglia displayed delayed and attenuated ROS production following viral infection. HSV-infected TLR2-/- microglia produced less neuronal oxidative damage to mixed neural cell cultures in comparison to HSV-infected wild-type microglia. Further, HSV-infected TLR2-/- microglia were found to be less cytotoxic to cultured neurons compared to HSV-infected wild-type microglia. These effects were associated with decreased activation of p38 MAPK and p42/p44 ERK in TLR2-/- mice. Conclusions These studies demonstrate the importance of microglial cell TLR2 in inducing oxidative stress and neuronal damage in response to viral infection.

ADAM13 Induces Cranial Neural Crest by Cleaving Class B Ephrins and Regulating Wnt Signaling

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Wei, Shuo; Xu, Guofeng; Bridges, Lance C.; Williams, Phoebe; White, Judith M.; DeSimone, Douglas W.

2010-01-01

SUMMARY The cranial neural crest (CNC) are multipotent embryonic cells that contribute to craniofacial structures and other cells and tissues of the vertebrate head. During embryogenesis, CNC is induced at the neural plate boundary through the interplay of several major signaling pathways. Here we report that the metalloproteinase activity of ADAM13 is required for early induction of CNC in Xenopus. In both cultured cells and X. tropicalis embryos, membrane-bound Ephrins (Efns) B1 and B2 were identified as substrates for ADAM13. ADAM13 upregulates canonical Wnt signaling and early expression of the transcription factor snail2, whereas EfnB1 inhibits the canonical Wnt pathway and snail2 expression. We propose that by cleaving class B Efns, ADAM13 promotes canonical Wnt signaling and early CNC induction. PMID:20708595

Interpretable neural networks with BP-SOM

NARCIS (Netherlands)

Weijters, A.J.M.M.; Bosch, van den A.P.J.; Pobil, del A.P.; Mira, J.; Ali, M.

1998-01-01

Artificial Neural Networks (ANNS) are used successfully in industry and commerce. This is not surprising since neural networks are especially competitive for complex tasks for which insufficient domain-specific knowledge is available. However, interpretation of models induced by ANNS is often

Artificial neural network for on-site quantitative analysis of soils using laser induced breakdown spectroscopy

Energy Technology Data Exchange (ETDEWEB)

El Haddad, J. [Univ. Bordeaux, LOMA, UMR 5798, F-33400 Talence (France); CNRS, LOMA, UMR 5798, F-33400 Talence (France); Villot-Kadri, M.; Ismaël, A.; Gallou, G. [IVEA Solution, Centre Scientifique d' Orsay, Bât 503, 91400 Orsay (France); Michel, K.; Bruyère, D.; Laperche, V. [BRGM, Service Métrologie, Monitoring et Analyse, 3 avenue Claude Guillemin, B.P 36009, 45060 Orléans Cedex (France); Canioni, L. [Univ. Bordeaux, LOMA, UMR 5798, F-33400 Talence (France); CNRS, LOMA, UMR 5798, F-33400 Talence (France); Bousquet, B., E-mail: bruno.bousquet@u-bordeaux1.fr [Univ. Bordeaux, LOMA, UMR 5798, F-33400 Talence (France); CNRS, LOMA, UMR 5798, F-33400 Talence (France)

2013-01-01

Nowadays, due to environmental concerns, fast on-site quantitative analyses of soils are required. Laser induced breakdown spectroscopy is a serious candidate to address this challenge and is especially well suited for multi-elemental analysis of heavy metals. However, saturation and matrix effects prevent from a simple treatment of the LIBS data, namely through a regular calibration curve. This paper details the limits of this approach and consequently emphasizes the advantage of using artificial neural networks well suited for non-linear and multi-variate calibration. This advanced method of data analysis is evaluated in the case of real soil samples and on-site LIBS measurements. The selection of the LIBS data as input data of the network is particularly detailed and finally, resulting errors of prediction lower than 20% for aluminum, calcium, copper and iron demonstrate the good efficiency of the artificial neural networks for on-site quantitative LIBS of soils. - Highlights: ► We perform on-site quantitative LIBS analysis of soil samples. ► We demonstrate that univariate analysis is not convenient. ► We exploit artificial neural networks for LIBS analysis. ► Spectral lines other than the ones from the analyte must be introduced.

Artificial neural network for on-site quantitative analysis of soils using laser induced breakdown spectroscopy

International Nuclear Information System (INIS)

El Haddad, J.; Villot-Kadri, M.; Ismaël, A.; Gallou, G.; Michel, K.; Bruyère, D.; Laperche, V.; Canioni, L.; Bousquet, B.

2013-01-01

Nowadays, due to environmental concerns, fast on-site quantitative analyses of soils are required. Laser induced breakdown spectroscopy is a serious candidate to address this challenge and is especially well suited for multi-elemental analysis of heavy metals. However, saturation and matrix effects prevent from a simple treatment of the LIBS data, namely through a regular calibration curve. This paper details the limits of this approach and consequently emphasizes the advantage of using artificial neural networks well suited for non-linear and multi-variate calibration. This advanced method of data analysis is evaluated in the case of real soil samples and on-site LIBS measurements. The selection of the LIBS data as input data of the network is particularly detailed and finally, resulting errors of prediction lower than 20% for aluminum, calcium, copper and iron demonstrate the good efficiency of the artificial neural networks for on-site quantitative LIBS of soils. - Highlights: ► We perform on-site quantitative LIBS analysis of soil samples. ► We demonstrate that univariate analysis is not convenient. ► We exploit artificial neural networks for LIBS analysis. ► Spectral lines other than the ones from the analyte must be introduced

Conversion of adult human peripheral blood mononuclear cells into induced neural stem cell by using episomal vectors

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Xihe Tang

2016-03-01

Full Text Available Human neural stem cells (NSCs hold great promise for research and therapy in neural diseases. Many studies have shown direct induction of NSCs from human fibroblasts, which require an invasive skin biopsy and a prolonged period of expansion in cell culture prior to use. Peripheral blood (PB is routinely used in medical diagnoses, and represents a noninvasive and easily accessible source of cells. Here we show direct derivation of NSCs from adult human PB mononuclear cells (PB-MNCs by employing episomal vectors for transgene delivery. These induced NSCs (iNSCs can expand more than 60 passages, can exhibit NSC morphology, gene expression, differentiation potential, and self-renewing capability and can give rise to multiple functional neural subtypes and glial cells in vitro. Furthermore, the iNSCs carry a specific regional identity and have electrophysiological activity upon differentiation. Our findings provide an easily accessible approach for generating human iNSCs which will facilitate disease modeling, drug screening, and possibly regenerative medicine.

Learning-induced neural plasticity of speech processing before birth.

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Partanen, Eino; Kujala, Teija; Näätänen, Risto; Liitola, Auli; Sambeth, Anke; Huotilainen, Minna

2013-09-10

Learning, the foundation of adaptive and intelligent behavior, is based on plastic changes in neural assemblies, reflected by the modulation of electric brain responses. In infancy, auditory learning implicates the formation and strengthening of neural long-term memory traces, improving discrimination skills, in particular those forming the prerequisites for speech perception and understanding. Although previous behavioral observations show that newborns react differentially to unfamiliar sounds vs. familiar sound material that they were exposed to as fetuses, the neural basis of fetal learning has not thus far been investigated. Here we demonstrate direct neural correlates of human fetal learning of speech-like auditory stimuli. We presented variants of words to fetuses; unlike infants with no exposure to these stimuli, the exposed fetuses showed enhanced brain activity (mismatch responses) in response to pitch changes for the trained variants after birth. Furthermore, a significant correlation existed between the amount of prenatal exposure and brain activity, with greater activity being associated with a higher amount of prenatal speech exposure. Moreover, the learning effect was generalized to other types of similar speech sounds not included in the training material. Consequently, our results indicate neural commitment specifically tuned to the speech features heard before birth and their memory representations.

Development of teeth in chick embryos after mouse neural crest transplantations.

Science.gov (United States)

Mitsiadis, Thimios A; Chéraud, Yvonnick; Sharpe, Paul; Fontaine-Pérus, Josiane

2003-05-27

Teeth were lost in birds 70-80 million years ago. Current thinking holds that it is the avian cranial neural crest-derived mesenchyme that has lost odontogenic capacity, whereas the oral epithelium retains the signaling properties required to induce odontogenesis. To investigate the odontogenic capacity of ectomesenchyme, we have used neural tube transplantations from mice to chick embryos to replace the chick neural crest cell populations with mouse neural crest cells. The mouse/chick chimeras obtained show evidence of tooth formation showing that avian oral epithelium is able to induce a nonavian developmental program in mouse neural crest-derived mesenchymal cells.

ADRA2B genotype differentially modulates stress-induced neural activity in the amygdala and hippocampus during emotional memory retrieval.

Science.gov (United States)

Li, Shijia; Weerda, Riklef; Milde, Christopher; Wolf, Oliver T; Thiel, Christiane M

2015-02-01

Noradrenaline interacts with stress hormones in the amygdala and hippocampus to enhance emotional memory consolidation, but the noradrenergic-glucocorticoid interaction at retrieval, where stress impairs memory, is less understood. We used a genetic neuroimaging approach to investigate whether a genetic variation of the noradrenergic system impacts stress-induced neural activity in amygdala and hippocampus during recognition of emotional memory. This study is based on genotype-dependent reanalysis of data from our previous publication (Li et al. Brain Imaging Behav 2014). Twenty-two healthy male volunteers were genotyped for the ADRA2B gene encoding the α2B-adrenergic receptor. Ten deletion carriers and 12 noncarriers performed an emotional face recognition task, while their brain activity was measured with fMRI. During encoding, 50 fearful and 50 neutral faces were presented. One hour later, they underwent either an acute stress (Trier Social Stress Test) or a control procedure which was followed immediately by the retrieval session, where participants had to discriminate between 100 old and 50 new faces. A genotype-dependent modulation of neural activity at retrieval was found in the bilateral amygdala and right hippocampus. Deletion carriers showed decreased neural activity in the amygdala when recognizing emotional faces in control condition and increased amygdala activity under stress. Noncarriers showed no differences in emotional modulated amygdala activation under stress or control. Instead, stress-induced increases during recognition of emotional faces were present in the right hippocampus. The genotype-dependent effects of acute stress on neural activity in amygdala and hippocampus provide evidence for noradrenergic-glucocorticoid interaction in emotional memory retrieval.

Study on the protective effect of MgSO4 on the radiation-induced neural stem cell injury

International Nuclear Information System (INIS)

Liu Ping; Tu Yu

2010-01-01

Objective: To explore the neuroprotective effect of magnesium sulfate on radiation induced neural stem cell injury. Methods: Brain tissue was obtained from new-born sprague-dawley rats within 24 hours, and the cerebral hemisphere was dissociated to culture the neural stem cells. After being identified by immunofluorescence method, the neural stem cells were randomly divided into 3 groups as blank control group, experimental control group and experimental group. The neural stem cells of experimental control group and experimental group were irradiated with 2 or 4 Gy of gamma rays. The proliferation and the cell cycle of neural stem cells were detected at different time-points ranging from 24 h,48 h, 72 h after irradiation with CCK-8 and FCM. Results: Compared with the blank control group, the proliferation rate of experimental control group was significantly reduced (t=5.33-8.44, P<0.05 ), and the G 1 phase arrest of experimental control group was significantly enhanced (t=30.60-71.22, P<0.05).Compared with the experimental control group, the proliferation of experimental group significantly increased excluding that of 24 h (t=2.45-4.71, P<0.05), the apoptosis rate of experimental group significantly decreased (t=6.73-41.12, P<0.05), which was closer to the blank control group.Conclusion: Magnesium sulfate can alleviate the injury of proliferation and decrease the cell apoptosis in the early stage after irradiation. (authors)

A comparative study of laser induced breakdown spectroscopy analysis for element concentrations in aluminum alloy using artificial neural networks and calibration methods

International Nuclear Information System (INIS)

Inakollu, Prasanthi; Philip, Thomas; Rai, Awadhesh K.; Yueh Fangyu; Singh, Jagdish P.

2009-01-01

A comparative study of analysis methods (traditional calibration method and artificial neural networks (ANN) prediction method) for laser induced breakdown spectroscopy (LIBS) data of different Al alloy samples was performed. In the calibration method, the intensity of the analyte lines obtained from different samples are plotted against their concentration to form calibration curves for different elements from which the concentrations of unknown elements were deduced by comparing its LIBS signal with the calibration curves. Using ANN, an artificial neural network model is trained with a set of input data of known composition samples. The trained neural network is then used to predict the elemental concentration from the test spectra. The present results reveal that artificial neural networks are capable of predicting values better than traditional method in most cases

Direct reprogramming of somatic cells into neural stem cells or neurons for neurological disorders.

Science.gov (United States)

Hou, Shaoping; Lu, Paul

2016-01-01

Direct reprogramming of somatic cells into neurons or neural stem cells is one of the most important frontier fields in current neuroscience research. Without undergoing the pluripotency stage, induced neurons or induced neural stem cells are a safer and timelier manner resource in comparison to those derived from induced pluripotent stem cells. In this prospective, we review the recent advances in generation of induced neurons and induced neural stem cells in vitro and in vivo and their potential treatments of neurological disorders.

Huperzine A protects neural stem cells against Aβ-induced apoptosis in a neural stem cells and microglia co-culture system

Science.gov (United States)

Zhu, Ning; Lin, Jizong; Wang, Kewan; Wei, Meidan; Chen, Qingzhuang; Wang, Yong

2015-01-01

Objectives: This study aims to explore whether Huperzine A (HupA) could protect neural stem cells against amyloid beta-peptide Aβ induced apoptosis in a neural stem cells (NSCs) and microglia co-culture system. Methods: Rat NSCs and microglial cells were isolated, cultured and identified with immunofluorescence Assays (IFA). Co-culture systems of NSCs and microglial cells were employed using Transwell Permeable Supports. The effects of Aβ1-42 on NSCs were studied in 4 groups using co-culture systems: NSCs, Aβ+NSCs, co-culture and Aβ+co-culture groups. Bromodeoxyuridine (BrdU) incorporation and flow cytometry were utilized to assess the differences of proliferation, differentiation and apoptosis of NSCs between the groups. LQ test was performed to assess the amounts of IL-6, TNF-α and MIP-α secreted, and flow cytometry and Western blotting were used to assess apoptosis of NSCs and the expressions of Bcl-2 and Bax in each group. Results: IFA results showed that isolated rat NSCs were nestin-positive and microglial cells were CD11b/c-positive. Among all the groups, the Aβ+co-culture group has the lowest BrdU expression level, the lowest MAP2-positive, ChAT-positive cell counts and the highest NSC apoptosis rate. Smaller amounts of IL-6, TNF-α and MIP-α were being secreted by microglial cells in the HupA+Aβ+co-culture group compared with those in the Aβ+ co-culture group. Also the Bcl-2: Bax ratio was much higher in the HupA+Aβ+co-culture group than in the Aβ+co-culture group. Conclusions: HupA inhibits cell apoptosis through restraining microglia’s inflammatory response induced by Aβ1-42. PMID:26261518

The response of early neural genes to FGF signaling or inhibition of BMP indicate the absence of a conserved neural induction module

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Rogers Crystal D

2011-12-01

Full Text Available Abstract Background The molecular mechanism that initiates the formation of the vertebrate central nervous system has long been debated. Studies in Xenopus and mouse demonstrate that inhibition of BMP signaling is sufficient to induce neural tissue in explants or ES cells respectively, whereas studies in chick argue that instructive FGF signaling is also required for the expression of neural genes. Although additional signals may be involved in neural induction and patterning, here we focus on the roles of BMP inhibition and FGF8a. Results To address the question of necessity and sufficiency of BMP inhibition and FGF signaling, we compared the temporal expression of the five earliest genes expressed in the neuroectoderm and determined their requirements for induction at the onset of neural plate formation in Xenopus. Our results demonstrate that the onset and peak of expression of the genes vary and that they have different regulatory requirements and are therefore unlikely to share a conserved neural induction regulatory module. Even though all require inhibition of BMP for expression, some also require FGF signaling; expression of the early-onset pan-neural genes sox2 and foxd5α requires FGF signaling while other early genes, sox3, geminin and zicr1 are induced by BMP inhibition alone. Conclusions We demonstrate that BMP inhibition and FGF signaling induce neural genes independently of each other. Together our data indicate that although the spatiotemporal expression patterns of early neural genes are similar, the mechanisms involved in their expression are distinct and there are different signaling requirements for the expression of each gene.

Rationale and Methodology of Reprogramming for Generation of Induced Pluripotent Stem Cells and Induced Neural Progenitor Cells

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Zuojun Tian

2016-04-01

Full Text Available Great progress has been made regarding the capabilities to modify somatic cell fate ever since the technology for generation of induced pluripotent stem cells (iPSCs was discovered in 2006. Later, induced neural progenitor cells (iNPCs were generated from mouse and human cells, bypassing some of the concerns and risks of using iPSCs in neuroscience applications. To overcome the limitation of viral vector induced reprogramming, bioactive small molecules (SM have been explored to enhance the efficiency of reprogramming or even replace transcription factors (TFs, making the reprogrammed cells more amenable to clinical application. The chemical induced reprogramming process is a simple process from a technical perspective, but the choice of SM at each step is vital during the procedure. The mechanisms underlying cell transdifferentiation are still poorly understood, although, several experimental data and insights have indicated the rationale of cell reprogramming. The process begins with the forced expression of specific TFs or activation/inhibition of cell signaling pathways by bioactive chemicals in defined culture condition, which initiates the further reactivation of endogenous gene program and an optimal stoichiometric expression of the endogenous pluri- or multi-potency genes, and finally leads to the birth of reprogrammed cells such as iPSCs and iNPCs. In this review, we first outline the rationale and discuss the methodology of iPSCs and iNPCs in a stepwise manner; and then we also discuss the chemical-based reprogramming of iPSCs and iNPCs.

The cholinergic-inducing effect of BMP4 on rat's cerebral neural stem cells

International Nuclear Information System (INIS)

Chang Yan; Xue Yilong; Luo Yun; Tian Lei; Pan Jingkun; Cui Xin

2004-01-01

The cholinergic-inducing effect of BMP4 on isolated and cultivated rat's cerebral neural stem cells (NSC) was examined. NSC isolated from two months old rat's brain region like hippocampus and striatum was cultivated in a DMEM/F12 medium containing EGF and bFGF, and was identified with morphological character and nestin immunocytochemistry test. After 24 hours, cultivating the NSC with the BMP4-added medium for 7-8 days, then the microscopical change were observed, ChAT and nestin double-labelling immunocytochemistry test was done. Results showed that about 34% NSC of neuron-like character was observed by microscope in the paper. That ChAT-positive cells coexist with nestin-positive cells was found by immunocytochemistry test. There were 28% ChAT-positive cells and 38% nestin-positive cells in the study. Cholinergic neurons differentiated from NSC could be induced by adding BMP4 to the medium

Differential Response of Neural Cells to Trauma-Induced Swelling In Vitro.

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Jayakumar, A R; Taherian, M; Panickar, K S; Shamaladevi, N; Rodriguez, M E; Price, B G; Norenberg, M D

2018-02-01

Brain edema and the associated increase in intracranial pressure are major consequences of traumatic brain injury (TBI) that accounts for most early deaths after TBI. We recently showed that acute severe trauma to cultured astrocytes results in cell swelling. We further examined whether trauma induces cell swelling in neurons and microglia. We found that severe trauma also caused cell swelling in cultured neurons, whereas no swelling was observed in microglia. While severe trauma caused cell swelling in both astrocytes and neurons, mild trauma to astrocytes, neurons, and microglia failed to cell swelling. Since extracellular levels of glutamate are increased in brain post-TBI and microglia are known to release cytokine, and direct exposure of astrocytes to these molecules are known to stimulate cell swelling, we examined whether glutamate or cytokines have any additive effect on trauma-induced cell swelling. Exposure of cultured astrocytes to trauma caused cell swelling, and such swelling was potentiated by the exposure of traumatized astrocytes to glutamate and cytokines. Conditioned medium (CM) from traumatized astrocytes had no effect on neuronal swelling post-trauma, while CM from traumatized neurons and microglia potentiated the effect of trauma on astrocyte swelling. Further, trauma significantly increased the Na-K-Cl co-transporter (NKCC) activity in neurons, and that inhibition of NKCC activity diminished the trauma-induced neuronal swelling. Our results indicate that a differential sensitivity to trauma-induced cell swelling exists in neural cells and that neurons and microglia are likely to be involved in the potentiation of the astrocyte swelling post-trauma.

Discrete Neural Signatures of Basic Emotions.

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Saarimäki, Heini; Gotsopoulos, Athanasios; Jääskeläinen, Iiro P; Lampinen, Jouko; Vuilleumier, Patrik; Hari, Riitta; Sams, Mikko; Nummenmaa, Lauri

2016-06-01

Categorical models of emotions posit neurally and physiologically distinct human basic emotions. We tested this assumption by using multivariate pattern analysis (MVPA) to classify brain activity patterns of 6 basic emotions (disgust, fear, happiness, sadness, anger, and surprise) in 3 experiments. Emotions were induced with short movies or mental imagery during functional magnetic resonance imaging. MVPA accurately classified emotions induced by both methods, and the classification generalized from one induction condition to another and across individuals. Brain regions contributing most to the classification accuracy included medial and inferior lateral prefrontal cortices, frontal pole, precentral and postcentral gyri, precuneus, and posterior cingulate cortex. Thus, specific neural signatures across these regions hold representations of different emotional states in multimodal fashion, independently of how the emotions are induced. Similarity of subjective experiences between emotions was associated with similarity of neural patterns for the same emotions, suggesting a direct link between activity in these brain regions and the subjective emotional experience. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Glucagon-like peptide-1 reduces pancreatic β-cell mass through hypothalamic neural pathways in high-fat diet-induced obese rats.

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Ando, Hisae; Gotoh, Koro; Fujiwara, Kansuke; Anai, Manabu; Chiba, Seiichi; Masaki, Takayuki; Kakuma, Tetsuya; Shibata, Hirotaka

2017-07-17

We examined whether glucagon-like peptide-1 (GLP-1) affects β-cell mass and proliferation through neural pathways, from hepatic afferent nerves to pancreatic efferent nerves via the central nervous system, in high-fat diet (HFD)-induced obese rats. The effects of chronic administration of GLP-1 (7-36) and liraglutide, a GLP-1 receptor agonist, on pancreatic morphological alterations, c-fos expression and brain-derived neurotrophic factor (BDNF) content in the hypothalamus, and glucose metabolism were investigated in HFD-induced obese rats that underwent hepatic afferent vagotomy (VgX) and/or pancreatic efferent sympathectomy (SpX). Chronic GLP-1 (7-36) administration to HFD-induced obese rats elevated c-fos expression and BDNF content in the hypothalamus, followed by a reduction in pancreatic β-cell hyperplasia and insulin content, thus resulting in improved glucose tolerance. These responses were abolished by VgX and SpX. Moreover, administration of liraglutide similarly activated the hypothalamic neural pathways, thus resulting in a more profound amelioration of glucose tolerance than native GLP-1 (7-36). These data suggest that GLP-1 normalizes the obesity-induced compensatory increase in β-cell mass and glucose intolerance through a neuronal relay system consisting of hepatic afferent nerves, the hypothalamus, and pancreatic efferent nerves.

Neural correlates of stress-induced and cue-induced drug craving: influences of sex and cocaine dependence.

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Potenza, Marc N; Hong, Kwang-ik Adam; Lacadie, Cheryl M; Fulbright, Robert K; Tuit, Keri L; Sinha, Rajita

2012-04-01

Although stress and drug cue exposure each increase drug craving and contribute to relapse in cocaine dependence, no previous research has directly examined the neural correlates of stress-induced and drug cue-induced craving in cocaine-dependent women and men relative to comparison subjects. Functional MRI was used to assess responses to individualized scripts for stress, drug/alcohol cue and neutral-relaxing-imagery conditions in 30 abstinent cocaine-dependent individuals (16 women, 14 men) and 36 healthy recreational-drinking comparison subjects (18 women, 18 men). Significant three-way interactions between diagnostic group, sex, and script condition were observed in multiple brain regions including the striatum, insula, and anterior and posterior cingulate. Within women, group-by-condition interactions were observed involving these regions and were attributable to relatively increased regional activations in cocaine-dependent women during the stress and, to a lesser extent, neutral-relaxing conditions. Within men, group main effects were observed involving these same regions, with cocaine-dependent men demonstrating relatively increased activation across conditions, with the main contributions from the drug and neutral-relaxing conditions. In men and women, subjective drug-induced craving measures correlated positively with corticostriatal-limbic activations. In cocaine dependence, corticostriatal-limbic hyperactivity appears to be linked to stress cues in women, drug cues in men, and neutral-relaxing conditions in both. These findings suggest that sex should be taken into account in the selection of therapies in the treatment of addiction, particularly those targeting stress reduction.

Autophagy protects against neural cell death induced by piperidine alkaloids present in Prosopis juliflora (Mesquite).

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Silva, Victor D A; Cuevas, Carlos; Muñoz, Patricia; Villa, Monica; Ahumada-Castro, Ulises; Huenchuguala, Sandro; Santos, Cleonice C Dos; Araujo, Fillipe M DE; Ferreira, Rafael S; Silva, Vanessa B DA; Silva, Juliana H C E; Soares, Érica N; Velozo, Eudes S; Segura-Aguilar, Juan; Costa, Silvia L

2017-01-01

Prosopis juliflora is a shrub that has been used to feed animals and humans. However, a synergistic action of piperidine alkaloids has been suggested to be responsible for neurotoxic damage observed in animals. We investigated the involvement of programmed cell death (PCD) and autophagy on the mechanism of cell death induced by a total extract (TAE) of alkaloids and fraction (F32) from P. juliflora leaves composed majoritary of juliprosopine in a model of neuron/glial cell co-culture. We saw that TAE (30 µg/mL) and F32 (7.5 µg/mL) induced reduction in ATP levels and changes in mitochondrial membrane potential at 12 h exposure. Moreover, TAE and F32 induced caspase-9 activation, nuclear condensation and neuronal death at 16 h exposure. After 4 h, they induced autophagy characterized by decreases of P62 protein level, increase of LC3II expression and increase in number of GFP-LC3 cells. Interestingly, we demonstrated that inhibition of autophagy by bafilomycin and vinblastine increased the cell death induced by TAE and autophagy induced by serum deprivation and rapamycin reduced cell death induced by F32 at 24 h. These results indicate that the mechanism neural cell death induced by these alkaloids involves PCD via caspase-9 activation and autophagy, which seems to be an important protective mechanism.

Autophagy protects against neural cell death induced by piperidine alkaloids present in Prosopis juliflora (Mesquite

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VICTOR D.A. SILVA

Full Text Available ABSTRACT Prosopis juliflora is a shrub that has been used to feed animals and humans. However, a synergistic action of piperidine alkaloids has been suggested to be responsible for neurotoxic damage observed in animals. We investigated the involvement of programmed cell death (PCD and autophagy on the mechanism of cell death induced by a total extract (TAE of alkaloids and fraction (F32 from P. juliflora leaves composed majoritary of juliprosopine in a model of neuron/glial cell co-culture. We saw that TAE (30 µg/mL and F32 (7.5 µg/mL induced reduction in ATP levels and changes in mitochondrial membrane potential at 12 h exposure. Moreover, TAE and F32 induced caspase-9 activation, nuclear condensation and neuronal death at 16 h exposure. After 4 h, they induced autophagy characterized by decreases of P62 protein level, increase of LC3II expression and increase in number of GFP-LC3 cells. Interestingly, we demonstrated that inhibition of autophagy by bafilomycin and vinblastine increased the cell death induced by TAE and autophagy induced by serum deprivation and rapamycin reduced cell death induced by F32 at 24 h. These results indicate that the mechanism neural cell death induced by these alkaloids involves PCD via caspase-9 activation and autophagy, which seems to be an important protective mechanism.

Oscillatory phase dynamics in neural entrainment underpin illusory percepts of time.

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Herrmann, Björn; Henry, Molly J; Grigutsch, Maren; Obleser, Jonas

2013-10-02

Neural oscillatory dynamics are a candidate mechanism to steer perception of time and temporal rate change. While oscillator models of time perception are strongly supported by behavioral evidence, a direct link to neural oscillations and oscillatory entrainment has not yet been provided. In addition, it has thus far remained unaddressed how context-induced illusory percepts of time are coded for in oscillator models of time perception. To investigate these questions, we used magnetoencephalography and examined the neural oscillatory dynamics that underpin pitch-induced illusory percepts of temporal rate change. Human participants listened to frequency-modulated sounds that varied over time in both modulation rate and pitch, and judged the direction of rate change (decrease vs increase). Our results demonstrate distinct neural mechanisms of rate perception: Modulation rate changes directly affected listeners' rate percept as well as the exact frequency of the neural oscillation. However, pitch-induced illusory rate changes were unrelated to the exact frequency of the neural responses. The rate change illusion was instead linked to changes in neural phase patterns, which allowed for single-trial decoding of percepts. That is, illusory underestimations or overestimations of perceived rate change were tightly coupled to increased intertrial phase coherence and changes in cerebro-acoustic phase lag. The results provide insight on how illusory percepts of time are coded for by neural oscillatory dynamics.

Methamphetamine induces apoptosis in immortalized neural cells: protection by the proto-oncogene, bcl-2.

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Cadet, J L; Ordonez, S V; Ordonez, J V

1997-02-01

Methamphetamine (METH) is an amphetamine analog that produces degeneration of the dopaminergic system in mammals. The neurotoxic effects of the drug are thought to be mediated by oxygen-based free radicals. In the present report, we have used immortalized neural cells obtained from rat mesencephalon in order to further assess the role of oxidative stress in METH-induced neurotoxicity. We thus tested if the anti-death proto-oncogene, bcl-2 could protect against METH-induced cytotoxicity. METH caused dose-dependent loss of cellular viability in control cells while bcl-2-expressing cells were protected against these deleterious effects. Using flow cytometry, immunofluorescent staining, and DNA electrophoresis, we also show that METH exposure can cause DNA strand breaks, chromatin condensation, nuclear fragmentation, and DNA laddering. All these changes were prevented by bcl-2 expression. These observations provide further support for the involvement of oxidative stress in the toxic effects of amphetamine analogs. They also document that METH-induced cytotoxicity is secondary to apoptosis. These findings may be of relevance to the cause(s) of Parkinson's disease which involves degeneration of the nigrostriatal dopaminergic pathway.

Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

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Harrill, Joshua A.; Freudenrich, Theresa M.; Robinette, Brian L.; Mundy, William R., E-mail: mundy.william@epa.gov

2011-11-15

There is a need for rapid, efficient and cost-effective alternatives to traditional in vivo developmental neurotoxicity testing. In vitro cell culture models can recapitulate many of the key cellular processes of nervous system development, including neurite outgrowth, and may be used as screening tools to identify potential developmental neurotoxicants. The present study compared primary rat cortical cultures and human embryonic stem cell-derived neural cultures in terms of: 1) reproducibility of high content image analysis based neurite outgrowth measurements, 2) dynamic range of neurite outgrowth measurements and 3) sensitivity to chemicals which have been shown to inhibit neurite outgrowth. There was a large increase in neurite outgrowth between 2 and 24 h in both rat and human cultures. Image analysis data collected across multiple cultures demonstrated that neurite outgrowth measurements in rat cortical cultures were more reproducible and had higher dynamic range as compared to human neural cultures. Human neural cultures were more sensitive than rat cortical cultures to chemicals previously shown to inhibit neurite outgrowth. Parallel analysis of morphological (neurite count, neurite length) and cytotoxicity (neurons per field) measurements were used to detect selective effects on neurite outgrowth. All chemicals which inhibited neurite outgrowth in rat cortical cultures did so at concentrations which did not concurrently affect the number of neurons per field, indicating selective effects on neurite outgrowth. In contrast, more than half the chemicals which inhibited neurite outgrowth in human neural cultures did so at concentrations which concurrently decreased the number of neurons per field, indicating that effects on neurite outgrowth were secondary to cytotoxicity. Overall, these data demonstrate that the culture models performed differently in terms of reproducibility, dynamic range and sensitivity to neurite outgrowth inhibitors. While human neural

Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

International Nuclear Information System (INIS)

Harrill, Joshua A.; Freudenrich, Theresa M.; Robinette, Brian L.; Mundy, William R.

2011-01-01

There is a need for rapid, efficient and cost-effective alternatives to traditional in vivo developmental neurotoxicity testing. In vitro cell culture models can recapitulate many of the key cellular processes of nervous system development, including neurite outgrowth, and may be used as screening tools to identify potential developmental neurotoxicants. The present study compared primary rat cortical cultures and human embryonic stem cell-derived neural cultures in terms of: 1) reproducibility of high content image analysis based neurite outgrowth measurements, 2) dynamic range of neurite outgrowth measurements and 3) sensitivity to chemicals which have been shown to inhibit neurite outgrowth. There was a large increase in neurite outgrowth between 2 and 24 h in both rat and human cultures. Image analysis data collected across multiple cultures demonstrated that neurite outgrowth measurements in rat cortical cultures were more reproducible and had higher dynamic range as compared to human neural cultures. Human neural cultures were more sensitive than rat cortical cultures to chemicals previously shown to inhibit neurite outgrowth. Parallel analysis of morphological (neurite count, neurite length) and cytotoxicity (neurons per field) measurements were used to detect selective effects on neurite outgrowth. All chemicals which inhibited neurite outgrowth in rat cortical cultures did so at concentrations which did not concurrently affect the number of neurons per field, indicating selective effects on neurite outgrowth. In contrast, more than half the chemicals which inhibited neurite outgrowth in human neural cultures did so at concentrations which concurrently decreased the number of neurons per field, indicating that effects on neurite outgrowth were secondary to cytotoxicity. Overall, these data demonstrate that the culture models performed differently in terms of reproducibility, dynamic range and sensitivity to neurite outgrowth inhibitors. While human neural

Beneficial effect of human induced pluripotent stem cell-derived neural precursors in spinal cord injury repair

Czech Academy of Sciences Publication Activity Database

Romanyuk, Nataliya; Amemori, Takashi; Turnovcová, Karolína; Procházka, Pavel; Onteniente, B.; Syková, Eva; Jendelová, Pavla

2015-01-01

Roč. 24, č. 9 (2015), s. 1781-1797 ISSN 0963-6897 R&D Projects: GA MŠk LH12024; GA ČR(CZ) GA13-00939S; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) ED1.1.00/02.0109; GA MŠk(CZ) LO1309 Institutional support: RVO:68378041 Keywords : human induced pluripotent stem cells * neural precursors * spinal cord injury Subject RIV: FH - Neurology Impact factor: 3.427, year: 2015

Dlx proteins position the neural plate border and determine adjacent cell fates.

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Woda, Juliana M; Pastagia, Julie; Mercola, Mark; Artinger, Kristin Bruk

2003-01-01

The lateral border of the neural plate is a major source of signals that induce primary neurons, neural crest cells and cranial placodes as well as provide patterning cues to mesodermal structures such as somites and heart. Whereas secreted BMP, FGF and Wnt proteins influence the differentiation of neural and non-neural ectoderm, we show here that members of the Dlx family of transcription factors position the border between neural and non-neural ectoderm and are required for the specification of adjacent cell fates. Inhibition of endogenous Dlx activity in Xenopus embryos with an EnR-Dlx homeodomain fusion protein expands the neural plate into non-neural ectoderm tissue whereas ectopic activation of Dlx target genes inhibits neural plate differentiation. Importantly, the stereotypic pattern of border cell fates in the adjacent ectoderm is re-established only under conditions where the expanded neural plate abuts Dlx-positive non-neural ectoderm. Experiments in which presumptive neural plate was grafted to ventral ectoderm reiterate induction of neural crest and placodal lineages and also demonstrate that Dlx activity is required in non-neural ectoderm for the production of signals needed for induction of these cells. We propose that Dlx proteins regulate intercellular signaling across the interface between neural and non-neural ectoderm that is critical for inducing and patterning adjacent cell fates.

Neural plasticity of development and learning.

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Galván, Adriana

2010-06-01

Development and learning are powerful agents of change across the lifespan that induce robust structural and functional plasticity in neural systems. An unresolved question in developmental cognitive neuroscience is whether development and learning share the same neural mechanisms associated with experience-related neural plasticity. In this article, I outline the conceptual and practical challenges of this question, review insights gleaned from adult studies, and describe recent strides toward examining this topic across development using neuroimaging methods. I suggest that development and learning are not two completely separate constructs and instead, that they exist on a continuum. While progressive and regressive changes are central to both, the behavioral consequences associated with these changes are closely tied to the existing neural architecture of maturity of the system. Eventually, a deeper, more mechanistic understanding of neural plasticity will shed light on behavioral changes across development and, more broadly, about the underlying neural basis of cognition. (c) 2010 Wiley-Liss, Inc.

Brain-Derived Neurotrophic Factor Loaded PS80 PBCA Nanocarrier for In Vitro Neural Differentiation of Mouse Induced Pluripotent Stem Cells

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Chiu-Yen Chung

2017-03-01

Full Text Available Brain derived neurotrophic factor (BDNF can induce neural differentiation in stem cells and has the potential for repair of the nervous system. In this study, a polysorbate 80-coated polybutylcyanoacrylate nanocarrier (PS80 PBCA NC was constructed to deliver plasmid DNAs (pDNAs containing BDNF gene attached to a hypoxia-responsive element (HRE-cmvBDNF. The hypoxia-sensing mechanism of BDNF expression and inductiveness of the nano-formulation on mouse induced pluripotent stem cells (iPSCs to differentiate into neurons following hypoxia was tested in vitro with immunofluorescent staining and Western blotting. The HRE-cmvBDNF appeared to adsorb onto the surface of PS80 PBCA NC, with a resultant mean diameter of 92.6 ± 1.0 nm and zeta potential of −14.1 ± 1.1 mV. HIF-1α level in iPSCs was significantly higher in hypoxia, which resulted in a 51% greater BDNF expression when transfected with PS80 PBCA NC/HRE-cmvBDNF than those without hypoxia. TrkB and phospho-Akt were also elevated which correlated with neural differentiation. The findings suggest that PS80 PBCA NC too can be endocytosed to serve as an efficient vector for genes coupled to the HRE in hypoxia-sensitive cells, and activation of the PI3/Akt pathway in iPSCs by BDNF is capable of neural lineage specification.

Contribution of neural cell death to depressive phenotypes of streptozotocin-induced diabetic mice

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Cheng Chen

2014-06-01

Full Text Available Major depression disorder (MDD or depression is highly prevalent in individuals with diabetes, and the depressive symptoms are more severe and less responsive to antidepressant therapies in these patients. The underlying mechanism is little understood. We hypothesized that the pathophysiology of comorbid depression was more complex than that proposed for MDD and that neural cell death played a role in the disease severity. To test this hypothesis, we generated streptozotocin (STZ-induced diabetic mice. These mice had blood glucose levels threefold above controls and exhibited depressive phenotypes as judged by a battery of behavioral tests, thus confirming the comorbidity in mice. Immunohistological studies showed markedly increased TUNEL-positive cells in the frontal cortex and hippocampus of the comorbid mice, indicating apoptosis. This finding was supported by increased caspase-3 and decreased Bcl-2 proteins in these brain regions. In addition, the serum brain-derived neurotrophic factor (BDNF level of comorbid mice was reduced compared with controls, further supporting the neurodegenerative change. Mechanistic analyses showed an increased expression of mitochondrial fission genes fission protein 1 (Fis1 and dynamin-related protein 1 (Drp1, and a decreased expression of mitochondrial fusion genes mitofusin 1 (Mfn1, mitofusin 2 (Mfn2 and optical atrophy 1 (Opa1. Representative assessment of the proteins Drp1 and Mfn2 mirrored the mRNA changes. The data demonstrated that neural cell death was associated with the depressive phenotype of comorbid mice and that a fission-dominant expression of genes and proteins mediating mitochondrial dynamics played a role in the hyperglycemia-induced cell death. The study provides new insight into the disease mechanism and could aid the development of novel therapeutics aimed at providing neuroprotection by modulating mitochondrial dynamics to treat comorbid depression with diabetes.

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

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Javanmard, F; Azadbakht, M; Pourmoradi, M

2016-01-01

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

The Protective Effect of Melatonin on Neural Stem Cell against LPS-Induced Inflammation

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Juhyun Song

2015-01-01

Full Text Available Stem cell therapy for tissue regeneration has several limitations in the fact that transplanted cells could not survive for a long time. For solving these limitations, many studies have focused on the antioxidants to increase survival rate of neural stem cells (NSCs. Melatonin, an antioxidant synthesized in the pineal gland, plays multiple roles in various physiological mechanisms. Melatonin exerts neuroprotective effects in the central nervous system. To determine the effect of melatonin on NSCs which is in LPS-induced inflammatory stress state, we first investigated nitric oxide (NO production and cytotoxicity using Griess reagent assays, LDH assay, and neurosphere counting. Also, we investigated the effect of melatonin on NSCs by measuring the mRNA levels of SOX2, TLX, and FGFR-2. In addition, western blot analyses were performed to examine the activation of PI3K/Akt/Nrf2 signaling in LPS-treated NSCs. In the present study, we suggested that melatonin inhibits NO production and protects NSCs against LPS-induced inflammatory stress. In addition, melatonin promoted the expression of SOX2 and activated the PI3K/Akt/Nrf2 signaling under LPS-induced inflammation condition. Based on our results, we conclude that melatonin may be an important factor for the survival and proliferation of NSCs in neuroinflammatory diseases.

Neural circuits of disgust induced by sexual stimuli in homosexual and heterosexual men: an fMRI study.

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Zhang, Minming; Hu, Shaohua; Xu, Lijuan; Wang, Qidong; Xu, Xiaojun; Wei, Erqing; Yan, Leqin; Hu, Jianbo; Wei, Ning; Zhou, Weihua; Huang, Manli; Xu, Yi

2011-11-01

Few studies demonstrated neural circuits related to disgust were influenced by internal sexual orientation in male. Here we used fMRI to study the neural responses to disgust in homosexual and heterosexual men to investigate that issue. Thirty-two healthy male volunteers (sixteen homosexual and sixteen heterosexual) were scanned while viewing alternating blocks of three types of erotic film: heterosexual couples (F-M), male homosexual couples (M-M), and female homosexual couples (F-F) engaged in sexual activity. All the participants rated their level of disgust and sexual arousal as well. The F-F and M-M stimuli induced disgust in homosexual and heterosexual men, respectively. The common activations related to disgusting stimuli included: bilateral frontal gyrus and occipital gyrus, right middle temporal gyrus, left superior temporal gyrus, right cerebellum, and right thalamus. Homosexual men had greater neural responses in the left medial frontal gyrus than did heterosexual men to the sexual disgusting stimuli; in contrast, heterosexual men showed significantly greater activation than homosexual men in the left cuneus. ROI analysis showed that negative correlation were found between the magnitude of MRI signals in the left medial frontal gyrus and scores of disgust in homosexual subjects (pmen. Crown Copyright © 2010. Published by Elsevier Ireland Ltd. All rights reserved.

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

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

2018-06-01

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

Non-Viral Generation of Neural Precursor-like Cells from Adult Human Fibroblasts

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Maucksch C

2012-01-01

Full Text Available Recent studies have reported direct reprogramming of human fibroblasts to mature neurons by the introduction of defined neural genes. This technology has potential use in the areas of neurological disease modeling and drug development. However, use of induced neurons for large-scale drug screening and cell-based replacement strategies is limited due to their inability to expand once reprogrammed. We propose it would be more desirable to induce expandable neural precursor cells directly from human fibroblasts. To date several pluripotent and neural transcription factors have been shown to be capable of converting mouse fibroblasts to neural stem/precursor-like cells when delivered by viral vectors. Here we extend these findings and demonstrate that transient ectopic insertion of the transcription factors SOX2 and PAX6 to adult human fibroblasts through use of non-viral plasmid transfection or protein transduction allows the generation of induced neural precursor (iNP colonies expressing a range of neural stem and pro-neural genes. Upon differentiation, iNP cells give rise to neurons exhibiting typical neuronal morphologies and expressing multiple neuronal markers including tyrosine hydroxylase and GAD65/67. Importantly, iNP-derived neurons demonstrate electrophysiological properties of functionally mature neurons with the capacity to generate action potentials. In addition, iNP cells are capable of differentiating into glial fibrillary acidic protein (GFAP-expressing astrocytes. This study represents a novel virus-free approach for direct reprogramming of human fibroblasts to a neural precursor fate.

Dissociable neural systems underwrite logical reasoning in the context of induced emotions with positive and negative valence.

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Smith, Kathleen W; Vartanian, Oshin; Goel, Vinod

2014-01-01

How emotions influence syllogistic reasoning is not well understood. fMRI was employed to investigate the effects of induced positive or negative emotion on syllogistic reasoning. Specifically, on a trial-by-trial basis participants were exposed to a positive, negative, or neutral picture, immediately prior to engagement in a reasoning task. After viewing and rating the valence and intensity of each picture, participants indicated by keypress whether or not the conclusion of the syllogism followed logically from the premises. The content of all syllogisms was neutral, and the influence of belief-bias was controlled for in the study design. Emotion did not affect reasoning performance, although there was a trend in the expected direction based on accuracy rates for the positive (63%) and negative (64%) versus neutral (70%) condition. Nevertheless, exposure to positive and negative pictures led to dissociable patterns of neural activation during reasoning. Therefore, the neural basis of deductive reasoning differs as a function of the valence of the context.

Dissociable Neural Systems Underwrite Logical Reasoning in the Context of Induced Emotions with Positive and Negative Valence

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Smith, Kathleen W.; Vartanian, Oshin; Goel, Vinod

2014-01-01

How emotions influence syllogistic reasoning is not well understood. fMRI was employed to investigate the effects of induced positive or negative emotion on syllogistic reasoning. Specifically, on a trial-by-trial basis participants were exposed to a positive, negative, or neutral picture, immediately prior to engagement in a reasoning task. After viewing and rating the valence and intensity of each picture, participants indicated by keypress whether or not the conclusion of the syllogism followed logically from the premises. The content of all syllogisms was neutral, and the influence of belief-bias was controlled for in the study design. Emotion did not affect reasoning performance, although there was a trend in the expected direction based on accuracy rates for the positive (63%) and negative (64%) versus neutral (70%) condition. Nevertheless, exposure to positive and negative pictures led to dissociable patterns of neural activation during reasoning. Therefore, the neural basis of deductive reasoning differs as a function of the valence of the context. PMID:25294997

Development of teeth in chick embryos after mouse neural crest transplantations

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Mitsiadis, Thimios A.; Chéraud, Yvonnick; Sharpe, Paul; Fontaine-Pérus, Josiane

2003-01-01

Teeth were lost in birds 70–80 million years ago. Current thinking holds that it is the avian cranial neural crest-derived mesenchyme that has lost odontogenic capacity, whereas the oral epithelium retains the signaling properties required to induce odontogenesis. To investigate the odontogenic capacity of ectomesenchyme, we have used neural tube transplantations from mice to chick embryos to replace the chick neural crest cell populations with mouse neural crest cells. The mouse/chick ...

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

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

2017-10-01

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

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

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

2004-01-01

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

Dual small-molecule targeting of SMAD signaling stimulates human induced pluripotent stem cells toward neural lineages.

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Methichit Wattanapanitch

Full Text Available Incurable neurological disorders such as Parkinson's disease (PD, Huntington's disease (HD, and Alzheimer's disease (AD are very common and can be life-threatening because of their progressive disease symptoms with limited treatment options. To provide an alternative renewable cell source for cell-based transplantation and as study models for neurological diseases, we generated induced pluripotent stem cells (iPSCs from human dermal fibroblasts (HDFs and then differentiated them into neural progenitor cells (NPCs and mature neurons by dual SMAD signaling inhibitors. Reprogramming efficiency was improved by supplementing the histone deacethylase inhibitor, valproic acid (VPA, and inhibitor of p160-Rho associated coiled-coil kinase (ROCK, Y-27632, after retroviral transduction. We obtained a number of iPS colonies that shared similar characteristics with human embryonic stem cells in terms of their morphology, cell surface antigens, pluripotency-associated gene and protein expressions as well as their in vitro and in vivo differentiation potentials. After treatment with Noggin and SB431542, inhibitors of the SMAD signaling pathway, HDF-iPSCs demonstrated rapid and efficient differentiation into neural lineages. Six days after neural induction, neuroepithelial cells (NEPCs were observed in the adherent monolayer culture, which had the ability to differentiate further into NPCs and neurons, as characterized by their morphology and the expression of neuron-specific transcripts and proteins. We propose that our study may be applied to generate neurological disease patient-specific iPSCs allowing better understanding of disease pathogenesis and drug sensitivity assays.

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

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

2005-01-01

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

Neural circuits of disgust induced by sexual stimuli in homosexual and heterosexual men: An fMRI study

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Zhang Minming; Hu Shaohua; Xu Lijuan; Wang Qidong; Xu Xiaojun; Wei Erqing; Yan Leqin; Hu Jianbo; Wei Ning; Zhou Weihua; Huang Manli; Xu Yi

2011-01-01

Few studies demonstrated neural circuits related to disgust were influenced by internal sexual orientation in male. Here we used fMRI to study the neural responses to disgust in homosexual and heterosexual men to investigate that issue. Thirty-two healthy male volunteers (sixteen homosexual and sixteen heterosexual) were scanned while viewing alternating blocks of three types of erotic film: heterosexual couples (F-M), male homosexual couples (M-M), and female homosexual couples (F-F) engaged in sexual activity. All the participants rated their level of disgust and sexual arousal as well. The F-F and M-M stimuli induced disgust in homosexual and heterosexual men, respectively. The common activations related to disgusting stimuli included: bilateral frontal gyrus and occipital gyrus, right middle temporal gyrus, left superior temporal gyrus, right cerebellum, and right thalamus. Homosexual men had greater neural responses in the left medial frontal gyrus than did heterosexual men to the sexual disgusting stimuli; in contrast, heterosexual men showed significantly greater activation than homosexual men in the left cuneus. ROI analysis showed that negative correlation were found between the magnitude of MRI signals in the left medial frontal gyrus and scores of disgust in homosexual subjects (p < 0.05). This study indicated that there were regions in common as well as regions specific for each type of erotic stimuli during disgust of homosexual and heterosexual men.

Neural circuits of disgust induced by sexual stimuli in homosexual and heterosexual men: An fMRI study

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Zhang Minming [Department of Radiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou (China); Hu Shaohua [Department of Mental Health, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qing Chun Road, Hangzhou, Zhejiang Province 310003 (China); Xu Lijuan [National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing (China); Wang Qidong [Department of Radiology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou (China); Xu Xiaojun [Department of Radiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou (China); Wei Erqing [College of Pharmacology, Zhejiang University (China); Yan Leqin [MD Anderson Cancer Center, Virginia Harris Cockrell Cancer Research Center, University of Texas, Austin (United States); Hu Jianbo; Wei Ning; Zhou Weihua; Huang Manli [Department of Mental Health, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qing Chun Road, Hangzhou, Zhejiang Province 310003 (China); Xu Yi, E-mail: xuyi61@yahoo.com.cn [Department of Mental Health, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qing Chun Road, Hangzhou, Zhejiang Province 310003 (China)

2011-11-15

Few studies demonstrated neural circuits related to disgust were influenced by internal sexual orientation in male. Here we used fMRI to study the neural responses to disgust in homosexual and heterosexual men to investigate that issue. Thirty-two healthy male volunteers (sixteen homosexual and sixteen heterosexual) were scanned while viewing alternating blocks of three types of erotic film: heterosexual couples (F-M), male homosexual couples (M-M), and female homosexual couples (F-F) engaged in sexual activity. All the participants rated their level of disgust and sexual arousal as well. The F-F and M-M stimuli induced disgust in homosexual and heterosexual men, respectively. The common activations related to disgusting stimuli included: bilateral frontal gyrus and occipital gyrus, right middle temporal gyrus, left superior temporal gyrus, right cerebellum, and right thalamus. Homosexual men had greater neural responses in the left medial frontal gyrus than did heterosexual men to the sexual disgusting stimuli; in contrast, heterosexual men showed significantly greater activation than homosexual men in the left cuneus. ROI analysis showed that negative correlation were found between the magnitude of MRI signals in the left medial frontal gyrus and scores of disgust in homosexual subjects (p < 0.05). This study indicated that there were regions in common as well as regions specific for each type of erotic stimuli during disgust of homosexual and heterosexual men.

Neural crest cells: from developmental biology to clinical interventions.

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Noisa, Parinya; Raivio, Taneli

2014-09-01

Neural crest cells are multipotent cells, which are specified in embryonic ectoderm in the border of neural plate and epiderm during early development by interconnection of extrinsic stimuli and intrinsic factors. Neural crest cells are capable of differentiating into various somatic cell types, including melanocytes, craniofacial cartilage and bone, smooth muscle, and peripheral nervous cells, which supports their promise for cell therapy. In this work, we provide a comprehensive review of wide aspects of neural crest cells from their developmental biology to applicability in medical research. We provide a simplified model of neural crest cell development and highlight the key external stimuli and intrinsic regulators that determine the neural crest cell fate. Defects of neural crest cell development leading to several human disorders are also mentioned, with the emphasis of using human induced pluripotent stem cells to model neurocristopathic syndromes. © 2014 Wiley Periodicals, Inc.

An investigation of the neural substrates of mind wandering induced by viewing traditional Chinese landscape paintings

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Tingting eWang

2015-01-01

Full Text Available The present study was conducted to investigate whether the calming effect induced by viewing traditional Chinese landscape paintings would make disengagement from that mental state more difficult, as measured by performance on a cognitive control task. In Experiment 1 we examined the subjective experience of viewing traditional Chinese landscape paintings vs. realistic oil landscape paintings in a behavioral study. Our results confirmed that, as predicted, traditional Chinese landscape paintings induce greater levels of relaxation and mind wandering and lower levels of object-oriented absorption and recognition, compared to realistic oil landscape paintings. In Experiment 2 we used functional Magnetic Resonance Imaging (fMRI to explore the behavioural and neural effects of viewing traditional Chinese landscape paintings on a task requiring cognitive control (i.e., the flanker task—administered immediately following exposure to paintings. Contrary to our prediction, the behavioural data demonstrated that compared to realistic oil landscape paintings, exposure to traditional Chinese landscape paintings had no effect on performance on the flanker task. However, the neural data demonstrated an interaction effect such that there was greater activation in the inferior parietal cortex (IPC and the superior frontal gyrus (SFG on incongruent compared with congruent flanker trials when participants switched from viewing traditional Chinese landscape paintings to the flanker task than when they switched from realistic oil landscape paintings. These results suggest that switching from traditional Chinese landscape paintings placed greater demands on the brain’s attention and working memory networks during the flanker task than did switching from realistic oil landscape paintings.

Longterm effects of cardiac mediastinal nerve cryoablation on neural inducibility of atrial fibrillation in canines.

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Leiria, Tiago Luiz Luz; Glavinovic, Tamara; Armour, J Andrew; Cardinal, René; de Lima, Gustavo Glotz; Kus, Teresa

2011-04-26

In canines, excessive activation of select mediastinal nerve inputs to the intrinsic cardiac nervous system induces atrial fibrillation (AF). Since ablation of neural elements is proposed as an adjunct to circumferential pulmonary vein ablation for AF, we investigated the short and long-term effects of mediastinal nerve ablation on AF inducibility. Under general anesthesia, in 11 dogs several mediastinal nerve sites were identified on the superior vena cava that, when stimulated electrically during the atrial refractory period, reproducibly initiated AF. Cryoablation of one nerve site was then performed and inducibility retested early (1-2 months post Cryo; n=7) or late (4 months post Cryo; n=4). Four additional dogs that underwent a sham procedure were retested 1 to 2 months post-surgery. Stimulation induced AF at 91% of nerve sites tested in control versus 21% nerve sites early and 54% late post-ablation (both P<0.05). Fewer stimuli were required to induce AF in controls versus the Early Cryo group; this capacity returned to normal values in the Late Cryo group. AF episodes were longer in control versus the Early or Late Cryo groups. Heart rate responses to vagal or stellate ganglion stimulation, as well as to local nicotine infusion into the right coronary artery, were similar in all groups. In conclusion, focal damage to intrinsic cardiac neuronal inputs causes short-term stunning of neuronal inducibility of AF without major loss of overall adrenergic or cholinergic efferent neuronal control. That recovery of AF inducibility occurs rapidly post-surgery indicates the plasticity of intrathoracic neuronal elements to focal injury. Copyright © 2011 Elsevier B.V. All rights reserved.

Exposure to titanium dioxide and other metallic oxide nanoparticles induces cytotoxicity on human neural cells and fibroblasts

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James C K Lai

2008-12-01

Full Text Available James C K Lai1, Maria B Lai1, Sirisha Jandhyam1, Vikas V Dukhande1, Alok Bhushan1, Christopher K Daniels1, Solomon W Leung21Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, and Biomedical Research Institute; 2Department of Civil and Environmental Engineering, College of Engineering and Biomedical Research Institute, Idaho State University, Pocatello, ID, USAAbstract: The use of titanium dioxide (TiO2 in various industrial applications (eg, production of paper, plastics, cosmetics, and paints has been expanding thereby increasing the occupational and other environmental exposure of these nanoparticles to humans and other species. However, the health effects of exposure to TiO2 nanoparticles have not been systematically assessed even though recent studies suggest that such exposure induces inflammatory responses in lung tissue and cells. Because the effects of such nanoparticles on human neural cells are unknown, we have determined the putative cytotoxic effects of these nanoparticles on human astrocytes-like astrocytoma U87 cells and compared their effects on normal human fibroblasts. We found that TiO2 micro- and nanoparticles induced cell death on both human cell types in a concentration-related manner. We further noted that zinc oxide (ZnO nanoparticles were the most effective, TiO2 nanoparticles the second most effective, and magnesium oxide (MgO nanoparticles the least effective in inducing cell death in U87 cells. The cell death mechanisms underlying the effects of TiO2 micro- and nanoparticles on U87 cells include apoptosis, necrosis, and possibly apoptosis-like and necrosis-like cell death types. Thus, our findings may have toxicological and other pathophysiological implications on exposure of humans and other mammalian species to metallic oxide nanoparticles.Keywords: cytotoxicity of titanium dioxide micro- and nanoparticles, cytotoxicity of zinc oxide and magnesium oxide nanoparticles, human neural cells

Identifying Emotions on the Basis of Neural Activation.

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Kassam, Karim S; Markey, Amanda R; Cherkassky, Vladimir L; Loewenstein, George; Just, Marcel Adam

2013-01-01

We attempt to determine the discriminability and organization of neural activation corresponding to the experience of specific emotions. Method actors were asked to self-induce nine emotional states (anger, disgust, envy, fear, happiness, lust, pride, sadness, and shame) while in an fMRI scanner. Using a Gaussian Naïve Bayes pooled variance classifier, we demonstrate the ability to identify specific emotions experienced by an individual at well over chance accuracy on the basis of: 1) neural activation of the same individual in other trials, 2) neural activation of other individuals who experienced similar trials, and 3) neural activation of the same individual to a qualitatively different type of emotion induction. Factor analysis identified valence, arousal, sociality, and lust as dimensions underlying the activation patterns. These results suggest a structure for neural representations of emotion and inform theories of emotional processing.

Proposal of a model of mammalian neural induction

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Levine, Ariel J.; Brivanlou, Ali H.

2009-01-01

How does the vertebrate embryo make a nervous system? This complex question has been at the center of developmental biology for many years. The earliest step in this process – the induction of neural tissue – is intimately linked to patterning of the entire early embryo, and the molecular and embryological basis these processes are beginning to emerge. Here, we analyze classic and cutting-edge findings on neural induction in the mouse. We find that data from genetics, tissue explants, tissue grafting, and molecular marker expression support a coherent framework for mammalian neural induction. In this model, the gastrula organizer of the mouse embryo inhibits BMP signaling to allow neural tissue to form as a default fate – in the absence of instructive signals. The first neural tissue induced is anterior and subsequent neural tissue is posteriorized to form the midbrain, hindbrain, and spinal cord. The anterior visceral endoderm protects the pre-specified anterior neural fate from similar posteriorization, allowing formation of forebrain. This model is very similar to the default model of neural induction in the frog, thus bridging the evolutionary gap between amphibians and mammals. PMID:17585896

Ferulic acid promotes survival and differentiation of neural stem cells to prevent gentamicin-induced neuronal hearing loss.

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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.

Active Engine Mounting Control Algorithm Using Neural Network

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Fadly Jashi Darsivan

2009-01-01

Full Text Available This paper proposes the application of neural network as a controller to isolate engine vibration in an active engine mounting system. It has been shown that the NARMA-L2 neurocontroller has the ability to reject disturbances from a plant. The disturbance is assumed to be both impulse and sinusoidal disturbances that are induced by the engine. The performance of the neural network controller is compared with conventional PD and PID controllers tuned using Ziegler-Nichols. From the result simulated the neural network controller has shown better ability to isolate the engine vibration than the conventional controllers.

Effects of vibratory stimulation-induced kinesthetic illusions on the neural activities of patients with stroke.

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Kodama, Takayuki; Nakano, Hideki; Ohsugi, Hironori; Murata, Shin

2016-01-01

[Purpose] This study evaluated the influence of vibratory stimulation-induced kinesthetic illusion on brain function after stroke. [Subjects] Twelve healthy individuals and 13 stroke patients without motor or sensory loss participated. [Methods] Electroencephalograms were taken at rest and during vibratory stimulation. As a neurophysiological index of brain function, we measured the μ-rhythm, which is present mainly in the kinesthetic cortex and is attenuated by movement or motor imagery and compared the data using source localization analyses in the Standardized Low Resolution Brain Electromagnetic Tomography (sLORETA) program. [Results] At rest, μ-rhythms appeared in the sensorimotor and supplementary motor cortices in both healthy controls and stroke patients. Under vibratory stimulation, no μ-rhythm appeared in the sensorimotor cortex of either group. Moreover, in the supplementary motor area, which stores the motor imagery required for kinesthetic illusions, the μ-rhythms of patients were significantly stronger than those of the controls, although the μ-rhythms of both groups were reduced. Thus, differences in neural activity in the supplementary motor area were apparent between the subject groups. [Conclusion] Kinesthetic illusions do occur in patients with motor deficits due to stroke. The neural basis of the supplementary motor area in stroke patients may be functionally different from that found in healthy controls.

Learning-induced pattern classification in a chaotic neural network

International Nuclear Information System (INIS)

Li, Yang; Zhu, Ping; Xie, Xiaoping; He, Guoguang; Aihara, Kazuyuki

2012-01-01

In this Letter, we propose a Hebbian learning rule with passive forgetting (HLRPF) for use in a chaotic neural network (CNN). We then define the indices based on the Euclidean distance to investigate the evolution of the weights in a simplified way. Numerical simulations demonstrate that, under suitable external stimulations, the CNN with the proposed HLRPF acts as a fuzzy-like pattern classifier that performs much better than an ordinary CNN. The results imply relationship between learning and recognition. -- Highlights: ► Proposing a Hebbian learning rule with passive forgetting (HLRPF). ► Defining indices to investigate the evolution of the weights simply. ► The chaotic neural network with HLRPF acts as a fuzzy-like pattern classifier. ► The pattern classifier ability of the network is improved much.

Quantized Synchronization of Chaotic Neural Networks With Scheduled Output Feedback Control.

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Wan, Ying; Cao, Jinde; Wen, Guanghui

In this paper, the synchronization problem of master-slave chaotic neural networks with remote sensors, quantization process, and communication time delays is investigated. The information communication channel between the master chaotic neural network and slave chaotic neural network consists of several remote sensors, with each sensor able to access only partial knowledge of output information of the master neural network. At each sampling instants, each sensor updates its own measurement and only one sensor is scheduled to transmit its latest information to the controller's side in order to update the control inputs for the slave neural network. Thus, such communication process and control strategy are much more energy-saving comparing with the traditional point-to-point scheme. Sufficient conditions for output feedback control gain matrix, allowable length of sampling intervals, and upper bound of network-induced delays are derived to ensure the quantized synchronization of master-slave chaotic neural networks. Lastly, Chua's circuit system and 4-D Hopfield neural network are simulated to validate the effectiveness of the main results.In this paper, the synchronization problem of master-slave chaotic neural networks with remote sensors, quantization process, and communication time delays is investigated. The information communication channel between the master chaotic neural network and slave chaotic neural network consists of several remote sensors, with each sensor able to access only partial knowledge of output information of the master neural network. At each sampling instants, each sensor updates its own measurement and only one sensor is scheduled to transmit its latest information to the controller's side in order to update the control inputs for the slave neural network. Thus, such communication process and control strategy are much more energy-saving comparing with the traditional point-to-point scheme. Sufficient conditions for output feedback control

Regional neural tube closure defined by the Grainy head-like transcription factors.

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Rifat, Yeliz; Parekh, Vishwas; Wilanowski, Tomasz; Hislop, Nikki R; Auden, Alana; Ting, Stephen B; Cunningham, John M; Jane, Stephen M

2010-09-15

Primary neurulation in mammals has been defined by distinct anatomical closure sites, at the hindbrain/cervical spine (closure 1), forebrain/midbrain boundary (closure 2), and rostral end of the forebrain (closure 3). Zones of neurulation have also been characterized by morphologic differences in neural fold elevation, with non-neural ectoderm-induced formation of paired dorso-lateral hinge points (DLHP) essential for neural tube closure in the cranial and lower spinal cord regions, and notochord-induced bending at the median hinge point (MHP) sufficient for closure in the upper spinal region. Here we identify a unifying molecular basis for these observations based on the function of the non-neural ectoderm-specific Grainy head-like genes in mice. Using a gene-targeting approach we show that deletion of Grhl2 results in failed closure 3, with mutants exhibiting a split-face malformation and exencephaly, associated with failure of neuro-epithelial folding at the DLHP. Loss of Grhl3 alone defines a distinct lower spinal closure defect, also with defective DLHP formation. The two genes contribute equally to closure 2, where only Grhl gene dosage is limiting. Combined deletion of Grhl2 and Grhl3 induces severe rostral and caudal neural tube defects, but DLHP-independent closure 1 proceeds normally in the upper spinal region. These findings provide a molecular basis for non-neural ectoderm mediated formation of the DLHP that is critical for complete neuraxis closure. (c) 2010 Elsevier Inc. All rights reserved.

Identifying Emotions on the Basis of Neural Activation.

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Karim S Kassam

Full Text Available We attempt to determine the discriminability and organization of neural activation corresponding to the experience of specific emotions. Method actors were asked to self-induce nine emotional states (anger, disgust, envy, fear, happiness, lust, pride, sadness, and shame while in an fMRI scanner. Using a Gaussian Naïve Bayes pooled variance classifier, we demonstrate the ability to identify specific emotions experienced by an individual at well over chance accuracy on the basis of: 1 neural activation of the same individual in other trials, 2 neural activation of other individuals who experienced similar trials, and 3 neural activation of the same individual to a qualitatively different type of emotion induction. Factor analysis identified valence, arousal, sociality, and lust as dimensions underlying the activation patterns. These results suggest a structure for neural representations of emotion and inform theories of emotional processing.

Nicotine Withdrawal Induces Neural Deficits in Reward Processing.

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Oliver, Jason A; Evans, David E; Addicott, Merideth A; Potts, Geoffrey F; Brandon, Thomas H; Drobes, David J

2017-06-01

Nicotine withdrawal reduces neurobiological responses to nonsmoking rewards. Insight into these reward deficits could inform the development of targeted interventions. This study examined the effect of withdrawal on neural and behavioral responses during a reward prediction task. Smokers (N = 48) attended two laboratory sessions following overnight abstinence. Withdrawal was manipulated by having participants smoke three regular nicotine (0.6 mg yield; satiation) or very low nicotine (0.05 mg yield; withdrawal) cigarettes. Electrophysiological recordings of neural activity were obtained while participants completed a reward prediction task that involved viewing four combinations of predictive and reward-determining stimuli: (1) Unexpected Reward; (2) Predicted Reward; (3) Predicted Punishment; (4) Unexpected Punishment. The task evokes a medial frontal negativity that mimics the phasic pattern of dopaminergic firing in ventral tegmental regions associated with reward prediction errors. Nicotine withdrawal decreased the amplitude of the medial frontal negativity equally across all trial types (p nicotine dependence (p Nicotine withdrawal had equivocal impact across trial types, suggesting reward processing deficits are unlikely to stem from changes in phasic dopaminergic activity during prediction errors. Effects on tonic activity may be more pronounced. Pharmacological interventions directly targeting the dopamine system and behavioral interventions designed to increase reward motivation and responsiveness (eg, behavioral activation) may aid in mitigating withdrawal symptoms and potentially improving smoking cessation outcomes. Findings from this study indicate nicotine withdrawal impacts reward processing signals that are observable in smokers' neural activity. This may play a role in the subjective aversive experience of nicotine withdrawal and potentially contribute to smoking relapse. Interventions that address abnormal responding to both pleasant and

hiPSC-derived neural stem cells from patients with schizophrenia induce an impaired angiogenesis.

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Casas, Bárbara S; Vitória, Gabriela; do Costa, Marcelo N; Madeiro da Costa, Rodrigo; Trindade, Pablo; Maciel, Renata; Navarrete, Nelson; Rehen, Stevens K; Palma, Verónica

2018-02-22

Schizophrenia is a neurodevelopmental disease characterized by cerebral connectivity impairment and loss of gray matter. It was described in adult schizophrenia patients (SZP) that concentration of VEGFA, a master angiogenic factor, is decreased. Recent evidence suggests cerebral hypoperfusion related to a dysfunctional Blood Brain Barrier (BBB) in SZP. Since neurogenesis and blood-vessel formation occur in a coincident and coordinated fashion, a defect in neurovascular development could result in increased vascular permeability and, therefore, in poor functionality of the SZP's neurons. Here, we characterized the conditioned media (CM) of human induced Pluripotent Stem Cells (hiPSC)-derived Neural Stem Cells of SZP (SZP NSC) versus healthy subjects (Ctrl NSC), and its impact on angiogenesis. Our results reveal that SZP NSC have an imbalance in the secretion and expression of several angiogenic factors, among them non-canonical neuro-angiogenic guidance factors. SZP NSC migrated less and their CM was less effective in inducing migration and angiogenesis both in vitro and in vivo. Since SZP originates during embryonic brain development, our findings suggest a defective crosstalk between NSC and endothelial cells (EC) during the formation of the neuro-angiogenic niche.

Arsenate-induced maternal glucose intolerance and neural tube defects in a mouse model

International Nuclear Information System (INIS)

Hill, Denise S.; Wlodarczyk, Bogdan J.; Mitchell, Laura E.; Finnell, Richard H.

2009-01-01

Background: Epidemiological studies have linked environmental arsenic (As) exposure to increased type 2 diabetes risk. Periconceptional hyperglycemia is a significant risk factor for neural tube defects (NTDs), the second most common structural birth defect. A suspected teratogen, arsenic (As) induces NTDs in laboratory animals. Objectives: We investigated whether maternal glucose homeostasis disruption was responsible for arsenate-induced NTDs in a well-established dosing regimen used in studies of arsenic's teratogenicity in early neurodevelopment. Methods: We evaluated maternal intraperitoneal (IP) exposure to As 9.6 mg/kg (as sodium arsenate) in LM/Bc/Fnn mice for teratogenicity and disruption of maternal plasma glucose and insulin levels. Selected compounds (insulin pellet, sodium selenate (SS), N-acetyl cysteine (NAC), L-methionine (L-Met), N-tert-Butyl-α-phenylnitrone (PBN)) were investigated for their potential to mitigate arsenate's effects. Results: Arsenate caused significant glucose elevation during an IP glucose tolerance test (IPGTT). Insulin levels were not different between arsenate and control dams before (arsenate, 0.55 ng/dl; control, 0.48 ng/dl) or after glucose challenge (arsenate, 1.09 ng/dl; control, 0.81 ng/dl). HOMA-IR index was higher for arsenate (3.9) vs control (2.5) dams (p = 0.0260). Arsenate caused NTDs (100%, p < 0.0001). Insulin pellet and NAC were the most successful rescue agents, reducing NTD rates to 45% and 35%. Conclusions: IPGTT, insulin assay, and HOMA-IR results suggest a modest failure of glucose stimulated insulin secretion and insulin resistance characteristic of glucose intolerance. Insulin's success in preventing arsenate-induced NTDs provides evidence that these arsenate-induced NTDs are secondary to elevated maternal glucose. The NAC rescue, which did not restore maternal glucose or insulin levels, suggests oxidative disruption plays a role.

An Aminopropyl Carbazole Derivative Induces Neurogenesis by Increasing Final Cell Division in Neural Stem Cells.

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Shin, Jae-Yeon; Kong, Sun-Young; Yoon, Hye Jin; Ann, Jihyae; Lee, Jeewoo; Kim, Hyun-Jung

2015-07-01

P7C3 and its derivatives, 1-(3,6-dibromo-9H-carbazol-9-yl)-3-(p-tolylamino)propan-2-ol (1) and N-(3-(3,6-dibromo-9H-carbazol-9-yl)-2-hydroxypropyl)-N-(3-methoxyphenyl)-4-methylbenzenesulfonamide (2), were previously reported to increase neurogenesis in rat neural stem cells (NSCs). Although P7C3 is known to increase neurogenesis by protecting newborn neurons, it is not known whether its derivatives also have protective effects to increase neurogenesis. In the current study, we examined how 1 induces neurogenesis. The treatment of 1 in NSCs increased numbers of cells in the absence of epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2), while not affecting those in the presence of growth factors. Compound 1 did not induce astrocytogenesis during NSC differentiation. 5-Bromo-2'-deoxyuridine (BrdU) pulsing experiments showed that 1 significantly enhanced BrdU-positive neurons. Taken together, our data suggest that 1 promotes neurogenesis by the induction of final cell division during NSC differentiation.

Local Dynamics in Trained Recurrent Neural Networks.

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Rivkind, Alexander; Barak, Omri

2017-06-23

Learning a task induces connectivity changes in neural circuits, thereby changing their dynamics. To elucidate task-related neural dynamics, we study trained recurrent neural networks. We develop a mean field theory for reservoir computing networks trained to have multiple fixed point attractors. Our main result is that the dynamics of the network's output in the vicinity of attractors is governed by a low-order linear ordinary differential equation. The stability of the resulting equation can be assessed, predicting training success or failure. As a consequence, networks of rectified linear units and of sigmoidal nonlinearities are shown to have diametrically different properties when it comes to learning attractors. Furthermore, a characteristic time constant, which remains finite at the edge of chaos, offers an explanation of the network's output robustness in the presence of variability of the internal neural dynamics. Finally, the proposed theory predicts state-dependent frequency selectivity in the network response.

Local Dynamics in Trained Recurrent Neural Networks

Science.gov (United States)

Rivkind, Alexander; Barak, Omri

2017-06-01

Learning a task induces connectivity changes in neural circuits, thereby changing their dynamics. To elucidate task-related neural dynamics, we study trained recurrent neural networks. We develop a mean field theory for reservoir computing networks trained to have multiple fixed point attractors. Our main result is that the dynamics of the network's output in the vicinity of attractors is governed by a low-order linear ordinary differential equation. The stability of the resulting equation can be assessed, predicting training success or failure. As a consequence, networks of rectified linear units and of sigmoidal nonlinearities are shown to have diametrically different properties when it comes to learning attractors. Furthermore, a characteristic time constant, which remains finite at the edge of chaos, offers an explanation of the network's output robustness in the presence of variability of the internal neural dynamics. Finally, the proposed theory predicts state-dependent frequency selectivity in the network response.

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

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Antonela Bonafina

2018-03-01

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

A stem cell medium containing neural stimulating factor induces a pancreatic cancer stem-like cell-enriched population

Science.gov (United States)

WATANABE, YUSAKU; YOSHIMURA, KIYOSHI; YOSHIKAWA, KOICHI; TSUNEDOMI, RYOICHI; SHINDO, YOSHITARO; MATSUKUMA, SOU; MAEDA, NORIKO; KANEKIYO, SHINSUKE; SUZUKI, NOBUAKI; KURAMASU, ATSUO; SONODA, KOUHEI; TAMADA, KOJI; KOBAYASHI, SEI; SAYA, HIDEYUKI; HAZAMA, SHOICHI; OKA, MASAAKI

2014-01-01

Cancer stem cells (CSCs) have been studied for their self-renewal capacity and pluripotency, as well as their resistance to anticancer therapy and their ability to metastasize to distant organs. CSCs are difficult to study because their population is quite low in tumor specimens. To overcome this problem, we established a culture method to induce a pancreatic cancer stem-like cell (P-CSLC)-enriched population from human pancreatic cancer cell lines. Human pancreatic cancer cell lines established at our department were cultured in CSC-inducing media containing epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), leukemia inhibitory factor (LIF), neural cell survivor factor-1 (NSF-1), and N-acetylcysteine. Sphere cells were obtained and then transferred to a laminin-coated dish and cultured for approximately two months. The surface markers, gene expression, aldehyde dehydrogenase (ALDH) activity, cell cycle, and tumorigenicity of these induced cells were examined for their stem cell-like characteristics. The population of these induced cells expanded within a few months. The ratio of CD24high, CD44high, epithelial specific antigen (ESA) high, and CD44variant (CD44v) high cells in the induced cells was greatly enriched. The induced cells stayed in the G0/G1 phase and demonstrated mesenchymal and stemness properties. The induced cells had high tumorigenic potential. Thus, we established a culture method to induce a P-CSLCenriched population from human pancreatic cancer cell lines. The CSLC population was enriched approximately 100-fold with this method. Our culture method may contribute to the precise analysis of CSCs and thus support the establishment of CSC-targeting therapy. PMID:25118635

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

Science.gov (United States)

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

2017-12-01

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

Low levels of endogenous or X-ray-induced DNA double-strand breaks activate apoptosis in adult neural stem cells.

Science.gov (United States)

Barazzuol, Lara; Rickett, Nicole; Ju, Limei; Jeggo, Penny A

2015-10-01

The embryonic neural stem cell compartment is characterised by rapid proliferation from embryonic day (E)11 to E16.5, high endogenous DNA double-strand break (DSB) formation and sensitive activation of apoptosis. Here, we ask whether DSBs arise in the adult neural stem cell compartments, the sub-ventricular zone (SVZ) of the lateral ventricles and the sub-granular zone (SGZ) of the hippocampal dentate gyrus, and whether they activate apoptosis. We used mice with a hypomorphic mutation in DNA ligase IV (Lig4(Y288C)), ataxia telangiectasia mutated (Atm(-/-)) and double mutant Atm(-/-)/Lig4(Y288C) mice. We demonstrate that, although DSBs do not arise at a high frequency in adult neural stem cells, the low numbers of DSBs that persist endogenously in Lig4(Y288C) mice or that are induced by low radiation doses can activate apoptosis. A temporal analysis shows that DSB levels in Lig4(Y288C) mice diminish gradually from the embryo to a steady state level in adult mice. The neonatal SVZ compartment of Lig4(Y288C) mice harbours diminished DSBs compared to its differentiated counterpart, suggesting a process selecting against unfit stem cells. Finally, we reveal high endogenous apoptosis in the developing SVZ of wild-type newborn mice. © 2015. Published by The Company of Biologists Ltd.

The Amount of Time Dilation for Visual Flickers Corresponds to the Amount of Neural Entrainments Measured by EEG.

Science.gov (United States)

Hashimoto, Yuki; Yotsumoto, Yuko

2018-01-01

The neural basis of time perception has long attracted the interests of researchers. Recently, a conceptual model consisting of neural oscillators was proposed and validated by behavioral experiments that measured the dilated duration in perception of a flickering stimulus (Hashimoto and Yotsumoto, 2015). The model proposed that flickering stimuli cause neural entrainment of oscillators, resulting in dilated time perception. In this study, we examined the oscillator-based model of time perception, by collecting electroencephalography (EEG) data during an interval-timing task. Initially, subjects observed a stimulus, either flickering at 10-Hz or constantly illuminated. The subjects then reproduced the duration of the stimulus by pressing a button. As reported in previous studies, the subjects reproduced 1.22 times longer durations for flickering stimuli than for continuously illuminated stimuli. The event-related potential (ERP) during the observation of a flicker oscillated at 10 Hz, reflecting the 10-Hz neural activity phase-locked to the flicker. Importantly, the longer reproduced duration was associated with a larger amplitude of the 10-Hz ERP component during the inter-stimulus interval, as well as during the presentation of the flicker. The correlation between the reproduced duration and the 10-Hz oscillation during the inter-stimulus interval suggested that the flicker-induced neural entrainment affected time dilation. While the 10-Hz flickering stimuli induced phase-locked entrainments at 10 Hz, we also observed event-related desynchronizations of spontaneous neural oscillations in the alpha-frequency range. These could be attributed to the activation of excitatory neurons while observing the flicker stimuli. In addition, neural activity at approximately the alpha frequency increased during the reproduction phase, indicating that flicker-induced neural entrainment persisted even after the offset of the flicker. In summary, our results suggest that the

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

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Kyeung Min Joo

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

Pressure-induced phase transitions in silicon studied by neural network-based metadynamics simulations

Energy Technology Data Exchange (ETDEWEB)

Behler, Joerg [Department of Chemistry and Applied Biosciences, ETH Zurich, USI-Campus, Lugano (Switzerland); Lehrstuhl fuer Theoretische Chemie, Ruhr-Universitaet Bochum, 44780 Bochum (Germany); Martonak, Roman [Department of Chemistry and Applied Biosciences, ETH Zurich, USI-Campus, Lugano (Switzerland); Department of Experimental Physics, Faculty of Mathematics, Physics and Informatics, Comenius University, Mlynska dolina F2, 84248 Bratislava (Slovakia); Donadio, Davide [Department of Chemistry and Applied Biosciences, ETH Zurich, USI-Campus, Lugano (Switzerland); Department of Chemistry, UC Davis, One Shields Ave., Davis, CA 95616 (United States); Parrinello, Michele [Department of Chemistry and Applied Biosciences, ETH Zurich, USI-Campus, Lugano (Switzerland)

2008-12-15

We present a combination of the metadynamics method for the investigation of pressure-induced phase transitions in solids with a neural network representation of high-dimensional density-functional theory (DFT) potential-energy surfaces. In a recent illustration of the method for the complex high-pressure phase diagram of silicon[Behler et al., Phys. Rev. Lett. 100, 185501 (2008)] we have shown that the full sequence of phases can be reconstructed by a series of subsequent simulations. In the present paper we give a detailed account of the underlying methodology and discuss the scope and limitations of the approach, which promises to be a valuable tool for the investigation of a variety of inorganic materials. The method is several orders of magnitude faster than a direct coupling of metadynamics with electronic structure calculations, while the accuracy is essentially maintained, thus providing access to extended simulations of large systems. (copyright 2008 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

Exploring the Combination of Dempster-Shafer Theory and Neural Network for Predicting Trust and Distrust

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Xin Wang

2016-01-01

Full Text Available In social media, trust and distrust among users are important factors in helping users make decisions, dissect information, and receive recommendations. However, the sparsity and imbalance of social relations bring great difficulties and challenges in predicting trust and distrust. Meanwhile, there are numerous inducing factors to determine trust and distrust relations. The relationship among inducing factors may be dependency, independence, and conflicting. Dempster-Shafer theory and neural network are effective and efficient strategies to deal with these difficulties and challenges. In this paper, we study trust and distrust prediction based on the combination of Dempster-Shafer theory and neural network. We firstly analyze the inducing factors about trust and distrust, namely, homophily, status theory, and emotion tendency. Then, we quantify inducing factors of trust and distrust, take these features as evidences, and construct evidence prototype as input nodes of multilayer neural network. Finally, we propose a framework of predicting trust and distrust which uses multilayer neural network to model the implementing process of Dempster-Shafer theory in different hidden layers, aiming to overcome the disadvantage of Dempster-Shafer theory without optimization method. Experimental results on a real-world dataset demonstrate the effectiveness of the proposed framework.

Development switch in neural circuitry underlying odor-malaise learning.

Science.gov (United States)

Shionoya, Kiseko; Moriceau, Stephanie; Lunday, Lauren; Miner, Cathrine; Roth, Tania L; Sullivan, Regina M

2006-01-01

Fetal and infant rats can learn to avoid odors paired with illness before development of brain areas supporting this learning in adults, suggesting an alternate learning circuit. Here we begin to document the transition from the infant to adult neural circuit underlying odor-malaise avoidance learning using LiCl (0.3 M; 1% of body weight, ip) and a 30-min peppermint-odor exposure. Conditioning groups included: Paired odor-LiCl, Paired odor-LiCl-Nursing, LiCl, and odor-saline. Results showed that Paired LiCl-odor conditioning induced a learned odor aversion in postnatal day (PN) 7, 12, and 23 pups. Odor-LiCl Paired Nursing induced a learned odor preference in PN7 and PN12 pups but blocked learning in PN23 pups. 14C 2-deoxyglucose (2-DG) autoradiography indicated enhanced olfactory bulb activity in PN7 and PN12 pups with odor preference and avoidance learning. The odor aversion in weanling aged (PN23) pups resulted in enhanced amygdala activity in Paired odor-LiCl pups, but not if they were nursing. Thus, the neural circuit supporting malaise-induced aversions changes over development, indicating that similar infant and adult-learned behaviors may have distinct neural circuits.

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

Science.gov (United States)

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

2009-01-01

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

Explicit versus implicit neural processing of musical emotions

OpenAIRE

Bogert, Brigitte; Numminen-Kontti, Taru; Gold, Benjamin; Sams, Mikko; Numminen, Jussi; Burunat, Iballa; Lampinen, Jouko; Brattico, Elvira

2016-01-01

Music is often used to regulate emotions and mood. Typically, music conveys and induces emotions even when one does not attend to them. Studies on the neural substrates of musical emotions have, however, only examined brain activity when subjects have focused on the emotional content of the music. Here we address with functional magnetic resonance imaging (fMRI) the neural processing of happy, sad, and fearful music with a paradigm in which 56 subjects were instructed to either classify the e...

Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke.

Science.gov (United States)

Chiva-Blanch, Gemma; Suades, Rosa; Crespo, Javier; Peña, Esther; Padró, Teresa; Jiménez-Xarrié, Elena; Martí-Fàbregas, Joan; Badimon, Lina

2016-01-01

Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke. Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3-7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells) were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls. Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions. Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process after stroke. Larger cerebral lesions

Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke.

Directory of Open Access Journals (Sweden)

Gemma Chiva-Blanch

Full Text Available Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke.Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3-7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls.Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions.Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process after stroke. Larger

Effect of ionizing radiation on the differentiation of neural stem cells

International Nuclear Information System (INIS)

Liu Ping; Tu Yu

2010-01-01

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

Quantitative Analysis of Ca, Mg, and K in the Roots of Angelica pubescens f. biserrata by Laser-Induced Breakdown Spectroscopy Combined with Artificial Neural Networks

Science.gov (United States)

Wang, J.; Shi, M.; Zheng, P.; Xue, Sh.; Peng, R.

2018-03-01

Laser-induced breakdown spectroscopy has been applied for the quantitative analysis of Ca, Mg, and K in the roots of Angelica pubescens Maxim. f. biserrata Shan et Yuan used in traditional Chinese medicine. Ca II 317.993 nm, Mg I 517.268 nm, and K I 769.896 nm spectral lines have been chosen to set up calibration models for the analysis using the external standard and artificial neural network methods. The linear correlation coefficients of the predicted concentrations versus the standard concentrations of six samples determined by the artificial neural network method are 0.9896, 0.9945, and 0.9911 for Ca, Mg, and K, respectively, which are better than for the external standard method. The artificial neural network method also gives better performance comparing with the external standard method for the average and maximum relative errors, average relative standard deviations, and most maximum relative standard deviations of the predicted concentrations of Ca, Mg, and K in the six samples. Finally, it is proved that the artificial neural network method gives better performance compared to the external standard method for the quantitative analysis of Ca, Mg, and K in the roots of Angelica pubescens.

Rapid fluctuations in extracellular brain glucose levels induced by natural arousing stimuli and intravenous cocaine: fueling the brain during neural activation

Science.gov (United States)

Lenoir, Magalie

2012-01-01

Glucose, a primary energetic substrate for neural activity, is continuously influenced by two opposing forces that tend to either decrease its extracellular levels due to enhanced utilization in neural cells or increase its levels due to entry from peripheral circulation via enhanced cerebral blood flow. How this balance is maintained under physiological conditions and changed during neural activation remains unclear. To clarify this issue, enzyme-based glucose sensors coupled with high-speed amperometry were used in freely moving rats to evaluate fluctuations in extracellular glucose levels induced by brief audio stimulus, tail pinch (TP), social interaction with another rat (SI), and intravenous cocaine (1 mg/kg). Measurements were performed in nucleus accumbens (NAcc) and substantia nigra pars reticulata (SNr), which drastically differ in neuronal activity. In NAcc, where most cells are powerfully excited after salient stimulation, glucose levels rapidly (latency 2–6 s) increased (30–70 μM or 6–14% over baseline) by all stimuli; the increase differed in magnitude and duration for each stimulus. In SNr, where most cells are transiently inhibited by salient stimuli, TP, SI, and cocaine induced a biphasic glucose response, with the initial decrease (−20–40 μM or 5–10% below baseline) followed by a reboundlike increase. The critical role of neuronal activity in mediating the initial glucose response was confirmed by monitoring glucose currents after local microinjections of glutamate (GLU) or procaine (PRO). While intra-NAcc injection of GLU transiently increased glucose levels in this structure, intra-SNr PRO injection resulted in rapid, transient decreases in SNr glucose. Therefore, extracellular glucose levels in the brain change very rapidly after physiological and pharmacological stimulation, the response is structure specific, and the pattern of neuronal activity appears to be a critical factor determining direction and magnitude of physiological

Chromatic assimilation unaffected by perceived depth of inducing light.

Science.gov (United States)

Shevell, Steven K; Cao, Dingcai

2004-01-01

Chromatic assimilation is a shift toward the color of nearby light. Several studies conclude that a neural process contributes to assimilation but the neural locus remains in question. Some studies posit a peripheral process, such as retinal receptive-field organization, while others claim the neural mechanism follows depth perception, figure/ground segregation, or perceptual grouping. The experiments here tested whether assimilation depends on a neural process that follows stereoscopic depth perception. By introducing binocular disparity, the test field judged in color was made to appear in a different depth plane than the light that induced assimilation. The chromaticity and spatial frequency of the inducing light, and the chromaticity of the test light, were varied. Chromatic assimilation was found with all inducing-light sizes and chromaticities, but the magnitude of assimilation did not depend on the perceived relative depth planes of the test and inducing fields. We found no evidence to support the view that chromatic assimilation depends on a neural process that follows binocular combination of the two eyes' signals.

Cue-induced Behavioral and Neural Changes among Excessive Internet Gamers and Possible Application of Cue Exposure Therapy to Internet Gaming Disorder

Directory of Open Access Journals (Sweden)

Yongjun eZhang

2016-05-01

Full Text Available Internet gaming disorder (IGD may lead to many negative consequences in everyday life, yet there is currently no effective treatment for IGD. Cue-reactivity paradigm is commonly used to evaluate craving for substance, food, and gambling; cue exposure therapy (CET is applied to treating substance use disorders (SUDs and some other psychological disorders such as pathological gambling (PG. However, no study has explored CET’s application to the treatment of IGD except two articles having implied that cues’ exposure may have therapeutic effect on IGD. This paper reviews studies on cue-induced behavioral and neural changes in excessive Internet gamers, indicating that behavioral and neural mechanisms of IGD mostly overlap with those of SUD. The CET’s effects in the treatment of SUDs and PG are also reviewed. We finally propose an optimized CET paradigm, which future studies should consider and investigate as a probable treatment of IGD.

Cue-induced Behavioral and Neural Changes among Excessive Internet Gamers and Possible Application of Cue Exposure Therapy to Internet Gaming Disorder.

Science.gov (United States)

Zhang, Yongjun; Ndasauka, Yamikani; Hou, Juan; Chen, Jiawen; Yang, Li Zhuang; Wang, Ying; Han, Long; Bu, Junjie; Zhang, Peng; Zhou, Yifeng; Zhang, Xiaochu

2016-01-01

Internet gaming disorder (IGD) may lead to many negative consequences in everyday life, yet there is currently no effective treatment for IGD. Cue-reactivity paradigm is commonly used to evaluate craving for substance, food, and gambling; cue exposure therapy (CET) is applied to treating substance use disorders (SUDs) and some other psychological disorders such as pathological gambling (PG). However, no study has explored CET's application to the treatment of IGD except two articles having implied that cues' exposure may have therapeutic effect on IGD. This paper reviews studies on cue-induced behavioral and neural changes in excessive Internet gamers, indicating that behavioral and neural mechanisms of IGD mostly overlap with those of SUD. The CET's effects in the treatment of SUDs and PG are also reviewed. We finally propose an optimized CET paradigm, which future studies should consider and investigate as a probable treatment of IGD.

(GAGs) in normal and ethanol-induced chick embryo during neural

African Journals Online (AJOL)

Administrator

2011-09-14

Sep 14, 2011 ... It is indicated that neural cell adhesion molecule (N-CAM), fibronectin, ... fenitoin, retinoic acid and alcohol), heavy metals (for example, Zn, Cr,) ... of neurons and glial cells during embryogenesis, frontonasal tissue loss, ...

The novel steroidal alkaloids dendrogenin A and B promote proliferation of adult neural stem cells

International Nuclear Information System (INIS)

Khalifa, Shaden A.M.; Medina, Philippe de; Erlandsson, Anna; El-Seedi, Hesham R.; Silvente-Poirot, Sandrine; Poirot, Marc

2014-01-01

Highlights: • Dendrogenin A and B are new aminoalkyl oxysterols. • Dendrogenins stimulated neural stem cells proliferation. • Dendrogenins induce neuronal outgrowth from neurospheres. • Dendrogenins provide new therapeutic options for neurodegenerative disorders. - Abstract: Dendrogenin A (DDA) and dendrogenin B (DDB) are new aminoalkyl oxysterols which display re-differentiation of tumor cells of neuronal origin at nanomolar concentrations. We analyzed the influence of dendrogenins on adult mice neural stem cell proliferation, sphere formation and differentiation. DDA and DDB were found to have potent proliferative effects in neural stem cells. Additionally, they induce neuronal outgrowth from neurospheres during in vitro cultivation. Taken together, our results demonstrate a novel role for dendrogenins A and B in neural stem cell proliferation and differentiation which further increases their likely importance to compensate for neuronal cell loss in the brain

The novel steroidal alkaloids dendrogenin A and B promote proliferation of adult neural stem cells

Energy Technology Data Exchange (ETDEWEB)

Khalifa, Shaden A.M., E-mail: shaden.khalifa@ki.se [Department of Neuroscience, Karolinska Institute, Stockholm (Sweden); Medina, Philippe de [Affichem, Toulouse (France); INSERM UMR 1037, Team “Sterol Metabolism and Therapeutic Innovations in Oncology”, Cancer Research Center of Toulouse, F-31052 Toulouse (France); Erlandsson, Anna [Department of Public Health and Caring Sciences, Uppsala University, Uppsala (Sweden); El-Seedi, Hesham R. [Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, Uppsala (Sweden); Silvente-Poirot, Sandrine [INSERM UMR 1037, Team “Sterol Metabolism and Therapeutic Innovations in Oncology”, Cancer Research Center of Toulouse, F-31052 Toulouse (France); University of Toulouse III, Toulouse (France); Institut Claudius Regaud, Toulouse (France); Poirot, Marc, E-mail: marc.poirot@inserm.fr [INSERM UMR 1037, Team “Sterol Metabolism and Therapeutic Innovations in Oncology”, Cancer Research Center of Toulouse, F-31052 Toulouse (France); University of Toulouse III, Toulouse (France); Institut Claudius Regaud, Toulouse (France)

2014-04-11

Highlights: • Dendrogenin A and B are new aminoalkyl oxysterols. • Dendrogenins stimulated neural stem cells proliferation. • Dendrogenins induce neuronal outgrowth from neurospheres. • Dendrogenins provide new therapeutic options for neurodegenerative disorders. - Abstract: Dendrogenin A (DDA) and dendrogenin B (DDB) are new aminoalkyl oxysterols which display re-differentiation of tumor cells of neuronal origin at nanomolar concentrations. We analyzed the influence of dendrogenins on adult mice neural stem cell proliferation, sphere formation and differentiation. DDA and DDB were found to have potent proliferative effects in neural stem cells. Additionally, they induce neuronal outgrowth from neurospheres during in vitro cultivation. Taken together, our results demonstrate a novel role for dendrogenins A and B in neural stem cell proliferation and differentiation which further increases their likely importance to compensate for neuronal cell loss in the brain.

Burst firing enhances neural output correlation

Directory of Open Access Journals (Sweden)

Ho Ka eChan

2016-05-01

Full Text Available Neurons communicate and transmit information predominantly through spikes. Given that experimentally observed neural spike trains in a variety of brain areas can be highly correlated, it is important to investigate how neurons process correlated inputs. Most previous work in this area studied the problem of correlation transfer analytically by making significant simplifications on neural dynamics. Temporal correlation between inputs that arises from synaptic filtering, for instance, is often ignored when assuming that an input spike can at most generate one output spike. Through numerical simulations of a pair of leaky integrate-and-fire (LIF neurons receiving correlated inputs, we demonstrate that neurons in the presence of synaptic filtering by slow synapses exhibit strong output correlations. We then show that burst firing plays a central role in enhancing output correlations, which can explain the above-mentioned observation because synaptic filtering induces bursting. The observed changes of correlations are mostly on a long time scale. Our results suggest that other features affecting the prevalence of neural burst firing in biological neurons, e.g., adaptive spiking mechanisms, may play an important role in modulating the overall level of correlations in neural networks.

(GAGs) in normal and ethanol-induced chick embryo during neural

African Journals Online (AJOL)

Administrator

2011-09-14

Sep 14, 2011 ... Alcohol as a teratogenic agent inhibits cell growth, function, proliferation and migration by affecting .... formed along the right and left side of the neural tube .... of neurons by harming the developing brain and also can.

Neural cell adhesion molecule-180-mediated homophilic binding induces epidermal growth factor receptor (EGFR) down-regulation and uncouples the inhibitory function of EGFR in neurite outgrowth

DEFF Research Database (Denmark)

Povlsen, Gro Klitgaard; Berezin, Vladimir; Bock, Elisabeth

2008-01-01

The neural cell adhesion molecule (NCAM) plays important roles in neuronal development, regeneration, and synaptic plasticity. NCAM homophilic binding mediates cell adhesion and induces intracellular signals, in which the fibroblast growth factor receptor plays a prominent role. Recent studies...... this NCAM-180-induced EGFR down-regulation involves increased EGFR ubiquitination and lysosomal EGFR degradation. Furthermore, NCAM-180-mediated EGFR down-regulation requires NCAM homophilic binding and interactions of the cytoplasmic domain of NCAM-180 with intracellular interaction partners, but does...

Regulation of Msx genes by a Bmp gradient is essential for neural crest specification.

Science.gov (United States)

Tribulo, Celeste; Aybar, Manuel J; Nguyen, Vu H; Mullins, Mary C; Mayor, Roberto

2003-12-01

There is evidence in Xenopus and zebrafish embryos that the neural crest/neural folds are specified at the border of the neural plate by a precise threshold concentration of a Bmp gradient. In order to understand the molecular mechanism by which a gradient of Bmp is able to specify the neural crest, we analyzed how the expression of Bmp targets, the Msx genes, is regulated and the role that Msx genes has in neural crest specification. As Msx genes are directly downstream of Bmp, we analyzed Msx gene expression after experimental modification in the level of Bmp activity by grafting a bead soaked with noggin into Xenopus embryos, by expressing in the ectoderm a dominant-negative Bmp4 or Bmp receptor in Xenopus and zebrafish embryos, and also through Bmp pathway component mutants in the zebrafish. All the results show that a reduction in the level of Bmp activity leads to an increase in the expression of Msx genes in the neural plate border. Interestingly, by reaching different levels of Bmp activity in animal cap ectoderm, we show that a specific concentration of Bmp induces msx1 expression to a level similar to that required to induce neural crest. Our results indicate that an intermediate level of Bmp activity specifies the expression of Msx genes in the neural fold region. In addition, we have analyzed the role that msx1 plays on neural crest specification. As msx1 has a role in dorsoventral pattering, we have carried out conditional gain- and loss-of-function experiments using different msx1 constructs fused to a glucocorticoid receptor element to avoid an early effect of this factor. We show that msx1 expression is able to induce all other early neural crest markers tested (snail, slug, foxd3) at the time of neural crest specification. Furthermore, the expression of a dominant negative of Msx genes leads to the inhibition of all the neural crest markers analyzed. It has been previously shown that snail is one of the earliest genes acting in the neural crest

Investigating Patterns for Self-Induced Emotion Recognition from EEG Signals

Science.gov (United States)

Zeng, Ying; Yang, Kai; Tong, Li; Yan, Bin

2018-01-01

Most current approaches to emotion recognition are based on neural signals elicited by affective materials such as images, sounds and videos. However, the application of neural patterns in the recognition of self-induced emotions remains uninvestigated. In this study we inferred the patterns and neural signatures of self-induced emotions from electroencephalogram (EEG) signals. The EEG signals of 30 participants were recorded while they watched 18 Chinese movie clips which were intended to elicit six discrete emotions, including joy, neutrality, sadness, disgust, anger and fear. After watching each movie clip the participants were asked to self-induce emotions by recalling a specific scene from each movie. We analyzed the important features, electrode distribution and average neural patterns of different self-induced emotions. Results demonstrated that features related to high-frequency rhythm of EEG signals from electrodes distributed in the bilateral temporal, prefrontal and occipital lobes have outstanding performance in the discrimination of emotions. Moreover, the six discrete categories of self-induced emotion exhibit specific neural patterns and brain topography distributions. We achieved an average accuracy of 87.36% in the discrimination of positive from negative self-induced emotions and 54.52% in the classification of emotions into six discrete categories. Our research will help promote the development of comprehensive endogenous emotion recognition methods. PMID:29534515

Investigating Patterns for Self-Induced Emotion Recognition from EEG Signals.

Science.gov (United States)

Zhuang, Ning; Zeng, Ying; Yang, Kai; Zhang, Chi; Tong, Li; Yan, Bin

2018-03-12

Most current approaches to emotion recognition are based on neural signals elicited by affective materials such as images, sounds and videos. However, the application of neural patterns in the recognition of self-induced emotions remains uninvestigated. In this study we inferred the patterns and neural signatures of self-induced emotions from electroencephalogram (EEG) signals. The EEG signals of 30 participants were recorded while they watched 18 Chinese movie clips which were intended to elicit six discrete emotions, including joy, neutrality, sadness, disgust, anger and fear. After watching each movie clip the participants were asked to self-induce emotions by recalling a specific scene from each movie. We analyzed the important features, electrode distribution and average neural patterns of different self-induced emotions. Results demonstrated that features related to high-frequency rhythm of EEG signals from electrodes distributed in the bilateral temporal, prefrontal and occipital lobes have outstanding performance in the discrimination of emotions. Moreover, the six discrete categories of self-induced emotion exhibit specific neural patterns and brain topography distributions. We achieved an average accuracy of 87.36% in the discrimination of positive from negative self-induced emotions and 54.52% in the classification of emotions into six discrete categories. Our research will help promote the development of comprehensive endogenous emotion recognition methods.

Novel paths towards neural cellular products for neurological disorders.

Science.gov (United States)

Daadi, Marcel M

2011-11-01

The prospect of using neural cells derived from stem cells or from reprogrammed adult somatic cells provides a unique opportunity in cell therapy and drug discovery for developing novel strategies for brain repair. Cell-based therapeutic approaches for treating CNS afflictions caused by disease or injury aim to promote structural repair of the injured or diseased neural tissue, an outcome currently not achieved by drug therapy. Preclinical research in animal models of various diseases or injuries report that grafts of neural cells enhance endogenous repair, provide neurotrophic support to neurons undergoing degeneration and replace lost neural cells. In recent years, the sources of neural cells for treating neurological disorders have been rapidly expanding and in addition to offering therapeutic potential, neural cell products hold promise for disease modeling and drug discovery use. Specific neural cell types have been derived from adult or fetal brain, from human embryonic stem cells, from induced pluripotent stem cells and directly transdifferentiated from adult somatic cells, such as skin cells. It is yet to be determined if the latter approach will evolve into a paradigm shift in the fields of stem cell research and regenerative medicine. These multiple sources of neural cells cover a wide spectrum of safety that needs to be balanced with efficacy to determine the viability of the cellular product. In this article, we will review novel sources of neural cells and discuss current obstacles to developing them into viable cellular products for treating neurological disorders.

Glucocorticoid control of gene transcription in neural tissue

NARCIS (Netherlands)

Morsink, Maarten Christian

2007-01-01

Glucocorticoid hormones exert modulatory effects on neural function in a delayed genomic fashion. The two receptor types that can bind glucocorticoids, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR), are ligand-inducible transcription factors. Therefore, changes in gene

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

Science.gov (United States)

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

2016-10-01

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

Unique Preservation of Neural Cells in Hutchinson- Gilford Progeria Syndrome Is Due to the Expression of the Neural-Specific miR-9 MicroRNA

Directory of Open Access Journals (Sweden)

Xavier Nissan

2012-07-01

Full Text Available One puzzling observation in patients affected with Hutchinson-Gilford progeria syndrome (HGPS, who overall exhibit systemic and dramatic premature aging, is the absence of any conspicuous cognitive impairment. Recent studies based on induced pluripotent stem cells derived from HGPS patient cells have revealed a lack of expression in neural derivatives of lamin A, a major isoform of LMNA that is initially produced as a precursor called prelamin A. In HGPS, defective maturation of a mutated prelamin A induces the accumulation of toxic progerin in patient cells. Here, we show that a microRNA, miR-9, negatively controls lamin A and progerin expression in neural cells. This may bear major functional correlates, as alleviation of nuclear blebbing is observed in nonneural cells after miR-9 overexpression. Our results support the hypothesis, recently proposed from analyses in mice, that protection of neural cells from progerin accumulation in HGPS is due to the physiologically restricted expression of miR-9 to that cell lineage.

A Novel Approach for Blast-Induced Flyrock Prediction Based on Imperialist Competitive Algorithm and Artificial Neural Network

Science.gov (United States)

Marto, Aminaton; Jahed Armaghani, Danial; Tonnizam Mohamad, Edy; Makhtar, Ahmad Mahir

2014-01-01

Flyrock is one of the major disturbances induced by blasting which may cause severe damage to nearby structures. This phenomenon has to be precisely predicted and subsequently controlled through the changing in the blast design to minimize potential risk of blasting. The scope of this study is to predict flyrock induced by blasting through a novel approach based on the combination of imperialist competitive algorithm (ICA) and artificial neural network (ANN). For this purpose, the parameters of 113 blasting operations were accurately recorded and flyrock distances were measured for each operation. By applying the sensitivity analysis, maximum charge per delay and powder factor were determined as the most influential parameters on flyrock. In the light of this analysis, two new empirical predictors were developed to predict flyrock distance. For a comparison purpose, a predeveloped backpropagation (BP) ANN was developed and the results were compared with those of the proposed ICA-ANN model and empirical predictors. The results clearly showed the superiority of the proposed ICA-ANN model in comparison with the proposed BP-ANN model and empirical approaches. PMID:25147856

A Novel Approach for Blast-Induced Flyrock Prediction Based on Imperialist Competitive Algorithm and Artificial Neural Network

Directory of Open Access Journals (Sweden)

Aminaton Marto

2014-01-01

Full Text Available Flyrock is one of the major disturbances induced by blasting which may cause severe damage to nearby structures. This phenomenon has to be precisely predicted and subsequently controlled through the changing in the blast design to minimize potential risk of blasting. The scope of this study is to predict flyrock induced by blasting through a novel approach based on the combination of imperialist competitive algorithm (ICA and artificial neural network (ANN. For this purpose, the parameters of 113 blasting operations were accurately recorded and flyrock distances were measured for each operation. By applying the sensitivity analysis, maximum charge per delay and powder factor were determined as the most influential parameters on flyrock. In the light of this analysis, two new empirical predictors were developed to predict flyrock distance. For a comparison purpose, a predeveloped backpropagation (BP ANN was developed and the results were compared with those of the proposed ICA-ANN model and empirical predictors. The results clearly showed the superiority of the proposed ICA-ANN model in comparison with the proposed BP-ANN model and empirical approaches.

Neural plasticity and its initiating conditions in tinnitus.

Science.gov (United States)

Roberts, L E

2018-03-01

Deafferentation caused by cochlear pathology (which can be hidden from the audiogram) activates forms of neural plasticity in auditory pathways, generating tinnitus and its associated conditions including hyperacusis. This article discusses tinnitus mechanisms and suggests how these mechanisms may relate to those involved in normal auditory information processing. Research findings from animal models of tinnitus and from electromagnetic imaging of tinnitus patients are reviewed which pertain to the role of deafferentation and neural plasticity in tinnitus and hyperacusis. Auditory neurons compensate for deafferentation by increasing their input/output functions (gain) at multiple levels of the auditory system. Forms of homeostatic plasticity are believed to be responsible for this neural change, which increases the spontaneous and driven activity of neurons in central auditory structures in animals expressing behavioral evidence of tinnitus. Another tinnitus correlate, increased neural synchrony among the affected neurons, is forged by spike-timing-dependent neural plasticity in auditory pathways. Slow oscillations generated by bursting thalamic neurons verified in tinnitus animals appear to modulate neural plasticity in the cortex, integrating tinnitus neural activity with information in brain regions supporting memory, emotion, and consciousness which exhibit increased metabolic activity in tinnitus patients. The latter process may be induced by transient auditory events in normal processing but it persists in tinnitus, driven by phantom signals from the auditory pathway. Several tinnitus therapies attempt to suppress tinnitus through plasticity, but repeated sessions will likely be needed to prevent tinnitus activity from returning owing to deafferentation as its initiating condition.

SPR imaging combined with cyclic voltammetry for the detection of neural activity

Directory of Open Access Journals (Sweden)

Hui Li

2014-03-01

Full Text Available Surface plasmon resonance (SPR detects changes in refractive index at a metal-dielectric interface. In this study, SPR imaging (SPRi combined with cyclic voltammetry (CV was applied to detect neural activity in isolated bullfrog sciatic nerves. The neural activities induced by chemical and electrical stimulation led to an SPR response, and the activities were recorded in real time. The activities of different parts of the sciatic nerve were recorded and compared. The results demonstrated that SPR imaging combined with CV is a powerful tool for the investigation of neural activity.

Interaction of adult human neural crest-derived stem cells with a nanoporous titanium surface is sufficient to induce their osteogenic differentiation

Directory of Open Access Journals (Sweden)

Matthias Schürmann

2014-07-01

Full Text Available Osteogenic differentiation of various adult stem cell populations such as neural crest-derived stem cells is of great interest in the context of bone regeneration. Ideally, exogenous differentiation should mimic an endogenous differentiation process, which is partly mediated by topological cues. To elucidate the osteoinductive potential of porous substrates with different pore diameters (30 nm, 100 nm, human neural crest-derived stem cells isolated from the inferior nasal turbinate were cultivated on the surface of nanoporous titanium covered membranes without additional chemical or biological osteoinductive cues. As controls, flat titanium without any topological features and osteogenic medium was used. Cultivation of human neural crest-derived stem cells on 30 nm pores resulted in osteogenic differentiation as demonstrated by alkaline phosphatase activity after seven days as well as by calcium deposition after 3 weeks of cultivation. In contrast, cultivation on flat titanium and on membranes equipped with 100 nm pores was not sufficient to induce osteogenic differentiation. Moreover, we demonstrate an increase of osteogenic transcripts including Osterix, Osteocalcin and up-regulation of Integrin β1 and α2 in the 30 nm pore approach only. Thus, transplantation of stem cells pre-cultivated on nanostructured implants might improve the clinical outcome by support of the graft adherence and acceleration of the regeneration process.

Induced pluripotency with endogenous and inducible genes

International Nuclear Information System (INIS)

Duinsbergen, Dirk; Eriksson, Malin; Hoen, Peter A.C. 't; Frisen, Jonas; Mikkers, Harald

2008-01-01

The recent discovery that two partly overlapping sets of four genes induce nuclear reprogramming of mouse and even human cells has opened up new possibilities for cell replacement therapies. Although the combination of genes that induce pluripotency differs to some extent, Oct4 and Sox2 appear to be a prerequisite. The introduction of four genes, several of which been linked with cancer, using retroviral approaches is however unlikely to be suitable for future clinical applications. Towards developing a safer reprogramming protocol, we investigated whether cell types that express one of the most critical reprogramming genes endogenously are predisposed to reprogramming. We show here that three of the original four pluripotency transcription factors (Oct4, Klf4 and c-Myc or MYCER TAM ) induced reprogramming of mouse neural stem (NS) cells exploiting endogenous SoxB1 protein levels in these cells. The reprogrammed neural stem cells differentiated into cells of each germ layer in vitro and in vivo, and contributed to mouse development in vivo. Thus a combinatorial approach taking advantage of endogenously expressed genes and inducible transgenes may contribute to the development of improved reprogramming protocols

Controlling the dynamics of multi-state neural networks

International Nuclear Information System (INIS)

Jin, Tao; Zhao, Hong

2008-01-01

In this paper, we first analyze the distribution of local fields (DLF) which is induced by the memory patterns in the Q-Ising model. It is found that the structure of the DLF is closely correlated with the network dynamics and the system performance. However, the design rule adopted in the Q-Ising model, like the other rules adopted for multi-state neural networks with associative memories, cannot be applied to directly control the DLF for a given set of memory patterns, and thus cannot be applied to further study the relationships between the structure of the DLF and the dynamics of the network. We then extend a design rule, which was presented recently for designing binary-state neural networks, to make it suitable for designing general multi-state neural networks. This rule is able to control the structure of the DLF as expected. We show that controlling the DLF not only can affect the dynamic behaviors of the multi-state neural networks for a given set of memory patterns, but also can improve the storage capacity. With the change of the DLF, the network shows very rich dynamic behaviors, such as the 'chaos phase', the 'memory phase', and the 'mixture phase'. These dynamic behaviors are also observed in the binary-state neural networks; therefore, our results imply that they may be the universal behaviors of feedback neural networks

A neural hypothesis for stress-induced headache.

Science.gov (United States)

Cathcart, Stuart

2009-12-01

The mechanisms by which stress contributes to CTH are not clearly understood. The commonly accepted notion of muscle hyper-reactivity to stress in CTH sufferers is not supported in the research data. We propose a neural model whereby stress acts supra-spinally to aggravate already increased pain sensitivity in CTH sufferers. Indirect support for the model comes from emerging research elucidating complex supra-spinal networks through which psychological stress may contribute to and even cause pain. Similarly, emerging research demonstrates supra-spinal pain processing abnormalities in CTH sufferers. While research with CTH sufferers offering direct support for the model is lacking at present, initial work by our group is consistent with the models predictions, particularly, that stress aggravates already increased pain sensitivity in CTH sufferers.

Generation of Induced Pluripotent Stem Cells and Neural Stem/Progenitor Cells from Newborns with Spina Bifida Aperta.

Science.gov (United States)

Bamba, Yohei; Nonaka, Masahiro; Sasaki, Natsu; Shofuda, Tomoko; Kanematsu, Daisuke; Suemizu, Hiroshi; Higuchi, Yuichiro; Pooh, Ritsuko K; Kanemura, Yonehiro; Okano, Hideyuki; Yamasaki, Mami

2017-12-01

We established induced pluripotent stem cells (iPSCs) and neural stem/progenitor cells (NSPCs) from three newborns with spina bifida aperta (SBa) using clinically practical methods. We aimed to develop stem cell lines derived from newborns with SBa for future therapeutic use. SBa is a common congenital spinal cord abnormality that causes defects in neurological and urological functions. Stem cell transplantation therapies are predicted to provide beneficial effects for patients with SBa. However, the availability of appropriate cell sources is inadequate for clinical use because of their limited accessibility and expandability, as well as ethical issues. Fibroblast cultures were established from small fragments of skin obtained from newborns with SBa during SBa repair surgery. The cultured cells were transfected with episomal plasmid vectors encoding reprogramming factors necessary for generating iPSCs. These cells were then differentiated into NSPCs by chemical compound treatment, and NSPCs were expanded using neurosphere technology. We successfully generated iPSC lines from the neonatal dermal fibroblasts of three newborns with SBa. We confirmed that these lines exhibited the characteristics of human pluripotent stem cells. We successfully generated NSPCs from all SBa newborn-derived iPSCs with a combination of neural induction and neurosphere technology. We successfully generated iPSCs and iPSC-NSPCs from surgical samples obtained from newborns with SBa with the goal of future clinical use in patients with SBa.

Rainfall and earthquake-induced landslide susceptibility assessment using GIS and Artificial Neural Network

Directory of Open Access Journals (Sweden)

Y. Li

2012-08-01

Full Text Available A GIS-based method for the assessment of landslide susceptibility in a selected area of Qingchuan County in China is proposed by using the back-propagation Artificial Neural Network model (ANN. Landslide inventory was derived from field investigation and aerial photo interpretation. 473 landslides occurred before the Wenchuan earthquake (which were thought as rainfall-induced landslides (RIL in this study, and 885 earthquake-induced landslides (EIL were recorded into the landslide inventory map. To understand the different impacts of rainfall and earthquake on landslide occurrence, we first compared the variations between landslide spatial distribution and conditioning factors. Then, we compared the weight variation of each conditioning factor derived by adjusting ANN structure and factors combination respectively. Last, the weight of each factor derived from the best prediction model was applied to the entire study area to produce landslide susceptibility maps.

Results show that slope gradient has the highest weight for landslide susceptibility mapping for both RIL and EIL. The RIL model built with four different factors (slope gradient, elevation, slope height and distance to the stream shows the best success rate of 93%; the EIL model built with five different factors (slope gradient, elevation, slope height, distance to the stream and distance to the fault has the best success rate of 98%. Furthermore, the EIL data was used to verify the RIL model and the success rate is 92%; the RIL data was used to verify the EIL model and the success rate is 53%.

Neural regulation of the kidney function in rats with cisplatin induced renal failure

Science.gov (United States)

Goulding, Niamh E.; Johns, Edward J.

2015-01-01

Aim: Chronic kidney disease (CKD) is often associated with a disturbed cardiovascular homeostasis. This investigation explored the role of the renal innervation in mediating deranged baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory function in cisplatin-induced renal failure. Methods: Rats were either intact or bilaterally renally denervated 4 days prior to receiving cisplatin (5 mg/kg i.p.) and entered a chronic metabolic study for 8 days. At day 8, other groups of rats were prepared for acute measurement of RSNA or renal function with either intact or denervated kidneys. Results: Following the cisplatin challenge, creatinine clearance was 50% lower while fractional sodium excretion and renal cortical and medullary TGF-β1 concentrations were 3–4 fold higher in both intact and renally denervated rats compared to control rats. In cisplatin-treated rats, the maximal gain of the high-pressure baroreflex curve was only 20% that of control rats, but following renal denervation not different from that of renally denervated control rats. Volume expansion reduced RSNA by 50% in control and in cisplatin-treated rats but only following bilateral renal denervation. The volume expansion mediated natriuresis/diuresis was absent in the cisplatin-treated rats but was normalized following renal denervation. Conclusions: Cisplatin-induced renal injury impaired renal function and caused a sympatho-excitation with blunting of high and low pressure baroreflex regulation of RSNA, which was dependent on the renal innervation. It is suggested that in man with CKD there is a dysregulation of the neural control of the kidney mediated by its sensory innervation. PMID:26175693

Robo signaling regulates the production of cranial neural crest cells.

Science.gov (United States)

Li, Yan; Zhang, Xiao-Tan; Wang, Xiao-Yu; Wang, Guang; Chuai, Manli; Münsterberg, Andrea; Yang, Xuesong

2017-12-01

Slit/Robo signaling plays an important role in the guidance of developing neurons in developing embryos. However, it remains obscure whether and how Slit/Robo signaling is involved in the production of cranial neural crest cells. In this study, we examined Robo1 deficient mice to reveal developmental defects of mouse cranial frontal and parietal bones, which are derivatives of cranial neural crest cells. Therefore, we determined the production of HNK1 + cranial neural crest cells in early chick embryo development after knock-down (KD) of Robo1 expression. Detection of markers for pre-migratory and migratory neural crest cells, PAX7 and AP-2α, showed that production of both was affected by Robo1 KD. In addition, we found that the transcription factor slug is responsible for the aberrant delamination/EMT of cranial neural crest cells induced by Robo1 KD, which also led to elevated expression of E- and N-Cadherin. N-Cadherin expression was enhanced when blocking FGF signaling with dominant-negative FGFR1 in half of the neural tube. Taken together, we show that Slit/Robo signaling influences the delamination/EMT of cranial neural crest cells, which is required for cranial bone development. Copyright © 2017. Published by Elsevier Inc.

Influence of neural adaptation on dynamics and equilibrium state of neural activities in a ring neural network

Science.gov (United States)

Takiyama, Ken

2017-12-01

How neural adaptation affects neural information processing (i.e. the dynamics and equilibrium state of neural activities) is a central question in computational neuroscience. In my previous works, I analytically clarified the dynamics and equilibrium state of neural activities in a ring-type neural network model that is widely used to model the visual cortex, motor cortex, and several other brain regions. The neural dynamics and the equilibrium state in the neural network model corresponded to a Bayesian computation and statistically optimal multiple information integration, respectively, under a biologically inspired condition. These results were revealed in an analytically tractable manner; however, adaptation effects were not considered. Here, I analytically reveal how the dynamics and equilibrium state of neural activities in a ring neural network are influenced by spike-frequency adaptation (SFA). SFA is an adaptation that causes gradual inhibition of neural activity when a sustained stimulus is applied, and the strength of this inhibition depends on neural activities. I reveal that SFA plays three roles: (1) SFA amplifies the influence of external input in neural dynamics; (2) SFA allows the history of the external input to affect neural dynamics; and (3) the equilibrium state corresponds to the statistically optimal multiple information integration independent of the existence of SFA. In addition, the equilibrium state in a ring neural network model corresponds to the statistically optimal integration of multiple information sources under biologically inspired conditions, independent of the existence of SFA.

A neural cell adhesion molecule-derived peptide reduces neuropathological signs and cognitive impairment induced by Abeta25-35

DEFF Research Database (Denmark)

Klementiev, B; Novikova, T; Novitskaya, V

2007-01-01

death and brain atrophy in response to Abeta25-35. Finally, the Abeta25-35-administration led to a reduced short-term memory as determined by the social recognition test. A synthetic peptide termed FGL derived from the neural cell adhesion molecule (NCAM) was able to prevent or, if already manifest......, strongly reduce all investigated signs of Abeta25-35-induced neuropathology and cognitive impairment. The FGL peptide was recently demonstrated to be able to cross the blood-brain-barrier. Accordingly, we found that the beneficial effects of FGL were achieved not only by intracisternal, but also...... and cognitive impairment involves the modulation of intracellular signal-transduction mediated through GSK3beta....

Fast neutron spectra determination by threshold activation detectors using neural networks

International Nuclear Information System (INIS)

Kardan, M.R.; Koohi-Fayegh, R.; Setayeshi, S.; Ghiassi-Nejad, M.

2004-01-01

Neural network method was used for fast neutron spectra unfolding in spectrometry by threshold activation detectors. The input layer of the neural networks consisted of 11 neurons for the specific activities of neutron-induced nuclear reaction products, while the output layers were fast neutron spectra which had been subdivided into 6, 8, 10, 12, 15 and 20 energy bins. Neural network training was performed by 437 fast neutron spectra and corresponding threshold activation detector readings. The trained neural network have been applied for unfolding 50 spectra, which were not in training sets and the results were compared with real spectra and unfolded spectra by SANDII. The best results belong to 10 energy bin spectra. The neural network was also trained by detector readings with 5% uncertainty and the response of the trained neural network to detector readings with 5%, 10%, 15%, 20%, 25% and 50% uncertainty was compared with real spectra. Neural network algorithm, in comparison with other unfolding methods, is very fast and needless to detector response matrix and any prior information about spectra and also the outputs have low sensitivity to uncertainty in the activity measurements. The results show that the neural network algorithm is useful when a fast response is required with reasonable accuracy

Dysfunction of Rapid Neural Adaptation in Dyslexia.

Science.gov (United States)

Perrachione, Tyler K; Del Tufo, Stephanie N; Winter, Rebecca; Murtagh, Jack; Cyr, Abigail; Chang, Patricia; Halverson, Kelly; Ghosh, Satrajit S; Christodoulou, Joanna A; Gabrieli, John D E

2016-12-21

Identification of specific neurophysiological dysfunctions resulting in selective reading difficulty (dyslexia) has remained elusive. In addition to impaired reading development, individuals with dyslexia frequently exhibit behavioral deficits in perceptual adaptation. Here, we assessed neurophysiological adaptation to stimulus repetition in adults and children with dyslexia for a wide variety of stimuli, spoken words, written words, visual objects, and faces. For every stimulus type, individuals with dyslexia exhibited significantly diminished neural adaptation compared to controls in stimulus-specific cortical areas. Better reading skills in adults and children with dyslexia were associated with greater repetition-induced neural adaptation. These results highlight a dysfunction of rapid neural adaptation as a core neurophysiological difference in dyslexia that may underlie impaired reading development. Reduced neurophysiological adaptation may relate to prior reports of reduced behavioral adaptation in dyslexia and may reveal a difference in brain functions that ultimately results in a specific reading impairment. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

Mitani, S; Okamoto, H

1991-05-01

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

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.

Dynamic methylation and expression of Oct4 in early neural stem cells.

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Lee, Shih-Han; Jeyapalan, Jennie N; Appleby, Vanessa; Mohamed Noor, Dzul Azri; Sottile, Virginie; Scotting, Paul J

2010-09-01

Neural stem cells are a multipotent population of tissue-specific stem cells with a broad but limited differentiation potential. However, recent studies have shown that over-expression of the pluripotency gene, Oct4, alone is sufficient to initiate a process by which these can form 'induced pluripotent stem cells' (iPS cells) with the same broad potential as embryonic stem cells. This led us to examine the expression of Oct4 in endogenous neural stem cells, as data regarding its expression in neural stem cells in vivo are contradictory and incomplete. In this study we have therefore analysed the expression of Oct4 and other genes associated with pluripotency throughout development of the mouse CNS and in neural stem cells grown in vitro. We find that Oct4 is still expressed in the CNS by E8.5, but that this expression declines rapidly until it is undetectable by E15.5. This decline is coincident with the gradual methylation of the Oct4 promoter and proximal enhancer. Immunostaining suggests that the Oct4 protein is predominantly cytoplasmic in location. We also found that neural stem cells from all ages expressed the pluripotency associated genes, Sox2, c-Myc, Klf4 and Nanog. These data provide an explanation for the varying behaviour of cells from the early neuroepithelium at different stages of development. The expression of these genes also provides an indication of why Oct4 alone is sufficient to induce iPS formation in neural stem cells at later stages.

Neural Circuits via Which Single Prolonged Stress Exposure Leads to Fear Extinction Retention Deficits

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Knox, Dayan; Stanfield, Briana R.; Staib, Jennifer M.; David, Nina P.; Keller, Samantha M.; DePietro, Thomas

2016-01-01

Single prolonged stress (SPS) has been used to examine mechanisms via which stress exposure leads to post-traumatic stress disorder symptoms. SPS induces fear extinction retention deficits, but neural circuits critical for mediating these deficits are unknown. To address this gap, we examined the effect of SPS on neural activity in brain regions…

Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition.

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Bast, Tobias; Pezze, Marie; McGarrity, Stephanie

2017-10-01

contributes to clinically relevant cognitive deficits, and we consider pharmacological strategies for ameliorating cognitive deficits by rebalancing disinhibition-induced aberrant neural activity. Linked Articles This article is part of a themed section on Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.19/issuetoc. © 2017 The British Pharmacological Society.

Neural basis of scientific innovation induced by heuristic prototype.

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Junlong Luo

Full Text Available A number of major inventions in history have been based on bionic imitation. Heuristics, by applying biological systems to the creation of artificial devices and machines, might be one of the most critical processes in scientific innovation. In particular, prototype heuristics propositions that innovation may engage automatic activation of a prototype such as a biological system to form novel associations between a prototype's function and problem-solving. We speculated that the cortical dissociation between the automatic activation and forming novel associations in innovation is critical point to heuristic creativity. In the present study, novel and old scientific innovations (NSI and OSI were selected as experimental materials in using learning-testing paradigm to explore the neural basis of scientific innovation induced by heuristic prototype. College students were required to resolve NSI problems (to which they did not know the answers and OSI problems (to which they knew the answers. From two fMRI experiments, our results showed that the subjects could resolve NSI when provided with heuristic prototypes. In Experiment 1, it was found that the lingual gyrus (LG; BA18 might be related to prototype heuristics in college students resolving NSI after learning a relative prototype. In Experiment 2, the LG (BA18 and precuneus (BA31 were significantly activated for NSI compared to OSI when college students learned all prototypes one day before the test. In addition, the mean beta-values of these brain regions of NSI were all correlated with the behavior accuracy of NSI. As our hypothesis indicated, the findings suggested that the LG might be involved in forming novel associations using heuristic information, while the precuneus might be involved in the automatic activation of heuristic prototype during scientific innovation.

Neural basis of scientific innovation induced by heuristic prototype.

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Luo, Junlong; Li, Wenfu; Qiu, Jiang; Wei, Dongtao; Liu, Yijun; Zhang, Qinlin

2013-01-01

A number of major inventions in history have been based on bionic imitation. Heuristics, by applying biological systems to the creation of artificial devices and machines, might be one of the most critical processes in scientific innovation. In particular, prototype heuristics propositions that innovation may engage automatic activation of a prototype such as a biological system to form novel associations between a prototype's function and problem-solving. We speculated that the cortical dissociation between the automatic activation and forming novel associations in innovation is critical point to heuristic creativity. In the present study, novel and old scientific innovations (NSI and OSI) were selected as experimental materials in using learning-testing paradigm to explore the neural basis of scientific innovation induced by heuristic prototype. College students were required to resolve NSI problems (to which they did not know the answers) and OSI problems (to which they knew the answers). From two fMRI experiments, our results showed that the subjects could resolve NSI when provided with heuristic prototypes. In Experiment 1, it was found that the lingual gyrus (LG; BA18) might be related to prototype heuristics in college students resolving NSI after learning a relative prototype. In Experiment 2, the LG (BA18) and precuneus (BA31) were significantly activated for NSI compared to OSI when college students learned all prototypes one day before the test. In addition, the mean beta-values of these brain regions of NSI were all correlated with the behavior accuracy of NSI. As our hypothesis indicated, the findings suggested that the LG might be involved in forming novel associations using heuristic information, while the precuneus might be involved in the automatic activation of heuristic prototype during scientific innovation.

A model of microsaccade-related neural responses induced by short-term depression in thalamocortical synapses

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Wujie eYuan

2013-04-01

Full Text Available Microsaccades during fixation have been suggested to counteract visual fading. Recent experi- ments have also observed microsaccade-related neural responses from cellular record, scalp elec- troencephalogram (EEG and functional magnetic resonance imaging (fMRI. The underlying mechanism, however, is not yet understood and highly debated. It has been proposed that the neural activity of primary visual cortex (V1 is a crucial component for counteracting visual adaptation. In this paper, we use computational modeling to investigate how short-term depres- sion (STD in thalamocortical synapses might affect the neural responses of V1 in the presence of microsaccades. Our model not only gives a possible synaptic explanation for microsaccades in counteracting visual fading, but also reproduces several features in experimental findings. These modeling results suggest that STD in thalamocortical synapses plays an important role in microsaccade-related neural responses and the model may be useful for further investigation of behavioral properties and functional roles of microsaccades.

A model of microsaccade-related neural responses induced by short-term depression in thalamocortical synapses

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Yuan, Wu-Jie; Dimigen, Olaf; Sommer, Werner; Zhou, Changsong

2013-01-01

Microsaccades during fixation have been suggested to counteract visual fading. Recent experiments have also observed microsaccade-related neural responses from cellular record, scalp electroencephalogram (EEG), and functional magnetic resonance imaging (fMRI). The underlying mechanism, however, is not yet understood and highly debated. It has been proposed that the neural activity of primary visual cortex (V1) is a crucial component for counteracting visual adaptation. In this paper, we use computational modeling to investigate how short-term depression (STD) in thalamocortical synapses might affect the neural responses of V1 in the presence of microsaccades. Our model not only gives a possible synaptic explanation for microsaccades in counteracting visual fading, but also reproduces several features in experimental findings. These modeling results suggest that STD in thalamocortical synapses plays an important role in microsaccade-related neural responses and the model may be useful for further investigation of behavioral properties and functional roles of microsaccades. PMID:23630494

Glycoconjugates reveal diversity of human neural stem cells (hNSCs) derived from human induced pluripotent stem cells (hiPSCs).

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Kandasamy, Majury; Roll, Lars; Langenstroth, Daniel; Brüstle, Oliver; Faissner, Andreas

2017-06-01

Neural stem cells (NSCs) have the ability to self-renew and to differentiate into various cell types of the central nervous system. This potential can be recapitulated by human induced pluripotent stem cells (hiPSCs) in vitro. The differentiation capacity of hiPSCs is characterized by several stages with distinct morphologies and the expression of various marker molecules. We used the monoclonal antibodies (mAbs) 487 LeX , 5750 LeX and 473HD to analyze the expression pattern of particular carbohydrate motifs as potential markers at six differentiation stages of hiPSCs. Mouse ESCs were used as a comparison. At the pluripotent stage, 487 LeX -, 5750 LeX - and 473HD-related glycans were differently expressed. Later, cells of the three germ layers in embryoid bodies (hEBs) and, even after neuralization of hEBs, subpopulations of cells were labeled with these surface antibodies. At the human rosette-stage of NSCs (hR-NSC), LeX- and 473HD-related epitopes showed antibody-specific expression patterns. We also found evidence that these surface antibodies could be used to distinguish the hR-NSCs from the hSR-NSCs stages. Characterization of hNSCs FGF-2/EGF derived from hSR-NSCs revealed that both LeX antibodies and the 473HD antibody labeled subpopulations of hNSCs FGF-2/EGF . Finally, we identified potential LeX carrier molecules that were spatiotemporally regulated in early and late stages of differentiation. Our study provides new insights into the regulation of glycoconjugates during early human stem cell development. The mAbs 487 LeX , 5750 LeX and 473HD are promising tools for identifying distinct stages during neural differentiation.

Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress.

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Henckens, Marloes J A G; Klumpers, Floris; Everaerd, Daphne; Kooijman, Sabine C; van Wingen, Guido A; Fernández, Guillén

2016-04-01

Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus-pituitary-adrenal (HPA)-axis function. Here, we studied how interindividual variance in both basal cortisol levels and stress-induced cortisol responses predicts differences in neural vigilance processing during stress exposure. Implementing a randomized, counterbalanced, crossover design, 120 healthy male participants were exposed to a stress-induction and control procedure, followed by an emotional perception task (viewing fearful and happy faces) during fMRI scanning. Stress sensitivity was assessed using physiological (salivary cortisol levels) and psychological measures (trait questionnaires). High stress-induced cortisol responses were associated with increased stress sensitivity as assessed by psychological questionnaires, a stronger stress-induced increase in medial temporal activity and greater differential amygdala responses to fearful as opposed to happy faces under control conditions. In contrast, high basal cortisol levels were related to relative stress resilience as reflected by higher extraversion scores, a lower stress-induced increase in amygdala activity and enhanced differential processing of fearful compared with happy faces under stress. These findings seem to reflect a critical role for HPA-axis signaling in stress coping; higher basal levels indicate stress resilience, whereas higher cortisol responsivity to stress might facilitate recovery in those individuals prone to react sensitively to stress. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

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

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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.

Effects of craving behavioral intervention on neural substrates of cue-induced craving in Internet gaming disorder

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Jin-Tao Zhang

2016-01-01

Full Text Available Internet gaming disorder (IGD is characterized by high levels of craving for online gaming and related cues. Since addiction-related cues can evoke increased activation in brain areas involved in motivational and reward processing and may engender gaming behaviors or trigger relapse, ameliorating cue-induced craving may be a promising target for interventions for IGD. This study compared neural activation between 40 IGD and 19 healthy control (HC subjects during an Internet-gaming cue-reactivity task and found that IGD subjects showed stronger activation in multiple brain areas, including the dorsal striatum, brainstem, substantia nigra, and anterior cingulate cortex, but lower activation in the posterior insula. Furthermore, twenty-three IGD subjects (CBI+ group participated in a craving behavioral intervention (CBI group therapy, whereas the remaining 17 IGD subjects (CBI− group did not receive any intervention, and all IGD subjects were scanned during similar time intervals. The CBI+ group showed decreased IGD severity and cue-induced craving, enhanced activation in the anterior insula and decreased insular connectivity with the lingual gyrus and precuneus after receiving CBI. These findings suggest that CBI is effective in reducing craving and severity in IGD, and it may exert its effects by altering insula activation and its connectivity with regions involved in visual processing and attention bias.

Effects of craving behavioral intervention on neural substrates of cue-induced craving in Internet gaming disorder.

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Zhang, Jin-Tao; Yao, Yuan-Wei; Potenza, Marc N; Xia, Cui-Cui; Lan, Jing; Liu, Lu; Wang, Ling-Jiao; Liu, Ben; Ma, Shan-Shan; Fang, Xiao-Yi

2016-01-01

Internet gaming disorder (IGD) is characterized by high levels of craving for online gaming and related cues. Since addiction-related cues can evoke increased activation in brain areas involved in motivational and reward processing and may engender gaming behaviors or trigger relapse, ameliorating cue-induced craving may be a promising target for interventions for IGD. This study compared neural activation between 40 IGD and 19 healthy control (HC) subjects during an Internet-gaming cue-reactivity task and found that IGD subjects showed stronger activation in multiple brain areas, including the dorsal striatum, brainstem, substantia nigra, and anterior cingulate cortex, but lower activation in the posterior insula. Furthermore, twenty-three IGD subjects (CBI + group) participated in a craving behavioral intervention (CBI) group therapy, whereas the remaining 17 IGD subjects (CBI - group) did not receive any intervention, and all IGD subjects were scanned during similar time intervals. The CBI + group showed decreased IGD severity and cue-induced craving, enhanced activation in the anterior insula and decreased insular connectivity with the lingual gyrus and precuneus after receiving CBI. These findings suggest that CBI is effective in reducing craving and severity in IGD, and it may exert its effects by altering insula activation and its connectivity with regions involved in visual processing and attention bias.

Neural Plastic Effects of Cognitive Training on Aging Brain

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Natalie T. Y. Leung

2015-01-01

Full Text Available Increasing research has evidenced that our brain retains a capacity to change in response to experience until late adulthood. This implies that cognitive training can possibly ameliorate age-associated cognitive decline by inducing training-specific neural plastic changes at both neural and behavioral levels. This longitudinal study examined the behavioral effects of a systematic thirteen-week cognitive training program on attention and working memory of older adults who were at risk of cognitive decline. These older adults were randomly assigned to the Cognitive Training Group (n=109 and the Active Control Group (n=100. Findings clearly indicated that training induced improvement in auditory and visual-spatial attention and working memory. The training effect was specific to the experience provided because no significant difference in verbal and visual-spatial memory between the two groups was observed. This pattern of findings is consistent with the prediction and the principle of experience-dependent neuroplasticity. Findings of our study provided further support to the notion that the neural plastic potential continues until older age. The baseline cognitive status did not correlate with pre- versus posttraining changes to any cognitive variables studied, suggesting that the initial cognitive status may not limit the neuroplastic potential of the brain at an old age.

Neural Plastic Effects of Cognitive Training on Aging Brain.

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Leung, Natalie T Y; Tam, Helena M K; Chu, Leung W; Kwok, Timothy C Y; Chan, Felix; Lam, Linda C W; Woo, Jean; Lee, Tatia M C

2015-01-01

Increasing research has evidenced that our brain retains a capacity to change in response to experience until late adulthood. This implies that cognitive training can possibly ameliorate age-associated cognitive decline by inducing training-specific neural plastic changes at both neural and behavioral levels. This longitudinal study examined the behavioral effects of a systematic thirteen-week cognitive training program on attention and working memory of older adults who were at risk of cognitive decline. These older adults were randomly assigned to the Cognitive Training Group (n = 109) and the Active Control Group (n = 100). Findings clearly indicated that training induced improvement in auditory and visual-spatial attention and working memory. The training effect was specific to the experience provided because no significant difference in verbal and visual-spatial memory between the two groups was observed. This pattern of findings is consistent with the prediction and the principle of experience-dependent neuroplasticity. Findings of our study provided further support to the notion that the neural plastic potential continues until older age. The baseline cognitive status did not correlate with pre- versus posttraining changes to any cognitive variables studied, suggesting that the initial cognitive status may not limit the neuroplastic potential of the brain at an old age.

Transport and metabolism at blood-brain interfaces and in neural cells: relevance to bilirubin-induced encephalopathy

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Silvia eGazzin

2012-05-01

Full Text Available Bilirubin, the end-product of heme catabolism, circulates in non pathological plasma mostly as a protein-bound species. When bilirubin concentration builds up, the free fraction of the molecule increases. Unbound bilirubin then diffuses across blood-brain interfaces into the brain, where it accumulates and exerts neurotoxic effects. In this classical view of bilirubin neurotoxicity, blood-brain interfaces act merely as structural barriers impeding the penetration of the pigment-bound carrier protein, and neural cells are considered as passive targets of its toxicity. Yet, the role of blood-brain interfaces in the occurrence of bilirubin encephalopathy appears more complex than being simple barriers to the diffusion of bilirubin, and neural cells such as astrocytes and neurons can play an active role in controlling the balance between the neuroprotective and neurotoxic effects of bilirubin. This article reviews the emerging in vivo and in vitro data showing that transport and metabolic detoxification mechanisms at the blood-brain and blood-CSF barriers may modulate bilirubin flux across both cellular interfaces, and that these protective functions can be affected in chronic hyperbilirubinemia. Then the in vivo and in vitro arguments in favor of the physiological antioxidant function of intracerebral bilirubin are presented, as well as with the potential role of transporters such as ABCC-1 and metabolizing enzymes such as cytochromes P-450 in setting the cerebral cell- and structure-specific toxicity of bilirubin following hyperbilirubinemia. The relevance of these data to the pathophysiology of bilirubin-induced neurological diseases is discussed.

PSA-NCAM-Negative Neural Crest Cells Emerging during Neural Induction of Pluripotent Stem Cells Cause Mesodermal Tumors and Unwanted Grafts

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Lee, Dongjin R.; Yoo, Jeong-Eun; Lee, Jae Souk; Park, Sanghyun; Lee, Junwon; Park, Chul-Yong; Ji, Eunhyun; Kim, Han-Soo; Hwang, Dong-Youn; Kim, Dae-Sung; Kim, Dong-Wook

2015-01-01

Summary Tumorigenic potential of human pluripotent stem cells (hPSCs) is an important issue in clinical applications. Despite many efforts, PSC-derived neural precursor cells (NPCs) have repeatedly induced tumors in animal models even though pluripotent cells were not detected. We found that polysialic acid-neural cell adhesion molecule (PSA-NCAM)− cells among the early NPCs caused tumors, whereas PSA-NCAM+ cells were nontumorigenic. Molecular profiling, global gene analysis, and multilineage differentiation of PSA-NCAM− cells confirm that they are multipotent neural crest stem cells (NCSCs) that could differentiate into both ectodermal and mesodermal lineages. Transplantation of PSA-NCAM− cells in a gradient manner mixed with PSA-NCAM+ cells proportionally increased mesodermal tumor formation and unwanted grafts such as PERIPHERIN+ cells or pigmented cells in the rat brain. Therefore, we suggest that NCSCs are a critical target for tumor prevention in hPSC-derived NPCs, and removal of PSA-NCAM− cells eliminates the tumorigenic potential originating from NCSCs after transplantation. PMID:25937368

High sugar-induced insulin resistance in Drosophila relies on the lipocalin Neural Lazarillo.

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Matthieu Y Pasco

Full Text Available In multicellular organisms, insulin/IGF signaling (IIS plays a central role in matching energy needs with uptake and storage, participating in functions as diverse as metabolic homeostasis, growth, reproduction and ageing. In mammals, this pleiotropy of action relies in part on a dichotomy of action of insulin, IGF-I and their respective membrane-bound receptors. In organisms with simpler IIS, this functional separation is questionable. In Drosophila IIS consists of several insulin-like peptides called Dilps, activating a unique membrane receptor and its downstream signaling cascade. During larval development, IIS is involved in metabolic homeostasis and growth. We have used feeding conditions (high sugar diet, HSD that induce an important change in metabolic homeostasis to monitor possible effects on growth. Unexpectedly we observed that HSD-fed animals exhibited severe growth inhibition as a consequence of peripheral Dilp resistance. Dilp-resistant animals present several metabolic disorders similar to those observed in type II diabetes (T2D patients. By exploring the molecular mechanisms involved in Drosophila Dilp resistance, we found a major role for the lipocalin Neural Lazarillo (NLaz, a target of JNK signaling. NLaz expression is strongly increased upon HSD and animals heterozygous for an NLaz null mutation are fully protected from HSD-induced Dilp resistance. NLaz is a secreted protein homologous to the Retinol-Binding Protein 4 involved in the onset of T2D in human and mice. These results indicate that insulin resistance shares common molecular mechanisms in flies and human and that Drosophila could emerge as a powerful genetic system to study some aspects of this complex syndrome.

Modification of surface/neuron interfaces for neural cell-type specific responses: a review

International Nuclear Information System (INIS)

Chen, Cen; Kong, Xiangdong; Lee, In-Seop

2016-01-01

Surface/neuron interfaces have played an important role in neural repair including neural prostheses and tissue engineered scaffolds. This comprehensive literature review covers recent studies on the modification of surface/neuron interfaces. These interfaces are identified in cases both where the surfaces of substrates or scaffolds were in direct contact with cells and where the surfaces were modified to facilitate cell adhesion and controlling cell-type specific responses. Different sources of cells for neural repair are described, such as pheochromocytoma neuronal-like cell, neural stem cell (NSC), embryonic stem cell (ESC), mesenchymal stem cell (MSC) and induced pluripotent stem cell (iPS). Commonly modified methods are discussed including patterned surfaces at micro- or nano-scale, surface modification with conducting coatings, and functionalized surfaces with immobilized bioactive molecules. These approaches to control cell-type specific responses have enormous potential implications in neural repair. (paper)

Identifying the neural substrates of intrinsic motivation during task performance.

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Lee, Woogul; Reeve, Johnmarshall

2017-10-01

Intrinsic motivation is the inherent tendency to seek out novelty and challenge, to explore and investigate, and to stretch and extend one's capacities. When people imagine performing intrinsically motivating tasks, they show heightened anterior insular cortex (AIC) activity. To fully explain the neural system of intrinsic motivation, however, requires assessing neural activity while people actually perform intrinsically motivating tasks (i.e., while answering curiosity-inducing questions or solving competence-enabling anagrams). Using event-related functional magnetic resonance imaging, we found that the neural system of intrinsic motivation involves not only AIC activity, but also striatum activity and, further, AIC-striatum functional interactions. These findings suggest that subjective feelings of intrinsic satisfaction (associated with AIC activations), reward processing (associated with striatum activations), and their interactions underlie the actual experience of intrinsic motivation. These neural findings are consistent with the conceptualization of intrinsic motivation as the pursuit and satisfaction of subjective feelings (interest and enjoyment) as intrinsic rewards.

Neural Progenitors Adopt Specific Identities by Directly Repressing All Alternative Progenitor Transcriptional Programs.

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Kutejova, Eva; Sasai, Noriaki; Shah, Ankita; Gouti, Mina; Briscoe, James

2016-03-21

In the vertebrate neural tube, a morphogen-induced transcriptional network produces multiple molecularly distinct progenitor domains, each generating different neuronal subtypes. Using an in vitro differentiation system, we defined gene expression signatures of distinct progenitor populations and identified direct gene-regulatory inputs corresponding to locations of specific transcription factor binding. Combined with targeted perturbations of the network, this revealed a mechanism in which a progenitor identity is installed by active repression of the entire transcriptional programs of other neural progenitor fates. In the ventral neural tube, sonic hedgehog (Shh) signaling, together with broadly expressed transcriptional activators, concurrently activates the gene expression programs of several domains. The specific outcome is selected by repressive input provided by Shh-induced transcription factors that act as the key nodes in the network, enabling progenitors to adopt a single definitive identity from several initially permitted options. Together, the data suggest design principles relevant to many developing tissues. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Evolvable synthetic neural system

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Curtis, Steven A. (Inventor)

2009-01-01

An evolvable synthetic neural system includes an evolvable neural interface operably coupled to at least one neural basis function. Each neural basis function includes an evolvable neural interface operably coupled to a heuristic neural system to perform high-level functions and an autonomic neural system to perform low-level functions. In some embodiments, the evolvable synthetic neural system is operably coupled to one or more evolvable synthetic neural systems in a hierarchy.

Neural electrical activity and neural network growth.

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Gafarov, F M

2018-05-01

The development of central and peripheral neural system depends in part on the emergence of the correct functional connectivity in its input and output pathways. Now it is generally accepted that molecular factors guide neurons to establish a primary scaffold that undergoes activity-dependent refinement for building a fully functional circuit. However, a number of experimental results obtained recently shows that the neuronal electrical activity plays an important role in the establishing of initial interneuronal connections. Nevertheless, these processes are rather difficult to study experimentally, due to the absence of theoretical description and quantitative parameters for estimation of the neuronal activity influence on growth in neural networks. In this work we propose a general framework for a theoretical description of the activity-dependent neural network growth. The theoretical description incorporates a closed-loop growth model in which the neural activity can affect neurite outgrowth, which in turn can affect neural activity. We carried out the detailed quantitative analysis of spatiotemporal activity patterns and studied the relationship between individual cells and the network as a whole to explore the relationship between developing connectivity and activity patterns. The model, developed in this work will allow us to develop new experimental techniques for studying and quantifying the influence of the neuronal activity on growth processes in neural networks and may lead to a novel techniques for constructing large-scale neural networks by self-organization. Copyright © 2018 Elsevier Ltd. All rights reserved.

Neural decoding of visual imagery during sleep.

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Horikawa, T; Tamaki, M; Miyawaki, Y; Kamitani, Y

2013-05-03

Visual imagery during sleep has long been a topic of persistent speculation, but its private nature has hampered objective analysis. Here we present a neural decoding approach in which machine-learning models predict the contents of visual imagery during the sleep-onset period, given measured brain activity, by discovering links between human functional magnetic resonance imaging patterns and verbal reports with the assistance of lexical and image databases. Decoding models trained on stimulus-induced brain activity in visual cortical areas showed accurate classification, detection, and identification of contents. Our findings demonstrate that specific visual experience during sleep is represented by brain activity patterns shared by stimulus perception, providing a means to uncover subjective contents of dreaming using objective neural measurement.

The neural network z-vertex trigger for the Belle II detector

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Skambraks, Sebastian; Neuhaus, Sara [Technische Universitaet Muenchen (Germany); Chen, Yang; Kiesling, Christian [Max-Planck-Institut fuer Physik, Muenchen (Germany); Collaboration: Belle II-Collaboration

2016-07-01

We present a neural network based first level track trigger for the upcoming Belle II detector at the high luminosity SuperKEKB flavor factory. Using hit and drift time information from the Central Drift Chamber (CDC), neural networks estimate the z-coordinates of single track vertex positions. Especially beam induced background, with vertices outside of the interaction region, can clearly be rejected. This allows to relax the track trigger conditions and thus enhances the efficiency for events with a low track multiplicity. In the CDC trigger pipeline, the preceding 2D pattern recognition enables a unique per track input representation and a sectorization of the track parameter phase space. The precise z-vertices are then estimated by an ensemble of sector-specific local expert neural networks. After an introduction to the neural trigger system, the benefits of an improved 3D pattern recognition are discussed.

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

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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.

Gene expression profiling analysis of the effects of low-intensity pulsed ultrasound on induced pluripotent stem cell-derived neural crest stem cells.

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Xia, Bin; Zou, Yang; Xu, Zhiling; Lv, Yonggang

2017-11-01

Low-intensity pulsed ultrasound (LIPUS) is a noninvasive technique that has been shown to affect cell proliferation, migration, and differentiation and promote the regeneration of damaged peripheral nerve. Our previous studies had proved that LIPUS can significantly promote the neural differentiation of induced pluripotent stem cell-derived neural crest stem cells (iPSCs-NCSCs) and enhance the repair of rat-transected sciatic nerve. To further explore the underlying mechanisms of LIPUS treatment of iPSCs-NCSCs, this study reported the gene expression profiling analysis of iPSCs-NCSCs before and after LIPUS treatment using the RNA-sequencing (RNA-Seq) method. It was found that expression of 76 genes of iPSCs-NCSCs cultured in a serum-free neural induction medium and expression of 21 genes of iPSCs-NCSCs cultured in a neuronal differentiation medium were significantly changed by LIPUS treatment. The differentially expressed genes are related to angiogenesis, nervous system activity and functions, cell activities, and so on. The RNA-seq results were further verified by a quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR). High correlation was observed between the results obtained from qRT-PCR and RNA-Seq. This study presented new information on the global gene expression patterns of iPSCs-NCSCs after LIPUS treatment and may expand the understanding of the complex molecular mechanism of LIPUS treatment of iPSCs-NCSCs. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

Information-geometric measures estimate neural interactions during oscillatory brain states

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Yimin eNie

2014-02-01

Full Text Available The characterization of functional network structures among multiple neurons is essential to understanding neural information processing. Information geometry (IG, a theory developed for investigating a space of probability distributions has recently been applied to spike-train analysis and has provided robust estimations of neural interactions. Although neural firing in the equilibrium state is often assumed in these studies, in reality, neural activity is non-stationary. The brain exhibits various oscillations depending on cognitive demands or when an animal is asleep. Therefore, the investigation of the IG measures during oscillatory network states is important for testing how the IG method can be applied to real neural data. Using model networks of binary neurons or more realistic spiking neurons, we studied how the single- and pairwise-IG measures were influenced by oscillatory neural activity. Two general oscillatory mechanisms, externally driven oscillations and internally induced oscillations, were considered. In both mechanisms, we found that the single-IG measure was linearly related to the magnitude of the external input, and that the pairwise-IG measure was linearly related to the sum of connection strengths between two neurons. We also observed that the pairwise-IG measure was not dependent on the oscillation frequency. These results are consistent with the previous findings that were obtained under the equilibrium conditions. Therefore, we demonstrate that the IG method provides useful insights into neural interactions under the oscillatory condition that can often be observed in the real brain.

Soman poisoning increases neural progenitor proliferation and induces long-term glial activation in mouse brain

International Nuclear Information System (INIS)

Collombet, Jean-Marc; Four, Elise; Bernabe, Denis; Masqueliez, Catherine; Burckhart, Marie-France; Baille, Valerie; Baubichon, Dominique; Lallement, Guy

2005-01-01

To date, only short-term glial reaction has been extensively studied following soman or other warfare neurotoxicant poisoning. In a context of cell therapy by neural progenitor engraftment to repair brain damage, the long-term effect of soman on glial reaction and neural progenitor division was analyzed in the present study. The effect of soman poisoning was estimated in mouse brains at various times ranging from 1 to 90 days post-poisoning. Using immunochemistry and dye staining techniques (hemalun-eosin staining), the number of degenerating neurons, the number of dividing neural progenitors, and microglial, astroglial or oligodendroglial cell activation were studied. Soman poisoning led to rapid and massive (post-soman day 1) death of mature neurons as assessed by hemalun-eosin staining. Following this acute poisoning phase, a weak toxicity effect on mature neurons was still observed for a period of 1 month after poisoning. A massive short-termed microgliosis peaked on day 3 post-poisoning. Delayed astrogliosis was observed from 3 to 90 days after soman poisoning, contributing to glial scar formation. On the other hand, oligodendroglial cells or their precursors were practically unaffected by soman poisoning. Interestingly, neural progenitors located in the subgranular zone of the dentate gyrus (SGZ) or in the subventricular zone (SVZ) of the brain survived soman poisoning. Furthermore, soman poisoning significantly increased neural progenitor proliferation in both SGZ and SVZ brain areas on post-soman day 3 or day 8, respectively. This increased proliferation rate was detected up to 1 month after poisoning

Taurine Protected Against the Impairments of Neural Stem Cell Differentiated Neurons Induced by Oxygen-Glucose Deprivation.

Science.gov (United States)

Xiao, Bo; Liu, Huazhen; Gu, Zeyun; Liu, Sining; Ji, Cheng

2015-11-01

Cell transplantation of neural stem cells (NSCs) is a promising approach for neurological recovery both structurally and functionally. However, one big obstacle is to promote differentiation of NSCs into neurons and the followed maturation. In the present study, we aimed to investigate the protective effect of taurine on the differentiation of NSCs and subsequent maturation of their neuronal lineage, when exposed to oxygen-glucose deprivation (OGD). The results suggested that taurine (5-20 mM) promoted the viability and proliferation of NSCs, and it protected against 8 h of OGD induced impairments. Furthermore, 20 mM taurine promoted NSCs to differentiate into neurons after 7 days of culture, and it also protected against the suppressive impairments of 8 h of OGD. Consistently, taurine (20 mM) promoted the neurite sprouting and outgrowth of the NSC differentiated neurons after 14 days of differentiation, which were significantly inhibited by OGD (8 h). At D21, the mushroom spines and spine density were promoted or restored by 20 mM taurine. Taken together, the enhanced viability and proliferation of NSCs, more differentiated neurons and the promoted maturation of neurons by 20 mM taurine support its therapeutic application during stem cell therapy to enhance neurological recovery. Moreover, it protected against the impairments induced by OGD, which may highlight its role for a more direct therapeutic application especially in an ischemic stroke environment.

Sustained NMDA receptor hypofunction induces compromised neural systems integration and schizophrenia-like alterations in functional brain networks.

Science.gov (United States)

Dawson, Neil; Xiao, Xiaolin; McDonald, Martin; Higham, Desmond J; Morris, Brian J; Pratt, Judith A

2014-02-01

Compromised functional integration between cerebral subsystems and dysfunctional brain network organization may underlie the neurocognitive deficits seen in psychiatric disorders. Applying topological measures from network science to brain imaging data allows the quantification of complex brain network connectivity. While this approach has recently been used to further elucidate the nature of brain dysfunction in schizophrenia, the value of applying this approach in preclinical models of psychiatric disease has not been recognized. For the first time, we apply both established and recently derived algorithms from network science (graph theory) to functional brain imaging data from rats treated subchronically with the N-methyl-D-aspartic acid (NMDA) receptor antagonist phencyclidine (PCP). We show that subchronic PCP treatment induces alterations in the global properties of functional brain networks akin to those reported in schizophrenia. Furthermore, we show that subchronic PCP treatment induces compromised functional integration between distributed neural systems, including between the prefrontal cortex and hippocampus, that have established roles in cognition through, in part, the promotion of thalamic dysconnectivity. We also show that subchronic PCP treatment promotes the functional disintegration of discrete cerebral subsystems and also alters the connectivity of neurotransmitter systems strongly implicated in schizophrenia. Therefore, we propose that sustained NMDA receptor hypofunction contributes to the pathophysiology of dysfunctional brain network organization in schizophrenia.

Morphological neural networks

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Ritter, G.X.; Sussner, P. [Univ. of Florida, Gainesville, FL (United States)

1996-12-31

The theory of artificial neural networks has been successfully applied to a wide variety of pattern recognition problems. In this theory, the first step in computing the next state of a neuron or in performing the next layer neural network computation involves the linear operation of multiplying neural values by their synaptic strengths and adding the results. Thresholding usually follows the linear operation in order to provide for nonlinearity of the network. In this paper we introduce a novel class of neural networks, called morphological neural networks, in which the operations of multiplication and addition are replaced by addition and maximum (or minimum), respectively. By taking the maximum (or minimum) of sums instead of the sum of products, morphological network computation is nonlinear before thresholding. As a consequence, the properties of morphological neural networks are drastically different than those of traditional neural network models. In this paper we consider some of these differences and provide some particular examples of morphological neural network.

Structural alterations in rat liver proteins due to streptozotocin-induced diabetes and the recovery effect of selenium: Fourier transform infrared microspectroscopy and neural network study

Science.gov (United States)

Bozkurt, Ozlem; Haman Bayari, Sevgi; Severcan, Mete; Krafft, Christoph; Popp, Jürgen; Severcan, Feride

2012-07-01

The relation between protein structural alterations and tissue dysfunction is a major concern as protein fibrillation and/or aggregation due to structural alterations has been reported in many disease states. In the current study, Fourier transform infrared microspectroscopic imaging has been used to investigate diabetes-induced changes on protein secondary structure and macromolecular content in streptozotocin-induced diabetic rat liver. Protein secondary structural alterations were predicted using neural network approach utilizing the amide I region. Moreover, the role of selenium in the recovery of diabetes-induced alterations on macromolecular content and protein secondary structure was also studied. The results revealed that diabetes induced a decrease in lipid to protein and glycogen to protein ratios in diabetic livers. Significant alterations in protein secondary structure were observed with a decrease in α-helical and an increase in β-sheet content. Both doses of selenium restored diabetes-induced changes in lipid to protein and glycogen to protein ratios. However, low-dose selenium supplementation was not sufficient to recover the effects of diabetes on protein secondary structure, while a higher dose of selenium fully restored diabetes-induced alterations in protein structure.

Isolation and characterization of neural stem cells from human fetal striatum

International Nuclear Information System (INIS)

Li Xiaoxia; Xu Jinchong; Bai Yun; Wang Xuan; Dai Xin; Liu Yinan; Zhang Jun; Zou Junhua; Shen Li; Li Lingsong

2005-01-01

This paper described that neural stem cells (hsNSCs) were isolated and expanded rapidly from human fetal striatum in adherent culture. The population was serum- and growth factor-dependent and expressed neural stem cell markers. They were capable of multi-differentiation into neurons, astrocytes, and oligodendrocytes. When plated in the dopaminergic neuron inducing medium, human striatum neural stem cells could differentiate into tyrosine hydroxylase positive neurons. hsNSCs were morphologically homogeneous and possessed high proliferation ability. The population doubled every 44.28 h and until now it has divided for more than 82 generations in vitro. Normal human diploid karyotype was unchanged throughout the in vitro culture period. Together, this study has exploited a method for continuous and rapid expansion of human neural stem cells as pure population, which maintained the capacity to generate almost fifty percent neurons. The availability of such cells may hold great interest for basic and applied neuroscience

Fatigue sensation induced by the sounds associated with mental fatigue and its related neural activities: revealed by magnetoencephalography.

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Ishii, Akira; Tanaka, Masaaki; Iwamae, Masayoshi; Kim, Chongsoo; Yamano, Emi; Watanabe, Yasuyoshi

2013-06-13

It has been proposed that an inappropriately conditioned fatigue sensation could be one cause of chronic fatigue. Although classical conditioning of the fatigue sensation has been reported in rats, there have been no reports in humans. Our aim was to examine whether classical conditioning of the mental fatigue sensation can take place in humans and to clarify the neural mechanisms of fatigue sensation using magnetoencephalography (MEG). Ten and 9 healthy volunteers participated in a conditioning and a control experiment, respectively. In the conditioning experiment, we used metronome sounds as conditioned stimuli and two-back task trials as unconditioned stimuli to cause fatigue sensation. Participants underwent MEG measurement while listening to the metronome sounds for 6 min. Thereafter, fatigue-inducing mental task trials (two-back task trials), which are demanding working-memory task trials, were performed for 60 min; metronome sounds were started 30 min after the start of the task trials (conditioning session). The next day, neural activities while listening to the metronome for 6 min were measured. Levels of fatigue sensation were also assessed using a visual analogue scale. In the control experiment, participants listened to the metronome on the first and second days, but they did not perform conditioning session. MEG was not recorded in the control experiment. The level of fatigue sensation caused by listening to the metronome on the second day was significantly higher relative to that on the first day only when participants performed the conditioning session on the first day. Equivalent current dipoles (ECDs) in the insular cortex, with mean latencies of approximately 190 ms, were observed in six of eight participants after the conditioning session, although ECDs were not identified in any participant before the conditioning session. We demonstrated that the metronome sounds can cause mental fatigue sensation as a result of repeated pairings of the sounds

The neural basis of body form and body action agnosia.

Science.gov (United States)

Moro, Valentina; Urgesi, Cosimo; Pernigo, Simone; Lanteri, Paola; Pazzaglia, Mariella; Aglioti, Salvatore Maria

2008-10-23

Visual analysis of faces and nonfacial body stimuli brings about neural activity in different cortical areas. Moreover, processing body form and body action relies on distinct neural substrates. Although brain lesion studies show specific face processing deficits, neuropsychological evidence for defective recognition of nonfacial body parts is lacking. By combining psychophysics studies with lesion-mapping techniques, we found that lesions of ventromedial, occipitotemporal areas induce face and body recognition deficits while lesions involving extrastriate body area seem causatively associated with impaired recognition of body but not of face and object stimuli. We also found that body form and body action recognition deficits can be double dissociated and are causatively associated with lesions to extrastriate body area and ventral premotor cortex, respectively. Our study reports two category-specific visual deficits, called body form and body action agnosia, and highlights their neural underpinnings.

Absence of Rybp Compromises Neural Differentiation of Embryonic Stem Cells

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Gergo Kovacs

2016-01-01

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

Neural Networks

International Nuclear Information System (INIS)

Smith, Patrick I.

2003-01-01

Physicists use large detectors to measure particles created in high-energy collisions at particle accelerators. These detectors typically produce signals indicating either where ionization occurs along the path of the particle, or where energy is deposited by the particle. The data produced by these signals is fed into pattern recognition programs to try to identify what particles were produced, and to measure the energy and direction of these particles. Ideally, there are many techniques used in this pattern recognition software. One technique, neural networks, is particularly suitable for identifying what type of particle caused by a set of energy deposits. Neural networks can derive meaning from complicated or imprecise data, extract patterns, and detect trends that are too complex to be noticed by either humans or other computer related processes. To assist in the advancement of this technology, Physicists use a tool kit to experiment with several neural network techniques. The goal of this research is interface a neural network tool kit into Java Analysis Studio (JAS3), an application that allows data to be analyzed from any experiment. As the final result, a physicist will have the ability to train, test, and implement a neural network with the desired output while using JAS3 to analyze the results or output. Before an implementation of a neural network can take place, a firm understanding of what a neural network is and how it works is beneficial. A neural network is an artificial representation of the human brain that tries to simulate the learning process [5]. It is also important to think of the word artificial in that definition as computer programs that use calculations during the learning process. In short, a neural network learns by representative examples. Perhaps the easiest way to describe the way neural networks learn is to explain how the human brain functions. The human brain contains billions of neural cells that are responsible for processing

A Biophysical Neural Model To Describe Spatial Visual Attention

International Nuclear Information System (INIS)

Hugues, Etienne; Jose, Jorge V.

2008-01-01

Visual scenes have enormous spatial and temporal information that are transduced into neural spike trains. Psychophysical experiments indicate that only a small portion of a spatial image is consciously accessible. Electrophysiological experiments in behaving monkeys have revealed a number of modulations of the neural activity in special visual area known as V4, when the animal is paying attention directly towards a particular stimulus location. The nature of the attentional input to V4, however, remains unknown as well as to the mechanisms responsible for these modulations. We use a biophysical neural network model of V4 to address these issues. We first constrain our model to reproduce the experimental results obtained for different external stimulus configurations and without paying attention. To reproduce the known neuronal response variability, we found that the neurons should receive about equal, or balanced, levels of excitatory and inhibitory inputs and whose levels are high as they are in in vivo conditions. Next we consider attentional inputs that can induce and reproduce the observed spiking modulations. We also elucidate the role played by the neural network to generate these modulations

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

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Kamila Rosiak

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

Spinal TNFα is necessary for inactivity-induced phrenic motor facilitation

Science.gov (United States)

Broytman, Oleg; Baertsch, Nathan A; Baker-Herman, Tracy L

2013-01-01

A prolonged reduction in central neural respiratory activity elicits a form of plasticity known as inactivity-induced phrenic motor facilitation (iPMF), a ‘rebound’ increase in phrenic burst amplitude apparent once respiratory neural activity is restored. iPMF requires atypical protein kinase C (aPKC) activity within spinal segments containing the phrenic motor nucleus to stabilize an early transient increase in phrenic burst amplitude and to form long-lasting iPMF following reduced respiratory neural activity. Upstream signal(s) leading to spinal aPKC activation are unknown. We tested the hypothesis that spinal tumour necrosis factor-α (TNFα) is necessary for iPMF via an aPKC-dependent mechanism. Anaesthetized, ventilated rats were exposed to a 30 min neural apnoea; upon resumption of respiratory neural activity, a prolonged increase in phrenic burst amplitude (42 ± 9% baseline; P phrenic motor nucleus prior to neural apnoea blocked long-lasting iPMF (2 ± 8% baseline; P > 0.05). Intrathecal TNFα without neural apnoea was sufficient to elicit long-lasting phrenic motor facilitation (pMF; 62 ± 7% baseline; P < 0.05). Similar to iPMF, TNFα-induced pMF required spinal aPKC activity, as intrathecal delivery of a ζ-pseudosubstrate inhibitory peptide (PKCζ-PS) 35 min following intrathecal TNFα arrested TNFα-induced pMF (28 ± 8% baseline; P < 0.05). These data demonstrate that: (1) spinal TNFα is necessary for iPMF; and (2) spinal TNFα is sufficient to elicit pMF via a similar aPKC-dependent mechanism. These data are consistent with the hypothesis that reduced respiratory neural activity elicits iPMF via a TNFα-dependent increase in spinal aPKC activity. PMID:23878370

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

Dissecting Repulsive Guidance Molecule/Neogenin function and signaling during neural development

NARCIS (Netherlands)

van den Heuvel, D.M.A.

2013-01-01

During neural development a series of precisely ordered cellular processes acts to establish a functional brain comprising millions of neurons and many more neuronal connections. Neogenin and its repulsive guidance molecule (RGM) ligands contribute to neuronal network formation by inducing axon

Distinct Neural Mechanisms Mediate Olfactory Memory Formation at Different Timescales

Science.gov (United States)

McNamara, Ann Marie; Magidson, Phillip D.; Linster, Christiane; Wilson, Donald A.; Cleland, Thomas A.

2008-01-01

Habituation is one of the oldest forms of learning, broadly expressed across sensory systems and taxa. Here, we demonstrate that olfactory habituation induced at different timescales (comprising different odor exposure and intertrial interval durations) is mediated by different neural mechanisms. First, the persistence of habituation memory is…

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

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Li Xiaojie

2009-01-01

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

Identifying the Integrated Neural Networks Involved in Capsaicin-Induced Pain Using fMRI in Awake TRPV1 Knockout and Wild-Type Rats

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Jason Richard Yee

2015-02-01

Full Text Available In the present study, we used functional MRI in awake rats to investigate the pain response that accompanies intradermal injection of capsaicin into the hindpaw. To this end, we used BOLD imaging together with a 3D segmented, annotated rat atlas and computational analysis to identify the integrated neural circuits involved in capsaicin-induced pain. The specificity of the pain response to capsaicin was tested in a transgenic model that contains a biallelic deletion of the gene encoding for the transient receptor potential cation channel subfamily V member 1 (TRPV1. Capsaicin is an exogenous ligand for the TRPV1 receptor, and in wild-type rats, activated the putative pain neural circuit. In addition, capsaicin-treated wild-type rats exhibited activation in brain regions comprising the Papez circuit and habenular system, systems that play important roles in the integration of emotional information, and learning and memory of aversive information, respectively. As expected, capsaicin administration to TRPV1-KO rats failed to elicit the robust BOLD activation pattern observed in wild-type controls. However, the intradermal injection of formalin elicited a significant activation of the putative pain pathway as represented by such areas as the anterior cingulate, somatosensory cortex, parabrachial nucleus, and periaqueductal gray. Notably, comparison of neural responses to capsaicin in wild-type versus knock-out rats uncovered evidence that capsaicin may function in an antinociceptive capacity independent of TRPV1 signaling. Our data suggest that neuroimaging of pain in awake, conscious animals has the potential to inform the neurobiological basis of full and integrated perceptions of pain.

Improved Extension Neural Network and Its Applications

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Yu Zhou

2014-01-01

Full Text Available Extension neural network (ENN is a new neural network that is a combination of extension theory and artificial neural network (ANN. The learning algorithm of ENN is based on supervised learning algorithm. One of important issues in the field of classification and recognition of ENN is how to achieve the best possible classifier with a small number of labeled training data. Training data selection is an effective approach to solve this issue. In this work, in order to improve the supervised learning performance and expand the engineering application range of ENN, we use a novel data selection method based on shadowed sets to refine the training data set of ENN. Firstly, we use clustering algorithm to label the data and induce shadowed sets. Then, in the framework of shadowed sets, the samples located around each cluster centers (core data and the borders between clusters (boundary data are selected as training data. Lastly, we use selected data to train ENN. Compared with traditional ENN, the proposed improved ENN (IENN has a better performance. Moreover, IENN is independent of the supervised learning algorithms and initial labeled data. Experimental results verify the effectiveness and applicability of our proposed work.

Bilingualism provides a neural reserve for aging populations.

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Abutalebi, Jubin; Guidi, Lucia; Borsa, Virginia; Canini, Matteo; Della Rosa, Pasquale A; Parris, Ben A; Weekes, Brendan S

2015-03-01

It has been postulated that bilingualism may act as a cognitive reserve and recent behavioral evidence shows that bilinguals are diagnosed with dementia about 4-5 years later compared to monolinguals. In the present study, we investigated the neural basis of these putative protective effects in a group of aging bilinguals as compared to a matched monolingual control group. For this purpose, participants completed the Erikson Flanker task and their performance was correlated to gray matter (GM) volume in order to investigate if cognitive performance predicts GM volume specifically in areas affected by aging. We performed an ex-Gaussian analysis on the resulting RTs and report that aging bilinguals performed better than aging monolinguals on the Flanker task. Bilingualism was overall associated with increased GM in the ACC. Likewise, aging induced effects upon performance correlated only for monolinguals to decreased gray matter in the DLPFC. Taken together, these neural regions might underlie the benefits of bilingualism and act as a neural reserve that protects against the cognitive decline that occurs during aging. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

2016-01-01

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

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

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Song Chen

2016-01-01

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

Perfluorooctane sulfonate induces neuronal and oligodendrocytic differentiation in neural stem cells and alters the expression of PPARγ in vitro and in vivo

International Nuclear Information System (INIS)

Wan Ibrahim, Wan Norhamidah; Tofighi, Roshan; Onishchenko, Natalia; Rebellato, Paola; Bose, Raj; Uhlén, Per; Ceccatelli, Sandra

2013-01-01

Perfluorinated compounds are ubiquitous chemicals of major concern for their potential adverse effects on the human population. We have used primary rat embryonic neural stem cells (NSCs) to study the effects of perfluorooctane sulfonate (PFOS) on the process of NSC spontaneous differentiation. Upon removal of basic fibroblast growth factor, NSCs were exposed to nanomolar concentrations of PFOS for 48 h, and then allowed to differentiate for additional 5 days. Exposure to 25 or 50 nM concentration resulted in a lower number of proliferating cells and a higher number of neurite-bearing TuJ1-positive cells, indicating an increase in neuronal differentiation. Exposure to 50 nM also significantly increased the number of CNPase-positive cells, pointing to facilitation of oligodendrocytic differentiation. PPAR genes have been shown to be involved in PFOS toxicity. By q-PCR we detected an upregulation of PPARγ with no changes in PPARα or PPARδ genes. One of the downstream targets of PPARs, the mitochondrial uncoupling protein 2 (UCP2) was also upregulated. The number of TuJ1- and CNPase-positive cells increased after exposure to PPARγ agonist rosiglitazone (RGZ, 3 μM) and decreased after pre-incubation with the PPARγ antagonist GW9662 (5 μM). RGZ also upregulated the expression of PPARγ and UCP2 genes. Meanwhile GW9662 abolished the UCP2 upregulation and decreased Ca 2+ activity induced by PFOS. Interestingly, a significantly higher expression of PPARγ and UCP3 genes was also detected in mouse neonatal brain after prenatal exposure to PFOS. These data suggest that PPARγ plays a role in the alteration of spontaneous differentiation of NSCs induced by nanomolar concentrations of PFOS. - Highlights: • PFOS decreases proliferation of neural stem cells (NSCs). • PFOS induces neuronal and oligodendrocytic differentiation in NSCs. • PFOS alters expression of PPARγ and UCP2 in vitro. • PFOS alters expression of PPARγ and UCP3 in vivo. • Block of PPARγ by

Perfluorooctane sulfonate induces neuronal and oligodendrocytic differentiation in neural stem cells and alters the expression of PPARγ in vitro and in vivo

Energy Technology Data Exchange (ETDEWEB)

Wan Ibrahim, Wan Norhamidah, E-mail: hamidah@science.upm.edu.my [Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm (Sweden); Tofighi, Roshan, E-mail: Roshan.Tofighi@ki.se [Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm (Sweden); Onishchenko, Natalia, E-mail: Natalia.Onishchenko@ki.se [Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm (Sweden); Rebellato, Paola, E-mail: Paola.Rebellato@ki.se [Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-17177 Stockholm (Sweden); Bose, Raj, E-mail: Raj.Bose@ki.se [Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm (Sweden); Uhlén, Per, E-mail: Per.Uhlen@ki.se [Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-17177 Stockholm (Sweden); Ceccatelli, Sandra, E-mail: Sandra.Ceccatelli@ki.se [Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm (Sweden)

2013-05-15

Perfluorinated compounds are ubiquitous chemicals of major concern for their potential adverse effects on the human population. We have used primary rat embryonic neural stem cells (NSCs) to study the effects of perfluorooctane sulfonate (PFOS) on the process of NSC spontaneous differentiation. Upon removal of basic fibroblast growth factor, NSCs were exposed to nanomolar concentrations of PFOS for 48 h, and then allowed to differentiate for additional 5 days. Exposure to 25 or 50 nM concentration resulted in a lower number of proliferating cells and a higher number of neurite-bearing TuJ1-positive cells, indicating an increase in neuronal differentiation. Exposure to 50 nM also significantly increased the number of CNPase-positive cells, pointing to facilitation of oligodendrocytic differentiation. PPAR genes have been shown to be involved in PFOS toxicity. By q-PCR we detected an upregulation of PPARγ with no changes in PPARα or PPARδ genes. One of the downstream targets of PPARs, the mitochondrial uncoupling protein 2 (UCP2) was also upregulated. The number of TuJ1- and CNPase-positive cells increased after exposure to PPARγ agonist rosiglitazone (RGZ, 3 μM) and decreased after pre-incubation with the PPARγ antagonist GW9662 (5 μM). RGZ also upregulated the expression of PPARγ and UCP2 genes. Meanwhile GW9662 abolished the UCP2 upregulation and decreased Ca{sup 2+} activity induced by PFOS. Interestingly, a significantly higher expression of PPARγ and UCP3 genes was also detected in mouse neonatal brain after prenatal exposure to PFOS. These data suggest that PPARγ plays a role in the alteration of spontaneous differentiation of NSCs induced by nanomolar concentrations of PFOS. - Highlights: • PFOS decreases proliferation of neural stem cells (NSCs). • PFOS induces neuronal and oligodendrocytic differentiation in NSCs. • PFOS alters expression of PPARγ and UCP2 in vitro. • PFOS alters expression of PPARγ and UCP3 in vivo. • Block of PPAR�

Alterations in the neural circuits from peripheral afferents to the spinal cord: possible implications for diabetic polyneuropathy in streptozotocin-induced type 1 diabetic rats

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Zhen-Zhen eKou

2014-01-01

Full Text Available Diabetic polyneuropathy (DPN presents as a wide variety of sensorimotor symptoms and affects approximately 50% of diabetic patients. Changes in the neural circuits may occur in the early stages in diabetes and are implicated in the development of DPN. Therefore, we aimed to detect changes in the expression of isolectin B4 (IB4, the marker for nonpeptidergic unmyelinated fibers and their cell bodies and calcitonin gene-related peptide (CGRP, the marker for peptidergic fibers and their cell bodies in the dorsal root ganglion (DRG and spinal cord of streptozotocin (STZ-induced type 1 diabetic rats showing alterations in sensory and motor function. We also used cholera toxin B subunit (CTB to show the morphological changes of the myelinated fibers and motor neurons. STZ-induced diabetic rats exhibited hyperglycemia, decreased body weight gain, mechanical allodynia and impaired locomotor activity. In the DRG and spinal dorsal horn, IB4-labeled structures decreased, but both CGRP immunostaining and CTB labeling increased from day 14 to day 28 in diabetic rats. In spinal ventral horn, CTB labeling decreased in motor neurons in diabetic rats. Treatment with intrathecal injection of insulin at the early stages of DPN could alleviate mechanical allodynia and impaired locomotor activity in diabetic rats. The results suggest that the alterations of the neural circuits between spinal nerve and spinal cord via the DRG and ventral root might be involved in DPN.

Enhanced Neural Cell Adhesion and Neurite Outgrowth on Graphene-Based Biomimetic Substrates

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Suck Won Hong

2014-01-01

Full Text Available Neural cell adhesion and neurite outgrowth were examined on graphene-based biomimetic substrates. The biocompatibility of carbon nanomaterials such as graphene and carbon nanotubes (CNTs, that is, single-walled and multiwalled CNTs, against pheochromocytoma-derived PC-12 neural cells was also evaluated by quantifying metabolic activity (with WST-8 assay, intracellular oxidative stress (with ROS assay, and membrane integrity (with LDH assay. Graphene films were grown by using chemical vapor deposition and were then coated onto glass coverslips by using the scooping method. Graphene sheets were patterned on SiO2/Si substrates by using photolithography and were then covered with serum for a neural cell culture. Both types of CNTs induced significant dose-dependent decreases in the viability of PC-12 cells, whereas graphene exerted adverse effects on the neural cells just at over 62.5 ppm. This result implies that graphene and CNTs, even though they were the same carbon-based nanomaterials, show differential influences on neural cells. Furthermore, graphene-coated or graphene-patterned substrates were shown to substantially enhance the adhesion and neurite outgrowth of PC-12 cells. These results suggest that graphene-based substrates as biomimetic cues have good biocompatibility as well as a unique surface property that can enhance the neural cells, which would open up enormous opportunities in neural regeneration and nanomedicine.

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

Directory of Open Access Journals (Sweden)

Zhe-Hao Zhang

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

Acoustic leak detection at complicated topologies using neural netwoks

International Nuclear Information System (INIS)

Hessel, G.; Schmitt, W.; Weiss, F.P.

1994-01-01

Considering the shortcomings of all the existing leak detecting principles, a new method again based on the measurement of the leak induced sound but also applying pattern recognition is being developed. The capability of neural networks to localize leaks at the reactor pressure vessel (RPV) head of VVER-440 reactors is discussed. (orig./DG)

Neural networks

International Nuclear Information System (INIS)

Denby, Bruce; Lindsey, Clark; Lyons, Louis

1992-01-01

The 1980s saw a tremendous renewal of interest in 'neural' information processing systems, or 'artificial neural networks', among computer scientists and computational biologists studying cognition. Since then, the growth of interest in neural networks in high energy physics, fueled by the need for new information processing technologies for the next generation of high energy proton colliders, can only be described as explosive

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

Science.gov (United States)

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

2018-03-01

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

Artificial neural networks contribution to the operational security of embedded systems. Artificial neural networks contribution to fault tolerance of on-board functions in space environment

International Nuclear Information System (INIS)

Vintenat, Lionel

1999-01-01

A good quality often attributed to artificial neural networks is fault tolerance. In general presentation works, this property is almost always introduced as 'natural', i.e. being obtained without any specific precaution during learning. Besides, space environment is known to be aggressive towards on-board hardware, inducing various abnormal operations. Particularly, digital components suffer from upset phenomenon, i.e. misplaced switches of memory flip-flops. These two observations lead to the question: would neural chips constitute an interesting and robust solution to implement some board functions of spacecrafts? First, the various aspects of the problem are detailed: artificial neural networks and their fault tolerance, neural chips, space environment and resulting failures. Further to this presentation, a particular technique to carry out neural chips is selected because of its simplicity, and especially because it requires few memory flip-flops: random pulse streams. An original method for star recognition inside a field-of-view is then proposed for the board function 'attitude computation'. This method relies on a winner-takes-all competition network, and on a Kohonen self-organized map. An hardware implementation of those two neural models is then proposed using random pulse streams. Thanks to this realization, on one hand difficulties related to that particular implementation technique can be highlighted, and on the other hand a first evaluation of its practical fault tolerance can be carried out. (author) [fr

Neural correlates of sad feelings in healthy girls.

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Lévesque, J; Joanette, Y; Mensour, B; Beaudoin, G; Leroux, J-M; Bourgouin, P; Beauregard, M

2003-01-01

Emotional development is indisputably one of the cornerstones of personality development during infancy. According to the differential emotions theory (DET), primary emotions are constituted of three distinct components: the neural-evaluative, the expressive, and the experiential. The DET further assumes that these three components are biologically based and functional nearly from birth. Such a view entails that the neural substrate of primary emotions must be similar in children and adults. Guided by this assumption of the DET, the present functional magnetic resonance imaging study was conducted to identify the neural correlates of sad feelings in healthy children. Fourteen healthy girls (aged 8-10) were scanned while they watched sad film excerpts aimed at externally inducing a transient state of sadness (activation task). Emotionally neutral film excerpts were also presented to the subjects (reference task). The subtraction of the brain activity measured during the viewing of the emotionally neutral film excerpts from that noted during the viewing of the sad film excerpts revealed that sad feelings were associated with significant bilateral activations of the midbrain, the medial prefrontal cortex (Brodmann area [BA] 10), and the anterior temporal pole (BA 21). A significant locus of activation was also noted in the right ventrolateral prefrontal cortex (BA 47). These results are compatible with those of previous functional neuroimaging studies of sadness in adults. They suggest that the neural substrate underlying the subjective experience of sadness is comparable in children and adults. Such a similitude provides empirical support to the DET assumption that the neural substrate of primary emotions is biologically based.

Stress affects the neural ensemble for integrating new information and prior knowledge.

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Vogel, Susanne; Kluen, Lisa Marieke; Fernández, Guillén; Schwabe, Lars

2018-06-01

Prior knowledge, represented as a schema, facilitates memory encoding. This schema-related learning is assumed to rely on the medial prefrontal cortex (mPFC) that rapidly integrates new information into the schema, whereas schema-incongruent or novel information is encoded by the hippocampus. Stress is a powerful modulator of prefrontal and hippocampal functioning and first studies suggest a stress-induced deficit of schema-related learning. However, the underlying neural mechanism is currently unknown. To investigate the neural basis of a stress-induced schema-related learning impairment, participants first acquired a schema. One day later, they underwent a stress induction or a control procedure before learning schema-related and novel information in the MRI scanner. In line with previous studies, learning schema-related compared to novel information activated the mPFC, angular gyrus, and precuneus. Stress, however, affected the neural ensemble activated during learning. Whereas the control group distinguished between sets of brain regions for related and novel information, stressed individuals engaged the hippocampus even when a relevant schema was present. Additionally, stressed participants displayed aberrant functional connectivity between brain regions involved in schema processing when encoding novel information. The failure to segregate functional connectivity patterns depending on the presence of prior knowledge was linked to impaired performance after stress. Our results show that stress affects the neural ensemble underlying the efficient use of schemas during learning. These findings may have relevant implications for clinical and educational settings. Copyright © 2018 Elsevier Inc. All rights reserved.

Emotionally anesthetized: media violence induces neural changes during emotional face processing

OpenAIRE

Stockdale, Laura A.; Morrison, Robert G.; Kmiecik, Matthew J.; Garbarino, James; Silton, Rebecca L.

2015-01-01

Media violence exposure causes increased aggression and decreased prosocial behavior, suggesting that media violence desensitizes people to the emotional experience of others. Alterations in emotional face processing following exposure to media violence may result in desensitization to others’ emotional states. This study used scalp electroencephalography methods to examine the link between exposure to violence and neural changes associated with emotional face processing. Twenty-five particip...

Signs of noise-induced neural degeneration in humans

DEFF Research Database (Denmark)

Holtegaard, Pernille; Olsen, Steen Østergaard

2015-01-01

of background noise, while leaving the processing of low-level stimuli unaffected. The purpose of this study was to investigate if signs of such primary neural damage from noise-exposure could also be found in noiseexposed human individuals. It was investigated: (1) if noise-exposed listeners with hearing......Animal studies demonstrated that noise exposure causes a primary and selective loss of auditory-nerve fibres with low spontaneous firing rate. This neuronal impairment, if also present in humans, can be assumed to affect the processing of supra-threshold stimuli, especially in the presence...... thresholds within the “normal” range perform poorer, in terms of their speech recognition threshold in noise (SRTN), and (2) if auditory brainstem responses (ABR) reveal lower amplitude of wave I in the noise-exposed listeners. A test group of noise/music-exposed individuals and a control group were...

Acoustic stimulation can induce a selective neural network response mediated by piezoelectric nanoparticles

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Rojas, Camilo; Tedesco, Mariateresa; Massobrio, Paolo; Marino, Attilio; Ciofani, Gianni; Martinoia, Sergio; Raiteri, Roberto

2018-06-01

Objective. We aim to develop a novel non-invasive or minimally invasive method for neural stimulation to be applied in the study and treatment of brain (dys)functions and neurological disorders. Approach. We investigate the electrophysiological response of in vitro neuronal networks when subjected to low-intensity pulsed acoustic stimulation, mediated by piezoelectric nanoparticles adsorbed on the neuronal membrane. Main results. We show that the presence of piezoelectric barium titanate nanoparticles induces, in a reproducible way, an increase in network activity when excited by stationary ultrasound waves in the MHz regime. Such a response can be fully recovered when switching the ultrasound pulse off, depending on the generated pressure field amplitude, whilst it is insensitive to the duration of the ultrasound pulse in the range 0.5 s–1.5 s. We demonstrate that the presence of piezoelectric nanoparticles is necessary, and when applying the same acoustic stimulation to neuronal cultures without nanoparticles or with non-piezoelectric nanoparticles with the same size distribution, no network response is observed. Significance. We believe that our results open up an extremely interesting approach when coupled with suitable functionalization strategies of the nanoparticles in order to address specific neurons and/or brain areas and applied in vivo, thus enabling remote, non-invasive, and highly selective modulation of the activity of neuronal subpopulations of the central nervous system of mammalians.

Efficient and Rapid Derivation of Primitive Neural Stem Cells and Generation of Brain Subtype Neurons From Human Pluripotent Stem Cells

OpenAIRE

Yan, Yiping; Shin, Soojung; Jha, Balendu Shekhar; Liu, Qiuyue; Sheng, Jianting; Li, Fuhai; Zhan, Ming; Davis, Janine; Bharti, Kapil; Zeng, Xianmin; Rao, Mahendra; Malik, Nasir; Vemuri, Mohan C.

2013-01-01

This study developed a highly efficient serum-free pluripotent stem cell (PSC) neural induction medium that can induce human PSCs into primitive neural stem cells (NSCs) in 7 days, obviating the need for time-consuming, laborious embryoid body generation or rosette picking. This method of primitive NSC derivation sets the stage for the scalable production of clinically relevant neural cells for cell therapy applications in good manufacturing practice conditions.

Neural Basis of Intrinsic Motivation: Evidence from Event-Related Potentials.

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Jin, Jia; Yu, Liping; Ma, Qingguo

2015-01-01

Human intrinsic motivation is of great importance in human behavior. However, although researchers have focused on this topic for decades, its neural basis was still unclear. The current study employed event-related potentials to investigate the neural disparity between an interesting stop-watch (SW) task and a boring watch-stop task (WS) to understand the neural mechanisms of intrinsic motivation. Our data showed that, in the cue priming stage, the cue of the SW task elicited smaller N2 amplitude than that of the WS task. Furthermore, in the outcome feedback stage, the outcome of the SW task induced smaller FRN amplitude and larger P300 amplitude than that of the WS task. These results suggested that human intrinsic motivation did exist and that it can be detected at the neural level. Furthermore, intrinsic motivation could be quantitatively indexed by the amplitude of ERP components, such as N2, FRN, and P300, in the cue priming stage or feedback stage. Quantitative measurements would also be convenient for intrinsic motivation to be added as a candidate social factor in the construction of a machine learning model.

Compositionality in Neural Control:An Interdisciplinary Study of Scribbling Movements in Primates

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Moshe eAbeles

2013-09-01

Full Text Available This article discusses the compositional structure of hand movements by analyzing and modeling neural and behavioral data obtained from experiments where a monkey (Macaca fascicularis performed scribbling movements induced by a search task. Using geometrically based approaches to movement segmentation, it is shown that the hand trajectories are composed of elementary segments that are primarily parabolic in shape. The segments could be categorized into a small number of classes on the basis of decreasing intra-class variance over the course of training. A separate classification of the neural data employing a hidden Markov model showed a coincidence of the neural states with the behavioral categories. An additional analysis of both types of data by a data mining method provided evidence that the neural activity patterns underlying the behavioral primitives were formed by sets of specific and precise spike patterns. A geometric description of the movement trajectories, together with precise neural timing data indicates a compositional variant of a realistic synfire chain model. This model reproduces the typical shapes and temporal properties of the trajectories; hence the structure and composition of the primitives may reflect meaningful behavior.

Different Neural Correlates of Emotion-Label Words and Emotion-Laden Words: An ERP Study

OpenAIRE

Zhang, Juan; Wu, Chenggang; Meng, Yaxuan; Yuan, Zhen

2017-01-01

It is well-documented that both emotion-label words (e.g., sadness, happiness) and emotion-laden words (e.g., death, wedding) can induce emotion activation. However, the neural correlates of emotion-label words and emotion-laden words recognition have not been examined. The present study aimed to compare the underlying neural responses when processing the two kinds of words by employing event-related potential (ERP) measurements. Fifteen Chinese native speakers were asked to perform a lexical...

Effective electric fields along realistic DTI-based neural trajectories for modelling the stimulation mechanisms of TMS

NARCIS (Netherlands)

De Geeter, N.; Crevecoeur, G.; Leemans, A.; Dupré, L.

2015-01-01

In transcranial magnetic stimulation (TMS), an applied alternating magnetic field induces an electric field in the brain that can interact with the neural system. It is generally assumed that this induced electric field is the crucial effect exciting a certain region of the brain. More specifically,

Antenatal dexamethasone before asphyxia promotes cystic neural injury in preterm fetal sheep by inducing hyperglycemia.

Science.gov (United States)

Lear, Christopher A; Davidson, Joanne O; Mackay, Georgia R; Drury, Paul P; Galinsky, Robert; Quaedackers, Josine S; Gunn, Alistair J; Bennet, Laura

2018-04-01

Antenatal glucocorticoid therapy significantly improves the short-term systemic outcomes of prematurely born infants, but there is limited information available on their impact on neurodevelopmental outcomes in at-risk preterm babies exposed to perinatal asphyxia. Preterm fetal sheep (0.7 of gestation) were exposed to a maternal injection of 12 mg dexamethasone or saline followed 4 h later by asphyxia induced by 25 min of complete umbilical cord occlusion. In a subsequent study, fetuses received titrated glucose infusions followed 4 h later by asphyxia to examine the hypothesis that hyperglycemia mediated the effects of dexamethasone. Post-mortems were performed 7 days after asphyxia for cerebral histology. Maternal dexamethasone before asphyxia was associated with severe, cystic brain injury compared to diffuse injury after saline injection, with increased numbers of seizures, worse recovery of brain activity, and increased arterial glucose levels before, during, and after asphyxia. Glucose infusions before asphyxia replicated these adverse outcomes, with a strong correlation between greater increases in glucose before asphyxia and greater neural injury. These findings strongly suggest that dexamethasone exposure and hyperglycemia can transform diffuse injury into cystic brain injury after asphyxia in preterm fetal sheep.

Neural Correlates of Traditional Chinese Medicine Induced Advantageous Risk-Taking Decision Making

Science.gov (United States)

Lee, Tiffany M. Y.; Guo, Li-guo; Shi, Hong-zhi; Li, Yong-zhi; Luo, Yue-jia; Sung, Connie Y. Y.; Chan, Chetwyn C. H.; Lee, Tatia M. C.

2009-01-01

This fMRI study examined the neural correlates of the observed improvement in advantageous risk-taking behavior, as measured by the number of adjusted pumps in the Balloon Analogue Risk Task (BART), following a 60-day course of a Traditional Chinese Medicine (TCM) recipe, specifically designed to regulate impulsiveness in order to modulate…

Evolvable Neural Software System

Science.gov (United States)

Curtis, Steven A.

2009-01-01

The Evolvable Neural Software System (ENSS) is composed of sets of Neural Basis Functions (NBFs), which can be totally autonomously created and removed according to the changing needs and requirements of the software system. The resulting structure is both hierarchical and self-similar in that a given set of NBFs may have a ruler NBF, which in turn communicates with other sets of NBFs. These sets of NBFs may function as nodes to a ruler node, which are also NBF constructs. In this manner, the synthetic neural system can exhibit the complexity, three-dimensional connectivity, and adaptability of biological neural systems. An added advantage of ENSS over a natural neural system is its ability to modify its core genetic code in response to environmental changes as reflected in needs and requirements. The neural system is fully adaptive and evolvable and is trainable before release. It continues to rewire itself while on the job. The NBF is a unique, bilevel intelligence neural system composed of a higher-level heuristic neural system (HNS) and a lower-level, autonomic neural system (ANS). Taken together, the HNS and the ANS give each NBF the complete capabilities of a biological neural system to match sensory inputs to actions. Another feature of the NBF is the Evolvable Neural Interface (ENI), which links the HNS and ANS. The ENI solves the interface problem between these two systems by actively adapting and evolving from a primitive initial state (a Neural Thread) to a complicated, operational ENI and successfully adapting to a training sequence of sensory input. This simulates the adaptation of a biological neural system in a developmental phase. Within the greater multi-NBF and multi-node ENSS, self-similar ENI s provide the basis for inter-NBF and inter-node connectivity.

Neural and behavioural changes in male periadolescent mice after prolonged nicotine-MDMA treatment.

Science.gov (United States)

Adeniyi, Philip A; Ishola, Azeez O; Laoye, Babafemi J; Olatunji, Babawale P; Bankole, Oluwamolakun O; Shallie, Philemon D; Ogundele, Olalekan M

2016-02-01

The interaction between MDMA and Nicotine affects multiple brain centres and neurotransmitter systems (serotonin, dopamine and glutamate) involved in motor coordination and cognition. In this study, we have elucidated the effect of prolonged (10 days) MDMA, Nicotine and a combined Nicotine-MDMA treatment on motor-cognitive neural functions. In addition, we have shown the correlation between the observed behavioural change and neural structural changes induced by these treatments in BALB/c mice. We observed that MDMA (2 mg/Kg body weight; subcutaneous) induced a decline in motor function, while Nicotine (2 mg/Kg body weight; subcutaneous) improved motor function in male periadolescent mice. In combined treatment, Nicotine reduced the motor function decline observed in MDMA treatment, thus no significant change in motor function for the combined treatment versus the control. Nicotine or MDMA treatment reduced memory function and altered hippocampal structure. Similarly, a combined Nicotine-MDMA treatment reduced memory function when compared with the control. Ultimately, the metabolic and structural changes in these neural systems were seen to vary for the various forms of treatment. It is noteworthy to mention that a combined treatment increased the rate of lipid peroxidation in brain tissue.

Direct Neural Conversion from Human Fibroblasts Using Self-Regulating and Nonintegrating Viral Vectors

Directory of Open Access Journals (Sweden)

Shong Lau

2014-12-01

Full Text Available Summary: Recent findings show that human fibroblasts can be directly programmed into functional neurons without passing via a proliferative stem cell intermediate. These findings open up the possibility of generating subtype-specific neurons of human origin for therapeutic use from fetal cell, from patients themselves, or from matched donors. In this study, we present an improved system for direct neural conversion of human fibroblasts. The neural reprogramming genes are regulated by the neuron-specific microRNA, miR-124, such that each cell turns off expression of the reprogramming genes once the cell has reached a stable neuronal fate. The regulated system can be combined with integrase-deficient vectors, providing a nonintegrative and self-regulated conversion system that rids problems associated with the integration of viral transgenes into the host genome. These modifications make the system suitable for clinical use and therefore represent a major step forward in the development of induced neurons for cell therapy. : Lau et al. now use miRNA targeting to build a self-regulating neural conversion system. Combined with nonintegrating vectors, this system can efficiently drive conversion of human fibroblasts into functional induced neurons (iNs suitable for clinical applications.

ETOH inhibits embryonic neural stem/precursor cell proliferation via PLD signaling

International Nuclear Information System (INIS)

Fujita, Yuko; Hiroyama, Masami; Sanbe, Atsushi; Yamauchi, Junji; Murase, Shoko; Tanoue, Akito

2008-01-01

While a mother's excessive alcohol consumption during pregnancy is known to have adverse effects on fetal neural development, little is known about the underlying mechanism of these effects. In order to investigate these mechanisms, we investigated the toxic effect of ethanol (ETOH) on neural stem/precursor cell (NSC) proliferation. In cultures of NSCs, phospholipase D (PLD) is activated following stimulation with epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2). Exposure of NSCs to ETOH suppresses cell proliferation, while it has no effect on cell death. Phosphatidic acid (PA), which is a signaling messenger produced by PLD, reverses ETOH inhibition of NSC proliferation. Blocking the PLD signal by 1-butanol suppresses the proliferation. ETOH-induced suppression of NSC proliferation and the protective effect of PA for ETOH-induced suppression are mediated through extracellular signal-regulated kinase signaling. These results indicate that exposure to ETOH impairs NSC proliferation by altering the PLD signaling pathway

Hedgehog regulates Norrie disease protein to drive neural progenitor self-renewal.

Science.gov (United States)

McNeill, Brian; Mazerolle, Chantal; Bassett, Erin A; Mears, Alan J; Ringuette, Randy; Lagali, Pamela; Picketts, David J; Paes, Kim; Rice, Dennis; Wallace, Valerie A

2013-03-01

Norrie disease (ND) is a congenital disorder characterized by retinal hypovascularization and cognitive delay. ND has been linked to mutations in 'Norrie Disease Protein' (Ndp), which encodes the secreted protein Norrin. Norrin functions as a secreted angiogenic factor, although its role in neural development has not been assessed. Here, we show that Ndp expression is initiated in retinal progenitors in response to Hedgehog (Hh) signaling, which induces Gli2 binding to the Ndp promoter. Using a combination of genetic epistasis and acute RNAi-knockdown approaches, we show that Ndp is required downstream of Hh activation to induce retinal progenitor proliferation in the retina. Strikingly, Ndp regulates the rate of cell-cycle re-entry and not cell-cycle kinetics, thereby uncoupling the self-renewal and cell-cycle progression functions of Hh. Taken together, we have uncovered a cell autonomous function for Ndp in retinal progenitor proliferation that is independent of its function in the retinal vasculature, which could explain the neural defects associated with ND.

Cell death in neural precursor cells and neurons before neurite formation prevents the emergence of abnormal neural structures in the Drosophila optic lobe.

Science.gov (United States)

Hara, Yusuke; Sudo, Tatsuya; Togane, Yu; Akagawa, Hiromi; Tsujimura, Hidenobu

2018-04-01

Programmed cell death is a conserved strategy for neural development both in vertebrates and invertebrates and is recognized at various developmental stages in the brain from neurogenesis to adulthood. To understand the development of the central nervous system, it is essential to reveal not only molecular mechanisms but also the role of neural cell death (Pinto-Teixeira et al., 2016). To understand the role of cell death in neural development, we investigated the effect of inhibition of cell death on optic lobe development. Our data demonstrate that, in the optic lobe of Drosophila, cell death occurs in neural precursor cells and neurons before neurite formation and functions to prevent various developmental abnormalities. When neuronal cell death was inhibited by an effector caspase inhibitor, p35, multiple abnormal neuropil structures arose during optic lobe development-e.g., enlarged or fused neuropils, misrouted neurons and abnormal neurite lumps. Inhibition of cell death also induced morphogenetic defects in the lamina and medulla development-e.g., failures in the separation of the lamina and medulla cortices and the medulla rotation. These defects were reproduced in the mutant of an initiator caspase, dronc. If cell death was a mechanism for removing the abnormal neuropil structures, we would also expect to observe them in mutants defective for corpse clearance. However, they were not observed in these mutants. When dead cell-membranes were visualized with Apoliner, they were observed only in cortices and not in neuropils. These results suggest that the cell death occurs before mature neurite formation. Moreover, we found that inhibition of cell death induced ectopic neuroepithelial cells, neuroblasts and ganglion mother cells in late pupal stages, at sites where the outer and inner proliferation centers were located at earlier developmental stages. Caspase-3 activation was observed in the neuroepithelial cells and neuroblasts in the proliferation centers

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

Science.gov (United States)

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

2014-03-01

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

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

Directory of Open Access Journals (Sweden)

Z. Xiong

2014-03-01

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

Chronic exposure to graphene-based nanomaterials induces behavioral deficits and neural damage in Caenorhabditis elegans.

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Li, Ping; Xu, Tiantian; Wu, Siyu; Lei, Lili; He, Defu

2017-10-01

Nanomaterials of graphene and its derivatives have been widely applied in recent years, but whose impacts on the environment and health are still not well understood. In the present study, the potential adverse effects of graphite (G), graphite oxide nanoplatelets (GO) and graphene quantum dots (GQDs) on the motor nervous system were investigated using nematode Caenorhabditis elegans as the assay system. After being characterized using TEM, SEM, XPS and PLE, three nanomaterials were chronically exposed to C. elegans for 6 days. In total, 50-100 mg l -1 GO caused a significant reduction in the survival rate, but G and GDDs showed low lethality on nematodes. After chronic exposure of sub-lethal dosages, three nanomaterials were observed to distribute primarily in the pharynx and intestine; but GQDs were widespread in nematode body. Three graphene-based nanomaterials resulted in significant declines in locomotor frequency of body bending, head thrashing and pharynx pumping. In addition, mean speed, bending angle-frequency and wavelength of the crawling movement were significantly reduced after exposure. Using transgenic nematodes, we found high concentrations of graphene-based nanomaterials induced down-expression of dat-1::GFP and eat-4::GFP, but no significant changes in unc-47::GFP. This indicates that graphene-based nanomaterials can lead to damages in the dopaminergic and glutamatergic neurons. The present data suggest that chronic exposure of graphene-based nanomaterials may cause neurotoxicity risks of inducing behavioral deficits and neural damage. These findings provide useful information to understand the toxicity and safe application of graphene-based nanomaterials. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Chaotic diagonal recurrent neural network

International Nuclear Information System (INIS)

Wang Xing-Yuan; Zhang Yi

2012-01-01

We propose a novel neural network based on a diagonal recurrent neural network and chaos, and its structure and learning algorithm are designed. The multilayer feedforward neural network, diagonal recurrent neural network, and chaotic diagonal recurrent neural network are used to approach the cubic symmetry map. The simulation results show that the approximation capability of the chaotic diagonal recurrent neural network is better than the other two neural networks. (interdisciplinary physics and related areas of science and technology)

Computational modeling of neural plasticity for self-organization of neural networks.

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Chrol-Cannon, Joseph; Jin, Yaochu

2014-11-01

Self-organization in biological nervous systems during the lifetime is known to largely occur through a process of plasticity that is dependent upon the spike-timing activity in connected neurons. In the field of computational neuroscience, much effort has been dedicated to building up computational models of neural plasticity to replicate experimental data. Most recently, increasing attention has been paid to understanding the role of neural plasticity in functional and structural neural self-organization, as well as its influence on the learning performance of neural networks for accomplishing machine learning tasks such as classification and regression. Although many ideas and hypothesis have been suggested, the relationship between the structure, dynamics and learning performance of neural networks remains elusive. The purpose of this article is to review the most important computational models for neural plasticity and discuss various ideas about neural plasticity's role. Finally, we suggest a few promising research directions, in particular those along the line that combines findings in computational neuroscience and systems biology, and their synergetic roles in understanding learning, memory and cognition, thereby bridging the gap between computational neuroscience, systems biology and computational intelligence. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Mindfulness Meditation-Based Pain Relief Employs Different Neural Mechanisms Than Placebo and Sham Mindfulness Meditation-Induced Analgesia

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Emerson, Nichole M.; Farris, Suzan R.; Ray, Jenna N.; Jung, Youngkyoo; McHaffie, John G.; Coghill, Robert C.

2015-01-01

Mindfulness meditation reduces pain in experimental and clinical settings. However, it remains unknown whether mindfulness meditation engages pain-relieving mechanisms other than those associated with the placebo effect (e.g., conditioning, psychosocial context, beliefs). To determine whether the analgesic mechanisms of mindfulness meditation are different from placebo, we randomly assigned 75 healthy, human volunteers to 4 d of the following: (1) mindfulness meditation, (2) placebo conditioning, (3) sham mindfulness meditation, or (4) book-listening control intervention. We assessed intervention efficacy using psychophysical evaluation of experimental pain and functional neuroimaging. Importantly, all cognitive manipulations (i.e., mindfulness meditation, placebo conditioning, sham mindfulness meditation) significantly attenuated pain intensity and unpleasantness ratings when compared to rest and the control condition (p Mindfulness meditation reduced pain intensity (p = 0.032) and pain unpleasantness (p Mindfulness meditation also reduced pain intensity (p = 0.030) and pain unpleasantness (p = 0.043) ratings more than sham mindfulness meditation. Mindfulness-meditation-related pain relief was associated with greater activation in brain regions associated with the cognitive modulation of pain, including the orbitofrontal, subgenual anterior cingulate, and anterior insular cortex. In contrast, placebo analgesia was associated with activation of the dorsolateral prefrontal cortex and deactivation of sensory processing regions (secondary somatosensory cortex). Sham mindfulness meditation-induced analgesia was not correlated with significant neural activity, but rather by greater reductions in respiration rate. This study is the first to demonstrate that mindfulness-related pain relief is mechanistically distinct from placebo analgesia. The elucidation of this distinction confirms the existence of multiple, cognitively driven, supraspinal mechanisms for pain

Mindfulness Meditation-Based Pain Relief Employs Different Neural Mechanisms Than Placebo and Sham Mindfulness Meditation-Induced Analgesia.

Science.gov (United States)

Zeidan, Fadel; Emerson, Nichole M; Farris, Suzan R; Ray, Jenna N; Jung, Youngkyoo; McHaffie, John G; Coghill, Robert C

2015-11-18

Mindfulness meditation reduces pain in experimental and clinical settings. However, it remains unknown whether mindfulness meditation engages pain-relieving mechanisms other than those associated with the placebo effect (e.g., conditioning, psychosocial context, beliefs). To determine whether the analgesic mechanisms of mindfulness meditation are different from placebo, we randomly assigned 75 healthy, human volunteers to 4 d of the following: (1) mindfulness meditation, (2) placebo conditioning, (3) sham mindfulness meditation, or (4) book-listening control intervention. We assessed intervention efficacy using psychophysical evaluation of experimental pain and functional neuroimaging. Importantly, all cognitive manipulations (i.e., mindfulness meditation, placebo conditioning, sham mindfulness meditation) significantly attenuated pain intensity and unpleasantness ratings when compared to rest and the control condition (p pain intensity (p = 0.032) and pain unpleasantness (p pain intensity (p = 0.030) and pain unpleasantness (p = 0.043) ratings more than sham mindfulness meditation. Mindfulness-meditation-related pain relief was associated with greater activation in brain regions associated with the cognitive modulation of pain, including the orbitofrontal, subgenual anterior cingulate, and anterior insular cortex. In contrast, placebo analgesia was associated with activation of the dorsolateral prefrontal cortex and deactivation of sensory processing regions (secondary somatosensory cortex). Sham mindfulness meditation-induced analgesia was not correlated with significant neural activity, but rather by greater reductions in respiration rate. This study is the first to demonstrate that mindfulness-related pain relief is mechanistically distinct from placebo analgesia. The elucidation of this distinction confirms the existence of multiple, cognitively driven, supraspinal mechanisms for pain modulation. Recent findings have demonstrated that mindfulness meditation

Neural processes underlying cultural differences in cognitive persistence.

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Telzer, Eva H; Qu, Yang; Lin, Lynda C

2017-08-01

Self-improvement motivation, which occurs when individuals seek to improve upon their competence by gaining new knowledge and improving upon their skills, is critical for cognitive, social, and educational adjustment. While many studies have delineated the neural mechanisms supporting extrinsic motivation induced by monetary rewards, less work has examined the neural processes that support intrinsically motivated behaviors, such as self-improvement motivation. Because cultural groups traditionally vary in terms of their self-improvement motivation, we examined cultural differences in the behavioral and neural processes underlying motivated behaviors during cognitive persistence in the absence of extrinsic rewards. In Study 1, 71 American (47 females, M=19.68 years) and 68 Chinese (38 females, M=19.37 years) students completed a behavioral cognitive control task that required cognitive persistence across time. In Study 2, 14 American and 15 Chinese students completed the same cognitive persistence task during an fMRI scan. Across both studies, American students showed significant declines in cognitive performance across time, whereas Chinese participants demonstrated effective cognitive persistence. These behavioral effects were explained by cultural differences in self-improvement motivation and paralleled by increasing activation and functional coupling between the inferior frontal gyrus (IFG) and ventral striatum (VS) across the task among Chinese participants, neural activation and coupling that remained low in American participants. These findings suggest a potential neural mechanism by which the VS and IFG work in concert to promote cognitive persistence in the absence of extrinsic rewards. Thus, frontostriatal circuitry may be a neurobiological signal representing intrinsic motivation for self-improvement that serves an adaptive function, increasing Chinese students' motivation to engage in cognitive persistence. Copyright © 2017 Elsevier Inc. All rights

Perlecan is required for FGF-2 signaling in the neural stem cell niche

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Aurelien Kerever

2014-03-01

Full Text Available In the adult subventricular zone (neurogenic niche, neural stem cells double-positive for two markers of subsets of neural stem cells in the adult central nervous system, glial fibrillary acidic protein and CD133, lie in proximity to fractones and to blood vessel basement membranes, which contain the heparan sulfate proteoglycan perlecan. Here, we demonstrate that perlecan deficiency reduces the number of both GFAP/CD133-positive neural stem cells in the subventricular zone and new neurons integrating into the olfactory bulb. We also show that FGF-2 treatment induces the expression of cyclin D2 through the activation of the Akt and Erk1/2 pathways and promotes neurosphere formation in vitro. However, in the absence of perlecan, FGF-2 fails to promote neurosphere formation. These results suggest that perlecan is a component of the neurogenic niche that regulates FGF-2 signaling and acts by promoting neural stem cell self-renewal and neurogenesis.

Electrically polarized PLLA nanofibers as neural tissue engineering scaffolds with improved neuritogenesis.

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Barroca, Nathalie; Marote, Ana; Vieira, Sandra I; Almeida, Abílio; Fernandes, Maria H V; Vilarinho, Paula M; da Cruz E Silva, Odete A B

2018-07-01

Tissue engineering is evolving towards the production of smart platforms exhibiting stimulatory cues to guide tissue regeneration. This work explores the benefits of electrical polarization to produce more efficient neural tissue engineering platforms. Poly (l-lactic) acid (PLLA)-based scaffolds were prepared as solvent cast films and electrospun aligned nanofibers, and electrically polarized by an in-lab built corona poling device. The characterization of the platforms by thermally stimulated depolarization currents reveals a polarization of 60 × 10 -10 C cm -2 that is stable on poled electrospun nanofibers for up to 6 months. Further in vitro studies using neuroblastoma cells reveals that platforms' polarization potentiates Retinoic Acid-induced neuronal differentiation. Additionally, in differentiating embryonic cortical neurons, poled aligned nanofibers further increased neurite outgrowth by 30% (+70 μm) over non-poled aligned nanofibers, and by 50% (+100 μm) over control conditions. Therefore, the synergy of topographical cues and electrical polarization of poled aligned nanofibers places them as promising biocompatible and bioactive platforms for neural tissue regeneration. Given their long lasting induced polarization, these PLLA poled nanofibrous scaffolds can be envisaged as therapeutic devices of long shelf life for neural repair applications. Copyright © 2018 Elsevier B.V. All rights reserved.

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

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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.

Intranasal oxytocin reduces social perception in women: Neural activation and individual variation.

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Hecht, Erin E; Robins, Diana L; Gautam, Pritam; King, Tricia Z

2017-02-15

Most intranasal oxytocin research to date has been carried out in men, but recent studies indicate that females' responses can differ substantially from males'. This randomized, double-blind, placebo-controlled study involved an all-female sample of 28 women not using hormonal contraception. Participants viewed animations of geometric shapes depicting either random movement or social interactions such as playing, chasing, or fighting. Probe questions asked whether any shapes were "friends" or "not friends." Social videos were preceded by cues to attend to either social relationships or physical size changes. All subjects received intranasal placebo spray at scan 1. While the experimenter was not blinded to nasal spray contents at Scan 1, the participants were. Scan 2 followed a randomized, double-blind design. At scan 2, half received a second placebo dose while the other half received 24 IU of intranasal oxytocin. We measured neural responses to these animations at baseline, as well as the change in neural activity induced by oxytocin. Oxytocin reduced activation in early visual cortex and dorsal-stream motion processing regions for the social > size contrast, indicating reduced activity related to social attention. Oxytocin also reduced endorsements that shapes were "friends" or "not friends," and this significantly correlated with reduction in neural activation. Furthermore, participants who perceived fewer social relationships at baseline were more likely to show oxytocin-induced increases in a broad network of regions involved in social perception and social cognition, suggesting that lower social processing at baseline may predict more positive neural responses to oxytocin. Copyright © 2016 Elsevier Inc. All rights reserved.

TopologyNet: Topology based deep convolutional and multi-task neural networks for biomolecular property predictions

Science.gov (United States)

2017-01-01

Although deep learning approaches have had tremendous success in image, video and audio processing, computer vision, and speech recognition, their applications to three-dimensional (3D) biomolecular structural data sets have been hindered by the geometric and biological complexity. To address this problem we introduce the element-specific persistent homology (ESPH) method. ESPH represents 3D complex geometry by one-dimensional (1D) topological invariants and retains important biological information via a multichannel image-like representation. This representation reveals hidden structure-function relationships in biomolecules. We further integrate ESPH and deep convolutional neural networks to construct a multichannel topological neural network (TopologyNet) for the predictions of protein-ligand binding affinities and protein stability changes upon mutation. To overcome the deep learning limitations from small and noisy training sets, we propose a multi-task multichannel topological convolutional neural network (MM-TCNN). We demonstrate that TopologyNet outperforms the latest methods in the prediction of protein-ligand binding affinities, mutation induced globular protein folding free energy changes, and mutation induced membrane protein folding free energy changes. Availability: weilab.math.msu.edu/TDL/ PMID:28749969

Neural Parallel Engine: A toolbox for massively parallel neural signal processing.

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Tam, Wing-Kin; Yang, Zhi

2018-05-01

Large-scale neural recordings provide detailed information on neuronal activities and can help elicit the underlying neural mechanisms of the brain. However, the computational burden is also formidable when we try to process the huge data stream generated by such recordings. In this study, we report the development of Neural Parallel Engine (NPE), a toolbox for massively parallel neural signal processing on graphical processing units (GPUs). It offers a selection of the most commonly used routines in neural signal processing such as spike detection and spike sorting, including advanced algorithms such as exponential-component-power-component (EC-PC) spike detection and binary pursuit spike sorting. We also propose a new method for detecting peaks in parallel through a parallel compact operation. Our toolbox is able to offer a 5× to 110× speedup compared with its CPU counterparts depending on the algorithms. A user-friendly MATLAB interface is provided to allow easy integration of the toolbox into existing workflows. Previous efforts on GPU neural signal processing only focus on a few rudimentary algorithms, are not well-optimized and often do not provide a user-friendly programming interface to fit into existing workflows. There is a strong need for a comprehensive toolbox for massively parallel neural signal processing. A new toolbox for massively parallel neural signal processing has been created. It can offer significant speedup in processing signals from large-scale recordings up to thousands of channels. Copyright © 2018 Elsevier B.V. All rights reserved.

A central neural circuit for itch sensation.

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Mu, Di; Deng, Juan; Liu, Ke-Fei; Wu, Zhen-Yu; Shi, Yu-Feng; Guo, Wei-Min; Mao, Qun-Quan; Liu, Xing-Jun; Li, Hui; Sun, Yan-Gang

2017-08-18

Although itch sensation is an important protective mechanism for animals, chronic itch remains a challenging clinical problem. Itch processing has been studied extensively at the spinal level. However, how itch information is transmitted to the brain and what central circuits underlie the itch-induced scratching behavior remain largely unknown. We found that the spinoparabrachial pathway was activated during itch processing and that optogenetic suppression of this pathway impaired itch-induced scratching behaviors. Itch-mediating spinal neurons, which express the gastrin-releasing peptide receptor, are disynaptically connected to the parabrachial nucleus via glutamatergic spinal projection neurons. Blockade of synaptic output of glutamatergic neurons in the parabrachial nucleus suppressed pruritogen-induced scratching behavior. Thus, our studies reveal a central neural circuit that is critical for itch signal processing. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Neural chips, neural computers and application in high and superhigh energy physics experiments

International Nuclear Information System (INIS)

Nikityuk, N.M.; )

2001-01-01

Architecture peculiarity and characteristics of series of neural chips and neural computes used in scientific instruments are considered. Tendency of development and use of them in high energy and superhigh energy physics experiments are described. Comparative data which characterize the efficient use of neural chips for useful event selection, classification elementary particles, reconstruction of tracks of charged particles and for search of hypothesis Higgs particles are given. The characteristics of native neural chips and accelerated neural boards are considered [ru

Fluctuation-Driven Neural Dynamics Reproduce Drosophila Locomotor Patterns.

Directory of Open Access Journals (Sweden)

Andrea Maesani

2015-11-01

Full Text Available The neural mechanisms determining the timing of even simple actions, such as when to walk or rest, are largely mysterious. One intriguing, but untested, hypothesis posits a role for ongoing activity fluctuations in neurons of central action selection circuits that drive animal behavior from moment to moment. To examine how fluctuating activity can contribute to action timing, we paired high-resolution measurements of freely walking Drosophila melanogaster with data-driven neural network modeling and dynamical systems analysis. We generated fluctuation-driven network models whose outputs-locomotor bouts-matched those measured from sensory-deprived Drosophila. From these models, we identified those that could also reproduce a second, unrelated dataset: the complex time-course of odor-evoked walking for genetically diverse Drosophila strains. Dynamical models that best reproduced both Drosophila basal and odor-evoked locomotor patterns exhibited specific characteristics. First, ongoing fluctuations were required. In a stochastic resonance-like manner, these fluctuations allowed neural activity to escape stable equilibria and to exceed a threshold for locomotion. Second, odor-induced shifts of equilibria in these models caused a depression in locomotor frequency following olfactory stimulation. Our models predict that activity fluctuations in action selection circuits cause behavioral output to more closely match sensory drive and may therefore enhance navigation in complex sensory environments. Together these data reveal how simple neural dynamics, when coupled with activity fluctuations, can give rise to complex patterns of animal behavior.

Chronic Restraint Stress Induces an Isoform-Specific Regulation on the Neural Cell Adhesion Molecule in the Hippocampus

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Touyarot, K.; Sandi, C.

2002-01-01

Existing evidence indicates that 21-days exposure of rats to restraint stress induces dendritic atrophy in pyramidal cells of the hippocampus. This phenomenon has been related to altered performance in hippocampal-dependent learning tasks. Prior studies have shown that hippocampal expression of cell adhesion molecules is modified by such stress treatment, with the neural cell adhesion molecule (NCAM) decreasing and L1 increasing, their expression, at both the mRNA and protein levels. Given that NCAM comprises several isoforms, we investigated here whether chronic stress might differentially affect the expression of the three major isoforms (NCAM-120, NCAM-140, NCAM-180) in the hippocampus. In addition, as glucocorticoids have been implicated in the deleterious effects induced by chronic stress, we also evaluated plasma corticosterone levels and the hippocampal expression of the corticosteroid mineralocorticoid receptor (MR) and glucocorticoid receptor (GR). The results showed that the protein concentration of the NCAM-140 isoform decreased in the hippoampus of stressed rats. This effect was isoform-specific, because NCAM-120 and NCAM-180 levels were not significantly modified. In addition, whereas basal levels of plasma corticosterone tended to be increased, MR and GR concentrations were not significantly altered. Although possible changes in NCAM-120, NCAM-180 and corticosteroid receptors at earlier time points of the stress period cannot be ignored; this study suggests that a down-regulation of NCAM-140 might be implicated in the structural alterations consistently shown to be induced in the hippocampus by chronic stress exposure. As NCAM-140 is involved in cell-cell adhesion and neurite outgrowth, these findings suggest that this molecule might be one of the molecular mechanisms involved in the complex interactions among neurodegeneration-related events. PMID:12757368

Can Intrinsic Fluctuations Increase Efficiency in Neural Information Processing?

Science.gov (United States)

Liljenström, Hans

2003-05-01

All natural processes are accompanied by fluctuations, characterized as noise or chaos. Biological systems, which have evolved during billions of years, are likely to have adapted, not only to cope with such fluctuations, but also to make use of them. We investigate how the complex dynamics of the brain, including oscillations, chaos and noise, can affect the efficiency of neural information processing. In particular, we consider the amplification and functional role of internal fluctuations. Using computer simulations of a neural network model of the olfactory cortex and hippocampus, we demonstrate how microscopic fluctuations can result in global effects at the network level. We show that the rate of information processing in associative memory tasks can be maximized for optimal noise levels, analogous to stochastic resonance phenomena. Noise can also induce transitions between different dynamical states, which could be of significance for learning and memory. A chaotic-like behavior, induced by noise or by an increase in neuronal excitability, can enhance system performance if it is transient and converges to a limit cycle memory state. We speculate whether this dynamical behavior perhaps could be related to (creative) thinking.

Neural tissue-spheres

DEFF Research Database (Denmark)

Andersen, Rikke K; Johansen, Mathias; Blaabjerg, Morten

2007-01-01

By combining new and established protocols we have developed a procedure for isolation and propagation of neural precursor cells from the forebrain subventricular zone (SVZ) of newborn rats. Small tissue blocks of the SVZ were dissected and propagated en bloc as free-floating neural tissue...... content, thus allowing experimental studies of neural precursor cells and their niche...

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

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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.

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

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

2013-01-01

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

SOX10-Nano-Lantern Reporter Human iPS Cells; A Versatile Tool for Neural Crest Research.

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Tomoko Horikiri

Full Text Available The neural crest is a source to produce multipotent neural crest stem cells that have a potential to differentiate into diverse cell types. The transcription factor SOX10 is expressed through early neural crest progenitors and stem cells in vertebrates. Here we report the generation of SOX10-Nano-lantern (NL reporter human induced pluripotent stem cells (hiPS by using CRISPR/Cas9 systems, that are beneficial to investigate the generation and maintenance of neural crest progenitor cells. SOX10-NL positive cells are produced transiently from hiPS cells by treatment with TGFβ inhibitor SB431542 and GSK3 inhibitor CHIR99021. We found that all SOX10-NL-positive cells expressed an early neural crest marker NGFR, however SOX10-NL-positive cells purified from differentiated hiPS cells progressively attenuate their NL-expression under proliferation. We therefore attempted to maintain SOX10-NL-positive cells with additional signaling on the plane and sphere culture conditions. These SOX10-NL cells provide us to investigate mass culture with neural crest cells for stem cell research.

Neural-network-directed alignment of optical systems using the laser-beam spatial filter as an example

Science.gov (United States)

Decker, Arthur J.; Krasowski, Michael J.; Weiland, Kenneth E.

1993-01-01

This report describes an effort at NASA Lewis Research Center to use artificial neural networks to automate the alignment and control of optical measurement systems. Specifically, it addresses the use of commercially available neural network software and hardware to direct alignments of the common laser-beam-smoothing spatial filter. The report presents a general approach for designing alignment records and combining these into training sets to teach optical alignment functions to neural networks and discusses the use of these training sets to train several types of neural networks. Neural network configurations used include the adaptive resonance network, the back-propagation-trained network, and the counter-propagation network. This work shows that neural networks can be used to produce robust sequencers. These sequencers can learn by example to execute the step-by-step procedures of optical alignment and also can learn adaptively to correct for environmentally induced misalignment. The long-range objective is to use neural networks to automate the alignment and operation of optical measurement systems in remote, harsh, or dangerous aerospace environments. This work also shows that when neural networks are trained by a human operator, training sets should be recorded, training should be executed, and testing should be done in a manner that does not depend on intellectual judgments of the human operator.

Roles of bHLH genes in neural stem cell differentiation

International Nuclear Information System (INIS)

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

2005-01-01

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

Oscillatory neural representations in the sensory thalamus predict neuropathic pain relief by deep brain stimulation.

Science.gov (United States)

Huang, Yongzhi; Green, Alexander L; Hyam, Jonathan; Fitzgerald, James; Aziz, Tipu Z; Wang, Shouyan

2018-01-01

Understanding the function of sensory thalamic neural activity is essential for developing and improving interventions for neuropathic pain. However, there is a lack of investigation of the relationship between sensory thalamic oscillations and pain relief in patients with neuropathic pain. This study aims to identify the oscillatory neural characteristics correlated with pain relief induced by deep brain stimulation (DBS), and develop a quantitative model to predict pain relief by integrating characteristic measures of the neural oscillations. Measures of sensory thalamic local field potentials (LFPs) in thirteen patients with neuropathic pain were screened in three dimensional feature space according to the rhythm, balancing, and coupling neural behaviours, and correlated with pain relief. An integrated approach based on principal component analysis (PCA) and multiple regression analysis is proposed to integrate the multiple measures and provide a predictive model. This study reveals distinct thalamic rhythms of theta, alpha, high beta and high gamma oscillations correlating with pain relief. The balancing and coupling measures between these neural oscillations were also significantly correlated with pain relief. The study enriches the series research on the function of thalamic neural oscillations in neuropathic pain and relief, and provides a quantitative approach for predicting pain relief by DBS using thalamic neural oscillations. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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

2010-02-02

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

The murine homeobox gene Msx-3 shows highly restricted expression in the developing neural tube.

Science.gov (United States)

Shimeld, S M; McKay, I J; Sharpe, P T

1996-04-01

The mouse homeobox-genes Msx-1 and Msx-2 are expressed in several areas of the developing embryo, including the neural tube, neural crest, facial processes and limb buds. Here we report the characterisation of a third mouse Msx gene, which we designate Msx-3. The embryonic expression of Msx-3 was found to differ from that of Msx-1 and -2 in that it was confined to the dorsal neural tube. In embryos with 5-8 somites a segmental pattern of expression was observed in the hindbrain, with rhombomeres 3 and 5 lacking Msx-3 while other rhombomeres expressed Msx-3. This pattern was transient, however, such that in embryos with 18 or more somites expression was continuous throughout the dorsal hindbrain and anterior dorsal spinal cord. Differentiation of dorsal cell types in the neural tube can be induced by addition of members of the Tgf-beta family. Additionally, Msx-1 and -2 have been shown to be activated by addition of the Tgf-beta family member Bmp-4. To determine if Bmp-4 could activate Msx-3, we incubated embryonic hindbrain explants with exogenous Bmp-4. The dorsal expression of Msx-3 was seen to expand into more ventral regions of the neurectoderm in Bmp-4-treated cultures, implying that Bmp-4 may be able to mimic an in vivo signal that induces Msx-3.

Possible Roles of Neural Electron Spin Networks in Memory and Consciousness

CERN Document Server

Hu, H P

2004-01-01

Spin is the origin of quantum effects in both Bohm and Hestenes quantum formulism and a fundamental quantum process associated with the structure of space-time. Thus, we have recently theorized that spin is the mind-pixel and developed a qualitative model of consciousness based on nuclear spins inside neural membranes and proteins. In this paper, we explore the possibility of unpaired electron spins being the mind-pixels. Besides free O2 and NO, the main sources of unpaired electron spins in neural membranes and proteins are transition metal ions and O2 and NO bound/absorbed to large molecules, free radicals produced through biochemical reactions and excited molecular triplet states induced by fluctuating internal magnetic fields. We show that unpaired electron spin networks inside neural membranes and proteins are modulated by action potentials through exchange and dipolar coupling tensors and spin-orbital coupling and g-factor tensors and perturbed by microscopically strong and fluctuating internal magnetic...

Nanosized zinc oxide particles induce neural stem cell apoptosis

International Nuclear Information System (INIS)

Deng Xiaoyong; Luan Qixia; Wu Minghong; Zhang Haijiao; Jiao Zheng; Chen Wenting; Wang Yanli

2009-01-01

Given the intensive application of nanoscale zinc oxide (ZnO) materials in our life, growing concerns have arisen about its unintentional health and environmental impacts. In this study, the neurotoxicity of different sized ZnO nanoparticles in mouse neural stem cells (NSCs) was investigated. A cell viability assay indicated that ZnO nanoparticles manifested dose-dependent, but no size-dependent toxic effects on NSCs. Apoptotic cells were observed and analyzed by confocal microscopy, transmission electron microscopy examination, and flow cytometry. All the results support the viewpoint that the ZnO nanoparticle toxicity comes from the dissolved Zn 2+ in the culture medium or inside cells. Our results highlight the need for caution during the use and disposal of ZnO manufactured nanomaterials to prevent the unintended environmental and health impacts.

Relative cortico-subcortical shift in brain activity but preserved training-induced neural modulation in older adults during bimanual motor learning.

Science.gov (United States)

Santos Monteiro, Thiago; Beets, Iseult A M; Boisgontier, Matthieu P; Gooijers, Jolien; Pauwels, Lisa; Chalavi, Sima; King, Brad; Albouy, Geneviève; Swinnen, Stephan P

2017-10-01

To study age-related differences in neural activation during motor learning, functional magnetic resonance imaging scans were acquired from 25 young (mean 21.5-year old) and 18 older adults (mean 68.6-year old) while performing a bimanual coordination task before (pretest) and after (posttest) a 2-week training intervention on the task. We studied whether task-related brain activity and training-induced brain activation changes differed between age groups, particularly with respect to the hyperactivation typically observed in older adults. Findings revealed that older adults showed lower performance levels than younger adults but similar learning capability. At the cerebral level, the task-related hyperactivation in parietofrontal areas and underactivation in subcortical areas observed in older adults were not differentially modulated by the training intervention. However, brain activity related to task planning and execution decreased from pretest to posttest in temporo-parieto-frontal areas and subcortical areas in both age groups, suggesting similar processes of enhanced activation efficiency with advanced skill level. Furthermore, older adults who displayed higher activity in prefrontal regions at pretest demonstrated larger training-induced performance gains. In conclusion, in spite of prominent age-related brain activation differences during movement planning and execution, the mechanisms of learning-related reduction of brain activation appear to be similar in both groups. Importantly, cerebral activity during early learning can differentially predict the amplitude of the training-induced performance benefit between young and older adults. Copyright © 2017 Elsevier Inc. All rights reserved.

A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination.

Science.gov (United States)

Zhao, Chunnian; Sun, GuoQiang; Li, Shengxiu; Shi, Yanhong

2009-04-01

MicroRNAs have been implicated as having important roles in stem cell biology. MicroRNA-9 (miR-9) is expressed specifically in neurogenic areas of the brain and may be involved in neural stem cell self-renewal and differentiation. We showed previously that the nuclear receptor TLX is an essential regulator of neural stem cell self-renewal. Here we show that miR-9 suppresses TLX expression to negatively regulate neural stem cell proliferation and accelerate neural differentiation. Introducing a TLX expression vector that is not prone to miR-9 regulation rescued miR-9-induced proliferation deficiency and inhibited precocious differentiation. In utero electroporation of miR-9 in embryonic brains led to premature differentiation and outward migration of the transfected neural stem cells. Moreover, TLX represses expression of the miR-9 pri-miRNA. By forming a negative regulatory loop with TLX, miR-9 provides a model for controlling the balance between neural stem cell proliferation and differentiation.

GBM secretome induces transient transformation of human neural precursor cells.

Science.gov (United States)

Venugopal, Chitra; Wang, X Simon; Manoranjan, Branavan; McFarlane, Nicole; Nolte, Sara; Li, Meredith; Murty, Naresh; Siu, K W Michael; Singh, Sheila K

2012-09-01

Glioblastoma (GBM) is the most aggressive primary brain tumor in humans, with a uniformly poor prognosis. The tumor microenvironment is composed of both supportive cellular substrates and exogenous factors. We hypothesize that exogenous factors secreted by brain tumor initiating cells (BTICs) could predispose normal neural precursor cells (NPCs) to transformation. When NPCs are grown in GBM-conditioned media, and designated as "tumor-conditioned NPCs" (tcNPCs), they become highly proliferative and exhibit increased stem cell self-renewal, or the unique ability of stem cells to asymmetrically generate another stem cell and a daughter cell. tcNPCs also show an increased transcript level of stem cell markers such as CD133 and ALDH and growth factor receptors such as VEGFR1, VEGFR2, EGFR and PDGFRα. Media analysis by ELISA of GBM-conditioned media reveals an elevated secretion of growth factors such as EGF, VEGF and PDGF-AA when compared to normal neural stem cell-conditioned media. We also demonstrate that tcNPCs require prolonged or continuous exposure to the GBM secretome in vitro to retain GBM BTIC characteristics. Our in vivo studies reveal that tcNPCs are unable to form tumors, confirming that irreversible transformation events may require sustained or prolonged presence of the GBM secretome. Analysis of GBM-conditioned media by mass spectrometry reveals the presence of secreted proteins Chitinase-3-like 1 (CHI3L1) and H2A histone family member H2AX. Collectively, our data suggest that GBM-secreted factors are capable of transiently altering normal NPCs, although for retention of the transformed phenotype, sustained or prolonged secretome exposure or additional transformation events are likely necessary.

Mechanisms of Virus-Induced Neural Cell Death

National Research Council Canada - National Science Library

Tyler, Kenneth

2002-01-01

Virtually all known neurotropic viruses are capable of killing infected cells by inducing a specific pattern of cell death known as apoptosis, yet the mechanism by which this occurs and its relevance...

miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells.

Science.gov (United States)

Sun, GuoQiang; Ye, Peng; Murai, Kiyohito; Lang, Ming-Fei; Li, Shengxiu; Zhang, Heying; Li, Wendong; Fu, Chelsea; Yin, Jason; Wang, Allen; Ma, Xiaoxiao; Shi, Yanhong

2011-11-08

miR-137 is a brain-enriched microRNA. Its role in neural development remains unknown. Here we show that miR-137 has an essential role in controlling embryonic neural stem cell fate determination. miR-137 negatively regulates cell proliferation and accelerates neural differentiation of embryonic neural stem cells. In addition, we show that the histone lysine-specific demethylase 1 (LSD1), a transcriptional co-repressor of nuclear receptor TLX, is a downstream target of miR-137. In utero electroporation of miR-137 in embryonic mouse brains led to premature differentiation and outward migration of the transfected cells. Introducing a LSD1 expression vector lacking the miR-137 recognition site rescued miR-137-induced precocious differentiation. Furthermore, we demonstrate that TLX, an essential regulator of neural stem cell self-renewal, represses the expression of miR-137 by recruiting LSD1 to the genomic regions of miR-137. Thus, miR-137 forms a feedback regulatory loop with TLX and LSD1 to control the dynamics between neural stem cell proliferation and differentiation during neural development.

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.

Asymmetric continuous-time neural networks without local traps for solving constraint satisfaction problems.

Directory of Open Access Journals (Sweden)

Botond Molnár

Full Text Available There has been a long history of using neural networks for combinatorial optimization and constraint satisfaction problems. Symmetric Hopfield networks and similar approaches use steepest descent dynamics, and they always converge to the closest local minimum of the energy landscape. For finding global minima additional parameter-sensitive techniques are used, such as classical simulated annealing or the so-called chaotic simulated annealing, which induces chaotic dynamics by addition of extra terms to the energy landscape. Here we show that asymmetric continuous-time neural networks can solve constraint satisfaction problems without getting trapped in non-solution attractors. We concentrate on a model solving Boolean satisfiability (k-SAT, which is a quintessential NP-complete problem. There is a one-to-one correspondence between the stable fixed points of the neural network and the k-SAT solutions and we present numerical evidence that limit cycles may also be avoided by appropriately choosing the parameters of the model. This optimal parameter region is fairly independent of the size and hardness of instances, this way parameters can be chosen independently of the properties of problems and no tuning is required during the dynamical process. The model is similar to cellular neural networks already used in CNN computers. On an analog device solving a SAT problem would take a single operation: the connection weights are determined by the k-SAT instance and starting from any initial condition the system searches until finding a solution. In this new approach transient chaotic behavior appears as a natural consequence of optimization hardness and not as an externally induced effect.

Neural networks for aircraft control

Science.gov (United States)

Linse, Dennis

1990-01-01

Current research in Artificial Neural Networks indicates that networks offer some potential advantages in adaptation and fault tolerance. This research is directed at determining the possible applicability of neural networks to aircraft control. The first application will be to aircraft trim. Neural network node characteristics, network topology and operation, neural network learning and example histories using neighboring optimal control with a neural net are discussed.

Neural plasticity expressed in central auditory structures with and without tinnitus

Directory of Open Access Journals (Sweden)

Larry E Roberts

2012-05-01

Full Text Available Sensory training therapies for tinnitus are based on the assumption that, notwithstanding neural changes related to tinnitus, auditory training can alter the response properties of neurons in auditory pathways. To address this question, we investigated whether brain changes induced by sensory training in tinnitus sufferers and measured by EEG are similar to those induced in age and hearing loss matched individuals without tinnitus trained on the same auditory task. Auditory training was given using a 5 kHz 40-Hz amplitude-modulated sound that was in the tinnitus frequency region of the tinnitus subjects and enabled extraction of the 40-Hz auditory steady-state response (ASSR and P2 transient response known to localize to primary and nonprimary auditory cortex, respectively. P2 amplitude increased with training equally in participants with tinnitus and in control subjects, suggesting normal remodeling of nonprimary auditory regions in tinnitus. However, training-induced changes in the ASSR differed between the tinnitus and control groups. In controls ASSR phase advanced toward the stimulus waveform by about ten degrees over training, in agreement with previous results obtained in young normal hearing individuals. However, ASSR phase did not change significantly with training in the tinnitus group, although some participants showed phase shifts resembling controls. On the other hand, ASSR amplitude increased with training in the tinnitus group, whereas in controls this response (which is difficult to remodel in young normal hearing subjects did not change with training. These results suggest that neural changes related to tinnitus altered how neural plasticity was expressed in the region of primary but not nonprimary auditory cortex. Auditory training did not reduce tinnitus loudness although a small effect on the tinnitus spectrum was detected.

Response variance in functional maps: neural darwinism revisited.

Directory of Open Access Journals (Sweden)

Hirokazu Takahashi

Full Text Available The mechanisms by which functional maps and map plasticity contribute to cortical computation remain controversial. Recent studies have revisited the theory of neural Darwinism to interpret the learning-induced map plasticity and neuronal heterogeneity observed in the cortex. Here, we hypothesize that the Darwinian principle provides a substrate to explain the relationship between neuron heterogeneity and cortical functional maps. We demonstrate in the rat auditory cortex that the degree of response variance is closely correlated with the size of its representational area. Further, we show that the response variance within a given population is altered through training. These results suggest that larger representational areas may help to accommodate heterogeneous populations of neurons. Thus, functional maps and map plasticity are likely to play essential roles in Darwinian computation, serving as effective, but not absolutely necessary, structures to generate diverse response properties within a neural population.

Response variance in functional maps: neural darwinism revisited.

Science.gov (United States)

Takahashi, Hirokazu; Yokota, Ryo; Kanzaki, Ryohei

2013-01-01

The mechanisms by which functional maps and map plasticity contribute to cortical computation remain controversial. Recent studies have revisited the theory of neural Darwinism to interpret the learning-induced map plasticity and neuronal heterogeneity observed in the cortex. Here, we hypothesize that the Darwinian principle provides a substrate to explain the relationship between neuron heterogeneity and cortical functional maps. We demonstrate in the rat auditory cortex that the degree of response variance is closely correlated with the size of its representational area. Further, we show that the response variance within a given population is altered through training. These results suggest that larger representational areas may help to accommodate heterogeneous populations of neurons. Thus, functional maps and map plasticity are likely to play essential roles in Darwinian computation, serving as effective, but not absolutely necessary, structures to generate diverse response properties within a neural population.

Notch signaling patterns neurogenic ectoderm and regulates the asymmetric division of neural progenitors in sea urchin embryos.

Science.gov (United States)

Mellott, Dan O; Thisdelle, Jordan; Burke, Robert D

2017-10-01

We have examined regulation of neurogenesis by Delta/Notch signaling in sea urchin embryos. At gastrulation, neural progenitors enter S phase coincident with expression of Sp-SoxC. We used a BAC containing GFP knocked into the Sp-SoxC locus to label neural progenitors. Live imaging and immunolocalizations indicate that Sp-SoxC-expressing cells divide to produce pairs of adjacent cells expressing GFP. Over an interval of about 6 h, one cell fragments, undergoes apoptosis and expresses high levels of activated Caspase3. A Notch reporter indicates that Notch signaling is activated in cells adjacent to cells expressing Sp-SoxC. Inhibition of γ-secretase, injection of Sp-Delta morpholinos or CRISPR/Cas9-induced mutation of Sp-Delta results in supernumerary neural progenitors and neurons. Interfering with Notch signaling increases neural progenitor recruitment and pairs of neural progenitors. Thus, Notch signaling restricts the number of neural progenitors recruited and regulates the fate of progeny of the asymmetric division. We propose a model in which localized signaling converts ectodermal and ciliary band cells to neural progenitors that divide asymmetrically to produce a neural precursor and an apoptotic cell. © 2017. Published by The Company of Biologists Ltd.

Enhancement of signal sensitivity in a heterogeneous neural network refined from synaptic plasticity

Energy Technology Data Exchange (ETDEWEB)

Li Xiumin; Small, Michael, E-mail: ensmall@polyu.edu.h, E-mail: 07901216r@eie.polyu.edu.h [Department of Electronic and Information Engineering, Hong Kong Polytechnic University, Hung Hom, Kowloon (Hong Kong)

2010-08-15

Long-term synaptic plasticity induced by neural activity is of great importance in informing the formation of neural connectivity and the development of the nervous system. It is reasonable to consider self-organized neural networks instead of prior imposition of a specific topology. In this paper, we propose a novel network evolved from two stages of the learning process, which are respectively guided by two experimentally observed synaptic plasticity rules, i.e. the spike-timing-dependent plasticity (STDP) mechanism and the burst-timing-dependent plasticity (BTDP) mechanism. Due to the existence of heterogeneity in neurons that exhibit different degrees of excitability, a two-level hierarchical structure is obtained after the synaptic refinement. This self-organized network shows higher sensitivity to afferent current injection compared with alternative archetypal networks with different neural connectivity. Statistical analysis also demonstrates that it has the small-world properties of small shortest path length and high clustering coefficients. Thus the selectively refined connectivity enhances the ability of neuronal communications and improves the efficiency of signal transmission in the network.

Enhancement of signal sensitivity in a heterogeneous neural network refined from synaptic plasticity

International Nuclear Information System (INIS)

Li Xiumin; Small, Michael

2010-01-01

Long-term synaptic plasticity induced by neural activity is of great importance in informing the formation of neural connectivity and the development of the nervous system. It is reasonable to consider self-organized neural networks instead of prior imposition of a specific topology. In this paper, we propose a novel network evolved from two stages of the learning process, which are respectively guided by two experimentally observed synaptic plasticity rules, i.e. the spike-timing-dependent plasticity (STDP) mechanism and the burst-timing-dependent plasticity (BTDP) mechanism. Due to the existence of heterogeneity in neurons that exhibit different degrees of excitability, a two-level hierarchical structure is obtained after the synaptic refinement. This self-organized network shows higher sensitivity to afferent current injection compared with alternative archetypal networks with different neural connectivity. Statistical analysis also demonstrates that it has the small-world properties of small shortest path length and high clustering coefficients. Thus the selectively refined connectivity enhances the ability of neuronal communications and improves the efficiency of signal transmission in the network.

GH mediates exercise-dependent activation of SVZ neural precursor cells in aged mice.

Directory of Open Access Journals (Sweden)

Daniel G Blackmore

Full Text Available Here we demonstrate, both in vivo and in vitro, that growth hormone (GH mediates precursor cell activation in the subventricular zone (SVZ of the aged (12-month-old brain following exercise, and that GH signaling stimulates precursor activation to a similar extent to exercise. Our results reveal that both addition of GH in culture and direct intracerebroventricular infusion of GH stimulate neural precursor cells in the aged brain. In contrast, no increase in neurosphere numbers was observed in GH receptor null animals following exercise. Continuous infusion of a GH antagonist into the lateral ventricle of wild-type animals completely abolished the exercise-induced increase in neural precursor cell number. Given that the aged brain does not recover well after injury, we investigated the direct effect of exercise and GH on neural precursor cell activation following irradiation. This revealed that physical exercise as well as infusion of GH promoted repopulation of neural precursor cells in irradiated aged animals. Conversely, infusion of a GH antagonist during exercise prevented recovery of precursor cells in the SVZ following irradiation.

GH Mediates Exercise-Dependent Activation of SVZ Neural Precursor Cells in Aged Mice

Science.gov (United States)

Blackmore, Daniel G.; Vukovic, Jana; Waters, Michael J.; Bartlett, Perry F.

2012-01-01

Here we demonstrate, both in vivo and in vitro, that growth hormone (GH) mediates precursor cell activation in the subventricular zone (SVZ) of the aged (12-month-old) brain following exercise, and that GH signaling stimulates precursor activation to a similar extent to exercise. Our results reveal that both addition of GH in culture and direct intracerebroventricular infusion of GH stimulate neural precursor cells in the aged brain. In contrast, no increase in neurosphere numbers was observed in GH receptor null animals following exercise. Continuous infusion of a GH antagonist into the lateral ventricle of wild-type animals completely abolished the exercise-induced increase in neural precursor cell number. Given that the aged brain does not recover well after injury, we investigated the direct effect of exercise and GH on neural precursor cell activation following irradiation. This revealed that physical exercise as well as infusion of GH promoted repopulation of neural precursor cells in irradiated aged animals. Conversely, infusion of a GH antagonist during exercise prevented recovery of precursor cells in the SVZ following irradiation. PMID:23209615

Visual awareness suppression by pre-stimulus brain stimulation; a neural effect.

Science.gov (United States)

Jacobs, Christianne; Goebel, Rainer; Sack, Alexander T

2012-01-02

Transcranial magnetic stimulation (TMS) has established the functional relevance of early visual cortex (EVC) for visual awareness with great temporal specificity non-invasively in conscious human volunteers. Many studies have found a suppressive effect when TMS was applied over EVC 80-100 ms after the onset of the visual stimulus (post-stimulus TMS time window). Yet, few studies found task performance to also suffer when TMS was applied even before visual stimulus presentation (pre-stimulus TMS time window). This pre-stimulus TMS effect, however, remains controversially debated and its origin had mainly been ascribed to TMS-induced eye-blinking artifacts. Here, we applied chronometric TMS over EVC during the execution of a visual discrimination task, covering an exhaustive range of visual stimulus-locked TMS time windows ranging from -80 pre-stimulus to 300 ms post-stimulus onset. Electrooculographical (EoG) recordings, sham TMS stimulation, and vertex TMS stimulation controlled for different types of non-neural TMS effects. Our findings clearly reveal TMS-induced masking effects for both pre- and post-stimulus time windows, and for both objective visual discrimination performance and subjective visibility. Importantly, all effects proved to be still present after post hoc removal of eye blink trials, suggesting a neural origin for the pre-stimulus TMS suppression effect on visual awareness. We speculate based on our data that TMS exerts its pre-stimulus effect via generation of a neural state which interacts with subsequent visual input. Copyright © 2011 Elsevier Inc. All rights reserved.

Characterization of the central neural projections to brown, white, and beige adipose tissue.

Science.gov (United States)

Wiedmann, Nicole M; Stefanidis, Aneta; Oldfield, Brian J

2017-11-01

The functional recruitment of classic brown adipose tissue (BAT) and inducible brown-like or beige fat is, to a large extent, dependent on intact sympathetic neural input. Whereas the central neural circuits directed specifically to BAT or white adipose tissue (WAT) are well established, there is only a developing insight into the nature of neural inputs common to both fat types. Moreover, there is no clear view of the specific central and peripheral innervation of the browned component of WAT: beige fat. The objective of the present study is to examine the neural input to both BAT and WAT in the same animal and, by exposing different cohorts of rats to either thermoneutral or cold conditions, define changes in central neural organization that will ensure that beige fat is appropriately recruited and modulated after browning of inguinal WAT (iWAT). At thermoneutrality, injection of the neurotropic (pseudorabies) viruses into BAT and WAT demonstrates that there are dedicated axonal projections, as well as collateral axonal branches of command neurons projecting to both types of fat. After cold exposure, central neural circuits directed to iWAT showed evidence of reorganization with a greater representation of command neurons projecting to both brown and beiged WAT in hypothalamic (paraventricular nucleus and lateral hypothalamus) and brainstem (raphe pallidus and locus coeruleus) sites. This shift was driven by a greater number of supraspinal neurons projecting to iWAT under cold conditions. These data provide evidence for a reorganization of the nervous system at the level of neural connectivity following browning of WAT.-Wiedmann, N. M., Stefanidis, A., Oldfield, B. J. Characterization of the central neural projections to brown, white, and beige adipose tissue. © FASEB.

Application of neural networks and neutron noise for diagnostics of reactor internals vibration

International Nuclear Information System (INIS)

Garis, N.S.; Pazsit, I.; Gloeckler, O.

1995-01-01

It has long been known that vibration of reactor internals, in particular excessive vibrations of control rods, can be detected via the neutron noise they induce. Noise measurements are actually suitable to determine important diagnostic parameters such as the location of the vibrating rod and the vibration amplitude. An algorithm was earlier elaborated for this purpose, which is based on inversion of the expression describing the neutron noise as a function of vibration parameters. This inversion procedure is nevertheless complicated and not always unique. It was investigated whether a properly trained neural network can perform the inversion more effectively. It was found that artificial neural networks can be trained effectively to perform vibration diagnostics from neutron noise data fast, effectively and reliably. The present paper gives a description of the development and use of the neural networks for purposes of vibration diagnostics

Neural network regulation driven by autonomous neural firings

Science.gov (United States)

Cho, Myoung Won

2016-07-01

Biological neurons naturally fire spontaneously due to the existence of a noisy current. Such autonomous firings may provide a driving force for network formation because synaptic connections can be modified due to neural firings. Here, we study the effect of autonomous firings on network formation. For the temporally asymmetric Hebbian learning, bidirectional connections lose their balance easily and become unidirectional ones. Defining the difference between reciprocal connections as new variables, we could express the learning dynamics as if Ising model spins interact with each other in magnetism. We present a theoretical method to estimate the interaction between the new variables in a neural system. We apply the method to some network systems and find some tendencies of autonomous neural network regulation.

FOXOs modulate proteasome activity in human-induced pluripotent stem cells of Huntington's disease and their derived neural cells.

Science.gov (United States)

Liu, Yanying; Qiao, Fangfang; Leiferman, Patricia C; Ross, Alan; Schlenker, Evelyn H; Wang, Hongmin

2017-11-15

Although it has been speculated that proteasome dysfunction may contribute to the pathogenesis of Huntington's disease (HD), a devastating neurodegenerative disorder, how proteasome activity is regulated in HD affected stem cells and somatic cells remains largely unclear. To better understand the pathogenesis of HD, we analyzed proteasome activity and the expression of FOXO transcription factors in three wild-type (WT) and three HD induced-pluripotent stem cell (iPSC) lines. HD iPSCs exhibited elevated proteasome activity and higher levels of FOXO1 and FOXO4 proteins. Knockdown of FOXO4 but not FOXO1 expression decreased proteasome activity. Following neural differentiation, the HD-iPSC-derived neural progenitor cells (NPCs) demonstrated lower levels of proteasome activity and FOXO expressions than their WT counterparts. More importantly, overexpression of FOXO4 but not FOXO1 in HD NPCs dramatically enhanced proteasome activity. When HD NPCs were further differentiated into DARPP32-positive neurons, these HD neurons were more susceptible to death than WT neurons and formed Htt aggregates under the condition of oxidative stress. Similar to HD NPCs, HD-iPSC-derived neurons showed reduced proteasome activity and diminished FOXO4 expression compared to WT-iPSC-derived neurons. Furthermore, HD iPSCs had lower AKT activities than WT iPSCs, whereas the neurons derived from HD iPSC had higher AKT activities than their WT counterparts. Inhibiting AKT activity increased both FOXO4 level and proteasome activity, indicating a potential role of AKT in regulating FOXO levels. These data suggest that FOXOs modulate proteasome activity, and thus represents a potentially valuable therapeutic target for HD. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dynamics of neural cryptography.

Science.gov (United States)

Ruttor, Andreas; Kinzel, Wolfgang; Kanter, Ido

2007-05-01

Synchronization of neural networks has been used for public channel protocols in cryptography. In the case of tree parity machines the dynamics of both bidirectional synchronization and unidirectional learning is driven by attractive and repulsive stochastic forces. Thus it can be described well by a random walk model for the overlap between participating neural networks. For that purpose transition probabilities and scaling laws for the step sizes are derived analytically. Both these calculations as well as numerical simulations show that bidirectional interaction leads to full synchronization on average. In contrast, successful learning is only possible by means of fluctuations. Consequently, synchronization is much faster than learning, which is essential for the security of the neural key-exchange protocol. However, this qualitative difference between bidirectional and unidirectional interaction vanishes if tree parity machines with more than three hidden units are used, so that those neural networks are not suitable for neural cryptography. In addition, the effective number of keys which can be generated by the neural key-exchange protocol is calculated using the entropy of the weight distribution. As this quantity increases exponentially with the system size, brute-force attacks on neural cryptography can easily be made unfeasible.

Dynamics of neural cryptography

International Nuclear Information System (INIS)

Ruttor, Andreas; Kinzel, Wolfgang; Kanter, Ido

2007-01-01

Synchronization of neural networks has been used for public channel protocols in cryptography. In the case of tree parity machines the dynamics of both bidirectional synchronization and unidirectional learning is driven by attractive and repulsive stochastic forces. Thus it can be described well by a random walk model for the overlap between participating neural networks. For that purpose transition probabilities and scaling laws for the step sizes are derived analytically. Both these calculations as well as numerical simulations show that bidirectional interaction leads to full synchronization on average. In contrast, successful learning is only possible by means of fluctuations. Consequently, synchronization is much faster than learning, which is essential for the security of the neural key-exchange protocol. However, this qualitative difference between bidirectional and unidirectional interaction vanishes if tree parity machines with more than three hidden units are used, so that those neural networks are not suitable for neural cryptography. In addition, the effective number of keys which can be generated by the neural key-exchange protocol is calculated using the entropy of the weight distribution. As this quantity increases exponentially with the system size, brute-force attacks on neural cryptography can easily be made unfeasible

Dynamics of neural cryptography

Science.gov (United States)

Ruttor, Andreas; Kinzel, Wolfgang; Kanter, Ido

2007-05-01

Synchronization of neural networks has been used for public channel protocols in cryptography. In the case of tree parity machines the dynamics of both bidirectional synchronization and unidirectional learning is driven by attractive and repulsive stochastic forces. Thus it can be described well by a random walk model for the overlap between participating neural networks. For that purpose transition probabilities and scaling laws for the step sizes are derived analytically. Both these calculations as well as numerical simulations show that bidirectional interaction leads to full synchronization on average. In contrast, successful learning is only possible by means of fluctuations. Consequently, synchronization is much faster than learning, which is essential for the security of the neural key-exchange protocol. However, this qualitative difference between bidirectional and unidirectional interaction vanishes if tree parity machines with more than three hidden units are used, so that those neural networks are not suitable for neural cryptography. In addition, the effective number of keys which can be generated by the neural key-exchange protocol is calculated using the entropy of the weight distribution. As this quantity increases exponentially with the system size, brute-force attacks on neural cryptography can easily be made unfeasible.

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

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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.

Toward a neural chronometry for the aesthetic experience of music.

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Brattico, Elvira; Bogert, Brigitte; Jacobsen, Thomas

2013-01-01

Music is often studied as a cognitive domain alongside language. The emotional aspects of music have also been shown to be important, but views on their nature diverge. For instance, the specific emotions that music induces and how they relate to emotional expression are still under debate. Here we propose a mental and neural chronometry of the aesthetic experience of music initiated and mediated by external and internal contexts such as intentionality, background mood, attention, and expertise. The initial stages necessary for an aesthetic experience of music are feature analysis, integration across modalities, and cognitive processing on the basis of long-term knowledge. These stages are common to individuals belonging to the same musical culture. The initial emotional reactions to music include the startle reflex, core "liking," and arousal. Subsequently, discrete emotions are perceived and induced. Presumably somatomotor processes synchronizing the body with the music also come into play here. The subsequent stages, in which cognitive, affective, and decisional processes intermingle, require controlled cross-modal neural processes to result in aesthetic emotions, aesthetic judgments, and conscious liking. These latter aesthetic stages often require attention, intentionality, and expertise for their full actualization.

Shakeout: A New Approach to Regularized Deep Neural Network Training.

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Kang, Guoliang; Li, Jun; Tao, Dacheng

2018-05-01

Recent years have witnessed the success of deep neural networks in dealing with a plenty of practical problems. Dropout has played an essential role in many successful deep neural networks, by inducing regularization in the model training. In this paper, we present a new regularized training approach: Shakeout. Instead of randomly discarding units as Dropout does at the training stage, Shakeout randomly chooses to enhance or reverse each unit's contribution to the next layer. This minor modification of Dropout has the statistical trait: the regularizer induced by Shakeout adaptively combines , and regularization terms. Our classification experiments with representative deep architectures on image datasets MNIST, CIFAR-10 and ImageNet show that Shakeout deals with over-fitting effectively and outperforms Dropout. We empirically demonstrate that Shakeout leads to sparser weights under both unsupervised and supervised settings. Shakeout also leads to the grouping effect of the input units in a layer. Considering the weights in reflecting the importance of connections, Shakeout is superior to Dropout, which is valuable for the deep model compression. Moreover, we demonstrate that Shakeout can effectively reduce the instability of the training process of the deep architecture.

Toward a Neural Chronometry for the Aesthetic Experience of Music

Science.gov (United States)

Brattico, Elvira; Bogert, Brigitte; Jacobsen, Thomas

2013-01-01

Music is often studied as a cognitive domain alongside language. The emotional aspects of music have also been shown to be important, but views on their nature diverge. For instance, the specific emotions that music induces and how they relate to emotional expression are still under debate. Here we propose a mental and neural chronometry of the aesthetic experience of music initiated and mediated by external and internal contexts such as intentionality, background mood, attention, and expertise. The initial stages necessary for an aesthetic experience of music are feature analysis, integration across modalities, and cognitive processing on the basis of long-term knowledge. These stages are common to individuals belonging to the same musical culture. The initial emotional reactions to music include the startle reflex, core “liking,” and arousal. Subsequently, discrete emotions are perceived and induced. Presumably somatomotor processes synchronizing the body with the music also come into play here. The subsequent stages, in which cognitive, affective, and decisional processes intermingle, require controlled cross-modal neural processes to result in aesthetic emotions, aesthetic judgments, and conscious liking. These latter aesthetic stages often require attention, intentionality, and expertise for their full actualization. PMID:23641223

Bioprinting for Neural Tissue Engineering.

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Knowlton, Stephanie; Anand, Shivesh; Shah, Twisha; Tasoglu, Savas

2018-01-01

Bioprinting is a method by which a cell-encapsulating bioink is patterned to create complex tissue architectures. Given the potential impact of this technology on neural research, we review the current state-of-the-art approaches for bioprinting neural tissues. While 2D neural cultures are ubiquitous for studying neural cells, 3D cultures can more accurately replicate the microenvironment of neural tissues. By bioprinting neuronal constructs, one can precisely control the microenvironment by specifically formulating the bioink for neural tissues, and by spatially patterning cell types and scaffold properties in three dimensions. We review a range of bioprinted neural tissue models and discuss how they can be used to observe how neurons behave, understand disease processes, develop new therapies and, ultimately, design replacement tissues. Copyright © 2017 Elsevier Ltd. All rights reserved.

A population of serumdeprivation-induced bone marrow stem cells (SD-BMSC) expresses marker typical for embryonic and neural stem cells

International Nuclear Information System (INIS)

Sauerzweig, Steven; Munsch, Thomas; Lessmann, Volkmar; Reymann, Klaus G.; Braun, Holger

2009-01-01

The bone marrow represents an easy accessible source of adult stem cells suitable for various cell based therapies. Several studies in recent years suggested the existence of pluripotent stem cells within bone marrow stem cells (BMSC) expressing marker proteins of both embryonic and tissue committed stem cells. These subpopulations were referred to as MAPC, MIAMI and VSEL-cells. Here we describe SD-BMSC (serumdeprivation-induced BMSC) which are induced as a distinct subpopulation after complete serumdeprivation. SD-BMSC are generated from small-sized nestin-positive BMSC (S-BMSC) organized as round-shaped cells in the top layer of BMSC-cultures. The generation of SD-BMSC is caused by a selective proliferation of S-BMSC and accompanied by changes in both morphology and gene expression. SD-BMSC up-regulate not only markers typical for neural stem cells like nestin and GFAP, but also proteins characteristic for embryonic cells like Oct4 and SOX2. We hypothesize, that SD-BMSC like MAPC, MIAMI and VSEL-cells represent derivatives from a single pluripotent stem cell fraction within BMSC exhibiting characteristics of embryonic and tissue committed stem cells. The complete removal of serum might offer a simple way to specifically enrich this fraction of pluripotent embryonic like stem cells in BMSC cultures

The development of a PZT-based microdrive for neural signal recording

International Nuclear Information System (INIS)

Park, Sangkyu; Yoon, Euisung; Park, Sukho; Lee, Sukchan; Shin, Hee-sup; Park, Hyunjun; Kim, Byungkyu; Kim, Daesoo; Park, Jongoh

2008-01-01

A hand-controlled microdrive has been used to obtain neural signals from rodents such as rats and mice. However, it places severe physical stress on the rodents during its manipulation, and this stress leads to alertness in the mice and low efficiency in obtaining neural signals from the mice. To overcome this issue, we developed a novel microdrive, which allows one to adjust the electrodes by a piezoelectric device (PZT) with high precision. Its mass is light enough to install on the mouse's head. The proposed microdrive has three H-type PZT actuators and their guiding structure. The operation principle of the microdrive is based on the well known inchworm mechanism. When the three PZT actuators are synchronized, linear motion of the electrode is produced along the guiding structure. The electrodes used for the recording of the neural signals from neuron cells were fixed at one of the PZT actuators. Our proposed microdrive has an accuracy of about 400 nm and a long stroke of about 5 mm. In response to formalin-induced pain, single unit activities are robustly measured at the thalamus with electrodes whose vertical depth is adjusted by the microdrive under urethane anesthesia. In addition, the microdrive was efficient in detecting neural signals from mice that were moving freely. Thus, the present study suggests that the PZT-based microdrive could be an alternative for the efficient detection of neural signals from mice during behavioral states without any stress to the mice. (technical note)

Neural regeneration protein is a novel chemoattractive and neuronal survival-promoting factor

International Nuclear Information System (INIS)

Gorba, Thorsten; Bradoo, Privahini; Antonic, Ana; Marvin, Keith; Liu, Dong-Xu; Lobie, Peter E.; Reymann, Klaus G.; Gluckman, Peter D.; Sieg, Frank

2006-01-01

Neurogenesis and neuronal migration are the prerequisites for the development of the central nervous system. We have identified a novel rodent gene encoding for a neural regeneration protein (NRP) with an activity spectrum similar to the chemokine stromal-derived factor (SDF)-1, but with much greater potency. The Nrp gene is encoded as a forward frameshift to the hypothetical alkylated DNA repair protein AlkB. The predicted protein sequence of NRP contains domains with homology to survival-promoting peptide (SPP) and the trefoil protein TFF-1. The Nrp gene is first expressed in neural stem cells and expression continues in glial lineages. Recombinant NRP and NRP-derived peptides possess biological activities including induction of neural migration and proliferation, promotion of neuronal survival, enhancement of neurite outgrowth and promotion of neuronal differentiation from neural stem cells. NRP exerts its effect on neuronal survival by phosphorylation of the ERK1/2 and Akt kinases, whereas NRP stimulation of neural migration depends solely on p44/42 MAP kinase activity. Taken together, the expression profile of Nrp, the existence in its predicted protein structure of domains with similarities to known neuroprotective and migration-inducing factors and the high potency of NRP-derived synthetic peptides acting in femtomolar concentrations suggest it to be a novel gene of relevance in cellular and developmental neurobiology

Social behaviour shapes hypothalamic neural ensemble representations of conspecific sex

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Remedios, Ryan; Kennedy, Ann; Zelikowsky, Moriel; Grewe, Benjamin F.; Schnitzer, Mark J.; Anderson, David J.

2017-10-01

All animals possess a repertoire of innate (or instinctive) behaviours, which can be performed without training. Whether such behaviours are mediated by anatomically distinct and/or genetically specified neural pathways remains unknown. Here we report that neural representations within the mouse hypothalamus, that underlie innate social behaviours, are shaped by social experience. Oestrogen receptor 1-expressing (Esr1+) neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl) control mating and fighting in rodents. We used microendoscopy to image Esr1+ neuronal activity in the VMHvl of male mice engaged in these social behaviours. In sexually and socially experienced adult males, divergent and characteristic neural ensembles represented male versus female conspecifics. However, in inexperienced adult males, male and female intruders activated overlapping neuronal populations. Sex-specific neuronal ensembles gradually separated as the mice acquired social and sexual experience. In mice permitted to investigate but not to mount or attack conspecifics, ensemble divergence did not occur. However, 30 minutes of sexual experience with a female was sufficient to promote the separation of male and female ensembles and to induce an attack response 24 h later. These observations uncover an unexpected social experience-dependent component to the formation of hypothalamic neural assemblies controlling innate social behaviours. More generally, they reveal plasticity and dynamic coding in an evolutionarily ancient deep subcortical structure that is traditionally viewed as a ‘hard-wired’ system.

Neural correlates and neural computations in posterior parietal cortex during perceptual decision-making

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Alexander eHuk

2012-10-01

Full Text Available A recent line of work has found remarkable success in relating perceptual decision-making and the spiking activity in the macaque lateral intraparietal area (LIP. In this review, we focus on questions about the neural computations in LIP that are not answered by demonstrations of neural correlates of psychological processes. We highlight three areas of limitations in our current understanding of the precise neural computations that might underlie neural correlates of decisions: (1 empirical questions not yet answered by existing data; (2 implementation issues related to how neural circuits could actually implement the mechanisms suggested by both physiology and psychology; and (3 ecological constraints related to the use of well-controlled laboratory tasks and whether they provide an accurate window on sensorimotor computation. These issues motivate the adoption of a more general encoding-decoding framework that will be fruitful for more detailed contemplation of how neural computations in LIP relate to the formation of perceptual decisions.

Transcranial magnetic stimulation and connectivity mapping: tools for studying the neural bases of brain disorders.

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Hampson, M; Hoffman, R E

2010-01-01

There has been an increasing emphasis on characterizing pathophysiology underlying psychiatric and neurological disorders in terms of altered neural connectivity and network dynamics. Transcranial magnetic stimulation (TMS) provides a unique opportunity for investigating connectivity in the human brain. TMS allows researchers and clinicians to directly stimulate cortical regions accessible to electromagnetic coils positioned on the scalp. The induced activation can then propagate through long-range connections to other brain areas. Thus, by identifying distal regions activated during TMS, researchers can infer connectivity patterns in the healthy human brain and can examine how those patterns may be disrupted in patients with different brain disorders. Conversely, connectivity maps derived using neuroimaging methods can identify components of a dysfunctional network. Nodes in this dysfunctional network accessible as targets for TMS by virtue of their proximity to the scalp may then permit TMS-induced alterations of components of the network not directly accessible to TMS via propagated effects. Thus TMS can provide a portal for accessing and altering neural dynamics in networks that are widely distributed anatomically. Finally, when long-term modulation of network dynamics is induced by trains of repetitive TMS, changes in functional connectivity patterns can be studied in parallel with changes in patient symptoms. These correlational data can elucidate neural mechanisms underlying illness and recovery. In this review, we focus on the application of these approaches to the study of psychiatric and neurological illnesses.

Transcranial magnetic stimulation and connectivity mapping: tools for studying the neural bases of brain disorders.

Directory of Open Access Journals (Sweden)

Michelle Hampson

2010-08-01

Full Text Available There has been an increasing emphasis on characterizing pathophysiology underlying psychiatric and neurological disorders in terms of altered neural connectivity and network dynamics. Transcranial magnetic stimulation (TMS provides a unique opportunity for investigating connectivity in the human brain. TMS allows researchers and clinicians to directly stimulate cortical regions accessible to electromagnetic coils positioned on the scalp. The induced activation can then propagate through long-range connections to other brain areas. Thus, by identifying distal regions activated during TMS, researchers can infer connectivity patterns in the healthy human brain and can examine how those patterns may be disrupted in patients with different brain disorders. Conversely, connectivity maps derived using neuroimaging methods can identify components of a dysfunctional network. Nodes in this dysfunctional network accessible as targets for TMS by virtue of their proximity to the scalp may then permit TMS-induced alterations of components of the network not directly accessible to TMS via propagated effects. Thus TMS can provide a portal for accessing and altering neural dynamics in networks that are widely distributed anatomically. Finally, when long-term modulation of network dynamics is induced by trains of repetitive TMS, changes in functional connectivity patterns can be studied in parallel with changes in patient symptoms. These correlational data can elucidate neural mechanisms underlying illness and recovery. In this review, we focus on the application of these approaches to the study of psychiatric and neurological illnesses.

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

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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.

Deep Learning Neural Networks and Bayesian Neural Networks in Data Analysis

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Chernoded Andrey

2017-01-01

Full Text Available Most of the modern analyses in high energy physics use signal-versus-background classification techniques of machine learning methods and neural networks in particular. Deep learning neural network is the most promising modern technique to separate signal and background and now days can be widely and successfully implemented as a part of physical analysis. In this article we compare Deep learning and Bayesian neural networks application as a classifiers in an instance of top quark analysis.

Neural Tube Defects

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Neural tube defects are birth defects of the brain, spine, or spinal cord. They happen in the ... that she is pregnant. The two most common neural tube defects are spina bifida and anencephaly. In ...

Resting-state brain activity in the motor cortex reflects task-induced activity: A multi-voxel pattern analysis.

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Kusano, Toshiki; Kurashige, Hiroki; Nambu, Isao; Moriguchi, Yoshiya; Hanakawa, Takashi; Wada, Yasuhiro; Osu, Rieko

2015-08-01

It has been suggested that resting-state brain activity reflects task-induced brain activity patterns. In this study, we examined whether neural representations of specific movements can be observed in the resting-state brain activity patterns of motor areas. First, we defined two regions of interest (ROIs) to examine brain activity associated with two different behavioral tasks. Using multi-voxel pattern analysis with regularized logistic regression, we designed a decoder to detect voxel-level neural representations corresponding to the tasks in each ROI. Next, we applied the decoder to resting-state brain activity. We found that the decoder discriminated resting-state neural activity with accuracy comparable to that associated with task-induced neural activity. The distribution of learned weighted parameters for each ROI was similar for resting-state and task-induced activities. Large weighted parameters were mainly located on conjunctive areas. Moreover, the accuracy of detection was higher than that for a decoder whose weights were randomly shuffled, indicating that the resting-state brain activity includes multi-voxel patterns similar to the neural representation for the tasks. Therefore, these results suggest that the neural representation of resting-state brain activity is more finely organized and more complex than conventionally considered.

The Neural Basis of Changing Social Norms through Persuasion

OpenAIRE

Yomogida, Yukihito; Matsumoto, Madoka; Aoki, Ryuta; Sugiura, Ayaka; Phillips, Adam N.; Matsumoto, Kenji

2017-01-01

Social norms regulate behavior, and changes in norms have a great impact on society. In most modern societies, norms change through interpersonal communication and persuasive messages found in media. Here, we examined the neural basis of persuasion-induced changes in attitude toward and away from norms using fMRI. We measured brain activity while human participants were exposed to persuasive messages directed toward specific norms. Persuasion directed toward social norms specifically activate...

Transmigration of neural stem cells across the blood brain barrier induced by glioma cells.

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Mónica Díaz-Coránguez

Full Text Available Transit of human neural stem cells, ReNcell CX, through the blood brain barrier (BBB was evaluated in an in vitro model of BBB and in nude mice. The BBB model was based on rat brain microvascular endothelial cells (RBMECs cultured on Millicell inserts bathed from the basolateral side with conditioned media (CM from astrocytes or glioma C6 cells. Glioma C6 CM induced a significant transendothelial migration of ReNcells CX in comparison to astrocyte CM. The presence in glioma C6 CM of high amounts of HGF, VEGF, zonulin and PGE2, together with the low abundance of EGF, promoted ReNcells CX transmigration. In contrast cytokines IFN-α, TNF-α, IL-12p70, IL-1β, IL-6, IL-8 and IL-10, as well as metalloproteinases -2 and -9 were present in equal amounts in glioma C6 and astrocyte CMs. ReNcells expressed the tight junction proteins occludin and claudins 1, 3 and 4, and the cell adhesion molecule CRTAM, while RBMECs expressed occludin, claudins 1 and 5 and CRTAM. Competing CRTAM mediated adhesion with soluble CRTAM, inhibited ReNcells CX transmigration, and at the sites of transmigration, the expression of occludin and claudin-5 diminished in RBMECs. In nude mice we found that ReNcells CX injected into systemic circulation passed the BBB and reached intracranial gliomas, which overexpressed HGF, VEGF and zonulin/prehaptoglobin 2.

Transmigration of neural stem cells across the blood brain barrier induced by glioma cells.

Science.gov (United States)

Díaz-Coránguez, Mónica; Segovia, José; López-Ornelas, Adolfo; Puerta-Guardo, Henry; Ludert, Juan; Chávez, Bibiana; Meraz-Cruz, Noemi; González-Mariscal, Lorenza

2013-01-01

Transit of human neural stem cells, ReNcell CX, through the blood brain barrier (BBB) was evaluated in an in vitro model of BBB and in nude mice. The BBB model was based on rat brain microvascular endothelial cells (RBMECs) cultured on Millicell inserts bathed from the basolateral side with conditioned media (CM) from astrocytes or glioma C6 cells. Glioma C6 CM induced a significant transendothelial migration of ReNcells CX in comparison to astrocyte CM. The presence in glioma C6 CM of high amounts of HGF, VEGF, zonulin and PGE2, together with the low abundance of EGF, promoted ReNcells CX transmigration. In contrast cytokines IFN-α, TNF-α, IL-12p70, IL-1β, IL-6, IL-8 and IL-10, as well as metalloproteinases -2 and -9 were present in equal amounts in glioma C6 and astrocyte CMs. ReNcells expressed the tight junction proteins occludin and claudins 1, 3 and 4, and the cell adhesion molecule CRTAM, while RBMECs expressed occludin, claudins 1 and 5 and CRTAM. Competing CRTAM mediated adhesion with soluble CRTAM, inhibited ReNcells CX transmigration, and at the sites of transmigration, the expression of occludin and claudin-5 diminished in RBMECs. In nude mice we found that ReNcells CX injected into systemic circulation passed the BBB and reached intracranial gliomas, which overexpressed HGF, VEGF and zonulin/prehaptoglobin 2.

Trichothecenes induce accumulation of glucosylceramide in neural cells by interfering with lactosylceramide synthase activity

International Nuclear Information System (INIS)

Kralj, Ana; Gurgui, Mihaela; Koenig, Gabriele M.; Echten-Deckert, Gerhild van

2007-01-01

Trichothecenes are sesquiterpenoid metabolites produced by several fungal strains that impair human and animal health. Since sphingolipids were connected with fungal toxicity the aim of the present study was to test the influence of fungal metabolites on sphingolipid metabolism in neural cells. The crude extract of fungal strain Spicellum roseum induced accumulation of glucosylceramide (GlcCer), and simultaneous reduction of the formation of lactosylceramide (LacCer) and complex gangliosides in primary cultured neurons. Following a bioassay-guided fractionation of the respective fungal extract we could demonstrate that the two isolated trichothecene derivatives, 8-deoxy-trichothecin (8-dT) and trichodermol (Td-ol) were responsible for this effect. Thus, incubation of primary cultured neurons as well as of neuroblastoma B104 cells for 24 h with 30 μM of either of the two fungal metabolites resulted in uncoupling of sphingolipid biosynthesis at the level of LacCer. For the observed reduction of LacCer synthase activity by about 90% cell integrity was crucial in both cell types. In neuroblastoma cells the amount of LacCer synthase mRNA was reduced in the presence of trichothecenes, whereas in primary cultured neurons this was not the case, suggesting a post-transcriptional mechanism of action in the latter cell type. The data also show that the compounds did not interfere with the translocation of GlcCer in neuroblastoma cells. Collectively, our results demonstrate that trichodermol and 8-deoxy-trichothecin inhibit LacCer synthase activity in a cell-type-specific manner

The neural mechanisms of re-experiencing mental fatigue sensation: a magnetoencephalography study.

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Akira Ishii

Full Text Available There have been several studies which have tried to clarify the neural mechanisms of fatigue sensation; however fatigue sensation has multiple aspects. We hypothesized that past experience related to fatigue sensation is an important factor which contributes to future formation of fatigue sensation through the transfer to memories that are located within specific brain structures. Therefore, we aimed to investigate the neural mechanisms of fatigue sensation related to memory. In the present study, we investigated the neural activity caused by re-experiencing the fatigue sensation that had been experienced during a fatigue-inducing session. Thirteen healthy volunteers participated in fatigue and non-fatigue experiments in a crossover fashion. In the fatigue experiment, they performed a 2-back test session for 40 min to induce fatigue sensation, a rest session for 15 min to recover from fatigue, and a magnetoencephalography (MEG session in which they were asked to re-experience the state of their body with fatigue that they had experienced in the 2-back test session. In the non-fatigue experiment, the participants performed a free session for 15 min, a rest session for 15 min, and an MEG session in which they were asked to re-experience the state of their body without fatigue that they had experienced in the free session. Spatial filtering analyses of oscillatory brain activity showed that the delta band power in the left Brodmann's area (BA 39, alpha band power in the right pulvinar nucleus and the left BA 40, and beta band power in the left BA 40 were lower when they re-experienced the fatigue sensation than when they re-experienced the fatigue-free sensation, indicating that these brain regions are related to re-experiencing the fatigue sensation. Our findings may help clarify the neural mechanisms underlying fatigue sensation.

The neural mechanisms of re-experiencing mental fatigue sensation: a magnetoencephalography study.

Science.gov (United States)

Ishii, Akira; Karasuyama, Takuma; Kikuchi, Taiki; Tanaka, Masaaki; Yamano, Emi; Watanabe, Yasuyoshi

2015-01-01

There have been several studies which have tried to clarify the neural mechanisms of fatigue sensation; however fatigue sensation has multiple aspects. We hypothesized that past experience related to fatigue sensation is an important factor which contributes to future formation of fatigue sensation through the transfer to memories that are located within specific brain structures. Therefore, we aimed to investigate the neural mechanisms of fatigue sensation related to memory. In the present study, we investigated the neural activity caused by re-experiencing the fatigue sensation that had been experienced during a fatigue-inducing session. Thirteen healthy volunteers participated in fatigue and non-fatigue experiments in a crossover fashion. In the fatigue experiment, they performed a 2-back test session for 40 min to induce fatigue sensation, a rest session for 15 min to recover from fatigue, and a magnetoencephalography (MEG) session in which they were asked to re-experience the state of their body with fatigue that they had experienced in the 2-back test session. In the non-fatigue experiment, the participants performed a free session for 15 min, a rest session for 15 min, and an MEG session in which they were asked to re-experience the state of their body without fatigue that they had experienced in the free session. Spatial filtering analyses of oscillatory brain activity showed that the delta band power in the left Brodmann's area (BA) 39, alpha band power in the right pulvinar nucleus and the left BA 40, and beta band power in the left BA 40 were lower when they re-experienced the fatigue sensation than when they re-experienced the fatigue-free sensation, indicating that these brain regions are related to re-experiencing the fatigue sensation. Our findings may help clarify the neural mechanisms underlying fatigue sensation.

Human neural progenitors express functional lysophospholipid receptors that regulate cell growth and morphology

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Callihan Phillip

2008-12-01

Full Text Available Abstract Background Lysophospholipids regulate the morphology and growth of neurons, neural cell lines, and neural progenitors. A stable human neural progenitor cell line is not currently available in which to study the role of lysophospholipids in human neural development. We recently established a stable, adherent human embryonic stem cell-derived neuroepithelial (hES-NEP cell line which recapitulates morphological and phenotypic features of neural progenitor cells isolated from fetal tissue. The goal of this study was to determine if hES-NEP cells express functional lysophospholipid receptors, and if activation of these receptors mediates cellular responses critical for neural development. Results Our results demonstrate that Lysophosphatidic Acid (LPA and Sphingosine-1-phosphate (S1P receptors are functionally expressed in hES-NEP cells and are coupled to multiple cellular signaling pathways. We have shown that transcript levels for S1P1 receptor increased significantly in the transition from embryonic stem cell to hES-NEP. hES-NEP cells express LPA and S1P receptors coupled to Gi/o G-proteins that inhibit adenylyl cyclase and to Gq-like phospholipase C activity. LPA and S1P also induce p44/42 ERK MAP kinase phosphorylation in these cells and stimulate cell proliferation via Gi/o coupled receptors in an Epidermal Growth Factor Receptor (EGFR- and ERK-dependent pathway. In contrast, LPA and S1P stimulate transient cell rounding and aggregation that is independent of EGFR and ERK, but dependent on the Rho effector p160 ROCK. Conclusion Thus, lysophospholipids regulate neural progenitor growth and morphology through distinct mechanisms. These findings establish human ES cell-derived NEP cells as a model system for studying the role of lysophospholipids in neural progenitors.

Highly efficient methods to obtain homogeneous dorsal neural progenitor cells from human and mouse embryonic stem cells and induced pluripotent stem cells.

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Zhang, Meixiang; Ngo, Justine; Pirozzi, Filomena; Sun, Ying-Pu; Wynshaw-Boris, Anthony

2018-03-15

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been widely used to generate cellular models harboring specific disease-related genotypes. Of particular importance are ESC and iPSC applications capable of producing dorsal telencephalic neural progenitor cells (NPCs) that are representative of the cerebral cortex and overcome the challenges of maintaining a homogeneous population of cortical progenitors over several passages in vitro. While previous studies were able to derive NPCs from pluripotent cell types, the fraction of dorsal NPCs in this population is small and decreases over several passages. Here, we present three protocols that are highly efficient in differentiating mouse and human ESCs, as well as human iPSCs, into a homogeneous and stable population of dorsal NPCs. These protocols will be useful for modeling cerebral cortical neurological and neurodegenerative disorders in both mouse and human as well as for high-throughput drug screening for therapeutic development. We optimized three different strategies for generating dorsal telencephalic NPCs from mouse and human pluripotent cell types through single or double inhibition of bone morphogenetic protein (BMP) and/or SMAD pathways. Mouse and human pluripotent cells were aggregated to form embryoid bodies in suspension and were treated with dorsomorphin alone (BMP inhibition) or combined with SB431542 (double BMP/SMAD inhibition) during neural induction. Neural rosettes were then selected from plated embryoid bodies to purify the population of dorsal NPCs. We tested the expression of key dorsal NPC markers as well as nonectodermal markers to confirm the efficiency of our three methods in comparison to published and commercial protocols. Single and double inhibition of BMP and/or SMAD during neural induction led to the efficient differentiation of dorsal NPCs, based on the high percentage of PAX6-positive cells and the NPC gene expression profile. There were no statistically

YAP/TAZ enhance mammalian embryonic neural stem cell characteristics in a Tead-dependent manner

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Han, Dasol; Byun, Sung-Hyun; Park, Soojeong; Kim, Juwan; Kim, Inhee; Ha, Soobong; Kwon, Mookwang; Yoon, Keejung, E-mail: keejung@skku.edu

2015-02-27

Mammalian brain development is regulated by multiple signaling pathways controlling cell proliferation, migration and differentiation. Here we show that YAP/TAZ enhance embryonic neural stem cell characteristics in a cell autonomous fashion using diverse experimental approaches. Introduction of retroviral vectors expressing YAP or TAZ into the mouse embryonic brain induced cell localization in the ventricular zone (VZ), which is the embryonic neural stem cell niche. This change in cell distribution in the cortical layer is due to the increased stemness of infected cells; YAP-expressing cells were colabeled with Sox2, a neural stem cell marker, and YAP/TAZ increased the frequency and size of neurospheres, indicating enhanced self-renewal- and proliferative ability of neural stem cells. These effects appear to be TEA domain family transcription factor (Tead)–dependent; a Tead binding-defective YAP mutant lost the ability to promote neural stem cell characteristics. Consistently, in utero gene transfer of a constitutively active form of Tead2 (Tead2-VP16) recapitulated all the features of YAP/TAZ overexpression, and dominant negative Tead2-EnR resulted in marked cell exit from the VZ toward outer cortical layers. Taken together, these results indicate that the Tead-dependent YAP/TAZ signaling pathway plays important roles in neural stem cell maintenance by enhancing stemness of neural stem cells during mammalian brain development. - Highlights: • Roles of YAP and Tead in vivo during mammalian brain development are clarified. • Expression of YAP promotes embryonic neural stem cell characteristics in vivo in a cell autonomous fashion. • Enhancement of neural stem cell characteristics by YAP depends on Tead. • Transcriptionally active form of Tead alone can recapitulate the effects of YAP. • Transcriptionally repressive form of Tead severely reduces stem cell characteristics.

YAP/TAZ enhance mammalian embryonic neural stem cell characteristics in a Tead-dependent manner

International Nuclear Information System (INIS)

Han, Dasol; Byun, Sung-Hyun; Park, Soojeong; Kim, Juwan; Kim, Inhee; Ha, Soobong; Kwon, Mookwang; Yoon, Keejung

2015-01-01

Mammalian brain development is regulated by multiple signaling pathways controlling cell proliferation, migration and differentiation. Here we show that YAP/TAZ enhance embryonic neural stem cell characteristics in a cell autonomous fashion using diverse experimental approaches. Introduction of retroviral vectors expressing YAP or TAZ into the mouse embryonic brain induced cell localization in the ventricular zone (VZ), which is the embryonic neural stem cell niche. This change in cell distribution in the cortical layer is due to the increased stemness of infected cells; YAP-expressing cells were colabeled with Sox2, a neural stem cell marker, and YAP/TAZ increased the frequency and size of neurospheres, indicating enhanced self-renewal- and proliferative ability of neural stem cells. These effects appear to be TEA domain family transcription factor (Tead)–dependent; a Tead binding-defective YAP mutant lost the ability to promote neural stem cell characteristics. Consistently, in utero gene transfer of a constitutively active form of Tead2 (Tead2-VP16) recapitulated all the features of YAP/TAZ overexpression, and dominant negative Tead2-EnR resulted in marked cell exit from the VZ toward outer cortical layers. Taken together, these results indicate that the Tead-dependent YAP/TAZ signaling pathway plays important roles in neural stem cell maintenance by enhancing stemness of neural stem cells during mammalian brain development. - Highlights: • Roles of YAP and Tead in vivo during mammalian brain development are clarified. • Expression of YAP promotes embryonic neural stem cell characteristics in vivo in a cell autonomous fashion. • Enhancement of neural stem cell characteristics by YAP depends on Tead. • Transcriptionally active form of Tead alone can recapitulate the effects of YAP. • Transcriptionally repressive form of Tead severely reduces stem cell characteristics

Taurine Induces Proliferation of Neural Stem Cells and Synapse Development in the Developing Mouse Brain

Science.gov (United States)

Shivaraj, Mattu Chetana; Marcy, Guillaume; Low, Guoliang; Ryu, Jae Ryun; Zhao, Xianfeng; Rosales, Francisco J.; Goh, Eyleen L. K.

2012-01-01

Taurine is a sulfur-containing amino acid present in high concentrations in mammalian tissues. It has been implicated in several processes involving brain development and neurotransmission. However, the role of taurine in hippocampal neurogenesis during brain development is still unknown. Here we show that taurine regulates neural progenitor cell (NPC) proliferation in the dentate gyrus of the developing brain as well as in cultured early postnatal (P5) hippocampal progenitor cells and hippocampal slices derived from P5 mice brains. Taurine increased cell proliferation without having a significant effect on neural differentiation both in cultured P5 NPCs as well as cultured hippocampal slices and in vivo. Expression level analysis of synaptic proteins revealed that taurine increases the expression of Synapsin 1 and PSD 95. We also found that taurine stimulates the phosphorylation of ERK1/2 indicating a possible role of the ERK pathway in mediating the changes that we observed, especially in proliferation. Taken together, our results demonstrate a role for taurine in neural stem/progenitor cell proliferation in developing brain and suggest the involvement of the ERK1/2 pathways in mediating these actions. Our study also shows that taurine influences the levels of proteins associated with synapse development. This is the first evidence showing the effect of taurine on early postnatal neuronal development using a combination of in vitro, ex-vivo and in vivo systems. PMID:22916184

Endogenous and Exogenous Attention Shifts are Mediated by the Same Large-Scale Neural Network.

NARCIS (Netherlands)

Peelen, M.V.; Heslenfeld, D.J.; Theeuwes, J.

2004-01-01

Event-related fMRI was used to examine the neural basis of endogenous (top-down) and exogenous (bottom-up) spatial orienting. Shifts of attention were induced by central (endogenous) or peripheral (exogenous) cues. Reaction times on subsequently presented targets showed the expected pattern of

Heparan Sulfate Proteoglycans as Drivers of Neural Progenitors Derived From Human Mesenchymal Stem Cells.

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Okolicsanyi, Rachel K; Oikari, Lotta E; Yu, Chieh; Griffiths, Lyn R; Haupt, Larisa M

2018-01-01

Background: Due to their relative ease of isolation and their high ex vivo and in vitro expansive potential, human mesenchymal stem cells (hMSCs) are an attractive candidate for therapeutic applications in the treatment of brain injury and neurological diseases. Heparan sulfate proteoglycans (HSPGs) are a family of ubiquitous proteins involved in a number of vital cellular processes including proliferation and stem cell lineage differentiation. Methods: Following the determination that hMSCs maintain neural potential throughout extended in vitro expansion, we examined the role of HSPGs in mediating the neural potential of hMSCs. hMSCs cultured in basal conditions (undifferentiated monolayer cultures) were found to co-express neural markers and HSPGs throughout expansion with modulation of the in vitro niche through the addition of exogenous HS influencing cellular HSPG and neural marker expression. Results: Conversion of hMSCs into hMSC Induced Neurospheres (hMSC IN) identified distinctly localized HSPG staining within the spheres along with altered gene expression of HSPG core protein and biosynthetic enzymes when compared to undifferentiated hMSCs. Conclusion: Comparison of markers of pluripotency, neural self-renewal and neural lineage specification between hMSC IN, hMSC and human neural stem cell (hNSC H9) cultures suggest that in vitro generated hMSC IN may represent an intermediary neurogenic cell type, similar to a common neural progenitor cell. In addition, this data demonstrates HSPGs and their biosynthesis machinery, are associated with hMSC IN formation. The identification of specific HSPGs driving hMSC lineage-specification will likely provide new markers to allow better use of hMSCs in therapeutic applications and improve our understanding of human neurogenesis.

Neural Plasticity following Abacus Training in Humans: A Review and Future Directions

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Yongxin Li

2016-01-01

Full Text Available The human brain has an enormous capacity to adapt to a broad variety of environmental demands. Previous studies in the field of abacus training have shown that this training can induce specific changes in the brain. However, the neural mechanism underlying these changes remains elusive. Here, we reviewed the behavioral and imaging findings of comparisons between abacus experts and average control subjects and focused on changes in activation patterns and changes in brain structure. Finally, we noted the limitations and the future directions of this field. We concluded that although current studies have provided us with information about the mechanisms of abacus training, more research on abacus training is needed to understand its neural impact.

Characterization of calcium responses and electrical activity in differentiating mouse neural progenitor cells in vitro

NARCIS (Netherlands)

de Groot, Martje W G D M; Dingemans, Milou M L; Rus, Katinka H; de Groot, Aart; Westerink, Remco H S

In vitro methods for developmental neurotoxicity (DNT) testing have the potential to reduce animal use and increase insight into cellular and molecular mechanisms underlying chemical-induced alterations in the development of functional neuronal networks. Mouse neural progenitor cells (mNPCs)

Anti-correlations in the degree distribution increase stimulus detection performance in noisy spiking neural networks

NARCIS (Netherlands)

Martens, M.B. (Marijn B.); A.R. Houweling (Arthur); E. Tiesinga, P.H. (Paul H.)

2017-01-01

textabstractNeuronal circuits in the rodent barrel cortex are characterized by stable low firing rates. However, recent experiments show that short spike trains elicited by electrical stimulation in single neurons can induce behavioral responses. Hence, the underlying neural networks provide

Hidden neural networks

DEFF Research Database (Denmark)

Krogh, Anders Stærmose; Riis, Søren Kamaric

1999-01-01

A general framework for hybrids of hidden Markov models (HMMs) and neural networks (NNs) called hidden neural networks (HNNs) is described. The article begins by reviewing standard HMMs and estimation by conditional maximum likelihood, which is used by the HNN. In the HNN, the usual HMM probability...... parameters are replaced by the outputs of state-specific neural networks. As opposed to many other hybrids, the HNN is normalized globally and therefore has a valid probabilistic interpretation. All parameters in the HNN are estimated simultaneously according to the discriminative conditional maximum...... likelihood criterion. The HNN can be viewed as an undirected probabilistic independence network (a graphical model), where the neural networks provide a compact representation of the clique functions. An evaluation of the HNN on the task of recognizing broad phoneme classes in the TIMIT database shows clear...

NeuroMEMS: Neural Probe Microtechnologies

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Sam Musallam

2008-10-01

Full Text Available Neural probe technologies have already had a significant positive effect on our understanding of the brain by revealing the functioning of networks of biological neurons. Probes are implanted in different areas of the brain to record and/or stimulate specific sites in the brain. Neural probes are currently used in many clinical settings for diagnosis of brain diseases such as seizers, epilepsy, migraine, Alzheimer’s, and dementia. We find these devices assisting paralyzed patients by allowing them to operate computers or robots using their neural activity. In recent years, probe technologies were assisted by rapid advancements in microfabrication and microelectronic technologies and thus are enabling highly functional and robust neural probes which are opening new and exciting avenues in neural sciences and brain machine interfaces. With a wide variety of probes that have been designed, fabricated, and tested to date, this review aims to provide an overview of the advances and recent progress in the microfabrication techniques of neural probes. In addition, we aim to highlight the challenges faced in developing and implementing ultralong multi-site recording probes that are needed to monitor neural activity from deeper regions in the brain. Finally, we review techniques that can improve the biocompatibility of the neural probes to minimize the immune response and encourage neural growth around the electrodes for long term implantation studies.

Network evolution induced by asynchronous stimuli through spike-timing-dependent plasticity.

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Wu-Jie Yuan

Full Text Available In sensory neural system, external asynchronous stimuli play an important role in perceptual learning, associative memory and map development. However, the organization of structure and dynamics of neural networks induced by external asynchronous stimuli are not well understood. Spike-timing-dependent plasticity (STDP is a typical synaptic plasticity that has been extensively found in the sensory systems and that has received much theoretical attention. This synaptic plasticity is highly sensitive to correlations between pre- and postsynaptic firings. Thus, STDP is expected to play an important role in response to external asynchronous stimuli, which can induce segregative pre- and postsynaptic firings. In this paper, we study the impact of external asynchronous stimuli on the organization of structure and dynamics of neural networks through STDP. We construct a two-dimensional spatial neural network model with local connectivity and sparseness, and use external currents to stimulate alternately on different spatial layers. The adopted external currents imposed alternately on spatial layers can be here regarded as external asynchronous stimuli. Through extensive numerical simulations, we focus on the effects of stimulus number and inter-stimulus timing on synaptic connecting weights and the property of propagation dynamics in the resulting network structure. Interestingly, the resulting feedforward structure induced by stimulus-dependent asynchronous firings and its propagation dynamics reflect both the underlying property of STDP. The results imply a possible important role of STDP in generating feedforward structure and collective propagation activity required for experience-dependent map plasticity in developing in vivo sensory pathways and cortices. The relevance of the results to cue-triggered recall of learned temporal sequences, an important cognitive function, is briefly discussed as well. Furthermore, this finding suggests a potential

Patterns of interval correlations in neural oscillators with adaptation

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Tilo eSchwalger

2013-11-01

Full Text Available Neural firing is often subject to negative feedback by adaptationcurrents. These currents can induce strong correlations among the timeintervals between spikes. Here we study analytically the intervalcorrelations of a broad class of noisy neural oscillators withspike-triggered adaptation of arbitrary strength and time scale. Ourweak-noise theory provides a general relation between the correlationsand the phase-response curve (PRC of the oscillator, provesanti-correlations between neighboring intervals for adapting neuronswith type I PRC and identifies a single order parameter thatdetermines the qualitative pattern of correlations. Monotonicallydecaying or oscillating correlation structures can be related toqualitatively different voltage traces after spiking, which can beexplained by the phase plane geometry. At high firing rates, thelong-term variability of the spike train associated with thecumulative interval correlations becomes small, independent of modeldetails. Our results are verified by comparison with stochasticsimulations of the exponential, leaky, and generalizedintegrate-and-fire models with adaptation.

Radiation-induced apoptosis of neural precursors cell cultures: early modulation of the response mediated by reactive oxygen and nitrogen species (ROS/RNS)

Energy Technology Data Exchange (ETDEWEB)

Gisone, P.; Dubner, D.; Robello, E.; Michelin, S.; Perez, M. R.

2004-07-01

Apoptosis, the typical mode of radiation-induced cell death in developing Central Nervous System (CNS), is closely related with the oxidative status. Enhanced radiation-induced generation of ROS/RNS has been observed after exposures to low radiation doses leading to cellular amplification of signal transduction and further molecular and cellular radiation-responses. Moreover Nitric oxide (NO) and hydroxyl radical are implicated in dopaminergic neurotoxicity in different parading. This study is an attempt to address the participation of radiation-induced free radicals production, the contribution of endogenous NO generation, and the excitonic pathway, in the radiation-induced apoptosis of neural cortical precursors. Cortical cells obtained from at 17 gestational day (gd) were irradiated with doses from 0,2 Gy to 2 Gy at a dose-rate of 0.3 Gy/m. A significant decrease of Luminol-dependent Chemiluminescence was evident 30 m after irradiation reaching basal levels at 120 m follow for a tendency to increasing values Incubations with Superoxide Dismatuse (SOD) decreased significantly the chemiluminescence in irradiated samples NO content estimated by measuring the stable products NO{sub 2} and NO{sub 3} released to the culture medium in the same period, has shown a time-dependent accumulation from 1 h post-irradiation. the apoptosis, determined 24 h post-irradiation by flow cytometry, morphology and DNA fragmentation revealed a dose-effect relationship with significant differences from 0.4 Gy. The samples pre-treated with 10 mM of N-acetyl cysteine (NAC) a precursor of intracellular GSH synthesis, shown a significant decrease of the apoptosis. Apoptosis was significantly increased in irradiated cells after inhibition of nitric oxide synthase (NOS) byL-NAME. We conclude that ROS/RNS play a pivotal role in the early signaling pathways leading to a radiation-induced cell death. (Author) 40 refs.

Radiation-induced apoptosis of neural precursors cell cultures: early modulation of the response mediated by reactive oxygen and nitrogen species (ROS/RNS)

International Nuclear Information System (INIS)

Gisone, P.; Dubner, D.; Robello, E.; Michelin, S.; Perez, M. R.

2004-01-01

Apoptosis, the typical mode of radiation-induced cell death in developing Central Nervous System (CNS), is closely related with the oxidative status. Enhanced radiation-induced generation of ROS/RNS has been observed after exposures to low radiation doses leading to cellular amplification of signal transduction and further molecular and cellular radiation-responses. Moreover Nitric oxide (NO) and hydroxyl radical are implicated in dopaminergic neurotoxicity in different parading. This study is an attempt to address the participation of radiation-induced free radicals production, the contribution of endogenous NO generation, and the excitonic pathway, in the radiation-induced apoptosis of neural cortical precursors. Cortical cells obtained from at 17 gestational day (gd) were irradiated with doses from 0,2 Gy to 2 Gy at a dose-rate of 0.3 Gy/m. A significant decrease of Luminol-dependent Chemiluminescence was evident 30 m after irradiation reaching basal levels at 120 m follow for a tendency to increasing values Incubations with Superoxide Dismatuse (SOD) decreased significantly the chemiluminescence in irradiated samples NO content estimated by measuring the stable products NO 2 and NO 3 released to the culture medium in the same period, has shown a time-dependent accumulation from 1 h post-irradiation. the apoptosis, determined 24 h post-irradiation by flow cytometry, morphology and DNA fragmentation revealed a dose-effect relationship with significant differences from 0.4 Gy. The samples pre-treated with 10 mM of N-acetyl cysteine (NAC) a precursor of intracellular GSH synthesis, shown a significant decrease of the apoptosis. Apoptosis was significantly increased in irradiated cells after inhibition of nitric oxide synthase (NOS) byL-NAME. We conclude that ROS/RNS play a pivotal role in the early signaling pathways leading to a radiation-induced cell death. (Author) 40 refs

Simulation of lung motions using an artificial neural network

International Nuclear Information System (INIS)

Laurent, R.; Henriet, J.; Sauget, M.; Gschwind, R.; Makovicka, L.; Salomon, M.; Nguyen, F.

2011-01-01

Purpose. A way to improve the accuracy of lung radiotherapy for a patient is to get a better understanding of its lung motion. Indeed, thanks to this knowledge it becomes possible to follow the displacements of the clinical target volume (CTV) induced by the lung breathing. This paper presents a feasibility study of an original method to simulate the positions of points in patient's lung at all breathing phases. Patients and methods. This method, based on an artificial neural network, allowed learning the lung motion on real cases and then to simulate it for new patients for which only the beginning and the end breathing data are known. The neural network learning set is made up of more than 600 points. These points, shared out on three patients and gathered on a specific lung area, were plotted by a MD. Results. - The first results are promising: an average accuracy of 1 mm is obtained for a spatial resolution of 1 x 1 x 2.5 mm 3 . Conclusion. We have demonstrated that it is possible to simulate lung motion with accuracy using an artificial neural network. As future work we plan to improve the accuracy of our method with the addition of new patient data and a coverage of the whole lungs. (authors)

Neural Correlates of Impaired Reward-Effort Integration in Remitted Bulimia Nervosa.

Science.gov (United States)

Mueller, Stefanie Verena; Morishima, Yosuke; Schwab, Simon; Wiest, Roland; Federspiel, Andrea; Hasler, Gregor

2018-03-01

The integration of reward magnitudes and effort costs is required for an effective behavioral guidance. This reward-effort integration was reported to be dependent on dopaminergic neurotransmission. As bulimia nervosa has been associated with a dysregulated dopamine system and catecholamine depletion led to reward-processing deficits in remitted bulimia nervosa, the purpose of this study was to identify the role of catecholamine dysfunction and its relation to behavioral and neural reward-effort integration in bulimia nervosa. To investigate the interaction between catecholamine functioning and behavioral, and neural responses directly, 17 remitted bulimic (rBN) and 21 healthy individuals (HC) received alpha-methyl-paratyrosine (AMPT) over 24 h to achieve catecholamine depletion in a randomized, crossover study design. We used functional magnetic resonance imaging (fMRI) and the monetary incentive delay (MID) task to assess reward-effort integration in relation to catecholaminergic neurotransmission at the behavioral and neural level. AMPT reduced the ability to integrate rewards and efforts effectively in HC participants. In contrast, in rBN participants, the reduced reward-effort integration was associated with illness duration in the sham condition and unrelated to catecholamine depletion. Regarding neural activation, AMPT decreased the reward anticipation-related neural activation in the anteroventral striatum. This decrease was associated with the AMPT-induced reduction of monetary earning in HC in contrast to rBN participants. Our findings contributed to the theory of a desensitized dopaminergic system in bulimia nervosa. A disrupted processing of reward magnitudes and effort costs might increase the probability of maintenance of bulimic symptoms.

SoxB1-driven transcriptional network underlies neural-specific interpretation of morphogen signals.

Science.gov (United States)

Oosterveen, Tony; Kurdija, Sanja; Ensterö, Mats; Uhde, Christopher W; Bergsland, Maria; Sandberg, Magnus; Sandberg, Rickard; Muhr, Jonas; Ericson, Johan

2013-04-30

The reiterative deployment of a small cadre of morphogen signals underlies patterning and growth of most tissues during embyogenesis, but how such inductive events result in tissue-specific responses remains poorly understood. By characterizing cis-regulatory modules (CRMs) associated with genes regulated by Sonic hedgehog (Shh), retinoids, or bone morphogenetic proteins in the CNS, we provide evidence that the neural-specific interpretation of morphogen signaling reflects a direct integration of these pathways with SoxB1 proteins at the CRM level. Moreover, expression of SoxB1 proteins in the limb bud confers on mesodermal cells the potential to activate neural-specific target genes upon Shh, retinoid, or bone morphogenetic protein signaling, and the collocation of binding sites for SoxB1 and morphogen-mediatory transcription factors in CRMs faithfully predicts neural-specific gene activity. Thus, an unexpectedly simple transcriptional paradigm appears to conceptually explain the neural-specific interpretation of pleiotropic signaling during vertebrate development. Importantly, genes induced in a SoxB1-dependent manner appear to constitute repressive gene regulatory networks that are directly interlinked at the CRM level to constrain the regional expression of patterning genes. Accordingly, not only does the topology of SoxB1-driven gene regulatory networks provide a tissue-specific mode of gene activation, but it also determines the spatial expression pattern of target genes within the developing neural tube.

The neural correlates of perceptual load induced attentional selection: an fMRI study.

Science.gov (United States)

Wei, P; Szameitat, A J; Müller, H J; Schubert, T; Zhou, X

2013-10-10

The neural correlates of perceptual load induced attentional selection were investigated in an functional magnetic resonance imaging (fMRI) experiment in which attentional selection was manipulated through the variation of perceptual load in target search. Participants searched for a vertically or horizontally oriented bar among heterogeneously (the high load condition) or homogeneously (the low load condition) oriented distractor bars in the central display, which was flanked by a vertical or horizontal bar presented at the left or the right periphery. The search reaction times were longer when the central display was of high load than of low load, and were longer when the flanker was incongruent than congruent with the target. Importantly, the flanker congruency effect was manifested only in the low load condition, not in the high load condition, indicating that the perceptual load in target search determined whether the task-irrelevant flanker was processed. Imaging analyses revealed a set of fronto-parietal regions having higher activations in the high than in the low load condition. Anterior cingulate cortex (ACC) was more activated for the incongruent than for the congruent trials. Moreover, ACC and bilateral anterior insula were sensitive to the interaction between perceptual load and flanker congruency such that the activation differences between the incongruent and congruent conditions were significant in the low, but not in the high load condition. These results are consistent with the claim that ACC and bilateral anterior insula may exert executive control by selectively biasing processing in favor of task-relevant information and this biasing depends on the resources currently available to the control system. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Towards a neural chronometric framework for the aesthetic experience of music

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Elvira eBrattico

2013-05-01

Full Text Available Music is often studied as a cognitive domain alongside language. The emotional aspects of music have also been shown to be important, but views on their nature diverge. For instance, the specific emotions that music induces and how they relate to emotional expression are still under debate. Here we propose a mental and neural chronometry of the aesthetic experience of music initiated and mediated by external and internal contexts such as intentionality, background mood, attention, and expertise. The initial stages necessary for an aesthetic experience of music are feature analysis, integration across modalities, and cognitive processing on the basis of long-term knowledge. These stages are common to individuals belonging to the same musical culture. The initial emotional reactions to music include the startle reflex, core ‘liking’, and arousal. Subsequently, discrete emotions are perceived and induced. Presumably somatomotor processes synchronizing the body with the music also come into play here. The subsequent stages, in which cognitive, affective, and decisional processes intermingle, require controlled cross-modal neural processes to result in aesthetic emotions, aesthetic judgments, and conscious liking. These latter aesthetic stages often require attention, intentionality, and expertise for their full actualization.

Concurrent OCT imaging of stimulus evoked retinal neural activation and hemodynamic responses

Science.gov (United States)

Son, Taeyoon; Wang, Benquan; Lu, Yiming; Chen, Yanjun; Cao, Dingcai; Yao, Xincheng

2017-02-01

It is well established that major retinal diseases involve distortions of the retinal neural physiology and blood vascular structures. However, the details of distortions in retinal neurovascular coupling associated with major eye diseases are not well understood. In this study, a multi-modal optical coherence tomography (OCT) imaging system was developed to enable concurrent imaging of retinal neural activity and vascular hemodynamics. Flicker light stimulation was applied to mouse retinas to evoke retinal neural responses and hemodynamic changes. The OCT images were acquired continuously during the pre-stimulation, light-stimulation, and post-stimulation phases. Stimulus-evoked intrinsic optical signals (IOSs) and hemodynamic changes were observed over time in blood-free and blood regions, respectively. Rapid IOSs change occurred almost immediately after stimulation. Both positive and negative signals were observed in adjacent retinal areas. The hemodynamic changes showed time delays after stimulation. The signal magnitudes induced by light stimulation were observed in blood regions and did not show significant changes in blood-free regions. These differences may arise from different mechanisms in blood vessels and neural tissues in response to light stimulation. These characteristics agreed well with our previous observations in mouse retinas. Further development of the multimodal OCT may provide a new imaging method for studying how retinal structures and metabolic and neural functions are affected by age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and other diseases, which promises novel noninvasive biomarkers for early disease detection and reliable treatment evaluations of eye diseases.

A peptide derived from a trans-homophilic binding site in neural cell adhesion molecule induces neurite outgrowth and neuronal survival

DEFF Research Database (Denmark)

Køhler, Lene B; Soroka, Vladislav; Korshunova, Irina

2010-01-01

The neural cell adhesion molecule (NCAM) plays a key role in neural development, regeneration, and synaptic plasticity. The crystal structure of a fragment of NCAM comprising the three N-terminal immunoglobulin (Ig)-like modules indicates that the first and second Ig modules bind to each other, t...

The frog vestibular system as a model for lesion-induced plasticity: basic neural principles and implications for posture control

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Francois M Lambert

2012-04-01

Full Text Available Studies of behavioral consequences after unilateral labyrinthectomy have a long tradition in the quest of determining rules and limitations of the CNS to exert plastic changes that assist the recuperation from the loss of sensory inputs. Frogs were among the first animal models to illustrate general principles of regenerative capacity and reorganizational neural flexibility after a vestibular lesion. The continuous successful use of the latter animals is in part based on the easy access and identifiability of nerve branches to inner ear organs for surgical intervention, the possibility to employ whole brain preparations for in vitro studies and the limited degree of freedom of postural reflexes for quantification of behavioral impairments and subsequent improvements. Major discoveries that increased the knowledge of post-lesional reactive mechanisms in the central nervous system include alterations in vestibular commissural signal processing and activation of cooperative changes in excitatory and inhibitory inputs to disfacilitated neurons. Moreover, the observed increase of synaptic efficacy in propriospinal circuits illustrates the importance of limb proprioceptive inputs for postural recovery. Accumulated evidence suggests that the lesion-induced neural plasticity is not a goal-directed process that aims towards a meaningful restoration of vestibular reflexes but rather attempts a survival of those neurons that have lost their excitatory inputs. Accordingly, the reaction mechanism causes an improvement of some components but also a deterioration of other aspects as seen by spatio-temporally inappropriate vestibulo-motor responses, similar to the consequences of plasticity processes in various sensory systems and species. The generality of the findings indicate that frogs continue to form a highly amenable vertebrate model system for exploring molecular and physiological events during cellular and network reorganization after a loss of

Behaviors induced or disrupted by complex partial seizures.

Science.gov (United States)

Leung, L S; Ma, J; McLachlan, R S

2000-09-01

We reviewed the neural mechanisms underlying some postictal behaviors that are induced or disrupted by temporal lobe seizures in humans and animals. It is proposed that the psychomotor behaviors and automatisms induced by temporal lobe seizures are mediated by the nucleus accumbens. A non-convulsive hippocampal afterdischarge in rats induced an increase in locomotor activity, which was suppressed by the injection of dopamine D(2) receptor antagonist in the nucleus accumbens, and blocked by inactivation of the medial septum. In contrast, a convulsive hippocampal or amygdala seizure induced behavioral hypoactivity, perhaps by the spread of the seizure into the frontal cortex and opiate-mediated postictal depression. Mechanisms underlying postictal psychosis, memory disruption and other long-term behavioral alterations after temporal lobe seizures, are discussed. In conclusion, many of the changes of postictal behaviors observed after temporal lobe seizures in humans may be found in animals, and the basis of the behavioral change may be explained as a change in neural processing in the temporal lobe and the connecting subcortical structures.

Neural Networks: Implementations and Applications

OpenAIRE

Vonk, E.; Veelenturf, L.P.J.; Jain, L.C.

1996-01-01

Artificial neural networks, also called neural networks, have been used successfully in many fields including engineering, science and business. This paper presents the implementation of several neural network simulators and their applications in character recognition and other engineering areas

Evaluation of Induced Settlements of Piled Rafts in the Coupled Static-Dynamic Loads Using Neural Networks and Evolutionary Polynomial Regression

Directory of Open Access Journals (Sweden)

Ali Ghorbani

2017-01-01

Full Text Available Coupled Piled Raft Foundations (CPRFs are broadly applied to share heavy loads of superstructures between piles and rafts and reduce total and differential settlements. Settlements induced by static/coupled static-dynamic loads are one of the main concerns of engineers in designing CPRFs. Evaluation of induced settlements of CPRFs has been commonly carried out using three-dimensional finite element/finite difference modeling or through expensive real-scale/prototype model tests. Since the analyses, especially in the case of coupled static-dynamic loads, are not simply conducted, this paper presents two practical methods to gain the values of settlement. First, different nonlinear finite difference models under different static and coupled static-dynamic loads are developed to calculate exerted settlements. Analyses are performed with respect to different axial loads and pile’s configurations, numbers, lengths, diameters, and spacing for both loading cases. Based on the results of well-validated three-dimensional finite difference modeling, artificial neural networks and evolutionary polynomial regressions are then applied and introduced as capable methods to accurately present both static and coupled static-dynamic settlements. Also, using a sensitivity analysis based on Cosine Amplitude Method, axial load is introduced as the most influential parameter, while the ratio l/d is reported as the least effective parameter on the settlements of CPRFs.

Tricyclic antidepressant amitriptyline indirectly increases the proliferation of adult dentate gyrus-derived neural precursors: an involvement of astrocytes.

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Shuken Boku

Full Text Available Antidepressants increase the proliferation of neural precursors in adult dentate gyrus (DG, which is considered to be involved in the therapeutic action of antidepressants. However, the mechanism underlying it remains unclear. By using cultured adult rat DG-derived neural precursors (ADP, we have already shown that antidepressants have no direct effects on ADP. Therefore, antidepressants may increase the proliferation of neural precursors in adult DG via unknown indirect mechanism. We have also shown that amitriptyline (AMI, a tricyclic antidepressant, induces the expressions of GDNF, BDNF, FGF2 and VEGF, common neurogenic factors, in primary cultured astrocytes (PCA. These suggest that AMI-induced factors in astrocytes may increase the proliferation of neural precursors in adult DG. To test this hypothesis, we examined the effects of AMI-induced factors and conditioned medium (CM from PCA treated with AMI on ADP proliferation. The effects of CM and factors on ADP proliferation were examined with BrdU immunocytochemistry. AMI had no effect on ADP proliferation, but AMI-treated CM increased it. The receptors of GDNF, BDNF and FGF2, but not VEGF, were expressed in ADP. FGF2 significantly increased ADP proliferation, but not BDNF and GDNF. In addition, both of a specific inhibitor of FGF receptors and anti-FGF2 antibody significantly counteracted the increasing effect of CM on ADP proliferation. In addition, FGF2 in brain is mainly derived from astrocytes that are key components of the neurogenic niches in adult DG. These suggest that AMI may increase ADP proliferation indirectly via PCA and that FGF2 may a potential candidate to mediate such an indirect effect of AMI on ADP proliferation via astrocytes.

Inflammation- and tumor-induced anorexia and weight loss require MyD88 in hematopoietic/myeloid cells but not in brain endothelial or neural cells.

Science.gov (United States)

Ruud, Johan; Wilhelms, Daniel Björk; Nilsson, Anna; Eskilsson, Anna; Tang, Yan-Juan; Ströhle, Peter; Caesar, Robert; Schwaninger, Markus; Wunderlich, Thomas; Bäckhed, Fredrik; Engblom, David; Blomqvist, Anders

2013-05-01

Loss of appetite is a hallmark of inflammatory diseases. The underlying mechanisms remain undefined, but it is known that myeloid differentiation primary response gene 88 (MyD88), an adaptor protein critical for Toll-like and IL-1 receptor family signaling, is involved. Here we addressed the question of determining in which cells the MyD88 signaling that results in anorexia development occurs by using chimeric mice and animals with cell-specific deletions. We found that MyD88-knockout mice, which are resistant to bacterial lipopolysaccharide (LPS)-induced anorexia, displayed anorexia when transplanted with wild-type bone marrow cells. Furthermore, mice with a targeted deletion of MyD88 in hematopoietic or myeloid cells were largely protected against LPS-induced anorexia and displayed attenuated weight loss, whereas mice with MyD88 deletion in hepatocytes or in neural cells or the cerebrovascular endothelium developed anorexia and weight loss of similar magnitude as wild-type mice. Furthermore, in a model for cancer-induced anorexia-cachexia, deletion of MyD88 in hematopoietic cells attenuated the anorexia and protected against body weight loss. These findings demonstrate that MyD88-dependent signaling within the brain is not required for eliciting inflammation-induced anorexia. Instead, we identify MyD88 signaling in hematopoietic/myeloid cells as a critical component for acute inflammatory-driven anorexia, as well as for chronic anorexia and weight loss associated with malignant disease.

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

International Nuclear Information System (INIS)

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

2015-01-01

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

Involvement of Atm and Trp53 in neural cell loss due to Terf2 inactivation during mouse brain development.

Science.gov (United States)

Kim, Jusik; Choi, Inseo; Lee, Youngsoo

2017-11-01

Maintenance of genomic integrity is one of the critical features for proper neurodevelopment and inhibition of neurological diseases. The signals from both ATM and ATR to TP53 are well-known mechanisms to remove neural cells with DNA damage during neurogenesis. Here we examined the involvement of Atm and Atr in genomic instability due to Terf2 inactivation during mouse brain development. Selective inactivation of Terf2 in neural progenitors induced apoptosis, resulting in a complete loss of the brain structure. This neural loss was rescued partially in both Atm and Trp53 deficiency, but not in an Atr-deficient background in the mouse. Atm inactivation resulted in incomplete brain structures, whereas p53 deficiency led to the formation of multinucleated giant neural cells and the disruption of the brain structure. These giant neural cells disappeared in Lig4 deficiency. These data demonstrate ATM and TP53 are important for the maintenance of telomere homeostasis and the surveillance of telomere dysfunction during neurogenesis.

Conversion of Human Fibroblasts to Stably Self-Renewing Neural Stem Cells with a Single Zinc-Finger Transcription Factor

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Ebrahim Shahbazi

2016-04-01

Full Text Available Direct conversion of somatic cells into neural stem cells (NSCs by defined factors holds great promise for mechanistic studies, drug screening, and potential cell therapies for different neurodegenerative diseases. Here, we report that a single zinc-finger transcription factor, Zfp521, is sufficient for direct conversion of human fibroblasts into long-term self-renewable and multipotent NSCs. In vitro, Zfp521-induced NSCs maintained their characteristics in the absence of exogenous factor expression and exhibited morphological, molecular, developmental, and functional properties that were similar to control NSCs. In addition, the single-seeded induced NSCs were able to form NSC colonies with efficiency comparable with control NSCs and expressed NSC markers. The converted cells were capable of surviving, migrating, and attaining neural phenotypes after transplantation into neonatal mouse and adult rat brains, without forming tumors. Moreover, the Zfp521-induced NSCs predominantly expressed rostral genes. Our results suggest a facilitated approach for establishing human NSCs through Zfp521-driven conversion of fibroblasts.

Neurophysiology and neural engineering: a review.

Science.gov (United States)

Prochazka, Arthur

2017-08-01

Neurophysiology is the branch of physiology concerned with understanding the function of neural systems. Neural engineering (also known as neuroengineering) is a discipline within biomedical engineering that uses engineering techniques to understand, repair, replace, enhance, or otherwise exploit the properties and functions of neural systems. In most cases neural engineering involves the development of an interface between electronic devices and living neural tissue. This review describes the origins of neural engineering, the explosive development of methods and devices commencing in the late 1950s, and the present-day devices that have resulted. The barriers to interfacing electronic devices with living neural tissues are many and varied, and consequently there have been numerous stops and starts along the way. Representative examples are discussed. None of this could have happened without a basic understanding of the relevant neurophysiology. I also consider examples of how neural engineering is repaying the debt to basic neurophysiology with new knowledge and insight. Copyright © 2017 the American Physiological Society.

Fast and Efficient Asynchronous Neural Computation with Adapting Spiking Neural Networks

NARCIS (Netherlands)

D. Zambrano (Davide); S.M. Bohte (Sander)

2016-01-01

textabstractBiological neurons communicate with a sparing exchange of pulses - spikes. It is an open question how real spiking neurons produce the kind of powerful neural computation that is possible with deep artificial neural networks, using only so very few spikes to communicate. Building on

The hypoxia factor Hif-1α controls neural crest chemotaxis and epithelial to mesenchymal transition

Science.gov (United States)

Barriga, Elias H.; Maxwell, Patrick H.

2013-01-01

One of the most important mechanisms that promotes metastasis is the stabilization of Hif-1 (hypoxia-inducible transcription factor 1). We decided to test whether Hif-1α also was required for early embryonic development. We focused our attention on the development of the neural crest, a highly migratory embryonic cell population whose behavior has been likened to cancer metastasis. Inhibition of Hif-1α by antisense morpholinos in Xenopus laevis or zebrafish embryos led to complete inhibition of neural crest migration. We show that Hif-1α controls the expression of Twist, which in turn represses E-cadherin during epithelial to mesenchymal transition (EMT) of neural crest cells. Thus, Hif-1α allows cells to initiate migration by promoting the release of cell–cell adhesions. Additionally, Hif-1α controls chemotaxis toward the chemokine SDF-1 by regulating expression of its receptor Cxcr4. Our results point to Hif-1α as a novel and key regulator that integrates EMT and chemotaxis during migration of neural crest cells. PMID:23712262

From sensation to percept: the neural signature of auditory event-related potentials.

Science.gov (United States)

Joos, Kathleen; Gilles, Annick; Van de Heyning, Paul; De Ridder, Dirk; Vanneste, Sven

2014-05-01

An external auditory stimulus induces an auditory sensation which may lead to a conscious auditory perception. Although the sensory aspect is well known, it is still a question how an auditory stimulus results in an individual's conscious percept. To unravel the uncertainties concerning the neural correlates of a conscious auditory percept, event-related potentials may serve as a useful tool. In the current review we mainly wanted to shed light on the perceptual aspects of auditory processing and therefore we mainly focused on the auditory late-latency responses. Moreover, there is increasing evidence that perception is an active process in which the brain searches for the information it expects to be present, suggesting that auditory perception requires the presence of both bottom-up, i.e. sensory and top-down, i.e. prediction-driven processing. Therefore, the auditory evoked potentials will be interpreted in the context of the Bayesian brain model, in which the brain predicts which information it expects and when this will happen. The internal representation of the auditory environment will be verified by sensation samples of the environment (P50, N100). When this incoming information violates the expectation, it will induce the emission of a prediction error signal (Mismatch Negativity), activating higher-order neural networks and inducing the update of prior internal representations of the environment (P300). Copyright © 2014 Elsevier Ltd. All rights reserved.

Artificial neural networks in NDT

International Nuclear Information System (INIS)

Abdul Aziz Mohamed

2001-01-01

Artificial neural networks, simply known as neural networks, have attracted considerable interest in recent years largely because of a growing recognition of the potential of these computational paradigms as powerful alternative models to conventional pattern recognition or function approximation techniques. The neural networks approach is having a profound effect on almost all fields, and has been utilised in fields Where experimental inter-disciplinary work is being carried out. Being a multidisciplinary subject with a broad knowledge base, Nondestructive Testing (NDT) or Nondestructive Evaluation (NDE) is no exception. This paper explains typical applications of neural networks in NDT/NDE. Three promising types of neural networks are highlighted, namely, back-propagation, binary Hopfield and Kohonen's self-organising maps. (Author)

Advances in reprogramming somatic cells to induced pluripotent stem cells.

Science.gov (United States)

Patel, Minal; Yang, Shuying

2010-09-01

Traditionally, nuclear reprogramming of cells has been performed by transferring somatic cell nuclei into oocytes, by combining somatic and pluripotent cells together through cell fusion and through genetic integration of factors through somatic cell chromatin. All of these techniques changes gene expression which further leads to a change in cell fate. Here we discuss recent advances in generating induced pluripotent stem cells, different reprogramming methods and clinical applications of iPS cells. Viral vectors have been used to transfer transcription factors (Oct4, Sox2, c-myc, Klf4, and nanog) to induce reprogramming of mouse fibroblasts, neural stem cells, neural progenitor cells, keratinocytes, B lymphocytes and meningeal membrane cells towards pluripotency. Human fibroblasts, neural cells, blood and keratinocytes have also been reprogrammed towards pluripotency. In this review we have discussed the use of viral vectors for reprogramming both animal and human stem cells. Currently, many studies are also involved in finding alternatives to using viral vectors carrying transcription factors for reprogramming cells. These include using plasmid transfection, piggyback transposon system and piggyback transposon system combined with a non viral vector system. Applications of these techniques have been discussed in detail including its advantages and disadvantages. Finally, current clinical applications of induced pluripotent stem cells and its limitations have also been reviewed. Thus, this review is a summary of current research advances in reprogramming cells into induced pluripotent stem cells.

Command Filtered Adaptive Fuzzy Neural Network Backstepping Control for Marine Power System

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Xin Zhang

2014-01-01

Full Text Available In order to retrain chaotic oscillation of marine power system which is excited by periodic electromagnetism perturbation, a novel command-filtered adaptive fuzzy neural network backstepping control method is designed. First, the mathematical model of marine power system is established based on the two parallel nonlinear model. Then, main results of command-filtered adaptive fuzzy neural network backstepping control law are given. And the Lyapunov stability theory is applied to prove that the system can remain closed-loop asymptotically stable with this controller. Finally, simulation results indicate that the designed controller can suppress chaotic oscillation with fast convergence speed that makes the system return to the equilibrium point quickly; meanwhile, the parameter which induces chaotic oscillation can also be discriminated.

Direct imaging of neural currents using ultra-low field magnetic resonance techniques

Science.gov (United States)

Volegov, Petr L [Los Alamos, NM; Matlashov, Andrei N [Los Alamos, NM; Mosher, John C [Los Alamos, NM; Espy, Michelle A [Los Alamos, NM; Kraus, Jr., Robert H.

2009-08-11

Using resonant interactions to directly and tomographically image neural activity in the human brain using magnetic resonance imaging (MRI) techniques at ultra-low field (ULF), the present inventors have established an approach that is sensitive to magnetic field distributions local to the spin population in cortex at the Larmor frequency of the measurement field. Because the Larmor frequency can be readily manipulated (through varying B.sub.m), one can also envision using ULF-DNI to image the frequency distribution of the local fields in cortex. Such information, taken together with simultaneous acquisition of MEG and ULF-NMR signals, enables non-invasive exploration of the correlation between local fields induced by neural activity in cortex and more `distant` measures of brain activity such as MEG and EEG.

Fractional Hopfield Neural Networks: Fractional Dynamic Associative Recurrent Neural Networks.

Science.gov (United States)

Pu, Yi-Fei; Yi, Zhang; Zhou, Ji-Liu

2017-10-01

This paper mainly discusses a novel conceptual framework: fractional Hopfield neural networks (FHNN). As is commonly known, fractional calculus has been incorporated into artificial neural networks, mainly because of its long-term memory and nonlocality. Some researchers have made interesting attempts at fractional neural networks and gained competitive advantages over integer-order neural networks. Therefore, it is naturally makes one ponder how to generalize the first-order Hopfield neural networks to the fractional-order ones, and how to implement FHNN by means of fractional calculus. We propose to introduce a novel mathematical method: fractional calculus to implement FHNN. First, we implement fractor in the form of an analog circuit. Second, we implement FHNN by utilizing fractor and the fractional steepest descent approach, construct its Lyapunov function, and further analyze its attractors. Third, we perform experiments to analyze the stability and convergence of FHNN, and further discuss its applications to the defense against chip cloning attacks for anticounterfeiting. The main contribution of our work is to propose FHNN in the form of an analog circuit by utilizing a fractor and the fractional steepest descent approach, construct its Lyapunov function, prove its Lyapunov stability, analyze its attractors, and apply FHNN to the defense against chip cloning attacks for anticounterfeiting. A significant advantage of FHNN is that its attractors essentially relate to the neuron's fractional order. FHNN possesses the fractional-order-stability and fractional-order-sensitivity characteristics.

Like or dislike? Affective preference modulates neural response to others' gains and losses.

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Yang Wang

Full Text Available Previous studies have demonstrated that the brain responds differentially to others' gains and losses relative to one's own, moderated by social context factors such as competition and interpersonal relationships. In the current study, we tested the hypothesis that the neural response to others' outcomes could be modulated by a short-term induced affective preference. We engaged 17 men and 18 women in a social-exchange game, in which two confederates played fairly or unfairly. Both men and women rated the fair player as likable and the unfair players as unlikable. Afterwards, ERPs were recorded while participants observed each confederates playing a gambling game individually. This study examines feedback related negativity (FRN, an ERP component sensitive to negative feedback. ANOVA showed a significant interaction in which females but not males displayed stronger FRNs when observing likable players' outcomes compared to unlikable ones'. However, males did not respond differently under either circumstance. These findings suggest that, at least in females, the neural response is influenced by a short-term induced affective preference.

Death and rebirth of neural activity in sparse inhibitory networks

Science.gov (United States)

Angulo-Garcia, David; Luccioli, Stefano; Olmi, Simona; Torcini, Alessandro

2017-05-01

Inhibition is a key aspect of neural dynamics playing a fundamental role for the emergence of neural rhythms and the implementation of various information coding strategies. Inhibitory populations are present in several brain structures, and the comprehension of their dynamics is strategical for the understanding of neural processing. In this paper, we clarify the mechanisms underlying a general phenomenon present in pulse-coupled heterogeneous inhibitory networks: inhibition can induce not only suppression of neural activity, as expected, but can also promote neural re-activation. In particular, for globally coupled systems, the number of firing neurons monotonically reduces upon increasing the strength of inhibition (neuronal death). However, the random pruning of connections is able to reverse the action of inhibition, i.e. in a random sparse network a sufficiently strong synaptic strength can surprisingly promote, rather than depress, the activity of neurons (neuronal rebirth). Thus, the number of firing neurons reaches a minimum value at some intermediate synaptic strength. We show that this minimum signals a transition from a regime dominated by neurons with a higher firing activity to a phase where all neurons are effectively sub-threshold and their irregular firing is driven by current fluctuations. We explain the origin of the transition by deriving a mean field formulation of the problem able to provide the fraction of active neurons as well as the first two moments of their firing statistics. The introduction of a synaptic time scale does not modify the main aspects of the reported phenomenon. However, for sufficiently slow synapses the transition becomes dramatic, and the system passes from a perfectly regular evolution to irregular bursting dynamics. In this latter regime the model provides predictions consistent with experimental findings for a specific class of neurons, namely the medium spiny neurons in the striatum.

MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate Neurogenesis

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Francisca F. Vasconcelos

2016-10-01

Full Text Available The generation of neurons from neural stem cells requires large-scale changes in gene expression that are controlled to a large extent by proneural transcription factors, such as Ascl1. While recent studies have characterized the differentiation genes activated by proneural factors, less is known on the mechanisms that suppress progenitor cell identity. Here, we show that Ascl1 induces the transcription factor MyT1 while promoting neuronal differentiation. We combined functional studies of MyT1 during neurogenesis with the characterization of its transcriptional program. MyT1 binding is associated with repression of gene transcription in neural progenitor cells. It promotes neuronal differentiation by counteracting the inhibitory activity of Notch signaling at multiple levels, targeting the Notch1 receptor and many of its downstream targets. These include regulators of the neural progenitor program, such as Hes1, Sox2, Id3, and Olig1. Thus, Ascl1 suppresses Notch signaling cell-autonomously via MyT1, coupling neuronal differentiation with repression of the progenitor fate.

Bidirectional neural interface: Closed-loop feedback control for hybrid neural systems.

Science.gov (United States)

Chou, Zane; Lim, Jeffrey; Brown, Sophie; Keller, Melissa; Bugbee, Joseph; Broccard, Frédéric D; Khraiche, Massoud L; Silva, Gabriel A; Cauwenberghs, Gert

2015-01-01

Closed-loop neural prostheses enable bidirectional communication between the biological and artificial components of a hybrid system. However, a major challenge in this field is the limited understanding of how these components, the two separate neural networks, interact with each other. In this paper, we propose an in vitro model of a closed-loop system that allows for easy experimental testing and modification of both biological and artificial network parameters. The interface closes the system loop in real time by stimulating each network based on recorded activity of the other network, within preset parameters. As a proof of concept we demonstrate that the bidirectional interface is able to establish and control network properties, such as synchrony, in a hybrid system of two neural networks more significantly more effectively than the same system without the interface or with unidirectional alternatives. This success holds promise for the application of closed-loop systems in neural prostheses, brain-machine interfaces, and drug testing.

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.

Interleukin-6 Regulates Adult Neural Stem Cell Numbers during Normal and Abnormal Post-natal Development

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Mekayla A. Storer

2018-05-01

Full Text Available Summary: Circulating systemic factors can regulate adult neural stem cell (NSC biology, but the identity of these circulating cues is still being defined. Here, we have focused on the cytokine interleukin-6 (IL-6, since increased circulating levels of IL-6 are associated with neural pathologies such as autism and bipolar disorder. We show that IL-6 promotes proliferation of post-natal murine forebrain NSCs and that, when the IL-6 receptor is inducibly knocked out in post-natal or adult neural precursors, this causes a long-term decrease in forebrain NSCs. Moreover, a transient circulating surge of IL-6 in perinatal or adult mice causes an acute increase in neural precursor proliferation followed by long-term depletion of adult NSC pools. Thus, IL-6 signaling is both necessary and sufficient for adult NSC self-renewal, and acute perturbations in circulating IL-6, as observed in many pathological situations, have long-lasting effects on the size of adult NSC pools. : In this report, Storer and colleagues demonstrate that the circulating cytokine IL-6, which is elevated in humans in different pathological situations, can perturb neural stem cell biology after birth. They show that IL-6 signaling is essential for self-renewal and maintenance of post-natal and adult NSCs in the murine forebrain under normal homeostatic conditions. Keywords: interleukin-6, neural stem cell, adult neurogenesis, CNS cytokines, postnatal brain development, stem cell depletion, neural stem cell niche, circulating stem cell factors, olfactory bulb

The positional identity of iPSC-derived neural progenitor cells along the anterior-posterior axis is controlled in a dosage-dependent manner by bFGF and EGF

DEFF Research Database (Denmark)

Zhou, Shuling; Ochalek, Anna; Szczesna, Karolina

2016-01-01

Neural rosettes derived from human induced pluripotent stem cells (iPSCs) have been claimed to be a highly robust in vitro cellular model for biomedical application. They are able to propagate in vitro in the presence of mitogens, including basic fibroblast growth factor (bFGF) and epidermal growth...... factor (EGF). However, these two mitogens are also involved in anterior-posterior patterning in a gradient dependent manner along the neural tube axis. Here, we compared the regional identity of neural rosette cells and specific neural subtypes of their progeny propagated with low and high concentrations...... of the neural rosettes, resulting in subsequent cholinergic neuron differentiation. Thus, our results indicate that different concentrations of bFGF and EGF supplemented during propagation of neural rosettes are involved in altering the identity of the resultant neural cells....

Sequential neural models with stochastic layers

DEFF Research Database (Denmark)

Fraccaro, Marco; Sønderby, Søren Kaae; Paquet, Ulrich

2016-01-01

How can we efficiently propagate uncertainty in a latent state representation with recurrent neural networks? This paper introduces stochastic recurrent neural networks which glue a deterministic recurrent neural network and a state space model together to form a stochastic and sequential neural...... generative model. The clear separation of deterministic and stochastic layers allows a structured variational inference network to track the factorization of the model's posterior distribution. By retaining both the nonlinear recursive structure of a recurrent neural network and averaging over...

Origin-Dependent Neural Cell Identities in Differentiated Human iPSCs In Vitro and after Transplantation into the Mouse Brain

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Gunnar Hargus

2014-09-01

Full Text Available The differentiation capability of induced pluripotent stem cells (iPSCs toward certain cell types for disease modeling and drug screening assays might be influenced by their somatic cell of origin. Here, we have compared the neural induction of human iPSCs generated from fetal neural stem cells (fNSCs, dermal fibroblasts, or cord blood CD34+ hematopoietic progenitor cells. Neural progenitor cells (NPCs and neurons could be generated at similar efficiencies from all iPSCs. Transcriptomics analysis of the whole genome and of neural genes revealed a separation of neuroectoderm-derived iPSC-NPCs from mesoderm-derived iPSC-NPCs. Furthermore, we found genes that were similarly expressed in fNSCs and neuroectoderm, but not in mesoderm-derived iPSC-NPCs. Notably, these neural signatures were retained after transplantation into the cortex of mice and paralleled with increased survival of neuroectoderm-derived cells in vivo. These results indicate distinct origin-dependent neural cell identities in differentiated human iPSCs both in vitro and in vivo.

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

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Yan Liang

2017-01-01

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

Induction of Skin-Derived Precursor Cells from Human Induced Pluripotent Stem Cells.

Science.gov (United States)

Sugiyama-Nakagiri, Yoriko; Fujimura, Tsutomu; Moriwaki, Shigeru

2016-01-01

The generation of full thickness human skin from dissociated cells is an attractive approach not only for treating skin diseases, but also for treating many systemic disorders. However, it is currently not possible to obtain an unlimited number of skin dermal cells. The goal of this study was to develop a procedure to produce skin dermal stem cells from induced pluripotent stem cells (iPSCs). Skin-derived precursor cells (SKPs) were isolated as adult dermal precursors that could differentiate into both neural and mesodermal progenies and could reconstitute the dermis. Thus, we attempted to generate SKPs from iPSCs that could reconstitute the skin dermis. Human iPSCs were initially cultured with recombinant noggin and SB431542, an inhibitor of activin/nodal and TGFβ signaling, to induce neural crest progenitor cells. Those cells were then treated with SKP medium that included CHIR99021, a WNT signal activator. The induction efficacy from neural crest progenitor cells to SKPs was more than 97%. No other modifiers tested were able to induce those cells. Those human iPSC-derived SKPs (hiPSC-SKPs) showed a similar gene expression signature to SKPs isolated from human skin dermis. Human iPSC-SKPs differentiated into neural and mesodermal progenies, including adipocytes, skeletogenic cell types and Schwann cells. Moreover, they could be induced to follicular type keratinization when co-cultured with human epidermal keratinocytes. We here provide a new efficient protocol to create human skin dermal stem cells from hiPSCs that could contribute to the treatment of various skin disorders.

Studies on the Belle II L1 CDC track trigger's z-vertex resolution with neural networks

Energy Technology Data Exchange (ETDEWEB)

Skambraks, Sebastian; Neuhaus, Sara; Chen, Yang [Technische Universitaet Muenchen (Germany); Abudinen, Fernando; Kiesling, Christian [Max-Planck-Institut fuer Physik, Muenchen (Germany)

2015-07-01

We present the use of a neural network ensemble for the first level (L1) track trigger subsystem of Belle II. Our method employs hit and drift time information from the Central Drift Chamber (CDC). Estimating the z-coordinates of the vertex positions improves the signal to background ratio in the recorded data. Especially beam induced background can clearly be rejected, allowing to relax the 2D trigger conditions and thus enhancing the physics gain for low multiplicity events (e.g. tau pair production). Neural networks enable an improvement of the z-vertex resolution compared to linear least squares track fitting. As general function approximators, they are capable of learning nonlinearities solely from a training dataset. We propose a combined setup, integrating the benefits of the linear fit and enriching it with the nonlinear prediction capabilities of the neural networks. The precise z-vertices of single tracks are estimated by an ensemble of local expert neural networks, specialized to sectors in the track parameter phase space. A comparison is presented, demonstrating the differences of the linear fit and the neural network approach.

Cocaine action on peripheral, non-monoamine neural substrates as a trigger of electroencephalographic desynchronization and electromyographic activation following i.v. administration in freely moving rats.

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Smirnov, M S; Kiyatkin, E A

2010-01-20

Many important physiological, behavioral and subjective effects of i.v. cocaine (COC) are exceptionally rapid and transient, suggesting a possible involvement of peripheral neural substrates in their triggering. In the present study, we used high-speed electroencephalographic (EEG) and electromyographic (EMG) recordings (4-s resolution) in freely moving rats to characterize the central electrophysiological effects of i.v. COC at low doses within a self-administration range (0.25-1.0 mg/kg). We found that COC induces rapid, strong, and prolonged desynchronization of cortical EEG (decrease in alpha and increase in beta and gamma activity) and activation of the neck EMG that begin within 2-6 s following the start of a 10-s injection; immediate components of both effects were dose-independent. The rapid effects of COC were mimicked by i.v. COC methiodide (COC-MET), a derivative that cannot cross the blood-brain barrier. At equimolar doses (0.33-1.33 mg/kg), COC-MET had equally fast and strong effects on EEG and EMG total powers, decreasing alpha and increasing beta and gamma activities. Rapid EEG desynchronization and EMG activation was also induced by i.v. procaine, a structurally similar, short-acting local anesthetic with virtually no effects on monoamine uptake; at equipotential doses (1.25-5.0 mg/kg), these effects were weaker and shorter in duration than those of COC. Surprisingly, i.v. saline injection delivered during slow-wave sleep (but not during quiet wakefulness) also induced a transient EEG desynchronization but without changes in EMG and motor activity; these effects were significantly weaker and much shorter than those induced by all tested drugs. These data suggest that in awake animals, i.v. COC induces rapid cortical activation and a subsequent motor response via its action on peripheral non-monoamine neural elements, involving neural transmission via visceral sensory pathways. By providing a rapid neural signal and triggering neural activation, such

The influence of mental fatigue and motivation on neural network dynamics; an EEG coherence study

NARCIS (Netherlands)

Lorist, Monicque M.; Bezdan, Eniko; Caat, Michael ten; Span, Mark M.; Roerdink, Jos B.T.M.; Maurits, Natasha M.

2009-01-01

The purpose of the present study is to examine the effects of mental fatigue and motivation on neural network dynamics activated during task switching. Mental fatigue was induced by 2 h of continuous performance; after which subjects were motivated by using social comparison and monetary reward as

Physiological and Neural Adaptations to Eccentric Exercise: Mechanisms and Considerations for Training

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Nosratollah Hedayatpour

2015-01-01

Full Text Available Eccentric exercise is characterized by initial unfavorable effects such as subcellular muscle damage, pain, reduced fiber excitability, and initial muscle weakness. However, stretch combined with overload, as in eccentric contractions, is an effective stimulus for inducing physiological and neural adaptations to training. Eccentric exercise-induced adaptations include muscle hypertrophy, increased cortical activity, and changes in motor unit behavior, all of which contribute to improved muscle function. In this brief review, neuromuscular adaptations to different forms of exercise are reviewed, the positive training effects of eccentric exercise are presented, and the implications for training are considered.

Neural correlates underlying naloxone-induced amelioration of sexual behavior deterioration due to an alarm pheromone

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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.

The Use of Human-Induced Pluripotent Stem Cell-Derived Neural Precursors in the Treatment of Brain and Spinal Cord Injury

Czech Academy of Sciences Publication Activity Database

Jendelová, Pavla; Kozubenko, Nataliya; Amemori, Takashi; Turnovcová, Karolína; Seminatore, CH.; Jirák, D.; Onteniente, B.; Syková, Eva

2011-01-01

Roč. 20, č. 4 (2011), s. 564-564 ISSN 0963-6897. [International Neural Transplantatioin and Repair Meeting/18th Annual Meeting of the American-Society-for- Neural - Therapy - and -Repair /11./. 04.05.2011-08.05.2011, Clearwater] Institutional research plan: CEZ:AV0Z50390703 Keywords : spinal cord * stem cell Subject RIV: FH - Neurology

Neural fate decisions mediated by combinatorial regulation of Hes1 and miR-9.

Science.gov (United States)

Li, Shanshan; Liu, Yanwei; Liu, Zengrong; Wang, Ruiqi

2016-01-01

In the nervous system, Hes1 shows an oscillatory manner in neural progenitors but a persistent one in neurons. Many models involving Hes1 have been provided for the study of neural differentiation but few of them take the role of microRNA into account. It is known that a microRNA, miR-9, plays crucial roles in modulating Hes1 oscillations. However, the roles of miR-9 in controlling Hes1 oscillations and inducing transition between different cell fates still need to be further explored. Here we provide a mathematical model to show the interaction between miR-9 and Hes1, with the aim of understanding how the Hes1 oscillations are produced, how they are controlled, and further, how they are terminated. Based on the experimental findings, the model demonstrates the essential roles of Hes1 and miR-9 in regulating the dynamics of the system. In particular, the model suggests that the balance between miR-9 and Hes1 plays important roles in the choice between progenitor maintenance and neural differentiation. In addition, the synergistic (or antagonistic) effects of several important regulations are investigated so as to elucidate the effects of combinatorial regulation in neural decision-making. Our model provides a qualitative mechanism for understanding the process in neural fate decisions regulated by Hes1 and miR-9.

Parallel consensual neural networks.

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Benediktsson, J A; Sveinsson, J R; Ersoy, O K; Swain, P H

1997-01-01

A new type of a neural-network architecture, the parallel consensual neural network (PCNN), is introduced and applied in classification/data fusion of multisource remote sensing and geographic data. The PCNN architecture is based on statistical consensus theory and involves using stage neural networks with transformed input data. The input data are transformed several times and the different transformed data are used as if they were independent inputs. The independent inputs are first classified using the stage neural networks. The output responses from the stage networks are then weighted and combined to make a consensual decision. In this paper, optimization methods are used in order to weight the outputs from the stage networks. Two approaches are proposed to compute the data transforms for the PCNN, one for binary data and another for analog data. The analog approach uses wavelet packets. The experimental results obtained with the proposed approach show that the PCNN outperforms both a conjugate-gradient backpropagation neural network and conventional statistical methods in terms of overall classification accuracy of test data.

Creative-Dynamics Approach To Neural Intelligence

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Zak, Michail A.

1992-01-01

Paper discusses approach to mathematical modeling of artificial neural networks exhibiting complicated behaviors reminiscent of creativity and intelligence of biological neural networks. Neural network treated as non-Lipschitzian dynamical system - as described in "Non-Lipschitzian Dynamics For Modeling Neural Networks" (NPO-17814). System serves as tool for modeling of temporal-pattern memories and recognition of complicated spatial patterns.

Autonomous dynamics in neural networks: the dHAN concept and associative thought processes

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Gros, Claudius

2007-02-01

The neural activity of the human brain is dominated by self-sustained activities. External sensory stimuli influence this autonomous activity but they do not drive the brain directly. Most standard artificial neural network models are however input driven and do not show spontaneous activities. It constitutes a challenge to develop organizational principles for controlled, self-sustained activity in artificial neural networks. Here we propose and examine the dHAN concept for autonomous associative thought processes in dense and homogeneous associative networks. An associative thought-process is characterized, within this approach, by a time-series of transient attractors. Each transient state corresponds to a stored information, a memory. The subsequent transient states are characterized by large associative overlaps, which are identical to acquired patterns. Memory states, the acquired patterns, have such a dual functionality. In this approach the self-sustained neural activity has a central functional role. The network acquires a discrimination capability, as external stimuli need to compete with the autonomous activity. Noise in the input is readily filtered-out. Hebbian learning of external patterns occurs coinstantaneous with the ongoing associative thought process. The autonomous dynamics needs a long-term working-point optimization which acquires within the dHAN concept a dual functionality: It stabilizes the time development of the associative thought process and limits runaway synaptic growth, which generically occurs otherwise in neural networks with self-induced activities and Hebbian-type learning rules.

Mixed Stimulus-Induced Mode Selection in Neural Activity Driven by High and Low Frequency Current under Electromagnetic Radiation

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Lulu Lu

2017-01-01

Full Text Available The electrical activities of neurons are dependent on the complex electrophysiological condition in neuronal system, the three-variable Hindmarsh-Rose (HR neuron model is improved to describe the dynamical behaviors of neuronal activities with electromagnetic induction being considered, and the mode transition of electrical activities in neuron is detected when external electromagnetic radiation is imposed on the neuron. In this paper, different types of electrical stimulus impended with a high-low frequency current are imposed on new HR neuron model, and mixed stimulus-induced mode selection in neural activity is discussed in detail. It is found that mode selection of electrical activities stimulated by high-low frequency current, which also changes the excitability of neuron, can be triggered owing to adding the Gaussian white noise. Meanwhile, the mode selection of the neuron electrical activity is much dependent on the amplitude B of the high frequency current under the same noise intensity, and the high frequency response is selected preferentially by applying appropriate parameters and noise intensity. Our results provide insights into the transmission of complex signals in nerve system, which is valuable in engineering prospective applications such as information encoding.

Partial Least Squares and Neural Networks for Quantitative Calibration of Laser-induced Breakdown Spectroscopy (LIBs) of Geologic Samples

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Anderson, R. B.; Morris, Richard V.; Clegg, S. M.; Humphries, S. D.; Wiens, R. C.; Bell, J. F., III; Mertzman, S. A.

2010-01-01

The ChemCam instrument [1] on the Mars Science Laboratory (MSL) rover will be used to obtain the chemical composition of surface targets within 7 m of the rover using Laser Induced Breakdown Spectroscopy (LIBS). ChemCam analyzes atomic emission spectra (240-800 nm) from a plasma created by a pulsed Nd:KGW 1067 nm laser. The LIBS spectra can be used in a semiquantitative way to rapidly classify targets (e.g., basalt, andesite, carbonate, sulfate, etc.) and in a quantitative way to estimate their major and minor element chemical compositions. Quantitative chemical analysis from LIBS spectra is complicated by a number of factors, including chemical matrix effects [2]. Recent work has shown promising results using multivariate techniques such as partial least squares (PLS) regression and artificial neural networks (ANN) to predict elemental abundances in samples [e.g. 2-6]. To develop, refine, and evaluate analysis schemes for LIBS spectra of geologic materials, we collected spectra of a diverse set of well-characterized natural geologic samples and are comparing the predictive abilities of PLS, cascade correlation ANN (CC-ANN) and multilayer perceptron ANN (MLP-ANN) analysis procedures.

Engrafted human induced pluripotent stem cell-derived anterior specified neural progenitors protect the rat crushed optic nerve.

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Leila Satarian

Full Text Available BACKGROUND: Degeneration of retinal ganglion cells (RGCs is a common occurrence in several eye diseases. This study examined the functional improvement and protection of host RGCs in addition to the survival, integration and neuronal differentiation capabilities of anterior specified neural progenitors (NPs following intravitreal transplantation. METHODOLOGY/PRINCIPAL FINDINGS: NPs were produced under defined conditions from human induced pluripotent stem cells (hiPSCs and transplanted into rats whose optic nerves have been crushed (ONC. hiPSCs were induced to differentiate into anterior specified NPs by the use of Noggin and retinoic acid. The hiPSC-NPs were labeled by green fluorescent protein or a fluorescent tracer 1,1' -dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI and injected two days after induction of ONC in hooded rats. Functional analysis according to visual evoked potential recordings showed significant amplitude recovery in animals transplanted with hiPSC-NPs. Retrograde labeling by an intra-collicular DiI injection showed significantly higher numbers of RGCs and spared axons in ONC rats treated with hiPSC-NPs or their conditioned medium (CM. The analysis of CM of hiPSC-NPs showed the secretion of ciliary neurotrophic factor, basic fibroblast growth factor, and insulin-like growth factor. Optic nerve of cell transplanted groups also had increased GAP43 immunoreactivity and myelin staining by FluoroMyelin™ which imply for protection of axons and myelin. At 60 days post-transplantation hiPSC-NPs were integrated into the ganglion cell layer of the retina and expressed neuronal markers. CONCLUSIONS/SIGNIFICANCE: The transplantation of anterior specified NPs may improve optic nerve injury through neuroprotection and differentiation into neuronal lineages. These NPs possibly provide a promising new therapeutic approach for traumatic optic nerve injuries and loss of RGCs caused by other diseases.

Neural Oscillations and Synchrony in Brain Dysfunction and Neuropsychiatric Disorders: It's About Time.

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Mathalon, Daniel H; Sohal, Vikaas S

2015-08-01

Neural oscillations are rhythmic fluctuations over time in the activity or excitability of single neurons, local neuronal populations or "assemblies," and/or multiple regionally distributed neuronal assemblies. Synchronized oscillations among large numbers of neurons are evident in electrocorticographic, electroencephalographic, magnetoencephalographic, and local field potential recordings and are generally understood to depend on inhibition that paces assemblies of excitatory neurons to produce alternating temporal windows of reduced and increased excitability. Synchronization of neural oscillations is supported by the extensive networks of local and long-range feedforward and feedback bidirectional connections between neurons. Here, we review some of the major methods and measures used to characterize neural oscillations, with a focus on gamma oscillations. Distinctions are drawn between stimulus-independent oscillations recorded during resting states or intervals between task events, stimulus-induced oscillations that are time locked but not phase locked to stimuli, and stimulus-evoked oscillations that are both time and phase locked to stimuli. Synchrony of oscillations between recording sites, and between the amplitudes and phases of oscillations of different frequencies (cross-frequency coupling), is described and illustrated. Molecular mechanisms underlying gamma oscillations are also reviewed. Ultimately, understanding the temporal organization of neuronal network activity, including interactions between neural oscillations, is critical for elucidating brain dysfunction in neuropsychiatric disorders.

[Simulation of lung motions using an artificial neural network].

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Laurent, R; Henriet, J; Salomon, M; Sauget, M; Nguyen, F; Gschwind, R; Makovicka, L

2011-04-01

A way to improve the accuracy of lung radiotherapy for a patient is to get a better understanding of its lung motion. Indeed, thanks to this knowledge it becomes possible to follow the displacements of the clinical target volume (CTV) induced by the lung breathing. This paper presents a feasibility study of an original method to simulate the positions of points in patient's lung at all breathing phases. This method, based on an artificial neural network, allowed learning the lung motion on real cases and then to simulate it for new patients for which only the beginning and the end breathing data are known. The neural network learning set is made up of more than 600 points. These points, shared out on three patients and gathered on a specific lung area, were plotted by a MD. The first results are promising: an average accuracy of 1mm is obtained for a spatial resolution of 1 × 1 × 2.5mm(3). We have demonstrated that it is possible to simulate lung motion with accuracy using an artificial neural network. As future work we plan to improve the accuracy of our method with the addition of new patient data and a coverage of the whole lungs. Copyright © 2010 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Engaged listeners: shared neural processing of powerful political speeches.

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Schmälzle, Ralf; Häcker, Frank E K; Honey, Christopher J; Hasson, Uri

2015-08-01

Powerful speeches can captivate audiences, whereas weaker speeches fail to engage their listeners. What is happening in the brains of a captivated audience? Here, we assess audience-wide functional brain dynamics during listening to speeches of varying rhetorical quality. The speeches were given by German politicians and evaluated as rhetorically powerful or weak. Listening to each of the speeches induced similar neural response time courses, as measured by inter-subject correlation analysis, in widespread brain regions involved in spoken language processing. Crucially, alignment of the time course across listeners was stronger for rhetorically powerful speeches, especially for bilateral regions of the superior temporal gyri and medial prefrontal cortex. Thus, during powerful speeches, listeners as a group are more coupled to each other, suggesting that powerful speeches are more potent in taking control of the listeners' brain responses. Weaker speeches were processed more heterogeneously, although they still prompted substantially correlated responses. These patterns of coupled neural responses bear resemblance to metaphors of resonance, which are often invoked in discussions of speech impact, and contribute to the literature on auditory attention under natural circumstances. Overall, this approach opens up possibilities for research on the neural mechanisms mediating the reception of entertaining or persuasive messages. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Asymmetric generalization in adaptation to target displacement errors in humans and in a neural network model.

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Westendorff, Stephanie; Kuang, Shenbing; Taghizadeh, Bahareh; Donchin, Opher; Gail, Alexander

2015-04-01

Different error signals can induce sensorimotor adaptation during visually guided reaching, possibly evoking different neural adaptation mechanisms. Here we investigate reach adaptation induced by visual target errors without perturbing the actual or sensed hand position. We analyzed the spatial generalization of adaptation to target error to compare it with other known generalization patterns and simulated our results with a neural network model trained to minimize target error independent of prediction errors. Subjects reached to different peripheral visual targets and had to adapt to a sudden fixed-amplitude displacement ("jump") consistently occurring for only one of the reach targets. Subjects simultaneously had to perform contralateral unperturbed saccades, which rendered the reach target jump unnoticeable. As a result, subjects adapted by gradually decreasing reach errors and showed negative aftereffects for the perturbed reach target. Reach errors generalized to unperturbed targets according to a translational rather than rotational generalization pattern, but locally, not globally. More importantly, reach errors generalized asymmetrically with a skewed generalization function in the direction of the target jump. Our neural network model reproduced the skewed generalization after adaptation to target jump without having been explicitly trained to produce a specific generalization pattern. Our combined psychophysical and simulation results suggest that target jump adaptation in reaching can be explained by gradual updating of spatial motor goal representations in sensorimotor association networks, independent of learning induced by a prediction-error about the hand position. The simulations make testable predictions about the underlying changes in the tuning of sensorimotor neurons during target jump adaptation. Copyright © 2015 the American Physiological Society.

Pulse-coupled neural nets: translation, rotation, scale, distortion, and intensity signal invariance for images.

Science.gov (United States)

Johnson, J L

1994-09-10

The linking-field neural network model of Eckhorn et al. [Neural Comput. 2, 293-307 (1990)] was introduced to explain the experimentally observed synchronous activity among neural assemblies in the cat cortex induced by feature-dependent visual activity. The model produces synchronous bursts of pulses from neurons with similar activity, effectively grouping them by phase and pulse frequency. It gives a basic new function: grouping by similarity. The synchronous bursts are obtained in the limit of strong linking strengths. The linking-field model in the limit of moderate-to-weak linking characterized by few if any multiple bursts is investigated. In this limit dynamic, locally periodic traveling waves exist whose time signal encodes the geometrical structure of a two-dimensional input image. The signal can be made insensitive to translation, scale, rotation, distortion, and intensity. The waves transmit information beyond the physical interconnect distance. The model is implemented in an optical hybrid demonstration system. Results of the simulations and the optical system are presented.

Toward a Neural Chronometry for the Aesthetic Experience of Music

OpenAIRE

Brattico, Elvira; Bogert, Brigitte; Jacobsen, Thomas

2013-01-01

Music is often studied as a cognitive domain alongside language. The emotional aspects of music have also been shown to be important, but views on their nature diverge. For instance, the specific emotions that music induces and how they relate to emotional expression are still under debate. Here we propose a mental and neural chronometry of the aesthetic experience of music initiated and mediated by external and internal contexts such as intentionality, background mood, attention, and experti...

Association of contextual cues with morphine reward increases neural and synaptic plasticity in the ventral hippocampus of rats.

Science.gov (United States)

Alvandi, Mina Sadighi; Bourmpoula, Maria; Homberg, Judith R; Fathollahi, Yaghoub

2017-11-01

Drug addiction is associated with aberrant memory and permanent functional changes in neural circuits. It is known that exposure to drugs like morphine is associated with positive emotional states and reward-related memory. However, the underlying mechanisms in terms of neural plasticity in the ventral hippocampus, a region involved in associative memory and emotional behaviors, are not fully understood. Therefore, we measured adult neurogenesis, dendritic spine density and brain-derived neurotrophic factor (BDNF) and TrkB mRNA expression as parameters for synaptic plasticity in the ventral hippocampus. Male Sprague Dawley rats were subjected to the CPP (conditioned place preference) paradigm and received 10 mg/kg morphine. Half of the rats were used to evaluate neurogenesis by immunohistochemical markers Ki67 and doublecortin (DCX). The other half was used for Golgi staining to measure spine density and real-time quantitative reverse transcription-polymerase chain reaction to assess BDNF/TrkB expression levels. We found that morphine-treated rats exhibited more place conditioning as compared with saline-treated rats and animals that were exposed to the CPP without any injections. Locomotor activity did not change significantly. Morphine-induced CPP significantly increased the number of Ki67 and DCX-labeled cells in the ventral dentate gyrus. Additionally, we found increased dendritic spine density in both CA1 and dentate gyrus and an enhancement of BDNF/TrkB mRNA levels in the whole ventral hippocampus. Ki67, DCX and spine density were significantly correlated with CPP scores. In conclusion, we show that morphine-induced reward-related memory is associated with neural and synaptic plasticity changes in the ventral hippocampus. Such neural changes could underlie context-induced drug relapse. © 2017 Society for the Study of Addiction.

Orphan nuclear receptor TLX activates Wnt/β-catenin signalling to stimulate neural stem cell proliferation and self-renewal

Science.gov (United States)

Qu, Qiuhao; Sun, Guoqiang; Li, Wenwu; Yang, Su; Ye, Peng; Zhao, Chunnian; Yu, Ruth T.; Gage, Fred H.; Evans, Ronald M.; Shi, Yanhong

2010-01-01

The nuclear receptor TLX (also known as NR2E1) is essential for adult neural stem cell self-renewal; however, the molecular mechanisms involved remain elusive. Here we show that TLX activates the canonical Wnt/β-catenin pathway in adult mouse neural stem cells. Furthermore, we demonstrate that Wnt/β-catenin signalling is important in the proliferation and self-renewal of adult neural stem cells in the presence of epidermal growth factor and fibroblast growth factor. Wnt7a and active β-catenin promote neural stem cell self-renewal, whereas the deletion of Wnt7a or the lentiviral transduction of axin, a β-catenin inhibitor, led to decreased cell proliferation in adult neurogenic areas. Lentiviral transduction of active β-catenin led to increased numbers of type B neural stem cells in the subventricular zone of adult brains, whereas deletion of Wnt7a or TLX resulted in decreased numbers of neural stem cells retaining bromodeoxyuridine label in the adult brain. Both Wnt7a and active β-catenin significantly rescued a TLX (also known as Nr2e1) short interfering RNA-induced deficiency in neural stem cell proliferation. Lentiviral transduction of an active β-catenin increased cell proliferation in neurogenic areas of TLX-null adult brains markedly. These results strongly support the hypothesis that TLX acts through the Wnt/β-catenin pathway to regulate neural stem cell proliferation and self-renewal. Moreover, this study suggests that neural stem cells can promote their own self-renewal by secreting signalling molecules that act in an autocrine/paracrine mode. PMID:20010817

Orphan nuclear receptor TLX activates Wnt/beta-catenin signalling to stimulate neural stem cell proliferation and self-renewal.

Science.gov (United States)

Qu, Qiuhao; Sun, Guoqiang; Li, Wenwu; Yang, Su; Ye, Peng; Zhao, Chunnian; Yu, Ruth T; Gage, Fred H; Evans, Ronald M; Shi, Yanhong

2010-01-01

The nuclear receptor TLX (also known as NR2E1) is essential for adult neural stem cell self-renewal; however, the molecular mechanisms involved remain elusive. Here we show that TLX activates the canonical Wnt/beta-catenin pathway in adult mouse neural stem cells. Furthermore, we demonstrate that Wnt/beta-catenin signalling is important in the proliferation and self-renewal of adult neural stem cells in the presence of epidermal growth factor and fibroblast growth factor. Wnt7a and active beta-catenin promote neural stem cell self-renewal, whereas the deletion of Wnt7a or the lentiviral transduction of axin, a beta-catenin inhibitor, led to decreased cell proliferation in adult neurogenic areas. Lentiviral transduction of active beta-catenin led to increased numbers of type B neural stem cells in the subventricular zone of adult brains, whereas deletion of Wnt7a or TLX resulted in decreased numbers of neural stem cells retaining bromodeoxyuridine label in the adult brain. Both Wnt7a and active beta-catenin significantly rescued a TLX (also known as Nr2e1) short interfering RNA-induced deficiency in neural stem cell proliferation. Lentiviral transduction of an active beta-catenin increased cell proliferation in neurogenic areas of TLX-null adult brains markedly. These results strongly support the hypothesis that TLX acts through the Wnt/beta-catenin pathway to regulate neural stem cell proliferation and self-renewal. Moreover, this study suggests that neural stem cells can promote their own self-renewal by secreting signalling molecules that act in an autocrine/paracrine mode.

A model of stimulus-specific neural assemblies in the insect antennal lobe.

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Dominique Martinez

2008-08-01

Full Text Available It has been proposed that synchronized neural assemblies in the antennal lobe of insects encode the identity of olfactory stimuli. In response to an odor, some projection neurons exhibit synchronous firing, phase-locked to the oscillations of the field potential, whereas others do not. Experimental data indicate that neural synchronization and field oscillations are induced by fast GABA(A-type inhibition, but it remains unclear how desynchronization occurs. We hypothesize that slow inhibition plays a key role in desynchronizing projection neurons. Because synaptic noise is believed to be the dominant factor that limits neuronal reliability, we consider a computational model of the antennal lobe in which a population of oscillatory neurons interact through unreliable GABA(A and GABA(B inhibitory synapses. From theoretical analysis and extensive computer simulations, we show that transmission failures at slow GABA(B synapses make the neural response unpredictable. Depending on the balance between GABA(A and GABA(B inputs, particular neurons may either synchronize or desynchronize. These findings suggest a wiring scheme that triggers stimulus-specific synchronized assemblies. Inhibitory connections are set by Hebbian learning and selectively activated by stimulus patterns to form a spiking associative memory whose storage capacity is comparable to that of classical binary-coded models. We conclude that fast inhibition acts in concert with slow inhibition to reformat the glomerular input into odor-specific synchronized neural assemblies.