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Sample records for neuronal substrate fuel

  1. Growth behavior of cochlear nucleus neuronal cells on semiconductor substrates.

    PubMed

    Rak, Kristen; Wasielewski, Natalia; Radeloff, Andreas; Scherzed, Agmal; Jablonka, Sibylle; Hagen, Rudolf; Mlynski, Robert

    2011-05-01

    Auditory brainstem implants provide sound information by direct stimulation of the cochlear nucleus to patients with dysfunctional or absent cranial nerve VIII. In contrast to patients with cochlear implants, the use of the auditory brainstem implants is less successful. This cannot be fully explained by the difference location of stimulation but a rather unspecific neuronal stimulation. The aim of this study was to further examine neuronal cells of the cochlear nucleus and to test their interactions with semiconductor substrates as a potential electrode material for improved auditory brainstem implants. The cochlear nuclei of postnatal day 7 rats were microsurgically dissected. The tissue was dissociated enzymatically and plated on coverslips as control and on the semiconductor substrates silicon or silicon nitride. After 4 days in culture the morphology and growth of dissociated cells was determined by fluorescence and scanning electron microscopy. Dissociated cells of the cochlear nucleus showed reduced cell growth on semiconductor substrates compared with controls. SEM analysis demonstrated close contact of neurons with supporting cells in culture and good adherence of neuronal growth cones on the used materials. These findings present basic knowledge for the development of neuron-electrode interfaces for future auditory brainstem implants. PMID:21370446

  2. Neuronal oscillations as a mechanistic substrate of auditory temporal prediction

    PubMed Central

    Morillon, Benjamin; Schroeder, Charles E.

    2014-01-01

    Neuronal oscillations are comprised of rhythmic fluctuations of excitability that are synchronized in ensembles of neurons and thus function as temporal filters that dynamically organize sensory processing. When perception relies on anticipatory mechanisms, ongoing oscillations also provide a neurophysiological substrate for temporal prediction. In this article we review evidence for this account with a focus on auditory perception. We argue that such “oscillatory temporal predictions” can selectively amplify neuronal sensitivity to inputs that occur in a predicted, task-relevant rhythm and optimize temporal selection. We elaborate this argument for a prototypic example, speech processing, where information is present at multiple time scales, with delta, theta, and low-gamma oscillations being specifically and simultaneously engaged, enabling multiplexing. We then consider the origin of temporal predictions, specifically the idea that the motor system is involved in the generation of such prior information. Finally, we place temporal predictions in the general context of internal models, discussing how they interact with feature-based or spatial predictions. We propose that complementary predictions interact synergistically according to a dominance hierarchy, shaping perception in the form of a multidimensional filter mechanism. PMID:25773613

  3. Decoding the Substrate Supply to Human Neuronal Nitric Oxide Synthase

    PubMed Central

    Habermeier, Alice; Closs, Ellen I.

    2013-01-01

    Nitric oxide, produced by the neuronal nitric oxide synthase (nNOS) from L-arginine is an important second messenger molecule in the central nervous system: It influences the synthesis and release of neurotransmitters and plays an important role in long-term potentiation, long-term depression and neuroendocrine secretion. However, under certain pathological conditions such as Alzheimer’s or Parkinson’s disease, stroke and multiple sclerosis, excessive NO production can lead to tissue damage. It is thus desirable to control NO production in these situations. So far, little is known about the substrate supply to human nNOS as a determinant of its activity. Measuring bioactive NO via cGMP formation in reporter cells, we demonstrate here that nNOS in both, human A673 neuroepithelioma and TGW-nu-I neuroblastoma cells can be fast and efficiently nourished by extracellular arginine that enters the cells via membrane transporters (pool I that is freely exchangeable with the extracellular space). When this pool was depleted, NO synthesis was partially sustained by intracellular arginine sources not freely exchangeable with the extracellular space (pool II). Protein breakdown made up by far the largest part of pool II in both cell types. In contrast, citrulline to arginine conversion maintained NO synthesis only in TGW-nu-I neuroblastoma, but not A673 neuroepithelioma cells. Histidine mimicked the effect of protease inhibitors causing an almost complete nNOS inhibition in cells incubated additionally in lysine that depletes the exchangeable arginine pool. Our results identify new ways to modulate nNOS activity by modifying its substrate supply. PMID:23874440

  4. The neuronal substrates of human olfactory based kin recognition.

    PubMed

    Lundström, Johan N; Boyle, Julie A; Zatorre, Robert J; Jones-Gotman, Marilyn

    2009-08-01

    Kin recognition, an evolutionary phenomenon ubiquitous among phyla, is thought to promote an individual's genes by facilitating nepotism and avoidance of inbreeding. Whereas isolating and studying kin recognition mechanisms in humans using auditory and visual stimuli is problematic because of the high degree of conscious recognition of the individual involved, kin recognition based on body odors is done predominantly without conscious recognition. Using this, we mapped the neural substrates of human kin recognition by acquiring measures of regional cerebral blood flow from women smelling the body odors of either their sister or their same-sex friend. The initial behavioral experiment demonstrated that accurate identification of kin is performed with a low conscious recognition. The subsequent neuroimaging experiment demonstrated that olfactory based kin recognition in women recruited the frontal-temporal junction, the insula, and the dorsomedial prefrontal cortex; the latter area is implicated in the coding of self-referent processing and kin recognition. We further show that the neuronal response is seemingly independent of conscious identification of the individual source, demonstrating that humans have an odor based kin detection system akin to what has been shown for other mammals. PMID:19067327

  5. Patterning human neuronal networks on photolithographically engineered silicon dioxide substrates functionalized with glial analogues.

    PubMed

    Hughes, Mark A; Brennan, Paul M; Bunting, Andrew S; Cameron, Katherine; Murray, Alan F; Shipston, Mike J

    2014-05-01

    Interfacing neurons with silicon semiconductors is a challenge being tackled through various bioengineering approaches. Such constructs inform our understanding of neuronal coding and learning and ultimately guide us toward creating intelligent neuroprostheses. A fundamental prerequisite is to dictate the spatial organization of neuronal cells. We sought to pattern neurons using photolithographically defined arrays of polymer parylene-C, activated with fetal calf serum. We used a purified human neuronal cell line [Lund human mesencephalic (LUHMES)] to establish whether neurons remain viable when isolated on-chip or whether they require a supporting cell substrate. When cultured in isolation, LUHMES neurons failed to pattern and did not show any morphological signs of differentiation. We therefore sought a cell type with which to prepattern parylene regions, hypothesizing that this cellular template would enable secondary neuronal adhesion and network formation. From a range of cell lines tested, human embryonal kidney (HEK) 293 cells patterned with highest accuracy. LUHMES neurons adhered to pre-established HEK 293 cell clusters and this coculture environment promoted morphological differentiation of neurons. Neurites extended between islands of adherent cell somata, creating an orthogonally arranged neuronal network. HEK 293 cells appear to fulfill a role analogous to glia, dictating cell adhesion, and generating an environment conducive to neuronal survival. We next replaced HEK 293 cells with slower growing glioma-derived precursors. These primary human cells patterned accurately on parylene and provided a similarly effective scaffold for neuronal adhesion. These findings advance the use of this microfabrication-compatible platform for neuronal patterning. PMID:23733444

  6. Patterned growth of neuronal cells on modified diamond-like carbon substrates.

    PubMed

    Kelly, Stephen; Regan, Edward M; Uney, James B; Dick, Andrew D; McGeehan, Joseph P; Mayer, Eric J; Claeyssens, Frederik

    2008-06-01

    Diamond-like carbon (DLC) has been explored as a biomaterial with potential use for coating implantable devices and surgical instruments. In this study the interaction of DLC with mammalian neuronal cells has been studied along with its modifications to improve its function as a biomaterial. We describe the use of DLC, oxidised DLC and phosphorus-doped DLC to support the growth and survival of primary central nervous system neurones and neuroblastoma cells. None of these substrates were cytotoxic and primary neurones adhered better to phosphorus-doped DLC than unmodified DLC. This property was used to culture cortical neurones in a predetermined micropattern. This raises the potential of DLC as a biomaterial for central nervous system (CNS) implantation. Furthermore, patterned DLC and phosphorus-doped DLC can direct neuronal growth, generating a powerful tool to study neuronal networks in a spatially distinct way. This study reports the generation of nerve cell patterns via patterned deposition of DLC. PMID:18359076

  7. Patterning human neuronal networks on photolithographically engineered silicon dioxide substrates functionalized with glial analogues

    PubMed Central

    Hughes, Mark A; Brennan, Paul M; Bunting, Andrew S; Cameron, Katherine; Murray, Alan F; Shipston, Mike J

    2014-01-01

    Interfacing neurons with silicon semiconductors is a challenge being tackled through various bioengineering approaches. Such constructs inform our understanding of neuronal coding and learning and ultimately guide us toward creating intelligent neuroprostheses. A fundamental prerequisite is to dictate the spatial organization of neuronal cells. We sought to pattern neurons using photolithographically defined arrays of polymer parylene-C, activated with fetal calf serum. We used a purified human neuronal cell line [Lund human mesencephalic (LUHMES)] to establish whether neurons remain viable when isolated on-chip or whether they require a supporting cell substrate. When cultured in isolation, LUHMES neurons failed to pattern and did not show any morphological signs of differentiation. We therefore sought a cell type with which to prepattern parylene regions, hypothesizing that this cellular template would enable secondary neuronal adhesion and network formation. From a range of cell lines tested, human embryonal kidney (HEK) 293 cells patterned with highest accuracy. LUHMES neurons adhered to pre-established HEK 293 cell clusters and this coculture environment promoted morphological differentiation of neurons. Neurites extended between islands of adherent cell somata, creating an orthogonally arranged neuronal network. HEK 293 cells appear to fulfill a role analogous to glia, dictating cell adhesion, and generating an environment conducive to neuronal survival. We next replaced HEK 293 cells with slower growing glioma-derived precursors. These primary human cells patterned accurately on parylene and provided a similarly effective scaffold for neuronal adhesion. These findings advance the use of this microfabrication-compatible platform for neuronal patterning. © 2013 The Authors. Journal ofBiomedicalMaterials Research Part APublished byWiley Periodicals, Inc.Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 1350–1360, 2014. PMID:23733444

  8. Agarose-Based Substrate Modification Technique for Chemical and Physical Guiding of Neurons In Vitro.

    PubMed

    Krumpholz, Katharina; Rogal, Julia; El Hasni, Akram; Schnakenberg, Uwe; Bräunig, Peter; Bui-Göbbels, Katrin

    2015-08-26

    A new low cost and highly reproducible technique is presented that provides patterned cell culture substrates. These allow for selective positioning of cells and a chemically and mechanically directed guiding of their extensions. The patterned substrates consist of structured agarose hydrogels molded from reusable silicon micro templates. These templates consist of pins arranged equidistantly in squares, connected by bars, which mold corresponding wells and channels in the nonadhesive agarose hydrogel. Subsequent slice production with a standard vibratome, comprising the described template pattern, completes substrate production. Invertebrate neurons of locusts and pond snails are used for this application as they offer the advantage over vertebrate cells as being very large and suitable for cultivation in low cell density. Their neurons adhere to and grow only on the adhesive areas not covered by the agarose. Agarose slices of 50 μm thickness placed on glass, polystyrene, or MEA surfaces position and immobilize the neurons in the wells, and the channels guide their neurite outgrowth toward neighboring wells. In addition to the application with invertebrate neurons, the technique may also provide the potential for the application of a wide range of cell types. Long-term objective is the achievement of isolated low-density neuronal networks on MEAs or different culture substrates for various network analysis applications. PMID:26237337

  9. Guiding neuron development with planar surface gradients of substrate cues deposited using microfluidic devices

    PubMed Central

    Millet, Larry J.; Stewart, Matthew E.; Nuzzo, Ralph G.

    2010-01-01

    Wiring the nervous system relies on the interplay of intrinsic and extrinsic signaling molecules that control neurite extension, neuronal polarity, process maturation and experience-dependent refinement. Extrinsic signals establish and enrich neuron-neuron interactions during development. Understanding how such extrinsic cues direct neurons to establish neural connections in vitro will facilitate the development of organised neural networks for investigating the development and function of nervous system networks. Producing ordered networks of neurons with defined connectivity in vitro presents special technical challenges because the results must be compliant with the biological requirements of rewiring neural networks. Here we demonstrate the ability to form stable, instructive surface-bound gradients of laminin that guide postnatal hippocampal neuron development in vitro. Our work uses a three-channel, interconnected microfluidic device that permits the production of adlayers of planar substrates through the combination of laminar flow, diffusion and physisorption. Through simple flow modifications, a variety of patterns and gradients of laminin (LN) and flourescein-conjugated poly-lysine (FITC-PLL) were deposited to present neurons with an instructive substratum to guide neuronal development. We present three variations in substrate design that produce distinct growth regimens for postnatal neurons in dispersed cell cultures. In the first approach, diffusion-mediated gradients of LN were formed on coverslips to guide neurons toward increasing LN concentrations. In the second approach, a combined gradient of LN and FITC-PLL was produced using aspiration-driven laminar flow to restrict neuronal growth to a 15 μm-wide growth zone at the center of the two superimposed gradients. The last approach demonstrates the capacity to combine binary lines of FITC-PLL in conjunction with surface gradients of LN and bovine serum albumin (BSA) to produce substrate adlayers

  10. Probing Mechanoregulation of Neuronal Differentiation by Plasma Lithography Patterned Elastomeric Substrates

    NASA Astrophysics Data System (ADS)

    Nam, Ki-Hwan; Jamilpour, Nima; Mfoumou, Etienne; Wang, Fei-Yue; Zhang, Donna D.; Wong, Pak Kin

    2014-11-01

    Cells sense and interpret mechanical cues, including cell-cell and cell-substrate interactions, in the microenvironment to collectively regulate various physiological functions. Understanding the influences of these mechanical factors on cell behavior is critical for fundamental cell biology and for the development of novel strategies in regenerative medicine. Here, we demonstrate plasma lithography patterning on elastomeric substrates for elucidating the influences of mechanical cues on neuronal differentiation and neuritogenesis. The neuroblastoma cells form neuronal spheres on plasma-treated regions, which geometrically confine the cells over two weeks. The elastic modulus of the elastomer is controlled simultaneously by the crosslinker concentration. The cell-substrate mechanical interactions are also investigated by controlling the size of neuronal spheres with different cell seeding densities. These physical cues are shown to modulate with the formation of focal adhesions, neurite outgrowth, and the morphology of neuroblastoma. By systematic adjustment of these cues, along with computational biomechanical analysis, we demonstrate the interrelated mechanoregulatory effects of substrate elasticity and cell size. Taken together, our results reveal that the neuronal differentiation and neuritogenesis of neuroblastoma cells are collectively regulated via the cell-substrate mechanical interactions.

  11. Substrate Three-Dimensionality Induces Elemental Morphological Transformation of Sensory Neurons on a Physiologic Timescale

    PubMed Central

    Ribeiro, Andreia; Vargo, Shelby; Powell, Elizabeth M.

    2012-01-01

    The natural environment of a neuron is the three-dimensional (3D) tissue. In vivo, embryonic sensory neurons transiently express a bipolar morphology with two opposing neurites before undergoing cytoplasmic and cytoskeletal rearrangement to a more mature pseudo-unipolar axonal arbor before birth. The unipolar morphology is crucial in the adult for correct information transmission from the periphery to the central nervous system. On two-dimensional (2D) substrates this transformation is delayed significantly or absent. We report that a 3D culture platform can invoke the characteristic transformation to the unipolar axonal arbor within a time frame similar to in vivo, overcoming the loss of this essential milestone in 2D substrates. Additionally, 3D substrates alone provided an environment that promoted axonal branching features that reflect morphological patterns observed in vivo. We have also analyzed the involvement of soluble cues in these morphogenic processes by culturing the neurons in the presence and absence of nerve growth factor (NGF), a molecule that plays distinct roles in the development of the peripheral and central nervous systems. Without NGF, both 2D and 3D cultures had significant decreases in the relative population of unipolar neurons as well as shorter neurite lengths and fewer branch points compared to cultures with NGF. Interestingly, branching features of neurons cultured in 3D without NGF resemble those of neurons cultured in 2D with NGF. Therefore, neurons cultured in 3D without NGF lost the ability to differentiate into unipolar neurons, suggesting that this morphological hallmark requires not only presentation of soluble cues like NGF, but also the surrounding 3D presentation of adhesive ligands to allow for realization of the innate morphogenic program. We propose that in a 3D environment, various matrix and soluble cues are presented toward all surfaces of the cell; this optimized milieu allows neurons to elaborate their genuine

  12. Macroscopic and Macromolecular Specificity of Alkylphenol Anesthetics for Neuronal Substrates

    PubMed Central

    Weiser, Brian P.; Hall, Michael A.; Weinbren, Nathan L.; Woll, Kellie A.; Dailey, William P.; Eckenhoff, Maryellen F.; Eckenhoff, Roderic G.

    2015-01-01

    We used a photoactive general anesthetic called meta-azi-propofol (AziPm) to test the selectivity and specificity of alkylphenol anesthetic binding in mammalian brain. Photolabeling of rat brain sections with [3H]AziPm revealed widespread but heterogeneous ligand distribution, with [3H]AziPm preferentially binding to synapse-dense areas compared to areas composed largely of cell bodies or myelin. With [3H]AziPm and propofol, we determined that alkylphenol general anesthetics bind selectively and specifically to multiple synaptic protein targets. In contrast, the alkylphenol anesthetics do not bind to specific sites on abundant phospholipids or cholesterol, although [3H]AziPm shows selectivity for photolabeling phosphatidylethanolamines. Together, our experiments suggest that alkylphenol anesthetic substrates are widespread in number and distribution, similar to those of volatile general anesthetics, and that multi-target mechanisms likely underlie their pharmacology. PMID:25853337

  13. Identification of Phosphorylation Consensus Sequences and Endogenous Neuronal Substrates of the Psychiatric Risk Kinase TNIK.

    PubMed

    Wang, Qi; Amato, Stephen P; Rubitski, David M; Hayward, Matthew M; Kormos, Bethany L; Verhoest, Patrick R; Xu, Lan; Brandon, Nicholas J; Ehlers, Michael D

    2016-02-01

    Traf2- and Nck-interacting kinase (TNIK) is a serine/threonine kinase highly expressed in the brain and enriched in the postsynaptic density of glutamatergic synapses in the mammalian brain. Accumulating genetic evidence and functional data have implicated TNIK as a risk factor for psychiatric disorders. However, the endogenous substrates of TNIK in neurons are unknown. Here, we describe a novel selective small molecule inhibitor of the TNIK kinase family. Using this inhibitor, we report the identification of endogenous neuronal TNIK substrates by immunoprecipitation with a phosphomotif antibody followed by mass spectrometry. Phosphorylation consensus sequences were defined by phosphopeptide sequence analysis. Among the identified substrates were members of the delta-catenin family including p120-catenin, δ-catenin, and armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF), each of which is linked to psychiatric or neurologic disorders. Using p120-catenin as a representative substrate, we show TNIK-induced p120-catenin phosphorylation in cells requires intact kinase activity and phosphorylation of TNIK at T181 and T187 in the activation loop. Addition of the small molecule TNIK inhibitor or knocking down TNIK by two shRNAs reduced endogenous p120-catenin phosphorylation in cells. Together, using a TNIK inhibitor and phosphomotif antibody, we identify endogenous substrates of TNIK in neurons, define consensus sequences for TNIK, and suggest signaling pathways by which TNIK influences synaptic development and function linked to psychiatric and neurologic disorders. PMID:26645429

  14. Gradients of substrate-bound laminin orient axonal specification of neurons

    PubMed Central

    Dertinger, Stephan K. W.; Jiang, Xingyu; Li, Zhiying; Murthy, Venkatesh N.; Whitesides, George M.

    2002-01-01

    Little is known about the influence of substrate-bound gradients on neuronal development, since it has been difficult to fabricate gradients over the distances typically required for biological studies (a few hundred micrometers). This article demonstrates a generally applicable technique for the fabrication of substrate-bound gradients of proteins with complex shapes, using laminar flows in microchannels. Gradients that range from pure laminin to pure BSA were formed in solution by using a network of microchannels, and these proteins were allowed to adsorb onto a homogeneous layer of poly-l-lysine. Rat hippocampal neurons were cultivated on these substrate-bound gradients. Analysis of optical images of these neurons showed that axon specification is oriented in the direction of increasing surface density of laminin. Linear gradients in laminin adsorbed from a gradient in solution having a slope of ∇[laminin] > about 0.06 μg (ml⋅μm)−1 (defined by dividing the change of concentration of laminin in solution over the distance of the gradient) orient axon specification, whereas those with ∇[laminin] < about 0.06 μg (ml⋅μm)−1 have no effect. PMID:12237407

  15. Functional mapping of the neuronal substrates for drug tolerance in Drosophila.

    PubMed

    Ghezzi, Alfredo; Al-Hasan, Yazan M; Krishnan, Harish R; Wang, Yan; Atkinson, Nigel S

    2013-05-01

    Physical dependence on alcohol and anesthetics stems from neuroadaptive changes that act to counter the effects of sedation in the brain. In Drosophila, exposure to either alcohol or solvent anesthetics have been shown to induce changes in expression of the BK-type Ca(2+)-activated K(+) channel gene slo. An increase in slo expression produces an adaptive modulation of neural activity that generates resistance to sedation and promotes drug tolerance and dependence. Increased BK channel activity counteracts the sedative effects of these drugs by reducing the neuronal refractory period and enhancing the capacity of neurons for repetitive firing. However, the brain regions or neuronal populations capable of producing inducible resistance or tolerance remain unknown. Here we map the neuronal substrates relevant for the slo-dependent modulation of drug sensitivity. Using spatially-controlled induction of slo expression we identify the mushroom bodies, the ellipsoid body and a subset of the circadian clock neurons as pivotal regions for the control of recovery from sedation. PMID:23371357

  16. Ceria catalyst for inert-substrate-supported tubular solid oxide fuel cells running on methane fuel

    NASA Astrophysics Data System (ADS)

    Zhao, Kai; Kim, Bok-Hee; Du, Yanhai; Xu, Qing; Ahn, Byung-Guk

    2016-05-01

    A ceria catalyst is applied to an inert-substrate supported tubular single cell for direct operation on methane fuel. The tubular single cell comprises a porous yttria-stabilized zirconia (YSZ) supporter, a Ni-Ce0.8Sm0.2O1.9 anode, a YSZ/Ce0.8Sm0.2O1.9 bi-layer electrolyte, and a La0.6Sr0.4Co0.2Fe0.8O3-δ cathode. The ceria catalyst is incorporated into the porous YSZ supporter layer by a cerium nitrate impregnation. The effects of ceria on the microstructure and electrochemical performance of the tubular single cell are investigated with respect to the number of impregnations. The optimum number of impregnations is determined to be four based on the maximum power density and polarization property of the tubular single cell in hydrogen and methane fuels. At 700 °C, the tubular single cell shows similar maximum power densities of ∼260 mW cm-2 in hydrogen and methane fuels, respectively. Moreover, the ceria catalyst significantly improves the performance stability of the cell running on methane fuel. At a current density of 350 mA cm-2, the single cell shows a low degradation rate of 2.5 mV h-1 during the 13 h test in methane fuel. These results suggest the feasibility of applying the ceria catalyst to the inert-substrate supported tubular single cell for direct operation on methane fuel.

  17. The Effect of Substrate Topography on Direct Reprogramming of Fibroblasts to Induced Neurons

    PubMed Central

    Kulangara, Karina; Adler, Andrew F.; Wang, Hong; Chellappan, Malathi; Hammett, Ellen; Yasuda, Ryohei; Leong, Kam W.

    2014-01-01

    Cellular reprogramming holds tremendous potential for cell therapy and regenerative medicine. Recently, fibroblasts have been directly converted into induced neurons (iNs) by overexpression of the neuronal transcription factors Ascl1, Brn2 and Myt1L. Hypothesizing that cell-topography interactions could influence the fibroblast-to-neuron reprogramming process, we investigated the effects of various topographies on iNs produced by direct reprogramming. Final iN purity and conversion efficiency were increased on micrograting substrates. Neurite branching was increased on microposts and decreased on microgratings, with a simplified dendritic arbor characterized by the reduction of MAP2+ neurites. Neurite outgrowth increased significantly on various topographies. DNA microarray analysis detected 20 differentially expressed genes in iNs reprogrammed on smooth versus microgratings, and quantitative PCR (qPCR) confirmed the upregulation of Vip and downregulation of Thy1 and Bmp5 on microgratings. Electrophysiology and calcium imaging verified the functionality of these iNs. This study demonstrates the potential of applying topographical cues to optimize cellular reprogramming. PMID:24709523

  18. The structural development of primary cultured hippocampal neurons on a graphene substrate.

    PubMed

    He, Zuhong; Zhang, Shasha; Song, Qin; Li, Wenyan; Liu, Dong; Li, Huawei; Tang, Mingliang; Chai, Renjie

    2016-10-01

    The potential of graphene-based nanomaterials as a neural interfacing material for neural repair and regeneration remains poorly understood. In the present study, the response to the graphene substrate by neurons was determined in a hippocampal culture model. The results revealed the growth and maturation of hippocampal cultures on graphene substrates were significantly improved compared to the commercial control. In details, graphene promoted growth cone growth and microtubule formation inside filopodia 24h after seeding as evidenced by a higher average number of filopodia emerging from growth cones, a longer average length of filopodia, and a larger growth cone area. Graphene also significantly boosted neurite sprouting and outgrowth. The dendritic length, the number of branch points, and the dendritic complex index were significantly improved on the graphene substrate during culture. Moreover, the spine density was enhanced and the maturation of dendritic spines from thin to stubby spines was significantly promoted on graphene at 21 days after seeding. Lastly, graphene significantly elevated the synapse density and synaptic activity in the hippocampal cultures. The present study highlights graphene's potential as a neural interfacing material for neural repair and regeneration and sheds light on the future biomedical applications of graphene-based nanomaterials. PMID:27395037

  19. Characterization of a variety of standard collagen substrates: ultrastructure, uniformity, and capacity to bind and promote growth of neurons

    SciTech Connect

    Iversen, P.L.; Partlow, L.M.; Stensaas, L.J.; Moatamed, F.

    1981-06-01

    Collagen substrates were characterized after preparation by the four methods most commonly used for tissue culture (saline precipitation, exposure to ammonium hydroxide vapor, exposure to ultraviolet light, and air drying). Although roughly equivalent percentages of collagen were precipitated by each technique (87 to 97%), marked differences were found in surface uniformity and ultrastructure. Substrates were quite uniform if precipitated by exposure to ammonium hydroxide or ultraviolet light, of intermediate uniformity if saline precipitated, and not at all uniform if air dried. Scanning electron microscopy revealed that (a) ammonium hydroxide and saline precipitation primarily resulted in formation of collagen fibrils, (b) air drying produced a small number of fibrils plus a large amount of amorphous material, and (c) exposure to ultraviolet light only resulted in the formation of globular, nonfibrillar collagen aggregates. The capacity of collagen substrates to bind and grow neurons differed markedly with the method of preparation and the amount of collagen plated per unit area. Quantifications of binding and growth of both cerebral and sympathetic neurons revealed that these are separate measures of the biocompatibility of a surface and that growth was uniformly inferior on globular collagen that had been precipitated by ultraviolet light. Long-term (greater than or equal to 2 wk) growth of sympathetic neurons was optimal on thick beds of saline-precipitated collagen, whereas short-term growth was best on thin layers of either saline or ammonium hydroxide-precipitated collagen. Cerebral neurons bound and grew optimally on thick collagen beds after both short- and long-term culture. In addition, cerebral neurons were found to be more dependent on the method of precipitation of the thin collagen substrates than were sympathetic neurons.

  20. Specific Neuron Placement on Gold and Silicon Nitride-Patterned Substrates through a Two-Step Functionalization Method.

    PubMed

    Mescola, Andrea; Canale, Claudio; Prato, Mirko; Diaspro, Alberto; Berdondini, Luca; Maccione, Alessandro; Dante, Silvia

    2016-06-28

    The control of neuron-substrate adhesion has been always a challenge for fabricating neuron-based cell chips and in particular for multielectrode array (MEA) devices, which warrants the investigation of the electrophysiological activity of neuronal networks. The recent introduction of high-density chips based on the complementary metal oxide semiconductor (CMOS) technology, integrating thousands of electrodes, improved the possibility to sense large networks and raised the challenge to develop newly adapted functionalization techniques to further increase neuron electrode localization to avoid the positioning of cells out of the recording area. Here, we present a simple and straightforward chemical functionalization method that leads to the precise and exclusive positioning of the neural cell bodies onto modified electrodes and inhibits, at the same time, cellular adhesion in the surrounding insulator areas. Different from other approaches, this technique does not require any adhesion molecule as well as complex patterning technique such as μ-contact printing. The functionalization was first optimized on gold (Au) and silicon nitride (Si3N4)-patterned surfaces. The procedure consisted of the introduction of a passivating layer of hydrophobic silane molecules (propyltriethoxysilane [PTES]) followed by a treatment of the Au surface using 11-amino-1-undecanethiol hydrochloride (AT). On model substrates, well-ordered neural networks and an optimal coupling between a single neuron and single micrometric functionalized Au surface were achieved. In addition, we presented the preliminary results of this functionalization method directly applied on a CMOS-MEA: the electrical spontaneous spiking and bursting activities of the network recorded for up to 4 weeks demonstrate an excellent and stable neural adhesion and functional behavior comparable with what expected using a standard adhesion factor, such as polylysine or laminin, thus demonstrating that this procedure can be

  1. Effects of substrate mineralogy on the biodegradability of fuel components

    SciTech Connect

    Apitz, S.E.; Meyers-Schulte, K.J.

    1996-11-01

    Experiments were carried out to determine the effects of mineralogy on the biodegradability of components of a whole fuel by a soil microbial consortium. Samples of quartz sand (Fischer Sea Sand) and illite clay (API 35) were spiked with marine diesel fuel, aged, slurried, and inoculated, and concentrations of fuel components were monitored over time. To help distinguish biotic from abiotic processes, identical samples were poisoned with mercuric chloride and were run in parallel. While there was a chromatographic and biomarker evidence of n-alkane biodegradation in the sand samples, illite samples showed no evidence of biogenic loss of aliphatic components. Polycyclic aromatic hydrocarbons, on the other hand, were lost equivalently on both minerals and in both cases were lost to a much greater extent than were total petroleum hydrocarbons (TPHs). These results suggest that under experimental conditions, illite inhibited the bioavailability of some TPH components to the soil microbial consortium.

  2. Colloids as Mobile Substrates for the Implantation and Integration of Differentiated Neurons into the Mammalian Brain

    PubMed Central

    Jgamadze, Dennis; Bergen, Jamie; Stone, Daniel; Jang, Jae-Hyung; Schaffer, David V.; Isacoff, Ehud Y.; Pautot, Sophie

    2012-01-01

    Neuronal degeneration and the deterioration of neuronal communication lie at the origin of many neuronal disorders, and there have been major efforts to develop cell replacement therapies for treating such diseases. One challenge, however, is that differentiated cells are challenging to transplant due to their sensitivity both to being uprooted from their cell culture growth support and to shear forces inherent in the implantation process. Here, we describe an approach to address these problems. We demonstrate that rat hippocampal neurons can be grown on colloidal particles or beads, matured and even transfected in vitro, and subsequently transplanted while adhered to the beads into the young adult rat hippocampus. The transplanted cells have a 76% cell survival rate one week post-surgery. At this time, most transplanted neurons have left their beads and elaborated long processes, similar to the host neurons. Additionally, the transplanted cells distribute uniformly across the host hippocampus. Expression of a fluorescent protein and the light-gated glutamate receptor in the transplanted neurons enabled them to be driven to fire by remote optical control. At 1-2 weeks after transplantation, calcium imaging of host brain slice shows that optical excitation of the transplanted neurons elicits activity in nearby host neurons, indicating the formation of functional transplant-host synaptic connections. After 6 months, the transplanted cell survival and overall cell distribution remained unchanged, suggesting that cells are functionally integrated. This approach, which could be extended to other cell classes such as neural stem cells and other regions of the brain, offers promising prospects for neuronal circuit repair via transplantation of in vitro differentiated, genetically engineered neurons. PMID:22295079

  3. Regeneration of Aplysia Bag Cell Neurons is Synergistically Enhanced by Substrate-Bound Hemolymph Proteins and Laminin

    NASA Astrophysics Data System (ADS)

    Hyland, Callen; Dufrense, Eric R.; Forscher, Paul

    2014-04-01

    We have investigated Aplysia hemolymph as a source of endogenous factors to promote regeneration of bag cell neurons. We describe a novel synergistic effect between substrate-bound hemolymph proteins and laminin. This combination increased outgrowth and branching relative to either laminin or hemolymph alone. Notably, the addition of hemolymph to laminin substrates accelerated growth cone migration rate over ten-fold. Our results indicate that the active factor is either a high molecular weight protein or protein complex and is not the respiratory protein hemocyanin. Substrate-bound factor(s) from central nervous system-conditioned media also had a synergistic effect with laminin, suggesting a possible cooperation between humoral proteins and nervous system extracellular matrix. Further molecular characterization of active factors and their cellular targets is warranted on account of the magnitude of the effects reported here and their potential relevance for nervous system repair.

  4. Effects of elevated magnesium and substrate on neuronal numbers and neurite outgrowth of neural stem/progenitor cells in vitro.

    PubMed

    Vennemeyer, John J; Hopkins, Tracy; Kuhlmann, Julia; Heineman, William R; Pixley, Sarah K

    2014-07-01

    Because a potential treatment for brain injuries could be elevating magnesium ions (Mg(2+)) intracerebrally, we characterized the effects of elevating external Mg(2+) in cultures of neonatal murine brain-derived neural stem/progenitor cells (NSCs). Using a crystal violet assay, which avoids interference of Mg(2+) in the assay, it was determined that substrate influenced Mg(2+) effects on cell numbers. On uncoated plastic, elevating Mg(2+) levels to between 2.5 and 10mM above basal increased NSC numbers, and at higher concentrations numbers decreased to control or lower levels. Similar biphasic curves were observed with different plating densities, treatment durations and length of time in culture. When cells were plated on laminin-coated plastic, NSC numbers were higher even in basal medium and no further effects were observed with Mg(2+). NSC differentiation into neurons was not altered by either substrate or Mg(2+) supplementation. Some parameters of neurite outgrowth were increased by elevated Mg(2+) when NSCs differentiated into neurons on uncoated plastic. Differentiation on laminin resulted in increased neurites even in basal medium and no further effects were seen when Mg(2+) was elevated. This system can now be used to study the multiple mechanisms by which Mg(2+) influences neuronal biology. PMID:24815060

  5. Monoaminergic substrates underlying cocaine-induced enhancement of somatosensory-evoked discharges in rat barrel field cortical neurons.

    PubMed

    Waterhouse, B D; Gould, E M; Bekavac, I

    1996-11-01

    Previously, we have described a selective potentiating effect of systemically administered cocaine (0.25-1.0 mg/kg i.v.) on long-latency excitatory responses (E2) of rat "barrel field" cortical neurons to mystacial vibrissae stimulation. The rat trigeminal system receives both norepinephrine (NE) and serotonin (5-HT)-containing afferents, but only minimal input from dopaminergic sources. The goal of the present study was to determine which of these monoamine systems was responsible for the previously observed facilitating action of cocaine on E2 responses of barrel field cortical neurons. Two approaches were used: 1) evaluation of cocaine effects on cortical neuron responses to whisker stimulation in NE- or 5-HT-depleted animals and 2) assessment of the effects of selective monoamine uptake blockers on cortical neuron responses to whisker deflection. Extracellular recordings were obtained from spontaneously active neurons in the barrel field cortex of halothane-anesthetized rats. Spontaneous activity and cellular responses to mechanical displacement of a single whisker were monitored before and after systemic (i.v.) administration of either cocaine or one of the following selective uptake blockers, fluoxetine (5-HT), desipramine (NE) and GBR12909 (dopamine). Cocaine-induced increases in the E2 response were observed in N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4, noradrenergic neurotoxin)-treated animals, but were reduced or abolished in p-chlorophenylalanine-treated (5-HT depletion) rats. Fluoxetine and desipramine, but not GBR12909, produced cocaine-like potentiation of the E2 response to whisker stimulation. These results point to a 5-HT-dependent mechanism as the substrate underlying cocaine's facilitating effects on long-latency somatosensory cortical neuron responses to receptive field stimulation. PMID:8930160

  6. Honeybee retinal glial cells transform glucose and supply the neurons with metabolic substrate

    SciTech Connect

    Tsacopoulos, M.; Evequoz-Mercier, V.; Perrottet, P.; Buchner, E.

    1988-11-01

    The retina of the honeybee drone is a nervous tissue in which glial cells and photoreceptor cells (sensory neurons) constitute two distinct metabolic compartments. Retinal slices incubated with 2-deoxy(/sup 3/H)glucose convert this glucose analogue to 2-deoxy(/sup 3/H)glucose 6-phosphate, but this conversion is made only in the glial cells. Hence, glycolysis occurs only in glial cells. In contrast, the neurons consume O/sub 2/ and this consumption is sustained by the hydrolysis of glycogen, which is contained in large amounts in the glia. During photostimulation the increased oxidative metabolism of the neurons is sustained by a higher supply of carbohydrates from the glia. This clear case of metabolic interaction between neurons and glial cells supports Golgi's original hypothesis, proposed nearly 100 years ago, about the nutritive function of glial cells in the nervous system.

  7. Integrins establish dendrite-substrate relationships that promote dendritic self-avoidance and patterning in Drosophila sensory neurons

    PubMed Central

    Kim, Michelle E.; Shrestha, Brikha R.; Blazeski, Richard; Mason, Carol A.; Grueber, Wesley B.

    2012-01-01

    Summary Dendrites achieve characteristic spacing patterns during development to ensure appropriate coverage of territories. Mechanisms of dendrite positioning via repulsive dendrite-dendrite interactions are beginning to be elucidated, but the control, and importance, of dendrite positioning relative to their substrate is poorly understood. We found that dendritic branches of Drosophila dendritic arborization sensory neurons can be positioned either at the basal surface of epidermal cells, or enclosed within epidermal invaginations. We show that integrins control dendrite positioning on or within the epidermis in a cell autonomous manner by promoting dendritic retention on the basal surface. Loss of integrin function in neurons resulted in excessive self-crossing and dendrite maintenance defects, the former indicating a novel role for substrate interactions in self-avoidance. In contrast to a contact-mediated mechanism, we find that integrins prevent crossings that are non-contacting between dendrites in different three-dimensional positions, revealing a requirement for combined dendrite-dendrite and dendrite-substrate interactions in self-avoidance. PMID:22243748

  8. Substrates and pathway of electricity generation in a nitrification-based microbial fuel cell.

    PubMed

    Chen, Hui; Zheng, Ping; Zhang, Jiqiang; Xie, Zuofu; Ji, Junyuan; Ghulam, Abbas

    2014-06-01

    Nitrification-based microbial fuel cell (N-MFC) is a novel inorganic microbial fuel cell based on nitrification in the anode compartment. So far, little information is available on the substrates and pathway of N-MFC. The results of this study indicated that apart from the primary nitrification substrate (ammonium), the intermediates (hydroxylamine and nitrite) could also serve as anodic fuel to generate current, and the end product nitrate showed an inhibitory effect on electricity generation. Based on the research, a pathway of electricity generation was proposed for N-MFC: ammonium was oxidized first to nitrite by ammonia-oxidizing bacteria (AOB), then the nitrite in anolyte and the potassium permanganate in catholyte constituted a chemical cell to generate current. In other words, the electricity generation in N-MFC was not only supported by microbial reaction as we expected, but both biological and electrochemical reactions contributed. PMID:24704886

  9. Hypothalamic AgRP-neurons control peripheral substrate utilization and nutrient partitioning

    PubMed Central

    Joly-Amado, Aurélie; Denis, Raphaël G P; Castel, Julien; Lacombe, Amélie; Cansell, Céline; Rouch, Claude; Kassis, Nadim; Dairou, Julien; Cani, Patrice D; Ventura-Clapier, Renée; Prola, Alexandre; Flamment, Melissa; Foufelle, Fabienne; Magnan, Christophe; Luquet, Serge

    2012-01-01

    Obesity-related diseases such as diabetes and dyslipidemia result from metabolic alterations including the defective conversion, storage and utilization of nutrients, but the central mechanisms that regulate this process of nutrient partitioning remain elusive. As positive regulators of feeding behaviour, agouti-related protein (AgRP) producing neurons are indispensible for the hypothalamic integration of energy balance. Here, we demonstrate a role for AgRP-neurons in the control of nutrient partitioning. We report that ablation of AgRP-neurons leads to a change in autonomic output onto liver, muscle and pancreas affecting the relative balance between lipids and carbohydrates metabolism. As a consequence, mice lacking AgRP-neurons become obese and hyperinsulinemic on regular chow but display reduced body weight gain and paradoxical improvement in glucose tolerance on high-fat diet. These results provide a direct demonstration of a role for AgRP-neurons in the coordination of efferent organ activity and nutrient partitioning, providing a mechanistic link between obesity and obesity-related disorders. PMID:22990237

  10. Neuronal Nicotinic Acetylcholine Receptors: Common Molecular Substrates of Nicotine and Alcohol Dependence

    PubMed Central

    Hendrickson, Linzy M.; Guildford, Melissa J.; Tapper, Andrew R.

    2013-01-01

    Alcohol and nicotine are often co-abused. As many as 80–95% of alcoholics are also smokers, suggesting that ethanol and nicotine, the primary addictive component of tobacco smoke, may functionally interact in the central nervous system and/or share a common mechanism of action. While nicotine initiates dependence by binding to and activating neuronal nicotinic acetylcholine receptors (nAChRs), ligand-gated cation channels normally activated by endogenous acetylcholine (ACh), ethanol is much less specific with the ability to modulate multiple gene products including those encoding voltage-gated ion channels, and excitatory/inhibitory neurotransmitter receptors. However, emerging data indicate that ethanol interacts with nAChRs, both directly and indirectly, in the mesocorticolimbic dopaminergic (DAergic) reward circuitry to affect brain reward systems. Like nicotine, ethanol activates DAergic neurons of the ventral tegmental area (VTA) which project to the nucleus accumbens (NAc). Blockade of VTA nAChRs reduces ethanol-mediated activation of DAergic neurons, NAc DA release, consumption, and operant responding for ethanol in rodents. Thus, ethanol may increase ACh release into the VTA driving activation of DAergic neurons through nAChRs. In addition, ethanol potentiates distinct nAChR subtype responses to ACh and nicotine in vitro and in DAergic neurons. The smoking cessation therapeutic and nAChR partial agonist, varenicline, reduces alcohol consumption in heavy drinking smokers and rodent models of alcohol consumption. Finally, single nucleotide polymorphisms in nAChR subunit genes are associated with alcohol dependence phenotypes and smoking behaviors in human populations. Together, results from pre-clinical, clinical, and genetic studies indicate that nAChRs may have an inherent role in the abusive properties of ethanol, as well as in nicotine and alcohol co-dependence. PMID:23641218

  11. Effect of Substrate Thickness on Oxide Scale Spallation for Solid Oxide Fuel Cells

    SciTech Connect

    Liu, Wenning N.; Sun, Xin; Stephens, Elizabeth V.; Khaleel, Mohammad A.

    2011-07-01

    In this paper, the effect of the ferritic substrate's thickness on the delamination/spallation of the oxide scale was investigated experimentally and numerically. At the high-temperature oxidation environment of solid oxide fuel cells (SOFCs), a combination of growth stress with thermal stresses may lead to scale delamination/buckling and eventual spallation during SOFC stack cooling, even leading to serious degradation of cell performance. The growth stress is induced by the growth of the oxide scale on the scale/substrate interface, and thermal stress is induced by a mismatch of the coefficient of thermal expansion between the oxide scale and the substrate. The numerical results show that the interfacial shear stresses, which are the driving force of scale delamination between the oxide scale and the ferritic substrate, increase with the growth of the oxide scale and also with the thickness of the ferritic substrate; i.e., the thick ferritic substrate can easily lead to scale delamination and spallation. Experimental observation confirmed the predicted results of the delamination and spallation of the oxide scale on the ferritic substrate.

  12. Fracture toughness of solid oxide fuel cell anode substrates determined by a double-torsion technique

    NASA Astrophysics Data System (ADS)

    Pećanac, G.; Wei, J.; Malzbender, J.

    2016-09-01

    Planar solid oxide fuel cell anode substrates are exposed to high mechanical loads during assembly, start-up, steady-state operation and thermal cycling. Hence, characterization of mechanical stability of anode substrates under different oxidation states and at relevant temperatures is essential to warrant a reliable operation of solid oxide fuel cells. As a basis for mechanical assessment of brittle supports, two most common anode substrate material variants, NiO-3YSZ and NiO-8YSZ, were analyzed in this study with respect to their fracture toughness at room temperature and at a typical stack operation temperature of 800 °C. The study considered both, oxidized and reduced materials' states, where also an outlook is given on the behavior of the re-oxidized state that might be induced by malfunctions of sealants or other functional components. Aiming at the improvement of material's production, different types of warm pressed and tape cast NiO-8YSZ substrates were characterized in oxidized and reduced states. Overall, the results confirmed superior fracture toughness of 3YSZ compared to 8YSZ based composites in the oxidized state, whereas in the reduced state 3YSZ based composites showed similar fracture toughness at room temperature, but a higher value at 800 °C compared to 8YSZ based composites. Complementary microstructural analysis aided the interpretation of mechanical characterization.

  13. Characterization of spiral ganglion neurons cultured on silicon micro-pillar substrates for new auditory neuro-electronic interfaces

    NASA Astrophysics Data System (ADS)

    Mattotti, M.; Micholt, L.; Braeken, D.; Kovačić, D.

    2015-04-01

    Objective. One of the strategies to improve cochlear implant technology is to increase the number of electrodes in the neuro-electronic interface. The objective was to characterize in vitro cultures of spiral ganglion neurons (SGN) cultured on surfaces of novel silicon micro-pillar substrates (MPS). Approach. SGN from P5 rat pups were cultured on MPS with different micro-pillar widths (1-5.6 μm) and spacings (0.6-15 μm) and were compared with control SGN cultures on glass coverslips by immunocytochemistry and scanning electron microscopy (SEM). Main results. Overall, MPS support SGN growth equally well as the control glass surfaces. Micro-pillars of a particular size-range (1.2-2.4 μm) were optimal in promoting SGN presence, neurite growth and alignment. On this specific micro-pillar size, more SGN were present, and neurites were longer and more aligned. SEM pictures highlight how cells on micro-pillars with smaller spacings grow directly on top of pillars, while at wider spacings (from 3.2 to 15 μm) they grow on the bottom of the surface, losing contact guidance. Further, we found that MPS encourage more monopolar and bipolar SGN morphologies compared to the control condition. Finally, MPS induce longest neurite growth with minimal interaction of S100+ glial cells. Significance. These results indicate that silicon micro-pillar substrates create a permissive environment for the growth of primary auditory neurons promoting neurite sprouting and are a promising technology for future high-density three-dimensional CMOS-based auditory neuro-electronic interfaces.

  14. Phylogenetic and metagenomic analyses of substrate-dependent bacterial temporal dynamics in microbial fuel cells.

    PubMed

    Zhang, Husen; Chen, Xi; Braithwaite, Daniel; He, Zhen

    2014-01-01

    Understanding the microbial community structure and genetic potential of anode biofilms is key to improve extracellular electron transfers in microbial fuel cells. We investigated effect of substrate and temporal dynamics of anodic biofilm communities using phylogenetic and metagenomic approaches in parallel with electrochemical characterizations. The startup non-steady state anodic bacterial structures were compared for a simple substrate, acetate, and for a complex substrate, landfill leachate, using a single-chamber air-cathode microbial fuel cell. Principal coordinate analysis showed that distinct community structures were formed with each substrate type. The bacterial diversity measured as Shannon index decreased with time in acetate cycles, and was restored with the introduction of leachate. The change of diversity was accompanied by an opposite trend in the relative abundance of Geobacter-affiliated phylotypes, which were acclimated to over 40% of total Bacteria at the end of acetate-fed conditions then declined in the leachate cycles. The transition from acetate to leachate caused a decrease in output power density from 243±13 mW/m2 to 140±11 mW/m2, accompanied by a decrease in Coulombic electron recovery from 18±3% to 9±3%. The leachate cycles selected protein-degrading phylotypes within phylum Synergistetes. Metagenomic shotgun sequencing showed that leachate-fed communities had higher cell motility genes including bacterial chemotaxis and flagellar assembly, and increased gene abundance related to metal resistance, antibiotic resistance, and quorum sensing. These differentially represented genes suggested an altered anodic biofilm community in response to additional substrates and stress from the complex landfill leachate. PMID:25202990

  15. Monosynaptic convergence of somatic and visceral C-fiber afferents on projection and local circuit neurons in lamina I: a substrate for referred pain

    PubMed Central

    Luz, Liliana L.; Fernandes, Elisabete C.; Sivado, Miklos; Kokai, Eva; Szucs, Peter; Safronov, Boris V.

    2015-01-01

    Abstract Referred pain is a phenomenon of feeling pain at a site other than the site of the painful stimulus origin. It arises from a pathological mixing of nociceptive processing pathways for visceral and somatic inputs. Despite numerous studies based on unit recordings from spinal and supraspinal neurons, the exact mechanism and site of this mixing within the central nervous system are not known. Here, we selectively recorded from lamina I neurons, using a visually guided patch-clamp technique, in thoracic spinal cord preparation with preserved intercostal (somatic) and splanchnic (visceral) nerves. We show that somatic and visceral C fibers converge monosynaptically onto a group of lamina I neurons, which includes both projection and local circuit neurons. Other groups of lamina I neurons received inputs from either somatic or visceral afferents. We have also identified a population of lamina I local circuit neurons showing overall inhibitory responses upon stimulation of both nerves. Thus, the present data allow us to draw two major conclusions. First, lamina I of the spinal cord is the first site in the central nervous system where somatic and visceral pathways directly converge onto individual projection and local circuit neurons. Second, the mechanism of somatovisceral convergence is complex and based on functional integration of monosynaptic and polysynaptic excitatory as well as inhibitory inputs in specific groups of neurons. This complex pattern of convergence provides a substrate for alterations in the balance between visceral and somatic inputs causing referred pain. PMID:26098437

  16. Largely overlapping neuronal substrates of reactivity to drug, gambling, food and sexual cues: A comprehensive meta-analysis.

    PubMed

    Noori, Hamid R; Cosa Linan, Alejandro; Spanagel, Rainer

    2016-09-01

    Cue reactivity to natural and social rewards is essential for motivational behavior. However, cue reactivity to drug rewards can also elicit craving in addicted subjects. The degree to which drug and natural rewards share neural substrates is not known. The objective of this study is to conduct a comprehensive meta-analysis of neuroimaging studies on drug, gambling and natural stimuli (food and sex) to identify the common and distinct neural substrates of cue reactivity to drug and natural rewards. Neural cue reactivity studies were selected for the meta-analysis by means of activation likelihood estimations, followed by sensitivity and clustering analyses of averaged neuronal response patterns. Data from 176 studies (5573 individuals) suggests largely overlapping neural response patterns towards all tested reward modalities. Common cue reactivity to natural and drug rewards was expressed by bilateral neural responses within anterior cingulate gyrus, insula, caudate head, inferior frontal gyrus, middle frontal gyrus and cerebellum. However, drug cues also generated distinct activation patterns in medial frontal gyrus, middle temporal gyrus, posterior cingulate gyrus, caudate body and putamen. Natural (sexual) reward cues induced unique activation of the pulvinar in thalamus. Neural substrates of cue reactivity to alcohol, drugs of abuse, food, sex and gambling are largely overlapping and comprise a network that processes reward, emotional responses and habit formation. This suggests that cue-mediated craving involves mechanisms that are not exclusive for addictive disorders but rather resemble the intersection of information pathways for processing reward, emotional responses, non-declarative memory and obsessive-compulsive behavior. PMID:27397863

  17. Neuronal substrate and effective connectivity of abnormal movement sequencing in schizophrenia.

    PubMed

    Zemankova, Petra; Lungu, Ovidiu; Huttlova, Jitka; Kerkovsky, Milos; Zubor, Jozef; Lipova, Petra; Bares, Martin; Kasparek, Tomas

    2016-06-01

    Movement sequencing difficulties are part of the neurological soft signs (NSS), they have high clinical value because they are not always present in schizophrenia. We investigated the neuronal correlates of movement sequencing in 24 healthy controls and 24 schizophrenia patients, with (SZP SQ+) or without (SZP SQ-) sequencing difficulties. We characterized simultaneous and lagged functional connectivity between brain regions involved in movement sequencing using psychophysiological interaction (PPI) and the Granger causality modeling (GCM), respectively. Left premotor cortex (PMC) and superior parietal lobule (SPL) were specifically activated during sequential movements in all participants. Right PMC and precuneus, ipsilateral to the hand executing the task, activated during sequential movements only in healthy controls and SZP SQ-. SZP SQ+ showed hyperactivation in contralateral PMC, as compared to the other groups. PPI analysis revealed a deficit in inhibitory connections within this fronto-parietal network in SZP SQ+ during sequential task. GCM showed a significant lagged effective connectivity from right PMC to left SPL during task and rest periods in all groups and from right PMC to right precuneus in SZP SQ+ group only. Both SZP groups had a significant lagged connectivity from right to left PMC, during sequential task. Our results indicate that aberrant fronto-parietal network connectivity with cortical inhibition deficit and abnormal reliance on previous network activity are related to movement sequencing in SZP. The overactivation of motor cortex seems to be a good compensating strategy, the hyperactivation of parietal cortex is linked to motor deficit symptoms. PMID:26780603

  18. Substrate arrays of iridium oxide microelectrodes for in vitro neuronal interfacing.

    PubMed

    Gawad, Shady; Giugliano, Michele; Heuschkel, Marc; Wessling, Börge; Markram, Henry; Schnakenberg, Uwe; Renaud, Philippe; Morgan, Hywel

    2009-01-01

    The design of novel bidirectional interfaces for in vivo and in vitro nervous systems is an important step towards future functional neuroprosthetics. Small electrodes, structures and devices are necessary to achieve high-resolution and target-selectivity during stimulation and recording of neuronal networks, while significant charge transfer and large signal-to-noise ratio are required for accurate time resolution. In addition, the physical properties of the interface should remain stable across time, especially when chronic in vivo applications or in vitro long-term studies are considered, unless a procedure to actively compensate for degradation is provided. In this short report, we describe the use and fabrication of arrays of 120 planar microelectrodes (MEAs) of sputtered Iridium Oxide (IrOx). The effective surface area of individual microelectrodes is significantly increased using electrochemical activation, a procedure that may also be employed to restore the properties of the electrodes as required. The electrode activation results in a very low interface impedance, especially in the lower frequency domain, which was characterized by impedance spectroscopy. The increase in the roughness of the microelectrodes surface was imaged using digital holographic microscopy and electron microscopy. Aging of the activated electrodes was also investigated, comparing storage in saline with storage in air. Demonstration of concept was achieved by recording multiple single-unit spike activity in acute brain slice preparations of rat neocortex. Data suggests that extracellular recording of action potentials can be achieved with planar IrOx MEAs with good signal-to-noise ratios. PMID:19194527

  19. Influence of substrate on electricity generation of Shewanella loihica PV-4 in microbial fuel cells

    PubMed Central

    2014-01-01

    Background The substrate, serving as carbon and energy source, is one of the major factors affecting the performance of microbial fuel cells (MFCs). We utilized BIOLOG system to rapidly screen substrates for electricigens, and further evaluated influence of these substrates on electricity generation of Shewanella loihica PV-4 in MFCs. Results Three of most favorable substrates (lactate acid, formic acid and cyclodextrin) with OD590/750 of 0.952, 0.880 and 0.849 as well as three of most unfavorable substrates (galactose, arabinose and glucose) with OD590/750 of 0.248, 0.137 and 0.119 were selected by BIOLOG system under aerobic conditions. The chronoamperometry results showed that MFCs fed with these substrates exhibited different current behaviors. Cyclic voltammograms results showed that arabinose, galactose and glucose promoted electron transfer from outer membrane c-Cyts of cells to the electrode surface. Lactic acid, formic acid and cyclodextrin produced lower quantity of electric charge of 10.13 C, 9.83 C and 10.10 C, the corresponding OD600 value was 0.180, 0.286 and 0.152 in BES; while galactose, arabinose and glucose generated higher quantity of electric charge of 12.34 C, 13.42 C and 17.45 C, and increased OD600 values were 0.338, 0.558 and 0.409 in BES. SEMs results showed that plenty of plump and stretched cells as well as appendages were observed when lactic acid, formic acid, and cyclodextrin were utilized as substrates, while sparse cells in short shape were obtained when galactose, arabinose and glucose were used as substrates. Conclusions These results suggest that substrate not only has important role in electrochemical performances of MFCs but also in biological properties of electricigens. Lactic acid, formic acid, and cyclodextrin beneficial for cell growth under aerobic conditions are unfavourable for planktonic cell growth and current generation under anaerobic conditions, while consumptions of galactose, arabinose and glucose adverse to cell

  20. Influence of substrate concentration and feed frequency on ammonia inhibition in microbial fuel cells

    NASA Astrophysics Data System (ADS)

    Tice, Ryan C.; Kim, Younggy

    2014-12-01

    Excessive amounts of ammonia are known to inhibit exoelectrogenic activities in microbial fuel cells (MFCs). However, the threshold ammonia concentration that triggers toxic effects is not consistent among literature papers, indicating that ammonia inhibition can be affected by other operational factors. Here, we examined the effect of substrate concentration and feed frequency on the capacity of exoelectrogenic bacteria to resist against ammonia inhibition. The high substrate condition (2 g L-1 sodium acetate, 2-day feed) maintained high electricity generation (between 1.1 and 1.9 W m-2) for total ammonia concentration up to 4000 mg-N L-1. The less frequent feed condition (2 g L-1 sodium acetate, 6-day feed) and the low substrate condition (0.67 g L-1 sodium acetate, 2-day feed) resulted in substantial decreases in electricity generation at total ammonia concentration of 2500 and 3000 mg-N L-1, respectively. It was determined that the power density curve serves as a better indicator than continuously monitored electric current for predicting ammonia inhibition in MFCs. The chemical oxygen demand (COD) removal gradually decreased at high ammonia concentration even without ammonia inhibition in electricity generation. The experimental results demonstrated that high substrate concentration and frequent feed substantially enhance the capacity of exoelectrogenic bacteria to resist against ammonia inhibition.

  1. Evaluation of normalized energy recovery (NER) in microbial fuel cells affected by reactor dimensions and substrates.

    PubMed

    Xiao, Li; Ge, Zheng; Kelly, Patrick; Zhang, Fei; He, Zhen

    2014-04-01

    The objective of this study is to provide an initial evaluation of normalized energy recovery (NER - a new parameter for presenting energy performance) in microbial fuel cells (MFCs) through investigation of the effects of reactor dimensions and anode substrates. Although the larger-size MFCs generally have lower maximum power densities, their maximum NER is comparable to that of the smaller MFCs at the same anolyte flow rate. The mixed messages obtained from the MFC size tests suggest that MFCs can be further scaled up without decreasing energy recovery under certain conditions. The low-strength substrates seem to be more suitable for MFC treatment of wastewater, in terms of both energy recovery and organic removal. However, because the MFCs could not achieve the maximum NER and the maximum organic removal efficiency at the same time, one must determine a major goal for MFCs treating wastewater between energy recovery and contaminant removal. PMID:24534787

  2. Carbon Nanofibers Modified Graphite Felt for High Performance Anode in High Substrate Concentration Microbial Fuel Cells

    PubMed Central

    Shen, Youliang; Zhou, Yan; Chen, Shuiliang; Yang, Fangfang; Zheng, Suqi; Hou, Haoqing

    2014-01-01

    Carbon nanofibers modified graphite fibers (CNFs/GF) composite electrode was prepared for anode in high substrate concentration microbial fuel cells. Electrochemical tests showed that the CNFs/GF anode generated a peak current density of 2.42 mA cm−2 at a low acetate concentration of 20 mM, which was 54% higher than that from bare GF. Increase of the acetate concentration to 80 mM, in which the peak current density of the CNFs/GF anode greatly increased and was up to 3.57 mA cm−2, was seven times as that of GF anode. Morphology characterization revealed that the biofilms in the CNFs/GF anode were much denser than those in the bare GF. This result revealed that the nanostructure in the anode not only enhanced current generation but also could tolerate high substrate concentration. PMID:24883348

  3. Neuronal Substrates Underlying Performance Variability in Well-Trained Skillful Motor Task in Humans

    PubMed Central

    2016-01-01

    Motor performance fluctuates trial by trial even in a well-trained motor skill. Here we show neural substrates underlying such behavioral fluctuation in humans. We first scanned brain activity with functional magnetic resonance imaging while healthy participants repeatedly performed a 10 s skillful sequential finger-tapping task. Before starting the experiment, the participants had completed intensive training. We evaluated task performance per trial (number of correct sequences in 10 s) and depicted brain regions where the activity changes in association with the fluctuation of the task performance across trials. We found that the activity in a broader range of frontoparietocerebellar network, including the bilateral dorsolateral prefrontal cortex (DLPFC), anterior cingulate and anterior insular cortices, and left cerebellar hemisphere, was negatively correlated with the task performance. We further showed in another transcranial direct current stimulation (tDCS) experiment that task performance deteriorated, when we applied anodal tDCS to the right DLPFC. These results indicate that fluctuation of brain activity in the nonmotor frontoparietocerebellar network may underlie trial-by-trial performance variability even in a well-trained motor skill, and its neuromodulation with tDCS may affect the task performance. PMID:27516909

  4. Quantitative characterization of crude oils and fuels in mineral substrates using reflectance spectroscopy: Implications for remote sensing

    NASA Astrophysics Data System (ADS)

    Scafutto, Rebecca Del'Papa Moreira; Souza Filho, Carlos Roberto de

    2016-08-01

    The near and shortwave infrared spectral reflectance properties of several mineral substrates impregnated with crude oils (°APIs 19.2, 27.5 and 43.2), diesel, gasoline and ethanol were measured and assembled in a spectral library. These data were examined using Principal Component Analysis (PCA) and Partial Least Squares (PLS) Regression. Unique and characteristic absorption features were identified in the mixtures, besides variations of the spectral signatures related to the compositional difference of the crude oils and fuels. These features were used for qualitative and quantitative determination of the contaminant impregnated in the substrates. Specific wavelengths, where key absorption bands occur, were used for the individual characterization of oils and fuels. The intensity of these features can be correlated to the abundance of the contaminant in the mixtures. Grain size and composition of the impregnated substrate directly influence the variation of the spectral signatures. PCA models applied to the spectral library proved able to differentiate the type and density of the hydrocarbons. The calibration models generated by PLS are robust, of high quality and can also be used to predict the concentration of oils and fuels in mixtures with mineral substrates. Such data and models are employable as a reference for classifying unknown samples of contaminated substrates. The results of this study have important implications for onshore exploration and environmental monitoring of oil and fuels leaks using proximal and far range multispectral, hyperspectral and ultraespectral remote sensing.

  5. Designing Photoelectrodes for Photocatalytic Fuel Cells and Elucidating the Effects of Organic Substrates.

    PubMed

    Hu, Chenyan; Kelm, Denis; Schreiner, Manuel; Wollborn, Tobias; Mädler, Lutz; Teoh, Wey Yang

    2015-12-01

    Photocatalytic fuel cells (PFCs) are constructed from anodized photoanodes with the aim of effectively converting organic materials into solar electricity. The syntheses of the photoanodes (TiO2 , WO3 , and Nb2 O5 ) were optimized using the statistical 2(k) factorial design. A systematic study was carried out to catalog the influence of eleven types of organic substrate on the photocurrent responses of the photoanodes, showing dependence on the adsorption of the organic substrates and on the associated photocatalytic degradation mechanisms. Strong adsorbates, such as carboxylic acids, generated high photocurrent enhancements. Simple and short-chained molecules, such as formic acid and methanol, are the most efficient in the corresponding carboxylic acid and alcohol groups as a result of their fast degradation kinetics. The TiO2 -based PFC yielded the highest photocurrent and obtainable power, whereas the Nb2 O5 -based PFC achieved the highest open-circuit voltage, which is consistent with its most negative Fermi level. PMID:26564312

  6. Fuel availability and fate in cardiac metabolism: A tale of two substrates.

    PubMed

    Pascual, Florencia; Coleman, Rosalind A

    2016-10-01

    The heart's extraordinary metabolic flexibility allows it to adapt to normal changes in physiology in order to preserve its function. Alterations in the metabolic profile of the heart have also been attributed to pathological conditions such as ischemia and hypertrophy; however, research during the past decade has established that cardiac metabolic adaptations can precede the onset of pathologies. It is therefore critical to understand how changes in cardiac substrate availability and use trigger events that ultimately result in heart dysfunction. This review examines the mechanisms by which the heart obtains fuels from the circulation or from mobilization of intracellular stores. We next describe experimental models that exhibit either an increase in glucose use or a decrease in FA oxidation, and how these aberrant conditions affect cardiac metabolism and function. Finally, we highlight the importance of alternative, relatively under-investigated strategies for the treatment of heart failure. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID:26993579

  7. Impaired Neurite Contact Guidance in Ubiquitin Ligase E3a (Ube3a)-Deficient Hippocampal Neurons on Nanostructured Substrates.

    PubMed

    Tonazzini, I; Meucci, S; Van Woerden, G M; Elgersma, Y; Cecchini, M

    2016-04-01

    Recent discoveries indicate that during neuronal development the signaling processes that regulate extracellular sensing (e.g., adhesion, cytoskeletal dynamics) are important targets for ubiquitination-dependent regulation, in particular through E3 ubiquitin ligases. Among these, Ubiquitin E3a ligase (UBE3A) has a key role in brain functioning, but its function and how its deficiency results in the neurodevelopmental disorder Angelman syndrome is still unclear. Here, the role of UBE3A is investigated in neurite contact guidance during neuronal development, in vitro. The microtopography sensing of wild-type and Ube3a-deficient hippocampal neurons is studied by exploiting gratings with different topographical characteristics, with the aim to compare their capabilities to read and follow physical directional stimuli. It is shown that neuronal contact guidance is defective in Ube3a-deficient neurons, and this behavior is linked to an impaired activation of the focal adhesion signaling pathway. Taken together, the results suggest that the neuronal contact sensing machinery might be affected in Angelman syndrome. PMID:26845073

  8. Epidermis-Derived Semaphorin Promotes Dendrite Self-Avoidance by Regulating Dendrite-Substrate Adhesion in Drosophila Sensory Neurons.

    PubMed

    Meltzer, Shan; Yadav, Smita; Lee, Jiae; Soba, Peter; Younger, Susan H; Jin, Peng; Zhang, Wei; Parrish, Jay; Jan, Lily Yeh; Jan, Yuh-Nung

    2016-02-17

    Precise patterning of dendritic arbors is critical for the wiring and function of neural circuits. Dendrite-extracellular matrix (ECM) adhesion ensures that the dendrites of Drosophila dendritic arborization (da) sensory neurons are properly restricted in a 2D space, and thereby facilitates contact-mediated dendritic self-avoidance and tiling. However, the mechanisms regulating dendrite-ECM adhesion in vivo are poorly understood. Here, we show that mutations in the semaphorin ligand sema-2b lead to a dramatic increase in self-crossing of dendrites due to defects in dendrite-ECM adhesion, resulting in a failure to confine dendrites to a 2D plane. Furthermore, we find that Sema-2b is secreted from the epidermis and signals through the Plexin B receptor in neighboring neurons. Importantly, we find that Sema-2b/PlexB genetically and physically interacts with TORC2 complex, Tricornered (Trc) kinase, and integrins. These results reveal a novel role for semaphorins in dendrite patterning and illustrate how epidermal-derived cues regulate neural circuit assembly. PMID:26853303

  9. Power densities and microbial communities of brewery wastewater-fed microbial fuel cells according to the initial substrates.

    PubMed

    Yu, Jaecheul; Park, Younghyun; Kim, Byunggoon; Lee, Taeho

    2015-01-01

    Single-chamber microbial fuel cells (MFCs) acclimated with glucose, butyrate, propionate, acetate, and a mixture of the four were operated with brewery wastewater (BWW) under a fed-batch mode. Glucose-fed MFC (GW-MFC) showed the highest maximum power density (PDmax) of 1,519 mW/m(2), followed in order by acetate-fed MFC (AW-MFC), mixed substrates-fed MFC (MW-MFC), butyrate-fed MFC (BW-MFC), and propionate-fed MFC (PW-MFC). After changing to BWW, power production was decreased for all MFCs. MFC acclimated with glucose showed the highest PDmax of 890 ± 12 mW/m(2), followed in order by MW-MFC, AW-MFC, BW-MFC, and PW-MFC. The PDmax in BWW-MFC, which was acclimated and operated with BWW, of 552 mW/m(2) was less than that of GW-MFC and MW-MFC but more than that of AW-MFC, BW-MFC, and PW-MFC. MFCs with fermentable substrates were less affected by the BWW. Gammaproteobacteria, including Pseudomonas sp., Acinetobacter sp. and Xanthomonas axonopodis, were found in all MFCs with pure substrates and Rubrivivax benzoatilyticus, thiobacillus sp. and Denitratisoma oestradiolicum belonging to Betaproteobacteria were newly detected in all MFCs when the substrate was changed to BWW. PMID:24973903

  10. β-Hydroxybutyrate is the preferred substrate for GABA and glutamate synthesis while glucose is indispensable during depolarization in cultured GABAergic neurons.

    PubMed

    Lund, Trine M; Obel, Linea F; Risa, Øystein; Sonnewald, Ursula

    2011-08-01

    The ketogenic diet has multiple beneficial effects not only in treatment of epilepsy, but also in that of glucose transporter 1 deficiency, cancer, Parkinson's disease, obesity and pain. Thus, there is an increasing interest in understanding the mechanism behind this metabolic therapy. Patients on a ketogenic diet reach high plasma levels of ketone bodies, which are used by the brain as energy substrates. The interaction between glucose and ketone bodies is complex and there is still controversy as to what extent it affects the homeostasis of the neurotransmitters glutamate, aspartate and GABA. The present study was conducted to study this metabolic interaction in cultured GABAergic neurons exposed to different combinations of (13)C-labeled and unlabeled glucose and β-hydroxybutyrate. Depolarization was induced and the incorporation of (13)C into glutamate, GABA and aspartate was analyzed. The presence of β-hydroxybutyrate together with glucose did not affect the total GABA content but did, however, decrease the aspartate content to a lower value than when either glucose or β-hydroxybutyrate was employed alone. When combinations of the two substrates were used (13)C-atoms from β-hydroxybutyrate were found in all three amino acids to a greater extent than (13)C-atoms from glucose, but only the (13)C contribution from [1,6-(13)C]glucose increased upon depolarization. In conclusion, β-hydroxybutyrate was preferred over glucose as substrate for amino acid synthesis but the total content of aspartate decreased when both substrates were present. Furthermore only the use of glucose increased upon depolarization. PMID:21684314

  11. Role of an isoform-specific substrate access channel residue in CO ligand accessibilities of neuronal and inducible nitric oxide synthase isoforms.

    PubMed

    Feng, Changjian; Fan, Weihong; Ghosh, Dipak K; Tollin, Gordon

    2011-03-01

    The rates of the bimolecular CO rebinding to the oxygenase domains of inducible and neuronal NOS proteins (iNOSoxy and nNOSoxy, respectively) after photolytic dissociation have been determined by laser flash photolysis. The following mutants at the isoform-specific sites (murine iNOSoxy N115L and rat nNOSoxy L337N, L337F) have been constructed to investigate role of the residues in the CO ligand accessibilities of the NOS isoforms. These residues are in the NOS distal substrate access channel. The effect of the (6R)-5,6,7,8-tetrahydrobiopterin (H(4)B) cofactor and l-arginine (Arg) substrate on the rates of CO rebinding have also been assessed. Addition of l-Arg to the iNOSoxy N115L mutant results in much faster CO rebinding rates, compared to the wild type. The results indicate that modifications to the iNOS channel in which the hydrophilic residue N115 is replaced by leucine (to resemble its nNOS cognate) open the channel somewhat, thereby improving access to the axial heme ligand binding position. On the other hand, introduction of a hydrophilic residue (L337N) or a bulky rigid aromatic residue (L337F) in the nNOS isoform does not significantly affect the kinetics profile, suggesting that the geometry of the substrate access pocket is not greatly altered. The bimolecular CO rebinding rate data indicate that the opening of the substrate access channel in the iNOS N115L mutant may be due to more widespread structural alterations induced by the mutation. PMID:21146639

  12. QSpike tools: a generic framework for parallel batch preprocessing of extracellular neuronal signals recorded by substrate microelectrode arrays

    PubMed Central

    Mahmud, Mufti; Pulizzi, Rocco; Vasilaki, Eleni; Giugliano, Michele

    2014-01-01

    Micro-Electrode Arrays (MEAs) have emerged as a mature technique to investigate brain (dys)functions in vivo and in in vitro animal models. Often referred to as “smart” Petri dishes, MEAs have demonstrated a great potential particularly for medium-throughput studies in vitro, both in academic and pharmaceutical industrial contexts. Enabling rapid comparison of ionic/pharmacological/genetic manipulations with control conditions, MEAs are employed to screen compounds by monitoring non-invasively the spontaneous and evoked neuronal electrical activity in longitudinal studies, with relatively inexpensive equipment. However, in order to acquire sufficient statistical significance, recordings last up to tens of minutes and generate large amount of raw data (e.g., 60 channels/MEA, 16 bits A/D conversion, 20 kHz sampling rate: approximately 8 GB/MEA,h uncompressed). Thus, when the experimental conditions to be tested are numerous, the availability of fast, standardized, and automated signal preprocessing becomes pivotal for any subsequent analysis and data archiving. To this aim, we developed an in-house cloud-computing system, named QSpike Tools, where CPU-intensive operations, required for preprocessing of each recorded channel (e.g., filtering, multi-unit activity detection, spike-sorting, etc.), are decomposed and batch-queued to a multi-core architecture or to a computers cluster. With the commercial availability of new and inexpensive high-density MEAs, we believe that disseminating QSpike Tools might facilitate its wide adoption and customization, and inspire the creation of community-supported cloud-computing facilities for MEAs users. PMID:24678297

  13. QSpike tools: a generic framework for parallel batch preprocessing of extracellular neuronal signals recorded by substrate microelectrode arrays.

    PubMed

    Mahmud, Mufti; Pulizzi, Rocco; Vasilaki, Eleni; Giugliano, Michele

    2014-01-01

    Micro-Electrode Arrays (MEAs) have emerged as a mature technique to investigate brain (dys)functions in vivo and in in vitro animal models. Often referred to as "smart" Petri dishes, MEAs have demonstrated a great potential particularly for medium-throughput studies in vitro, both in academic and pharmaceutical industrial contexts. Enabling rapid comparison of ionic/pharmacological/genetic manipulations with control conditions, MEAs are employed to screen compounds by monitoring non-invasively the spontaneous and evoked neuronal electrical activity in longitudinal studies, with relatively inexpensive equipment. However, in order to acquire sufficient statistical significance, recordings last up to tens of minutes and generate large amount of raw data (e.g., 60 channels/MEA, 16 bits A/D conversion, 20 kHz sampling rate: approximately 8 GB/MEA,h uncompressed). Thus, when the experimental conditions to be tested are numerous, the availability of fast, standardized, and automated signal preprocessing becomes pivotal for any subsequent analysis and data archiving. To this aim, we developed an in-house cloud-computing system, named QSpike Tools, where CPU-intensive operations, required for preprocessing of each recorded channel (e.g., filtering, multi-unit activity detection, spike-sorting, etc.), are decomposed and batch-queued to a multi-core architecture or to a computers cluster. With the commercial availability of new and inexpensive high-density MEAs, we believe that disseminating QSpike Tools might facilitate its wide adoption and customization, and inspire the creation of community-supported cloud-computing facilities for MEAs users. PMID:24678297

  14. Atomic layer deposition of ultrathin blocking layer for low-temperature solid oxide fuel cell on nanoporous substrate

    SciTech Connect

    Yu, Wonjong; Cho, Gu Young; Noh, Seungtak; Tanveer, Waqas Hassan; Cha, Suk Won; Ji, Sanghoon; An, Jihwan

    2015-01-15

    An ultrathin yttria-stabilized zirconia (YSZ) blocking layer deposited by atomic layer deposition (ALD) was utilized for improving the performance and reliability of low-temperature solid oxide fuel cells (SOFCs) supported by an anodic aluminum oxide substrate. Physical vapor-deposited YSZ and gadolinia-doped ceria (GDC) electrolyte layers were deposited by a sputtering method. The ultrathin ALD YSZ blocking layer was inserted between the YSZ and GDC sputtered layers. To investigate the effects of an inserted ultrathin ALD blocking layer, SOFCs with and without an ultrathin ALD blocking layer were electrochemically characterized. The open circuit voltage (1.14 V) of the ALD blocking-layered SOFC was visibly higher than that (1.05 V) of the other cell. Furthermore, the ALD blocking layer augmented the power density and improved the reproducibility.

  15. Surface engineering of nanoporous substrate for solid oxide fuel cells with atomic layer-deposited electrolyte

    PubMed Central

    Ji, Sanghoon; Tanveer, Waqas Hassan; Yu, Wonjong; Kang, Sungmin; Cho, Gu Young; Kim, Sung Han

    2015-01-01

    Summary Solid oxide fuel cells with atomic layer-deposited thin film electrolytes supported on anodic aluminum oxide (AAO) are electrochemically characterized with varying thickness of bottom electrode catalyst (BEC); BECs which are 0.5 and 4 times thicker than the size of AAO pores are tested. The thicker BEC ensures far more active mass transport on the BEC side and resultantly the thicker BEC cell generates ≈11 times higher peak power density than the thinner BEC cell at 500 °C. PMID:26425432

  16. Surface engineering of nanoporous substrate for solid oxide fuel cells with atomic layer-deposited electrolyte.

    PubMed

    Ji, Sanghoon; Tanveer, Waqas Hassan; Yu, Wonjong; Kang, Sungmin; Cho, Gu Young; Kim, Sung Han; An, Jihwan; Cha, Suk Won

    2015-01-01

    Solid oxide fuel cells with atomic layer-deposited thin film electrolytes supported on anodic aluminum oxide (AAO) are electrochemically characterized with varying thickness of bottom electrode catalyst (BEC); BECs which are 0.5 and 4 times thicker than the size of AAO pores are tested. The thicker BEC ensures far more active mass transport on the BEC side and resultantly the thicker BEC cell generates ≈11 times higher peak power density than the thinner BEC cell at 500 °C. PMID:26425432

  17. Regulation of Blood Pressure, Appetite, and Glucose by Leptin After Inactivation of Insulin Receptor Substrate 2 Signaling in the Entire Brain or in Proopiomelanocortin Neurons.

    PubMed

    do Carmo, Jussara M; da Silva, Alexandre A; Wang, Zhen; Freeman, Nathan J; Alsheik, Ammar J; Adi, Ahmad; Hall, John E

    2016-02-01

    Insulin receptor substrate 2 (IRS2) is one of the 3 major leptin receptor signaling pathways, but its role in mediating the chronic effects of leptin on blood pressure, food intake, and glucose regulation is unclear. We tested whether genetic inactivation of IRS2 in the entire brain (IRS2/Nestin-cre mice) or specifically in proopiomelanocortin (POMC) neurons (IRS2/POMC-cre mice) attenuates the chronic cardiovascular, metabolic, and antidiabetic effects of leptin. Mice were instrumented with telemetry probes for measurement of blood pressure and heart rate and with venous catheters for intravenous infusions. After a 5-day control period, mice received leptin infusion (2 μg/kg per minute) for 7 days. Compared with control IRS2(flox/flox) mice, IRS2/POMC-cre mice had similar body weight and food intake (33±1 versus 35±1 g and 3.6±0.5 versus 3.8±0.2 g per day) but higher mean arterial pressure (MAP) and heart rate (110±2 versus 102±2 mm Hg and 641±9 versus 616±5 bpm). IRS2/Nestin-cre mice were heavier (38±2 g), slightly hyperphagic (4.5±1.0 g per day), and had higher MAP and heart rate (108±2 mm Hg and 659±9 bpm) compared with control mice. Leptin infusion gradually increased MAP despite decreasing food intake by 31% in IRS2(flox/flox) and in Nestin-cre control mice. In contrast, leptin infusion did not change MAP in IRS2/Nestin-cre or IRS2/POMC-cre mice. The anorexic and antidiabetic effects of leptin, however, were similar in all 3 groups. These results indicate that IRS2 signaling in the central nervous system, and particularly in POMC neurons, is essential for the chronic actions of leptin to raise MAP but not for its anorexic or antidiabetic effects. PMID:26628674

  18. Metabolism Regulates the Spontaneous Firing of Substantia Nigra Pars Reticulata Neurons via KATP and Nonselective Cation Channels

    PubMed Central

    Lutas, Andrew; Birnbaumer, Lutz

    2014-01-01

    Neurons use glucose to fuel glycolysis and provide substrates for mitochondrial respiration, but neurons can also use alternative fuels that bypass glycolysis and feed directly into mitochondria. To determine whether neuronal pacemaking depends on active glucose metabolism, we switched the metabolic fuel from glucose to alternative fuels, lactate or β-hydroxybutyrate, while monitoring the spontaneous firing of GABAergic neurons in mouse substantia nigra pars reticulata (SNr) brain slices. We found that alternative fuels, in the absence of glucose, sustained SNr spontaneous firing at basal rates, but glycolysis may still be supported by glycogen in the absence of glucose. To prevent any glycogen-fueled glycolysis, we directly inhibited glycolysis using either 2-deoxyglucose or iodoacetic acid. Inhibiting glycolysis in the presence of alternative fuels lowered SNr firing to a slower sustained firing rate. Surprisingly, we found that the decrease in SNr firing was not mediated by ATP-sensitive potassium (KATP) channel activity, but if we lowered the perfusion flow rate or omitted the alternative fuel, KATP channels were activated and could silence SNr firing. The KATP-independent slowing of SNr firing that occurred with glycolytic inhibition in the presence of alternative fuels was consistent with a decrease in a nonselective cationic conductance. Although mitochondrial metabolism alone can prevent severe energy deprivation and KATP channel activation in SNr neurons, active glucose metabolism appears important for keeping open a class of ion channels that is crucial for the high spontaneous firing rate of SNr neurons. PMID:25471572

  19. Brain-borne IL-1 adjusts glucoregulation and provides fuel support to astrocytes and neurons in an autocrine/paracrine manner.

    PubMed

    Del Rey, A; Verdenhalven, M; Lörwald, A C; Meyer, C; Hernangómez, M; Randolf, A; Roggero, E; König, A M; Heverhagen, J T; Guaza, C; Besedovsky, H O

    2016-09-01

    It is still controversial which mediators regulate energy provision to activated neural cells, as insulin does in peripheral tissues. Interleukin-1β (IL-1β) may mediate this effect as it can affect glucoregulation, it is overexpressed in the 'healthy' brain during increased neuronal activity, and it supports high-energy demanding processes such as long-term potentiation, memory and learning. Furthermore, the absence of sustained neuroendocrine and behavioral counterregulation suggests that brain glucose-sensing neurons do not perceive IL-1β-induced hypoglycemia. Here, we show that IL-1β adjusts glucoregulation by inducing its own production in the brain, and that IL-1β-induced hypoglycemia is myeloid differentiation primary response 88 protein (MyD88)-dependent and only partially counteracted by Kir6.2-mediated sensing signaling. Furthermore, we found that, opposite to insulin, IL-1β stimulates brain metabolism. This effect is absent in MyD88-deficient mice, which have neurobehavioral alterations associated to disorders in glucose homeostasis, as during several psychiatric diseases. IL-1β effects on brain metabolism are most likely maintained by IL-1β auto-induction and may reflect a compensatory increase in fuel supply to neural cells. We explore this possibility by directly blocking IL-1 receptors in neural cells. The results showed that, in an activity-dependent and paracrine/autocrine manner, endogenous IL-1 produced by neurons and astrocytes facilitates glucose uptake by these cells. This effect is exacerbated following glutamatergic stimulation and can be passively transferred between cell types. We conclude that the capacity of IL-1β to provide fuel to neural cells underlies its physiological effects on glucoregulation, synaptic plasticity, learning and memory. However, deregulation of IL-1β production could contribute to the alterations in brain glucose metabolism that are detected in several neurologic and psychiatric diseases. PMID:26643538

  20. Neurochemical Pathways That Converge on Thalamic Trigeminovascular Neurons: Potential Substrate for Modulation of Migraine by Sleep, Food Intake, Stress and Anxiety

    PubMed Central

    Noseda, Rodrigo; Kainz, Vanessa; Borsook, David; Burstein, Rami

    2014-01-01

    Dynamic thalamic regulation of sensory signals allows the cortex to adjust better to rapidly changing behavioral, physiological and environmental demands. To fulfill this role, thalamic neurons must themselves be subjected to constantly changing modulatory inputs that originate in multiple neurochemical pathways involved in autonomic, affective and cognitive functions. Our overall goal is to define an anatomical framework for conceptualizing how a ‘decision’ is made on whether a trigeminovascular thalamic neuron fires, for how long, and at what frequency. To begin answering this question, we determine which neuropeptides/neurotransmitters are in a position to modulate thalamic trigeminovascular neurons. Using a combination of in-vivo single-unit recording, juxtacellular labeling with tetramethylrhodamine dextran (TMR) and in-vitro immunohistochemistry, we found that thalamic trigeminovascular neurons were surrounded by high density of axons containing biomarkers of glutamate, GABA, dopamine and serotonin; moderate density of axons containing noradrenaline and histamine; low density of axons containing orexin and melanin concentrating hormone (MCH); but not axons containing CGRP, serotonin 1D receptor, oxytocin or vasopressin. In the context of migraine, the findings suggest that the transmission of headache-related nociceptive signals from the thalamus to the cortex may be modulated by opposing forces (i.e., facilitatory, inhibitory) that are governed by continuous adjustments needed to keep physiological, behavioral, cognitive and emotional homeostasis. PMID:25090640

  1. Analysis of chitin particle size on maximum power generation, power longevity, and Coulombic efficiency in solid-substrate microbial fuel cells

    NASA Astrophysics Data System (ADS)

    Rezaei, Farzaneh; Richard, Tom L.; Logan, Bruce E.

    Microbial fuel cells (MFCs) produce bioelectricity from a wide variety of organic and inorganic substrates. Chitin can be used as a slowly degrading substrate in MFCs and thus as a long-term fuel to sustain power by these devices in remote locations. However, little is known about the effects of particle size on power density and length of the power cycle (longevity). We therefore examined power generation from chitin particles sieved to produce three average particle sizes (0.28, 0.46 and 0.78 mm). The longevity increased from 9 to 33 days with an increase in the particle diameter from 0.28 to 0.78 mm. Coulombic efficiency also increased with particle size from 18% to 56%. The maximum power density was lower for the largest (0.78 mm) particles (176 mW m -2), with higher power densities for the 0.28 mm (272 mW m -2) and 0.46 mm (252 mW m -2) particle sizes. The measured lifetimes of these particles scaled with particle diameter to the 1.3 power. Application of a fractal dissolution model indicates chitin particles had a three-dimensional fractal dimension between 2 and 2.3. These results demonstrate particles can be used as a sustainable fuel in MFCs, but that particle sizes will need to be controlled to achieve desired power levels.

  2. Plasma-enhanced atomic layer deposition of nanoscale yttria-stabilized zirconia electrolyte for solid oxide fuel cells with porous substrate.

    PubMed

    Ji, Sanghoon; Cho, Gu Young; Yu, Wonjong; Su, Pei-Chen; Lee, Min Hwan; Cha, Suk Won

    2015-02-11

    Nanoscale yttria-stabilized zirconia (YSZ) electrolyte film was deposited by plasma-enhanced atomic layer deposition (PEALD) on a porous anodic aluminum oxide supporting substrate for solid oxide fuel cells. The minimum thickness of PEALD-YSZ electrolyte required for a consistently high open circuit voltage of 1.17 V at 500 °C is 70 nm, which is much thinner than the reported thickness of 180 nm using nonplasmatic ALD and is also the thinnest attainable value reported in the literatures on a porous supporting substrate. By further reducing the electrolyte thickness, the grain size reduction resulted in high surface grain boundary density at the cathode/electrolyte interface. PMID:25625537

  3. Vestibular Neuronitis

    MedlinePlus

    ... Prevent Painful Swimmer's Ear Additional Content Medical News Vestibular Neuronitis By Lawrence R. Lustig, MD NOTE: This ... Drugs Herpes Zoster Oticus Meniere Disease Purulent Labyrinthitis Vestibular Neuronitis Vestibular neuronitis is a disorder characterized by ...

  4. Yeast fermentation affected by homo- and hetero-fermentative Lactobacilli isolated from fuel ethanol distilleries with sugarcane products as substrates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The antagonism between by yeast and lactobacilli is largely dependent on the initial population of each organism. While homo-fermentative lactobacillus present higher inhibitory effect upon yeast when in equal cell number, in industrial fuel ethanol conditions where high yeast cell densities prevail...

  5. Cellular pathways of energy metabolism in the brain: is glucose used by neurons or astrocytes?

    PubMed

    Nehlig, Astrid; Coles, Jonathan A

    2007-09-01

    Most techniques presently available to measure cerebral activity in humans and animals, i.e. positron emission tomography (PET), autoradiography, and functional magnetic resonance imaging, do not record the activity of neurons directly. Furthermore, they do not allow the investigator to discriminate which cell type is using glucose, the predominant fuel provided to the brain by the blood. Here, we review the experimental approaches aimed at determining the percentage of glucose that is taken up by neurons and by astrocytes. This review is integrated in an overview of the current concepts on compartmentation and substrate trafficking between astrocytes and neurons. In the brain in vivo, about half of the glucose leaving the capillaries crosses the extracellular space and directly enters neurons. The other half is taken up by astrocytes. Calculations suggest that neurons consume more energy than do astrocytes, implying that astrocytes transfer an intermediate substrate to neurons. Experimental approaches in vitro on the honeybee drone retina and on the isolated vagus nerve also point to a continuous transfer of intermediate metabolites from glial cells to neurons in these tissues. Solid direct evidence of such transfer in the mammalian brain in vivo is still lacking. PET using [(18)F]fluorodeoxyglucose reflects in part glucose uptake by astrocytes but does not indicate to which step the glucose taken up is metabolized within this cell type. Finally, the sequence of metabolic changes occurring during a transient increase of electrical activity in specific regions of the brain remains to be clarified. PMID:17659529

  6. Electrolyte supported solid oxide fuel cells with the super large size and thin ytterbia stabilized zirconia substrate

    NASA Astrophysics Data System (ADS)

    Xue, Ye Jian; Miao, He; He, Chang Rong; Wang, Jian Xin; Liu, Man; Sun, Shan Shan; Wang, Qin; Wang, Wei Guo

    2015-04-01

    In this work, the (ZrO2)0.95(Yb2O3)0.05(5YbSZ) electrolyte supported SOFCs with the large area of 10 cm × 10 cm and thin substrate of about 70 μm are prepared, and the microstructures, electrochemical and anti-redox properties of the single cells are investigated systematically. The powders of 5YbSZ with the tetragonal and cubic mixed phase are synthesized by the so-called "solid-liquid composite method" at a somewhat low temperature of 1100 °C. The 5YbSZ electrolyte substrates which are prepared by the tape-casting, multilayer-lamination and sintering method showed the optimal comprehensive performances with the sintering temperature being 1500 °C. By using these electrolyte substrates, the NiO+GDC/5YbSZ/LSM+5YbSZ single cells are obtained at the co-sinter temperature of 1100 °C. The power densities of these cells can reach 0.56 W cm-2 at the output voltage of 0.7 V, and the degradation rate can attain 1.45% kh-1 under a constant current density of 0.2 A cm-2 at the temperature of 830 °C. After 11 redox cycles, no crack through the 5YbSZ electrolyte can be found in the single cells, and the electrochemical properties of the 5YbSZ electrolyte supported single cells show an acceptable degradation.

  7. Polyacrylamide gel substrates that simulate the mechanical stiffness of normal and malignant neuronal tissues increase protoporphyin IX synthesis in glioma cells

    NASA Astrophysics Data System (ADS)

    Niu, Carolyn J.; Fisher, Carl; Scheffler, Kira; Wan, Rachel; Maleki, Hoda; Liu, Haijiao; Sun, Yu; Simmons, Craig A.; Birngruber, Reginald; Lilge, Lothar

    2015-09-01

    Protoporphyrin IX (PPIX) produced following the administration of exogenous 5d-aminolevulinic acid is clinically approved for photodynamic therapy and fluorescence-guided resection in various jurisdictions around the world. For both applications, quantification of PPIX forms the basis for accurate therapeutic dose calculation and identification of malignant tissues for resection. While it is well established that the PPIX synthesis and accumulation rates are subject to the cell's biochemical microenvironment, the effect of the physical microenvironment, such as matrix stiffness, has received little attention to date. Here we studied the proliferation rate and PPIX synthesis and accumulation in two glioma cell lines U373 and U118 cultured under five different substrate conditions, including the conventional tissue culture plastic and polyacrylamide gels that simulated tissue stiffness of normal brain (1 kPa) and glioblastoma tumors (12 kPa). We found that the proliferation rate increased with substrate stiffness for both cell lines, but not in a linear fashion. PPIX concentration was significantly higher in cells cultured on tissue-simulating gels than on the much stiffer tissue culture plastic for both cell lines. These findings, albeit preliminary, suggest that the physical microenvironment might be an important determinant of tumor aggressiveness and PPIX synthesis in glioma cells.

  8. Modulation of Heme/Substrate Binding Cleft of Neuronal Nitric-oxide Synthase (nNOS) Regulates Binding of Hsp90 and Hsp70 Proteins and nNOS Ubiquitination*

    PubMed Central

    Peng, Hwei-Ming; Morishima, Yoshihiro; Pratt, William B.; Osawa, Yoichi

    2012-01-01

    Like other nitric-oxide synthase (NOS) enzymes, neuronal NOS (nNOS) turnover and activity are regulated by the Hsp90/Hsp70-based chaperone machinery, which regulates signaling proteins by modulating ligand binding clefts (Pratt, W. B., Morishima, Y., and Osawa, Y. (2008) J. Biol. Chem. 283, 22885–22889). We have previously shown that nNOS turnover is due to Hsp70/CHIP-dependent ubiquitination and proteasomal degradation. In this work, we use an intracellular cross-linking approach to study both chaperone binding and nNOS ubiquitination in intact HEK293 cells. Treatment of cells with NG-nitro-l-arginine, a slowly reversible competitive inhibitor that stabilizes nNOS, decreases both nNOS ubiquitination and binding of Hsp90, Hsp70, and CHIP. Treatment with the calcium ionophore A23187, which increases Ca2+-calmodulin binding to nNOS, increases nNOS ubiquitination and binding of Hsp90, Hsp70, and CHIP in a manner that is specific for changes in the heme/substrate binding cleft. Both Hsp90 and Hsp70 are bound to the expressed nNOS oxygenase domain, which contains the heme/substrate binding cleft, but not to the reductase domain, and binding is increased to an expressed fragment containing both the oxygenase domain and the calmodulin binding site. Overexpression of Hsp70 promotes nNOS ubiquitination and decreases nNOS protein, and overexpression of Hsp90 inhibits nNOS ubiquitination and increases nNOS protein, showing the opposing effects of the two chaperones as they participate in nNOS quality control in the cell. These observations support the notion that changes in the state of the heme/substrate binding cleft affect chaperone binding and thus nNOS ubiquitination. PMID:22128174

  9. Microalgae as substrate in low cost terracotta-based microbial fuel cells: Novel application of the catholyte produced.

    PubMed

    Salar-García, M J; Gajda, I; Ortiz-Martínez, V M; Greenman, J; Hanczyc, M M; de los Ríos, A P; Ieropoulos, I A

    2016-06-01

    In this work, the by-product generated during the operation of cylindrical MFCs, made out of terracotta material, is investigated as a feasible means of degrading live microalgae for the first time. In addition to the low cost materials of this design, the reuse of the solution produced in the cathode renders the technology truly green and capable of generating bioenergy. In this study, the effect of a light/dark cycle or dark conditions only on the digestion of live microalgae with the catholyte is investigated. The results show that a combination of light/dark improves degradation and allows algae to be used as substrate in the anode. The addition of 12.5mL of a 1:1 mix of catholyte and microalgae (pre-digested over 5days under light/dark) to the anode, increases the power generation from 7μW to 44μW once all the organic matter in the anode had been depleted. PMID:26995319

  10. Neuronal migration on laminin in vitro.

    PubMed

    Liang, S; Crutcher, K A

    1992-03-20

    Chick sympathetic (E-9) or telencephalic (E-7) neurons were cultured at low density on poly-DL-ornithine (PORN), poly-L-lysine (POLS), laminin or laminin-covered PORN or POLS and monitored with time-lapse videomicroscopy. Neurons migrated on laminin, or laminin-covered PORN or POLS, but not on PORN or POLS alone. Neuronal migration did not involve interactions with other cells indicating that neurons are capable of independent migration when exposed to a laminin substrate. PMID:1600626

  11. Effects of hydrophobic agent content in macro-porous substrates on the fracture behavior of the gas diffusion layer for proton exchange membrane fuel cells

    NASA Astrophysics Data System (ADS)

    Kim, Sanwi; Jeong, Byeong-Heon; Hong, Bo Ki; Kim, Taek-Soo

    2014-12-01

    Although the adhesion between the macro-porous substrate (MPS) and micro-porous layer (MPL) of a gas diffusion layer (GDL) is a critical factor that affects the reliability and durability of proton exchange membrane fuel cells, systematic studies quantifying the interfacial fracture energy of GDL have not yet been reported. Therefore, in this study, the interfacial fracture energy of GDLs with different contents of hydrophobic agents in the MPS is quantitatively measured. GDL samples with 0, 5, 10, and 20 wt% of hydrophobic agent content are tested using double cantilever beam fracture mechanics tests. It is observed that the interfacial fracture energy of the GDLs increases as the content of hydrophobic agent increases, due to more favorable interactions between the hydrophobic agents of the MPL and MPS. Optical microscope, scanning electron microscope, and energy-dispersive X-ray spectroscope analyses are performed on the bare and delaminated surfaces in order to investigate the mechanism of the interfacial fracture energy increase of the GDLs.

  12. Functional connectivity in in vitro neuronal assemblies

    PubMed Central

    Poli, Daniele; Pastore, Vito P.; Massobrio, Paolo

    2015-01-01

    Complex network topologies represent the necessary substrate to support complex brain functions. In this work, we reviewed in vitro neuronal networks coupled to Micro-Electrode Arrays (MEAs) as biological substrate. Networks of dissociated neurons developing in vitro and coupled to MEAs, represent a valid experimental model for studying the mechanisms governing the formation, organization and conservation of neuronal cell assemblies. In this review, we present some examples of the use of statistical Cluster Coefficients and Small World indices to infer topological rules underlying the dynamics exhibited by homogeneous and engineered neuronal networks. PMID:26500505

  13. Micropatterning neuronal networks.

    PubMed

    Hardelauf, Heike; Waide, Sarah; Sisnaiske, Julia; Jacob, Peter; Hausherr, Vanessa; Schöbel, Nicole; Janasek, Dirk; van Thriel, Christoph; West, Jonathan

    2014-07-01

    Spatially organised neuronal networks have wide reaching applications, including fundamental research, toxicology testing, pharmaceutical screening and the realisation of neuronal implant interfaces. Despite the large number of methods catalogued in the literature there remains the need to identify a method that delivers high pattern compliance, long-term stability and is widely accessible to neuroscientists. In this comparative study, aminated (polylysine/polyornithine and aminosilanes) and cytophobic (poly(ethylene glycol) (PEG) and methylated) material contrasts were evaluated. Backfilling plasma stencilled PEGylated substrates with polylysine does not produce good material contrasts, whereas polylysine patterned on methylated substrates becomes mobilised by agents in the cell culture media which results in rapid pattern decay. Aminosilanes, polylysine substitutes, are prone to hydrolysis and the chemistries prove challenging to master. Instead, the stable coupling between polylysine and PLL-g-PEG can be exploited: Microcontact printing polylysine onto a PLL-g-PEG coated glass substrate provides a simple means to produce microstructured networks of primary neurons that have superior pattern compliance during long term (>1 month) culture. PMID:24855658

  14. Neuronal polarization.

    PubMed

    Takano, Tetsuya; Xu, Chundi; Funahashi, Yasuhiro; Namba, Takashi; Kaibuchi, Kozo

    2015-06-15

    Neurons are highly polarized cells with structurally and functionally distinct processes called axons and dendrites. This polarization underlies the directional flow of information in the central nervous system, so the establishment and maintenance of neuronal polarization is crucial for correct development and function. Great progress in our understanding of how neurons establish their polarity has been made through the use of cultured hippocampal neurons, while recent technological advances have enabled in vivo analysis of axon specification and elongation. This short review and accompanying poster highlight recent advances in this fascinating field, with an emphasis on the signaling mechanisms underlying axon and dendrite specification in vitro and in vivo. PMID:26081570

  15. HEME-DEPENDENT ACTIVATION OF NEURONAL NITRIC-OXIDE SYNTHASE BY CYTOSOL IS DUE TO AN HSP70-DEPENDENT, THIOREDOXIN-MEDIATED THIOL-DISULFIDE INTERCHANGE IN THE HEME/SUBSTRATE BINDING CLEFT†

    PubMed Central

    Morishima, Yoshihiro; Lau, Miranda; Peng, Hwei-Ming; Miyata, Yoshinari; Gestwicki, Jason E.; Pratt, William B.; Osawa, Yoichi

    2011-01-01

    We have reported that heme-dependent activation of apo-neuronal nitric oxide synthase (apo-nNOS) to the active holo-enzyme dimer is dependent upon factors present in reticulocyte lysate and other cytosols. Here, we find that both Hsp70 and thioredoxin are components of the activation system. The apo-nNOS activating activity of reticulocyte lysate is retained in a pool of fractions containing Hsp70 that elute from DE52 prior to Hsp90. All of the activating activity and 20–30% of the Hsp70 elute in the flow-through fraction upon subsequent ATP-agarose chromatography. Apo-nNOS activation by this flow-through fraction is inhibited by pifithrin-μ, a small molecule inhibitor of Hsp70, suggesting that a non-ATP-binding form of Hsp70 is involved in heme-dependent apo-nNOS activation. Previous work has shown that apo-nNOS can be activated by thiol-disulfide exchange, and we show substantial activation with a small molecule dithiol modeled on the active motifs of thioredoxin and protein disulfide isomerase. Further fractionation of the ATP-agarose flow-through on Sephacryl S-300 separates free thioredoxin from apo-nNOS activating activity, Hsp70, and a small amount of thioredoxin, all of which are eluted throughout the macromolecular peak. Incubation of apo-nNOS with the macromolecular fraction in combination with either the thioredoxin-containing fraction or with purified recombinant human thioredoxin restores full heme-dependent activating activity. This supports a model in which Hsp70 binding to apo-nNOS stabilizes an open state of the heme/substrate binding cleft to facilitate thioredoxin access to the active site cysteine that coordinates with heme iron, permitting heme binding and dimerization to the active enzyme. PMID:21755988

  16. Heme-dependent activation of neuronal nitric oxide synthase by cytosol is due to an Hsp70-dependent, thioredoxin-mediated thiol-disulfide interchange in the heme/substrate binding cleft.

    PubMed

    Morishima, Yoshihiro; Lau, Miranda; Peng, Hwei-Ming; Miyata, Yoshinari; Gestwicki, Jason E; Pratt, William B; Osawa, Yoichi

    2011-08-23

    We have reported that heme-dependent activation of apo-neuronal nitric oxide synthase (apo-nNOS) to the active holo-enzyme dimer is dependent upon factors present in reticulocyte lysate and other cytosols. Here, we find that both Hsp70 and thioredoxin are components of the activation system. The apo-nNOS activating activity of reticulocyte lysate is retained in a pool of fractions containing Hsp70 that elute from DE52 prior to Hsp90. All of the activating activity and 20-30% of the Hsp70 elute in the flow-through fraction upon subsequent ATP-agarose chromatography. Apo-nNOS activation by this flow-through fraction is inhibited by pifithrin-μ, a small molecule inhibitor of Hsp70, suggesting that a non-ATP-binding form of Hsp70 is involved in heme-dependent apo-nNOS activation. Previous work has shown that apo-nNOS can be activated by thiol-disulfide exchange, and we show substantial activation with a small molecule dithiol modeled on the active motifs of thioredoxin and protein disulfide isomerase. Further fractionation of the ATP-agarose flow-through on Sephacryl S-300 separates free thioredoxin from apo-nNOS activating activity, Hsp70, and a small amount of thioredoxin, all of which are eluted throughout the macromolecular peak. Incubation of apo-nNOS with the macromolecular fraction in combination either with the thioredoxin-containing fraction or with purified recombinant human thioredoxin restores full heme-dependent activating activity. This supports a model in which Hsp70 binding to apo-nNOS stabilizes an open state of the heme/substrate binding cleft to facilitate thioredoxin access to the active site cysteine that coordinates with heme iron, permitting heme binding and dimerization to the active enzyme. PMID:21755988

  17. Effects of surface asymmetry on neuronal growth

    NASA Astrophysics Data System (ADS)

    Staii, Cristian

    Understanding the brain is of tremendous fundamental importance, but it is immensely challenging because of the complexity of both its architecture and function. A growing body of evidence shows that physical stimuli (stiffness of the growth substrate, gradients of various molecular species, geometry of the surrounding environment, traction forces etc.) play a key role in the wiring up of the nervous system. I will present a systematic experimental and theoretical investigation of neuronal growth on substrates with asymmetric geometries and textures. The experimental results show unidirectional axonal growth on these substrates. We demonstrate that the unidirectional bias is imparted by the surface ratchet geometry and quantify the geometrical guidance cues that control neuronal growth. Our results provide new insight into the role played by physical cues in neuronal growth, and could lead to new methods for stimulating neuronal regeneration and the engineering of artificial neuronal tissue. We acknowledge support from NSF through CBET 1067093.

  18. Predominant enhancement of glucose uptake in astrocytes versus neurons during activation of the somatosensory cortex

    PubMed Central

    Chuquet, Julien; Quilichini, Pascale; Nimchinsky, Esther A.; Buzsáki, György

    2010-01-01

    Glucose is the primary energetic substrate of the brain and measurements of its metabolism are the basis of major functional cerebral imaging methods. Contrary to the general view that neurons are fueled solely by glucose in proportion to their energetic needs, recent in vitro and ex vivo analyses suggest that glucose preferentially feeds astrocytes. However, the cellular fate of glucose in the intact brain has not yet been directly observed. We have used a real-time method for measuring glucose uptake in astrocytes and neurons in vivo in male rats by imaging the trafficking of the non-metabolizable glucose analog 6-NBDG using two-photon microscopy. During resting conditions we found that astrocytes and neurons both uptake 6-NBDG at the same rate in the barrel cortex of the rat. However, during intense neuronal activity triggered by whisker stimulation, astrocytes rapidly accelerated their uptake whereas neuronal uptake remained almost unchanged. Following the stimulation period, astrocytes returned to their pre-activation rates of uptake paralleling the neuronal rate of uptake. These observations suggest that glucose is primarily taken-up by astrocytes, supporting the view that functional imaging experiments based on glucose analogs extraction may predominantly reflect the metabolic activity of the astrocytic network. PMID:21068334

  19. Neuronal arithmetic

    PubMed Central

    Silver, R. Angus

    2016-01-01

    The vast computational power of the brain has traditionally been viewed as arising from the complex connectivity of neural networks, in which an individual neuron acts as a simple linear summation and thresholding device. However, recent studies show that individual neurons utilize a wealth of nonlinear mechanisms to transform synaptic input into output firing. These mechanisms can arise from synaptic plasticity, synaptic noise, and somatic and dendritic conductances. This tool kit of nonlinear mechanisms confers considerable computational power on both morphologically simple and more complex neurons, enabling them to perform a range of arithmetic operations on signals encoded in a variety of different ways. PMID:20531421

  20. Neuron Biomechanics Probed by Atomic Force Microscopy

    PubMed Central

    Spedden, Elise; Staii, Cristian

    2013-01-01

    Mechanical interactions play a key role in many processes associated with neuronal growth and development. Over the last few years there has been significant progress in our understanding of the role played by the substrate stiffness in neuronal growth, of the cell-substrate adhesion forces, of the generation of traction forces during axonal elongation, and of the relationships between the neuron soma elastic properties and its health. The particular capabilities of the Atomic Force Microscope (AFM), such as high spatial resolution, high degree of control over the magnitude and orientation of the applied forces, minimal sample damage, and the ability to image and interact with cells in physiologically relevant conditions make this technique particularly suitable for measuring mechanical properties of living neuronal cells. This article reviews recent advances on using the AFM for studying neuronal biomechanics, provides an overview about the state-of-the-art measurements, and suggests directions for future applications. PMID:23921683

  1. Neuron biomechanics probed by atomic force microscopy.

    PubMed

    Spedden, Elise; Staii, Cristian

    2013-01-01

    Mechanical interactions play a key role in many processes associated with neuronal growth and development. Over the last few years there has been significant progress in our understanding of the role played by the substrate stiffness in neuronal growth, of the cell-substrate adhesion forces, of the generation of traction forces during axonal elongation, and of the relationships between the neuron soma elastic properties and its health. The particular capabilities of the Atomic Force Microscope (AFM), such as high spatial resolution, high degree of control over the magnitude and orientation of the applied forces, minimal sample damage, and the ability to image and interact with cells in physiologically relevant conditions make this technique particularly suitable for measuring mechanical properties of living neuronal cells. This article reviews recent advances on using the AFM for studying neuronal biomechanics, provides an overview about the state-of-the-art measurements, and suggests directions for future applications. PMID:23921683

  2. Motor Neuron Diseases

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Motor Neuron Diseases Information Page Condensed from Motor Neuron Diseases ... and Information Publicaciones en Español What are Motor Neuron Diseases? The motor neuron diseases (MNDs) are a ...

  3. Motor Neuron Diseases

    MedlinePlus

    ... called upper motor neurons ) are transmitted to nerve cells in the brain stem and spinal cord (called lower motor neurons ) and from them to particular muscles. Upper motor neurons direct the lower motor neurons ...

  4. Tuning supramolecular mechanics to guide neuron development

    PubMed Central

    Sur, Shantanu; Newcomb, Christina J.; Webber, Matthew J.; Stupp, Samuel I.

    2013-01-01

    The mechanical properties of the extracellular matrix (ECM) are known to influence neuronal differentiation and maturation, though the mechanism by which neuronal cells respond to these biophysical cues is not completely understood. Here we design ECM mimics using self-assembled peptide nanofibers, in which fiber rigidity is tailored by supramolecular interactions, in order to investigate the relationship between matrix stiffness and morphological development of hippocampal neurons. We observe that development of neuronal polarity is accelerated on soft nanofiber substrates, and results from the dynamics of neuronal processes. While the total neurite outgrowth of non-polar neurons remains conserved, weaker adhesion of neurites to soft PA substrate facilitates easier retraction, thus enhancing the frequency of “extension-retraction” events. We hypothesize that higher neurite motility enhances the probability of one neurite to reach a critical length relative to others, thereby initiating the developmental sequence of axon differentiation. Our results suggest that substrate stiffness can influence neuronal development by regulating its dynamics, thus providing useful information on scaffold design for applications in neural regeneration. PMID:23562052

  5. Context-aware modeling of neuronal morphologies

    PubMed Central

    Torben-Nielsen, Benjamin; De Schutter, Erik

    2014-01-01

    Neuronal morphologies are pivotal for brain functioning: physical overlap between dendrites and axons constrain the circuit topology, and the precise shape and composition of dendrites determine the integration of inputs to produce an output signal. At the same time, morphologies are highly diverse and variant. The variance, presumably, originates from neurons developing in a densely packed brain substrate where they interact (e.g., repulsion or attraction) with other actors in this substrate. However, when studying neurons their context is never part of the analysis and they are treated as if they existed in isolation. Here we argue that to fully understand neuronal morphology and its variance it is important to consider neurons in relation to each other and to other actors in the surrounding brain substrate, i.e., their context. We propose a context-aware computational framework, NeuroMaC, in which large numbers of neurons can be grown simultaneously according to growth rules expressed in terms of interactions between the developing neuron and the surrounding brain substrate. As a proof of principle, we demonstrate that by using NeuroMaC we can generate accurate virtual morphologies of distinct classes both in isolation and as part of neuronal forests. Accuracy is validated against population statistics of experimentally reconstructed morphologies. We show that context-aware generation of neurons can explain characteristics of variation. Indeed, plausible variation is an inherent property of the morphologies generated by context-aware rules. We speculate about the applicability of this framework to investigate morphologies and circuits, to classify healthy and pathological morphologies, and to generate large quantities of morphologies for large-scale modeling. PMID:25249944

  6. Multi-timescale Modeling of Activity-Dependent Metabolic Coupling in the Neuron-Glia-Vasculature Ensemble

    PubMed Central

    Jolivet, Renaud; Coggan, Jay S.; Allaman, Igor; Magistretti, Pierre J.

    2015-01-01

    Glucose is the main energy substrate in the adult brain under normal conditions. Accumulating evidence, however, indicates that lactate produced in astrocytes (a type of glial cell) can also fuel neuronal activity. The quantitative aspects of this so-called astrocyte-neuron lactate shuttle (ANLS) are still debated. To address this question, we developed a detailed biophysical model of the brain’s metabolic interactions. Our model integrates three modeling approaches, the Buxton-Wang model of vascular dynamics, the Hodgkin-Huxley formulation of neuronal membrane excitability and a biophysical model of metabolic pathways. This approach provides a template for large-scale simulations of the neuron-glia-vasculature (NGV) ensemble, and for the first time integrates the respective timescales at which energy metabolism and neuronal excitability occur. The model is constrained by relative neuronal and astrocytic oxygen and glucose utilization, by the concentration of metabolites at rest and by the temporal dynamics of NADH upon activation. These constraints produced four observations. First, a transfer of lactate from astrocytes to neurons emerged in response to activity. Second, constrained by activity-dependent NADH transients, neuronal oxidative metabolism increased first upon activation with a subsequent delayed astrocytic glycolysis increase. Third, the model correctly predicted the dynamics of extracellular lactate and oxygen as observed in vivo in rats. Fourth, the model correctly predicted the temporal dynamics of tissue lactate, of tissue glucose and oxygen consumption, and of the BOLD signal as reported in human studies. These findings not only support the ANLS hypothesis but also provide a quantitative mathematical description of the metabolic activation in neurons and glial cells, as well as of the macroscopic measurements obtained during brain imaging. PMID:25719367

  7. Multi-timescale modeling of activity-dependent metabolic coupling in the neuron-glia-vasculature ensemble.

    PubMed

    Jolivet, Renaud; Coggan, Jay S; Allaman, Igor; Magistretti, Pierre J

    2015-02-01

    Glucose is the main energy substrate in the adult brain under normal conditions. Accumulating evidence, however, indicates that lactate produced in astrocytes (a type of glial cell) can also fuel neuronal activity. The quantitative aspects of this so-called astrocyte-neuron lactate shuttle (ANLS) are still debated. To address this question, we developed a detailed biophysical model of the brain's metabolic interactions. Our model integrates three modeling approaches, the Buxton-Wang model of vascular dynamics, the Hodgkin-Huxley formulation of neuronal membrane excitability and a biophysical model of metabolic pathways. This approach provides a template for large-scale simulations of the neuron-glia-vasculature (NGV) ensemble, and for the first time integrates the respective timescales at which energy metabolism and neuronal excitability occur. The model is constrained by relative neuronal and astrocytic oxygen and glucose utilization, by the concentration of metabolites at rest and by the temporal dynamics of NADH upon activation. These constraints produced four observations. First, a transfer of lactate from astrocytes to neurons emerged in response to activity. Second, constrained by activity-dependent NADH transients, neuronal oxidative metabolism increased first upon activation with a subsequent delayed astrocytic glycolysis increase. Third, the model correctly predicted the dynamics of extracellular lactate and oxygen as observed in vivo in rats. Fourth, the model correctly predicted the temporal dynamics of tissue lactate, of tissue glucose and oxygen consumption, and of the BOLD signal as reported in human studies. These findings not only support the ANLS hypothesis but also provide a quantitative mathematical description of the metabolic activation in neurons and glial cells, as well as of the macroscopic measurements obtained during brain imaging. PMID:25719367

  8. Ex situ evaluation of nanometer range gold coating on stainless steel substrate for automotive polymer electrolyte membrane fuel cell bipolar plate

    NASA Astrophysics Data System (ADS)

    Kumar, A.; Ricketts, M.; Hirano, S.

    The bipolar plate in polymer electrolyte membrane (PEM) fuel cell helps to feed reactant gases to the membrane electrode assembly (MEA) and collect current from the MEA. To facilitate these functions, the bipolar plate material should exhibit excellent electrical conductivity and corrosion resistance under fuel cell operating conditions, and simultaneously be of low-cost to meet commercialization enabling targets for automotive fuel cells. In the present work, we focus on the benchmarking of 10 nm gold coated SS316L (a.k.a. Au Nanoclad ®) bipolar plate material through ex situ tests, which is provided by Daido Steel (Japan). The use of nanometer range Au coatings help to retain the noble properties of gold while significantly reducing the cost of the bipolar plate. The area specific resistance of the flat sample is 0.9 mΩ cm 2 while that for the formed bipolar plate is 6.3 mΩ cm 2 at compaction force of 60 N cm -2. The corrosion current density was less than 1 μA cm -2 at 0.8 V/NHE with air sparge simulating cathodic conditions. Additionally, gold coated SS316L showed anodic passivation of SS316L, thereby exhibiting robustness towards coating defects including surface scratches that may originate during the manufacturing of the bipolar plate. These series of ex situ tests indicate that 10 nm gold coated SS316L has good potential to be considered for commercial bipolar plates in automotive fuel cell stack.

  9. Graphene electrodes for stimulation of neuronal cells

    NASA Astrophysics Data System (ADS)

    Koerbitzer, Berit; Krauss, Peter; Nick, Christoph; Yadav, Sandeep; Schneider, Joerg J.; Thielemann, Christiane

    2016-06-01

    Graphene has the ability to improve the electrical interface between neuronal cells and electrodes used for recording and stimulation purposes. It provides a biocompatible coating for common electrode materials such as gold and improves the electrode properties. Graphene electrodes are also prepared on SiO2 substrate to benefit from its optical properties like transparency. We perform electrochemical and Raman characterization of gold electrodes with graphene coating and compare them with graphene on SiO2 substrate. It was found that the substrate plays an important role in the performance of graphene and show that graphene on SiO2 substrate is a very promising material combination for stimulation electrodes.

  10. Advanced bioreactor concepts for gaseous substrates: Conversion of synthesis gas to liquid fuels and removal of SO{sub x} and NO{sub x} from coal combustion gases. CRADA final report

    SciTech Connect

    Kaufman, E.N.; Selvaraj, P.T.

    1997-10-01

    The purpose of the proposed research program was the development and demonstration of a new generation of gaseous substrate-based bioreactors for the production of liquid fuels from coal synthesis gas and the removal of NO{sub x} and SO{sub x} species from coal combustion flue gas. This study addressed the further investigation of optimal bacterial strains, growth media and kinetics for the biocatalytic conversion of coal synthesis gas to liquid fuel such as ethanol and the reduction of gaseous flue gas constituents. The primary emphasis was on the development of advanced bioreactor systems coupled with innovative biocatalytic systems that will provide increased productivity under controlled conditions. It was hoped that this would result in bioprocessing options that have both technical and economic feasibility, thus, ensuring early industrial use. Predictive mathematical models were formulated to accommodate hydrodynamics, mass transport, and conversion kinetics, and provide the data base for design and scale-up. The program was separated into four tasks: (1) Optimization of Biocatalytic Kinetics; (2) Development of Well-mixed and Columnar Reactors; (3) Development of Predictive Mathematical Models; and (4) Industrial Demonstration. Research activities addressing both synthesis gas conversion and flue gas removal were conducted in parallel by BRI and ORNL respectively.

  11. Advanced bioreactor systems for gaseous substrates: Conversion of synthesis gas to liquid fuels and removal of SO{sub X} and NO{sub X} from coal combustion gases

    SciTech Connect

    Selvaraj, P.T.; Kaufman, E.N.

    1996-06-01

    The purpose of this research program is the development and demonstration of a new generation of gaseous substrate based bioreactors for the production of liquid fuels from coal synthesis gas and the removal of NO{sub x} and SO{sub x} species from combustion flue gas. This R&D program is a joint effort between the staff of the Bioprocessing Research and Development Center (BRDC) of ORNL and the staff of Bioengineering Resources, Inc. (BRI) under a Cooperative Research and Development Agreement (CRADA). The Federal Coordinating Council for Science, Engineering, and Technology report entitled {open_quotes}Biotechnology for the 21st Century{close_quotes} and the recent Energy Policy Act of 1992 emphasizes research, development, and demonstration of the conversion of coal to gaseous and liquid fuels and the control of sulfur and nitrogen oxides in effluent streams. This R&D program presents an innovative approach to the use of bioprocessing concepts that will have utility in both of these identified areas.

  12. Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro.

    PubMed

    Bardy, Cedric; van den Hurk, Mark; Eames, Tameji; Marchand, Cynthia; Hernandez, Ruben V; Kellogg, Mariko; Gorris, Mark; Galet, Ben; Palomares, Vanessa; Brown, Joshua; Bang, Anne G; Mertens, Jerome; Böhnke, Lena; Boyer, Leah; Simon, Suzanne; Gage, Fred H

    2015-05-19

    Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely used to culture neurons. We found that classic basal media, as well as serum, impair action potential generation and synaptic communication. To overcome this problem, we designed a new neuronal medium (BrainPhys basal + serum-free supplements) in which we adjusted the concentrations of inorganic salts, neuroactive amino acids, and energetic substrates. We then tested that this medium adequately supports neuronal activity and survival of human neurons in culture. Long-term exposure to this physiological medium also improved the proportion of neurons that were synaptically active. The medium was designed to culture human neurons but also proved adequate for rodent neurons. The improvement in BrainPhys basal medium to support neurophysiological activity is an important step toward reducing the gap between brain physiological conditions in vivo and neuronal models in vitro. PMID:25870293

  13. Programmed to Learn? The Ontogeny of Mirror Neurons

    ERIC Educational Resources Information Center

    Del Giudice, Marco; Manera, Valeria; Keysers, Christian

    2009-01-01

    Mirror neurons are increasingly recognized as a crucial substrate for many developmental processes, including imitation and social learning. Although there has been considerable progress in describing their function and localization in the primate and adult human brain, we still know little about their ontogeny. The idea that mirror neurons result…

  14. Olfactory Receptor Neuron Dysfunction in Schizophrenia

    PubMed Central

    Turetsky, Bruce I; Hahn, Chang-Gyu; Arnold, Steven E; Moberg, Paul J

    2012-01-01

    Olfactory impairments are a common feature of schizophrenia. Impairments in odor detection and odor identification are present early in the course of illness and among those at risk for the disorder. These behavioral impairments have been linked to both physiological and anatomical abnormalities in the neural substrates subserving olfaction, including relatively peripheral elements of the olfactory system. The location of olfactory receptor neurons in the nasal epithelium allows noninvasive access to these neurons in living subjects. This offers a unique opportunity to directly assess neuronal integrity in vivo in patients. The peripheral olfactory receptor neuron response to odor stimulation was assessed in 21 schizophrenia patients and 18 healthy comparison subjects. The electroolfactogram, representing the electrical depolarization of the olfactory receptor neurons, was recording following stimulation with different doses and durations of hydrogen sulfide, a pure olfactory nerve stimulant. Schizophrenia patients had abnormally large depolarization responses following odor stimulation, independent of clinical symptomatology, antipsychotic medication dosage or smoking history. Although the precise pathophysiological mechanism is unknown, this olfactory receptor neuron abnormality is consistent with several lines of evidence suggesting altered proliferation or maturation of olfactory receptor neuron cell lineages in schizophrenia. It is also consistent with emerging evidence of disruptions of cyclic AMP-mediated intracellular signaling mechanisms, and may be a marker of these disruptions. It unambiguously demonstrates that neurophysiological disturbances in schizophrenia are not limited to cortical and subcortical structures, but rather include even the most peripheral sensory neurons. PMID:18754006

  15. Olfactory receptor neuron dysfunction in schizophrenia.

    PubMed

    Turetsky, Bruce I; Hahn, Chang-Gyu; Arnold, Steven E; Moberg, Paul J

    2009-02-01

    Olfactory impairments are a common feature of schizophrenia. Impairments in odor detection and odor identification are present early in the course of illness and among those at risk for the disorder. These behavioral impairments have been linked to both physiological and anatomical abnormalities in the neural substrates subserving olfaction, including relatively peripheral elements of the olfactory system. The location of olfactory receptor neurons in the nasal epithelium allows noninvasive access to these neurons in living subjects. This offers a unique opportunity to directly assess neuronal integrity in vivo in patients. The peripheral olfactory receptor neuron response to odor stimulation was assessed in 21 schizophrenia patients and 18 healthy comparison subjects. The electroolfactogram, representing the electrical depolarization of the olfactory receptor neurons, was recording following stimulation with different doses and durations of hydrogen sulfide, a pure olfactory nerve stimulant. Schizophrenia patients had abnormally large depolarization responses following odor stimulation, independent of clinical symptomatology, antipsychotic medication dosage or smoking history. Although the precise pathophysiological mechanism is unknown, this olfactory receptor neuron abnormality is consistent with several lines of evidence suggesting altered proliferation or maturation of olfactory receptor neuron cell lineages in schizophrenia. It is also consistent with emerging evidence of disruptions of cyclic AMP-mediated intracellular signaling mechanisms, and may be a marker of these disruptions. It unambiguously demonstrates that neurophysiological disturbances in schizophrenia are not limited to cortical and subcortical structures, but rather include even the most peripheral sensory neurons. PMID:18754006

  16. Lactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia

    PubMed Central

    Herzog, Raimund I.; Jiang, Lihong; Herman, Peter; Zhao, Chen; Sanganahalli, Basavaraju G.; Mason, Graeme F.; Hyder, Fahmeed; Rothman, Douglas L.; Sherwin, Robert S.; Behar, Kevin L.

    2013-01-01

    Hypoglycemia occurs frequently during intensive insulin therapy in patients with both type 1 and type 2 diabetes and remains the single most important obstacle in achieving tight glycemic control. Using a rodent model of hypoglycemia, we demonstrated that exposure to antecedent recurrent hypoglycemia leads to adaptations of brain metabolism so that modest increments in circulating lactate allow the brain to function normally under acute hypoglycemic conditions. We characterized 3 major factors underlying this effect. First, we measured enhanced transport of lactate both into as well as out of the brain that resulted in only a small increase of its contribution to total brain oxidative capacity, suggesting that it was not the major fuel. Second, we observed a doubling of the glucose contribution to brain metabolism under hypoglycemic conditions that restored metabolic activity to levels otherwise only observed at euglycemia. Third, we determined that elevated lactate is critical for maintaining glucose metabolism under hypoglycemia, which preserves neuronal function. These unexpected findings suggest that while lactate uptake was enhanced, it is insufficient to support metabolism as an alternate substrate to replace glucose. Lactate is, however, able to modulate metabolic and neuronal activity, serving as a “metabolic regulator” instead. PMID:23543056

  17. Growth Cone Biomechanics in Peripheral and Central Nervous System Neurons

    NASA Astrophysics Data System (ADS)

    Urbach, Jeffrey; Koch, Daniel; Rosoff, Will; Geller, Herbert

    2012-02-01

    The growth cone, a highly motile structure at the tip of an axon, integrates information about the local environment and modulates outgrowth and guidance, but little is known about effects of external mechanical cues and internal mechanical forces on growth-cone mediated guidance. We have investigated neurite outgrowth, traction forces and cytoskeletal substrate coupling on soft elastic substrates for dorsal root ganglion (DRG) neurons (from the peripheral nervous system) and hippocampal neurons (from the central) to see how the mechanics of the microenvironment affect different populations. We find that the biomechanics of DRG neurons are dramatically different from hippocampal, with DRG neurons displaying relatively large, steady traction forces and maximal outgrowth and forces on substrates of intermediate stiffness, while hippocampal neurons display weak, intermittent forces and limited dependence of outgrowth and forces on substrate stiffness. DRG growth cones have slower rates of retrograde actin flow and higher density of localized paxillin (a protein associated with substrate adhesion complexes) compared to hippocampal neurons, suggesting that the difference in force generation is due to stronger adhesions and therefore stronger substrate coupling in DRG growth cones.

  18. Optimization of bioelectricity generation in fed-batch microbial fuel cell: effect of electrode material, initial substrate concentration, and cycle time.

    PubMed

    Cirik, Kevser

    2014-05-01

    Effective wastewater treatment and electricity generation using dual-chamber microbial fuel cell (MFC) will require a better understanding of how operational parameters affect system performance. Therefore, the main aim of this study is to investigate the bioelectricity production in a dual-chambered MFC-operated batch mode under different operational conditions. Initially, platinum (Pt) and mixed metal oxide titanium (Ti-TiO2) electrodes were used to investigate the influence of the electrode materials on the power generation at initial dissolved organic carbon (DOC) concentration of 400 mg/L and cycle time of 15 days. MFC equipped with Ti-TiO2 electrode performed better and was used to examine the effect of influent DOC concentration and cycle time on MFC performance. Increasing influent DOC concentration resulted in improving electricity generation, corresponding to a 1.65-fold increase in power density. However, decrease in cycle time from 15 to 5 days adversely affected reactor performance. Maximum DOC removal was 90 ± 3 %, which was produced at 15-day cycle time with an initial DOC of 3,600 mg/L, corresponding to maximum power generation of about 7,205 mW/m(2). PMID:24639089

  19. Cytochrome c is released from mitochondria in a reactive oxygen species (ROS)-dependent fashion and can operate as a ROS scavenger and as a respiratory substrate in cerebellar neurons undergoing excitotoxic death.

    PubMed

    Atlante, A; Calissano, P; Bobba, A; Azzariti, A; Marra, E; Passarella, S

    2000-11-24

    In rat cerebellar granule cells both reactive oxygen species production and release of cytochrome c take place during glutamate toxicity. This investigation was aimed (i) to ascertain whether and how these two processes are related and (ii) to gain insight into the role played by the released cytochrome c in the onset of neurotoxicity. Cytochrome c release takes place owing to the generation of reactive oxygen species both in glutamate-treated cerebellar granule cells and in sister control cultures incubated in the presence of the reactive oxygen species-generating system consisting of xanthine plus xanthine oxidase. In the early phase of neurotoxicity (30-min glutamate exposure) about 40% of the maximum (as measured at 3 h of glutamate exposure) cytochrome c release was found to occur in cerebellar granule cells from mitochondria that were essentially coupled and intact and that had a negligible production of oxygen free radicals. Contrarily, mitochondria from cells treated with glutamate for 3 h were mostly uncoupled and produced reactive oxygen species at a high rate. The cytosolic fraction containing the released cytochrome c was able to transfer electrons from superoxide anion to molecular oxygen via the respiratory chain and was found to partially prevent glutamate toxicity when added externally to cerebellar neurons undergoing necrosis. In the light of these findings, we propose that in the early phase of neurotoxicity, cytochrome c release can be part of a cellular and mitochondrial defense mechanism against oxidative stress. PMID:10980192

  20. Dorsal Raphe Dopamine Neurons Represent the Experience of Social Isolation.

    PubMed

    Matthews, Gillian A; Nieh, Edward H; Vander Weele, Caitlin M; Halbert, Sarah A; Pradhan, Roma V; Yosafat, Ariella S; Glober, Gordon F; Izadmehr, Ehsan M; Thomas, Rain E; Lacy, Gabrielle D; Wildes, Craig P; Ungless, Mark A; Tye, Kay M

    2016-02-11

    The motivation to seek social contact may arise from either positive or negative emotional states, as social interaction can be rewarding and social isolation can be aversive. While ventral tegmental area (VTA) dopamine (DA) neurons may mediate social reward, a cellular substrate for the negative affective state of loneliness has remained elusive. Here, we identify a functional role for DA neurons in the dorsal raphe nucleus (DRN), in which we observe synaptic changes following acute social isolation. DRN DA neurons show increased activity upon social contact following isolation, revealed by in vivo calcium imaging. Optogenetic activation of DRN DA neurons increases social preference but causes place avoidance. Furthermore, these neurons are necessary for promoting rebound sociability following an acute period of isolation. Finally, the degree to which these neurons modulate behavior is predicted by social rank, together supporting a role for DRN dopamine neurons in mediating a loneliness-like state. PAPERCLIP. PMID:26871628

  1. Dorsal Raphe Dopamine Neurons Represent the Experience of Social Isolation

    PubMed Central

    Matthews, Gillian A.; Nieh, Edward H.; Vander Weele, Caitlin M.; Halbert, Sarah A.; Pradhan, Roma V.; Yosafat, Ariella S.; Glober, Gordon F.; Izadmehr, Ehsan M.; Thomas, Rain E.; Lacy, Gabrielle D.; Wildes, Craig P.; Ungless, Mark A.; Tye, Kay M.

    2016-01-01

    Summary The motivation to seek social contact may arise from either positive or negative emotional states, as social interaction can be rewarding and social isolation can be aversive. While ventral tegmental area (VTA) dopamine (DA) neurons may mediate social reward, a cellular substrate for the negative affective state of loneliness has remained elusive. Here, we identify a functional role for DA neurons in the dorsal raphe nucleus (DRN), in which we observe synaptic changes following acute social isolation. DRN DA neurons show increased activity upon social contact following isolation, revealed by in vivo calcium imaging. Optogenetic activation of DRN DA neurons increases social preference but causes place avoidance. Furthermore, these neurons are necessary for promoting rebound sociability following an acute period of isolation. Finally, the degree to which these neurons modulate behavior is predicted by social rank, together supporting a role for DRN dopamine neurons in mediating a loneliness-like state. PaperClip PMID:26871628

  2. Physiology and pharmacology of striatal neurons.

    PubMed

    Kreitzer, Anatol C

    2009-01-01

    The basal ganglia occupy the core of the forebrain and consist of evolutionarily conserved motor nuclei that form recurrent circuits critical for motivation and motor planning. The striatum is the main input nucleus of the basal ganglia and a key neural substrate for procedural learning and memory. The vast majority of striatal neurons are spiny GABAergic projection neurons, which exhibit slow but temporally precise spiking in vivo. Contributing to this precision are several different types of interneurons that constitute only a small fraction of total neuron number but play a critical role in regulating striatal output. This review examines the cellular physiology and modulation of striatal neurons that give rise to their unique properties and function. PMID:19400717

  3. Electrophysiological recordings of patterned rat brain stem slice neurons.

    PubMed

    Lauer, L; Vogt, A; Yeung, C K; Knoll, W; Offenhäusser, A

    2002-08-01

    Dissociated neuronal cultures on substrates patterned with extracellular matrix (ECM) proteins have yielded much information in the past. However, although the culture of brain slices has many advantages over dissociated neuronal cultures, its feasibility on patterned substrates has not been demonstrated to date. In the present study, neuronal outgrowth from brain stem slices onto homogeneous control substrates, and onto laminin structures of grid- and line-shape was achieved. Cultures were evaluated by means of phase contrast microscopy, antibody staining, and patch-clamp measurements. Only patterns with line sizes of more than 4 microm yielded satisfactory neuronal outgrowth. The size of the nodes in the pattern influenced the nodal compliance of the spreading cells and the amount of unstructured overgrowth. Best grid patterns were 4 microm lines and 10 microm nodes, best line patterns were 4 microm lines and 20 microm nodes. On patterned substrates, average sodium and potassium currents were reduced by approximately 50% compared to controls, whereas area-normalized ion-currents were in the same order of magnitude. This indicates that as a consequence of the pattern-enforced geometrical confinement, neurons tend to have a smaller surface. In addition, neurons on patterned substrates were rapidly covered with glial overgrowth. This was shown by antibody staining. PMID:12102183

  4. Simple and effective graphene laser processing for neuron patterning application

    PubMed Central

    Lorenzoni, Matteo; Brandi, Fernando; Dante, Silvia; Giugni, Andrea; Torre, Bruno

    2013-01-01

    A straightforward fabrication technique to obtain patterned substrates promoting ordered neuron growth is presented. Chemical vapor deposition (CVD) single layer graphene (SLG) was machined by means of single pulse UV laser ablation technique at the lowest effective laser fluence in order to minimize laser damage effects. Patterned substrates were then coated with poly-D-lysine by means of a simple immersion in solution. Primary embryonic hippocampal neurons were cultured on our substrate, demonstrating an ordered interconnected neuron pattern mimicking the pattern design. Surprisingly, the functionalization is more effective on the SLG, resulting in notably higher alignment for neuron adhesion and growth. Therefore the proposed technique should be considered a valuable candidate to realize a new generation of highly specialized biosensors. PMID:23739674

  5. Advanced bioreactor systems for gaseous substrates: Conversion of synthesis gas to liquid fuels and removal of SO{sub x} and NO{sub x} from coal combustion gases

    SciTech Connect

    Selvaraj, P.T.; Kaufman, E.N.

    1995-06-01

    The purpose of the proposed research program is the development and demonstration of a new generation of gaseous substrate-based bioreactors for the production of liquid fuels from coal synthesis gas and the removal of NO{sub x} and SO{sub x} species from combustion flue gas. Coal is thermochemically converted to synthesis gas consisting of carbon monoxide, hydrogen, and carbon dioxide. Conventional catalytic upgrading of coal synthesis gas into alcohols or other oxychemicals is subject to several processing problems such as interference of the other constituents in the synthesis gases, strict CO/H{sub 2} ratios required to maintain a particular product distribution and yield, and high processing cost due to the operation at high temperatures and pressures. Recently isolated and identified bacterial strains capable of utilizing CO as a carbon source and coverting CO and H{sub 2} into mixed alcohols offer the potential of performing synthesis gas conversion using biocatalysts. Biocatalytic conversion, though slower than the conventional process, has several advantages such as decreased interference of the other constituents in the synthesis gases, no requirement for strict CO/H{sub 2} ratios, and decreased capital and oeprating costs as the biocatalytic reactions occur at ambient temperatures and pressures.

  6. The SH2 domain is crucial for function of Fyn in neuronal migration and cortical lamination

    PubMed Central

    Lu, Xi; Hu, Xinde; Song, Lingzhen; An, Lei; Duan, Minghui; Chen, Shulin; Zhao, Shanting

    2015-01-01

    Neurons in the developing brain form the cortical plate (CP) in an inside-out manner, in which the late-born neurons are located more superficially than the early-born neurons. Fyn, a member of the Src family kinases, plays an important role in neuronal migration by binding to many substrates. However, the role of the Src-homology 2 (SH2) domain in function of Fyn in neuronal migration remains poorly understood. Here, we demonstrate that the SH2 domain is essential for the action of Fyn in neuronal migration and cortical lamination. A point mutation in the Fyn SH2 domain (FynR176A) impaired neuronal migration and their final location in the cerebral cortex, by inducing neuronal aggregation and branching. Thus, we provide the first evidence of the Fyn SH2 domain contributing to neuronal migration and neuronal morphogenesis. [BMB Reports 2015; 48(2): 97-102] PMID:24912779

  7. Fuel flexible fuel injector

    SciTech Connect

    Tuthill, Richard S; Davis, Dustin W; Dai, Zhongtao

    2015-02-03

    A disclosed fuel injector provides mixing of fuel with airflow by surrounding a swirled fuel flow with first and second swirled airflows that ensures mixing prior to or upon entering the combustion chamber. Fuel tubes produce a central fuel flow along with a central airflow through a plurality of openings to generate the high velocity fuel/air mixture along the axis of the fuel injector in addition to the swirled fuel/air mixture.

  8. Controlling Neurite Outgrowth with Patterned Substrates

    PubMed Central

    Yang, In Hong; Co, Carlos C.; Ho, Chia-Chi

    2011-01-01

    In vivo, neurons form neurites, one of which develops into the axon while others become dendrites. While this neuritogenesis process is well programmed in vivo, there are limited methods to control the number and location of neurite extension in vitro. Here we report a method to control neuritogenesis by confining neurons in specific regions using cell resistant poly(oligoethyleneglycol methacrylate-co-methacrylic acid (OEGMA-co-MA)) or poly(ethyleneglycol-block-lactic acid) PEG-PLA. Line patterned substrates reduce multiple extension of neurites and stimulate bi-directional neurite budding for PC12 and cortical neurons. PC12 cells on 20 and 30 µm line patterns extended one neurite in each direction along the line pattern while cortical neuron on 20 and 30 µm line patterns extended one or two neurites in each direction along the line pattern. Statistical analysis of neurite lengths revealed that PC12 cells and cortical neurons on line patterns extend longer neurites. The ability to guide formation of neurites on patterned substrates is useful for generating neural networks and promoting neurite elongation. PMID:21484989

  9. Process entanglement as a neuronal anchorage mechanism to rough surfaces

    NASA Astrophysics Data System (ADS)

    Sorkin, Raya; Greenbaum, Alon; David-Pur, Moshe; Anava, Sarit; Ayali, Amir; Ben-Jacob, Eshel; Hanein, Yael

    2009-01-01

    The organization of neurons and glia cells on substrates composed of pristine carbon nanotube islands was investigated using high resolution scanning electron microscopy, immunostaining and confocal microscopy. Neurons were found bound and preferentially anchored to the rough surfaces; moreover, the morphology of the neuronal processes on the small, isolated islands of high density carbon nanotubes was found to be conspicuously curled and entangled. We further demonstrate that the roughness of the surface must match the diameter of the neuronal processes in order to allow them to bind. The results presented here suggest that entanglement, a mechanical effect, may constitute an additional mechanism by which neurons (and possibly other cell types) anchor themselves to rough surfaces. Understanding the nature of the interface between neurons and carbon nanotubes is essential to effectively harness carbon nanotube technology in neurological applications such as neuro-prosthetic and retinal electrodes.

  10. Effects of surface asymmetry on neuronal growth.

    PubMed

    Spedden, Elise; Wiens, Matthew R; Demirel, Melik C; Staii, Cristian

    2014-01-01

    Detailed knowledge of how the surface physical properties, such as mechanics, topography and texture influence axonal outgrowth and guidance is essential for understanding the processes that control neuron development, the formation of functional neuronal connections and nerve regeneration. Here we synthesize asymmetric surfaces with well-controlled topography and texture and perform a systematic experimental and theoretical investigation of axonal outgrowth on these substrates. We demonstrate unidirectional axonal bias imparted by the surface ratchet-based topography and quantify the topographical guidance cues that control neuronal growth. We describe the growth cone dynamics using a general stochastic model (Fokker-Planck formalism) and use this model to extract two key dynamical parameters: diffusion (cell motility) coefficient and asymmetric drift coefficient. The drift coefficient is identified with the torque caused by the asymmetric ratchet topography. We relate the observed directional bias in axonal outgrowth to cellular contact guidance behavior, which results in an increase in the cell-surface coupling with increased surface anisotropy. We also demonstrate that the disruption of cytoskeletal dynamics through application of Taxol (stabilizer of microtubules) and Blebbistatin (inhibitor of myosin II activity) greatly reduces the directional bias imparted by these asymmetric surfaces. These results provide new insight into the role played by topographical cues in neuronal growth and could lead to new methods for stimulating neuronal regeneration and the engineering of artificial neuronal tissue. PMID:25184796

  11. Catalyst Substrates Remove Contaminants, Produce Fuel

    NASA Technical Reports Server (NTRS)

    2012-01-01

    A spacecraft is the ultimate tight building. We don t want any leaks, and there is very little fresh air coming in, says Jay Perry, an aerospace engineer at Marshall Space Flight Center. As a result, there is a huge potential for a buildup of contaminants from a host of sources. Inside a spacecraft, contaminants can be introduced from the materials that make spacecraft components, electronics boxes, or activities by the crew such as food preparation or cleaning. Humans also generate contaminants by breathing and through the body s natural metabolic processes. As part of the sophisticated Environmental Control and Life Support System on the International Space Station (ISS), a trace contaminant control system removes carbon dioxide and other impurities from the cabin atmosphere. To maintain healthy levels, the system uses adsorbent media to filter chemical contaminant molecules and a high-temperature catalytic oxidizer to change the chemical structure of the contaminants to something more benign, usually carbon dioxide and water. In the 1990s, while researching air quality control technology for extended spaceflight travel, Perry and others at Marshall were looking for a regenerable process for the continuous removal of carbon dioxide and trace chemical contaminants on long-duration manned space flights. At the time, the existing technology used on U.S. spacecraft could only be used once, which meant that a spacecraft had to carry additional spare parts for use in case the first one was depleted, or the spacecraft would have to return to Earth to exchange the components.

  12. Studying neuronal biomechanics and its role in CNS development

    NASA Astrophysics Data System (ADS)

    Franze, Kristian; Svoboda, Hanno; da F. Costa, Luciano; Guck, Jochen; Holt, Christine

    2013-03-01

    During the development of the nervous system, neurons migrate and grow over great distances. Currently, our understanding of nervous tissue development is, in large part, based on studies of biochemical signaling. Despite the fact that forces are involved in any kind of cell motion, mechanical aspects have so far rarely been considered. Here we used deformable cell culture substrates, traction force microscopy and calcium imaging to investigate how neurons probe and respond to their mechanical environment. While the growth rate of retinal ganglion cell axons was increased on stiffer substrates, their tendency to grow in bundles, which they show in vivo, was significantly enhanced on more compliant substrates. Moreover, if grown on substrates incorporating linear stiffness gradients, neuronal axons were repelled by stiff substrates. Mechanosensing involved the application of forces driven by the interaction of actin and myosin II, and the activation of stretch-activated ion channels leading to calcium influxes into the cells. Applying a modified atomic force microscopy techniquein vivo, we found mechanical gradients in developing brain tissue along which neurons grow. The application of chondroitin sulfate, which is a major extracellular matrix component in the developing brain, changed tissue mechanics and disrupted axonal pathfinding. Hence, our data suggest that neuronal growth is not only guided by chemical signals - as it is currently assumed - but also by the nervous tissue's mechanical properties.

  13. From migration to settlement: the pathways, migration modes and dynamics of neurons in the developing brain

    PubMed Central

    HATANAKA, Yumiko; ZHU, Yan; TORIGOE, Makio; KITA, Yoshiaki; MURAKAMI, Fujio

    2016-01-01

    Neuronal migration is crucial for the construction of the nervous system. To reach their correct destination, migrating neurons choose pathways using physical substrates and chemical cues of either diffusible or non-diffusible nature. Migrating neurons extend a leading and a trailing process. The leading process, which extends in the direction of migration, determines navigation, in particular when a neuron changes its direction of migration. While most neurons simply migrate radially, certain neurons switch their mode of migration between radial and tangential, with the latter allowing migration to destinations far from the neurons’ site of generation. Consequently, neurons with distinct origins are intermingled, which results in intricate neuronal architectures and connectivities and provides an important basis for higher brain function. The trailing process, in contrast, contributes to the late stage of development by turning into the axon, thus contributing to the formation of neuronal circuits. PMID:26755396

  14. Nuclear fuel element

    DOEpatents

    Armijo, Joseph S.; Coffin, Jr., Louis F.

    1983-01-01

    A nuclear fuel element for use in the core of a nuclear reactor is disclosed and has a composite cladding having a substrate and a metal barrier metallurgically bonded on the inside surface of the substrate so that the metal barrier forms a shield between the substrate and the nuclear fuel material held within the cladding. The metal barrier forms about 1 to about 30 percent of the thickness of the cladding and is comprised of a low neutron absorption metal of substantially pure zirconium. The metal barrier serves as a preferential reaction site for gaseous impurities and fission products and protects the substrate from contact and reaction with such impurities and fission products. The substrate of the composite cladding is selected from conventional cladding materials and preferably is a zirconium alloy. Methods of manufacturing the composite cladding are also disclosed.

  15. Power electronics substrate for direct substrate cooling

    DOEpatents

    Le, Khiet; Ward, Terence G.; Mann, Brooks S.; Yankoski, Edward P.; Smith, Gregory S.

    2012-05-01

    Systems and apparatus are provided for power electronics substrates adapted for direct substrate cooling. A power electronics substrate comprises a first surface configured to have electrical circuitry disposed thereon, a second surface, and a plurality of physical features on the second surface. The physical features are configured to promote a turbulent boundary layer in a coolant impinged upon the second surface.

  16. Mesmerising mirror neurons.

    PubMed

    Heyes, Cecilia

    2010-06-01

    Mirror neurons have been hailed as the key to understanding social cognition. I argue that three currents of thought-relating to evolution, atomism and telepathy-have magnified the perceived importance of mirror neurons. When they are understood to be a product of associative learning, rather than an adaptation for social cognition, mirror neurons are no longer mesmerising, but they continue to raise important questions about both the psychology of science and the neural bases of social cognition. PMID:20167276

  17. Signal transfer within a cultured asymmetric cortical neuron circuit

    NASA Astrophysics Data System (ADS)

    Isomura, Takuya; Shimba, Kenta; Takayama, Yuzo; Takeuchi, Akimasa; Kotani, Kiyoshi; Jimbo, Yasuhiko

    2015-12-01

    Objective. Simplified neuronal circuits are required for investigating information representation in nervous systems and for validating theoretical neural network models. Here, we developed patterned neuronal circuits using micro fabricated devices, comprising a micro-well array bonded to a microelectrode-array substrate. Approach. The micro-well array consisted of micrometre-scale wells connected by tunnels, all contained within a silicone slab called a micro-chamber. The design of the micro-chamber confined somata to the wells and allowed axons to grow through the tunnels bidirectionally but with a designed, unidirectional bias. We guided axons into the point of the arrow structure where one of the two tunnel entrances is located, making that the preferred direction. Main results. When rat cortical neurons were cultured in the wells, their axons grew through the tunnels and connected to neurons in adjoining wells. Unidirectional burst transfers and other asymmetric signal-propagation phenomena were observed via the substrate-embedded electrodes. Seventy-nine percent of burst transfers were in the forward direction. We also observed rapid propagation of activity from sites of local electrical stimulation, and significant effects of inhibitory synapse blockade on bursting activity. Significance. These results suggest that this simple, substrate-controlled neuronal circuit can be applied to develop in vitro models of the function of cortical microcircuits or deep neural networks, better to elucidate the laws governing the dynamics of neuronal networks.

  18. Neuronal substrates and functional consequences of prenatal cannabis exposure

    PubMed Central

    Calvigioni, Daniela; Hurd, Yasmin L.; Keimpema, Erik

    2015-01-01

    Cannabis remains one of the world’s most widely used substance of abuse amongst pregnant women. Trends of the last 50 years show an increase in popularity in child-bearing women together with a constant increase in cannabis potency. In addition, potent herbal “legal” highs containing synthetic cannabinoids that mimic the effects of cannabis with unknown pharmacological and toxicological effects have gained rapid popularity amongst young adults. Despite the surge in cannabis use during pregnancy, little is known about the neurobiological and psychological consequences in the exposed offspring. In this review, we emphasize the importance of maternal programming, defined as the intrauterine presentation of maternal stimuli to the foetus, in neurodevelopment. In particular, we focus on cannabis-mediated maternal adverse effects, resulting in direct central nervous system alteration or sensitization to late-onset chronic and neuropsychiatric disorders. We compare clinical and preclinical experimental studies on the effects of foetal cannabis exposure until early adulthood, to stress the importance of animal models that permit the fine control of environmental variables and allow the dissection of cannabis-mediated molecular cascades in the developing central nervous system. In sum, we conclude that preclinical experimental models confirm clinical studies and that cannabis exposure evokes significant molecular modifications to neurodevelopmental programs leading to neurophysiological and behavioural abnormalities. PMID:24793873

  19. Neuronal-glial networks as substrate for CNS integration.

    PubMed

    Verkhratsky, A; Toescu, E C

    2006-01-01

    Astrocytes have been considered, for a long time, as the support and house-keeping cells of the nervous system. Indeed, the astrocytes play very important metabolic roles in the brain, but the catalogue of nervous system functions or activities that involve directly glial participation has extended dramatically in the last decade. In addition to the further refining of the signalling capacity of the neuroglial networks and the detailed reassessment of the interactions between glia and vascular bed in the brain, one of the important salient features of the increased glioscience activity in the last few years was the morphological and functional demonstration that protoplasmic astrocytes occupy well defined spatial territories, with only limited areas of morphological overlapping, but still able to communicate with adjacent neighbours through intercellular junctions. All these features form the basis for a possible reassessment of the nature of integration of activity in the central nervous system that could raise glia to a role of central integrator. PMID:17125587

  20. Neuronal-glial networks as substrate for CNS integration

    PubMed Central

    Verkhratsky, A; Toescu, E C

    2006-01-01

    Astrocytes have been considered, for a long time, as the support and house-keeping cells of the nervous system. Indeed, the astrocytes play very important metabolic roles in the brain, but the catalogue of nervous system functions or activities that involve directly glial participation has extended dramatically in the last decade. In addition to the further refining of the signalling capacity of the neuroglial networks and the detailed reassessment of the interactions between glia and vascular bed in the brain, one of the important salient features of the increased glioscience activity in the last few years was the morphological and functional demonstration that protoplasmic astrocytes occupy well defined spatial territories, with only limited areas of morphological overlapping, but still able to communicate with adjacent neighbours through intercellular junctions. All these features form the basis for a possible reassessment of the nature of integration of activity in the central nervous system that could raise glia to a role of central integrator.

  1. Life and death of neurons in the aging brain

    NASA Technical Reports Server (NTRS)

    Morrison, J. H.; Hof, P. R.; Bloom, F. E. (Principal Investigator)

    1997-01-01

    Neurodegenerative disorders are characterized by extensive neuron death that leads to functional decline, but the neurobiological correlates of functional decline in normal aging are less well defined. For decades, it has been a commonly held notion that widespread neuron death in the neocortex and hippocampus is an inevitable concomitant of brain aging, but recent quantitative studies suggest that neuron death is restricted in normal aging and unlikely to account for age-related impairment of neocortical and hippocampal functions. In this article, the qualitative and quantitative differences between aging and Alzheimer's disease with respect to neuron loss are discussed, and age-related changes in functional and biochemical attributes of hippocampal circuits that might mediate functional decline in the absence of neuron death are explored. When these data are viewed comprehensively, it appears that the primary neurobiological substrates for functional impairment in aging differ in important ways from those in neurodegenerative disorders such as Alzheimer's disease.

  2. Protein palmitoylation in neuronal development and synaptic plasticity.

    PubMed

    Fukata, Yuko; Fukata, Masaki

    2010-03-01

    Protein palmitoylation, a classical and common lipid modification, regulates diverse aspects of neuronal protein trafficking and function. The reversible nature of palmitoylation provides a potential general mechanism for protein shuttling between intracellular compartments. The recent discovery of palmitoylating enzymes--a large DHHC (Asp-His-His-Cys) protein family--and the development of new proteomic and imaging methods have accelerated palmitoylation analysis. It is becoming clear that individual DHHC enzymes generate and maintain the specialized compartmentalization of substrates in polarized neurons. Here, we discuss the regulatory mechanisms for dynamic protein palmitoylation and the emerging roles of protein palmitoylation in various aspects of pathophysiology, including neuronal development and synaptic plasticity. PMID:20168314

  3. Transport mechanisms for adenosine and uridine in primary-cultured rat cortical neurons and astrocytes.

    PubMed

    Nagai, Katsuhito; Nagasawa, Kazuki; Fujimoto, Sadaki

    2005-09-01

    Endogenous adenosine and uridine are important modulators of neural survival and activity. In the present study, we examined transport mechanisms of adenosine and uridine in primary-cultured rat cortical neurons, and compared the results for neurons with those for astrocytes. Reverse transcription-polymerase chain reaction identified the mRNAs for ENT1, ENT2, and CNT2, but not CNT1 and CNT3, in neurons and astrocytes. [3H]Adenosine and [3H]uridine were time-, temperature-, and concentration-dependently taken up into neurons and astrocytes. In kinetic analyses, the uptake of both substrates by neurons and astrocytes consisted of two and one, respectively, saturable transport components. The uptake clearance for both substrates by neurons was greater than that by astrocytes. The relative contribution of the high-affinity major component of both substrates to total uptake was estimated to be approximately 80% in neurons. The uptake of [3H]adenosine and [3H]uridine by both neurons and astrocytes was almost entirely Na+-independent, and sensitive to micro, but not nano, molar concentrations of nitrobenzylmercaptopurine riboside, which are transport characteristics of ENT2. Therefore, it was indicated that adenosine and uridine are more efficiently taken up into neurons than into astrocytes, and ENT2 may predominantly contribute to the transport of the nucleosides as a high-affinity transport system in neurons, as in the case of astrocytes. PMID:16043124

  4. Multifunctional role of astrocytes as gatekeepers of neuronal energy supply

    PubMed Central

    Stobart, Jillian L.; Anderson, Christopher M.

    2013-01-01

    Dynamic adjustments to neuronal energy supply in response to synaptic activity are critical for neuronal function. Glial cells known as astrocytes have processes that ensheath most central synapses and express G-protein-coupled neurotransmitter receptors and transporters that respond to neuronal activity. Astrocytes also release substrates for neuronal oxidative phosphorylation and have processes that terminate on the surface of brain arterioles and can influence vascular smooth muscle tone and local blood flow. Membrane receptor or transporter-mediated effects of glutamate represent a convergence point of astrocyte influence on neuronal bioenergetics. Astrocytic glutamate uptake drives glycolysis and subsequent shuttling of lactate from astrocytes to neurons for oxidative metabolism. Astrocytes also convert synaptically reclaimed glutamate to glutamine, which is returned to neurons for glutamate salvage or oxidation. Finally, astrocytes store brain energy currency in the form of glycogen, which can be mobilized to produce lactate for neuronal oxidative phosphorylation in response to glutamatergic neurotransmission. These mechanisms couple synaptically driven astrocytic responses to glutamate with release of energy substrates back to neurons to match demand with supply. In addition, astrocytes directly influence the tone of penetrating brain arterioles in response to glutamatergic neurotransmission, coordinating dynamic regulation of local blood flow. We will describe the role of astrocytes in neurometabolic and neurovascular coupling in detail and discuss, in turn, how astrocyte dysfunction may contribute to neuronal bioenergetic deficit and neurodegeneration. Understanding the role of astrocytes as a hub for neurometabolic and neurovascular coupling mechanisms is a critical underpinning for therapeutic development in a broad range of neurodegenerative disorders characterized by chronic generalized brain ischemia and brain microvascular dysfunction. PMID:23596393

  5. Quantum neuron design

    NASA Astrophysics Data System (ADS)

    Behrman, Elizabeth; Steck, James

    2014-03-01

    In previous work, we have developed quantum systems that can learn and do information processing much like artificial neural networks. These learning methods have some advantages over other implementations of quantum computing in that they construct their own algorithms and could be robust to noise and decoherence. Here we take the next step, by designing quantum neurons that have some of the important behaviors of biological neurons, yet have the advantage of being complex valued and having quantum computing power. Our neuron model consists of a two-level system coupled to a Gaussian bath representing the environment. Simulations of a interconnected network of these neurons show that the model can both learn standard AI tasks, as similar networks of classical neurons have been shown to do, and, in addition, perform quantum mechanical calculations.

  6. Direct evidence for activity-dependent glucose phosphorylation in neurons with implications for the astrocyte-to-neuron lactate shuttle

    PubMed Central

    Patel, Anant B.; Lai, James C. K.; Chowdhury, Golam M. I.; Hyder, Fahmeed; Rothman, Douglas L.; Shulman, Robert G.; Behar, Kevin L.

    2014-01-01

    Previous 13C magnetic resonance spectroscopy experiments have shown that over a wide range of neuronal activity, approximately one molecule of glucose is oxidized for every molecule of glutamate released by neurons and recycled through astrocytic glutamine. The measured kinetics were shown to agree with the stoichiometry of a hypothetical astrocyte-to-neuron lactate shuttle model, which predicted negligible functional neuronal uptake of glucose. To test this model, we measured the uptake and phosphorylation of glucose in nerve terminals isolated from rats infused with the glucose analog, 2-fluoro-2-deoxy-d-glucose (FDG) in vivo. The concentrations of phosphorylated FDG (FDG6P), normalized with respect to known neuronal metabolites, were compared in nerve terminals, homogenate, and cortex of anesthetized rats with and without bicuculline-induced seizures. The increase in FDG6P in nerve terminals agreed well with the increase in cortical neuronal glucose oxidation measured previously under the same conditions in vivo, indicating that direct uptake and oxidation of glucose in nerve terminals is substantial under resting and activated conditions. These results suggest that neuronal glucose-derived pyruvate is the major oxidative fuel for activated neurons, not lactate-derived from astrocytes, contradicting predictions of the original astrocyte-to-neuron lactate shuttle model under the range of study conditions. PMID:24706914

  7. Neural substrates underlying intentional empathy

    PubMed Central

    Wang, Gang; Yang, Xuedong; Wang, Xiaoying; Northoff, Georg; Han, Shihui

    2012-01-01

    Although empathic responses to stimuli with emotional contents may occur automatically, humans are capable to intentionally empathize with other individuals. Intentional empathy for others is even possible when they do not show emotional expressions. However, little is known about the neuronal mechanisms of this intentionally controlled empathic process. To investigate the neuronal substrates underlying intentional empathy, we scanned 20 healthy Chinese subjects, using fMRI, when they tried to feel inside the emotional states of neutral or angry faces of familiar (Asian) and unfamiliar (Caucasian) models. Skin color evaluation of the same stimuli served as a control task. Compared to a baseline condition, the empathy task revealed a network of established empathy regions, including the anterior cingulate cortex, bilateral inferior frontal cortex and bilateral anterior insula. The contrast of intentional empathy vs skin color evaluation, however, revealed three regions: the bilateral inferior frontal cortex, whose hemodynamic responses were independent of perceived emotion and familiarity and the right-middle temporal gyrus, whose activity was modulated by emotion but not by familiarity. These findings extend our understanding of the role of the inferior frontal cortex and the middle temporal gyrus in empathy by demonstrating their involvement in intentional empathy. PMID:21511824

  8. Transporting mitochondria in neurons

    PubMed Central

    Course, Meredith M.; Wang, Xinnan

    2016-01-01

    Neurons demand vast and vacillating supplies of energy. As the key contributors of this energy, as well as primary pools of calcium and signaling molecules, mitochondria must be where the neuron needs them, when the neuron needs them. The unique architecture and length of neurons, however, make them a complex system for mitochondria to navigate. To add to this difficulty, mitochondria are synthesized mainly in the soma, but must be transported as far as the distant terminals of the neuron. Similarly, damaged mitochondria—which can cause oxidative stress to the neuron—must fuse with healthy mitochondria to repair the damage, return all the way back to the soma for disposal, or be eliminated at the terminals. Increasing evidence suggests that the improper distribution of mitochondria in neurons can lead to neurodegenerative and neuropsychiatric disorders. Here, we will discuss the machinery and regulatory systems used to properly distribute mitochondria in neurons, and how this knowledge has been leveraged to better understand neurological dysfunction. PMID:27508065

  9. How microglia kill neurons.

    PubMed

    Brown, Guy C; Vilalta, Anna

    2015-12-01

    Microglia are resident brain macrophages that become inflammatory activated in most brain pathologies. Microglia normally protect neurons, but may accidentally kill neurons when attempting to limit infections or damage, and this may be more common with degenerative disease as there was no significant selection pressure on the aged brain in the past. A number of mechanisms by which activated microglia kill neurons have been identified, including: (i) stimulation of the phagocyte NADPH oxidase (PHOX) to produce superoxide and derivative oxidants, (ii) expression of inducible nitric oxide synthase (iNOS) producing NO and derivative oxidants, (iii) release of glutamate and glutaminase, (iv) release of TNFα, (v) release of cathepsin B, (vi) phagocytosis of stressed neurons, and (vii) decreased release of nutritive BDNF and IGF-1. PHOX stimulation contributes to microglial activation, but is not directly neurotoxic unless NO is present. NO is normally neuroprotective, but can react with superoxide to produce neurotoxic peroxynitrite, or in the presence of hypoxia inhibit mitochondrial respiration. Glutamate can be released by glia or neurons, but is neurotoxic only if the neurons are depolarised, for example as a result of mitochondrial inhibition. TNFα is normally neuroprotective, but can become toxic if caspase-8 or NF-κB activation are inhibited. If the above mechanisms do not kill neurons, they may still stress the neurons sufficiently to make them susceptible to phagocytosis by activated microglia. We review here whether microglial killing of neurons is an artefact, makes evolutionary sense or contributes in common neuropathologies and by what mechanisms. This article is part of a Special Issue entitled SI: Neuroprotection. PMID:26341532

  10. Morphology and Intrinsic Excitability of Regenerating Sensory and Motor Neurons Grown on a Line Micropattern

    PubMed Central

    Benzina, Ouafa; Cloitre, Thierry; Martin, Marta; Raoul, Cédric; Gergely, Csilla; Scamps, Frédérique

    2014-01-01

    Axonal regeneration is one of the greatest challenges in severe injuries of peripheral nerve. To provide the bridge needed for regeneration, biological or synthetic tubular nerve constructs with aligned architecture have been developed. A key point for improving axonal regeneration is assessing the effects of substrate geometry on neuronal behavior. In the present study, we used an extracellular matrix-micropatterned substrate comprising 3 µm wide lines aimed to physically mimic the in vivo longitudinal axonal growth of mice peripheral sensory and motor neurons. Adult sensory neurons or embryonic motoneurons were seeded and processed for morphological and electrical activity analyses after two days in vitro. We show that micropattern-guided sensory neurons grow one or two axons without secondary branching. Motoneurons polarity was kept on micropattern with a long axon and small dendrites. The micro-patterned substrate maintains the growth promoting effects of conditioning injury and demonstrates, for the first time, that neurite initiation and extension could be differentially regulated by conditioning injury among DRG sensory neuron subpopulations. The micro-patterned substrate impacts the excitability of sensory neurons and promotes the apparition of firing action potentials characteristic for a subclass of mechanosensitive neurons. The line pattern is quite relevant for assessing the regenerative and developmental growth of sensory and motoneurons and offers a unique model for the analysis of the impact of geometry on the expression and the activity of mechanosensitive channels in DRG sensory neurons. PMID:25329060

  11. Signal Propagation between Neuronal Populations Controlled by Micropatterning

    PubMed Central

    Albers, Jonas; Offenhäusser, Andreas

    2016-01-01

    The central nervous system consists of an unfathomable number of functional networks enabling highly sophisticated information processing. Guided neuronal growth with a well-defined connectivity and accompanying polarity is essential for the formation of these networks. To investigate how two-dimensional protein patterns influence neuronal outgrowth with respect to connectivity and functional polarity between adjacent populations of neurons, a microstructured model system was established. Exclusive cell growth on patterned substrates was achieved by transferring a mixture of poly-l-lysine and laminin to a cell-repellent glass surface by microcontact printing. Triangular structures with different opening angle, height, and width were chosen as a pattern to achieve network formation with defined behavior at the junction of adjacent structures. These patterns were populated with dissociated primary cortical embryonic rat neurons and investigated with respect to their impact on neuronal outgrowth by immunofluorescence analysis, as well as their functional connectivity by calcium imaging. Here, we present a highly reproducible technique to devise neuronal networks in vitro with a predefined connectivity induced by the design of the gateway. Daisy-chained neuronal networks with predefined connectivity and functional polarity were produced using the presented micropatterning method. Controlling the direction of signal propagation among populations of neurons provides insights to network communication and offers the chance to investigate more about learning processes in networks by external manipulation of cells and signal cascades. PMID:27379230

  12. Signal Propagation between Neuronal Populations Controlled by Micropatterning.

    PubMed

    Albers, Jonas; Offenhäusser, Andreas

    2016-01-01

    The central nervous system consists of an unfathomable number of functional networks enabling highly sophisticated information processing. Guided neuronal growth with a well-defined connectivity and accompanying polarity is essential for the formation of these networks. To investigate how two-dimensional protein patterns influence neuronal outgrowth with respect to connectivity and functional polarity between adjacent populations of neurons, a microstructured model system was established. Exclusive cell growth on patterned substrates was achieved by transferring a mixture of poly-l-lysine and laminin to a cell-repellent glass surface by microcontact printing. Triangular structures with different opening angle, height, and width were chosen as a pattern to achieve network formation with defined behavior at the junction of adjacent structures. These patterns were populated with dissociated primary cortical embryonic rat neurons and investigated with respect to their impact on neuronal outgrowth by immunofluorescence analysis, as well as their functional connectivity by calcium imaging. Here, we present a highly reproducible technique to devise neuronal networks in vitro with a predefined connectivity induced by the design of the gateway. Daisy-chained neuronal networks with predefined connectivity and functional polarity were produced using the presented micropatterning method. Controlling the direction of signal propagation among populations of neurons provides insights to network communication and offers the chance to investigate more about learning processes in networks by external manipulation of cells and signal cascades. PMID:27379230

  13. Neuronal Functions of ESCRTs

    PubMed Central

    Gao, Fen-Biao

    2012-01-01

    The endosomal sorting complexes required for transport (ESCRTs) regulate protein trafficking from endosomes to lysosomes. Recent studies have shown that ESCRTs are involved in various cellular processes, including membrane scission, microRNA function, viral budding, and the autophagy pathway in many tissues, including the nervous system. Indeed, dysfunctional ESCRTs are associated with neurodegeneration. However, it remains largely elusive how ESCRTs act in post-mitotic neurons, a highly specialized cell type that requires dynamic changes in neuronal structures and signaling for proper function. This review focuses on our current understandings of the functions of ESCRTs in neuronal morphology, synaptic plasticity, and neurodegenerative diseases. PMID:22438674

  14. Coated substrates and process

    DOEpatents

    Chu, Wei-kan; Childs, Charles B.

    1991-01-01

    Disclosed herein is a coated substrate and a process for forming films on substrates and for providing a particularly smooth film on a substrate. The method of this invention involves subjecting a surface of a substrate to contact with a stream of ions of an inert gas having sufficient force and energy to substantially change the surface characteristics of said substrate, and then exposing a film-forming material to a stream of ions of an inert gas having sufficient energy to vaporize the atoms of said film-forming material and to transmit the vaporized atoms to the substrate surface with sufficient force to form a film bonded to the substrate. This process is particularly useful commercially because it forms strong bonds at room temperature. This invention is particularly useful for adhering a gold film to diamond and forming ohmic electrodes on diamond, but also can be used to bond other films to substrates.

  15. Ribbed electrode substrates

    DOEpatents

    Breault, Richard D.; Goller, Glen J.

    1983-01-01

    A ribbed substrate for an electrochemical cell electrode is made from a mixture of carbon fibers and carbonizable resin and has a mean pore size in the ribs which is 60-75% of the mean pore size of the web portions of the substrate which interconnect the ribs. Preferably the mean pore size of the web portion is 25-45 microns; and, if the substrate includes edge seals parallel to the ribs, the edge seals preferably have a mean pore size no greater than about ten microns. Most preferably the substrate has the same ratio of carbon fibers to polymeric carbon in all areas, including the ribs, webs, and edge seals. A substrate according to the present invention will have better overall performance than prior art substrates and minimizes the substrate thickness required for the substrate to perform all its functions well.

  16. Corrosion resistant PEM fuel cell

    DOEpatents

    Fronk, Matthew Howard; Borup, Rodney Lynn; Hulett, Jay S.; Brady, Brian K.; Cunningham, Kevin M.

    2002-01-01

    A PEM fuel cell having electrical contact elements comprising a corrosion-susceptible substrate metal coated with an electrically conductive, corrosion-resistant polymer containing a plurality of electrically conductive, corrosion-resistant filler particles. The substrate may have an oxidizable metal first layer (e.g., stainless steel) underlying the polymer coating.

  17. Corrosion resistant PEM fuel cell

    DOEpatents

    Fronk, Matthew Howard; Borup, Rodney Lynn; Hulett, Jay S.; Brady, Brian K. NY); Cunningham, Kevin M.

    2011-06-07

    A PEM fuel cell having electrical contact elements comprising a corrosion-susceptible substrate metal coated with an electrically conductive, corrosion-resistant polymer containing a plurality of electrically conductive, corrosion-resistant filler particles. The substrate may have an oxidizable metal first layer (e.g., stainless steel) underlying the polymer coating.

  18. Neuronal polarity selection by topography-induced focal adhesion control.

    PubMed

    Ferrari, Aldo; Cecchini, Marco; Serresi, Michela; Faraci, Paolo; Pisignano, Dario; Beltram, Fabio

    2010-06-01

    Interaction between differentiating neurons and the extracellular environment guides the establishment of cell polarity during nervous system development. Developing neurons read the physical properties of the local substrate in a contact-dependent manner and retrieve essential guidance cues. In previous works we demonstrated that PC12 cell interaction with nanogratings (alternating lines of ridges and grooves of submicron size) promotes bipolarity and alignment to the substrate topography. Here, we investigate the role of focal adhesions, cell contractility, and actin dynamics in this process. Exploiting nanoimprint lithography techniques and a cyclic olefin copolymer, we engineered biocompatible nanostructured substrates designed for high-resolution live-cell microscopy. Our results reveal that neuronal polarization and contact guidance are based on a geometrical constraint of focal adhesions resulting in an angular modulation of their maturation and persistence. We report on ROCK1/2-myosin-II pathway activity and demonstrate that ROCK-mediated contractility contributes to polarity selection during neuronal differentiation. Importantly, the selection process confined the generation of actin-supported membrane protrusions and the initiation of new neurites at the poles. Maintenance of the established polarity was independent from NGF stimulation. Altogether our results imply that focal adhesions and cell contractility stably link the topographical configuration of the extracellular environment to a corresponding neuronal polarity state. PMID:20304485

  19. Growth of primary motor neurons on horizontally aligned carbon nanotube thin films and striped patterns

    NASA Astrophysics Data System (ADS)

    Roberts, Megan J.; Leach, Michelle K.; Bedewy, Mostafa; Meshot, Eric R.; Copic, Davor; Corey, Joseph M.; Hart, A. John

    2014-06-01

    Objective. Carbon nanotubes (CNTs) are attractive for use in peripheral nerve interfaces because of their unique combination of strength, flexibility, electrical conductivity and nanoscale surface texture. Here we investigated the growth of motor neurons on thin films of horizontally aligned CNTs (HACNTs). Approach. We cultured primary embryonic rat motor neurons on HACNTs and performed statistical analysis of the length and orientation of neurites. We next presented motor neurons with substrates of alternating stripes of HACNTs and SiO2. Main results. The neurons survived on HACNT substrates for up to eight days, which was the full duration of our experiments. Statistical analysis of the length and orientation of neurites indicated that the longest neurites on HACNTs tended to align with the CNT direction, although the average neurite length was similar between HACNTs and glass control substrates. We observed that when motor neurons were presented with alternating stripes of HACNTs and SiO2, the proportion of neurons on HACNTs increases over time, suggesting that neurons selectively migrate toward and adhere to the HACNT surface. Significance. The behavior of motor neurons on CNTs has not been previously investigated, and we show that aligned CNTs could provide a viable interface material to motor neurons. Combined with emerging techniques to build complex hierarchical structures of CNTs, our results suggest that organised CNTs could be incorporated into nerve grafts that use physical and electrical cues to guide regenerating axons.

  20. Polished polymide substrate

    DOEpatents

    Farah, John; Sudarshanam, Venkatapuram S.

    2003-05-13

    Polymer substrates, in particular polyimide substrates, and polymer laminates for optical applications are described. Polyimide substrates are polished on one or both sides depending on their thickness, and single-layer or multi-layer waveguide structures are deposited on the polished polyimide substrates. Optical waveguide devices are machined by laser ablation using a combination of IR and UV lasers. A waveguide-fiber coupler with a laser-machined groove for retaining the fiber is also disclosed.

  1. Recovery of EUVL substrates

    SciTech Connect

    Vernon, S.P.; Baker, S.L.

    1995-01-19

    Mo/Si multilayers, were removed from superpolished zerodur and fused silica substrates with a dry etching process that, under suitable processing conditions, produces negligible change in either the substrate surface figure or surface roughness. Full recovery of the initial normal incidence extreme ultra-violet (EUV) reflectance response has been demonstrated on reprocessed substrates.

  2. Neuromorphic silicon neuron circuits.

    PubMed

    Indiveri, Giacomo; Linares-Barranco, Bernabé; Hamilton, Tara Julia; van Schaik, André; Etienne-Cummings, Ralph; Delbruck, Tobi; Liu, Shih-Chii; Dudek, Piotr; Häfliger, Philipp; Renaud, Sylvie; Schemmel, Johannes; Cauwenberghs, Gert; Arthur, John; Hynna, Kai; Folowosele, Fopefolu; Saighi, Sylvain; Serrano-Gotarredona, Teresa; Wijekoon, Jayawan; Wang, Yingxue; Boahen, Kwabena

    2011-01-01

    Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain-machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance-based Hodgkin-Huxley models to bi-dimensional generalized adaptive integrate and fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips. PMID:21747754

  3. Neuronal ubiquitin homeostasis

    PubMed Central

    Hallengren, Jada; Chen, Ping-Chung; Wilson, Scott M.

    2013-01-01

    Neurons have highly specialized intracellular compartments that facilitate the development and activity of the nervous system. Ubiquitination is a post-translational modification that controls many aspects of neuronal function by regulating protein abundance. Disruption of this signaling pathway has been demonstrated in neurological disorders such as Parkinson’s disease, Amyotrophic Lateral Sclerosis and Angleman Syndrome. Since many neurological disorders exhibit ubiquitinated protein aggregates, the loss of neuronal ubiquitin homeostasis may be an important contributor of disease. This review discusses the mechanisms utilized by neurons to control the free pool of ubiquitin necessary for normal nervous system development and function as well as new roles of protein ubiquitination in regulating synaptic activity. PMID:23686613

  4. Neuromorphic Silicon Neuron Circuits

    PubMed Central

    Indiveri, Giacomo; Linares-Barranco, Bernabé; Hamilton, Tara Julia; van Schaik, André; Etienne-Cummings, Ralph; Delbruck, Tobi; Liu, Shih-Chii; Dudek, Piotr; Häfliger, Philipp; Renaud, Sylvie; Schemmel, Johannes; Cauwenberghs, Gert; Arthur, John; Hynna, Kai; Folowosele, Fopefolu; Saighi, Sylvain; Serrano-Gotarredona, Teresa; Wijekoon, Jayawan; Wang, Yingxue; Boahen, Kwabena

    2011-01-01

    Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain–machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance-based Hodgkin–Huxley models to bi-dimensional generalized adaptive integrate and fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips. PMID:21747754

  5. Cellular Links between Neuronal Activity and Energy Homeostasis

    PubMed Central

    Shetty, Pavan K.; Galeffi, Francesca; Turner, Dennis A.

    2012-01-01

    Neuronal activity, astrocytic responses to this activity, and energy homeostasis are linked together during baseline, conscious conditions, and short-term rapid activation (as occurs with sensory or motor function). Nervous system energy homeostasis also varies during long-term physiological conditions (i.e., development and aging) and with adaptation to pathological conditions, such as ischemia or low glucose. Neuronal activation requires increased metabolism (i.e., ATP generation) which leads initially to substrate depletion, induction of a variety of signals for enhanced astrocytic function, and increased local blood flow and substrate delivery. Energy generation (particularly in mitochondria) and use during ATP hydrolysis also lead to considerable heat generation. The local increases in blood flow noted following neuronal activation can both enhance local substrate delivery but also provides a heat sink to help cool the brain and removal of waste by-products. In this review we highlight the interactions between short-term neuronal activity and energy metabolism with an emphasis on signals and factors regulating astrocyte function and substrate supply. PMID:22470340

  6. Superoxide dismutase protects cultured neurons against death by starvation.

    PubMed Central

    Sáez, J C; Kessler, J A; Bennett, M V; Spray, D C

    1987-01-01

    Brief substrate deprivation resulted in high mortality of superior cervical ganglion neurons in culture, assayed 2 hr later by trypan blue exclusion. Involvement of superoxide anions was indicated by several observations. Survival was increased significantly by prior treatment that induced cells to take up superoxide dismutase. During starvation, neurons reduced nitroblue tetrazolium to form the blue precipitate formazan, and the color change was blocked in neurons preloaded with superoxide dismutase. The incidence of staining was comparable to the mortality. In many cells, brief starvation caused the appearance of fluorescence due to oxidation of 2',7'-dichlorofluorescin to dichlorofluorescein, which indicates that oxidants were generated intracellularly. In some cells fluorescence was transient, as would be caused by membrane breakdown, and these cells were then shown to be dead. Superoxide generation caused by substrate deprivation may contribute importantly to cell damage in a variety of pathological conditions. Images PMID:3472251

  7. Competing dopamine neurons drive oviposition choice for ethanol in Drosophila.

    PubMed

    Azanchi, Reza; Kaun, Karla R; Heberlein, Ulrike

    2013-12-24

    The neural circuits that mediate behavioral choice evaluate and integrate information from the environment with internal demands and then initiate a behavioral response. Even circuits that support simple decisions remain poorly understood. In Drosophila melanogaster, oviposition on a substrate containing ethanol enhances fitness; however, little is known about the neural mechanisms mediating this important choice behavior. Here, we characterize the neural modulation of this simple choice and show that distinct subsets of dopaminergic neurons compete to either enhance or inhibit egg-laying preference for ethanol-containing food. Moreover, activity in α'β' neurons of the mushroom body and a subset of ellipsoid body ring neurons (R2) is required for this choice. We propose a model where competing dopaminergic systems modulate oviposition preference to adjust to changes in natural oviposition substrates. PMID:24324162

  8. NeuronBank: A Tool for Cataloging Neuronal Circuitry

    PubMed Central

    Katz, Paul S.; Calin-Jageman, Robert; Dhawan, Akshaye; Frederick, Chad; Guo, Shuman; Dissanayaka, Rasanjalee; Hiremath, Naveen; Ma, Wenjun; Shen, Xiuyn; Wang, Hsui C.; Yang, Hong; Prasad, Sushil; Sunderraman, Rajshekhar; Zhu, Ying

    2010-01-01

    The basic unit of any nervous system is the neuron. Therefore, understanding the operation of nervous systems ultimately requires an inventory of their constituent neurons and synaptic connectivity, which form neural circuits. The presence of uniquely identifiable neurons or classes of neurons in many invertebrates has facilitated the construction of cellular-level connectivity diagrams that can be generalized across individuals within a species. Homologous neurons can also be recognized across species. Here we describe NeuronBank.org, a web-based tool that we are developing for cataloging, searching, and analyzing neuronal circuitry within and across species. Information from a single species is represented in an individual branch of NeuronBank. Users can search within a branch or perform queries across branches to look for similarities in neuronal circuits across species. The branches allow for an extensible ontology so that additional characteristics can be added as knowledge grows. Each entry in NeuronBank generates a unique accession ID, allowing it to be easily cited. There is also an automatic link to a Wiki page allowing an encyclopedic explanation of the entry. All of the 44 previously published neurons plus one previously unpublished neuron from the mollusc, Tritonia diomedea, have been entered into a branch of NeuronBank as have 4 previously published neurons from the mollusc, Melibe leonina. The ability to organize information about neuronal circuits will make this information more accessible, ultimately aiding research on these important models. PMID:20428500

  9. Physical and Biological Regulation of Neuron Regenerative Growth and Network Formation on Recombinant Dragline Silks

    PubMed Central

    Huang, Wenwen; He, Jiuyang; Jones, Justin; Lewis, Randolph V.; Kaplan, David L.

    2015-01-01

    Recombinant spider silks produced in transgenic goat milk were studied as cell culture matrices for neuronal growth. Major ampullate spidroin 1 (MaSp1) supported neuronal growth, axon extension and network connectivity, with cell morphology comparable to the gold standard poly-lysine. In addition, neurons growing on MaSp1 films had increased neural cell adhesion molecule (NCAM) expression at both mRNA and protein levels. The results indicate that MaSp1 films present useful surface charge and substrate stiffness to support the growth of primary rat cortical neurons. Moreover, a putative neuron-specific surface binding sequence GRGGL within MaSp1 may contribute to the biological regulation of neuron growth. These findings indicate that MaSp1 could regulate neuron growth through its physical and biological features. This dual regulation mode of MaSp1 could provide an alternative strategy for generating functional silk materials for neural tissue engineering. PMID:25701039

  10. Representation of retrieval confidence by single neurons in the human medial temporal lobe

    PubMed Central

    Rutishauser, Ueli; Ye, Shengxuan; Koroma, Matthieu; Tudusciuc, Oana; Ross, Ian B.; Chung, Jeffrey M.; Mamelak, Adam N.

    2015-01-01

    Memory-based decisions are often accompanied by an assessment of choice certainty, but the mechanisms of such confidence judgments remain unknown. We studied the response of 1065 individual neurons in the human hippocampus and amygdala while neurosurgical patients made memory retrieval decisions together with a confidence judgment. Combining behavioral, neuronal and computational analysis, we identified a population of memory-selective (MS) neurons whose activity signaled stimulus familiarity and confidence as assessed by subjective report. In contrast, the activity of visually selective (VS) neurons was not sensitive to memory strength. The groups further differed in response latency, tuning, and extracellular waveforms. The information provided by MS neurons was sufficient for a race model to decide stimulus familiarity and retrieval confidence. Together, this demonstrates a trial-by-trial relationship between a specific group of neurons and declared memory strength in humans. We suggest that VS and MS neurons are a substrate for declarative memories. PMID:26053402

  11. Cell-Type Dependent Effect of Surface-Patterned Microdot Arrays on Neuronal Growth

    PubMed Central

    Jang, Min Jee; Kim, Woon Ryoung; Joo, Sunghoon; Ryu, Jae Ryun; Lee, Eunsoo; Nam, Yoonkey; Sun, Woong

    2016-01-01

    Surface micropatterns have been widely used as chemical cues to control the microenvironment of cultured neurons, particularly for neurobiological assays and neurochip designs. However, the cell-type dependency on the interactions between neurons and underlying micropatterns has been rarely investigated despite the inherent differences in the morphology of neuronal types. In this study, we used surface-printed microdot arrays to investigate the effect of the same micropatterns on the growth of mouse spinal interneuron, mouse hippocampal neurons, and rat hippocampal neurons. While mouse hippocampal neurons showed no significantly different growth on control and patterned substrates, we found the microdot arrays had different effects on early neuronal growth depending on the cell type; spinal interneurons tended to grow faster in length, whereas hippocampal neurons tended to form more axon collateral branches in response to the microdot arrays. Although there was a similar trend in the neurite length and branch number of both neurons changed across the microdot arrays with the expanded range of size and spacing, the dominant responses of each neuron, neurite elongation of mouse spinal interneurons and branching augmentation of rat hippocampal neurons were still preserved. Therefore, our results demonstrate that the same design of micropatterns could cause different neuronal growth results, raising an intriguing issue of considering cell types in neural interface designs. PMID:27242421

  12. Cell-Type Dependent Effect of Surface-Patterned Microdot Arrays on Neuronal Growth.

    PubMed

    Jang, Min Jee; Kim, Woon Ryoung; Joo, Sunghoon; Ryu, Jae Ryun; Lee, Eunsoo; Nam, Yoonkey; Sun, Woong

    2016-01-01

    Surface micropatterns have been widely used as chemical cues to control the microenvironment of cultured neurons, particularly for neurobiological assays and neurochip designs. However, the cell-type dependency on the interactions between neurons and underlying micropatterns has been rarely investigated despite the inherent differences in the morphology of neuronal types. In this study, we used surface-printed microdot arrays to investigate the effect of the same micropatterns on the growth of mouse spinal interneuron, mouse hippocampal neurons, and rat hippocampal neurons. While mouse hippocampal neurons showed no significantly different growth on control and patterned substrates, we found the microdot arrays had different effects on early neuronal growth depending on the cell type; spinal interneurons tended to grow faster in length, whereas hippocampal neurons tended to form more axon collateral branches in response to the microdot arrays. Although there was a similar trend in the neurite length and branch number of both neurons changed across the microdot arrays with the expanded range of size and spacing, the dominant responses of each neuron, neurite elongation of mouse spinal interneurons and branching augmentation of rat hippocampal neurons were still preserved. Therefore, our results demonstrate that the same design of micropatterns could cause different neuronal growth results, raising an intriguing issue of considering cell types in neural interface designs. PMID:27242421

  13. Neuronal avalanches and learning

    NASA Astrophysics Data System (ADS)

    de Arcangelis, Lucilla

    2011-05-01

    Networks of living neurons represent one of the most fascinating systems of biology. If the physical and chemical mechanisms at the basis of the functioning of a single neuron are quite well understood, the collective behaviour of a system of many neurons is an extremely intriguing subject. Crucial ingredient of this complex behaviour is the plasticity property of the network, namely the capacity to adapt and evolve depending on the level of activity. This plastic ability is believed, nowadays, to be at the basis of learning and memory in real brains. Spontaneous neuronal activity has recently shown features in common to other complex systems. Experimental data have, in fact, shown that electrical information propagates in a cortex slice via an avalanche mode. These avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems and successful models have been developed to describe their behaviour. In this contribution we discuss a statistical mechanical model for the complex activity in a neuronal network. The model implements the main physiological properties of living neurons and is able to reproduce recent experimental results. Then, we discuss the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules, in particular the exclusive OR (XOR) and a random rule with three inputs. The learning dynamics exhibits universal features as function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

  14. SV2 mediates entry of tetanus neurotoxin into central neurons.

    PubMed

    Yeh, Felix L; Dong, Min; Yao, Jun; Tepp, William H; Lin, Guangyun; Johnson, Eric A; Chapman, Edwin R

    2010-01-01

    Tetanus neurotoxin causes the disease tetanus, which is characterized by rigid paralysis. The toxin acts by inhibiting the release of neurotransmitters from inhibitory neurons in the spinal cord that innervate motor neurons and is unique among the clostridial neurotoxins due to its ability to shuttle from the periphery to the central nervous system. Tetanus neurotoxin is thought to interact with a high affinity receptor complex that is composed of lipid and protein components; however, the identity of the protein receptor remains elusive. In the current study, we demonstrate that toxin binding, to dissociated hippocampal and spinal cord neurons, is greatly enhanced by driving synaptic vesicle exocytosis. Moreover, tetanus neurotoxin entry and subsequent cleavage of synaptobrevin II, the substrate for this toxin, was also dependent on synaptic vesicle recycling. Next, we identified the potential synaptic vesicle binding protein for the toxin and found that it corresponded to SV2; tetanus neurotoxin was unable to cleave synaptobrevin II in SV2 knockout neurons. Toxin entry into knockout neurons was rescued by infecting with viruses that express SV2A or SV2B. Tetanus toxin elicited the hyper excitability in dissociated spinal cord neurons - due to preferential loss of inhibitory transmission - that is characteristic of the disease. Surprisingly, in dissociated cortical cultures, low concentrations of the toxin preferentially acted on excitatory neurons. Further examination of the distribution of SV2A and SV2B in both spinal cord and cortical neurons revealed that SV2B is to a large extent localized to excitatory terminals, while SV2A is localized to inhibitory terminals. Therefore, the distinct effects of tetanus toxin on cortical and spinal cord neurons are not due to differential expression of SV2 isoforms. In summary, the findings reported here indicate that SV2A and SV2B mediate binding and entry of tetanus neurotoxin into central neurons. PMID:21124874

  15. Somatosensory Substrates of Flight Control in Bats

    PubMed Central

    Marshall, Kara L.; Chadha, Mohit; deSouza, Laura A.; Sterbing-D’Angelo, Susanne J.; Moss, Cynthia F.; Lumpkin, Ellen A.

    2015-01-01

    Summary Flight maneuvers require rapid sensory integration to generate adaptive motor output. Bats achieve remarkable agility with modified forelimbs that serve as airfoils while retaining capacity for object manipulation. Wing sensory inputs provide behaviorally relevant information to guide flight; however, components of wing sensory-motor circuits have not been analyzed. Here, we elucidate the organization of wing innervation in an insectivore, the big brown bat, Eptesicus fuscus. We demonstrate that wing sensory innervation differs from other vertebrate forelimbs, revealing a peripheral basis for the atypical topographic organization reported for bat somatosensory nuclei. Furthermore, the wing is innervated by an unusual complement of sensory neurons poised to report airflow and touch. Finally, we report that cortical neurons encode tactile and airflow inputs with sparse activity patterns. Together, our findings identify neural substrates of somatosensation in the bat wing and imply that evolutionary pressures giving rise to mammalian flight led to unusual sensorimotor projections. PMID:25937277

  16. Multistructural biomimetic substrates for controlled cellular differentiation

    NASA Astrophysics Data System (ADS)

    Orza, Anamaria I.; Mihu, Carmen; Soritau, Olga; Diudea, Mircea; Florea, Adrian; Matei, Horea; Balici, Stefana; Mudalige, Thilak; Kanarpardy, Ganesh K.; Biris, Alexandru S.

    2014-02-01

    Multidimensional scaffolds are considered to be ideal candidates for regenerative medicine and tissue engineering based on their potential to provide an excellent microenvironment and direct the fate of the cultured cells. More recently, the use of stem cells in medicine has opened a new technological opportunity for controlled tissue formation. However, the mechanism through which the substrate directs the differentiation of stem cells is still rather unclear. Data concerning its specific surface chemistry, topology, and its signaling ability need to be further understood and analyzed. In our study, atomic force microscopy was used to study the stiffness, roughness, and topology of the collagen (Coll) and metallized collagen (MC) substrates, proposed as an excellent substrate for regenerative medicine. The importance of signaling molecules was studied by constructing a new hybrid signaling substrate that contains both collagen and laminin extracellular matrix (ECM) proteins. The cellular response—such as attachment capability, proliferation and cardiac and neuronal phenotype expression on the metallized and non-metallized hybrid substrates (collagen + laminin)—was studied using MTT viability assay and immunohistochemistry studies. Our findings indicate that such hybrid materials could play an important role in the regeneration of complex tissues.

  17. Neurite outgrowth and synapse formation by identified leech neurones in culture.

    PubMed

    Chiquet, M; Nicholls, J G

    1987-09-01

    After injury, neurones in the central nervous system (CNS) of the leech regenerate with a high degree of specificity. The aim of our experiments has been to study the sequential steps involved in neurite growth and synapse formation using isolated identified neurones in culture. An important requirement for sprouting of leech neurones is the substrate. Neurites grow only slowly and sparsely on polylysine or vertebrate laminin. The extracellular matrix of leech ganglion capsules contains a protease-sensitive factor which can be extracted with urea. With this material as substrate, growth proceeds rapidly in defined medium. Another neurite-promoting substrate is provided by the plant lectin concanavalin A (Con A). The activity of Con A, but not of the capsule matrix factor, is blocked by the Con A-specific hapten methyl alpha-D-mannoside. The morphology and branching pattern of the neurites in culture depend on the specific substrate and on the type of neurone. During stimulation, less Ca2+ uptake occurs into growth cones than in cell bodies. The mechanism of neurite growth seems not to depend on activity-mediated Ca2+ influx or on interactions between neuronal cell surfaces. However, even without profuse outgrowth, electrical and chemical synapses develop between neighbouring neurones. The type of synapse depends predictably on the types of neurones within the cell pair. Since the development of a synapse can be followed with time in culture, the sequential events can each be studied separately for this multi-step process. PMID:3323399

  18. The role of dimensionality in neuronal network dynamics.

    PubMed

    Ulloa Severino, Francesco Paolo; Ban, Jelena; Song, Qin; Tang, Mingliang; Bianconi, Ginestra; Cheng, Guosheng; Torre, Vincent

    2016-01-01

    Recent results from network theory show that complexity affects several dynamical properties of networks that favor synchronization. Here we show that synchronization in 2D and 3D neuronal networks is significantly different. Using dissociated hippocampal neurons we compared properties of cultures grown on a flat 2D substrates with those formed on 3D graphene foam scaffolds. Both 2D and 3D cultures had comparable glia to neuron ratio and the percentage of GABAergic inhibitory neurons. 3D cultures because of their dimension have many connections among distant neurons leading to small-world networks and their characteristic dynamics. After one week, calcium imaging revealed moderately synchronous activity in 2D networks, but the degree of synchrony of 3D networks was higher and had two regimes: a highly synchronized (HS) and a moderately synchronized (MS) regime. The HS regime was never observed in 2D networks. During the MS regime, neuronal assemblies in synchrony changed with time as observed in mammalian brains. After two weeks, the degree of synchrony in 3D networks decreased, as observed in vivo. These results show that dimensionality determines properties of neuronal networks and that several features of brain dynamics are a consequence of its 3D topology. PMID:27404281

  19. The role of dimensionality in neuronal network dynamics

    PubMed Central

    Ulloa Severino, Francesco Paolo; Ban, Jelena; Song, Qin; Tang, Mingliang; Bianconi, Ginestra; Cheng, Guosheng; Torre, Vincent

    2016-01-01

    Recent results from network theory show that complexity affects several dynamical properties of networks that favor synchronization. Here we show that synchronization in 2D and 3D neuronal networks is significantly different. Using dissociated hippocampal neurons we compared properties of cultures grown on a flat 2D substrates with those formed on 3D graphene foam scaffolds. Both 2D and 3D cultures had comparable glia to neuron ratio and the percentage of GABAergic inhibitory neurons. 3D cultures because of their dimension have many connections among distant neurons leading to small-world networks and their characteristic dynamics. After one week, calcium imaging revealed moderately synchronous activity in 2D networks, but the degree of synchrony of 3D networks was higher and had two regimes: a highly synchronized (HS) and a moderately synchronized (MS) regime. The HS regime was never observed in 2D networks. During the MS regime, neuronal assemblies in synchrony changed with time as observed in mammalian brains. After two weeks, the degree of synchrony in 3D networks decreased, as observed in vivo. These results show that dimensionality determines properties of neuronal networks and that several features of brain dynamics are a consequence of its 3D topology. PMID:27404281

  20. Fossil fuels -- future fuels

    SciTech Connect

    1998-03-01

    Fossil fuels -- coal, oil, and natural gas -- built America`s historic economic strength. Today, coal supplies more than 55% of the electricity, oil more than 97% of the transportation needs, and natural gas 24% of the primary energy used in the US. Even taking into account increased use of renewable fuels and vastly improved powerplant efficiencies, 90% of national energy needs will still be met by fossil fuels in 2020. If advanced technologies that boost efficiency and environmental performance can be successfully developed and deployed, the US can continue to depend upon its rich resources of fossil fuels.

  1. Lactate involvement in neuron-glia metabolic interaction: (13)C-NMR spectroscopy contribution.

    PubMed

    Bouzier-Sore, A-K; Serres, S; Canioni, P; Merle, M

    2003-09-01

    Glucose is commonly admitted to be the main substrate for brain energy requirement. However, it has been recently proposed that lactate, generated from glucose via glycolysis, would be the oxidative substrate for neurons, particularly during neuronal activation, according to a mechanism called the astrocyte-neuron lactate shuttle hypothesis (ANLSH). In that mechanism, glutamate released in the synaptic cleft during brain activation is taken up by astrocytes. This uptake, via the glutamate/Na(+) transporter, induces the entry of sodium, which is then excluded from the astrocytes via the Na(+)/K(+) ATPase. This exclusion consumes ATP, which stimulates glycolysis and thus lactate formation in astrocytes. This lactate is then transferred to neurons where it is utilized as oxidative substrate. This review tries to gather the recent evidences that support this hypothesis and presents the contribution of NMR to this matter. PMID:14652173

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

    PubMed Central

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

    2014-01-01

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons are identified by their Go-like immunoreactivity, and show a distinct spatial distribution within the olfactory epithelium, similar to, but significantly different from that of crypt neurons. Furthermore, kappe neurons project to a single identified target glomerulus within the olfactory bulb, mdg5 of the mediodorsal cluster, whereas crypt neurons are known to project exclusively to the mdg2 glomerulus. Kappe neurons are negative for established markers of ciliated, microvillous and crypt neurons, but appear to have microvilli. Kappe neurons constitute the fourth type of olfactory sensory neurons reported in teleost fishes and their existence suggests that encoding of olfactory stimuli may require a higher complexity than hitherto assumed already in the peripheral olfactory system. PMID:24509431

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

    NASA Astrophysics Data System (ADS)

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

    2014-02-01

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

  4. Imaging voltage in neurons

    PubMed Central

    Peterka, Darcy S.; Takahashi, Hiroto; Yuste, Rafael

    2011-01-01

    In the last decades, imaging membrane potential has become a fruitful approach to study neural circuits, especially in invertebrate preparations with large, resilient neurons. At the same time, particularly in mammalian preparations, voltage imaging methods suffer from poor signal to noise and secondary side effects, and they fall short of providing single-cell resolution when imaging of the activity of neuronal populations. As an introduction to these techniques, we briefly review different voltage imaging methods (including organic fluorophores, SHG chromophores, genetic indicators, hybrid, nanoparticles and intrinsic approaches), and illustrate some of their applications to neuronal biophysics and mammalian circuit analysis. We discuss their mechanisms of voltage sensitivity, from reorientation, electrochromic or electro-optical phenomena, to interaction among chromophores or membrane scattering, and highlight their advantages and shortcomings, commenting on the outlook for development of novel voltage imaging methods. PMID:21220095

  5. Patterned neuronal networks using nanodiamonds and the effect of varying nanodiamond properties on neuronal adhesion and outgrowth

    NASA Astrophysics Data System (ADS)

    Edgington, R. J.; Thalhammer, A.; Welch, J. O.; Bongrain, A.; Bergonzo, P.; Scorsone, E.; Jackman, R. B.; Schoepfer, R.

    2013-10-01

    Objective. Detonation nanodiamond monolayer coatings are exceptionally biocompatible substrates for in vitro cell culture. However, the ability of nanodiamond coatings of different origin, size, surface chemistry and morphology to promote neuronal adhesion, and the ability to pattern neurons with nanodiamonds have yet to be investigated. Approach. Various nanodiamond coatings of different type are investigated for their ability to promote neuronal adhesion with respect to surface coating parameters and neurite extension. Nanodiamond tracks are patterned using photolithography and reactive ion etching. Main results. Universal promotion of neuronal adhesion is observed on all coatings tested and analysis shows surface roughness to not be a sufficient metric to describe biocompatibility, but instead nanoparticle size and curvature shows a significant correlation with neurite extension. Furthermore, neuronal patterning is achieved with high contrast using patterned nanodiamond coatings down to at least 10 µm. Significance. The results of nanoparticle size and curvature being influential upon neuronal adhesion has great implications towards biomaterial design, and the ability to pattern neurons using nanodiamond tracks shows great promise for applications both in vitro and in vivo.

  6. Josephson junction simulation of neurons

    NASA Astrophysics Data System (ADS)

    Crotty, Patrick; Schult, Dan; Segall, Ken

    2010-07-01

    With the goal of understanding the intricate behavior and dynamics of collections of neurons, we present superconducting circuits containing Josephson junctions that model biologically realistic neurons. These “Josephson junction neurons” reproduce many characteristic behaviors of biological neurons such as action potentials, refractory periods, and firing thresholds. They can be coupled together in ways that mimic electrical and chemical synapses. Using existing fabrication technologies, large interconnected networks of Josephson junction neurons would operate fully in parallel. They would be orders of magnitude faster than both traditional computer simulations and biological neural networks. Josephson junction neurons provide a new tool for exploring long-term large-scale dynamics for networks of neurons.

  7. Opportunity fuels

    SciTech Connect

    Lutwen, R.C.

    1994-12-31

    Opportunity fuels - fuels that can be converted to other forms of energy at lower cost than standard fossil fuels - are discussed in outline form. The type and source of fuels, types of fuels, combustability, methods of combustion, refinery wastes, petroleum coke, garbage fuels, wood wastes, tires, and economics are discussed.

  8. Cold shock induces apoptosis of dorsal root ganglion neurons plated on infrared windows.

    PubMed

    Aboualizadeh, Ebrahim; Mattson, Eric C; O'Hara, Crystal L; Smith, Amanda K; Stucky, Cheryl L; Hirschmugl, Carol J

    2015-06-21

    The chemical status of live sensory neurons is accessible with infrared microspectroscopy of appropriately prepared cells. In this paper, individual dorsal root ganglion (DRG) neurons have been prepared with two different protocols, and plated on glass cover slips, BaF2 and CaF2 substrates. The first protocol exposes the intact DRGs to 4 °C for between 20-30 minutes before dissociating individual neurons and plating 2 hours later. The second protocol maintains the neurons at 23 °C for the entire duration of the sample preparation. The visual appearance of the neurons is similar. The viability was assessed by means of trypan blue exclusion method to determine the viability of the neurons. The neurons prepared under the first protocol (cold exposure) and plated on BaF2 reveal a distinct chemical signature and chemical distribution that is different from the other sample preparations described in the paper. Importantly, results for other sample preparation methods, using various substrates and temperature protocols, when compared across the overlapping spectral bandwidth, present normal chemical distribution within the neurons. The unusual chemically specific spatial variation is dominated by a lack of protein and carbohydrates in the center of the neurons and signatures of unraveling DNA are detected. We suggest that cold shock leads to apoptosis of DRGs, followed by osmotic stress originating from ion gradients across the cell membrane leading to cell lysis. PMID:26000346

  9. Neuroanatomical association of hypothalamic HSD2-containing neurons with ERα, catecholamines, or oxytocin: implications for feeding?

    PubMed Central

    Askew, Maegan L.; Muckelrath, Halie D.; Johnston, Jonathon R.; Curtis, Kathleen S.

    2015-01-01

    This study used immunohistochemical methods to investigate the possibility that hypothalamic neurons that contain 11-β-hydroxysteroid dehydrogenase type 2 (HSD2) are involved in the control of feeding by rats via neuroanatomical associations with the α subtype of estrogen receptor (ERα), catecholamines, and/or oxytocin (OT). An aggregate of HSD2-containing neurons is located laterally in the hypothalamus, and the numbers of these neurons were greatly increased by estradiol treatment in ovariectomized (OVX) rats compared to numbers in male rats and in OVX rats that were not given estradiol. However, HSD2-containing neurons were anatomically segregated from ERα-containing neurons in the Ventromedial Hypothalamus and the Arcuate Nucleus. There was an absence of OT-immunolabeled fibers in the area of HSD2-labeled neurons. Taken together, these findings provide no support for direct associations between hypothalamic HSD2 and ERα or OT neurons in the control of feeding. In contrast, there was catecholamine-fiber labeling in the area of HSD2-labeled neurons, and these fibers occasionally were in close apposition to HSD2-labeled neurons. Therefore, we cannot rule out interactions between HSD2 and catecholamines in the control of feeding; however, given the relative sparseness of the appositions, any such interaction would appear to be modest. Thus, these studies do not conclusively identify a neuroanatomical substrate by which HSD2-containing neurons in the hypothalamus may alter feeding, and leave the functional role of hypothalamic HSD2-containing neurons subject to further investigation. PMID:26124709

  10. Nanoresolution radiology of neurons

    SciTech Connect

    Wu, H.R.; Chen, S.T.; Chu, Y.S.; Conley, R.; Bouet, N.; Chien, C.C.; Chen, H.H.; Lin, C.H.; Tung, H.T.; Chen, Y.S.; Margaritondo, G.; Je, J.H.; Hwu, Y.

    2013-04-08

    We report recent advances in hard-x-ray optics - including record spatial resolution - and in staining techniques that enable synchrotron microradiology to produce neurobiology images of quality comparable to electron and visible microscopy. In addition, microradiology offers excellent penetration and effective three-dimensional detection as required for many neuron studies. Our tests include tomographic reconstruction based on projection image sets.

  11. Nanoresolution radiology of neurons

    SciTech Connect

    Wu, H. R.; Chen, S. T.; Chu, Y. S.; Conley, R.; Bouet, N.; Chien, C. C.; Chen, H. H.; Lin, C. H.; Tung, H. T.; Chen, Y. S.; Margaritondo, G.; Je, J. H.; Hwu, Y.

    2012-05-29

    We report recent advances in hard-x-ray optics—including record spatial resolution—and in staining techniques that enable synchrotron microradiology to produce neurobiology images of quality comparable to electron and visible microscopy. In addition, microradiology offers excellent penetration and effective three-dimensional detection as required for many neuron studies. Our tests include tomographic reconstruction based on projection image sets.

  12. Neuronal porosome lipidome

    PubMed Central

    Lewis, Kenneth T; Maddipati, Krishna R; Taatjes, Douglas J; Jena, Bhanu P

    2014-01-01

    Cup-shaped lipoprotein structures called porosomes are the universal secretory portals at the cell plasma membrane, where secretory vesicles transiently dock and fuse to release intravesicular contents. In neurons, porosomes measure ∼15 nm and are comprised of nearly 40 proteins, among them SNAREs, ion channels, the Gαo G-protein and several structural proteins. Earlier studies report the interaction of specific lipids and their influence on SNAREs, ion channels and G-protein function. Our own studies demonstrate the requirement of cholesterol for the maintenance of neuronal porosome integrity, and the influence of lipids on SNARE complex assembly. In this study, to further understand the role of lipids on porosome structure-function, the lipid composition of isolated neuronal porosome was determined using mass spectrometry. Using lipid-binding assays, the affinity of porosome-associated syntaxin-1A to various lipids was determined. Our mass spectrometry results demonstrate the presence of phosphatidylinositol phosphates (PIP's) and phosphatidic acid (PA) among other lipids, and the enriched presence of ceramide (Cer), lysophosphatidylinositol phosphates (LPIP) and diacylglycerol (DAG). Lipid binding assays demonstrate the binding of neuronal porosome to cardiolipin, and confirm its association with PIP's and PA. The ability of exogenous PA to alter protein–protein interaction and neurotransmitter release is further demonstrated from the study. PMID:25224862

  13. GaAs-based optoelectronic neurons

    NASA Technical Reports Server (NTRS)

    Lin, Steven H. (Inventor); Kim, Jae H. (Inventor); Psaltis, Demetri (Inventor)

    1993-01-01

    An integrated, optoelectronic, variable thresholding neuron implemented monolithically in GaAs integrated circuit and exhibiting high differential optical gain and low power consumption is presented. Two alternative embodiments each comprise an LED monolithically integrated with a detector and two transistors. One of the transistors is responsive to a bias voltage applied to its gate for varying the threshold of the neuron. One embodiment is implemented as an LED monolithically integrated with a double heterojunction bipolar phototransistor (detector) and two metal semiconductor field effect transistors (MESFET's) on a single GaAs substrate and another embodiment is implemented as an LED monolithically integrated with three MESFET's (one of which is an optical FET detector) on a single GaAs substrate. The first noted embodiment exhibits a differential optical gain of 6 and an optical switching energy of 10 pJ. The second embodiment has a differential optical gain of 80 and an optical switching energy of 38 pJ. Power consumption is 2.4 and 1.8 mW, respectively. Input 'light' power needed to turn on the LED is 2 micro-W and 54 nW, respectively. In both embodiments the detector is in series with a biasing MESFET and saturates the other MESFET upon detecting light above a threshold level. The saturated MESFET turns on the LED. Voltage applied to the biasing MESFET gate controls the threshold.

  14. Epigenomic Landscapes Reflect Neuronal Diversity.

    PubMed

    Henikoff, Steven

    2015-06-17

    Epigenomic profiling of complex tissues obscures regulatory elements that distinguish one cell type from another. In this issue of Neuron, Mo et al. (2015) apply cell-type-specific profiling to mouse neuronal subtypes and discover an unprecedented level of neuronal diversity. PMID:26087157

  15. What can neurons do for their brain? Communicate selectivity with bursts

    PubMed Central

    Balduzzi, D.; Tononi, G.

    2012-01-01

    Neurons deep in cortex interact with the environment extremely indirectly; the spikes they receive and produce are pre- and post-processed by millions of other neurons. This paper proposes two information-theoretic constraints guiding the production of spikes, that help ensure bursting activity deep in cortex relates meaningfully to events in the environment. First, neurons should emphasize selective responses with bursts. Second, neurons should propagate selective inputs by burst-firing in response to them. We show the constraints are necessary for bursts to dominate information-transfer within cortex, thereby providing a substrate allowing neurons to distribute credit amongst themselves. Finally, since synaptic plasticity degrades the ability of neurons to burst selectively, we argue that homeostatic regulation of synaptic weights is necessary, and that it is best performed offline during sleep. PMID:22956291

  16. Neuronal cell cycle: the neuron itself and its circumstances

    PubMed Central

    Frade, José M; Ovejero-Benito, María C

    2015-01-01

    Neurons are usually regarded as postmitotic cells that undergo apoptosis in response to cell cycle reactivation. Nevertheless, recent evidence indicates the existence of a defined developmental program that induces DNA replication in specific populations of neurons, which remain in a tetraploid state for the rest of their adult life. Similarly, de novo neuronal tetraploidization has also been described in the adult brain as an early hallmark of neurodegeneration. The aim of this review is to integrate these recent developments in the context of cell cycle regulation and apoptotic cell death in neurons. We conclude that a variety of mechanisms exists in neuronal cells for G1/S and G2/M checkpoint regulation. These mechanisms, which are connected with the apoptotic machinery, can be modulated by environmental signals and the neuronal phenotype itself, thus resulting in a variety of outcomes ranging from cell death at the G1/S checkpoint to full proliferation of differentiated neurons. PMID:25590687

  17. Metastasis suppressor 1 regulates neurite outgrowth in primary neuron cultures.

    PubMed

    Yu, Juan; Lin, Shuyun; Wang, Mei; Liang, Lijun; Zou, Zijiao; Zhou, Xinfeng; Wang, Meichi; Chen, Ping; Wang, Ying

    2016-10-01

    Metastasis suppressor 1 (MTSS1) or missing in metastasis (MIM) is an actin- and membrane-binding protein with tumor suppressor functions. MTSS1 is important for cell morphology, motility, metastasis. The role of MTSS1 in cell morphology has been widely investigated in non-neuronal tissues; however the role of MTSS1 in neurite outgrowth remains unclear. Here we investigated the effect of MTSS1 on neurite outgrowth in primary cerebellar granule and hippocampal neurons of mouse. We found that overexpression of MTSS1 in cerebellar granule neurons significantly enhanced dendrite elaboration but inhibited axon elongation. This phenotype was significantly reduced by deletion of the Wiskott-Aldrich homology 2 (WH2) motif and point mutation in the insulin receptor substrate p53 (IRSp53) and MIM/MTSS1 homology (IMD) domain. Furthermore, inhibition of Rac1 activity or blocking of phosphatidyl inositol phosphates (PIPs) signaling decreased the effect of MTSS1 markedly. In accordance with the over-expression data, knockdown of MTSS1 in cerebellar granule neurons could increase the axon length but decrease the dendrite length and the number of dendrites. In addition, MTSS1 knock down in embryonic hippocampal neurons suppressed neurite branching and reduced dendrite length. Our findings have demonstrated that MTSS1 modulates neuronal morphology, possibly through a Rac1-PIPs signaling pathway. PMID:27401056

  18. Palatability Can Drive Feeding Independent of AgRP Neurons.

    PubMed

    Denis, Raphaël G P; Joly-Amado, Aurélie; Webber, Emily; Langlet, Fanny; Schaeffer, Marie; Padilla, Stéphanie L; Cansell, Céline; Dehouck, Bénédicte; Castel, Julien; Delbès, Anne-Sophie; Martinez, Sarah; Lacombe, Amélie; Rouch, Claude; Kassis, Nadim; Fehrentz, Jean-Alain; Martinez, Jean; Verdié, Pascal; Hnasko, Thomas S; Palmiter, Richard D; Krashes, Michael J; Güler, Ali D; Magnan, Christophe; Luquet, Serge

    2015-10-01

    Feeding behavior is exquisitely regulated by homeostatic and hedonic neural substrates that integrate energy demand as well as the reinforcing and rewarding aspects of food. Understanding the net contribution of homeostatic and reward-driven feeding has become critical because of the ubiquitous source of energy-dense foods and the consequent obesity epidemic. Hypothalamic agouti-related peptide-secreting neurons (AgRP neurons) provide the primary orexigenic drive of homeostatic feeding. Using models of neuronal inhibition or ablation, we demonstrate that the feeding response to a fast ghrelin or serotonin receptor agonist relies on AgRP neurons. However, when palatable food is provided, AgRP neurons are dispensable for an appropriate feeding response. In addition, AgRP-ablated mice present exacerbated stress-induced anorexia and palatable food intake--a hallmark of comfort feeding. These results suggest that, when AgRP neuron activity is impaired, neural circuits sensitive to emotion and stress are engaged and modulated by food palatability and dopamine signaling. PMID:26278050

  19. Neuronal cell growth on polymeric scaffolds studied by CARS microscopy

    NASA Astrophysics Data System (ADS)

    Enejder, Annika; Fink, Helen; Kuhn, Hans-Georg

    2012-03-01

    For studies of neuronal cell integration and neurite outgrowth in polymeric scaffold materials as a future alternative for the treatment of damages in the neuronal system, we have developed a protocol employing CARS microscopy for imaging of neuronal networks. The benefits of CARS microscopy come here to their best use; (i) the overall three-dimensional (3D) arrangement of multiple cells and their neurites can be visualized without the need for chemical preparations or physical sectioning, potentially affecting the architecture of the soft, fragile scaffolds and (ii) details on the interaction between single cells and scaffold fibrils can be investigated by close-up images at sub-micron resolution. The establishment of biologically more relevant 3D neuronal networks in a soft hydrogel composed of native Extra Cellular Matrix (ECM) components was compared with conventional two-dimensional networks grown on a stiff substrate. Images of cells in the hydrogel scaffold reveal significantly different networking characteristics compared to the 2D networks, raising the question whether the functionality of neurons grown as layers in conventional cultivation dishes represents that of neurons in the central and peripheral nervous systems.

  20. Phosphoinositide signaling in somatosensory neurons.

    PubMed

    Rohacs, Tibor

    2016-05-01

    Somatosensory neurons of the dorsal root ganglia (DRG) and trigeminal ganglia (TG) are responsible for detecting thermal and tactile stimuli. They are also the primary neurons mediating pain and itch. A large number of cell surface receptors in these neurons couple to phospholipase C (PLC) enzymes leading to the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and the generation of downstream signaling molecules. These neurons also express many different ion channels, several of which are regulated by phosphoinositides. This review will summarize the knowledge on phosphoinositide signaling in DRG neurons, with special focus on effects on sensory and other ion channels. PMID:26724974

  1. Catalytic combustion with incompletely vaporized residual fuel

    NASA Technical Reports Server (NTRS)

    Rosfjord, T. J.

    1981-01-01

    Catalytic combustion of fuel lean mixtures of incompletely vaporized residual fuel and air was investigated. The 7.6 cm diameter, graded cell reactor was constructed from zirconia spinel substrate and catalyzed with a noble metal catalyst. Streams of luminous particles exited the rector as a result of fuel deposition and carbonization on the substrate. Similar results were obtained with blends of No. 6 and No. 2 oil. Blends of shale residual oil and No. 2 oil resulted in stable operation. In shale oil blends the combustor performance degraded with a reduced degree of fuel vaporization. In tests performed with No. 2 oil a similar effect was observed.

  2. Neuronal synchrony: peculiarity and generality.

    PubMed

    Nowotny, Thomas; Huerta, Ramon; Rabinovich, Mikhail I

    2008-09-01

    Synchronization in neuronal systems is a new and intriguing application of dynamical systems theory. Why are neuronal systems different as a subject for synchronization? (1) Neurons in themselves are multidimensional nonlinear systems that are able to exhibit a wide variety of different activity patterns. Their "dynamical repertoire" includes regular or chaotic spiking, regular or chaotic bursting, multistability, and complex transient regimes. (2) Usually, neuronal oscillations are the result of the cooperative activity of many synaptically connected neurons (a neuronal circuit). Thus, it is necessary to consider synchronization between different neuronal circuits as well. (3) The synapses that implement the coupling between neurons are also dynamical elements and their intrinsic dynamics influences the process of synchronization or entrainment significantly. In this review we will focus on four new problems: (i) the synchronization in minimal neuronal networks with plastic synapses (synchronization with activity dependent coupling), (ii) synchronization of bursts that are generated by a group of nonsymmetrically coupled inhibitory neurons (heteroclinic synchronization), (iii) the coordination of activities of two coupled neuronal networks (partial synchronization of small composite structures), and (iv) coarse grained synchronization in larger systems (synchronization on a mesoscopic scale). PMID:19045493

  3. RNA Protein Interaction in Neurons

    PubMed Central

    Darnell, Robert B.

    2013-01-01

    Neurons have their own systems for regulating RNA. Several multigene families encode RNA binding proteins (RNABPs) that are uniquely expressed in neurons, including the well-known neuron-specific markers ELAV and NeuN, and the disease antigen NOVA. New technologies have emerged in recent years to assess the function of these proteins in vivo, and the answers are yielding insights into how and why neurons may regulate RNA in special ways—to increase cellular complexity, to spatially localize mRNA, and to regulate their expression in response to synaptic stimuli. The functions of such restricted neuronal proteins is likely to be complimented by more widely expressed RNABPs that may themselves have developed specialized functions in neurons, including Argonaute/miRNAs. Here we review what is known about such RNABPs, and explore the potential biologic and neurologic significance of neuronal RNA regulatory systems. PMID:23701460

  4. Add neurons, subtract anxiety

    PubMed Central

    Kheirbek, Mazen A.; Hen, René

    2014-01-01

    IN BRIEF To keep memories from becoming jumbled, the brain must encode the distinct features of events and situations in a way that allows them to be distinguished from one another—a process called pattern separation. Pattern separation enables us to distinguish dangerous situations from similar ones that pose no risk. People with defects in this ability may be prone to anxiety disorders. The process occurs in one of the two regions of the brain that generate neurons throughout life. These fledgling cells seem to be critical to pattern separation. Interventions that specifically boost the ranks of rookie neurons could provide new ways to regulate mood and possibly treat conditions such as post-traumatic stress disorder. PMID:24974712

  5. Lightweight Substrates For Mirrors

    NASA Technical Reports Server (NTRS)

    Brown, D. Kyle

    1991-01-01

    New substrate uses conventional quasi-isotropic fabric laminate with surfacing layer of carbon-fiber paper consisting of randomly oriented chopped carbon fibers. Layered structure of fabric and paper relatively easy to manufacture. When impregnated with carbon, structure rigid and stable. Substrates of this type made quite thin, thus keeping areal weights to minimum. Mirrors of this type made faster, and cost less, than predecessors.

  6. Single neuron modeling and data assimilation in BNST neurons

    NASA Astrophysics Data System (ADS)

    Farsian, Reza

    Neurons, although tiny in size, are vastly complicated systems, which are responsible for the most basic yet essential functions of any nervous system. Even the most simple models of single neurons are usually high dimensional, nonlinear, and contain many parameters and states which are unobservable in a typical neurophysiological experiment. One of the most fundamental problems in experimental neurophysiology is the estimation of these parameters and states, since knowing their values is essential in identification, model construction, and forward prediction of biological neurons. Common methods of parameter and state estimation do not perform well for neural models due to their high dimensionality and nonlinearity. In this dissertation, two alternative approaches for parameters and state estimation of biological neurons have been demonstrated: dynamical parameter estimation (DPE) and a Markov Chain Monte Carlo (MCMC) method. The first method uses elements of chaos control and synchronization theory for parameter and state estimation. MCMC is a statistical approach which uses a path integral formulation to evaluate a mean and an error bound for these unobserved parameters and states. These methods have been applied to biological system of neurons in Bed Nucleus of Stria Termialis neurons (BNST) of rats. State and parameters of neurons in both systems were estimated, and their value were used for recreating a realistic model and predicting the behavior of the neurons successfully. The knowledge of biological parameters can ultimately provide a better understanding of the internal dynamics of a neuron in order to build robust models of neuron networks.

  7. Simple neuron models of ITD sensitive neurons

    NASA Astrophysics Data System (ADS)

    Dasika, Vasant; White, John A.; Colburn, H. Steven

    2002-05-01

    Neurons which show sensitivity to interaural time delay (ITD) exist in both mammalian medial superior olive (MSO), and bird nucleus laminaris (NL). In this study, we examine simple mathematical models of single MSO and NL cells which respond probabilistically to a pair of isolated inputs with a response probability that depends on the input interpulse interval. Inputs are either isolated pulse pairs or pairs of periodic trains, with or without random jitter added to their event times. Refractoriness is incorporated in the input description and/or in the cell model in specified simulations. We find that periodic rate-ITD shapes are shaped by three interacting factors: the cell's temporal response (described by the paired-pulse response), input frequency, and the degree of input synchrony. Paired-pulse responses are able to predict the widths of rate-ITD curves obtained from deterministic periodic input simulations. Reduced input synchrony predictably smears rate-ITD curves. Larger numbers of weaker inputs yield stronger rate-ITD modulation than a few strong inputs. Model response is compared with in vivo and in vitro MSO and NL physiological data. Comparisons with published analytical models as well as more complex and realistic physiological cell models are examined.

  8. Adhesion to Carbon Nanotube Conductive Scaffolds Forces Action-Potential Appearance in Immature Rat Spinal Neurons

    PubMed Central

    Toma, Francesca Maria; Calura, Enrica; Rizzetto, Lisa; Carrieri, Claudia; Roncaglia, Paola; Martinelli, Valentina; Scaini, Denis; Masten, Lara; Turco, Antonio; Gustincich, Stefano; Prato, Maurizio; Ballerini, Laura

    2013-01-01

    In the last decade, carbon nanotube growth substrates have been used to investigate neurons and neuronal networks formation in vitro when guided by artificial nano-scaled cues. Besides, nanotube-based interfaces are being developed, such as prosthesis for monitoring brain activity. We recently described how carbon nanotube substrates alter the electrophysiological and synaptic responses of hippocampal neurons in culture. This observation highlighted the exceptional ability of this material in interfering with nerve tissue growth. Here we test the hypothesis that carbon nanotube scaffolds promote the development of immature neurons isolated from the neonatal rat spinal cord, and maintained in vitro. To address this issue we performed electrophysiological studies associated to gene expression analysis. Our results indicate that spinal neurons plated on electro-conductive carbon nanotubes show a facilitated development. Spinal neurons anticipate the expression of functional markers of maturation, such as the generation of voltage dependent currents or action potentials. These changes are accompanied by a selective modulation of gene expression, involving neuronal and non-neuronal components. Our microarray experiments suggest that carbon nanotube platforms trigger reparative activities involving microglia, in the absence of reactive gliosis. Hence, future tissue scaffolds blended with conductive nanotubes may be exploited to promote cell differentiation and reparative pathways in neural regeneration strategies. PMID:23951361

  9. Fuel pin

    DOEpatents

    Christiansen, D.W.; Karnesky, R.A.; Leggett, R.D.; Baker, R.B.

    1987-11-24

    A fuel pin for a liquid metal nuclear reactor is provided. The fuel pin includes a generally cylindrical cladding member with metallic fuel material disposed therein. At least a portion of the fuel material extends radially outwardly to the inner diameter of the cladding member to promote efficient transfer of heat to the reactor coolant system. The fuel material defines at least one void space therein to facilitate swelling of the fuel material during fission.

  10. Colloidal Drop Deposition on Porous Substrates

    NASA Astrophysics Data System (ADS)

    Sun, Ying; Pack, Min; Hu, Han; Kim, Dong-Ook; Yang, Xin

    2015-11-01

    Printable electronics and in particular paper and textile-based electronics have fueled research in inkjet printing on porous substrates. On nonporous substrates, the particle motion of the particles and evaporation of the solvent are the two main mechanisms that drive the final deposition morphology. For porous substrates another factor, mainly infiltration, adds a layer of complexity to the deposition patterns that has not yet been elucidated in literature. In this study, a high-speed camera was used to capture the imbibition of picoliter-sized polystyrene nanoparticles in water droplets into nano-porous anodic aluminum oxide substrates of various porosities and wettabilities. For water, the infiltration rate is much faster than both evaporation and particle motion and thus when the substrate fully imbibes the droplet, the well-known ``coffee ring'' is suppressed. However, when a residual droplet forms upon the termination of the infiltration regime, the competing particle motion and evaporation regimes, tP and tEI respectively, define the critical time scales for which the coffee ring will be formed (tP /tEI <1) or suppressed (tP /tEI >1). National Science Foundation under Grant No. CMMI-1401438.

  11. Neuronal nitric oxide synthase expressing neurons: a journey from birth to neuronal circuits

    PubMed Central

    Tricoire, Ludovic; Vitalis, Tania

    2012-01-01

    Nitric oxide (NO) is an important signaling molecule crucial for many physiological processes such as synaptic plasticity, vasomotricity, and inflammation. Neuronal nitric oxide synthase (nNOS) is the enzyme responsible for the synthesis of NO by neurons. In the juvenile and mature hippocampus and neocortex nNOS is primarily expressed by subpopulations of GABAergic interneurons. Over the past two decades, many advances have been achieved in the characterization of neocortical and hippocampal nNOS expressing neurons. In this review, we summarize past and present studies that have characterized the electrophysiological, morphological, molecular, and synaptic properties of these neurons. We also discuss recent studies that have shed light on the developmental origins and specification of GABAergic neurons with specific attention to neocortical and hippocampal nNOS expressing GABAergic neurons. Finally, we summarize the roles of NO and nNOS-expressing inhibitory neurons. PMID:23227003

  12. Consistent estimation of complete neuronal connectivity in large neuronal populations using sparse "shotgun" neuronal activity sampling.

    PubMed

    Mishchenko, Yuriy

    2016-10-01

    We investigate the properties of recently proposed "shotgun" sampling approach for the common inputs problem in the functional estimation of neuronal connectivity. We study the asymptotic correctness, the speed of convergence, and the data size requirements of such an approach. We show that the shotgun approach can be expected to allow the inference of complete connectivity matrix in large neuronal populations under some rather general conditions. However, we find that the posterior error of the shotgun connectivity estimator grows quickly with the size of unobserved neuronal populations, the square of average connectivity strength, and the square of observation sparseness. This implies that the shotgun connectivity estimation will require significantly larger amounts of neuronal activity data whenever the number of neurons in observed neuronal populations remains small. We present a numerical approach for solving the shotgun estimation problem in general settings and use it to demonstrate the shotgun connectivity inference in the examples of simulated synfire and weakly coupled cortical neuronal networks. PMID:27515518

  13. Fuel cell oxygen electrode

    DOEpatents

    Shanks, Howard R.; Bevolo, Albert J.; Danielson, Gordon C.; Weber, Michael F.

    1980-11-04

    An oxygen electrode for a fuel cell utilizing an acid electrolyte has a substrate of an alkali metal tungsten bronze of the formula: A.sub.x WO.sub.3 where A is an alkali metal and x is at least 0.2, which is covered with a thin layer of platinum tungsten bronze of the formula: Pt.sub.y WO.sub.3 where y is at least 0.8.

  14. Fuel cell oxygen electrode

    DOEpatents

    Shanks, H.R.; Bevolo, A.J.; Danielson, G.C.; Weber, M.F.

    An oxygen electrode for a fuel cell utilizing an acid electrolyte has a substrate of an alkali metal tungsten bronze of the formula: A/sub x/WO/sub 3/ where A is an alkali metal and x is at least 0.2, which is covered with a thin layer of platinum tungsten bronze of the formula: Pt/sub y/WO/sub 3/ where y is at least 0.8.

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

    PubMed Central

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

    2015-01-01

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

  16. Metabolic reprogramming during neuronal differentiation.

    PubMed

    Agostini, M; Romeo, F; Inoue, S; Niklison-Chirou, M V; Elia, A J; Dinsdale, D; Morone, N; Knight, R A; Mak, T W; Melino, G

    2016-09-01

    Newly generated neurons pass through a series of well-defined developmental stages, which allow them to integrate into existing neuronal circuits. After exit from the cell cycle, postmitotic neurons undergo neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. Lack of a global metabolic analysis during early cortical neuronal development led us to explore the role of cellular metabolism and mitochondrial biology during ex vivo differentiation of primary cortical neurons. Unexpectedly, we observed a huge increase in mitochondrial biogenesis. Changes in mitochondrial mass, morphology and function were correlated with the upregulation of the master regulators of mitochondrial biogenesis, TFAM and PGC-1α. Concomitant with mitochondrial biogenesis, we observed an increase in glucose metabolism during neuronal differentiation, which was linked to an increase in glucose uptake and enhanced GLUT3 mRNA expression and platelet isoform of phosphofructokinase 1 (PFKp) protein expression. In addition, glutamate-glutamine metabolism was also increased during the differentiation of cortical neurons. We identified PI3K-Akt-mTOR signalling as a critical regulator role of energy metabolism in neurons. Selective pharmacological inhibition of these metabolic pathways indicate existence of metabolic checkpoint that need to be satisfied in order to allow neuronal differentiation. PMID:27058317

  17. Genetic Enhancement of Visual Learning by Activation of Protein Kinase C Pathways in Small Groups of Rat Cortical Neurons

    PubMed Central

    Zhang, Guo-rong; Wang, Xiaodan; Kong, Lingxin; Lu, Xiu-gui; Lee, Brian; Liu, Meng; Sun, Mei; Franklin, Corinna; Cook, Robert G.; Geller, Alfred I.

    2006-01-01

    Although learning and memory theories hypothesize that memories are encoded by specific circuits, it has proven difficult to localize learning within a cortical area. Neural network theories predict that activation of a small fraction of the neurons in a circuit can activate that circuit. Consequently, altering the physiology of a small group of neurons might potentiate a specific circuit and enhance learning, thereby localizing learning to that circuit. In this study, we activated protein kinase C (PKC) pathways in small groups of neurons in rat postrhinal (POR) cortex. We microinjected helper virus-free herpes simplex virus vectors that expressed a constitutively active PKC into POR cortex. This PKC was expressed predominantly in glutamatergic and GABAergic neurons in POR cortex. This intervention increased phosphorylation of five PKC substrates that play critical roles in neurotransmitter release (GAP-43 and dynamin) or glutamatergic neurotransmission (specific subunits of AMPA or NMDA receptors and myristoylated alanine-rich C kinase substrate). Additionally, activation of PKC pathways in cultured cortical neurons supported activation-dependent increases in release of glutamate and GABA. This intervention enhanced the learning rate and accuracy of visual object discriminations. In individual rats, the numbers of transfected neurons positively correlated with this learning. During learning, neuronal activity was increased in neurons proximal to the transfected neurons. These results demonstrate that potentiating small groups of glutamatergic and GABAergic neurons in POR cortex enhances visual object learning. More generally, these results suggest that learning can be mediated by specific cortical circuits. PMID:16162929

  18. Diesel fuel by fermentation of wastes

    SciTech Connect

    Pierce, S.M.; Wayman, M.

    1983-01-11

    An improved diesel fuel which is entirely capable of preparation from renewable resources. The fuel comprises a blend of fermentation produced butanol and fermentation produced glycerides. The substrates useful for the butanol fermentation are conventional industrial waste products, such as cheese whey and low value carbohydrate containing waste materials such as corn cobs, wood chips, etc. Similar substrate materials are used in the fermentation or growth culture of glyceride producing microbes.

  19. Zinc oxide nanostructures as low-cost templates for neuronal circuit

    NASA Astrophysics Data System (ADS)

    Kritharidou, A.; Georgoussi, Z.; Tsamis, C.; Makarona, E.

    2013-05-01

    ZnO nanostructures were explored as templates for the development of topography-mediated neuronal cultures. Nanostructures of varying features were produced on 4" Si substrates via a rapid, facile and low-cost technique that allows the systematic investigation of nanotopographically-mediated formation of neuronal cultures. The developed ZnO-nanowire based templates were seeded with Neuro-2A mouse neuroblastoma cells and their viability over the course of 1 to 4 days was assessed. Our studies demonstrate that the ZnO-templates can support neuronal cell growth and proliferation suggesting that ZnO substrate can be used for the development of neuronal cell-based platform technologies.

  20. Encephalization, neuronal excess, and neuronal index in rodents.

    PubMed

    Herculano-Houzel, Suzana

    2007-10-01

    Encephalization, or brain size larger than expected from body size, has long been considered to correlate with improved cognitive abilities across species and even intelligence. However, it is still unknown what characteristics of relatively large brains underlie their improved functions. Here, it is shown that more encephalized rodent species have the number of neurons expected for their brain size, but a larger number of neurons than expected for their body size. The number of neurons in excess relative to body size might be available for improved associative functions and, thus, be responsible for the cognitive advantage observed in more encephalized animals. It is further proposed that, if such neuronal excess does provide for improved cognitive abilities, then the total number of excess neurons in each species-here dubbed the neuronal index-should be a better indicator of cognitive abilities than the encephalization quotient (EQ). Because the neuronal index is a function of both the number of neurons expected from the size of the body and the absolute number of neurons in the brain, differences in this parameter across species that share similar EQs might explain why these often have different cognitive capabilities, particularly when comparing across mammalian orders. PMID:17847061

  1. Data in support on the shape of Schwann cells and sympathetic neurons onto microconically structured silicon surfaces

    PubMed Central

    Simitzi, C.; Efstathopoulos, P.; Kourgiantaki, A.; Ranella, A.; Charalampopoulos, I.; Fotakis, C.; Αthanassakis, Ι.; Stratakis, E.; Gravanis, A.

    2015-01-01

    This article contains data related to the research article entitled “Laser fabricated discontinuous anisotropic microconical substrates as a new model scaffold to control the directionality of neuronal network outgrowth” in the Biomaterials journal [1]. Scanning electron microscopy (SEM) analysis is performed to investigate whether Schwann cells and sympathetic neurons alter their morphology according to the underlying topography, comprising arrays of silicon microcones with anisotropic geometrical characteristics [1]. It is observed that although soma of sympathetic neurons always preserves its round shape, this is not the case for Schwann cells that become highly polarized in high roughness microconical substrates. PMID:26401519

  2. Pin1 in Neuronal Apoptosis

    PubMed Central

    Becker, Esther B.E.; Bonni, Azad

    2009-01-01

    While the role of the prolyl isomerase Pin1 in dividing cells has long been recognized, Pin1’s function in postmitotic neurons is poorly understood. We have identified a novel mechanism by which Pin1 mediates activation of the mitochondrial cell death machinery specifically in neurons. This perspective presents a sophisticated signaling pathway that triggers neuronal apoptosis upon JNK-mediated phosphorylation of the BH3-only protein BIMEL at serine 65. Pin1 is enriched at the mitochondria in neurons together with BIMEL and components of a neuron-specific JNK signaling complex and functions as a molecular switch that couples the phosphorylation of BIMEL by JNK to apoptosis specifically in neurons. We discuss how these findings relate to our understanding of the development of the nervous system and the pathogenesis of neurologic disorders. PMID:17568190

  3. Bonded semiconductor substrate

    DOEpatents

    Atwater, Jr.; Harry A. , Zahler; James M.

    2010-07-13

    Ge/Si and other nonsilicon film heterostructures are formed by hydrogen-induced exfoliation of the Ge film which is wafer bonded to a cheaper substrate, such as Si. A thin, single-crystal layer of Ge is transferred to Si substrate. The bond at the interface of the Ge/Si heterostructures is covalent to ensure good thermal contact, mechanical strength, and to enable the formation of an ohmic contact between the Si substrate and Ge layers. To accomplish this type of bond, hydrophobic wafer bonding is used, because as the invention demonstrates the hydrogen-surface-terminating species that facilitate van der Waals bonding evolves at temperatures above 600.degree. C. into covalent bonding in hydrophobically bound Ge/Si layer transferred systems.

  4. Decontamination of metal substrates

    SciTech Connect

    Vincent, L.D.

    1998-12-31

    A brief look at the history of surface corrosion and contamination of steel is important for understanding the best approach to proper cleaning of substrates prior to surface preparation and application of coatings and linings, particularly in immersion conditions such as encountered in railroad hopper and tank cars. All contaminants contribute to reduction of the coating or lining`s capacity to either protect the substrate or prevent contamination of the liquid cargo. This paper will explore the types of tests available to determine the levels of contamination, particularly sulfides, sulfates and chlorides, along with suggested methods to reduce theses contaminants to acceptable levels.

  5. Biaxially textured composite substrates

    DOEpatents

    Groves, James R.; Foltyn, Stephen R.; Arendt, Paul N.

    2005-04-26

    An article including a substrate, a layer of a metal phosphate material such as an aluminum phosphate material upon the surface of the substrate, and a layer of an oriented cubic oxide material having a rock-salt-like structure upon the metal phosphate material layer is provided together with additional layers such as a HTS top-layer of YBCO directly upon a layer of a buffer material such as a SrTi.sub.x Ru.sub.1-x O.sub.3 layer.

  6. The biophysics of neuronal growth

    NASA Astrophysics Data System (ADS)

    Franze, Kristian; Guck, Jochen

    2010-09-01

    For a long time, neuroscience has focused on biochemical, molecular biological and electrophysiological aspects of neuronal physiology and pathology. However, there is a growing body of evidence indicating the importance of physical stimuli for neuronal growth and development. In this review we briefly summarize the historical background of neurobiophysics and give an overview over the current understanding of neuronal growth from a physics perspective. We show how biophysics has so far contributed to a better understanding of neuronal growth and discuss current inconsistencies. Finally, we speculate how biophysics may contribute to the successful treatment of lesions to the central nervous system, which have been considered incurable until very recently.

  7. The straintronic spin-neuron.

    PubMed

    Biswas, Ayan K; Atulasimha, Jayasimha; Bandyopadhyay, Supriyo

    2015-07-17

    In artificial neural networks, neurons are usually implemented with highly dissipative CMOS-based operational amplifiers. A more energy-efficient implementation is a 'spin-neuron' realized with a magneto-tunneling junction (MTJ) that is switched with a spin-polarized current (representing weighted sum of input currents) that either delivers a spin transfer torque or induces domain wall motion in the soft layer of the MTJ to mimic neuron firing. Here, we propose and analyze a different type of spin-neuron in which the soft layer of the MTJ is switched with mechanical strain generated by a voltage (representing weighted sum of input voltages) and term it straintronic spin-neuron. It dissipates orders of magnitude less energy in threshold operations than the traditional current-driven spin neuron at 0 K temperature and may even be faster. We have also studied the room-temperature firing behaviors of both types of spin neurons and find that thermal noise degrades the performance of both types, but the current-driven type is degraded much more than the straintronic type if both are optimized for maximum energy-efficiency. On the other hand, if both are designed to have the same level of thermal degradation, then the current-driven version will dissipate orders of magnitude more energy than the straintronic version. Thus, the straintronic spin-neuron is superior to current-driven spin neurons. PMID:26112081

  8. Evolvable Neuronal Paths: A Novel Basis for Information and Search in the Brain

    PubMed Central

    Fernando, Chrisantha; Vasas, Vera; Szathmáry, Eörs; Husbands, Phil

    2011-01-01

    We propose a previously unrecognized kind of informational entity in the brain that is capable of acting as the basis for unlimited hereditary variation in neuronal networks. This unit is a path of activity through a network of neurons, analogous to a path taken through a hidden Markov model. To prove in principle the capabilities of this new kind of informational substrate, we show how a population of paths can be used as the hereditary material for a neuronally implemented genetic algorithm, (the swiss-army knife of black-box optimization techniques) which we have proposed elsewhere could operate at somatic timescales in the brain. We compare this to the same genetic algorithm that uses a standard ‘genetic’ informational substrate, i.e. non-overlapping discrete genotypes, on a range of optimization problems. A path evolution algorithm (PEA) is defined as any algorithm that implements natural selection of paths in a network substrate. A PEA is a previously unrecognized type of natural selection that is well suited for implementation by biological neuronal networks with structural plasticity. The important similarities and differences between a standard genetic algorithm and a PEA are considered. Whilst most experiments are conducted on an abstract network model, at the conclusion of the paper a slightly more realistic neuronal implementation of a PEA is outlined based on Izhikevich spiking neurons. Finally, experimental predictions are made for the identification of such informational paths in the brain. PMID:21887266

  9. Human Temporal Cortical Single Neuron Activity during Language: A Review

    PubMed Central

    Ojemann, George A.

    2013-01-01

    Findings from recordings of human temporal cortical single neuron activity during several measures of language, including object naming and word reading are reviewed and related to changes in activity in the same neurons during recent verbal memory and verbal associative learning measures, in studies conducted during awake neurosurgery for the treatment of epilepsy. The proportion of neurons changing activity with language tasks was similar in either hemisphere. Dominant hemisphere activity was characterized by relative inhibition, some of which occurred during overt speech, possibly to block perception of one’s own voice. However, the majority seems to represent a dynamic network becoming active with verbal memory encoding and especially verbal learning, but inhibited during performance of overlearned language tasks. Individual neurons are involved in different networks for different aspects of language, including naming or reading and naming in different languages. The majority of the changes in activity were tonic sustained shifts in firing. Patterned phasic activity for specific language items was very infrequently recorded. Human single neuron recordings provide a unique perspective on the biologic substrate for language, for these findings are in contrast to many of the findings from other techniques for investigating this. PMID:24961418

  10. Microglia Control Neuronal Network Excitability via BDNF Signalling

    PubMed Central

    2013-01-01

    Microglia-neuron interactions play a crucial role in several neurological disorders characterized by altered neural network excitability, such as epilepsy and neuropathic pain. While a series of potential messengers have been postulated as substrates of the communication between microglia and neurons, including cytokines, purines, prostaglandins, and nitric oxide, the specific links between messengers, microglia, neuronal networks, and diseases have remained elusive. Brain-derived neurotrophic factor (BDNF) released by microglia emerges as an exception in this riddle. Here, we review the current knowledge on the role played by microglial BDNF in controlling neuronal excitability by causing disinhibition. The efforts made by different laboratories during the last decade have collectively provided a robust mechanistic paradigm which elucidates the mechanisms involved in the synthesis and release of BDNF from microglia, the downstream TrkB-mediated signals in neurons, and the biophysical mechanism by which disinhibition occurs, via the downregulation of the K+-Cl− cotransporter KCC2, dysrupting Cl−homeostasis, and hence the strength of GABAA- and glycine receptor-mediated inhibition. The resulting altered network activity appears to explain several features of the associated pathologies. Targeting the molecular players involved in this canonical signaling pathway may lead to novel therapeutic approach for ameliorating a wide array of neural dysfunctions. PMID:24089642

  11. Ensemble Recording of Electrical Activity in Neurons Derived from P19 Embryonal Carcinoma Cells

    NASA Astrophysics Data System (ADS)

    Takayama, Yuzo; Saito, Atushi; Moriguchi, Hiroyuki; Kotani, Kiyoshi; Jimbo, Yasuhiko

    Regeneration of the central nervous system (CNS) is one of the most important research themes in neuroscience and neuroengineering. It is essential to replenish the lost neurons and to establish appropriate functional neuronal networks using pluripotent stem cells. Little is known, however, about the properties of stem cell-derived neuronal networks, particularly under the differentiation and development processes. In this work, we cultured P19 embryonal carcinoma cells on micro-electrode arrays (MEAs). P19 cells were differentiated into neurons by retinoic acid application and formed densely connected networks. Spontaneous electrical activity was extracellulary recorded through substrate electrodes and analyzed. Synchronized periodic bursts, which were the characteristic features in primary cultured CNS neurons, were observed. Pharmacological studies demonstrated that the glutamatergic excitatory synapses and the GABAergic inhibitory synapses were active in these P19-derived neuronal networks. The results suggested that MEA-based recording was useful for monitoring differentiation processes of stem cells. P19-derived neuronal networks had quite similar network properties to those of primary cultured neurons, and thus provide a novel model system to investigate stem cell-based neuronal regeneration.

  12. Multiple alternative substrate kinetics.

    PubMed

    Anderson, Vernon E

    2015-11-01

    The specificity of enzymes for their respective substrates has been a focal point of enzyme kinetics since the initial characterization of metabolic chemistry. Various processes to quantify an enzyme's specificity using kinetics have been utilized over the decades. Fersht's definition of the ratio kcat/Km for two different substrates as the "specificity constant" (ref [7]), based on the premise that the important specificity existed when the substrates were competing in the same reaction, has become a consensus standard for enzymes obeying Michaelis-Menten kinetics. The expansion of the theory for the determination of the relative specificity constants for a very large number of competing substrates, e.g. those present in a combinatorial library, in a single reaction mixture has been developed in this contribution. The ratio of kcat/Km for isotopologs has also become a standard in mechanistic enzymology where kinetic isotope effects have been measured by the development of internal competition experiments with extreme precision. This contribution extends the theory of kinetic isotope effects to internal competition between three isotopologs present at non-tracer concentrations in the same reaction mix. This article is part of a special issue titled: Enzyme Transition States from Theory and Experiment. PMID:26051088

  13. Substrate system for spray forming

    DOEpatents

    Chu, Men G.; Chernicoff, William P.

    2002-01-01

    A substrate system for receiving a deposit of sprayed metal droplets including a movable outer substrate on which the sprayed metal droplets are deposited. The substrate system also includes an inner substrate disposed adjacent the outer substrate where the sprayed metal droplets are deposited on the outer substrate. The inner substrate includes zones of differing thermal conductivity to resist substrate layer porosity and to resist formation of large grains and coarse constituent particles in a bulk layer of the metal droplets which have accumulated on the outer substrate. A spray forming apparatus and associated method of spray forming a molten metal to form a metal product using the substrate system of the invention is also provided.

  14. Substrate system for spray forming

    DOEpatents

    Chu, Men G.; Chernicoff, William P.

    2000-01-01

    A substrate system for receiving a deposit of sprayed metal droplets including a movable outer substrate on which the sprayed metal droplets are deposited. The substrate system also includes an inner substrate disposed adjacent the outer substrate where the sprayed metal droplets are deposited on the outer substrate. The inner substrate includes zones of differing thermal conductivity to resist substrate layer porosity and to resist formation of large grains and coarse constituent particles in a bulk layer of the metal droplets which have accumulated on the outer substrate. A spray forming apparatus and associated method of spray forming a molten metal to form a metal product using the substrate system of the invention is also provided.

  15. Sol-gel derived ceramic electrolyte films on porous substrates

    SciTech Connect

    Kueper, T.W.

    1992-05-01

    A process for the deposition of sol-gel derived thin films on porous substrates has been developed; such films should be useful for solid oxide fuel cells and related applications. Yttria-stabilized zirconia films have been formed from metal alkoxide starting solutions. Dense films have been deposited on metal substrates and ceramic substrates, both dense and porous, through dip-coating and spin-coating techniques, followed by a heat treatment in air. X-ray diffraction has been used to determine the crystalline phases formed and the extent of reactions with various substrates which may be encountered in gas/gas devices. Surface coatings have been successfully applied to porous substrates through the control of substrate pore size and deposition parameters. Wetting of the substrate pores by the coating solution is discussed, and conditions are defined for which films can be deposited over the pores without filling the interiors of the pores. Shrinkage cracking was encountered in films thicker than a critical value, which depended on the sol-gel process parameters and on the substrate characteristics. Local discontinuities were also observed in films which were thinner than a critical value which depended on the substrate pore size. A theoretical discussion of cracking mechanisms is presented for both types of cracking, and the conditions necessary for successful thin formation are defined. The applicability of these film gas/gas devices is discussed.

  16. The impact of JNK on neuronal migration.

    PubMed

    Zdrojewska, Justyna; Coffey, Eleanor T

    2014-01-01

    Incorrect placement of nerve cells during brain development leaves us at risk of diseases and conditions ranging from epilepsy and mental retardation to schizophrenia and dyslexia. The developing brain produces cells at an impressive rate, with up to 250,000 new cells generated every minute. These newborn cells migrate long distances in sequential waves to settle in the layers that make up the cerebral cortex. If a nerve cell moves too fast or too slow during this journey, it may not take the correct route or reach its appropriate destination. Much knowledge has been accumulated on molecular cues and transcriptional programs regulating cortical development. More recently, components of the c-Jun N-terminal signaling cascade have been brought to light as important intracellular regulators of nerve cell motility. In this chapter, we focus on this family of protein kinases, their upstream activators and downstream targets in the context of neuronal migration. We first present basic information on these molecules, much of which derives from studies outside the nervous system. We then highlight key findings on JNK signaling in brain where it phosphorylates brain-specific proteins that influence microtubule homeostasis. Finally, we summarize recent findings from transgenic mice on the regulation of neuronal migration by JNK cascade components and by JNK substrates. PMID:24243099

  17. Cognitive and Neuronal Systems Underlying Obesity

    PubMed Central

    Kanoski, Scott E.

    2012-01-01

    Since the late 1970’s obesity prevalence and per capita food intake in the USA have increased dramatically. Understanding the mechanisms underlying the hyperphagia that drives obesity requires focus on the cognitive processes and neuronal systems controlling feeding that occurs in the absence of metabolic need (i.e., "non-homeostatic” intake). Given that a portion of the increased caloric intake per capita since the late 1970’s is attributed to increased meal and snack frequency, and given the increased pervasiveness of environmental cues associated with energy dense, yet nutritionally deplete foods, there’s a need to examine the mechanisms through which food-related cues stimulate excessive energy intake. Here, learning and memory principles and their underlying neuronal substrates are discussed with regard to stimulus-driven food intake and excessive energy consumption. Particular focus is given to the hippocampus, a brain structure that utilizes interoceptive cues relevant to energy status (e.g., neurohormonal signals such as leptin) to modulate stimulus-driven food procurement and consumption. This type of hippocampal-dependent modulatory control of feeding behavior is compromised by consumption of foods common to Western diets, including saturated fats and simple carbohydrates. The development of more effective treatments for obesity will benefit from a more complete understanding of the complex interaction between dietary, environmental, cognitive, and neurophysiological mechanisms contributing to excessive food intake. PMID:22266286

  18. Synchronization by elastic neuronal latencies

    NASA Astrophysics Data System (ADS)

    Vardi, Roni; Timor, Reut; Marom, Shimon; Abeles, Moshe; Kanter, Ido

    2013-01-01

    Psychological and physiological considerations entail that formation and functionality of neuronal cell assemblies depend upon synchronized repeated activation such as zero-lag synchronization. Several mechanisms for the emergence of this phenomenon have been suggested, including the global network quantity, the greatest common divisor of neuronal circuit delay loops. However, they require strict biological prerequisites such as precisely matched delays and connectivity, and synchronization is represented as a stationary mode of activity instead of a transient phenomenon. Here we show that the unavoidable increase in neuronal response latency to ongoing stimulation serves as a nonuniform gradual stretching of neuronal circuit delay loops. This apparent nuisance is revealed to be an essential mechanism in various types of neuronal time controllers, where synchronization emerges as a transient phenomenon and without predefined precisely matched synaptic delays. These findings are described in an experimental procedure where conditioned stimulations were enforced on a circuit of neurons embedded within a large-scale network of cortical cells in vitro, and are corroborated and extended by simulations of circuits composed of Hodgkin-Huxley neurons with time-dependent latencies. These findings announce a cortical time scale for time controllers based on tens of microseconds stretching of neuronal circuit delay loops per spike. They call for a reexamination of the role of the temporal periodic mode in brain functionality using advanced in vitro and in vivo experiments.

  19. [Motor neuron disease: metabolic evaluation].

    PubMed

    Godoy, J M; Skacel, M; Balassiano, S L; Neves, J R

    1992-03-01

    The authors studied serum and urinary calcium and phosphorus levels, as well as abnormalities on the spine of 30 patients with motor neuron disease. The authors believe in multifactorial aspects in the pathogenesis of motor neuron disease, calling special attention to toxic and metabolic factors. PMID:1307483

  20. Neuronal avalanches and coherence potentials

    NASA Astrophysics Data System (ADS)

    Plenz, D.

    2012-05-01

    The mammalian cortex consists of a vast network of weakly interacting excitable cells called neurons. Neurons must synchronize their activities in order to trigger activity in neighboring neurons. Moreover, interactions must be carefully regulated to remain weak (but not too weak) such that cascades of active neuronal groups avoid explosive growth yet allow for activity propagation over long-distances. Such a balance is robustly realized for neuronal avalanches, which are defined as cortical activity cascades that follow precise power laws. In experiments, scale-invariant neuronal avalanche dynamics have been observed during spontaneous cortical activity in isolated preparations in vitro as well as in the ongoing cortical activity of awake animals and in humans. Theory, models, and experiments suggest that neuronal avalanches are the signature of brain function near criticality at which the cortex optimally responds to inputs and maximizes its information capacity. Importantly, avalanche dynamics allow for the emergence of a subset of avalanches, the coherence potentials. They emerge when the synchronization of a local neuronal group exceeds a local threshold, at which the system spawns replicas of the local group activity at distant network sites. The functional importance of coherence potentials will be discussed in the context of propagating structures, such as gliders in balanced cellular automata. Gliders constitute local population dynamics that replicate in space after a finite number of generations and are thought to provide cellular automata with universal computation. Avalanches and coherence potentials are proposed to constitute a modern framework of cortical synchronization dynamics that underlies brain function.

  1. The Neuronal Ceroid-Lipofuscinoses

    ERIC Educational Resources Information Center

    Bennett, Michael J.; Rakheja, Dinesh

    2013-01-01

    The neuronal ceroid-lipofuscinoses (NCL's, Batten disease) represent a group of severe neurodegenerative diseases, which mostly present in childhood. The phenotypes are similar and include visual loss, seizures, loss of motor and cognitive function, and early death. At autopsy, there is massive neuronal loss with characteristic storage in…

  2. Synthetic fuels

    SciTech Connect

    Sammons, V.O.

    1980-01-01

    This guide is designed for those who wish to learn more about the science and technology of synthetic fuels by reviewing materials in the collections of the Library of Congress. This is not a comprehensive bibliography, it is designed to put the reader on target. Subject headings used by the Library of Congress under which books on synthetic fuels can be located are: oil-shale industry; oil-shales; shale oils; synthetic fuels; synthetic fuels industry; coal gasification; coal liquefaction; fossil fuels; hydrogen as fuel; oil sands; petroleum, synthesis gas; biomass energy; pyrolysis; and thermal oil recovery. Basic texts, handbooks, government publications, journals, etc. were included. (DP)

  3. Opportunity fuels

    SciTech Connect

    Lutwen, R.C.

    1996-12-31

    The paper consists of viewgraphs from a conference presentation. A comparison is made of opportunity fuels, defined as fuels that can be converted to other forms of energy at lower cost than standard fossil fuels. Types of fuels for which some limited technical data is provided include petroleum coke, garbage, wood waste, and tires. Power plant economics and pollution concerns are listed for each fuel, and compared to coal and natural gas power plant costs. A detailed cost breakdown for different plant types is provided for use in base fuel pricing.

  4. Ethanol and neuronal metabolism.

    PubMed

    Mandel, P; Ledig, M; M'Paria, J R

    1980-01-01

    The effect of ethanol on membrane enzymes (Na+, K+ and Mg2+ ATPases, 5'-nucleotidase, adenylate cyclase) alcohol dehydrogenase, aldehyde dehydrogenase and superoxide dismutase were studied in nerve cells (established cell lines, primary cultures of chick and rat brain) cultured in the presence of 100 mM ethanol, and in total rat brain, following various ethanol treatments of the rats (20% ethanol as the sole liquid source, intraperitoneal injection). The results show a difference between neuronal and glial cells. Most of the observed changes in enzymatic activities returned rapidly to control values when ethanol was withdrawn from the culture medium or from the diet. Alcohol dehydrogenase was more stimulated by ethanol than aldehyde dehydrogenase; therefore acetaldehyde may be accumulated. The inhibition of superoxide dismutase activity may allow an accumulation of cytotoxic O2- radicals in nervous tissue and may explain the polymorphism of lesions brought about by alcohol intoxication. PMID:6264495

  5. Neuron's function revealed

    SciTech Connect

    2009-01-01

    There's a new way to explore biologys secrets. With a flash of light, scientists from the U.S. Department of Energys Lawrence Berkeley National Laboratory and the University of California, Berkeley zeroed in on the type of neural cell that controls swimming in larval zebrafish. Using innovative light-activated proteins and gene expression techniques, the scientists zapped several zebrafish with a pulse of light, and initiated a swimming action in a subset of fish that was traced back to the type of neuron that drives the side-to-side motion of their tail fins. The technique behind this needle-in-haystack search for the neural roots of a specific behavior could become a powerful way to learn how any biological system works. http://newscenter.lbl.gov/press-releases/2009/09/16/light-activated-protein/

  6. Multiplying with Neurons

    NASA Astrophysics Data System (ADS)

    Gabbiani, F.; Krapp, H.; Koch, C.; Laurent, G.

    1998-03-01

    LGMD and DCMD are a pair of identified neurons in the locust brain thought to be involved in visually triggered escape behavior. LGMD integrates visual inputs in its dendritic arbor, converts them into spikes transmitted in a 1:1 manner to DCMD which relays this information to motor centers. We measured the spike activity of DCMD during simulated object approach and observed that its peak occured prior to the expected collision. The time difference between peak activity and collision depended linearly on the ratio of object size to approach velocity, as expected if LGMD/DCMD were detecting the moment in time when the approaching object reaches a fixed angular threshold θ_thresh on the locust's retina. The response of LGMD/DCMD could be fitted by multiplying the angular velocity at which an approaching object is increasing in size over the retina, dot θ, with an exponential function of the object's angular size, θ: f(t) = g(dot θ(t-δ) e^-α θ(t-δ)) where g is a static non-linearity, α a constant related to the angular threshold detected by LGMD/DCMD (θ_thresh = arctan (2/α)) and δ denotes the lag of the neuronal response with respect to the stimulus. This suggests that LGMD/DCMD derives its angular threshold sensitivity by multiplying dot θ with an exponential of θ. A biophysical implementation would be through linear summation of excitatory and inhibitory inputs proportional to log(dot θ) and -α θ, followed by a conversion to spike rate according to the static non-linearity (g circ exp). We have performed several experiments to test this hypothesis.

  7. Neuronal cell lines as model dorsal root ganglion neurons

    PubMed Central

    Yin, Kathleen; Baillie, Gregory J

    2016-01-01

    Background Dorsal root ganglion neuron-derived immortal cell lines including ND7/23 and F-11 cells have been used extensively as in vitro model systems of native peripheral sensory neurons. However, while it is clear that some sensory neuron-specific receptors and ion channels are present in these cell lines, a systematic comparison of the molecular targets expressed by these cell lines with those expressed in intact peripheral neurons is lacking. Results In this study, we examined the expression of RNA transcripts in the human neuroblastoma-derived cell line, SH-SY5Y, and two dorsal root ganglion hybridoma cell lines, F-11 and ND7/23, using Illumina next-generation sequencing, and compared the results with native whole murine dorsal root ganglions. The gene expression profiles of these three cell lines did not resemble any specific defined dorsal root ganglion subclass. The cell lines lacked many markers for nociceptive sensory neurons, such as the Transient receptor potential V1 gene, but expressed markers for both myelinated and unmyelinated neurons. Global gene ontology analysis on whole dorsal root ganglions and cell lines showed similar enrichment of biological process terms across all samples. Conclusions This paper provides insights into the receptor repertoire expressed in common dorsal root ganglion neuron-derived cell lines compared with whole murine dorsal root ganglions, and illustrates the limits and potentials of these cell lines as tools for neuropharmacological exploration. PMID:27130590

  8. History-Dependent Excitability as a Single-Cell Substrate of Transient Memory for Information Discrimination

    PubMed Central

    Baroni, Fabiano; Torres, Joaquín J.; Varona, Pablo

    2010-01-01

    Neurons react differently to incoming stimuli depending upon their previous history of stimulation. This property can be considered as a single-cell substrate for transient memory, or context-dependent information processing: depending upon the current context that the neuron “sees” through the subset of the network impinging on it in the immediate past, the same synaptic event can evoke a postsynaptic spike or just a subthreshold depolarization. We propose a formal definition of History-Dependent Excitability (HDE) as a measure of the propensity to firing in any moment in time, linking the subthreshold history-dependent dynamics with spike generation. This definition allows the quantitative assessment of the intrinsic memory for different single-neuron dynamics and input statistics. We illustrate the concept of HDE by considering two general dynamical mechanisms: the passive behavior of an Integrate and Fire (IF) neuron, and the inductive behavior of a Generalized Integrate and Fire (GIF) neuron with subthreshold damped oscillations. This framework allows us to characterize the sensitivity of different model neurons to the detailed temporal structure of incoming stimuli. While a neuron with intrinsic oscillations discriminates equally well between input trains with the same or different frequency, a passive neuron discriminates better between inputs with different frequencies. This suggests that passive neurons are better suited to rate-based computation, while neurons with subthreshold oscillations are advantageous in a temporal coding scheme. We also address the influence of intrinsic properties in single-cell processing as a function of input statistics, and show that intrinsic oscillations enhance discrimination sensitivity at high input rates. Finally, we discuss how the recognition of these cell-specific discrimination properties might further our understanding of neuronal network computations and their relationships to the distribution and functional

  9. Mimics and chameleons in motor neurone disease

    PubMed Central

    Turner, Martin R; Talbot, Kevin

    2013-01-01

    The progression of motor neurone disease (MND) is currently irreversible, and the grave implications of diagnosis naturally fuels concern among neurologists over missing a potential mimic disorder. There is no diagnostic test for MND but in reality there are few plausible mimics in routine clinical practice. In the presence of a progressive pure motor disorder, signs such as florid fasciculations, bilateral tongue wasting, the ‘split hand’, head drop, emotionality, and cognitive or behavioural impairment carry high positive predictive value. MND is clinically heterogeneous, however, with some important chameleon-like presentations and considerable variation in clinical course. Lack of confidence about the scope of such variation, or an approach to diagnosis emphasising investigations over clinical common sense, has the potential to exacerbate diagnostic delay in MND and impede timely planning of the care which is essential to maximising quality of life. PMID:23616620

  10. Stochastic models of neuronal dynamics

    PubMed Central

    Harrison, L.M; David, O; Friston, K.J

    2005-01-01

    Cortical activity is the product of interactions among neuronal populations. Macroscopic electrophysiological phenomena are generated by these interactions. In principle, the mechanisms of these interactions afford constraints on biologically plausible models of electrophysiological responses. In other words, the macroscopic features of cortical activity can be modelled in terms of the microscopic behaviour of neurons. An evoked response potential (ERP) is the mean electrical potential measured from an electrode on the scalp, in response to some event. The purpose of this paper is to outline a population density approach to modelling ERPs. We propose a biologically plausible model of neuronal activity that enables the estimation of physiologically meaningful parameters from electrophysiological data. The model encompasses four basic characteristics of neuronal activity and organization: (i) neurons are dynamic units, (ii) driven by stochastic forces, (iii) organized into populations with similar biophysical properties and response characteristics and (iv) multiple populations interact to form functional networks. This leads to a formulation of population dynamics in terms of the Fokker–Planck equation. The solution of this equation is the temporal evolution of a probability density over state-space, representing the distribution of an ensemble of trajectories. Each trajectory corresponds to the changing state of a neuron. Measurements can be modelled by taking expectations over this density, e.g. mean membrane potential, firing rate or energy consumption per neuron. The key motivation behind our approach is that ERPs represent an average response over many neurons. This means it is sufficient to model the probability density over neurons, because this implicitly models their average state. Although the dynamics of each neuron can be highly stochastic, the dynamics of the density is not. This means we can use Bayesian inference and estimation tools that have

  11. Surface plasmon-enhanced optical trapping of quantum-dot-conjugated surface molecules on neurons cultured on a plasmonic chip

    NASA Astrophysics Data System (ADS)

    Miyauchi, Kohei; Tawa, Keiko; Kudoh, Suguru N.; Taguchi, Takahisa; Hosokawa, Chie

    2016-06-01

    Living neurons in a complex neuronal network communicate with each other through synaptic connections. The molecular dynamics of cell surface molecules localized at synaptic terminals is essential for functional connections via synaptic plasticity in the neuronal network. Here, we demonstrate surface-plasmon-resonance-based optical trapping using a plasmonic chip toward realizing effective manipulation of molecules on the surface of neurons. Surface-plasmon-enhanced optical trapping was evaluated by the fluorescence analysis of nanoparticles suspended in water and neural cell adhesion molecules (NCAMs) labeled with quantum dots (Q-dots) on rat hippocampal neurons. The motion of nanoparticles in water and the molecular dynamics of NCAMs on neuronal cells cultured on a plasmonic chip were constrained at the laser focus more effectively than those on a glass substrate because of the surface plasmon resonance effect.

  12. Synthetic Fuel

    ScienceCinema

    Idaho National Laboratory - Steve Herring, Jim O'Brien, Carl Stoots

    2010-01-08

    Two global energy priorities today are finding environmentally friendly alternatives to fossil fuels, and reducing greenhouse gass Two global energy priorities today are finding environmentally friendly alternatives to fossil fuels, and reducing greenhous

  13. Synthetic Fuel

    SciTech Connect

    Idaho National Laboratory - Steve Herring, Jim O'Brien, Carl Stoots

    2008-03-26

    Two global energy priorities today are finding environmentally friendly alternatives to fossil fuels, and reducing greenhouse gass Two global energy priorities today are finding environmentally friendly alternatives to fossil fuels, and reducing greenhous

  14. Alternate fuels

    SciTech Connect

    Ryan, T.W.; Worthen, R.P.

    1981-02-01

    The escalating oil prices and shortages of petroleum based fuels for transportation have made research work on various fuel alternatives, especially for transportation engines, a priority of both the private and public sectors. This book contains 18 papers on this subject. The range of options from the development of completely non-petroleum-based fuels and engines to the use of various non-petroleum gasoline and diesel fuel extenders and improvers are discussed.

  15. Two Cell Circuits of Oriented Adult Hippocampal Neurons on Self-Assembled Monolayers for Use in the Study of Neuronal Communication in a Defined System

    PubMed Central

    2013-01-01

    In this study, we demonstrate the directed formation of small circuits of electrically active, synaptically connected neurons derived from the hippocampus of adult rats through the use of engineered chemically modified culture surfaces that orient the polarity of the neuronal processes. Although synaptogenesis, synaptic communication, synaptic plasticity, and brain disease pathophysiology can be studied using brain slice or dissociated embryonic neuronal culture systems, the complex elements found in neuronal synapses makes specific studies difficult in these random cultures. The study of synaptic transmission in mature adult neurons and factors affecting synaptic transmission are generally studied in organotypic cultures, in brain slices, or in vivo. However, engineered neuronal networks would allow these studies to be performed instead on simple functional neuronal circuits derived from adult brain tissue. Photolithographic patterned self-assembled monolayers (SAMs) were used to create the two-cell “bidirectional polarity” circuit patterns. This pattern consisted of a cell permissive SAM, N-1[3-(trimethoxysilyl)propyl] diethylenetriamine (DETA), and was composed of two 25 μm somal adhesion sites connected with 5 μm lines acting as surface cues for guided axonal and dendritic regeneration. Surrounding the DETA pattern was a background of a non-cell-permissive poly(ethylene glycol) (PEG) SAM. Adult hippocampal neurons were first cultured on coverslips coated with DETA monolayers and were later passaged onto the PEG-DETA bidirectional polarity patterns in serum-free medium. These neurons followed surface cues, attaching and regenerating only along the DETA substrate to form small engineered neuronal circuits. These circuits were stable for more than 21 days in vitro (DIV), during which synaptic connectivity was evaluated using basic electrophysiological methods. PMID:23611164

  16. Fossil Fuels.

    ERIC Educational Resources Information Center

    Crank, Ron

    This instructional unit is one of 10 developed by students on various energy-related areas that deals specifically with fossil fuels. Some topics covered are historic facts, development of fuels, history of oil production, current and future trends of the oil industry, refining fossil fuels, and environmental problems. Material in each unit may…

  17. Generation and transplantation of reprogrammed human neurons in the brain using 3D microtopographic scaffolds

    PubMed Central

    Carlson, Aaron L.; Bennett, Neal K.; Francis, Nicola L.; Halikere, Apoorva; Clarke, Stephen; Moore, Jennifer C.; Hart, Ronald P.; Paradiso, Kenneth; Wernig, Marius; Kohn, Joachim; Pang, Zhiping P.; Moghe, Prabhas V.

    2016-01-01

    Cell replacement therapy with human pluripotent stem cell-derived neurons has the potential to ameliorate neurodegenerative dysfunction and central nervous system injuries, but reprogrammed neurons are dissociated and spatially disorganized during transplantation, rendering poor cell survival, functionality and engraftment in vivo. Here, we present the design of three-dimensional (3D) microtopographic scaffolds, using tunable electrospun microfibrous polymeric substrates that promote in situ stem cell neuronal reprogramming, neural network establishment and support neuronal engraftment into the brain. Scaffold-supported, reprogrammed neuronal networks were successfully grafted into organotypic hippocampal brain slices, showing an ∼3.5-fold improvement in neurite outgrowth and increased action potential firing relative to injected isolated cells. Transplantation of scaffold-supported neuronal networks into mouse brain striatum improved survival ∼38-fold at the injection site relative to injected isolated cells, and allowed delivery of multiple neuronal subtypes. Thus, 3D microscale biomaterials represent a promising platform for the transplantation of therapeutic human neurons with broad neuro-regenerative relevance. PMID:26983594

  18. Viscoelastic properties of individual glial cells and neurons in the CNS.

    PubMed

    Lu, Yun-Bi; Franze, Kristian; Seifert, Gerald; Steinhäuser, Christian; Kirchhoff, Frank; Wolburg, Hartwig; Guck, Jochen; Janmey, Paul; Wei, Er-Qing; Käs, Josef; Reichenbach, Andreas

    2006-11-21

    One hundred fifty years ago glial cells were discovered as a second, non-neuronal, cell type in the central nervous system. To ascribe a function to these new, enigmatic cells, it was suggested that they either glue the neurons together (the Greek word "gammalambdaiotaalpha" means "glue") or provide a robust scaffold for them ("support cells"). Although both speculations are still widely accepted, they would actually require quite different mechanical cell properties, and neither one has ever been confirmed experimentally. We investigated the biomechanics of CNS tissue and acutely isolated individual neurons and glial cells from mammalian brain (hippocampus) and retina. Scanning force microscopy, bulk rheology, and optically induced deformation were used to determine their viscoelastic characteristics. We found that (i) in all CNS cells the elastic behavior dominates over the viscous behavior, (ii) in distinct cell compartments, such as soma and cell processes, the mechanical properties differ, most likely because of the unequal local distribution of cell organelles, (iii) in comparison to most other eukaryotic cells, both neurons and glial cells are very soft ("rubber elastic"), and (iv) intriguingly, glial cells are even softer than their neighboring neurons. Our results indicate that glial cells can neither serve as structural support cells (as they are too soft) nor as glue (because restoring forces are dominant) for neurons. Nevertheless, from a structural perspective they might act as soft, compliant embedding for neurons, protecting them in case of mechanical trauma, and also as a soft substrate required for neurite growth and facilitating neuronal plasticity. PMID:17093050

  19. Dopaminergic neurons inhibit striatal output via non-canonical release of GABA

    PubMed Central

    Tritsch, Nicolas X.; Ding, Jun B.; Sabatini, Bernardo L.

    2012-01-01

    The substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) contain the two largest populations of dopamine (DA)-releasing neurons in the mammalian brain. These neurons extend elaborate projections in striatum, a large subcortical structure implicated in motor planning and reward-based learning. Phasic activation of dopaminergic neurons in response to salient or reward-predicting stimuli is thought to modulate striatal output via the release of DA to promote and reinforce motor action1–4. Here we show that activation of DA neurons in striatal slices rapidly inhibits action potential firing in both direct-and indirect-pathway striatal projection neurons (SPNs) through vesicular release of the inhibitory transmitter γ-aminobutyric acid (GABA). GABA is released directly from dopaminergic axons but in a manner that is independent of the vesicular GABA transporter VGAT. Instead GABA release requires activity of the vesicular monoamine transporter VMAT2, which is the vesicular transporter for DA. Furthermore, VMAT2 expression in GABAergic neurons lacking VGAT is sufficient to sustain GABA release. Thus, these findings expand the repertoire of synaptic mechanisms employed by DA neurons to influence basal ganglia circuits, reveal a novel substrate whose transport is dependent on VMAT2, and demonstrate that GABA can function as a bona fide co-transmitter in monoaminergic neurons. PMID:23034651

  20. Simulating synchronization in neuronal networks

    NASA Astrophysics Data System (ADS)

    Fink, Christian G.

    2016-06-01

    We discuss several techniques used in simulating neuronal networks by exploring how a network's connectivity structure affects its propensity for synchronous spiking. Network connectivity is generated using the Watts-Strogatz small-world algorithm, and two key measures of network structure are described. These measures quantify structural characteristics that influence collective neuronal spiking, which is simulated using the leaky integrate-and-fire model. Simulations show that adding a small number of random connections to an otherwise lattice-like connectivity structure leads to a dramatic increase in neuronal synchronization.

  1. Towards Automatic Classification of Neurons

    PubMed Central

    Armañanzas, Rubén; Ascoli, Giorgio A.

    2015-01-01

    The classification of neurons into types has been much debated since the inception of modern neuroscience. Recent experimental advances are accelerating the pace of data collection. The resulting information growth of morphological, physiological, and molecular properties encourages efforts to automate neuronal classification by powerful machine learning techniques. We review state-of-the-art analysis approaches and availability of suitable data and resources, highlighting prominent challenges and opportunities. The effective solution of the neuronal classification problem will require continuous development of computational methods, high-throughput data production, and systematic metadata organization to enable cross-lab integration. PMID:25765323

  2. Single neuron dynamics and computation.

    PubMed

    Brunel, Nicolas; Hakim, Vincent; Richardson, Magnus J E

    2014-04-01

    At the single neuron level, information processing involves the transformation of input spike trains into an appropriate output spike train. Building upon the classical view of a neuron as a threshold device, models have been developed in recent years that take into account the diverse electrophysiological make-up of neurons and accurately describe their input-output relations. Here, we review these recent advances and survey the computational roles that they have uncovered for various electrophysiological properties, for dendritic arbor anatomy as well as for short-term synaptic plasticity. PMID:24492069

  3. A fish on the hunt, observed neuron by neuron

    SciTech Connect

    2010-01-01

    This three-dimensional microscopy image reveals an output neuron of the optic tectum lighting up in response to visual information from the retina. The scientists used this state-of-the-art imaging technology to learn how neurons in the optic tectum take visual information and convert it into an output that drives action. More information: http://newscenter.lbl.gov/feature-stories/2010/10/29/zebrafish-vision/

  4. Structural Properties of the Caenorhabditis elegans Neuronal Network

    PubMed Central

    Varshney, Lav R.; Chen, Beth L.; Paniagua, Eric; Hall, David H.; Chklovskii, Dmitri B.

    2011-01-01

    Despite recent interest in reconstructing neuronal networks, complete wiring diagrams on the level of individual synapses remain scarce and the insights into function they can provide remain unclear. Even for Caenorhabditis elegans, whose neuronal network is relatively small and stereotypical from animal to animal, published wiring diagrams are neither accurate nor complete and self-consistent. Using materials from White et al. and new electron micrographs we assemble whole, self-consistent gap junction and chemical synapse networks of hermaphrodite C. elegans. We propose a method to visualize the wiring diagram, which reflects network signal flow. We calculate statistical and topological properties of the network, such as degree distributions, synaptic multiplicities, and small-world properties, that help in understanding network signal propagation. We identify neurons that may play central roles in information processing, and network motifs that could serve as functional modules of the network. We explore propagation of neuronal activity in response to sensory or artificial stimulation using linear systems theory and find several activity patterns that could serve as substrates of previously described behaviors. Finally, we analyze the interaction between the gap junction and the chemical synapse networks. Since several statistical properties of the C. elegans network, such as multiplicity and motif distributions are similar to those found in mammalian neocortex, they likely point to general principles of neuronal networks. The wiring diagram reported here can help in understanding the mechanistic basis of behavior by generating predictions about future experiments involving genetic perturbations, laser ablations, or monitoring propagation of neuronal activity in response to stimulation. PMID:21304930

  5. PPG neurons of the lower brain stem and their role in brain GLP-1 receptor activation.

    PubMed

    Trapp, Stefan; Cork, Simon C

    2015-10-15

    Within the brain, glucagon-like peptide-1 (GLP-1) affects central autonomic neurons, including those controlling the cardiovascular system, thermogenesis, and energy balance. Additionally, GLP-1 influences the mesolimbic reward system to modulate the rewarding properties of palatable food. GLP-1 is produced in the gut and by hindbrain preproglucagon (PPG) neurons, located mainly in the nucleus tractus solitarii (NTS) and medullary intermediate reticular nucleus. Transgenic mice expressing glucagon promoter-driven yellow fluorescent protein revealed that PPG neurons not only project to central autonomic control regions and mesolimbic reward centers, but also strongly innervate spinal autonomic neurons. Therefore, these brain stem PPG neurons could directly modulate sympathetic outflow through their spinal inputs to sympathetic preganglionic neurons. Electrical recordings from PPG neurons in vitro have revealed that they receive synaptic inputs from vagal afferents entering via the solitary tract. Vagal afferents convey satiation to the brain from signals like postprandial gastric distention or activation of peripheral GLP-1 receptors. CCK and leptin, short- and long-term satiety peptides, respectively, increased the electrical activity of PPG neurons, while ghrelin, an orexigenic peptide, had no effect. These findings indicate that satiation is a main driver of PPG neuronal activation. They also show that PPG neurons are in a prime position to respond to both immediate and long-term indicators of energy and feeding status, enabling regulation of both energy balance and general autonomic homeostasis. This review discusses the question of whether PPG neurons, rather than gut-derived GLP-1, are providing the physiological substrate for the effects elicited by central nervous system GLP-1 receptor activation. PMID:26290108

  6. INTRANUCLEAR MATRIX METALLOPROTEINASES PROMOTE DNA DAMAGE AND APOPTOSIS INDUCED BY OXYGEN–GLUCOSE DEPRIVATION IN NEURONS

    PubMed Central

    HILL, J. W.; PODDAR, R.; THOMPSON, J. F.; ROSENBERG, G. A.; YANG, Y.

    2016-01-01

    Degradation of the extracellular matrix by elevated matrix metalloproteinase (MMP) activity following ischemia/reperfusion is implicated in blood–brain barrier disruption and neuronal death. In contrast to their characterized extracellular roles, we previously reported that elevated intranuclear MMP-2 and -9 (gelatinase) activity degrades nuclear DNA repair proteins and promotes accumulation of oxidative DNA damage in neurons in rat brain at 3-h reperfusion after ischemic stroke. Here, we report that treatment with a broad-spectrum MMP inhibitor significantly reduced neuronal apoptosis in rat ischemic hemispheres at 48-h reperfusion after a 90-min middle cerebral artery occlusion (MCAO). Since extracellular gelatinases in brain tissue are known to be neurotoxic during acute stroke, the contribution of intranuclear MMP-2 and -9 activities in neurons to neuronal apoptosis has been unclear. To confirm and extend our in vivo observations, oxygen–glucose deprivation (OGD), an in vitro model of ischemia/reperfusion, was employed. Primary cortical neurons were subjected to 2-h OGD with reoxygenation. Increased intranuclear gelatinase activity was detected immediately after reoxygenation onset and was maximal at 24 h, while extracellular gelatinase levels remained unchanged. We detected elevated levels of both MMP-2 and -9 in neuronal nuclear extracts and gelatinase activity in neurons co-localized primarily with MMP-2. We found a marked decrease in PARP1, XRCC1, and OGG1, and decreased PARP1 activity. Pretreatment of neurons with selective MMP-2/9 inhibitor II significantly decreased gelatinase activity and downregulation of DNA repair enzymes, decreased accumulation of oxidative DNA damage, and promoted neuronal survival after OGD. Our results confirm the nuclear localization of gelatinases and their nuclear substrates observed in an animal stroke model, further supporting a novel role for intranuclear gelatinase activity in an intrinsic apoptotic pathway in neurons

  7. Alternative fuels

    NASA Technical Reports Server (NTRS)

    Grobman, J. S.; Butze, H. F.; Friedman, R.; Antoine, A. C.; Reynolds, T. W.

    1977-01-01

    Potential problems related to the use of alternative aviation turbine fuels are discussed and both ongoing and required research into these fuels is described. This discussion is limited to aviation turbine fuels composed of liquid hydrocarbons. The advantages and disadvantages of the various solutions to the problems are summarized. The first solution is to continue to develop the necessary technology at the refinery to produce specification jet fuels regardless of the crude source. The second solution is to minimize energy consumption at the refinery and keep fuel costs down by relaxing specifications.

  8. The neuronal and actin commitment: Why do neurons need rings?

    PubMed

    Leite, Sérgio Carvalho; Sousa, Mónica Mendes

    2016-09-01

    The role of the actin cytoskeleton in neurons has been extensively studied in actin-enriched compartments such as the growth cone and dendritic spines. The recent discovery of actin rings in the axon shaft and in dendrites, together with the identification of axon actin trails, has advanced our understanding on actin organization and dynamics in neurons. However, specifically in the case of actin rings, the mechanisms regulating their nucleation and assembly, and the functions that they may exert in axons and dendrites remain largely unexplored. Here we discuss the possible structural, mechanistic and functional properties of the subcortical neuronal cytoskeleton putting the current knowledge in perspective with the information available on actin rings formed in other biological contexts, and with the organization of actin-spectrin lattices in other cell types. The detailed analysis of these novel neuronal actin ring structures, together with the elucidation of the function of actin-binding proteins in neuron biology, has a large potential to uncover new mechanisms of neuronal function under normal conditions that may have impact in our understanding of axon degeneration and regeneration. © 2016 Wiley Periodicals, Inc. PMID:26784007

  9. Electrocatalyst for alcohol oxidation in fuel cells

    DOEpatents

    Adzic, Radoslav R.; Marinkovic, Nebojsa S.

    2001-01-01

    Binary and ternary electrocatalysts are provided for oxidizing alcohol in a fuel cell. The binary electrocatalyst includes 1) a substrate selected from the group consisting of NiWO.sub.4 or CoWO.sub.4 or a combination thereof, and 2) Group VIII noble metal catalyst supported on the substrate. The ternary electrocatalyst includes 1) a substrate as described above, and 2) a catalyst comprising Group VIII noble metal, and ruthenium oxide or molybdenum oxide or a combination thereof, said catalyst being supported on said substrate.

  10. Tinbergen on mirror neurons

    PubMed Central

    Heyes, Cecilia

    2014-01-01

    Fifty years ago, Niko Tinbergen defined the scope of behavioural biology with his four problems: causation, ontogeny, survival value and evolution. About 20 years ago, there was another highly significant development in behavioural biology—the discovery of mirror neurons (MNs). Here, I use Tinbergen's original four problems (rather than the list that appears in textbooks) to highlight the differences between two prominent accounts of MNs, the genetic and associative accounts; to suggest that the latter provides the defeasible ‘best explanation’ for current data on the causation and ontogeny of MNs; and to argue that functional analysis, of the kind that Tinbergen identified somewhat misleadingly with studies of ‘survival value’, should be a high priority for future research. In this kind of functional analysis, system-level theories would assign MNs a small, but potentially important, role in the achievement of action understanding—or another social cognitive function—by a production line of interacting component processes. These theories would be tested by experimental intervention in human and non-human animal samples with carefully documented and controlled developmental histories. PMID:24778376

  11. Optical Stimulation of Neurons

    PubMed Central

    Thompson, Alexander C.; Stoddart, Paul R.; Jansen, E. Duco

    2014-01-01

    Our capacity to interface with the nervous system remains overwhelmingly reliant on electrical stimulation devices, such as electrode arrays and cuff electrodes that can stimulate both central and peripheral nervous systems. However, electrical stimulation has to deal with multiple challenges, including selectivity, spatial resolution, mechanical stability, implant-induced injury and the subsequent inflammatory response. Optical stimulation techniques may avoid some of these challenges by providing more selective stimulation, higher spatial resolution and reduced invasiveness of the device, while also avoiding the electrical artefacts that complicate recordings of electrically stimulated neuronal activity. This review explores the current status of optical stimulation techniques, including optogenetic methods, photoactive molecule approaches and infrared neural stimulation, together with emerging techniques such as hybrid optical-electrical stimulation, nanoparticle enhanced stimulation and optoelectric methods. Infrared neural stimulation is particularly emphasised, due to the potential for direct activation of neural tissue by infrared light, as opposed to techniques that rely on the introduction of exogenous light responsive materials. However, infrared neural stimulation remains imperfectly understood, and techniques for accurately delivering light are still under development. While the various techniques reviewed here confirm the overall feasibility of optical stimulation, a number of challenges remain to be overcome before they can deliver their full potential. PMID:26322269

  12. Nitrification in a zeoponic substrate

    NASA Technical Reports Server (NTRS)

    McGilloway, R. L.; Weaver, R. W.; Ming, D. W.; Gruener, J. E.

    2003-01-01

    Clinoptilolite is a zeolite mineral with high cation exchange capacity used in zeoponic substrates that have been proposed as a solid medium for growing plants or as a fertilizer material. The kinetics of nitrification has not been measured for NH4+ saturated zeoponic substrate. Experiments were conducted to evaluate the production of NO2- and NO3-, and nitrifier populations in zeoponic substrates. Small columns were filled with zeoponic substrate inoculated with a commercial inoculum or soil enrichment culture of nitrifying bacteria. In addition to column studies, a growth chamber study was conducted to evaluate the kinetics of nitrification in zeoponic substrates used to grow radishes (Raphanus sativus L.). The zeoponic substrate provided a readily available source of NH4+, and nitrifying bacteria were active in the substrate. Ammonium oxidation rates in column studies ranged from 5 to 10 micrograms N g-1 substrate h-1, and NO2- oxidation rates were 2 to 9.5 micrograms N g-1 substrate h-1. Rates determined from the growth chamber study were approximately 1.2 micrograms N g-1 substrate h-1. Quantities of NH4+ oxidized to NO2- and NO3- in inoculated zeoponic substrate were in excess of plant up-take. Acidification as a result of NH4+ oxidation resulted in a pH decline, and the zeoponic substrate showed limited buffering capacity.

  13. Neuron-based microarray sensors for environmental sensing.

    PubMed

    Prasad, Shalini; Zhang, Xuan; Ozkan, Cengiz S; Ozkan, Mihrimah

    2004-11-01

    We present a novel sensing scheme for detecting the effects of unburned fossil fuels by integrating microarray technology and dielectrophoresis to develop single-neuron arrays. These arrays have the capability to sense and identify the two fuels, at parts per billion (ppb) concentrations, as well to determine the associated physiological changes at the single-cell level. Identification is achieved through frequency domain analysis of the measured changes to the extracellular electrical activity due to the effect of the fossil fuels. This yields unique electrical identifiers known as "signature patterns". Simultaneous optical visualization to the physiological changes is obtained by specific fluorescent staining. The correlation between the signature patterns and the cellular biological behavior establishes the veracity of this identification technique. PMID:15565684

  14. Fertilizer effects on annual growth in sweetgum, hickory, and cedar substrates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Expanded perlite has long been used as an amendment in container mediums because of its ability to add air space to container substrates without adding to bulk density or affecting substrate pH and EC. However, due to increased restrictions on the harvesting of peat, as well as fluctuations in fuel...

  15. Polyphenolic Antioxidants and Neuronal Regeneration.

    PubMed

    Ataie, Amin; Shadifar, Mohammad; Ataee, Ramin

    2016-04-01

    Many studies indicate that oxidative stress is involved in the pathophysiology of neurodegenerative diseases. Oxidative stress can induce neuronal damages, modulate intracellular signaling and ultimately leads to neuronal death by apoptosis or necrosis. To review antioxidants preventive effects on oxidative stress and neurodegenerative diseases we accumulated data from international medical journals and academic informations' sites. According to many studies, antioxidants could reduce toxic neuronal damages and many studies confirmed the efficacy of polyphenol antioxidants in fruits and vegetables to reduce neuronal death and to diminish oxidative stress. This systematic review showed the antioxidant activities of phytochemicals which play as natural neuroprotectives with low adverse effects against some neurodegenerative diseases as Parkinson or Alzheimer diseases. PMID:27303602

  16. [Direct neuronal effects of statins].

    PubMed

    Bösel, J; Endres, M

    2006-03-01

    Statins, i.e. HMG-CoA reductase inhibitors, reduce the risk of stroke and may have therapeutic potential for other neurologic diseases, including multiple sclerosis and Alzheimer's disease. In addition to lowering cholesterol levels, statins exert a number of cholesterol-independent (pleiotropic) effects. While endothelial, anti-thrombotic, anti-inflammatory, and immunomodulatory, i.e. peripheral, effects of statins are well known, little is known about the direct effects on neurons. This may be of clinical relevance because some statins are able to cross the blood-brain barrier. Recent experimental studies demonstrate that statins reduce the activity of neuronal glutamate receptors and protect neurons from excitotoxic insults. At higher doses, however, statins may also inhibit neurite sprouting and even induce neuronal apoptosis. PMID:16028081

  17. Polyphenolic Antioxidants and Neuronal Regeneration

    PubMed Central

    Ataie, Amin; Shadifar, Mohammad; Ataee, Ramin

    2016-01-01

    Many studies indicate that oxidative stress is involved in the pathophysiology of neurodegenerative diseases. Oxidative stress can induce neuronal damages, modulate intracellular signaling and ultimately leads to neuronal death by apoptosis or necrosis. To review antioxidants preventive effects on oxidative stress and neurodegenerative diseases we accumulated data from international medical journals and academic informations’ sites. According to many studies, antioxidants could reduce toxic neuronal damages and many studies confirmed the efficacy of polyphenol antioxidants in fruits and vegetables to reduce neuronal death and to diminish oxidative stress. This systematic review showed the antioxidant activities of phytochemicals which play as natural neuroprotectives with low adverse effects against some neurodegenerative diseases as Parkinson or Alzheimer diseases. PMID:27303602

  18. Neuronal migration and protein kinases

    PubMed Central

    Ohshima, Toshio

    2015-01-01

    The formation of the six-layered structure of the mammalian cortex via the inside-out pattern of neuronal migration is fundamental to neocortical functions. Extracellular cues such as Reelin induce intracellular signaling cascades through the protein phosphorylation. Migrating neurons also have intrinsic machineries to regulate cytoskeletal proteins and adhesion properties. Protein phosphorylation regulates these processes. Moreover, the balance between phosphorylation and dephosphorylation is modified by extracellular cues. Multipolar-bipolar transition, radial glia-guided locomotion and terminal translocation are critical steps of radial migration of cortical pyramidal neurons. Protein kinases such as Cyclin-dependent kinase 5 (Cdk5) and c-Jun N-terminal kinases (JNKs) involve these steps. In this review, I shall give an overview the roles of protein kinases in neuronal migration. PMID:25628530

  19. Neuronal boost to evolutionary dynamics.

    PubMed

    de Vladar, Harold P; Szathmáry, Eörs

    2015-12-01

    Standard evolutionary dynamics is limited by the constraints of the genetic system. A central message of evolutionary neurodynamics is that evolutionary dynamics in the brain can happen in a neuronal niche in real time, despite the fact that neurons do not reproduce. We show that Hebbian learning and structural synaptic plasticity broaden the capacity for informational replication and guided variability provided a neuronally plausible mechanism of replication is in place. The synergy between learning and selection is more efficient than the equivalent search by mutation selection. We also consider asymmetric landscapes and show that the learning weights become correlated with the fitness gradient. That is, the neuronal complexes learn the local properties of the fitness landscape, resulting in the generation of variability directed towards the direction of fitness increase, as if mutations in a genetic pool were drawn such that they would increase reproductive success. Evolution might thus be more efficient within evolved brains than among organisms out in the wild. PMID:26640653

  20. Neuronal boost to evolutionary dynamics

    PubMed Central

    de Vladar, Harold P.; Szathmáry, Eörs

    2015-01-01

    Standard evolutionary dynamics is limited by the constraints of the genetic system. A central message of evolutionary neurodynamics is that evolutionary dynamics in the brain can happen in a neuronal niche in real time, despite the fact that neurons do not reproduce. We show that Hebbian learning and structural synaptic plasticity broaden the capacity for informational replication and guided variability provided a neuronally plausible mechanism of replication is in place. The synergy between learning and selection is more efficient than the equivalent search by mutation selection. We also consider asymmetric landscapes and show that the learning weights become correlated with the fitness gradient. That is, the neuronal complexes learn the local properties of the fitness landscape, resulting in the generation of variability directed towards the direction of fitness increase, as if mutations in a genetic pool were drawn such that they would increase reproductive success. Evolution might thus be more efficient within evolved brains than among organisms out in the wild. PMID:26640653

  1. Experiments on clustered neuronal networks

    NASA Astrophysics Data System (ADS)

    Teller, S.; Soriano, J.

    2013-01-01

    Neuronal cultures show a rich repertoire of spontaneous activity. However, the mechanisms that relate a particular network architecture with a specific dynamic behavior are still not well understood. In order to investigate the dependence of neuronal network dynamics on architecture we study spontaneous activity in networks formed by interconnected aggregates of neurons (clustered neuronal networks). In the experiments we monitor the spontaneous activity using calcium fluorescence imaging. Network's firing is characterized by bursts of activity, in which the clusters fire sequentially in a short time window, remaining silent until the next bursting episode. We also investigate perturbations on the connectivity of the network. We mainly focus in physical damage. In some cases we observe important changes in the collective activity of the network, while in other cases some dynamic motifs are preserved, hinting at the existence of dynamic robustness.

  2. [Ambient modulation of neuronal excitability].

    PubMed

    Chen, Yi-Zhang

    2016-08-25

    Although the modulation of synaptic activity plays an important role in the modulation of neuronal excitability, the significance of the ambient modulation (AM) of neuronal excitability should be emphasized. The AM refers to the alterations of membrane potential of neuron resulted from distinct neural activities, such as the tonic inhibition and excitation through activation of extra-synaptic receptors, the paracrine actions of nearby neural and non-neural cells, endocrinal actions of blood borne hormones and other active chemical substances. The AM of neuronal excitability may have important bearings on distinct brain functions, such as the regulation and switching of cortical states, the appearance of chaotic and vague feelings, which are usually the characteristic features in many mental and neural disorders. PMID:27546499

  3. Systematic substrate identification indicates a central role for the metalloprotease ADAM10 in axon targeting and synapse function

    PubMed Central

    Kuhn, Peer-Hendrik; Colombo, Alessio Vittorio; Schusser, Benjamin; Dreymueller, Daniela; Wetzel, Sebastian; Schepers, Ute; Herber, Julia; Ludwig, Andreas; Kremmer, Elisabeth; Montag, Dirk; Müller, Ulrike; Schweizer, Michaela; Saftig, Paul; Bräse, Stefan; Lichtenthaler, Stefan F

    2016-01-01

    Metzincin metalloproteases have major roles in intercellular communication by modulating the function of membrane proteins. One of the proteases is the a-disintegrin-and-metalloprotease 10 (ADAM10) which acts as alpha-secretase of the Alzheimer's disease amyloid precursor protein. ADAM10 is also required for neuronal network functions in murine brain, but neuronal ADAM10 substrates are only partly known. With a proteomic analysis of Adam10-deficient neurons we identified 91, mostly novel ADAM10 substrate candidates, making ADAM10 a major protease for membrane proteins in the nervous system. Several novel substrates, including the neuronal cell adhesion protein NrCAM, are involved in brain development. Indeed, we detected mistargeted axons in the olfactory bulb of conditional ADAM10-/- mice, which correlate with reduced cleavage of NrCAM, NCAM and other ADAM10 substrates. In summary, the novel ADAM10 substrates provide a molecular basis for neuronal network dysfunctions in conditional ADAM10-/- mice and demonstrate a fundamental function of ADAM10 in the brain. DOI: http://dx.doi.org/10.7554/eLife.12748.001 PMID:26802628

  4. Mitogen and stress response kinase-1 (MSK1) mediates excitotoxic induced death of hippocampal neurones.

    PubMed

    Hughes, Jane P; Staton, Penny C; Wilkinson, Marc G; Strijbos, Paul J L M; Skaper, Stephen D; Arthur, J Simon C; Reith, Alastair D

    2003-07-01

    Activation of the mitogen-activated protein kinase (MAPK/ERK) signal transduction pathway may mediate excitotoxic neuronal cell death in vitro and during ischemic brain injury in vivo. However, little is known, of the upstream regulation or downstream consequences of ERK activation under these conditions. Magnesium removal has been described to induce hyperexcitability and degeneration in cultured hippocampal neurones. Here, we show that neurotoxicity evoked by Mg2+ removal in primary hippocampal neurones stimulates ERK, but not p38, phosphorylation. Removal of Mg2+ also resulted in induction of the MAPK/ERK substrate mitogen- and stress-response kinase 1 (MSK1) and induced phosphorylation of the MSK1 substrate, the transcription factor cAMP response element binding protein (CREB). Neuronal death and phosphorylation of components in this cascade were inhibited by the Raf inhibitor SB-386023, by the MEK inhibitor U0126, or by the MSK1 inhibitors H89 and Ro318220. Importantly, this form of cell death was inhibited in hippocampal neurones cultured from MSK1-/- mice and inhibitors of Raf or MEK had no additive neuroprotective effect. Together, these data indicate that MSK1 is a physiological kinase for CREB and that this activity is an essential component of activity-dependent neuronal cell death. PMID:12807421

  5. State-Dependent Propagation of Neuronal Sub-Population in Spontaneous Synchronized Bursts

    PubMed Central

    Yada, Yuichiro; Kanzaki, Ryohei; Takahashi, Hirokazu

    2016-01-01

    Repeating stable spatiotemporal patterns emerge in synchronized spontaneous activity in neuronal networks. The repertoire of such patterns can serve as memory, or a reservoir of information, in a neuronal network; moreover, the variety of patterns may represent the network memory capacity. However, a neuronal substrate for producing a repertoire of patterns in synchronization remains elusive. We herein hypothesize that state-dependent propagation of a neuronal sub-population is the key mechanism. By combining high-resolution measurement with a 4096-channel complementary metal-oxide semiconductor (CMOS) microelectrode array (MEA) and dimensionality reduction with non-negative matrix factorization (NMF), we investigated synchronized bursts of dissociated rat cortical neurons at approximately 3 weeks in vitro. We found that bursts had a repertoire of repeating spatiotemporal patterns, and different patterns shared a partially similar sequence of sub-population, supporting the idea of sequential structure of neuronal sub-populations during synchronized activity. We additionally found that similar spatiotemporal patterns tended to appear successively and periodically, suggesting a state-dependent fluctuation of propagation, which has been overlooked in existing literature. Thus, such a state-dependent property within the sequential sub-population structure is a plausible neural substrate for performing a repertoire of stable patterns during synchronized activity. PMID:27065820

  6. Glycolysis and oxidative phosphorylation in neurons and astrocytes during network activity in hippocampal slices

    PubMed Central

    Ivanov, Anton I; Malkov, Anton E; Waseem, Tatsiana; Mukhtarov, Marat; Buldakova, Svetlana; Gubkina, Olena; Zilberter, Misha; Zilberter, Yuri

    2014-01-01

    Network activation triggers a significant energy metabolism increase in both neurons and astrocytes. Questions of the primary neuronal energy substrate (e.g., glucose vs. lactate) as well as the relative contributions of glycolysis and oxidative phosphorylation and their cellular origin (neurons vs. astrocytes) are still a matter of debates. Using simultaneous measurements of electrophysiological and metabolic parameters during synaptic stimulation in hippocampal slices from mature mice, we show that neurons and astrocytes use both glycolysis and oxidative phosphorylation to meet their energy demands. Supplementation or replacement of glucose in artificial cerebrospinal fluid (ACSF) with pyruvate or lactate strongly modifies parameters related to network activity-triggered energy metabolism. These effects are not induced by changes in ATP content, pHi, [Ca2+]i or accumulation of reactive oxygen species. Our results suggest that during network activation, a significant fraction of NAD(P)H response (its overshoot phase) corresponds to glycolysis and the changes in cytosolic NAD(P)H and mitochondrial FAD are coupled. Our data do not support the hypothesis of a preferential utilization of astrocyte-released lactate by neurons during network activation in slices—instead, we show that during such activity glucose is an effective energy substrate for both neurons and astrocytes. PMID:24326389

  7. Behavioral State Modulates the Activity of Brainstem Sensorimotor Neurons

    PubMed Central

    McArthur, Kimberly L.

    2011-01-01

    Sensorimotor processing must be modulated according to the animal's behavioral state. A previous study demonstrated that motion responses were strongly state dependent in birds. Vestibular eye and head responses were significantly larger and more compensatory during simulated flight, and a flight-specific vestibular tail response was also characterized. In the current study, we investigated the neural substrates for these state-dependent vestibular behaviors by recording extracellularly from neurons in the vestibular nuclear complex and comparing their spontaneous activity and sensory responses during default and simulated flight states. We show that motion-sensitive neurons in the lateral vestibular nucleus are state dependent. Some neurons increased their spontaneous firing rates during flight, though their increased excitability was not reflected in higher sensory gains. However, other neurons exhibited state-dependent gating of sensory inputs, responding to rotational stimuli only during flight. These results demonstrate that vestibular processing in the brainstem is state dependent and lay the foundation for future studies to investigate the synaptic mechanisms responsible for these modifications. PMID:22090497

  8. Mitochondrial dysfunction in rabies virus infection of neurons.

    PubMed

    Alandijany, Thamir; Kammouni, Wafa; Roy Chowdhury, Subir K; Fernyhough, Paul; Jackson, Alan C

    2013-12-01

    Infection with the challenge virus standard-11 (CVS) strain of fixed rabies virus induces neuronal process degeneration in adult mice after hindlimb footpad inoculation. CVS-induced axonal swellings of primary rodent dorsal root ganglion neurons are associated with 4-hydroxy-2-nonenal protein adduct staining, indicating a critical role of oxidative stress. Mitochondrial dysfunction is the major cause of oxidative stress. We hypothesized that CVS infection induces mitochondrial dysfunction leading to oxidative stress. We investigated the effects of CVS infection on several mitochondrial parameters in different cell types. CVS infection significantly increased maximal uncoupled respiration and complex IV respiration and complex I and complex IV activities, but did not affect complex II-III or citrate synthase activities. Increases in complex I activity, but not complex IV activity, correlated with susceptibility of the cells to CVS infection. CVS infection maintained coupled respiration and rate of proton leak, indicating a tight mitochondrial coupling. Possibly as a result of enhanced complex activity and efficient coupling, a high mitochondrial membrane potential was generated. CVS infection reduced the intracellular ATP level and altered the cellular redox state as indicated by a high NADH/NAD+ ratio. The basal production of reactive oxygen species (ROS) was not affected in CVS-infected neurons. However, a higher rate of ROS generation occurred in CVS-infected neurons in the presence of mitochondrial substrates and inhibitors. We conclude that CVS infection induces mitochondrial dysfunction leading to ROS overgeneration and oxidative stress. PMID:24277436

  9. More sensitivity of cortical GABAergic neurons than glutamatergic neurons in response to acidosis.

    PubMed

    Liu, Hua; Li, Fang; Wang, Chunyan; Su, Zhiqiang

    2016-05-25

    Acidosis impairs brain functions. Neuron-specific mechanisms underlying acidosis-induced brain dysfunction remain elusive. We studied the sensitivity of cortical GABAergic neurons and glutamatergic neurons to acidosis by whole-cell recording in brain slices. The acidification to the neurons was induced by perfusing artificial cerebral spinal fluid with lower pH. This acidification impairs excitability and synaptic transmission in the glutamatergic and GABAergic neurons. Acidosis impairs spiking capacity in the GABAergic neurons more than in the glutamatergic neurons. Acidosis also strengthens glutamatergic synaptic transmission and attenuates GABAergic synaptic transmission on the GABAergic neurons more than the glutamatergic neurons, which results in the functional impairment of these GABAergic neurons. This acidosis-induced dysfunction predominantly in the cortical GABAergic neurons drives the homeostasis of neuronal networks toward overexcitation and exacerbates neuronal impairment. PMID:27116702

  10. Cooperative effects of neuronal ensembles.

    PubMed

    Rose, G; Siebler, M

    1995-01-01

    Electrophysiological properties of neurons as the basic cellular elements of the central nervous system and their synaptic connections are well characterized down to a molecular level. However, the behavior of complex noisy networks formed by these constituents usually cannot simply be derived from the knowledge of its microscopic parameters. As a consequence, cooperative phenomena based on the interaction of neurons were postulated. This is a report on a study of global network spike activity as a function of synaptic interaction. We performed experiments in dissociated cultured hippocampal neurons and, for comparison, simulations of a mathematical model closely related to electrophysiology. Numeric analyses revealed that at a critical level of synaptic connectivity the firing behavior undergoes a phase transition. This cooperative effect depends crucially on the interaction of numerous cells and cannot be attributed to the spike threshold of individual neurons. In the experiment a drastic increase in the firing level was observed upon increase of synaptic efficacy by lowering of the extracellular magnesium concentration, which is compatible with our theoretical predictions. This "on-off" phenomenon demonstrates that even in small neuronal ensembles collective behavior can emerge which is not explained by the characteristics of single neurons. PMID:8542966

  11. Neuronal polarity: an evolutionary perspective

    PubMed Central

    Rolls, Melissa M.; Jegla, Timothy J.

    2015-01-01

    Polarized distribution of signaling molecules to axons and dendrites facilitates directional information flow in complex vertebrate nervous systems. The topic we address here is when the key aspects of neuronal polarity evolved. All neurons have a central cell body with thin processes that extend from it to cover long distances, and they also all rely on voltage-gated ion channels to propagate signals along their length. The most familiar neurons, those in vertebrates, have additional cellular features that allow them to send directional signals efficiently. In these neurons, dendrites typically receive signals and axons send signals. It has been suggested that many of the distinct features of axons and dendrites, including the axon initial segment, are found only in vertebrates. However, it is now becoming clear that two key cytoskeletal features that underlie polarized sorting, a specialized region at the base of the axon and polarized microtubules, are found in invertebrate neurons as well. It thus seems likely that all bilaterians generate axons and dendrites in the same way. As a next step, it will be extremely interesting to determine whether the nerve nets of cnidarians and ctenophores also contain polarized neurons with true axons and dendrites, or whether polarity evolved in concert with the more centralized nervous systems found in bilaterians. PMID:25696820

  12. Network synchronization in hippocampal neurons.

    PubMed

    Penn, Yaron; Segal, Menahem; Moses, Elisha

    2016-03-22

    Oscillatory activity is widespread in dynamic neuronal networks. The main paradigm for the origin of periodicity consists of specialized pacemaking elements that synchronize and drive the rest of the network; however, other models exist. Here, we studied the spontaneous emergence of synchronized periodic bursting in a network of cultured dissociated neurons from rat hippocampus and cortex. Surprisingly, about 60% of all active neurons were self-sustained oscillators when disconnected, each with its own natural frequency. The individual neuron's tendency to oscillate and the corresponding oscillation frequency are controlled by its excitability. The single neuron intrinsic oscillations were blocked by riluzole, and are thus dependent on persistent sodium leak currents. Upon a gradual retrieval of connectivity, the synchrony evolves: Loose synchrony appears already at weak connectivity, with the oscillators converging to one common oscillation frequency, yet shifted in phase across the population. Further strengthening of the connectivity causes a reduction in the mean phase shifts until zero-lag is achieved, manifested by synchronous periodic network bursts. Interestingly, the frequency of network bursting matches the average of the intrinsic frequencies. Overall, the network behaves like other universal systems, where order emerges spontaneously by entrainment of independent rhythmic units. Although simplified with respect to circuitry in the brain, our results attribute a basic functional role for intrinsic single neuron excitability mechanisms in driving the network's activity and dynamics, contributing to our understanding of developing neural circuits. PMID:26961000

  13. Maintainable substrate carrier for electroplating

    SciTech Connect

    Chen, Chen-An; Abas, Emmanuel Chua; Divino, Edmundo Anida; Ermita, Jake Randal G.; Capulong, Jose Francisco S.; Castillo, Arnold Villamor; Ma; Diana Xiaobing

    2012-07-17

    One embodiment relates to a substrate carrier for use in electroplating a plurality of substrates. The carrier includes a non-conductive carrier body on which the substrates are placed and conductive lines embedded within the carrier body. A plurality of conductive clip attachment parts are attached in a permanent manner to the conductive lines embedded within the carrier body. A plurality of contact clips are attached in a removable manner to the clip attachment parts. The contact clips hold the substrates in place and conductively connecting the substrates with the conductive lines. Other embodiments, aspects and features are also disclosed.

  14. Maintainable substrate carrier for electroplating

    DOEpatents

    Chen, Chen-An; Abas, Emmanuel Chua; Divino, Edmundo Anida; Ermita, Jake Randal G.; Capulong, Jose Francisco S.; Castillo, Arnold Villamor; Ma, Diana Xiaobing

    2016-08-02

    One embodiment relates to a substrate carrier for use in electroplating a plurality of substrates. The carrier includes a non-conductive carrier body on which the substrates are placed and conductive lines embedded within the carrier body. A plurality of conductive clip attachment parts are attached in a permanent manner to the conductive lines embedded within the carrier body. A plurality of contact clips are attached in a removable manner to the clip attachment parts. The contact clips hold the substrates in place and conductively connecting the substrates with the conductive lines. Other embodiments, aspects and features are also disclosed.

  15. Communication among neurons.

    PubMed

    Marner, Lisbeth

    2012-04-01

    The communication among neurons is the prerequisite for the working brain. To understand the cellular, neurochemical, and structural basis of this communication, and the impacts of aging and disease on brain function, quantitative measures are necessary. This thesis evaluates several quantitative neurobiological methods with respect to possible bias and methodological issues. Stereological methods are suited for the unbiased estimation of number, length, and volumes of components of the nervous system. Stereological estimates of the total length of myelinated nerve fibers were made in white matter of post mortem brains, and the impact of aging and diseases as Schizophrenia and Alzheimer's disease were evaluated. Although stereological methods are in principle unbiased, shrinkage artifacts are difficult to account for. Positron emission tomography (PET) recordings, in conjunction with kinetic modeling, permit the quantitation of radioligand binding in brain. The novel serotonin 5-HT4 antagonist [11C]SB207145 was used as an example of the validation process for quantitative PET receptor imaging. Methods based on reference tissue as well as methods based on an arterial plasma input function were evaluated with respect to precision and accuracy. It was shown that [11C]SB207145 binding had high sensitivity to occupancy by unlabeled ligand, necessitating high specific activity in the radiosynthesis to avoid bias. The established serotonin 5-HT2A ligand [18F]altanersin was evaluated in a two-year follow-up study in elderly subjects. Application of partial volume correction of the PET data diminished the reliability of the measures, but allowed for the correct distinction between changes due to brain atrophy and receptor availability. Furthermore, a PET study of patients with Alzheimer's disease with the serotonin transporter ligand [11C]DASB showed relatively preserved serotonergic projections, despite a marked decrease in 5-HT2A receptor binding. Possible confounders are

  16. Chip integrated fuel cell accumulator

    NASA Astrophysics Data System (ADS)

    Frank, M.; Erdler, G.; Frerichs, H.-P.; Müller, C.; Reinecke, H.

    A unique new design of a chip integrated fuel cell accumulator is presented. The system combines an electrolyser and a self-breathing polymer electrolyte membrane (PEM) fuel cell with integrated palladium hydrogen storage on a silicon substrate. Outstanding advantages of this assembly are the fuel cell with integrated hydrogen storage, the possibility of refuelling it by electrolysis and the opportunity of simply refilling the electrolyte by adding water. By applying an electrical current, wiring the palladium hydrogen storage as cathode and the counter-electrode as anode, the electrolyser produces hydrogen at the palladium surface and oxygen at the electrolyser cell anode. The generated hydrogen is absorbed by the palladium electrode and the hydrogen storage is refilled consequently enabling the fuel cell to function.

  17. Distinct sites on tenascin-C mediate repellent or adhesive interactions with different neuronal cell types.

    PubMed

    Husmann, K; Carbonetto, S; Schachner, M

    1995-11-01

    In this study we have determined the binding specificities of four different neuronal cell types to tenascin-C (TN-C) and laminin using a cell adhesion assay. TN-C was repulsive for small cerebellar neurons and PC12 phaeochromocytoma cells, since after short-term adhesion to the substrate-bound molecule with a maximum of cell binding at 45 min, the cells detached from the substrate and after 22 h only about 25% of the originally adherent cells were still bound. For N2A neuroblastoma cells and retinal cells TN-C was an adhesive substrate, since the number of adherent cells did not decrease after the initial attachment period. All four cell types adhered well to laminin at all time points studied. For short-term adhesion of small cerebellar neurons and PC12 cells two binding sites were identified on TN-C, one being localized within the epidermal growth factor-like repeats three to five and the second within fibronectin type III-like repeats three and four. One binding site for N2A and retinal cells was localized within fibronectin type III-like repeat seven. Binding of small cerebellar neurons to TN-C was dependent on Ca2+, but not on Mg2+ and was inhibitable by polyclonal antibodies to beta 1 integrin. Short-term adhesion of small cerebellar neurons was also inhibitable with a mixture of recombinant fragments of TN-C encompassing the whole molecule, although the specific inhibitory activity of this mixture was ten-fold lower on a molar basis when compared to the native molecule. Our observations indicate that different neuronal cell types use distinct binding sites on TN-C for repellent or adhesive interactions and that beta 1 integrin is involved in the recognition event leading to repulsion of small cerebellar neurons. PMID:8821032

  18. Spinal Cord Neuronal Precursors Generate Multiple Neuronal Phenotypes in Culture

    PubMed Central

    Kalyani, Anjali J.; Piper, David; Mujtaba, Tahmina; Lucero, Mary T.; Rao, Mahendra S.

    2010-01-01

    Neuronal restricted precursors (NRPs) (Mayer-Proschel et al., 1997) can generate multiple neurotransmitter phenotypes during maturation in culture. Undifferentiated E-NCAM+ (embryonic neural cell adhesion molecule) immunoreactive NRPs are mitotically active and electrically immature, and they express only a subset of neuronal markers. Fully mature cells are postmitotic, process-bearing cells that are neurofilament-M and synaptophysin immunoreactive, and they synthesize and respond to different subsets of neurotransmitter molecules. Mature neurons that synthesize and respond to glycine, glutamate, GABA, dopamine, and acetylcholine can be identified by immunocytochemistry, RT-PCR, and calcium imaging in mass cultures. Individual NRPs also generate heterogeneous progeny as assessed by neurotransmitter response and synthesis, demonstrating the multipotent nature of the precursor cells. Differentiation can be modulated by sonic hedgehog (Shh) and bone morphogenetic protein (BMP)-2/4 molecules. Shh acts as a mitogen and inhibits differentiation (including cholinergic differentiation). BMP-2 and BMP-4, in contrast, inhibit cell division and promote differentiation (including cholinergic differentiation). Thus, a single neuronal precursor cell can differentiate into multiple classes of neurons, and this differentiation can be modulated by environmental signals. PMID:9742154

  19. Interfacing neurons with carbon nanotubes: (re)engineering neuronal signaling.

    PubMed

    Fabbro, Alessandra; Cellot, Giada; Prato, Maurizio; Ballerini, Laura

    2011-01-01

    Carbon nanotubes (CNTs) are cylindrically shaped nanostructures made by sheets of graphene rolled up to form hollow tubes. Owing to their unique range of thermal, electronic, and structural properties, CNTs have been rapidly developing as a technology platform for biological and medical applications, including those designed to develop novel neuro-implantable devices. Depending on their structure, CNTs combine an incredible strength with an extreme flexibility. Further, these materials exhibit physical and chemical properties which allow them to efficiently conduit electrical current in electrochemical interfaces. CNTs can be organized in scaffolds made up of small fibers or tubes with diameters similar to those of neural processes such as axons and dendrites. Recently, CNT scaffolds have been found to promote growth, differentiation, and survival of neurons and to modify their electrophysiological properties. These features make CNTs an attractive material for the design of nano-bio hybrid systems able to govern cell-specific behaviors in cultured neuronal networks. The leading scope of this short review is to highlight how nanotube scaffolds can impact on neuronal signaling ability. In particular, we will focus on the direct and specific interactions between this synthetic nanomaterial and biological cell membranes, and on the ability of CNTs to improve interfaces developed to record or to stimulate neuronal activity. CNTs hold the potential for the development of innovative nanomaterial-based neurological implants. Therefore, it is particularly relevant to improve our knowledge on the impact on neuronal performance of interfacing nerve cells with CNTs. PMID:21867808

  20. Substrate inhibition of transketolase.

    PubMed

    Solovjeva, Olga N; Kovina, Marina V; Kochetov, German A

    2016-03-01

    We studied the influence of the acceptor substrate of transketolase on the activity of the enzyme in the presence of reductants. Ribose-5-phosphate in the presence of cyanoborohydride decreased the transketolase catalytic activity. The inhibition is caused by the loss of catalytic function of the coenzyme-thiamine diphosphate. Similar inhibitory effect was observed in the presence of NADPH. This could indicate its possible regulatory role not only towards transketolase, but also towards the pentose phosphate pathway of carbohydrate metabolism overall, taking into account the fact that it inhibits not only transketolase but also another enzyme of the pentose phosphate pathway--glucose 6-phosphate dehydrogenase [Eggleston L.V., Krebs H.A. Regulation of the pentose phosphate cycle, Biochem. J. 138 (1974) 425-435]. PMID:26708478

  1. Differential innervation of direct- and indirect-pathway striatal projection neurons

    PubMed Central

    Wall, Nicholas R.; De La Parra, Mauricio; Callaway, Edward M.; Kreitzer, Anatol C.

    2013-01-01

    SUMMARY The striatum integrates information from multiple brain regions to shape motor learning. The two major projection cell types in striatum target different downstream basal ganglia targets and have opposing effects on motivated behavior, yet differential innervation of these neuronal subtypes is not well understood. To examine whether input specificity provides a substrate for information segregation in these circuits, we used a monosynaptic rabies virus system to generate brain-wide maps of neurons that form synapses with direct- or indirect-pathway striatal projection neurons. We discovered that sensory cortical and limbic structures preferentially innervated the direct pathway, whereas motor cortex preferentially targeted the indirect pathway. Thalamostriatal input, dopaminergic input, as well as input from specific cortical layers, was similar onto both pathways. We also confirm synaptic innervation of striatal projection neurons by the raphe and pedunculopontine nuclei. Together, these findings provide a framework for guiding future studies of basal ganglia circuit function. PMID:23810541

  2. Murine Mueller cells are progenitor cells for neuronal cells and fibrous tissue cells

    SciTech Connect

    Florian, Christian; Langmann, Thomas; Weber, Bernhard H.F.; Morsczeck, Christian

    2008-09-19

    Mammalian Mueller cells have been reported to possess retinal progenitor cell properties and generate new neurons after injury. This study investigates murine Mueller cells under in vitro conditions for their capability of dedifferentiation into retinal progenitor cells. Mueller cells were isolated from mouse retina, and proliferating cells were expanded in serum-containing medium. For dedifferentiation, the cultured cells were transferred to serum-replacement medium (SRM) at different points in time after their isolation. Interestingly, early cell passages produced fibrous tissue in which extracellular matrix proteins and connective tissue markers were differentially expressed. In contrast, aged Mueller cell cultures formed neurospheres in SRM that are characteristic for neuronal progenitor cells. These neurospheres differentiated into neuron-like cells after cultivation on laminin/ornithine cell culture substrate. Here, we report for the first time that murine Mueller cells can be progenitors for both, fibrous tissue cells and neuronal cells, depending on the age of the cell culture.

  3. The neuronal architecture of the mushroom body provides a logic for associative learning.

    PubMed

    Aso, Yoshinori; Hattori, Daisuke; Yu, Yang; Johnston, Rebecca M; Iyer, Nirmala A; Ngo, Teri-T B; Dionne, Heather; Abbott, L F; Axel, Richard; Tanimoto, Hiromu; Rubin, Gerald M

    2014-01-01

    We identified the neurons comprising the Drosophila mushroom body (MB), an associative center in invertebrate brains, and provide a comprehensive map describing their potential connections. Each of the 21 MB output neuron (MBON) types elaborates segregated dendritic arbors along the parallel axons of ∼2000 Kenyon cells, forming 15 compartments that collectively tile the MB lobes. MBON axons project to five discrete neuropils outside of the MB and three MBON types form a feedforward network in the lobes. Each of the 20 dopaminergic neuron (DAN) types projects axons to one, or at most two, of the MBON compartments. Convergence of DAN axons on compartmentalized Kenyon cell-MBON synapses creates a highly ordered unit that can support learning to impose valence on sensory representations. The elucidation of the complement of neurons of the MB provides a comprehensive anatomical substrate from which one can infer a functional logic of associative olfactory learning and memory. PMID:25535793

  4. Rapid Encoding of New Memories by Individual Neurons in the Human Brain

    PubMed Central

    Ison, Matias J.; Quian Quiroga, Rodrigo; Fried, Itzhak

    2015-01-01

    Summary The creation of memories about real-life episodes requires rapid neuronal changes that may appear after a single occurrence of an event. How is such demand met by neurons in the medial temporal lobe (MTL), which plays a fundamental role in episodic memory formation? We recorded the activity of MTL neurons in neurosurgical patients while they learned new associations. Pairs of unrelated pictures, one of a person and another of a place, were used to construct a meaningful association modeling the episodic memory of meeting a person in a particular place. We found that a large proportion of responsive MTL neurons expanded their selectivity to encode these specific associations within a few trials: cells initially responsive to one picture started firing to the associated one but not to others. Our results provide a plausible neural substrate for the inception of associations, which are crucial for the formation of episodic memories. PMID:26139375

  5. A glutamatergic reward input from the dorsal raphe to ventral tegmental area dopamine neurons

    PubMed Central

    Qi, Jia; Zhang, Shiliang; Wang, Hui-Ling; Wang, Huikun; de Jesus Aceves Buendia, Jose; Hoffman, Alexander F.; Lupica, Carl R.; Seal, Rebecca P.; Morales, Marisela

    2014-01-01

    Electrical stimulation of the dorsal raphe (DR) and ventral tegmental area (VTA) activates the fibers of the same reward pathway but the phenotype of this pathway and the direction of the reward-relevant fibers have not been determined. Here we report rewarding effects following activation of a DR-originating pathway consisting of vesicular glutamate transporter 3 (VGluT3) containing neurons that form asymmetric synapses onto VTA dopamine neurons that project to nucleus accumbens. Optogenetic VTA activation of this projection elicits AMPA-mediated synaptic excitatory currents in VTA mesoaccumbens dopaminergic neurons and causes dopamine release innucleus accumbens. Activation also reinforces instrumental behavior and establishes conditioned place preferences. These findings indicate that the DR-VGluT3 pathway to VTA utilizes glutamate as a neurotransmitter and is a substrate linking the DR—one of the most sensitive reward sites in the brain—to VTA dopaminergic neurons. PMID:25388237

  6. Six Networks on a Universal Neuromorphic Computing Substrate

    PubMed Central

    Pfeil, Thomas; Grübl, Andreas; Jeltsch, Sebastian; Müller, Eric; Müller, Paul; Petrovici, Mihai A.; Schmuker, Michael; Brüderle, Daniel; Schemmel, Johannes; Meier, Karlheinz

    2013-01-01

    In this study, we present a highly configurable neuromorphic computing substrate and use it for emulating several types of neural networks. At the heart of this system lies a mixed-signal chip, with analog implementations of neurons and synapses and digital transmission of action potentials. Major advantages of this emulation device, which has been explicitly designed as a universal neural network emulator, are its inherent parallelism and high acceleration factor compared to conventional computers. Its configurability allows the realization of almost arbitrary network topologies and the use of widely varied neuronal and synaptic parameters. Fixed-pattern noise inherent to analog circuitry is reduced by calibration routines. An integrated development environment allows neuroscientists to operate the device without any prior knowledge of neuromorphic circuit design. As a showcase for the capabilities of the system, we describe the successful emulation of six different neural networks which cover a broad spectrum of both structure and functionality. PMID:23423583

  7. Fatty acid biosynthesis from glutamate and glutamine is specifically induced in neuronal cells under hypoxia

    PubMed Central

    Brose, Stephen A.; Marquardt, Amanda L.; Golovko, Mikhail Y.

    2014-01-01

    Hypoxia is involved in many neuronal and non-neuronal diseases, and defining the mechanisms for tissue adaptation to hypoxia is critical for the understanding and treatment of these diseases. One mechanism for tissue adaptation to hypoxia is increased glutamine and/or glutamate (Gln/Glu) utilization. To address this mechanism, we determined total Gln/Glu incorporation into lipids and fatty acids in both primary neurons and a neuronal cell line under normoxic and hypoxic conditions and compared this to non-neuronal primary cells and non-neuronal cell lines. Incorporation of Gln/Glu into total lipids was dramatically and specifically increased under hypoxia in neuronal cells including both primary (2.0- and 3.0- fold for Gln and Glu, respectively) and immortalized cultures (3.5- and 8.0- fold for Gln and Glu, respectively), and 90% to 97% of this increase was accounted for by incorporation into fatty acids (FA) depending upon substrate and cell type. All other non-neuronal cells tested demonstrated decreased or unchanged FA synthesis from Gln/Glu under hypoxia. Consistent with these data, total FA mass was also increased in neuronal cells under hypoxia that was mainly accounted for by the increase in saturated and monounsaturated FA with carbon length from 14 to 24. Incorporation of FA synthesized from Gln/Glu was increased in all major lipid classes including cholesteryl esters, TAGs, DAGs, free FA, and phospholipids, with the highest rate of incorporation into TAGs. These results indicate that increased FA biosynthesis from Gln/Glu followed by esterification may be a neuronal specific pathway for adaptation to hypoxia. PMID:24266789

  8. Nanocrystalline diamond surfaces for adhesion and growth of primary neurons, conflicting results and rational explanation

    PubMed Central

    Ojovan, Silviya M.; McDonald, Mathew; Rabieh, Noha; Shmuel, Nava; Erez, Hadas; Nesladek, Milos; Spira, Micha E.

    2014-01-01

    Using a variety of proliferating cell types, it was shown that the surface of nanocrystalline diamond (NCD) provides a permissive substrate for cell adhesion and development without the need of complex chemical functionalization prior to cell seeding. In an extensive series of experiments we found that, unlike proliferating cells, post-mitotic primary neurons do not adhere to bare NCD surfaces when cultured in defined medium. These observations raise questions on the potential use of bare NCD as an interfacing layer for neuronal devices. Nevertheless, we also found that classical chemical functionalization methods render the “hostile” bare NCD surfaces with adhesive properties that match those of classically functionalized substrates used extensively in biomedical research and applications. Based on the results, we propose a mechanism that accounts for the conflicting results; which on one hand claim that un-functionalized NCD provides a permissive substrate for cell adhesion and growth, while other reports demonstrate the opposite. PMID:24966832

  9. Fuel cells 101

    SciTech Connect

    Hirschenhofer, J.H.

    1999-07-01

    This paper discusses the various types of fuel cells, the importance of cell voltage, fuel processing for natural gas, cell stacking, fuel cell plant description, advantages and disadvantages of the types of fuel cells, and applications. The types covered include: polymer electrolyte fuel cell, alkaline fuel cell, phosphoric acid fuel cell; molten carbonate fuel cell, and solid oxide fuel cell.

  10. Turtle Dorsal Cortex Pyramidal Neurons Comprise Two Distinct Cell Types with Indistinguishable Visual Responses

    PubMed Central

    Crockett, Thomas; Wright, Nathaniel; Thornquist, Stephen; Ariel, Michael; Wessel, Ralf

    2015-01-01

    A detailed inventory of the constituent pieces in cerebral cortex is considered essential to understand the principles underlying cortical signal processing. Specifically, the search for pyramidal neuron subtypes is partly motivated by the hypothesis that a subtype-specific division of labor could create a rich substrate for computation. On the other hand, the extreme integration of individual neurons into the collective cortical circuit promotes the hypothesis that cellular individuality represents a smaller computational role within the context of the larger network. These competing hypotheses raise the important question to what extent the computational function of a neuron is determined by its individual type or by its circuit connections. We created electrophysiological profiles from pyramidal neurons within the sole cellular layer of turtle visual cortex by measuring responses to current injection using whole-cell recordings. A blind clustering algorithm applied to these data revealed the presence of two principle types of pyramidal neurons. Brief diffuse light flashes triggered membrane potential fluctuations in those same cortical neurons. The apparently network driven variability of the visual responses concealed the existence of subtypes. In conclusion, our results support the notion that the importance of diverse intrinsic physiological properties is minimized when neurons are embedded in a synaptic recurrent network. PMID:26633877

  11. Agarose microwell based neuronal micro-circuit arrays on microelectrode arrays for high throughput drug testing.

    PubMed

    Kang, Gyumin; Lee, Ji-Hye; Lee, Chang-Soo; Nam, Yoonkey

    2009-11-21

    For cell-based biosensor applications, dissociated neurons have been cultured on planar microelectrode arrays (MEAs) to measure the network activity with substrate-embedded microelectrodes. There has been a need for a multi-well type platform to reduce the data collection time and increase the statistical power for data analysis. This study presents a novel method to convert a conventional MEA into a multi-well MEA with an array of micrometre-sized neuronal culture ('neuronal micro-circuit array'). An MEA was coated first with cell-adhesive layer (poly-D-lysine) which was subsequently patterned with a cell-repulsive layer (agarose hydrogel) to both pattern the cell adhesive region and isolate neuronal micro-circuits from each other. For a few weeks, primary hippocampal neurons were cultured on the agarose microwell MEA and the development of spontaneous electrical activities were characterized with extracellular action potentials. Using neurotransmission modulators, the simultaneous monitoring of drug responses from neuronal micro-circuit arrays was also demonstrated. The proposed approach will be powerful for neurobiological functional assay studies or neuron-based biosensor fields which require repeated trials to obtain a single data point due to biological variations. PMID:19865730

  12. Phosphorylation of drebrin by cyclin-dependent kinase 5 and its role in neuronal migration.

    PubMed

    Tanabe, Kazuya; Yamazaki, Hiroyuki; Inaguma, Yutaka; Asada, Akiko; Kimura, Taeko; Takahashi, Junya; Taoka, Masato; Ohshima, Toshio; Furuichi, Teiichi; Isobe, Toshiaki; Nagata, Koh-ichi; Shirao, Tomoaki; Hisanaga, Shin-ichi

    2014-01-01

    Cyclin-dependent kinase 5 (Cdk5)-p35 is a proline-directed Ser/Thr kinase which plays a key role in neuronal migration, neurite outgrowth, and spine formation during brain development. Dynamic remodeling of cytoskeletons is required for all of these processes. Cdk5-p35 phosphorylates many cytoskeletal proteins, but it is not fully understood how Cdk5-p35 regulates cytoskeletal reorganization associated with neuronal migration. Since actin filaments are critical for the neuronal movement and process formation, we aimed to find Cdk5 substrates among actin-binding proteins. In this study, we isolated actin gels from mouse brain extracts, which contain many actin-binding proteins, and phosphorylated them by Cdk5-p35 in vitro. Drebrin, a side binding protein of actin filaments and well known for spine formation, was identified as a phosphorylated protein. Drebrin has two isoforms, an embryonic form drebrin E and an adult type long isoform drebrin A. Ser142 was identified as a common phosphorylation site to drebrin E and A and Ser342 as a drebrin A-specific site. Phosphorylated drebrin is localized at the distal area of total drebrin in the growth cone of cultured primary neurons. By expressing nonphosphorylatable or phosphorylation mimicking mutants in developing neurons in utero, the reversible phosphorylation/dephosphorylation reaction of drebrin was shown to be involved in radial migration of cortical neurons. These results suggest that Cdk5-p35 regulates neuronal migration through phosphorylation of drebrin in growth cone processes. PMID:24637538

  13. Properties of Neurons in External Globus Pallidus Can Support Optimal Action Selection

    PubMed Central

    Bogacz, Rafal; Martin Moraud, Eduardo; Abdi, Azzedine; Magill, Peter J.; Baufreton, Jérôme

    2016-01-01

    The external globus pallidus (GPe) is a key nucleus within basal ganglia circuits that are thought to be involved in action selection. A class of computational models assumes that, during action selection, the basal ganglia compute for all actions available in a given context the probabilities that they should be selected. These models suggest that a network of GPe and subthalamic nucleus (STN) neurons computes the normalization term in Bayes’ equation. In order to perform such computation, the GPe needs to send feedback to the STN equal to a particular function of the activity of STN neurons. However, the complex form of this function makes it unlikely that individual GPe neurons, or even a single GPe cell type, could compute it. Here, we demonstrate how this function could be computed within a network containing two types of GABAergic GPe projection neuron, so-called ‘prototypic’ and ‘arkypallidal’ neurons, that have different response properties in vivo and distinct connections. We compare our model predictions with the experimentally-reported connectivity and input-output functions (f-I curves) of the two populations of GPe neurons. We show that, together, these dichotomous cell types fulfil the requirements necessary to compute the function needed for optimal action selection. We conclude that, by virtue of their distinct response properties and connectivities, a network of arkypallidal and prototypic GPe neurons comprises a neural substrate capable of supporting the computation of the posterior probabilities of actions. PMID:27389780

  14. Effects of Electrical Stimulation in Sympathetic Neuron-Cardiomyocyte Co-cultures

    NASA Astrophysics Data System (ADS)

    Takeuchi, Akimasa; Tani, Hiromasa; Mori, Masahide; Moriguchi, Hiroyuki; Kotani, Kiyoshi; Lee, Jong-Kook; Noshiro, Makoto; Jimbo, Yasuhiko

    The sympathetic nervous system is one of the principal sources for regulating cardiovascular functions. Little is known, however, about the network-level interactions between sympathetic neurons and cardiomyocytes. In this study, a semi-separated co-culture system of superior cervical ganglion (SCG) neurons and ventricular myocytes (VMs) was developed by using a polydimethylsyloxane (PDMS) chamber placed on a microelectrode-array (MEA) substrate. Neurites of SCG neurons passed through a conduit of the chamber and reached VMs. Evoked activities of SCG neurons were observed from several electrodes immediately after applying constant-voltage stimulation (1 V, 1 ms, biphasic square pulses) to SCG neurons by using 32 electrodes. Furthermore, this stimulation was applied to SCG neurons at the frequency of 1, 5 and 10 Hz. After applying these three kinds of stimulations, mean minute contraction rate of VMs increased with an increase in the frequency of stimulation. These results suggest that changes in contraction rate of VMs after applying electrical stimulations to SCG neurons depend on frequencies of these stimulations and that the heart-regulating mechanisms as well as that in the body were formed in this co-culture system.

  15. In Vivo Evidence for a Lactate Gradient from Astrocytes to Neurons.

    PubMed

    Mächler, Philipp; Wyss, Matthias T; Elsayed, Maha; Stobart, Jillian; Gutierrez, Robin; von Faber-Castell, Alexandra; Kaelin, Vincens; Zuend, Marc; San Martín, Alejandro; Romero-Gómez, Ignacio; Baeza-Lehnert, Felipe; Lengacher, Sylvain; Schneider, Bernard L; Aebischer, Patrick; Magistretti, Pierre J; Barros, L Felipe; Weber, Bruno

    2016-01-12

    Investigating lactate dynamics in brain tissue is challenging, partly because in vivo data at cellular resolution are not available. We monitored lactate in cortical astrocytes and neurons of mice using the genetically encoded FRET sensor Laconic in combination with two-photon microscopy. An intravenous lactate injection rapidly increased the Laconic signal in both astrocytes and neurons, demonstrating high lactate permeability across tissue. The signal increase was significantly smaller in astrocytes, pointing to higher basal lactate levels in these cells, confirmed by a one-point calibration protocol. Trans-acceleration of the monocarboxylate transporter with pyruvate was able to reduce intracellular lactate in astrocytes but not in neurons. Collectively, these data provide in vivo evidence for a lactate gradient from astrocytes to neurons. This gradient is a prerequisite for a carrier-mediated lactate flux from astrocytes to neurons and thus supports the astrocyte-neuron lactate shuttle model, in which astrocyte-derived lactate acts as an energy substrate for neurons. PMID:26698914

  16. Properties of Neurons in External Globus Pallidus Can Support Optimal Action Selection.

    PubMed

    Bogacz, Rafal; Martin Moraud, Eduardo; Abdi, Azzedine; Magill, Peter J; Baufreton, Jérôme

    2016-07-01

    The external globus pallidus (GPe) is a key nucleus within basal ganglia circuits that are thought to be involved in action selection. A class of computational models assumes that, during action selection, the basal ganglia compute for all actions available in a given context the probabilities that they should be selected. These models suggest that a network of GPe and subthalamic nucleus (STN) neurons computes the normalization term in Bayes' equation. In order to perform such computation, the GPe needs to send feedback to the STN equal to a particular function of the activity of STN neurons. However, the complex form of this function makes it unlikely that individual GPe neurons, or even a single GPe cell type, could compute it. Here, we demonstrate how this function could be computed within a network containing two types of GABAergic GPe projection neuron, so-called 'prototypic' and 'arkypallidal' neurons, that have different response properties in vivo and distinct connections. We compare our model predictions with the experimentally-reported connectivity and input-output functions (f-I curves) of the two populations of GPe neurons. We show that, together, these dichotomous cell types fulfil the requirements necessary to compute the function needed for optimal action selection. We conclude that, by virtue of their distinct response properties and connectivities, a network of arkypallidal and prototypic GPe neurons comprises a neural substrate capable of supporting the computation of the posterior probabilities of actions. PMID:27389780

  17. Brain Neurons as Quantum Computers:

    NASA Astrophysics Data System (ADS)

    Bershadskii, A.; Dremencov, E.; Bershadskii, J.; Yadid, G.

    The question: whether quantum coherent states can sustain decoherence, heating and dissipation over time scales comparable to the dynamical timescales of brain neurons, has been actively discussed in the last years. A positive answer on this question is crucial, in particular, for consideration of brain neurons as quantum computers. This discussion was mainly based on theoretical arguments. In the present paper nonlinear statistical properties of the Ventral Tegmental Area (VTA) of genetically depressive limbic brain are studied in vivo on the Flinders Sensitive Line of rats (FSL). VTA plays a key role in the generation of pleasure and in the development of psychological drug addiction. We found that the FSL VTA (dopaminergic) neuron signals exhibit multifractal properties for interspike frequencies on the scales where healthy VTA dopaminergic neurons exhibit bursting activity. For high moments the observed multifractal (generalized dimensions) spectrum coincides with the generalized dimensions spectrum calculated for a spectral measure of a quantum system (so-called kicked Harper model, actively used as a model of quantum chaos). This observation can be considered as a first experimental (in vivo) indication in the favor of the quantum (at least partially) nature of brain neurons activity.

  18. Chondroitin sulfate and neuronal disorders.

    PubMed

    Miyata, Shinji; Kitagawa, Hiroshi

    2016-01-01

    The brain extracellular matrix (ECM) is involved in several aspects of neuronal development, plasticity, and pathophysiology. Chondroitin sulfate proteoglycans (CSPGs), consisting of core proteins with covalently attached chondroitin sulfate (CS) chains, are essential components of the brain ECM. During late postnatal development, CSPGs condense around parvalbumin-expressing inhibitory neurons (PV-cells) and form lattice-like ECM structures called perineuronal nets (PNNs). Enzymatic or genetic manipulation of PNNs reactivates neuronal plasticity in the adult brain, probably by resetting the excitatory/inhibitory balance in neural networks. Recent studies have indicated that PNNs control PV-cell function by enhancing the accumulation of specific proteins at the cell surface and/or acting as neuroprotective shields against oxidative stress. Since dysfunction of PV-cells and remodeling of CSPGs are commonly observed in several disorders, including schizophrenia, Costello syndrome, Alzheimer's disease, and epilepsy, modulation of PV-cell function by CSPGs may provide a novel strategy for these neuronal disorders. Here we review the potential roles of CSPGs as therapeutic targets for neuronal disorders, with particular focus on structural changes of CS chains under pathological conditions. PMID:27100510

  19. Neuronal factors determining high intelligence.

    PubMed

    Dicke, Ursula; Roth, Gerhard

    2016-01-01

    Many attempts have been made to correlate degrees of both animal and human intelligence with brain properties. With respect to mammals, a much-discussed trait concerns absolute and relative brain size, either uncorrected or corrected for body size. However, the correlation of both with degrees of intelligence yields large inconsistencies, because although they are regarded as the most intelligent mammals, monkeys and apes, including humans, have neither the absolutely nor the relatively largest brains. The best fit between brain traits and degrees of intelligence among mammals is reached by a combination of the number of cortical neurons, neuron packing density, interneuronal distance and axonal conduction velocity--factors that determine general information processing capacity (IPC), as reflected by general intelligence. The highest IPC is found in humans, followed by the great apes, Old World and New World monkeys. The IPC of cetaceans and elephants is much lower because of a thin cortex, low neuron packing density and low axonal conduction velocity. By contrast, corvid and psittacid birds have very small and densely packed pallial neurons and relatively many neurons, which, despite very small brain volumes, might explain their high intelligence. The evolution of a syntactical and grammatical language in humans most probably has served as an additional intelligence amplifier, which may have happened in songbirds and psittacids in a convergent manner. PMID:26598734

  20. Stochastic phase-change neurons

    NASA Astrophysics Data System (ADS)

    Tuma, Tomas; Pantazi, Angeliki; Le Gallo, Manuel; Sebastian, Abu; Eleftheriou, Evangelos

    2016-08-01

    Artificial neuromorphic systems based on populations of spiking neurons are an indispensable tool in understanding the human brain and in constructing neuromimetic computational systems. To reach areal and power efficiencies comparable to those seen in biological systems, electroionics-based and phase-change-based memristive devices have been explored as nanoscale counterparts of synapses. However, progress on scalable realizations of neurons has so far been limited. Here, we show that chalcogenide-based phase-change materials can be used to create an artificial neuron in which the membrane potential is represented by the phase configuration of the nanoscale phase-change device. By exploiting the physics of reversible amorphous-to-crystal phase transitions, we show that the temporal integration of postsynaptic potentials can be achieved on a nanosecond timescale. Moreover, we show that this is inherently stochastic because of the melt-quench-induced reconfiguration of the atomic structure occurring when the neuron is reset. We demonstrate the use of these phase-change neurons, and their populations, in the detection of temporal correlations in parallel data streams and in sub-Nyquist representation of high-bandwidth signals.

  1. Stochastic phase-change neurons.

    PubMed

    Tuma, Tomas; Pantazi, Angeliki; Le Gallo, Manuel; Sebastian, Abu; Eleftheriou, Evangelos

    2016-08-01

    Artificial neuromorphic systems based on populations of spiking neurons are an indispensable tool in understanding the human brain and in constructing neuromimetic computational systems. To reach areal and power efficiencies comparable to those seen in biological systems, electroionics-based and phase-change-based memristive devices have been explored as nanoscale counterparts of synapses. However, progress on scalable realizations of neurons has so far been limited. Here, we show that chalcogenide-based phase-change materials can be used to create an artificial neuron in which the membrane potential is represented by the phase configuration of the nanoscale phase-change device. By exploiting the physics of reversible amorphous-to-crystal phase transitions, we show that the temporal integration of postsynaptic potentials can be achieved on a nanosecond timescale. Moreover, we show that this is inherently stochastic because of the melt-quench-induced reconfiguration of the atomic structure occurring when the neuron is reset. We demonstrate the use of these phase-change neurons, and their populations, in the detection of temporal correlations in parallel data streams and in sub-Nyquist representation of high-bandwidth signals. PMID:27183057

  2. Nuclear fuel elements having a composite cladding

    DOEpatents

    Gordon, Gerald M.; Cowan, II, Robert L.; Davies, John H.

    1983-09-20

    An improved nuclear fuel element is disclosed for use in the core of nuclear reactors. The improved nuclear fuel element has a composite cladding of an outer portion forming a substrate having on the inside surface a metal layer selected from the group consisting of copper, nickel, iron and alloys of the foregoing with a gap between the composite cladding and the core of nuclear fuel. The nuclear fuel element comprises a container of the elongated composite cladding, a central core of a body of nuclear fuel material disposed in and partially filling the container and forming an internal cavity in the container, an enclosure integrally secured and sealed at each end of said container and a nuclear fuel material retaining means positioned in the cavity. The metal layer of the composite cladding prevents perforations or failures in the cladding substrate from stress corrosion cracking or from fuel pellet-cladding interaction or both. The substrate of the composite cladding is selected from conventional cladding materials and preferably is a zirconium alloy.

  3. PLZT capacitor on glass substrate

    DOEpatents

    Fairchild, M. Ray; Taylor, Ralph S.; Berlin, Carl W.; Wong, Celine W. K.; Ma, Beihai; Balachandran, Uthamalingam

    2016-01-05

    A lead-lanthanum-zirconium-titanate (PLZT) capacitor on a substrate formed of glass. The first metallization layer is deposited on a top side of the substrate to form a first electrode. The dielectric layer of PLZT is deposited over the first metallization layer. The second metallization layer deposited over the dielectric layer to form a second electrode. The glass substrate is advantageous as glass is compatible with an annealing process used to form the capacitor.

  4. PLZT capacitor on glass substrate

    DOEpatents

    Fairchild, Manuel Ray; Taylor, Ralph S.; Berlin, Carl W.; Wong, Celine Wk; Ma, Beihai; Balachandran, Uthamalingam

    2016-03-29

    A lead-lanthanum-zirconium-titanate (PLZT) capacitor on a substrate formed of glass. The first metallization layer is deposited on a top side of the substrate to form a first electrode. The dielectric layer of PLZT is deposited over the first metallization layer. The second metallization layer deposited over the dielectric layer to form a second electrode. The glass substrate is advantageous as glass is compatible with an annealing process used to form the capacitor.

  5. Endogenous recovery after brain damage: molecular mechanisms that balance neuronal life/death fate.

    PubMed

    Tovar-y-Romo, Luis B; Penagos-Puig, Andrés; Ramírez-Jarquín, Josué O

    2016-01-01

    Neuronal survival depends on multiple factors that comprise a well-fueled energy metabolism, trophic input, clearance of toxic substances, appropriate redox environment, integrity of blood-brain barrier, suppression of programmed cell death pathways and cell cycle arrest. Disturbances of brain homeostasis lead to acute or chronic alterations that might ultimately cause neuronal death with consequent impairment of neurological function. Although we understand most of these processes well when they occur independently from one another, we still lack a clear grasp of the concerted cellular and molecular mechanisms activated upon neuronal damage that intervene in protecting damaged neurons from death. In this review, we summarize a handful of endogenously activated mechanisms that balance molecular cues so as to determine whether neurons recover from injury or die. We center our discussion on mechanisms that have been identified to participate in stroke, although we consider different scenarios of chronic neurodegeneration as well. We discuss two central processes that are involved in endogenous repair and that, when not regulated, could lead to tissue damage, namely, trophic support and neuroinflammation. We emphasize the need to construct integrated models of neuronal degeneration and survival that, in the end, converge in neuronal fate after injury. Under neurodegenerative conditions, endogenously activated mechanisms balance out molecular cues that determine whether neurons contend toxicity or die. Many processes involved in endogenous repair may as well lead to tissue damage depending on the strength of stimuli. Signaling mediated by trophic factors and neuroinflammation are examples of these processes as they regulate different mechanisms that mediate neuronal demise including necrosis, apoptosis, necroptosis, pyroptosis and autophagy. In this review, we discuss recent findings on balanced regulation and their involvement in neuronal death. PMID:26376102

  6. Fuel injector

    DOEpatents

    Lambeth, Malcolm David Dick

    2001-02-27

    A fuel injector comprises first and second housing parts, the first housing part being located within a bore or recess formed in the second housing part, the housing parts defining therebetween an inlet chamber, a delivery chamber axially spaced from the inlet chamber, and a filtration flow path interconnecting the inlet and delivery chambers to remove particulate contaminants from the flow of fuel therebetween.

  7. Pedestal substrate for coated optics

    DOEpatents

    Hale, Layton C.; Malsbury, Terry N.; Patterson, Steven R.

    2001-01-01

    A pedestal optical substrate that simultaneously provides high substrate dynamic stiffness, provides low surface figure sensitivity to mechanical mounting hardware inputs, and constrains surface figure changes caused by optical coatings to be primarily spherical in nature. The pedestal optical substrate includes a disk-like optic or substrate section having a top surface that is coated, a disk-like base section that provides location at which the substrate can be mounted, and a connecting cylindrical section between the base and optics or substrate sections. The connecting cylindrical section may be attached via three spaced legs or members. However, the pedestal optical substrate can be manufactured from a solid piece of material to form a monolith, thus avoiding joints between the sections, or the disk-like base can be formed separately and connected to the connecting section. By way of example, the pedestal optical substrate may be utilized in the fabrication of optics for an extreme ultraviolet (EUV) lithography imaging system, or in any optical system requiring coated optics and substrates with reduced sensitivity to mechanical mounts.

  8. Sealed substrate carrier for electroplating

    DOEpatents

    Ganti, Kalyana Bhargava

    2012-07-17

    One embodiment relates to a substrate carrier for use in electroplating a plurality of substrates. The substrate carrier includes a non-conductive carrier body on which the substrates are held, and conductive lines are embedded within the carrier body. A conductive bus bar is embedded into a top side of the carrier body and is conductively coupled to the conductive lines. A thermoplastic overmold covers a portion of the bus bar, and there is a plastic-to-plastic bond between the thermoplastic overmold and the non-conductive carrier body. Other embodiments, aspects and features are also disclosed.

  9. Chimera states in bursting neurons

    NASA Astrophysics Data System (ADS)

    Bera, Bidesh K.; Ghosh, Dibakar; Lakshmanan, M.

    2016-01-01

    We study the existence of chimera states in pulse-coupled networks of bursting Hindmarsh-Rose neurons with nonlocal, global, and local (nearest neighbor) couplings. Through a linear stability analysis, we discuss the behavior of the stability function in the incoherent (i.e., disorder), coherent, chimera, and multichimera states. Surprisingly, we find that chimera and multichimera states occur even using local nearest neighbor interaction in a network of identical bursting neurons alone. This is in contrast with the existence of chimera states in populations of nonlocally or globally coupled oscillators. A chemical synaptic coupling function is used which plays a key role in the emergence of chimera states in bursting neurons. The existence of chimera, multichimera, coherent, and disordered states is confirmed by means of the recently introduced statistical measures and mean phase velocity.

  10. Towards a Neuronal Gauge Theory.

    PubMed

    Sengupta, Biswa; Tozzi, Arturo; Cooray, Gerald K; Douglas, Pamela K; Friston, Karl J

    2016-03-01

    Given the amount of knowledge and data accruing in the neurosciences, is it time to formulate a general principle for neuronal dynamics that holds at evolutionary, developmental, and perceptual timescales? In this paper, we propose that the brain (and other self-organised biological systems) can be characterised via the mathematical apparatus of a gauge theory. The picture that emerges from this approach suggests that any biological system (from a neuron to an organism) can be cast as resolving uncertainty about its external milieu, either by changing its internal states or its relationship to the environment. Using formal arguments, we show that a gauge theory for neuronal dynamics--based on approximate Bayesian inference--has the potential to shed new light on phenomena that have thus far eluded a formal description, such as attention and the link between action and perception. PMID:26953636

  11. The neuronal code for number.

    PubMed

    Nieder, Andreas

    2016-06-01

    Humans and non-human primates share an elemental quantification system that resides in a dedicated neural network in the parietal and frontal lobes. In this cortical network, 'number neurons' encode the number of elements in a set, its cardinality or numerosity, irrespective of stimulus appearance across sensory motor systems, and from both spatial and temporal presentation arrays. After numbers have been extracted from sensory input, they need to be processed to support goal-directed behaviour. Studying number neurons provides insights into how information is maintained in working memory and transformed in tasks that require rule-based decisions. Beyond an understanding of how cardinal numbers are encoded, number processing provides a window into the neuronal mechanisms of high-level brain functions. PMID:27150407

  12. Microtubule dynamics in neuronal morphogenesis.

    PubMed

    Sakakibara, Akira; Ando, Ryota; Sapir, Tamar; Tanaka, Teruyuki

    2013-07-01

    Microtubules (MTs) are essential for neuronal morphogenesis in the developing brain. The MT cytoskeleton provides physical support to shape the fine structure of neuronal processes. MT-based motors play important roles in nucleokinesis, process formation and retraction. Regulation of MT stability downstream of extracellular cues is proposed to be critical for axonogenesis. Axons and dendrites exhibit different patterns of MT organization, underlying the divergent functions of these processes. Centrosomal positioning has drawn the attention of researchers because it is a major clue to understanding neuronal MT organization. In this review, we focus on how recent advances in live imaging have revealed the dynamics of MT organization and centrosome positioning during neural development. PMID:23864552

  13. Towards a Neuronal Gauge Theory

    PubMed Central

    Sengupta, Biswa; Tozzi, Arturo; Cooray, Gerald K.; Douglas, Pamela K.; Friston, Karl J.

    2016-01-01

    Given the amount of knowledge and data accruing in the neurosciences, is it time to formulate a general principle for neuronal dynamics that holds at evolutionary, developmental, and perceptual timescales? In this paper, we propose that the brain (and other self-organised biological systems) can be characterised via the mathematical apparatus of a gauge theory. The picture that emerges from this approach suggests that any biological system (from a neuron to an organism) can be cast as resolving uncertainty about its external milieu, either by changing its internal states or its relationship to the environment. Using formal arguments, we show that a gauge theory for neuronal dynamics—based on approximate Bayesian inference—has the potential to shed new light on phenomena that have thus far eluded a formal description, such as attention and the link between action and perception. PMID:26953636

  14. Correlations and Neuronal Population Information.

    PubMed

    Kohn, Adam; Coen-Cagli, Ruben; Kanitscheider, Ingmar; Pouget, Alexandre

    2016-07-01

    Brain function involves the activity of neuronal populations. Much recent effort has been devoted to measuring the activity of neuronal populations in different parts of the brain under various experimental conditions. Population activity patterns contain rich structure, yet many studies have focused on measuring pairwise relationships between members of a larger population-termed noise correlations. Here we review recent progress in understanding how these correlations affect population information, how information should be quantified, and what mechanisms may give rise to correlations. As population coding theory has improved, it has made clear that some forms of correlation are more important for information than others. We argue that this is a critical lesson for those interested in neuronal population responses more generally: Descriptions of population responses should be motivated by and linked to well-specified function. Within this context, we offer suggestions of where current theoretical frameworks fall short. PMID:27145916

  15. Microtubule dynamics in neuronal morphogenesis

    PubMed Central

    Sakakibara, Akira; Ando, Ryota; Sapir, Tamar; Tanaka, Teruyuki

    2013-01-01

    Microtubules (MTs) are essential for neuronal morphogenesis in the developing brain. The MT cytoskeleton provides physical support to shape the fine structure of neuronal processes. MT-based motors play important roles in nucleokinesis, process formation and retraction. Regulation of MT stability downstream of extracellular cues is proposed to be critical for axonogenesis. Axons and dendrites exhibit different patterns of MT organization, underlying the divergent functions of these processes. Centrosomal positioning has drawn the attention of researchers because it is a major clue to understanding neuronal MT organization. In this review, we focus on how recent advances in live imaging have revealed the dynamics of MT organization and centrosome positioning during neural development. PMID:23864552

  16. The microRNA bantam functions in epithelial cells to regulate scaling growth of dendrite arbors in Drosophila sensory neurons

    PubMed Central

    Parrish, Jay Z.; Xu, Peizhang; Kim, Charles C.; Jan, Lily Yeh; Jan, Yuh Nung

    2009-01-01

    Summary In addition to establishing dendritic coverage of the receptive field, neurons need to adjust their dendritic arbors to match changes of the receptive field. Here we show that dendrite arborization (da) sensory neurons establish dendritic coverage of the body wall early in Drosophila larval development and then grow in precise proportion to their substrate, the underlying body wall epithelium, as the larva more than triples in length. This phenomenon, referred to as scaling growth of dendrites, requires the function of the microRNA (miRNA) bantam (ban) in the epithelial cells rather than the da neurons themselves. We further show that ban in epithelial cells dampens Akt kinase activity in adjacent neurons to influence dendrite growth. This signaling between epithelial cells and neurons receiving sensory input from the body wall synchronizes their growth to ensure proper dendritic coverage of the receptive field. PMID:19778508

  17. Neuronal plasticity: adaptation and readaptation to the environment of space

    NASA Technical Reports Server (NTRS)

    Correia, M. J.

    1998-01-01

    While there have been few documented permanent neurological changes resulting from space travel, there is a growing literature which suggests that neural plasticity sometimes occurs within peripheral and central vestibular pathways during and following spaceflight. This plasticity probably has adaptive value within the context of the space environment, but it can be maladaptive upon return to the terrestrial environment. Fortunately, the maladaptive responses resulting from neuronal plasticity diminish following return to earth. However, the literature suggests that the longer the space travel, the more difficult the readaptation. With the possibility of extended space voyages and extended stays on board the international space station, it seems worthwhile to review examples of plastic vestibular responses and changes in the underlying neural substrates. Studies and facilities needed for space station investigation of plastic changes in the neural substrates are suggested. Copyright 1998 Elsevier Science B.V.

  18. ETHANOL ACTION ON DOPAMINERGIC NEURONS IN THE VENTRAL TEGMENTAL AREA: INTERACTION WITH INTRINSIC ION CHANNELS AND NEUROTRANSMITTER INPUTS

    PubMed Central

    Morikawa, Hitoshi; Morrisett, Richard A.

    2010-01-01

    The dopaminergic system originating in the midbrain ventral tegmental area (VTA) has been extensively studied over the past decades as a critical neural substrate involved in the development of alcoholism and addiction to other drugs of abuse. Accumulating evidence indicates that ethanol modulates the functional output of this system by directly affecting the firing activity of VTA dopamine neurons, whereas withdrawal from chronic ethanol exposure leads to a reduction in the functional output of these neurons. This chapter will provide an update on the mechanistic investigations of the acute ethanol action on dopamine neuron activity and the neuroadaptations/plasticities in the VTA produced by previous ethanol experience. PMID:20813245

  19. Copying and Evolution of Neuronal Topology

    PubMed Central

    Fernando, Chrisantha; Karishma, K. K.; Szathmáry, Eörs

    2008-01-01

    We propose a mechanism for copying of neuronal networks that is of considerable interest for neuroscience for it suggests a neuronal basis for causal inference, function copying, and natural selection within the human brain. To date, no model of neuronal topology copying exists. We present three increasingly sophisticated mechanisms to demonstrate how topographic map formation coupled with Spike-Time Dependent Plasticity (STDP) can copy neuronal topology motifs. Fidelity is improved by error correction and activity-reverberation limitation. The high-fidelity topology-copying operator is used to evolve neuronal topologies. Possible roles for neuronal natural selection are discussed. PMID:19020662

  20. Rescuing neurons in prion disease.

    PubMed

    Verity, Nicholas C; Mallucci, Giovanna R

    2011-01-01

    One of the major current challenges to both medicine and neuroscience is the treatment of neurodegenerative diseases, which pose an ever-increasing medical, social and economic burden in the developed world. These disorders, which include Alzheimer's, Huntington's and Parkinson's diseases, and the rarer prion diseases, are separate entities clinically but have common features, including aggregates of misfolded proteins and varying patterns of neurodegeneration. A key barrier to effective treatment is that patients present clinically with advanced, irreversible, neuronal loss. Critically, mechanisms of neurotoxicity are poorly understood. Prevention of neuronal loss, ideally by targeting underlying pathogenic mechanisms, must be the aim of therapy. The present review describes the rationale and experimental approaches that have allowed such prevention, rescuing neurons in mice with prion disease. This rescue cured animals of a rapidly fatal neurodegenerative condition, resulting in symptom-free survival for their natural lifespan. Early pathological changes were reversed; behavioural, cognitive and neurophysiological deficits were recovered; and there was no neuronal loss. This was achieved by targeting the central pathogenic process in prion disease rather than the presumed toxic species, first by proof-of-principle experiments in transgenic mice and then by treatment using RNA interference for gene knockdown. The results have been a new therapeutic target for prion disease, further insight into mechanisms of prion neurotoxicity and the discovery of a window of reversibility in neuronal damage. Furthermore, the work gives rise to new concepts for treatment strategies for other neurodegenerative disorders, and highlights the need for clinical detection of early neuronal dysfunction, so that similar early rescue can also be achieved for these disorders. PMID:21158739

  1. Neuronal Deletion of Ghrelin Receptor Almost Completely Prevents Diet-Induced Obesity.

    PubMed

    Lee, Jong Han; Lin, Ligen; Xu, Pingwen; Saito, Kenji; Wei, Qiong; Meadows, Adelina G; Bongmba, Odelia Y N; Pradhan, Geetali; Zheng, Hui; Xu, Yong; Sun, Yuxiang

    2016-08-01

    Ghrelin signaling has major effects on energy and glucose homeostasis, but it is unknown whether ghrelin's functions are centrally and/or peripherally mediated. The ghrelin receptor, growth hormone secretagogue receptor (GHS-R), is highly expressed in the brain and detectable in some peripheral tissues. To understand the roles of neuronal GHS-R, we generated a mouse line where Ghsr gene is deleted in all neurons using synapsin 1 (Syn1)-Cre driver. Our data showed that neuronal Ghsr deletion abolishes ghrelin-induced spontaneous food intake but has no effect on total energy intake. Remarkably, neuronal Ghsr deletion almost completely prevented diet-induced obesity (DIO) and significantly improved insulin sensitivity. The neuronal Ghsr-deleted mice also showed improved metabolic flexibility, indicative of better adaption to different fuels. In addition, gene expression analysis suggested that hypothalamus and/or midbrain might be the sites that mediate the effects of GHS-R in thermogenesis and physical activity, respectively. Collectively, our results indicate that neuronal GHS-R is a crucial regulator of energy metabolism and a key mediator of DIO. Neuronal Ghsr deletion protects against DIO by regulating energy expenditure, not by energy intake. These novel findings suggest that suppressing central ghrelin signaling may serve as a unique antiobesity strategy. PMID:27207529

  2. Nitric oxide in neuronal degeneration.

    PubMed

    Dawson, V L; Dawson, T M

    1996-01-01

    NO has clearly revolutionized our thinking about aspects of neurotransmission and neuronal signaling. NO is emerging as an important regulator of a variety of physiologic processes; however, under conditions of excessive or inappropriate formation, NO is also emerging as an important mediator of pathologic nervous tissue damage. Uncovering and understanding the targets of NO that contribute to the neuropathologic process will hopefully lead to the development of selective therapeutic agents and to a better understanding of basic processes underlying normal and pathological neuronal functions. PMID:8594616

  3. Carbon nanotubes on a substrate

    DOEpatents

    Gao, Yufei [Kennewick, WA; Liu, Jun [West Richland, WA

    2002-03-26

    The present invention includes carbon nanotubes whose hollow cores are 100% filled with conductive filler. The carbon nanotubes are in uniform arrays on a conductive substrate and are well-aligned and can be densely packed. The uniformity of the carbon nanotube arrays is indicated by the uniform length and diameter of the carbon nanotubes, both which vary from nanotube to nanotube on a given array by no more than about 5%. The alignment of the carbon nanotubes is indicated by the perpendicular growth of the nanotubes from the substrates which is achieved in part by the simultaneous growth of the conductive filler within the hollow core of the nanotube and the densely packed growth of the nanotubes. The present invention provides a densely packed carbon nanotube growth where each nanotube is in contact with at least one nearest-neighbor nanotube. The substrate is a conductive substrate coated with a growth catalyst, and the conductive filler can be single crystals of carbide formed by a solid state reaction between the substrate material and the growth catalyst. The present invention further provides a method for making the filled carbon nanotubes on the conductive substrates. The method includes the steps of depositing a growth catalyst onto the conductive substrate as a prepared substrate, creating a vacuum within a vessel which contains the prepared substrate, flowing H2/inert (e.g. Ar) gas within the vessel to increase and maintain the pressure within the vessel, increasing the temperature of the prepared substrate, and changing the H2/Ar gas to ethylene gas such that the ethylene gas flows within the vessel. Additionally, varying the density and separation of the catalyst particles on the conductive substrate can be used to control the diameter of the nanotubes.

  4. Morphological Substrates for Parallel Streams of Corticogeniculate Feedback Originating in Both V1 and V2 of the Macaque Monkey.

    PubMed

    Briggs, Farran; Kiley, Caitlin W; Callaway, Edward M; Usrey, W Martin

    2016-04-20

    Corticothalamic circuits are essential for reciprocal information exchange between the thalamus and cerebral cortex. Nevertheless, the role of corticothalamic circuits in sensory processing remains a mystery. In the visual system, afferents from retina to the lateral geniculate nucleus (LGN) and from LGN to primary visual cortex (V1) are organized into functionally distinct parallel processing streams. Physiological evidence suggests corticogeniculate feedback may be organized into parallel streams; however, little is known about the diversity of corticogeniculate neurons, their local computations, or the structure-function relationship among corticogeniculate neurons. We used a virus-mediated approach to label and reconstruct the complete dendritic and local axonal arbors of identified corticogeniculate neurons in the macaque monkey. Our results reveal morphological substrates for parallel streams of corticogeniculate feedback based on distinct classes of neurons in V1 and V2. These results support the hypothesis that distinct populations of feedback neurons provide independent and unique information to the LGN. PMID:27041497

  5. Characterization of cutaneous and articular sensory neurons

    PubMed Central

    da Silva Serra, Ines; Husson, Zoé; Bartlett, Jonathan D.

    2016-01-01

    Background A wide range of stimuli can activate sensory neurons and neurons innervating specific tissues often have distinct properties. Here, we used retrograde tracing to identify sensory neurons innervating the hind paw skin (cutaneous) and ankle/knee joints (articular), and combined immunohistochemistry and electrophysiology analysis to determine the neurochemical phenotype of cutaneous and articular neurons, as well as their electrical and chemical excitability. Results Immunohistochemistry analysis using RetroBeads as a retrograde tracer confirmed previous data that cutaneous and articular neurons are a mixture of myelinated and unmyelinated neurons, and the majority of both populations are peptidergic. In whole-cell patch-clamp recordings from cultured dorsal root ganglion neurons, voltage-gated inward currents and action potential parameters were largely similar between articular and cutaneous neurons, although cutaneous neuron action potentials had a longer half-peak duration (HPD). An assessment of chemical sensitivity showed that all neurons responded to a pH 5.0 solution, but that acid-sensing ion channel (ASIC) currents, determined by inhibition with the nonselective acid-sensing ion channel antagonist benzamil, were of a greater magnitude in cutaneous compared to articular neurons. Forty to fifty percent of cutaneous and articular neurons responded to capsaicin, cinnamaldehyde, and menthol, indicating similar expression levels of transient receptor potential vanilloid 1 (TRPV1), transient receptor potential ankyrin 1 (TRPA1), and transient receptor potential melastatin 8 (TRPM8), respectively. By contrast, significantly more articular neurons responded to ATP than cutaneous neurons. Conclusion This work makes a detailed characterization of cutaneous and articular sensory neurons and highlights the importance of making recordings from identified neuronal populations: sensory neurons innervating different tissues have subtly different properties

  6. Fuel cell-fuel cell hybrid system

    DOEpatents

    Geisbrecht, Rodney A.; Williams, Mark C.

    2003-09-23

    A device for converting chemical energy to electricity is provided, the device comprising a high temperature fuel cell with the ability for partially oxidizing and completely reforming fuel, and a low temperature fuel cell juxtaposed to said high temperature fuel cell so as to utilize remaining reformed fuel from the high temperature fuel cell. Also provided is a method for producing electricity comprising directing fuel to a first fuel cell, completely oxidizing a first portion of the fuel and partially oxidizing a second portion of the fuel, directing the second fuel portion to a second fuel cell, allowing the first fuel cell to utilize the first portion of the fuel to produce electricity; and allowing the second fuel cell to utilize the second portion of the fuel to produce electricity.

  7. Glutamate-induced metabolic changes influence the cytoplasmic redox state of hippocampal neurons.

    PubMed

    Porras, Omar H; Stutzin, Andrés

    2011-07-22

    Brain cell metabolism is intimately associated with intracellular oxidation-reduction (redox) balance. Glutamatergic transmission is accompanied with changes in substrate preference in neurons. Therefore, we studied cytoplasmatic redox changes in hippocampal neurons in culture exposed to glutamate. Neurons were transfected with HyPer, a genetically encoded redox biosensor for hydrogen peroxide which allows real-time imaging of the redox state. The rate of fluorescence decay, corresponding to the reduction of the biosensor was found to be augmented by low doses of glutamate (10 μM) as well as by pharmacological stimulation of NMDA glutamate receptors. Acute chelation of extracellular Ca(2+) abolished the glutamate-induced effect observed on HyPer fluorescence. Additional experiments indicated that mitochondrial function and hence energetic substrate availability commands the redox state of neurons and is required for the glutamate effect observed on the biosensor signal. Furthermore, our results implicated astrocytic metabolism in the changes of neuronal redox state observed with glutamate. PMID:21708127

  8. Controlled Adhesion and Growth of Long Term Glial and Neuronal Cultures on Parylene-C

    PubMed Central

    Delivopoulos, Evangelos; Murray, Alan F.

    2011-01-01

    This paper explores the long term development of networks of glia and neurons on patterns of Parylene-C on a SiO2 substrate. We harvested glia and neurons from the Sprague-Dawley (P1–P7) rat hippocampus and utilized an established cell patterning technique in order to investigate cellular migration, over the course of 3 weeks. This work demonstrates that uncontrolled glial mitosis gradually disrupts cellular patterns that are established early during culture. This effect is not attributed to a loss of protein from the Parylene-C surface, as nitrogen levels on the substrate remain stable over 3 weeks. The inclusion of the anti-mitotic cytarabine (Ara-C) in the culture medium moderates glial division and thus, adequately preserves initial glial and neuronal conformity to underlying patterns. Neuronal apoptosis, often associated with the use of Ara-C, is mitigated by the addition of brain derived neurotrophic factor (BDNF). We believe that with the right combination of glial inhibitors and neuronal promoters, the Parylene-C based cell patterning method can generate structured, active neural networks that can be sustained and investigated over extended periods of time. To our knowledge this is the first report on the concurrent application of Ara-C and BDNF on patterned cell cultures. PMID:21966523

  9. Which Neurons Will Be the Engram - Activated Neurons and/or More Excitable Neurons?

    PubMed Central

    Kim, Ji-il; Cho, Hye-Yeon; Han, Jin-Hee

    2016-01-01

    During past decades, the formation and storage principle of memory have received much attention in the neuroscience field. Although some studies have attempted to demonstrate the nature of the engram, elucidating the memory engram allocation mechanism was not possible because of the limitations of existing methods, which cannot specifically modulate the candidate neuronal population. Recently, the development of new techniques, which offer ways to mark and control specific populations of neurons, may accelerate solving this issue. Here, we review the recent advances, which have provided substantial evidence showing that both candidates (neuronal population that is activated by learning, and that has increased CREB level/excitability at learning) satisfy the criteria of the engram, which are necessary and sufficient for memory expression. PMID:27122991

  10. Substrate With Low Secondary Emissions

    NASA Technical Reports Server (NTRS)

    Jensen, Kenneth A. (Inventor); Curren, Arthur N. (Inventor); Roman, Robert F. (Inventor)

    2000-01-01

    The present invention is directed to a method and apparatus for producing a highly -textured surface on a copper substrate -with only extremely small amounts of texture-inducing seeding or masking material. The texture-inducing seeding material is delivered to the copper substrate electrically switching the seeding material in and out of a circuit loop.

  11. Photoresist substrate having robust adhesion

    DOEpatents

    Dentinger, Paul M.

    2005-07-26

    A substrate material for LIGA applications w hose general composition is Ti/Cu/Ti/SiO.sub.2. The SiO.sub.2 is preferably applied to the Ti/Cu/Ti wafer as a sputtered coating, typically about 100 nm thick. This substrate composition provides improved adhesion for epoxy-based photoresist materials, and particularly the photoresist material SU-8.

  12. Fuel ethanol

    SciTech Connect

    Not Available

    1989-02-01

    This report discusses the Omnibus Trade and Competitiveness Act of 1988 which requires GAO to examine fuel ethanol imports from Central America and the Caribbean and their impact on the U.S. fuel ethanol industry. Ethanol is the alcohol in beverages, such as beer, wine, and whiskey. It can also be used as a fuel by blending with gasoline. It can be made from renewable resources, such as corn, wheat, grapes, and sugarcane, through a process of fermentation. This report finds that, given current sugar and gasoline prices, it is not economically feasible for Caribbean ethanol producers to meet the current local feedstock requirement.

  13. FUEL ELEMENT

    DOEpatents

    Bean, R.W.

    1963-11-19

    A ceramic fuel element for a nuclear reactor that has improved structural stability as well as improved cooling and fission product retention characteristics is presented. The fuel element includes a plurality of stacked hollow ceramic moderator blocks arranged along a tubular raetallic shroud that encloses a series of axially apertured moderator cylinders spaced inwardly of the shroud. A plurality of ceramic nuclear fuel rods are arranged in the annular space between the shroud and cylinders of moderator and appropriate support means and means for directing gas coolant through the annular space are also provided. (AEC)

  14. Composite substrate for bipolar electrodes

    DOEpatents

    Tekkanat, B.; Bolstad, J.J.

    1992-12-22

    Substrates for electrode systems, particularly those to be used for bipolar electrodes in zinc-bromine batteries, are disclosed. The substrates preferably include carbon-black as a conductive filler in a polymeric matrix, with reinforcing materials such as glass fibers. Warpage of the zinc-bromine electrodes which was experienced in the prior art and which was believed to be caused by physical expansion of the electrodes due to bromine absorption by the carbon-black, is substantially eliminated when new substrate fabrication techniques are employed. In the present invention, substrates are prepared using a lamination process known as glass mat reinforced thermoplastics technology or, in an alternate embodiment, the substrate is made using a slurry process. 4 figs.

  15. Composite substrate for bipolar electrodes

    DOEpatents

    Tekkanat, Bora; Bolstad, James J.

    1992-12-22

    Substrates for electrode systems, particularly those to be used for bipolar electrodes in zinc-bromine batteries, are disclosed. The substrates preferably include carbon-black as a conductive filler in a polymeric matrix, with reinforcing materials such as glass fibers. Warpage of the zinc-bromine electrodes which was experienced in the prior art and which was believed to be caused by physical expansion of the electrodes due to bromine absorption by the carbon-black, is substantially eliminated when new substrate fabrication techniques are employed. In the pesent invention, substrates are prepared using a lamination process known as glass mat reinforced thermoplastics technology or, in an alternate embodiment, the substrate is made using a slurry process.

  16. Electrospray Ionization on Solid Substrates

    PubMed Central

    So, Pui-Kin; Hu, Bin; Yao, Zhong-Ping

    2014-01-01

    Development of electrospray ionization on solid substrates (solid-substrate ESI) avoids the clogging problem encountered in conventional capillary-based ESI, allows more convenient sampling and permits new applications. So far, solid-substrate ESI with various materials, e.g., metals, paper, wood, fibers and biological tissue, has been developed, and applications ranging from analysis of pure compounds to complex mixtures as well as in vivo study were demonstrated. Particularly, the capability of solid-substrate ESI in direct analysis of complex samples, e.g., biological fluids and foods, has significantly facilitated mass spectrometric analysis in real-life applications and led to increasingly important roles of these techniques nowadays. In this review, various solid-substrate ESI techniques and their applications are summarized and the prospects in this field are discussed. PMID:26819900

  17. Outputs of radula mechanoafferent neurons in Aplysia are modulated by motor neurons, interneurons, and sensory neurons.

    PubMed

    Rosen, S C; Miller, M W; Cropper, E C; Kupfermann, I

    2000-03-01

    The gain of sensory inputs into the nervous system can be modulated so that the nature and intensity of afferent input is variable. Sometimes the variability is a function of other sensory inputs or of the state of motor systems that generate behavior. A form of sensory modulation was investigated in the Aplysia feeding system at the level of a radula mechanoafferent neuron (B21) that provides chemical synaptic input to a group of motor neurons (B8a/b, B15) that control closure and retraction movements of the radula, a food grasping structure. B21 has been shown to receive both excitatory and inhibitory synaptic inputs from a variety of neuron types. The current study investigated the morphological basis of these heterosynaptic inputs, whether the inputs could serve to modulate the chemical synaptic outputs of B21, and whether the neurons producing the heterosynaptic inputs were periodically active during feeding motor programs that might modulate B21 outputs in a phase-specific manner. Four cell types making monosynaptic connections to B21 were found capable of heterosynaptically modulating the chemical synaptic output of B21 to motor neurons B8a and B15. These included the following: 1) other sensory neurons, e.g. , B22; 2) interneurons, e.g., B19; 3) motor neurons, e.g., B82; and 4) multifunction neurons that have sensory, motor, and interneuronal functions, e.g., B4/5. Each cell type was phasically active in one or more feeding motor programs driven by command-like interneurons, including an egestive motor program driven by CBI-1 and an ingestive motor program driven by CBI-2. Moreover, the phase of activity differed for each of the modulator cells. During the motor programs, shifts in B21 membrane potential were related to the activity patterns of some of the modulator cells. Inhibitory chemical synapses mediated the modulation produced by B4/5, whereas excitatory and/or electrical synapses were involved in the other instances. The data indicate that

  18. Turning Heads: Development of Vertebrate Branchiomotor Neurons

    PubMed Central

    Chandrasekhar, Anand

    2007-01-01

    The cranial motor neurons innervate muscles that control eye, jaw, and facial movements of the vertebrate head and parasympathetic neurons that innervate certain glands and organs. These efferent neurons develop at characteristic locations in the brainstem, and their axons exit the neural tube in well-defined trajectories to innervate target tissues. This review is focused on a subset of cranial motor neurons called the branchiomotor neurons, which innervate muscles derived from the branchial (pharyngeal) arches. First, the organization of the branchiomotor pathways in zebrafish, chick, and mouse embryos will be compared, and the underlying axon guidance mechanisms will be addressed. Next, the molecular mechanisms that generate branchiomotor neurons and specify their identities will be discussed. Finally, the caudally directed or tangential migration of facial branchiomotor neurons will be examined. Given the advances in the characterization and analysis of vertebrate genomes, we can expect rapid progress in elucidating the cellular and molecular mechanisms underlying the development of these vital neuronal networks. PMID:14699587

  19. Network of hypothalamic neurons that control appetite

    PubMed Central

    Sohn, Jong-Woo

    2015-01-01

    The central nervous system (CNS) controls food intake and energy expenditure via tight coordinations between multiple neuronal populations. Specifically, two distinct neuronal populations exist in the arcuate nucleus of hypothalamus (ARH): the anorexigenic (appetite-suppressing) pro-opiomelanocortin (POMC) neurons and the orexigenic (appetite-increasing) neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons. The coordinated regulation of neuronal circuit involving these neurons is essential in properly maintaining energy balance, and any disturbance therein may result in hyperphagia/obesity or hypophagia/starvation. Thus, adequate knowledge of the POMC and NPY/AgRP neuron physiology is mandatory to understand the pathophysiology of obesity and related metabolic diseases. This review will discuss the history and recent updates on the POMC and NPY/AgRP neuronal circuits, as well as the general anorexigenic and orexigenic circuits in the CNS. [BMB Reports 2015; 48(4): 229-233] PMID:25560696

  20. Neuronal activity controls transsynaptic geometry.

    PubMed

    Glebov, Oleg O; Cox, Susan; Humphreys, Lawrence; Burrone, Juan

    2016-01-01

    The neuronal synapse is comprised of several distinct zones, including presynaptic vesicle zone (SVZ), active zone (AZ) and postsynaptic density (PSD). While correct relative positioning of these zones is believed to be essential for synaptic function, the mechanisms controlling their mutual localization remain unexplored. Here, we employ high-throughput quantitative confocal imaging, super-resolution and electron microscopy to visualize organization of synaptic subdomains in hippocampal neurons. Silencing of neuronal activity leads to reversible reorganization of the synaptic geometry, resulting in a increased overlap between immunostained AZ and PSD markers; in contrast, the SVZ-AZ spatial coupling is decreased. Bayesian blinking and bleaching (3B) reconstruction reveals that the distance between the AZ-PSD distance is decreased by 30 nm, while electron microscopy shows that the width of the synaptic cleft is decreased by 1.1 nm. Our findings show that multiple aspects of synaptic geometry are dynamically controlled by neuronal activity and suggest mutual repositioning of synaptic components as a potential novel mechanism contributing to the homeostatic forms of synaptic plasticity. PMID:26951792

  1. Hypothalamic neuronal responses to cytokines.

    PubMed Central

    Shibata, M.

    1990-01-01

    Fever has been extensively studied in the past few decades. The hypothesis that hypothalamic thermosensitive neurons play a major role in both normal thermoregulation and in fever production and lysis has particularly helped to advance our understanding of the neuronal mechanisms underlying the response to pyrogens. Furthermore, new data in the study of host defense responses induced by pyrogenic cytokines such as interleukin 1, interferon alpha 2, tumor necrosis factor alpha, and interleukin 6 have demonstrated that those factors have multiple, yet coordinated, regulatory activities in the central nervous system, so that our understanding of the role of the brain in the activity of these agents requires a new perspective and dimension. Thus, recent evidence from our laboratory indicates that blood-borne cytokines may be detected in the organum vasculosum laminae terminalis and transduced there into neuronal signals. Such signals may then affect distinct, but partially overlapping, sets of neuronal systems in the preoptic area of the anterior hypothalamus, mediating directly and/or indirectly the array of various host defense responses characteristic of infection that are thought to be induced by blood-borne cytokines. PMID:2205055

  2. Regeneration: New Neurons Wire Up.

    PubMed

    Raymond, Pamela A

    2016-09-12

    Functional repair of damage in the nervous system requires re-establishment of precise patterns of synaptic connectivity. A new study shows that after selective ablation, zebrafish retinal neurons regenerate and reconstruct some, although not all, of their stereotypic wiring. PMID:27623258

  3. Glia Get Neurons in Shape.

    PubMed

    Sun, Lu O; Barres, Ben A

    2016-05-01

    Glial cells are essential components of the nervous system. In this issue, Singhvi et al. uncover cellular and molecular mechanisms through which C. elegans glia shape sensory neuron terminals and thus control animal thermosensing behaviors. PMID:27153490

  4. Modeling neuronal vulnerability in ALS.

    PubMed

    Roselli, Francesco; Caroni, Pico

    2014-08-20

    Using computational models of motor neuron ion fluxes, firing properties, and energy requirements, Le Masson et al. (2014) reveal how local imbalances in energy homeostasis may self-amplify and contribute to neurodegeneration in ALS. PMID:25144872

  5. Biomechanics of Single Cortical Neurons

    PubMed Central

    Bernick, Kristin B.; Prevost, Thibault P.; Suresh, Subra; Socrate, Simona

    2011-01-01

    This study presents experimental results and computational analysis of the large strain dynamic behavior of single neurons in vitro with the objective of formulating a novel quantitative framework for the biomechanics of cortical neurons. Relying on the atomic force microscopy (AFM) technique, novel testing protocols are developed to enable the characterization of neural soma deformability over a range of indentation rates spanning three orders of magnitude – 10, 1, and 0.1 μm/s. Modified spherical AFM probes were utilized to compress the cell bodies of neonatal rat cortical neurons in load, unload, reload and relaxation conditions. The cell response showed marked hysteretic features, strong non-linearities, and substantial time/rate dependencies. The rheological data were complemented with geometrical measurements of cell body morphology, i.e. cross-diameter and height estimates. A constitutive model, validated by the present experiments, is proposed to quantify the mechanical behavior of cortical neurons. The model aimed to correlate empirical findings with measurable degrees of (hyper-) elastic resilience and viscosity at the cell level. The proposed formulation, predicated upon previous constitutive model developments undertaken at the cortical tissue level, was implemented into a three-dimensional finite element framework. The simulated cell response was calibrated to the experimental measurements under the selected test conditions, providing a novel single cell model that could form the basis for further refinements. PMID:20971217

  6. Neuronal activity controls transsynaptic geometry

    PubMed Central

    Glebov, Oleg O.; Cox, Susan; Humphreys, Lawrence; Burrone, Juan

    2016-01-01

    The neuronal synapse is comprised of several distinct zones, including presynaptic vesicle zone (SVZ), active zone (AZ) and postsynaptic density (PSD). While correct relative positioning of these zones is believed to be essential for synaptic function, the mechanisms controlling their mutual localization remain unexplored. Here, we employ high-throughput quantitative confocal imaging, super-resolution and electron microscopy to visualize organization of synaptic subdomains in hippocampal neurons. Silencing of neuronal activity leads to reversible reorganization of the synaptic geometry, resulting in a increased overlap between immunostained AZ and PSD markers; in contrast, the SVZ-AZ spatial coupling is decreased. Bayesian blinking and bleaching (3B) reconstruction reveals that the distance between the AZ-PSD distance is decreased by 30 nm, while electron microscopy shows that the width of the synaptic cleft is decreased by 1.1 nm. Our findings show that multiple aspects of synaptic geometry are dynamically controlled by neuronal activity and suggest mutual repositioning of synaptic components as a potential novel mechanism contributing to the homeostatic forms of synaptic plasticity. PMID:26951792

  7. The Neuronal Infrastructure of Speaking

    ERIC Educational Resources Information Center

    Menenti, Laura; Segaert, Katrien; Hagoort, Peter

    2012-01-01

    Models of speaking distinguish producing meaning, words and syntax as three different linguistic components of speaking. Nevertheless, little is known about the brain's integrated neuronal infrastructure for speech production. We investigated semantic, lexical and syntactic aspects of speaking using fMRI. In a picture description task, we…

  8. Electrophysiology of raccoon cuneocerebellar neurons.

    PubMed

    Haring, J H; Rowinski, M J; Pubols, B H

    1984-01-01

    Electrophysiological experiments were undertaken in order to locate and functionally characterize cells of the raccoon main cuneate nucleus (MCN) that can be activated by electrical stimulation of the cerebellum. A total of 98 such units were studied in pentobarbital sodium-anesthetized, methoxyflurane-anesthetized, or decerebrate preparations. Aside from a greater likelihood of resting discharge in the decerebrate preparations, no appreciable variability in physiological properties of the neurons could be attributed to differences in the type of preparation. Using constant latency of response and ability to be blocked by collision as principal criteria, both antidromically (n = 31) and synaptically (n = 67) activated neurons of the main cuneate nucleus could be identified. A small number of MCN neurons could be activated by both cerebellar and thalamic stimulation, but no unit was antidromically activated from both locations. MCN neurons projecting to the cerebellum are located primarily in the ventral polymorphic cell region of the nucleus at and rostral to the obex, corresponding to the "medial tongue" region of Johnson et al. (1968). In contrast, neurons synaptically activated from the cerebellum are found throughout the dorsoventral extent of the rostral MCN, including the "clusters" region. The majority of antidromically activated units responded to mechanical stimulation of deeper tissues, and most of these were activated by muscle stretch. Only a small portion (13-15%) of either antidromically or synaptically activated units were classed as light touch units with peripheral receptive fields (RFs) restricted to glabrous surfaces of the forepaw. Glabrous skin RFs located on the digital surfaces are smaller than those located on the palm pads. In both cases, RFs are larger than those associated with primary afferent fibers, but toward the low end of the distribution for MCN neurons not activated by cerebellar stimulation. All MCN units activated by cerebellar

  9. Prospective Coding by Spiking Neurons

    PubMed Central

    Brea, Johanni; Gaál, Alexisz Tamás; Senn, Walter

    2016-01-01

    Animals learn to make predictions, such as associating the sound of a bell with upcoming feeding or predicting a movement that a motor command is eliciting. How predictions are realized on the neuronal level and what plasticity rule underlies their learning is not well understood. Here we propose a biologically plausible synaptic plasticity rule to learn predictions on a single neuron level on a timescale of seconds. The learning rule allows a spiking two-compartment neuron to match its current firing rate to its own expected future discounted firing rate. For instance, if an originally neutral event is repeatedly followed by an event that elevates the firing rate of a neuron, the originally neutral event will eventually also elevate the neuron’s firing rate. The plasticity rule is a form of spike timing dependent plasticity in which a presynaptic spike followed by a postsynaptic spike leads to potentiation. Even if the plasticity window has a width of 20 milliseconds, associations on the time scale of seconds can be learned. We illustrate prospective coding with three examples: learning to predict a time varying input, learning to predict the next stimulus in a delayed paired-associate task and learning with a recurrent network to reproduce a temporally compressed version of a sequence. We discuss the potential role of the learning mechanism in classical trace conditioning. In the special case that the signal to be predicted encodes reward, the neuron learns to predict the discounted future reward and learning is closely related to the temporal difference learning algorithm TD(λ). PMID:27341100

  10. Fuel composition

    SciTech Connect

    Johnson, T.H.

    1990-06-26

    This patent describes a motor fuel composition. It comprises: a mixture of hydrocarbons in the gasoline boiling range containing a deposit preventing or reducing effective amount of poly(olefin)-N-substituted- carbamate.

  11. Activation of brainstem neurons by underwater diving in the rat.

    PubMed

    Panneton, W Michael; Gan, Qi; Le, Jason; Livergood, Robert S; Clerc, Philip; Juric, Rajko

    2012-01-01

    The mammalian diving response is a powerful autonomic adjustment to underwater submersion greatly affecting heart rate, arterial blood pressure, and ventilation. The bradycardia is mediated by the parasympathetic nervous system, arterial blood pressure is mediated via the sympathetic system and still other circuits mediate the respiratory changes. In the present study we investigate the cardiorespiratory responses and the brainstem neurons activated by voluntary diving of trained rats, and, compare them to control and swimming animals which did not dive. We show that the bradycardia and increase in arterial blood pressure induced by diving were significantly different than that induced by swimming. Neuronal activation was calculated after immunohistochemical processing of brainstem sections for Fos protein. Labeled neurons were counted in the caudal pressor area, the medullary dorsal horn, subnuclei of the nucleus tractus solitarii (NTS), the nucleus raphe pallidus (RPa), the rostroventrolateral medulla, the A5 area, the nucleus locus coeruleus, the Kölliker-Fuse area, and the external lateral and superior lateral subnuclei of the parabrachial nucleus. All these areas showed significant increases in Fos labeling when data from voluntary diving rats were compared to control rats and all but the commissural subnucleus of the NTS, A5 area, and RPa were significantly different from swimming rats. These data provide a substrate for more precise experiments to determine the role of these nuclei in the reflex circuits driving the diving response. PMID:22563319

  12. In vitro studies of primary explosive blast loading on neurons.

    PubMed

    Zander, Nicole E; Piehler, Thuvan; Boggs, Mary E; Banton, Rohan; Benjamin, Richard

    2015-09-01

    In a military setting, traumatic brain injury (TBI) is frequently caused by blast waves that can trigger a series of neuronal biochemical changes. Although many animal models have been used to study the effects of primary blast waves, elucidating the mechanisms of damage in a whole-animal model is extremely complex. In vitro models of primary blast, which allow for the deconvolution of mechanisms, are relatively scarce. It is largely unknown how structural damage at the cellular level impacts the functional activity at variable time scales after the TBI event. A novel in vitro system was developed to probe the effects of explosive blast (ranging from ∼25 to 40 psi) on dissociated neurons. PC12 neurons were cultured on laminin-coated substrates, submerged underwater, and subjected to single and multiple blasts in a controlled environment. Changes in cell membrane permeability, viability, and cell morphology were evaluated. Significant increases in axonal beading were observed in the injured cells. In addition, although cell death was minimal after a single insult, cell viability decreased significantly following repeated blast exposure. PMID:25914380

  13. Activation of Brainstem Neurons by Underwater Diving in the Rat

    PubMed Central

    Panneton, W. Michael; Gan, Qi; Le, Jason; Livergood, Robert S.; Clerc, Philip; Juric, Rajko

    2012-01-01

    The mammalian diving response is a powerful autonomic adjustment to underwater submersion greatly affecting heart rate, arterial blood pressure, and ventilation. The bradycardia is mediated by the parasympathetic nervous system, arterial blood pressure is mediated via the sympathetic system and still other circuits mediate the respiratory changes. In the present study we investigate the cardiorespiratory responses and the brainstem neurons activated by voluntary diving of trained rats, and, compare them to control and swimming animals which did not dive. We show that the bradycardia and increase in arterial blood pressure induced by diving were significantly different than that induced by swimming. Neuronal activation was calculated after immunohistochemical processing of brainstem sections for Fos protein. Labeled neurons were counted in the caudal pressor area, the medullary dorsal horn, subnuclei of the nucleus tractus solitarii (NTS), the nucleus raphe pallidus (RPa), the rostroventrolateral medulla, the A5 area, the nucleus locus coeruleus, the Kölliker–Fuse area, and the external lateral and superior lateral subnuclei of the parabrachial nucleus. All these areas showed significant increases in Fos labeling when data from voluntary diving rats were compared to control rats and all but the commissural subnucleus of the NTS, A5 area, and RPa were significantly different from swimming rats. These data provide a substrate for more precise experiments to determine the role of these nuclei in the reflex circuits driving the diving response. PMID:22563319

  14. Mapping Generative Models onto a Network of Digital Spiking Neurons.

    PubMed

    Pedroni, Bruno U; Das, Srinjoy; Arthur, John V; Merolla, Paul A; Jackson, Bryan L; Modha, Dharmendra S; Kreutz-Delgado, Kenneth; Cauwenberghs, Gert

    2016-08-01

    Stochastic neural networks such as Restricted Boltzmann Machines (RBMs) have been successfully used in applications ranging from speech recognition to image classification, and are particularly interesting because of their potential for generative tasks. Inference and learning in these algorithms use a Markov Chain Monte Carlo procedure called Gibbs sampling, where a logistic function forms the kernel of this sampler. On the other side of the spectrum, neuromorphic systems have shown great promise for low-power and parallelized cognitive computing, but lack well-suited applications and automation procedures. In this work, we propose a systematic method for bridging the RBM algorithm and digital neuromorphic systems, with a generative pattern completion task as proof of concept. For this, we first propose a method of producing the Gibbs sampler using bio-inspired digital noisy integrate-and-fire neurons. Next, we describe the process of mapping generative RBMs trained offline onto the IBM TrueNorth neurosynaptic processor-a low-power digital neuromorphic VLSI substrate. Mapping these algorithms onto neuromorphic hardware presents unique challenges in network connectivity and weight and bias quantization, which, in turn, require architectural and design strategies for the physical realization. Generative performance is analyzed to validate the neuromorphic requirements and to best select the neuron parameters for the model. Lastly, we describe a design automation procedure which achieves optimal resource usage, accounting for the novel hardware adaptations. This work represents the first implementation of generative RBM inference on a neuromorphic VLSI substrate. PMID:27214915

  15. NEURONAL PHOSPHOPROTEINS: PHYSIOLOGICAL AND CLINICAL IMPLICATIONS

    EPA Science Inventory

    The presence of a great variety of neuron-specific phosproteins in nervous tissue supports the view that protein phosphorylation plays many roles in neuronal function. The physiological significance of several of these phosphoproteins has already been established. Some neuronal p...

  16. Primary Culture of Mouse Dopaminergic Neurons

    PubMed Central

    Gaven, Florence; Marin, Philippe; Claeysen, Sylvie

    2014-01-01

    Dopaminergic neurons represent less than 1% of the total number of neurons in the brain. This low amount of neurons regulates important brain functions such as motor control, motivation, and working memory. Nigrostriatal dopaminergic neurons selectively degenerate in Parkinson's disease (PD). This progressive neuronal loss is unequivocally associated with the motors symptoms of the pathology (bradykinesia, resting tremor, and muscular rigidity). The main agent responsible of dopaminergic neuron degeneration is still unknown. However, these neurons appear to be extremely vulnerable in diverse conditions. Primary cultures constitute one of the most relevant models to investigate properties and characteristics of dopaminergic neurons. These cultures can be submitted to various stress agents that mimic PD pathology and to neuroprotective compounds in order to stop or slow down neuronal degeneration. The numerous transgenic mouse models of PD that have been generated during the last decade further increased the interest of researchers for dopaminergic neuron cultures. Here, the video protocol focuses on the delicate dissection of embryonic mouse brains. Precise excision of ventral mesencephalon is crucial to obtain neuronal cultures sufficiently rich in dopaminergic cells to allow subsequent studies. This protocol can be realized with embryonic transgenic mice and is suitable for immunofluorescence staining, quantitative PCR, second messenger quantification, or neuronal death/survival assessment. PMID:25226064

  17. Spontaneous Calcium Changes in Micro Neuronal Networks

    NASA Astrophysics Data System (ADS)

    Saito, Aki; Moriguchi, Hiroyuki; Iwabuchi, Shin; Goto, Miho; Takayama, Yuzo; Kotani, Kiyoshi; Jimbo, Yasuhiko

    We have developed a practical experimental method to mass-produce and maintain a variation of minimal neuronal networks (“micro neuronal networks”) consisted of a single to several neurons in culture using spray-patterning technique. In this paper, we could maintain the micro-cultures for one month or more by adding conditioned medium and carried out optical recording of spontaneous activity in micro neuronal networks and considered the interactions between them. To determine the interactions between micro neuronal networks, fluorescence changes in several small networks were simultaneously measured using calcium indicator dye fluo-4 AM, and time-series analysis was carried out using surrogate arrangements. By using the spray-patterning method, a large number of cell-adhesive micro regions were formed. Neurons extended neurites along the edge of the cell-adhesive micro regions and form micro neuronal networks. In part of micro regions, some neurite was protruded from the region, and thus micro neuronal networks were connected with synapses. In these networks, a single neuron-induced network activity was observed. On the other hand, even in morphologically non-connected micro neuronal networks, synchronous oscillations between micro neuronal networks were observed. Our micro-patterning methods and results provide the possibility that synchronous activity is occurred between morphologically non-connected neuronal networks. This suggest that the humoral factor is also a important component for network-wide dynamics.

  18. Oscillating from Neurosecretion to Multitasking Dopamine Neurons

    PubMed Central

    Grattan, David R.; Akopian, Armen N.

    2016-01-01

    In this issue of Cell Reports, Stagkourakis et al. (2016) report that oscillating hypothalamic TIDA neurons, previously thought to be simple neurosecretory neurons controlling pituitary prolactin secretion, control dopamine output via autoregulatory mechanisms and thus could potentially regulate other physiologically important hypothalamic neuronal circuits. PMID:27119847

  19. Substrate-Sensitive Graphene Oxidation.

    PubMed

    Zhang, Zhuhua; Yin, Jun; Liu, Xiaofei; Li, Jidong; Zhang, Jiahuan; Guo, Wanlin

    2016-03-01

    The inertness of graphene toward reaction with ambient molecules is essential for realizing durable devices with stable performance. Many device applications require graphene to contact with substrates, but whose impact on the chemical property of graphene has been largely overlooked. Here, we combine comprehensive first-principles analyses with experiments to show that graphene oxidation is highly sensitive to substrates. Graphene remains inert on SiO2 and hexagonal boron nitride but becomes increasingly weak against oxidation on metal substrates because of enhanced charge transfer and chemical interaction between them. In particular, Ni and Co substrates lead to spontaneous oxidation of graphene, while a Cu substrate maximally promotes the oxygen diffusion on graphene, with an estimated diffusivity 13 orders of magnitude higher than that on freestanding graphene. Bilayer graphene is revealed to have high oxidation resistance independent of substrate and thus is a better choice for high-performance nanoelectronics. Our findings should be extendable to a wide spectrum of chemical functionalizations of two-dimensional materials mediated by substrates. PMID:26884318

  20. Neurophysical substrates of arousal and attention.

    PubMed

    Pop-Jordanov, Jordan; Pop-Jordanova, Nada

    2009-02-01

    The study of arousal and attention could be of prominent importance for elucidating both fundamental and practical aspects of the mind-brain puzzle. Defined as "general activation of mind" (Kahnemann in Attention and effort. Prentice-Hall, New Jersey, 1973), or "general operation of consciousness" (Thacher and John in Functional neuroscience: foundations of cognitive processing. Erlbaum, Hillsdale, 1977), arousal can be considered as a starting point of fundamental research on consciousness. Similar role could be assigned to attention, which can be defined by substituting the attributes "general" with "focused". Concerning the practical applications, the empirically established correlation between neuronal oscillations and arousal/attention levels is widely used in research and clinics, including neurofeedback, brain-computer communication, etc. However, the neurophysical mechanism underlying this correlation is still not clear enough. In this paper, after reviewing some present classical and quantum approaches, a transition probability concept of arousal based on field-dipole quantum interactions and information entropy is elaborated. The obtained analytical expressions and numerical values correspond to classical empirical results for arousal and attention, including the characteristic frequency dependence and intervals. Simultaneously, the fundamental (substrate) role of EEG spectrum has been enlightened, whereby the attention appears to be a bridge between arousal and the content of consciousness. Finally, some clinical implications, including the brain-rate parameter as an indicator of arousal and attention levels, are provided. PMID:18975019

  1. Method of processing a substrate

    DOEpatents

    Babayan, Steven E.; Hicks, Robert F.

    2008-02-12

    The invention is embodied in a plasma flow device or reactor having a housing that contains conductive electrodes with openings to allow gas to flow through or around them, where one or more of the electrodes are powered by an RF source and one or more are grounded, and a substrate or work piece is placed in the gas flow downstream of the electrodes, such that said substrate or work piece is substantially uniformly contacted across a large surface area with the reactive gases emanating therefrom. The invention is also embodied in a plasma flow device or reactor having a housing that contains conductive electrodes with openings to allow gas to flow through or around them, where one or more of the electrodes are powered by an RF source and one or more are grounded, and one of the grounded electrodes contains a means of mixing in other chemical precursors to combine with the plasma stream, and a substrate or work piece placed in the gas flow downstream of the electrodes, such that said substrate or work piece is contacted by the reactive gases emanating therefrom. In one embodiment, the plasma flow device removes organic materials from a substrate or work piece, and is a stripping or cleaning device. In another embodiment, the plasma flow device kills biological microorganisms on a substrate or work piece, and is a sterilization device. In another embodiment, the plasma flow device activates the surface of a substrate or work piece, and is a surface activation device. In another embodiment, the plasma flow device etches materials from a substrate or work piece, and is a plasma etcher. In another embodiment, the plasma flow device deposits thin films onto a substrate or work piece, and is a plasma-enhanced chemical vapor deposition device or reactor.

  2. Boron hydride polymer coated substrates

    DOEpatents

    Pearson, Richard K.; Bystroff, Roman I.; Miller, Dale E.

    1987-01-01

    A method is disclosed for coating a substrate with a uniformly smooth layer of a boron hydride polymer. The method comprises providing a reaction chamber which contains the substrate and the boron hydride plasma. A boron hydride feed stock is introduced into the chamber simultaneously with the generation of a plasma discharge within the chamber. A boron hydride plasma of ions, electrons and free radicals which is generated by the plasma discharge interacts to form a uniformly smooth boron hydride polymer which is deposited on the substrate.

  3. Boron hydride polymer coated substrates

    DOEpatents

    Pearson, R.K.; Bystroff, R.I.; Miller, D.E.

    1986-08-27

    A method is disclosed for coating a substrate with a uniformly smooth layer of a boron hydride polymer. The method comprises providing a reaction chamber which contains the substrate and the boron hydride plasma. A boron hydride feed stock is introduced into the chamber simultaneously with the generation of a plasma discharge within the chamber. A boron hydride plasma of ions, electrons and free radicals which is generated by the plasma discharge interacts to form a uniformly smooth boron hydride polymer which is deposited on the substrate.

  4. Direct cooled power electronics substrate

    DOEpatents

    Wiles, Randy H [Powell, TN; Wereszczak, Andrew A [Oak Ridge, TN; Ayers, Curtis W [Kingston, TN; Lowe, Kirk T [Knoxville, TN

    2010-09-14

    The disclosure describes directly cooling a three-dimensional, direct metallization (DM) layer in a power electronics device. To enable sufficient cooling, coolant flow channels are formed within the ceramic substrate. The direct metallization layer (typically copper) may be bonded to the ceramic substrate, and semiconductor chips (such as IGBT and diodes) may be soldered or sintered onto the direct metallization layer to form a power electronics module. Multiple modules may be attached to cooling headers that provide in-flow and out-flow of coolant through the channels in the ceramic substrate. The modules and cooling header assembly are preferably sized to fit inside the core of a toroidal shaped capacitor.

  5. Titanium oxide as substrate for neural cell growth.

    PubMed

    Carballo-Vila, Mónica; Moreno-Burriel, Berta; Chinarro, Eva; Jurado, José R; Casañ-Pastor, Nieves; Collazos-Castro, Jorge E

    2009-07-01

    Titanium oxide has antiinflammatory activity and tunable electrochemical behavior that make it an attractive material for the fabrication of implantable devices. The most stable composition is TiO2 and occurs mainly in three polymorphs, namely, anatase, rutile, and brookite, which differ in its crystallochemical properties. Here, we report the preparation of rutile surfaces that permit good adherence and axonal growth of cultured rat cerebral cortex neurons. Rutile disks were obtained by sinterization of TiO2 powders of commercial origin or precipitated from hydrolysis of Ti(IV)-isopropoxide. Commercial powders sintered at 1300-1600 degrees C produced rutile surfaces with abnormal grain growth, probably because of impurities of the powders. Neurons cultured on those surfaces survived in variable numbers and showed fewer neurites than on control materials. On the other hand, rutile sintered from precipitated powders had less contaminants and more homogenous grain growth. By adjusting the thermal treatment it was possible to obtain surfaces performing well as substrate for neuron survival for at least 10 days. Some surfaces permitted normal axonal elongation, whereas dendrite growth was generally impaired. These findings support the potential use of titanium oxide in neuroprostheses and other devices demanding materials with enhanced properties in terms of biocompatibility and axon growth promotion. PMID:18481786

  6. Functional Interaction between the Scaffold Protein Kidins220/ARMS and Neuronal Voltage-Gated Na+ Channels*

    PubMed Central

    Cesca, Fabrizia; Satapathy, Annyesha; Ferrea, Enrico; Nieus, Thierry; Benfenati, Fabio; Scholz-Starke, Joachim

    2015-01-01

    Kidins220 (kinase D-interacting substrate of 220 kDa)/ankyrin repeat-rich membrane spanning (ARMS) acts as a signaling platform at the plasma membrane and is implicated in a multitude of neuronal functions, including the control of neuronal activity. Here, we used the Kidins220−/− mouse model to study the effects of Kidins220 ablation on neuronal excitability. Multielectrode array recordings showed reduced evoked spiking activity in Kidins220−/− hippocampal networks, which was compatible with the increased excitability of GABAergic neurons determined by current-clamp recordings. Spike waveform analysis further indicated an increased sodium conductance in this neuronal subpopulation. Kidins220 association with brain voltage-gated sodium channels was shown by co-immunoprecipitation experiments and Na+ current recordings in transfected HEK293 cells, which revealed dramatic alterations of kinetics and voltage dependence. Finally, an in silico interneuronal model incorporating the Kidins220-induced Na+ current alterations reproduced the firing phenotype observed in Kidins220−/− neurons. These results identify Kidins220 as a novel modulator of Nav channel activity, broadening our understanding of the molecular mechanisms regulating network excitability. PMID:26037926

  7. Stepping Out of the Shade: Control of Neuronal Activity by the Scaffold Protein Kidins220/ARMS

    PubMed Central

    Scholz-Starke, Joachim; Cesca, Fabrizia

    2016-01-01

    The correct functioning of the nervous system depends on the exquisitely fine control of neuronal excitability and synaptic plasticity, which relies on an intricate network of protein-protein interactions and signaling that shapes neuronal homeostasis during development and in adulthood. In this complex scenario, Kinase D interacting substrate of 220 kDa/ankyrin repeat-rich membrane spanning (Kidins220/ARMS) acts as a multi-functional scaffold protein with preferential expression in the nervous system. Engaged in a plethora of interactions with membrane receptors, cytosolic signaling components and cytoskeletal proteins, Kidins220/ARMS is implicated in numerous cellular functions including neuronal survival, neurite outgrowth and maturation and neuronal activity, often in the context of neurotrophin (NT) signaling pathways. Recent studies have highlighted a number of cell- and context-specific roles for this protein in the control of synaptic transmission and neuronal excitability, which are at present far from being completely understood. In addition, some evidence has began to emerge, linking alterations of Kidins220 expression to the onset of various neurodegenerative diseases and neuropsychiatric disorders. In this review, we present a concise summary of our fragmentary knowledge of Kidins220/ARMS biological functions, focusing on the mechanism(s) by which it controls various aspects of neuronal activity. We have tried, where possible, to discuss the available evidence in the wider context of NT-mediated regulation, and to outline emerging roles of Kidins220/ARMS in human pathologies. PMID:27013979

  8. Internalization and proteolytic action of botulinum toxins in CNS neurons and astrocytes.

    PubMed

    Verderio, C; Coco, S; Rossetto, O; Montecucco, C; Matteoli, M

    1999-07-01

    Tetanus and botulinum toxins bind and are internalized at the neuromuscular junction. Botulinum neurotoxins (BoNTs) enter the cytosol at the motor nerve terminal; tetanus neurotoxin (TeNT) proceeds retroaxonally inside the motor axon to reach the spinal cord inhibitory interneurons. Although the major target of BoNTs is the peripheral cholinergic terminals, CNS neurons are susceptible to intoxication as well. We investigated the route of entry and the proteolytic activity of BoNT/B and BoNT/F in cultured hippocampal neurons and astrocytes. We show that, differently from TeNT, which enters hippocampal neurons via the process of synaptic vesicle (SV) recycling, BoNTs are internalized and cleave the substrate synaptobrevin/VAMP2 via a process independent of synaptic activity. Labeling of living neurons with Texas Red-conjugated BoNTs and fluoresceinated dextran revealed that these toxins enter hippocampal neurons via endocytic processes not mediated by SV recycling. Botulinum toxins also exploit endocytosis to enter cultured astrocytes, where they partially cleave cellubrevin, a ubiquitous synaptobrevin/VAMP isoform. These results indicate that, in spite of their closely related protein structure, TeNT and BoNTs use different routes to penetrate hippocampal neurons. These findings bear important implications for the identification of the protein receptors of clostridial toxins. PMID:10386990

  9. Light-emitting channelrhodopsins for combined optogenetic and chemical-genetic control of neurons.

    PubMed

    Berglund, Ken; Birkner, Elisabeth; Augustine, George J; Hochgeschwender, Ute

    2013-01-01

    Manipulation of neuronal activity through genetically targeted actuator molecules is a powerful approach for studying information flow in the brain. In these approaches the genetically targeted component, a receptor or a channel, is activated either by a small molecule (chemical genetics) or by light from a physical source (optogenetics). We developed a hybrid technology that allows control of the same neurons by both optogenetic and chemical genetic means. The approach is based on engineered chimeric fusions of a light-generating protein (luciferase) to a light-activated ion channel (channelrhodopsin). Ionic currents then can be activated by bioluminescence upon activation of luciferase by its substrate, coelenterazine (CTZ), as well as by external light. In cell lines, expression of the fusion of Gaussia luciferase to Channelrhodopsin-2 yielded photocurrents in response to CTZ. Larger photocurrents were produced by fusing the luciferase to Volvox Channelrhodopsin-1. This version allowed chemical modulation of neuronal activity when expressed in cultured neurons: CTZ treatment shifted neuronal responses to injected currents and sensitized neurons to fire action potentials in response to subthreshold synaptic inputs. These luminescent channelrhodopsins--or luminopsins--preserve the advantages of light-activated ion channels, while extending their capabilities. Our proof-of-principle results suggest that this novel class of tools can be improved and extended in numerous ways. PMID:23544095

  10. Depletion of catecholaminergic neurons of the rostral ventrolateral medulla in multiple systems atrophy with autonomic failure

    NASA Technical Reports Server (NTRS)

    Benarroch, E. E.; Smithson, I. L.; Low, P. A.; Parisi, J. E.

    1998-01-01

    The ventrolateral portion of the intermediate reticular formation of the medulla (ventrolateral medulla, VLM), including the C1/A1 groups of catecholaminergic neurons, is thought to be involved in control of sympathetic cardiovascular outflow, cardiorespiratory interactions, and reflex control of vasopressin release. As all these functions are affected in patients with multiple systems atrophy (MSA) with autonomic failure, we sought to test the hypothesis that catecholaminergic (tyrosine hydroxylase [TH]-positive) neurons of the VLM are depleted in these patients. Medullas were obtained at autopsy from 4 patients with MSA with prominent autonomic failure and 5 patients with no neurological disease. Patients with MSA had laboratory evidence of severe adrenergic sudomotor and cardiovagal failure. Tissue was immersion fixed in 2% paraformaldehyde at 4 degrees C for 24 hours and cut into 1-cm blocks in the coronal plane from throughout the medulla. Serial 50-microm sections were collected and one section every 300 microm was stained for TH. There was a pronounced depletion of TH neurons in the rostral VLM in all cases of MSA. There was also significant reduction of TH neurons in the caudal VLM in 3 MSA patients compared with 3 control subjects. In 2 MSA cases and in 2 control subjects, the thoracic spinal cord was available for study. There was also depletion of TH fibers and sympathetic preganglionic neurons (SPNs) in the 2 MSA cases examined. Thus, depletion of catecholaminergic neurons in the VLM may provide a substrate for some of the autonomic and endocrine manifestations of MSA.

  11. Morphological homogeneity of neurons: searching for outlier neuronal cells.

    PubMed

    Zawadzki, Krissia; Feenders, Christoph; Viana, Matheus P; Kaiser, Marcus; Costa, Luciano da F

    2012-10-01

    We report a morphology-based approach for the automatic identification of outlier neurons, as well as its application to the NeuroMorpho.org database, with more than 5,000 neurons. Each neuron in a given analysis is represented by a feature vector composed of 20 measurements, which are then projected into a two-dimensional space by applying principal component analysis. Bivariate kernel density estimation is then used to obtain the probability distribution for the group of cells, so that the cells with highest probabilities are understood as archetypes while those with the smallest probabilities are classified as outliers. The potential of the methodology is illustrated in several cases involving uniform cell types as well as cell types for specific animal species. The results provide insights regarding the distribution of cells, yielding single and multi-variate clusters, and they suggest that outlier cells tend to be more planar and tortuous. The proposed methodology can be used in several situations involving one or more categories of cells, as well as for detection of new categories and possible artifacts. PMID:22615032

  12. Sensory neurons and circuits mediating itch

    PubMed Central

    LaMotte, Robert H.; Dong, Xinzhong; Ringkamp, Matthias

    2014-01-01

    Chemicals used experimentally to evoke itch elicit activity in diverse subpopulations of cutaneous pruriceptive neurons, all of which also respond to painful stimuli. However, itch is distinct from pain: it evokes different behaviors, such as scratching, and originates from the skin or certain mucosae but not from muscle, joints or viscera. New insights regarding the neurons that mediate the sensation of itch have been gained from experiments in which gene expression has been manipulated in different types of pruriceptive neurons as well as from comparisons between psychophysical measurements of itch and the neuronal discharges and other properties of peripheral and central pruriceptive neurons. PMID:24356071

  13. Neuronal gap junctions play a role in the secondary neuronal death following controlled cortical impact.

    PubMed

    Belousov, Andrei B; Wang, Yongfu; Song, Ji-Hoon; Denisova, Janna V; Berman, Nancy E; Fontes, Joseph D

    2012-08-22

    In the mammalian CNS, excessive release of glutamate and overactivation of glutamate receptors are responsible for the secondary (delayed) neuronal death following neuronal injury, including ischemia, traumatic brain injury (TBI) and epilepsy. Recent studies in mice showed a critical role for neuronal gap junctions in NMDA receptor-mediated excitotoxicity and ischemia-mediated neuronal death. Here, using controlled cortical impact (CCI) in adult mice, as a model of TBI, and Fluoro-Jade B staining for analysis of neuronal death, we set to determine whether neuronal gap junctions play a role in the CCI-mediated secondary neuronal death. We report that 24h post-CCI, substantial neuronal death is detected in a number of brain regions outside the injury core, including the striatum. The striatal neuronal death is reduced both in wild-type mice by systemic administration of mefloquine (a relatively selective blocker of neuronal gap junctions) and in knockout mice lacking connexin 36 (neuronal gap junction protein). It is also reduced by inactivation of group II metabotropic glutamate receptors (with LY341495) which, as reported previously, control the rapid increase in neuronal gap junction coupling following different types of neuronal injury. The results suggest that neuronal gap junctions play a critical role in the CCI-induced secondary neuronal death. PMID:22781494

  14. Direct innervation and modulation of orexin neurons by lateral hypothalamic LepRb neurons

    PubMed Central

    Louis, Gwendolyn W.; Leinninger, Gina M.; Rhodes, Christopher J.; Myers, Martin G.

    2010-01-01

    Leptin, the adipose-derived hormonal signal of body energy stores, acts via the leptin receptor (LepRb) on neurons in multiple brain regions. We previously identified LepRb neurons in the lateral hypothalamic area (LHA), which are distinct from neighboring leptin-regulated melanin concentrating hormone (MCH)- or orexin (OX)-expressing cells. Neither the direct synaptic targets of LHA LepRb neurons nor their potential role in the regulation of other LHA neurons have been determined, however. We thus generated several adenoviral and transgenic systems in which cre recombinase promotes the expression of the tracer, wheat germ agglutinin (WGA), and utilized these in combination with LepRbcre mice to determine the neuronal targets of LHA LepRb neurons. This analysis revealed that, while some LHA LepRb neurons project to dopamine neurons in the ventral tegmental area (VTA), LHA LepRb neurons also densely innervate the LHA where they directly synapse with OX, but not MCH, neurons. Indeed, few other LepRb neurons in the brain project to the OX-containing region of the mouse LHA, and direct leptin action via LHA LepRb neurons regulates gene expression in OX neurons. These findings thus reveal a major role for LHA leptin action in the modulation of OX neurons, suggesting the importance of LHA LepRb neurons in the regulation of OX signaling that is crucial to leptin action and metabolic control. PMID:20739548

  15. Unconventional fuel: Tire derived fuel

    SciTech Connect

    Hope, M.W.

    1995-09-01

    Material recovery of scrap tires for their fuel value has moved from a pioneering concept in the early 1980`s to a proven and continuous use in the United States` pulp and paper, utility, industrial, and cement industry. Pulp and paper`s use of tire derived fuel (TDF) is currently consuming tires at the rate of 35 million passenger tire equivalents (PTEs) per year. Twenty mills are known to be burning TDF on a continuous basis. The utility industry is currently consuming tires at the rate of 48 million PTEs per year. Thirteen utilities are known to be burning TDF on a continuous basis. The cement industry is currently consuming tires at the rate of 28 million PTEs per year. Twenty two cement plants are known to be burning TDF on a continuous basis. Other industrial boilers are currently consuming tires at the rate of 6.5 million PTEs per year. Four industrial boilers are known to be burning TDF on a continuous basis. In total, 59 facilities are currently burning over 117 million PTEs per year. Although 93% of these facilities were not engineered to burn TDF, it has become clear that TDF has found acceptance as a supplemental fuel when blending with conventional fuels in existing combustion devices designed for normal operating conditions. The issues of TDF as a supplemental fuel and its proper specifications are critical to the successful development of this fuel alternative. This paper will focus primarily on TDF`s use in a boiler type unit.

  16. Response of pontomedullary reticulospinal neurons to vestibular stimuli in vertical planes. Role in vertical vestibulospinal reflexes of the decerebrate cat

    NASA Technical Reports Server (NTRS)

    Bolton, P. S.; Goto, T.; Schor, R. H.; Wilson, V. J.; Yamagata, Y.; Yates, B. J.

    1992-01-01

    1. To investigate the neural substrate of vestibulospinal reflexes in decerebrate cats, we studied the responses of pontomedullary reticulospinal neurons to natural stimulation of the labyrinth in vertical planes. Our principal aim was to determine whether reticulospinal neurons that terminate in, or are likely to give off collaterals to, the upper cervical segments had properties similar to those of the vestibulocollic reflex (VCR). 2. Antidromic stimulation was used to determine whether the neurons projected to the neck, lower cervical, thoracic, or lumbar levels. Dynamics of the responses of spontaneously firing neurons were studied with sinusoidal stimuli delivered at 0.05-1 Hz and aligned to the plane of body rotation, that produced maximal modulation of the neuron (response vector orientation). Each neuron was assigned a vestibular input classification of otolith, vertical canal, otolith + canal, or spatial-temporal convergence (STC). 3. We found, in agreement with previous studies, that the largest fraction of pontomedullary reticulospinal neurons projected to the lumbar cord, and that only a small number ended in the neck segments. Neurons projecting to all levels of the spinal cord had similar responses to labyrinth stimulation. 4. Reticulospinal neurons that received only vertical canal inputs were rare (1 of 67 units). Most reticulospinal neurons (48%) received predominant otolith inputs, 18% received otolith + canal input, and only 9% had STC behavior. These data are in sharp contrast to the results of our previous studies of vestibulospinal neurons. A considerable portion of vestibulospinal neurons receives vertical canal input (38%), fewer receive predominantly otolith input (22%), whereas the proportion that have otolith + canal input or STC behavior is similar to our present reticulospinal data. 5. The response vector orientations of our reticulospinal neurons, particularly those with canal inputs (canal, otolith + canal, STC) were predominantly in

  17. The Ketone Body, β-Hydroxybutyrate Stimulates the Autophagic Flux and Prevents Neuronal Death Induced by Glucose Deprivation in Cortical Cultured Neurons.

    PubMed

    Camberos-Luna, Lucy; Gerónimo-Olvera, Cristian; Montiel, Teresa; Rincon-Heredia, Ruth; Massieu, Lourdes

    2016-03-01

    Glucose is the major energy substrate in brain, however, during ketogenesis induced by starvation or prolonged hypoglycemia, the ketone bodies (KB), acetoacetate and β-hydroxybutyrate (BHB) can substitute for glucose. KB improve neuronal survival in diverse injury models, but the mechanisms by which KB prevent neuronal damage are still not well understood. In the present study we have investigated whether protection by the D isomer of BHB (D-BHB) against neuronal death induced by glucose deprivation (GD), is related to autophagy. Autophagy is a lysosomal-dependent degradation process activated during nutritional stress, which leads to the digestion of damaged proteins and organelles providing energy for cell survival. Results show that autophagy is activated in cortical cultured neurons during GD, as indicated by the increase in the levels of the lipidated form of the microtubule associated protein light chain 3 (LC3-II), and the number of autophagic vesicles. At early phases of glucose reintroduction (GR), the levels of p62 declined suggesting that the degradation of the autophagolysosomal content takes place at this time. In cultures exposed to GD and GR in the presence of D-BHB, the levels of LC3-II and p62 rapidly declined and remained low during GR, suggesting that the KB stimulates the autophagic flux preventing autophagosome accumulation and improving neuronal survival. PMID:26303508

  18. Forward engineering neuronal diversity using direct reprogramming.

    PubMed

    Tsunemoto, Rachel K; Eade, Kevin T; Blanchard, Joel W; Baldwin, Kristin K

    2015-06-01

    The nervous system is comprised of a vast diversity of distinct neural cell types. Differences between neuronal subtypes drive the assembly of neuronal circuits and underlie the subtype specificity of many neurological diseases. Yet, because neurons are irreversibly post-mitotic and not readily available from patients, it has not been feasible to study specific subtypes of human neurons in larger numbers. A powerful means to study neuronal diversity and neurological disease is to establish methods to produce desired neuronal subtypes in vitro. Traditionally this has been accomplished by treating pluripotent or neural stem cells with growth factors and morphogens that recapitulate exogenous developmental signals. These approaches often require extended periods of culture, which can limit their utility. However, more recently, it has become possible to produce neurons directly from fibroblasts using transcription factors and/or microRNAs. This technique referred to as direct reprogramming or transdifferentiation has proven to be a rapid, robust, and reproducible method to generate mature neurons of many different subtypes from multiple cell sources. Here, we highlight recent advances in generating neurons of specific subtypes using direct reprogramming and outline various scenarios in which induced neurons may be applied to studies of neuronal function and neurological disease. PMID:25908841

  19. Film Growth on Nanoporous Substrate

    NASA Astrophysics Data System (ADS)

    Zhang, Xue; Joy, James; Zhao, Chenwei; Xu, J. M.; Valles, James

    Self-ordered nanoporous anodic aluminum oxide (AAO) provides an easy way to fabricate nano structured material, such as nano wires and nano particles. We employ AAO as substrates and focus on the thermally evaporated film growth on the surface of the substrate. With various materials deposited onto the substrate, we find the films show different structures, e,g. ordered array of nano particles for Lead and nanohoneycomb structure for Silver. We relate the differing behaviors to the difference of surface energy and diffusion constant. To verify this, the effect of substrate temperature on the film growth has been explored and the structure of the film has been successfully changed through the process. We are grateful for the support of NSF Grants No. DMR-1307290.

  20. Ionic mechanisms of spinal neuronal cold hypersensitivity in ciguatera.

    PubMed

    Patel, Ryan; Brice, Nicola L; Lewis, Richard J; Dickenson, Anthony H

    2015-12-01

    Cold hypersensitivity is evident in a range of neuropathies and can evoke sensations of paradoxical burning cold pain. Ciguatoxin poisoning is known to induce a pain syndrome caused by consumption of contaminated tropical fish that can persist for months and include pruritus and cold allodynia; at present no suitable treatment is available. This study examined, for the first time, the neural substrates and molecular components of Pacific ciguatoxin-2-induced cold hypersensitivity. Electrophysiological recordings of dorsal horn lamina V/VI wide dynamic range neurones were made in non-sentient rats. Subcutaneous injection of 10 nm ciguatoxin-2 into the receptive field increased neuronal responses to innocuous and noxious cooling. In addition, neuronal responses to low-threshold but not noxious punctate mechanical stimuli were also elevated. The resultant cold hypersensitivity was not reversed by 6-({2-[2-fluoro-6-(trifluoromethyl)phenoxy]-2-methylpropyl}carbamoyl)pyridine-3-carboxylic acid, an antagonist of transient receptor potential melastatin 8 (TRPM8). Both mechanical and cold hypersensitivity were completely prevented by co-injection with the Nav 1.8 antagonist A803467, whereas the transient receptor potential ankyrin 1 (TRPA1) antagonist A967079 only prevented hypersensitivity to innocuous cooling and partially prevented hypersensitivity to noxious cooling. In naive rats, neither innocuous nor noxious cold-evoked neuronal responses were inhibited by antagonists of Nav 1.8, TRPA1 or TRPM8 alone. Ciguatoxins may confer cold sensitivity to a subpopulation of cold-insensitive Nav 1.8/TRPA1-positive primary afferents, which could underlie the cold allodynia reported in ciguatera. These data expand the understanding of central spinal cold sensitivity under normal conditions and the role of these ion channels in this translational rat model of ciguatoxin-induced hypersensitivity. PMID:26454262

  1. Cloning of three novel neuronal Cdk5 activator binding proteins.

    PubMed

    Ching, Y P; Qi, Z; Wang, J H

    2000-01-25

    Neuronal Cdc2-like kinase (Nclk) is involved in the regulation of neuronal differentiation and neuro-cytoskeleton dynamics. The active kinase consists of a catalytic subunit, Cdk5, and a 25 kDa activator protein (p25nck5a) derived from a 35 kDa neuronal-specific protein (p35nck5a). As an extension of our previous study (Qi, Z., Tang, D., Zhu, X., Fujita, D.J., Wang, J.H., 1998. Association of neurofilament proteins with neuronal Cdk5 activator. J. Biol. Chem. 270, 2329-2335), which showed that neurofilament is one of the p35nck5a-associated proteins, we now report the isolation of three other novel p35nck5a-associated proteins using the yeast two-hybrid screen. The full-length forms of these three novel proteins, designated C42, C48 and C53, have a molecular mass of 66, 24, and 57 kDa, respectively. Northern analysis indicates that these novel proteins are widely expressed in human tissues, including the heart, brain, skeletal muscle, placenta, lung, liver, kidney and pancreas. The bacterially expressed glutathione S-transferase (GST)-fusion forms of these three proteins were able to co-precipitate p35nck5a complexed with Cdk5 from insect cell lysate. Among these three proteins, only C48 and C53 can be phosphorylated by Nclk, suggesting that they may be the substrates of Nclk. Sequence homology searches have suggested that the C48 protein is marginally related to restin protein, whereas the C42 protein has homologues of unknown function in Caenorhabditis elegans and Arabidopsis thaliana. PMID:10721722

  2. Spatially selective photoconductive stimulation of live neurons

    PubMed Central

    Campbell, Jacob; Singh, Dipika; Hollett, Geoffrey; Dravid, Shashank M.; Sailor, Michael J.; Arikkath, Jyothi

    2014-01-01

    Synaptic activity is intimately linked to neuronal structure and function. Stimulation of live cultured primary neurons, coupled with fluorescent indicator imaging, is a powerful technique to assess the impact of synaptic activity on neuronal protein trafficking and function. Current technology for neuronal stimulation in culture include chemical techniques or microelectrode or optogenetic based techniques. While technically powerful, chemical stimulation has limited spatial resolution and microelectrode and optogenetic techniques require specialized equipment and expertise. We report an optimized and improved technique for laser based photoconductive stimulation of live neurons using an inverted confocal microscope that overcomes these limitations. The advantages of this approach include its non-invasive nature and adaptability to temporal and spatial manipulation. We demonstrate that the technique can be manipulated to achieve spatially selective stimulation of live neurons. Coupled with live imaging of fluorescent indicators, this simple and efficient technique should allow for significant advances in neuronal cell biology. PMID:24904287

  3. Using light to probe neuronal function

    NASA Astrophysics Data System (ADS)

    Daria, Vincent R.; Bachor, Hans-A.

    2015-08-01

    In the last few years a multi-disciplinary approach has been launched to investigate the brain using new techniques, which are capable of probing neuronal function across the entire length scales of the brain. Here, we discuss optical tools and spatial light patterning techniques to investigate brain function from the perspective of individual neurons and neuronal circuits. We discuss both biochemical and genetic tools to stimulate neurons, as well as techniques to record neuronal activity. We discuss optical projection and imaging tricks that can be dynamically customized to a particular neuron morphology and neuronal circuit layout facilitating a systematic study of their input/output transfer functions. These optical techniques will play a major role towards understanding the operation of a brain.

  4. GABAergic neurons in the ventral tegmental area receive dual GABA/enkephalin-mediated inhibitory inputs from the bed nucleus of the stria terminalis.

    PubMed

    Kudo, Takehiro; Konno, Kohtarou; Uchigashima, Motokazu; Yanagawa, Yuchio; Sora, Ichiro; Minami, Masabumi; Watanabe, Masahiko

    2014-06-01

    Activation of mu-opioid receptor (MOR) disinhibits dopaminergic neurons in the ventral tegmental area (VTA) through inhibition of γ-aminobutyric acid (GABA)ergic neurons. This mechanism is thought to play a pivotal role in mediating reward behaviors. Here, we characterised VTA-projecting enkephalinergic neurons in the anterior division of the bed nucleus of the stria terminalis (BST) and investigated their targets by examining MOR expression in the VTA. In the BST, neurons expressing preproenkephalin mRNA were exclusively GABAergic, and constituted 37.2% of the total GABAergic neurons. Using retrograde tracer injected into the VTA, 21.6% of VTA-projecting BST neurons were shown to express preproenkephalin mRNA. Enkephalinergic projections from the BST exclusively formed symmetrical synapses onto the dendrites of VTA neurons. In the VTA, 74.1% of MOR mRNA-expressing neurons were GABAergic, with the rest being glutamatergic neurons expressing type-2 vesicular glutamate transporter mRNA. However, MOR mRNA was below the detection threshold in dopaminergic neurons. By immunohistochemistry, MOR was highly expressed on the extrasynaptic membranes of dendrites in GABAergic VTA neurons, including dendrites innervated by BST-VTA projection terminals. MOR was also expressed weakly on GABAergic and glutamatergic terminals in the VTA. Given that GABAA α1 is expressed at GABAergic BST-VTA synapses on dendrites of GABAergic neurons [T. Kudo et al. (2012) J. Neurosci., 32, 18035-18046], our results collectively indicate that the BST sends dual inhibitory outputs targeting GABAergic VTA neurons; GABAergic inhibition via 'wired' transmission, and enkephalinergic inhibition via 'volume' transmission. This dual inhibitory system provides the neural substrate underlying the potent disinhibitory control over dopaminergic VTA neurons exerted by the BST. PMID:24580812

  5. Neuronal avalanches and brain plasticity

    NASA Astrophysics Data System (ADS)

    de Arcangelis, L.; Herrmann, H. J.; Perrone-Capano, C.

    2007-12-01

    Networks of living neurons exhibit an avalanche mode of activity, experimentally found in organotypic cultures. Moreover, experimental studies of morphology indicate that neurons develop a network of small-world-like connections, with the possibility of a very high connectivity degree. Here we discuss a recent model based on self-organized criticality, which consists of an electrical network with threshold firing and activity-dependent synapse strengths. The model is implemented on regular and small world lattices and on a scale-free network, the Apollonian network. The system exhibits an avalanche activity with a power law distribution of sizes and durations. The analysis of the power spectra of the electrical signal reproduces very robustly the power law behaviour with the exponent 0.8, experimentally measured in electroencephalogram (EEG) spectra. The exponents are found to be quite stable with respect to initial configurations and strength of plastic remodelling, indicating that universality holds for a wide class of neural network models.

  6. Local optimization of neuron arbors.

    PubMed

    Cherniak, C

    1992-01-01

    How parsimoniously is brain wiring laid out, that is, how well does a neuron minimize costs of connections among its synapses? Neural optimization of dendritic and axonic arbors can be evaluated using a generalization of the Steiner tree concept from combinatorial network optimization theory. Local branch-junction geometry of neuronal connecting structures fits a volume minimization model well. In addition, volume of the arborizations at this neighborhood level is significantly more strongly minimized than their length, signal propagation speed, or surface area. The mechanism of this local volume optimization resembles those involved in formation of nonliving tree structures such as river junctions and electric-discharge patterns, and appears to govern initial nerve growth-cone behavior through vector-mechanical energy minimization. PMID:1586674

  7. Manipulating neuronal activity with low frequency transcranial ultrasound

    NASA Astrophysics Data System (ADS)

    Moore, Michele Elizabeth

    Stimulation of the rodent cerebral cortex is used to investigate the underlying biological basis for the restorative effects of slow wave sleep. Neuronal activation by optogenetic and ultrasound stimulation elicits changes in action potentials across the cerebral cortex that are recorded as electroencephalograms. Optogenetic stimulation requires an invasive implantation procedure limiting its application in human studies. We sought to determine whether ultrasound stimulation could be as effective as optogenetic techniques currently used, in an effort to further understand the physiological and metabolic requirements of sleep. We successfully recorded electroencephalograms in response to transcranial ultrasound stimulation of the barrel cortex at 1 and 7 Hz frequencies, comparing them to those recorded in response to optogenetic stimuli applied at the same frequencies. Our results showed application of a 473 nm blue LED positioned 6 cm above the skull and ultrasound stimulation at an output voltage of 1000 mVpp produced electroencephalograms with physiological responses of similar amplitude. We concluded that there exists an intensity-proportionate response in the optogenetic stimulation, but not with ultrasound stimulation at the frequencies we surveyed. Activation of neuronal cells in response to optogenetic stimulation in a Thy1-ChR2 transgenic mouse line is specifically targeted to pyramidal cells in the cerebral cortex. ChR2 responses to optogenetic stimulation are mediated by a focal activation of neuronal ion channels. We measured electrophysiological responses to ultrasound stimulation, comparing them to those recorded from optogenetic stimuli. Our results show striking similarities between ultrasound-induced responses and optogenetically-induced responses, which may indicate that transcranial ultrasound stimulation is also mediated by ion channel dependent processes in cerebral cortical neurons. The biophysical substrates for electrical excitability of

  8. Neuronal Cell Death Induced by Mechanical Percussion Trauma in Cultured Neurons is not Preceded by Alterations in Glucose, Lactate and Glutamine Metabolism.

    PubMed

    Jayakumar, A R; Bak, L K; Rama Rao, K V; Waagepetersen, H S; Schousboe, A; Norenberg, M D

    2016-02-01

    Traumatic brain injury (TBI) is a devastating neurological disorder that usually presents in acute and chronic forms. Brain edema and associated increased intracranial pressure in the early phase following TBI are major consequences of acute trauma. On the other hand, neuronal injury, leading to neurobehavioral and cognitive impairments, that usually develop months to years after single or repetitive episodes of head trauma, are major consequences of chronic TBI. The molecular mechanisms responsible for TBI-induced injury, however, are unclear. Recent studies have suggested that early mitochondrial dysfunction and subsequent energy failure play a role in the pathogenesis of TBI. We therefore examined whether oxidative metabolism of (13)C-labeled glucose, lactate or glutamine is altered early following in vitro mechanical percussion-induced trauma (5 atm) to neurons (4-24 h), and whether such events contribute to the development of neuronal injury. Cell viability was assayed using the release of the cytoplasmic enzyme lactate dehydrogenase (LDH), together with fluorescence-based cell staining (calcein and ethidium homodimer-1 for live and dead cells, respectively). Trauma had no effect on the LDH release in neurons from 1 to 18 h. However, a significant increase in LDH release was detected at 24 h after trauma. Similar findings were identified when traumatized neurons were stained with fluorescent markers. Additionally (13)C-labeling of glutamate showed a small, but statistically significant decrease at 14 h after trauma. However, trauma had no effect on the cycling ratio of the TCA cycle at any time-period examined. These findings indicate that trauma does not cause a disturbance in oxidative metabolism of any of the substrates used for neurons. Accordingly, such metabolic disturbance does not appear to contribute to the neuronal death in the early stages following trauma. PMID:26729365

  9. Substrate channeling in proline metabolism

    PubMed Central

    Arentson, Benjamin W.; Sanyal, Nikhilesh; Becker, Donald F.

    2012-01-01

    Proline metabolism is an important pathway that has relevance in several cellular functions such as redox balance, apoptosis, and cell survival. Results from different groups have indicated that substrate channeling of proline metabolic intermediates may be a critical mechanism. One intermediate is pyrroline-5-carboxylate (P5C), which upon hydrolysis opens to glutamic semialdehyde (GSA). Recent structural and kinetic evidence indicate substrate channeling of P5C/GSA occurs in the proline catabolic pathway between the proline dehydrogenase and P5C dehydrogenase active sites of bifunctional proline utilization A (PutA). Substrate channeling in PutA is proposed to facilitate the hydrolysis of P5C to GSA which is unfavorable at physiological pH. The second intermediate, gamma-glutamyl phosphate, is part of the proline biosynthetic pathway and is extremely labile. Substrate channeling of gamma-glutamyl phosphate is thought to be necessary to protect it from bulk solvent. Because of the unfavorable equilibrium of P5C/GSA and the reactivity of gamma-glutamyl phosphate, substrate channeling likely improves the efficiency of proline metabolism. Here, we outline general strategies for testing substrate channeling and review the evidence for channeling in proline metabolism. PMID:22201749

  10. Neuronal responses to physiological stress.

    PubMed

    Kagias, Konstantinos; Nehammer, Camilla; Pocock, Roger

    2012-01-01

    Physiological stress can be defined as any external or internal condition that challenges the homeostasis of a cell or an organism. It can be divided into three different aspects: environmental stress, intrinsic developmental stress, and aging. Throughout life all living organisms are challenged by changes in the environment. Fluctuations in oxygen levels, temperature, and redox state for example, trigger molecular events that enable an organism to adapt, survive, and reproduce. In addition to external stressors, organisms experience stress associated with morphogenesis and changes in inner chemistry during normal development. For example, conditions such as intrinsic hypoxia and oxidative stress, due to an increase in tissue mass, have to be confronted by developing embryos in order to complete their development. Finally, organisms face the challenge of stochastic accumulation of molecular damage during aging that results in decline and eventual death. Studies have shown that the nervous system plays a pivotal role in responding to stress. Neurons not only receive and process information from the environment but also actively respond to various stresses to promote survival. These responses include changes in the expression of molecules such as transcription factors and microRNAs that regulate stress resistance and adaptation. Moreover, both intrinsic and extrinsic stresses have a tremendous impact on neuronal development and maintenance with implications in many diseases. Here, we review the responses of neurons to various physiological stressors at the molecular and cellular level. PMID:23112806

  11. Neuronal Responses to Physiological Stress

    PubMed Central

    Kagias, Konstantinos; Nehammer, Camilla; Pocock, Roger

    2012-01-01

    Physiological stress can be defined as any external or internal condition that challenges the homeostasis of a cell or an organism. It can be divided into three different aspects: environmental stress, intrinsic developmental stress, and aging. Throughout life all living organisms are challenged by changes in the environment. Fluctuations in oxygen levels, temperature, and redox state for example, trigger molecular events that enable an organism to adapt, survive, and reproduce. In addition to external stressors, organisms experience stress associated with morphogenesis and changes in inner chemistry during normal development. For example, conditions such as intrinsic hypoxia and oxidative stress, due to an increase in tissue mass, have to be confronted by developing embryos in order to complete their development. Finally, organisms face the challenge of stochastic accumulation of molecular damage during aging that results in decline and eventual death. Studies have shown that the nervous system plays a pivotal role in responding to stress. Neurons not only receive and process information from the environment but also actively respond to various stresses to promote survival. These responses include changes in the expression of molecules such as transcription factors and microRNAs that regulate stress resistance and adaptation. Moreover, both intrinsic and extrinsic stresses have a tremendous impact on neuronal development and maintenance with implications in many diseases. Here, we review the responses of neurons to various physiological stressors at the molecular and cellular level. PMID:23112806

  12. Membrane electrode assembly for a fuel cell

    NASA Technical Reports Server (NTRS)

    Prakash, Surya (Inventor); Narayanan, Sekharipuram R. (Inventor); Atti, Anthony (Inventor); Olah, George (Inventor); Smart, Marshall C. (Inventor)

    2006-01-01

    A catalyst ink for a fuel cell including a catalytic material and poly(vinylidene fluoride). The ink may be applied to a substrate to form an electrode, or bonded with other electrode layers to form a membrane electrode assembly (MEA).

  13. Densified edge seals for fuel cell components

    DOEpatents

    DeCasperis, Anthony J.; Roethlein, Richard J.; Breault, Richard D.

    1982-01-01

    A porous fuel cell component, such as an electrode substrate, has a densified edge which forms an improved gas seal during operation when soaked with electrolyte. The edges are made from the same composition as the rest of the component and are made by compressing an increased thickness of this material along the edges during the fabrication process.

  14. Alternative jet aircraft fuels

    NASA Technical Reports Server (NTRS)

    Grobman, J.

    1979-01-01

    Potential changes in jet aircraft fuel specifications due to shifts in supply and quality of refinery feedstocks are discussed with emphasis on the effects these changes would have on the performance and durability of aircraft engines and fuel systems. Combustion characteristics, fuel thermal stability, and fuel pumpability at low temperature are among the factors considered. Combustor and fuel system technology needs for broad specification fuels are reviewed including prevention of fuel system fouling and fuel system technology for fuels with higher freezing points.

  15. FUEL ELEMENT

    DOEpatents

    Fortescue, P.; Zumwalt, L.R.

    1961-11-28

    A fuel element was developed for a gas cooled nuclear reactor. The element is constructed in the form of a compacted fuel slug including carbides of fissionable material in some cases with a breeder material carbide and a moderator which slug is disposed in a canning jacket of relatively impermeable moderator material. Such canned fuel slugs are disposed in an elongated shell of moderator having greater gas permeability than the canning material wherefore application of reduced pressure to the space therebetween causes gas diffusing through the exterior shell to sweep fission products from the system. Integral fission product traps and/or exterior traps as well as a fission product monitoring system may be employed therewith. (AEC)

  16. Fuel compositions

    SciTech Connect

    Zaweski, E.F.; Niebylski, L.M.

    1986-09-23

    This patent describes a distillate fuel for indirect injection compression ignition engines containing at least the combination of (i) organic nitrate ignition accelerator, and (ii) an additive selected from the group consisting of alkenyl substituted succinimide, alkenyl substituted succinamide and mixtures thereof. The alkenyl substituent contains about 12-36 carbon atoms, the additive being made by the process comprising (a) isomerizing the double bond of an ..cap alpha..-olefin containing about 12-36 carbon atoms to obtain a mixture of internal olefins, (b) reacting the mixture of internal olefins with maleic acid, anhydride or ester to obtain an intermediate alkenyl substituted succinic acid, anhydride or ester, and (c) reacting the intermediate with ammonia to form a succinimide, succinamide or mixture thereof. The combination is present in an amount sufficient to minimize the coking characteristics of such fuel, especially throttling nozzle coking in the prechambers or swirl chambers of indirect injection compression ignition engines operated on such fuel.

  17. Direct targeting of peptidergic amygdalar neurons by noradrenergic afferents: linking stress-integrative circuitry

    PubMed Central

    Kravets, J. L.; Reyes, B. A. S.; Unterwald, E. M.; Van Bockstaele, E. J.

    2014-01-01

    Amygdalar norepinephrine (NE) plays a key role in regulating neural responses to emotionally arousing stimuli and is involved in memory consolidation of emotionally charged events. Corticotropin-releasing factor (CRF) and dynorphin (DYN), two neuropeptides that mediate the physiological and behavioral responses to stress, are abundant in the central nucleus of the amygdala (CeA), and directly innervate brainstem noradrenergic locus coeruleus (LC) neurons. Whether the CRF- and DYN-containing amygdalar neurons receive direct noradrenergic innervation has not yet been elucidated. The present study sought to define cellular substrates underlying noradrenergic modulation of CRF- and DYN-containing neurons in the CeA using immunohistochemistry and electron microscopy. Ultrastructural analysis revealed that NE-labeled axon terminals form synapses with CRF- and DYN-containing neurons in the CeA. Semi-quantitative analysis showed that approximately 31% of NET-labeled axon terminals targeted CeA neurons that co-expressed DYN and CRF. As a major source of CRF innervation to the LC, it is also not known whether CRF-containing CeA neurons are directly targeted by noradrenergic afferents. To test this, retrograde tract-tracing using FluoroGold (FG) from the LC was combined with immunocytochemical detection of CRF and NET in the CeA. Our results revealed a population of LC-projecting CRF-containing CeA neurons that are directly innervated by NE afferents. Analysis showed that approximately 34% of NET-labeled axon terminals targeted LC-projecting CeA neurons that contain CRF. Taken together, these results indicate significant interactions between NE, CRF, and DYN in this critical limbic region and reveal direct synaptic interactions of NE with amygdalar CRF that influence the LC-NE arousal system. PMID:24271021

  18. Viscoelastic properties of individual glial cells and neurons in the CNS

    PubMed Central

    Lu, Yun-Bi; Franze, Kristian; Seifert, Gerald; Steinhäuser, Christian; Kirchhoff, Frank; Wolburg, Hartwig; Guck, Jochen; Janmey, Paul; Wei, Er-Qing; Käs, Josef; Reichenbach, Andreas

    2006-01-01

    One hundred fifty years ago glial cells were discovered as a second, non-neuronal, cell type in the central nervous system. To ascribe a function to these new, enigmatic cells, it was suggested that they either glue the neurons together (the Greek word “γλια” means “glue”) or provide a robust scaffold for them (“support cells”). Although both speculations are still widely accepted, they would actually require quite different mechanical cell properties, and neither one has ever been confirmed experimentally. We investigated the biomechanics of CNS tissue and acutely isolated individual neurons and glial cells from mammalian brain (hippocampus) and retina. Scanning force microscopy, bulk rheology, and optically induced deformation were used to determine their viscoelastic characteristics. We found that (i) in all CNS cells the elastic behavior dominates over the viscous behavior, (ii) in distinct cell compartments, such as soma and cell processes, the mechanical properties differ, most likely because of the unequal local distribution of cell organelles, (iii) in comparison to most other eukaryotic cells, both neurons and glial cells are very soft (“rubber elastic”), and (iv) intriguingly, glial cells are even softer than their neighboring neurons. Our results indicate that glial cells can neither serve as structural support cells (as they are too soft) nor as glue (because restoring forces are dominant) for neurons. Nevertheless, from a structural perspective they might act as soft, compliant embedding for neurons, protecting them in case of mechanical trauma, and also as a soft substrate required for neurite growth and facilitating neuronal plasticity. PMID:17093050

  19. Neuronal hyperexcitability in the ventral posterior thalamus of neuropathic rats: modality selective effects of pregabalin

    PubMed Central

    Dickenson, Anthony H.

    2016-01-01

    Neuropathic pain represents a substantial clinical challenge; understanding the underlying neural mechanisms and back-translation of therapeutics could aid targeting of treatments more effectively. The ventral posterior thalamus (VP) is the major termination site for the spinothalamic tract and relays nociceptive activity to the somatosensory cortex; however, under neuropathic conditions, it is unclear how hyperexcitability of spinal neurons converges onto thalamic relays. This study aimed to identify neural substrates of hypersensitivity and the influence of pregabalin on central processing. In vivo electrophysiology was performed to record from VP wide dynamic range (WDR) and nociceptive-specific (NS) neurons in anesthetized spinal nerve-ligated (SNL), sham-operated, and naive rats. In neuropathic rats, WDR neurons had elevated evoked responses to low- and high-intensity punctate mechanical stimuli, dynamic brushing, and innocuous and noxious cooling, but less so to heat stimulation, of the receptive field. NS neurons in SNL rats also displayed increased responses to noxious punctate mechanical stimulation, dynamic brushing, noxious cooling, and noxious heat. Additionally, WDR, but not NS, neurons in SNL rats exhibited substantially higher rates of spontaneous firing, which may correlate with ongoing pain. The ratio of WDR-to-NS neurons was comparable between SNL and naive/sham groups, suggesting relatively few NS neurons gain sensitivity to low-intensity stimuli leading to a “WDR phenotype.” After neuropathy was induced, the proportion of cold-sensitive WDR and NS neurons increased, supporting the suggestion that changes in frequency-dependent firing and population coding underlie cold hypersensitivity. In SNL rats, pregabalin inhibited mechanical and heat responses but not cold-evoked or elevated spontaneous activity. PMID:27098028

  20. Reforming of fuel inside fuel cell generator

    DOEpatents

    Grimble, R.E.

    1988-03-08

    Disclosed is an improved method of reforming a gaseous reformable fuel within a solid oxide fuel cell generator, wherein the solid oxide fuel cell generator has a plurality of individual fuel cells in a refractory container, the fuel cells generating a partially spent fuel stream and a partially spent oxidant stream. The partially spent fuel stream is divided into two streams, spent fuel stream 1 and spent fuel stream 2. Spent fuel stream 1 is burned with the partially spent oxidant stream inside the refractory container to produce an exhaust stream. The exhaust stream is divided into two streams, exhaust stream 1 and exhaust stream 2, and exhaust stream 1 is vented. Exhaust stream 2 is mixed with spent fuel stream 2 to form a recycle stream. The recycle stream is mixed with the gaseous reformable fuel within the refractory container to form a fuel stream which is supplied to the fuel cells. Also disclosed is an improved apparatus which permits the reforming of a reformable gaseous fuel within such a solid oxide fuel cell generator. The apparatus comprises a mixing chamber within the refractory container, means for diverting a portion of the partially spent fuel stream to the mixing chamber, means for diverting a portion of exhaust gas to the mixing chamber where it is mixed with the portion of the partially spent fuel stream to form a recycle stream, means for injecting the reformable gaseous fuel into the recycle stream, and means for circulating the recycle stream back to the fuel cells. 1 fig.

  1. Reforming of fuel inside fuel cell generator

    DOEpatents

    Grimble, Ralph E.

    1988-01-01

    Disclosed is an improved method of reforming a gaseous reformable fuel within a solid oxide fuel cell generator, wherein the solid oxide fuel cell generator has a plurality of individual fuel cells in a refractory container, the fuel cells generating a partially spent fuel stream and a partially spent oxidant stream. The partially spent fuel stream is divided into two streams, spent fuel stream I and spent fuel stream II. Spent fuel stream I is burned with the partially spent oxidant stream inside the refractory container to produce an exhaust stream. The exhaust stream is divided into two streams, exhaust stream I and exhaust stream II, and exhaust stream I is vented. Exhaust stream II is mixed with spent fuel stream II to form a recycle stream. The recycle stream is mixed with the gaseous reformable fuel within the refractory container to form a fuel stream which is supplied to the fuel cells. Also disclosed is an improved apparatus which permits the reforming of a reformable gaseous fuel within such a solid oxide fuel cell generator. The apparatus comprises a mixing chamber within the refractory container, means for diverting a portion of the partially spent fuel stream to the mixing chamber, means for diverting a portion of exhaust gas to the mixing chamber where it is mixed with the portion of the partially spent fuel stream to form a recycle stream, means for injecting the reformable gaseous fuel into the recycle stream, and means for circulating the recycle stream back to the fuel cells.

  2. NBLAST: Rapid, Sensitive Comparison of Neuronal Structure and Construction of Neuron Family Databases.

    PubMed

    Costa, Marta; Manton, James D; Ostrovsky, Aaron D; Prohaska, Steffen; Jefferis, Gregory S X E

    2016-07-20

    Neural circuit mapping is generating datasets of tens of thousands of labeled neurons. New computational tools are needed to search and organize these data. We present NBLAST, a sensitive and rapid algorithm, for measuring pairwise neuronal similarity. NBLAST considers both position and local geometry, decomposing neurons into short segments; matched segments are scored using a probabilistic scoring matrix defined by statistics of matches and non-matches. We validated NBLAST on a published dataset of 16,129 single Drosophila neurons. NBLAST can distinguish neuronal types down to the finest level (single identified neurons) without a priori information. Cluster analysis of extensively studied neuronal classes identified new types and unreported topographical features. Fully automated clustering organized the validation dataset into 1,052 clusters, many of which map onto previously described neuronal types. NBLAST supports additional query types, including searching neurons against transgene expression patterns. Finally, we show that NBLAST is effective with data from other invertebrates and zebrafish. VIDEO ABSTRACT. PMID:27373836

  3. Glutamate neurons are intermixed with midbrain dopamine neurons in nonhuman primates and humans.

    PubMed

    Root, David H; Wang, Hui-Ling; Liu, Bing; Barker, David J; Mód, László; Szocsics, Péter; Silva, Afonso C; Maglóczky, Zsófia; Morales, Marisela

    2016-01-01

    The rodent ventral tegmental area (VTA) and substantia nigra pars compacta (SNC) contain dopamine neurons intermixed with glutamate neurons (expressing vesicular glutamate transporter 2; VGluT2), which play roles in reward and aversion. However, identifying the neuronal compositions of the VTA and SNC in higher mammals has remained challenging. Here, we revealed VGluT2 neurons within the VTA and SNC of nonhuman primates and humans by simultaneous detection of VGluT2 mRNA and tyrosine hydroxylase (TH; for identification of dopamine neurons). We found that several VTA subdivisions share similar cellular compositions in nonhuman primates and humans; their rostral linear nuclei have a high prevalence of VGluT2 neurons lacking TH; their paranigral and parabrachial pigmented nuclei have mostly TH neurons, and their parabrachial pigmented nuclei have dual VGluT2-TH neurons. Within nonhuman primates and humans SNC, the vast majority of neurons are TH neurons but VGluT2 neurons were detected in the pars lateralis subdivision. The demonstration that midbrain dopamine neurons are intermixed with glutamate or glutamate-dopamine neurons from rodents to humans offers new opportunities for translational studies towards analyzing the roles that each of these neurons play in human behavior and in midbrain-associated illnesses such as addiction, depression, schizophrenia, and Parkinson's disease. PMID:27477243

  4. Glutamate neurons are intermixed with midbrain dopamine neurons in nonhuman primates and humans

    PubMed Central

    Root, David H.; Wang, Hui-Ling; Liu, Bing; Barker, David J.; Mód, László; Szocsics, Péter; Silva, Afonso C.; Maglóczky, Zsófia; Morales, Marisela

    2016-01-01

    The rodent ventral tegmental area (VTA) and substantia nigra pars compacta (SNC) contain dopamine neurons intermixed with glutamate neurons (expressing vesicular glutamate transporter 2; VGluT2), which play roles in reward and aversion. However, identifying the neuronal compositions of the VTA and SNC in higher mammals has remained challenging. Here, we revealed VGluT2 neurons within the VTA and SNC of nonhuman primates and humans by simultaneous detection of VGluT2 mRNA and tyrosine hydroxylase (TH; for identification of dopamine neurons). We found that several VTA subdivisions share similar cellular compositions in nonhuman primates and humans; their rostral linear nuclei have a high prevalence of VGluT2 neurons lacking TH; their paranigral and parabrachial pigmented nuclei have mostly TH neurons, and their parabrachial pigmented nuclei have dual VGluT2-TH neurons. Within nonhuman primates and humans SNC, the vast majority of neurons are TH neurons but VGluT2 neurons were detected in the pars lateralis subdivision. The demonstration that midbrain dopamine neurons are intermixed with glutamate or glutamate-dopamine neurons from rodents to humans offers new opportunities for translational studies towards analyzing the roles that each of these neurons play in human behavior and in midbrain-associated illnesses such as addiction, depression, schizophrenia, and Parkinson’s disease. PMID:27477243

  5. FUEL ELEMENT

    DOEpatents

    Howard, R.C.; Bokros, J.C.

    1962-03-01

    A fueled matrlx eontnwinlng uncomblned carbon is deslgned for use in graphlte-moderated gas-cooled reactors designed for operatlon at temperatures (about 1500 deg F) at which conventional metallic cladding would ordlnarily undergo undesired carburization or physical degeneratlon. - The invention comprlses, broadly a fuel body containlng uncombined earbon, clad with a nickel alloy contalning over about 28 percent by' weight copper in the preferred embodlment. Thls element ls supporirted in the passageways in close tolerance with the walls of unclad graphite moderator materlal. (AEC)

  6. The Age of Enlightenment: Evolving Opportunities in Brain Research Through Optical Manipulation of Neuronal Activity

    PubMed Central

    Jerome, Jason; Heck, Detlef H.

    2011-01-01

    Optical manipulation of neuronal activity has rapidly developed into the most powerful and widely used approach to study mechanisms related to neuronal connectivity over a range of scales. Since the early use of single site uncaging to map network connectivity, rapid technological development of light modulation techniques has added important new options, such as fast scanning photostimulation, massively parallel control of light stimuli, holographic uncaging, and two-photon stimulation techniques. Exciting new developments in optogenetics complement neurotransmitter uncaging techniques by providing cell-type specificity and in vivo usability, providing optical access to the neural substrates of behavior. Here we review the rapid evolution of methods for the optical manipulation of neuronal activity, emphasizing crucial recent developments. PMID:22275886

  7. Identification and Rescue of α-Synuclein Toxicity in Parkinson Patient-Derived Neurons

    PubMed Central

    Chung, Chee Yeun; Khurana, Vikram; Auluck, Pavan K.; Tardiff, Daniel F.; Mazzulli, Joseph R.; Soldner, Frank; Baru, Valeriya; Lou, Yali; Freyzon, Yelena; Cho, Sukhee; Mungenast, Alison E.; Muffat, Julien; Mitalipova, Maisam; Pluth, Michael D; Jui, Nathan T.; Schüle, Birgitt; Lippard, Stephen J.; Tsai, Li-Huei; Krainc, Dimitri; Buchwald, Stephen L.; Jaenisch, Rudolf; Lindquist, Susan

    2014-01-01

    The induced pluripotent stem (iPS) cell field promises a new era for in vitro disease modeling. However, identifying innate cellular pathologies, particularly for age-related neurodegenerative diseases, has been challenging. Here, we exploited mutation correction of iPS cells and conserved proteotoxic mechanisms from yeast to human to discover and reverse phenotypic responses to α-Synuclein (αSyn), a key protein involved in Parkinson’s disease (PD). We generated cortical neurons from iPS cells of patients harboring αSyn mutations, who are at high risk of developing PD dementia. Genetic modifiers from unbiased screens in a yeast model of αSyn toxicity led to identification of early pathogenic phenotypes in patient neurons. These included nitrosative stress, accumulation of ER-associated degradation (ERAD) substrates and ER stress. A small molecule identified in a yeast screen, and the ubiquitin ligase Nedd4 it activates, reversed pathologic phenotypes in these neurons. PMID:24158904

  8. Lactate Effectively Covers Energy Demands during Neuronal Network Activity in Neonatal Hippocampal Slices

    PubMed Central

    Ivanov, Anton; Mukhtarov, Marat; Bregestovski, Piotr; Zilberter, Yuri

    2011-01-01

    Although numerous experimental data indicate that lactate is efficiently used for energy by the mature brain, the direct measurements of energy metabolism parameters during neuronal network activity in early postnatal development have not been performed. Therefore, the role of lactate in the energy metabolism of neurons at this age remains unclear. In this study, we monitored field potentials and contents of oxygen and NAD(P)H in correlation with oxidative metabolism during intense network activity in the CA1 hippocampal region of neonatal brain slices. We show that in the presence of glucose, lactate is effectively utilized as an energy substrate, causing an augmentation of oxidative metabolism. Moreover, in the absence of glucose lactate is fully capable of maintaining synaptic function. Therefore, during network activity in neonatal slices, lactate can be an efficient energy substrate capable of sustaining and enhancing aerobic energy metabolism. PMID:21602909

  9. Fuel cell development for transportation: Catalyst development

    SciTech Connect

    Doddapaneni, N.; Ingersoll, D.

    1996-12-31

    Fuel cells are being considered as alternative power sources for transportation and stationary applications. The degradation of commonly used electrode catalysts (e.g. Pt, Ag, and others) and corrosion of carbon substrates are making commercialization of fuel cells incorporating present day technologies economically problematic. Furthermore, due to the instability of the Pt catalyst, the performance of fuel cells declines on long-term operation. When methanol is used as the fuel, a voltage drop, as well as significant thermal management problems can be encountered, the later being due to chemical oxidation of methanol at the platinized carbon at the cathode. Though extensive work was conducted on platinized electrodes for both the oxidation and reduction reactions, due to the problems mentioned above, fuel cells have not been fully developed for widespread commercial use. Several investigators have previously evaluated metal macrocyclic complexes as alternative catalysts to Pt and Pt/Ru in fuel cells. Unfortunately, though they have demonstrated catalytic activity, these materials were found to be unstable on long term use in the fuel cell environment. In order to improve the long-term stability of metal macrocyclic complexes, we have chemically bonded these complexes to the carbon substrate, thereby enhancing their catalytic activity as well as their chemical stability in the fuel cell environment. We have designed, synthesized, and evaluated these catalysts for O{sub 2} reduction, H{sub 2} oxidation, and direct methanol oxidation in Proton Exchange Membrane (PEM) and aqueous carbonate fuel cells. These catalysts exhibited good catalytic activity and long-term stability. In this paper we confine our discussion to the initial performance results of some of these catalysts in H{sub 2}/O{sub 2} PEM fuel cells, including their long-term performance characteristics as well as CO poisoning effects on these catalysts.

  10. Mapping protease substrates using a biotinylated phage substrate library.

    SciTech Connect

    Scholle, M. D.; Kriplani, U.; Pabon, A.; Sishtla, K.; Glucksman, M. J.; Kay, B. K.; Biosciences Division; Chicago Medical School

    2005-05-05

    We describe a bacteriophage M13 substrate library encoding the AviTag (BirA substrate) and combinatorial heptamer peptides displayed at the N terminus of the mature form of capsid protein III. Phages are biotinylated efficiently (> or = 50%) when grown in E. coli cells coexpressing BirA, and such viral particles can be immobilized on a streptavidin-coated support and released by protease cleavage within the combinatorial peptide. We have used this library to map the specificity of human Factor Xa and a neuropeptidase, neurolysin (EC3.4.24.16). Validation by analysis of isolated peptide substrates has revealed that neurolysin recognizes the motif hydrophobic-X-Pro-Arg-hydrophobic, where Arg-hydrophobic is the scissile bond.

  11. Control of Neuronal Network in Caenorhabditis elegans

    PubMed Central

    Badhwar, Rahul; Bagler, Ganesh

    2015-01-01

    Caenorhabditis elegans, a soil dwelling nematode, is evolutionarily rudimentary and contains only ∼ 300 neurons which are connected to each other via chemical synapses and gap junctions. This structural connectivity can be perceived as nodes and edges of a graph. Controlling complex networked systems (such as nervous system) has been an area of excitement for mankind. Various methods have been developed to identify specific brain regions, which when controlled by external input can lead to achievement of control over the state of the system. But in case of neuronal connectivity network the properties of neurons identified as driver nodes is of much importance because nervous system can produce a variety of states (behaviour of the animal). Hence to gain insight on the type of control achieved in nervous system we implemented the notion of structural control from graph theory to C. elegans neuronal network. We identified ‘driver neurons’ which can provide full control over the network. We studied phenotypic properties of these neurons which are referred to as ‘phenoframe’ as well as the ‘genoframe’ which represents their genetic correlates. We find that the driver neurons are primarily motor neurons located in the ventral nerve cord and contribute to biological reproduction of the animal. Identification of driver neurons and its characterization adds a new dimension in controllability of C. elegans neuronal network. This study suggests the importance of driver neurons and their utility to control the behaviour of the organism. PMID:26413834

  12. The role of insulin receptor substrate 2 in hypothalamic and β cell function

    PubMed Central

    Choudhury, Agharul I.; Heffron, Helen; Smith, Mark A.; Al-Qassab, Hind; Xu, Allison W.; Selman, Colin; Simmgen, Marcus; Clements, Melanie; Claret, Marc; MacColl, Gavin; Bedford, David C.; Hisadome, Kazunari; Diakonov, Ivan; Moosajee, Vazira; Bell, Jimmy D.; Speakman, John R.; Batterham, Rachel L.; Barsh, Gregory S.; Ashford, Michael L.J.; Withers, Dominic J.

    2005-01-01

    Insulin receptor substrate 2 (Irs2) plays complex roles in energy homeostasis. We generated mice lacking Irs2 in β cells and a population of hypothalamic neurons (RIPCreIrs2KO), in all neurons (NesCreIrs2KO), and in proopiomelanocortin neurons (POMCCreIrs2KO) to determine the role of Irs2 in the CNS and β cell. RIPCreIrs2KO mice displayed impaired glucose tolerance and reduced β cell mass. Overt diabetes did not ensue, because β cells escaping Cre-mediated recombination progressively populated islets. RIPCreIrs2KO and NesCreIrs2KO mice displayed hyperphagia, obesity, and increased body length, which suggests altered melanocortin action. POMCCreIrs2KO mice did not display this phenotype. RIPCreIrs2KO and NesCreIrs2KO mice retained leptin sensitivity, which suggests that CNS Irs2 pathways are not required for leptin action. NesCreIrs2KO and POMCCreIrs2KO mice did not display reduced β cell mass, but NesCreIrs2KO mice displayed mild abnormalities of glucose homeostasis. RIPCre neurons did not express POMC or neuropeptide Y. Insulin and a melanocortin agonist depolarized RIPCre neurons, whereas leptin was ineffective. Insulin hyperpolarized and leptin depolarized POMC neurons. Our findings demonstrate a critical role for IRS2 in β cell and hypothalamic function and provide insights into the role of RIPCre neurons, a distinct hypothalamic neuronal population, in growth and energy homeostasis. PMID:15841180

  13. High performance, high durability non-precious metal fuel cell catalysts

    DOEpatents

    Wood, Thomas E.; Atanasoski, Radoslav; Schmoeckel, Alison K.

    2016-03-15

    This invention relates to non-precious metal fuel cell cathode catalysts, fuel cells that contain these catalysts, and methods of making the same. The fuel cell cathode catalysts are highly nitrogenated carbon materials that can contain a transition metal. The highly nitrogenated carbon materials can be supported on a nanoparticle substrate.

  14. Fuels characterization studies. [jet fuels

    NASA Technical Reports Server (NTRS)

    Seng, G. T.; Antoine, A. C.; Flores, F. J.

    1980-01-01

    Current analytical techniques used in the characterization of broadened properties fuels are briefly described. Included are liquid chromatography, gas chromatography, and nuclear magnetic resonance spectroscopy. High performance liquid chromatographic ground-type methods development is being approached from several directions, including aromatic fraction standards development and the elimination of standards through removal or partial removal of the alkene and aromatic fractions or through the use of whole fuel refractive index values. More sensitive methods for alkene determinations using an ultraviolet-visible detector are also being pursued. Some of the more successful gas chromatographic physical property determinations for petroleum derived fuels are the distillation curve (simulated distillation), heat of combustion, hydrogen content, API gravity, viscosity, flash point, and (to a lesser extent) freezing point.

  15. Nuclear Fuels.

    ERIC Educational Resources Information Center

    Nash, J. Thomas

    1983-01-01

    Trends in and factors related to the nuclear industry and nuclear fuel production are discussed. Topics addressed include nuclear reactors, survival of the U.S. uranium industry, production costs, budget cuts by the Department of Energy and U.S. Geological survey for resource studies, mining, and research/development activities. (JN)

  16. Future Fuel.

    ERIC Educational Resources Information Center

    Stover, Del

    1991-01-01

    Tough new environmental laws, coupled with fluctuating oil prices, are likely to prompt hundreds of school systems to examine alternative fuels. Literature reviews and interviews with 45 government, education, and industry officials provided data for a comparative analysis of gasoline, diesel, natural gas, methanol, and propane. (MLF)

  17. Alcohol fuels

    SciTech Connect

    Not Available

    1981-07-01

    The API publication 4312 reports a detailed study carried out by Battelle on the energy balances for five alcohol-fuel-producing technologies. The results indicate that processes for producing ethanol from corn are net consumers of energy while ethanol from sugar cane and methanol from wood are net energy producers.

  18. Fuel Cells

    ERIC Educational Resources Information Center

    Hawkins, M. D.

    1973-01-01

    Discusses the theories, construction, operation, types, and advantages of fuel cells developed by the American space programs. Indicates that the cell is an ideal small-scale power source characterized by its compactness, high efficiency, reliability, and freedom from polluting fumes. (CC)

  19. Bioactive DNA-Peptide Nanotubes Enhance the Differentiation of Neural Stem Cells Into Neurons

    PubMed Central

    2015-01-01

    We report the construction of DNA nanotubes covalently functionalized with the cell adhesion peptide RGDS as a bioactive substrate for neural stem cell differentiation. Alteration of the Watson–Crick base pairing program that builds the nanostructures allowed us to probe independently the effect of nanotube architecture and peptide bioactivity on stem cell differentiation. We found that both factors instruct synergistically the preferential differentiation of the cells into neurons rather than astrocytes. PMID:25546084

  20. Vacuum-assisted Fluid Flow in Microchannels to Pattern Substrates and Cells

    PubMed Central

    Shrirao, Anil B.; Kung, Frank H.; Yip, Derek; Cho, Cheul H.; Townes-Anderson, Ellen

    2014-01-01

    Substrate and cell patterning are widely used techniques in cell biology to study cell-to-cell and cell-to-substrate interactions. Conventional patterning techniques work well only with simple shapes, small areas and selected bio-materials. This paper describes a method to distribute cell suspensions as well as substrate solutions into complex, long, closed (dead-end) polydimethylsiloxane (PDMS) microchannels using negative pressure. Our method builds upon a previous vacuum-assisted method used for micromolding (Jeon, Choi et al. 1999) and successfully patterned collagen-I, fibronectin and Sal-1 substrates on glass and polystyrene surfaces, filling microchannels with lengths up to 120 mm and covering areas up to 13 × 10 mm2. Vacuum-patterned substrates were subsequently used to culture mammalian PC12 and fibroblast cells and amphibian neurons. Cells were also patterned directly by injecting cell suspensions into microchannels using vacuum. Fibroblast and neuronal cells patterned using vacuum showed normal growth and minimal cell death indicating no adverse effects of vacuum on cells. Our method fills reversibly sealed PDMS microchannels. This enables the user to remove the PDMS microchannel cast and access the patterned biomaterial or cells for further experimental purposes. Overall, this is a straightforward technique that has broad applicability for cell biology. PMID:24989641

  1. Spinophilin directs Protein Phosphatase 1 specificity by blocking substrate binding sites

    PubMed Central

    Ragusa, Michael J.; Dancheck, Barbara; Critton, David A.; Nairn, Angus C.; Page, Rebecca; Peti, Wolfgang

    2010-01-01

    The serine/threonine Protein Phosphatase 1 (PP1) dephosphorylates hundreds of key biological targets. PP1 associates with ≥200 regulatory proteins to form highly specific holoenzymes. These regulatory proteins target PP1 to its point of action within the cell and prime its enzymatic specificity for particular substrates. However, how they direct PP1’s specificity is not understood. Here we show that spinophilin, a neuronal PP1 regulator, is entirely unstructured in its unbound form and binds PP1, through a folding-upon-binding mechanism, in an elongated fashion, blocking one of PP1’s three putative substrate binding sites, without altering its active site. This mode of binding is sufficient for spinophilin to restrict PP1’s activity toward a model substrate in vitro, without affecting its ability to dephosphorylate its neuronal substrate GluR1. Thus, our work provides the molecular basis for the ability of spinophilin to dictate PP1 substrate specificity. PMID:20305656

  2. High spatial and temporal resolution wide-field imaging of neuron activity using quantum NV-diamond

    PubMed Central

    Hall, L. T.; Beart, G. C. G.; Thomas, E. A.; Simpson, D. A.; McGuinness, L. P.; Cole, J. H.; Manton, J. H.; Scholten, R. E.; Jelezko, F.; Wrachtrup, Jörg; Petrou, S.; Hollenberg, L. C. L.

    2012-01-01

    A quantitative understanding of the dynamics of biological neural networks is fundamental to gaining insight into information processing in the brain. While techniques exist to measure spatial or temporal properties of these networks, it remains a significant challenge to resolve the neural dynamics with subcellular spatial resolution. In this work we consider a fundamentally new form of wide-field imaging for neuronal networks based on the nanoscale magnetic field sensing properties of optically active spins in a diamond substrate. We analyse the sensitivity of the system to the magnetic field generated by an axon transmembrane potential and confirm these predictions experimentally using electronically-generated neuron signals. By numerical simulation of the time dependent transmembrane potential of a morphologically reconstructed hippocampal CA1 pyramidal neuron, we show that the imaging system is capable of imaging planar neuron activity non-invasively at millisecond temporal resolution and micron spatial resolution over wide-fields. PMID:22574249

  3. Human Cerebrospinal Fluid Promotes Neuronal Viability and Activity of Hippocampal Neuronal Circuits In Vitro

    PubMed Central

    Perez-Alcazar, Marta; Culley, Georgia; Lyckenvik, Tim; Mobarrez, Kristoffer; Bjorefeldt, Andreas; Wasling, Pontus; Seth, Henrik; Asztely, Frederik; Harrer, Andrea; Iglseder, Bernhard; Aigner, Ludwig; Hanse, Eric; Illes, Sebastian

    2016-01-01

    For decades it has been hypothesized that molecules within the cerebrospinal fluid (CSF) diffuse into the brain parenchyma and influence the function of neurons. However, the functional consequences of CSF on neuronal circuits are largely unexplored and unknown. A major reason for this is the absence of appropriate neuronal in vitro model systems, and it is uncertain if neurons cultured in pure CSF survive and preserve electrophysiological functionality in vitro. In this article, we present an approach to address how human CSF (hCSF) influences neuronal circuits in vitro. We validate our approach by comparing the morphology, viability, and electrophysiological function of single neurons and at the network level in rat organotypic slice and primary neuronal cultures cultivated either in hCSF or in defined standard culture media. Our results demonstrate that rodent hippocampal slices and primary neurons cultured in hCSF maintain neuronal morphology and preserve synaptic transmission. Importantly, we show that hCSF increases neuronal viability and the number of electrophysiologically active neurons in comparison to the culture media. In summary, our data indicate that hCSF represents a physiological environment for neurons in vitro and a superior culture condition compared to the defined standard media. Moreover, this experimental approach paves the way to assess the functional consequences of CSF on neuronal circuits as well as suggesting a novel strategy for central nervous system (CNS) disease modeling. PMID:26973467

  4. Fuel issues for fuel cell vehicles

    SciTech Connect

    Borroni-Bird, C.E.

    1995-12-31

    In the near-term, infrastructure and energy density concerns dictate that the most appropriate fuel for a light-duty fuel cell vehicle is probably not hydrogen; there are also several concerns with using methanol, the generally accepted most convenient fuel. In order to accelerate fuel cell commercialization it may be necessary to use petroleum-based fuels and on-board fuel processors. In the near-term, this approach may reduce fuel cell system efficiency to a level comparable with advanced diesel engines but in the long-term fuel cells powered by hydrogen should be the most efficient and cleanest of all automotive powertrains.

  5. A chimeric path to neuronal synchronization

    SciTech Connect

    Essaki Arumugam, Easwara Moorthy; Spano, Mark L.

    2015-01-15

    Synchronization of neuronal activity is associated with neurological disorders such as epilepsy. This process of neuronal synchronization is not fully understood. To further our understanding, we have experimentally studied the progression of this synchronization from normal neuronal firing to full synchronization. We implemented nine FitzHugh-Nagumo neurons (a simplified Hodgkin-Huxley model) via discrete electronics. For different coupling parameters (synaptic strengths), the neurons in the ring were either unsynchronized or completely synchronized when locally coupled in a ring. When a single long-range connection (nonlocal coupling) was introduced, an intermediate state known as a chimera appeared. The results indicate that (1) epilepsy is likely not only a dynamical disease but also a topological disease, strongly tied to the connectivity of the underlying network of neurons, and (2) the synchronization process in epilepsy may not be an “all or none” phenomenon, but can pass through an intermediate stage (chimera)

  6. A chimeric path to neuronal synchronization

    NASA Astrophysics Data System (ADS)

    Essaki Arumugam, Easwara Moorthy; Spano, Mark L.

    2015-01-01

    Synchronization of neuronal activity is associated with neurological disorders such as epilepsy. This process of neuronal synchronization is not fully understood. To further our understanding, we have experimentally studied the progression of this synchronization from normal neuronal firing to full synchronization. We implemented nine FitzHugh-Nagumo neurons (a simplified Hodgkin-Huxley model) via discrete electronics. For different coupling parameters (synaptic strengths), the neurons in the ring were either unsynchronized or completely synchronized when locally coupled in a ring. When a single long-range connection (nonlocal coupling) was introduced, an intermediate state known as a chimera appeared. The results indicate that (1) epilepsy is likely not only a dynamical disease but also a topological disease, strongly tied to the connectivity of the underlying network of neurons, and (2) the synchronization process in epilepsy may not be an "all or none" phenomenon, but can pass through an intermediate stage (chimera).

  7. Npas4: Linking Neuronal Activity to Memory.

    PubMed

    Sun, Xiaochen; Lin, Yingxi

    2016-04-01

    Immediate-early genes (IEGs) are rapidly activated after sensory and behavioral experience and are believed to be crucial for converting experience into long-term memory. Neuronal PAS domain protein 4 (Npas4), a recently discovered IEG, has several characteristics that make it likely to be a particularly important molecular link between neuronal activity and memory: it is among the most rapidly induced IEGs, is expressed only in neurons, and is selectively induced by neuronal activity. By orchestrating distinct activity-dependent gene programs in different neuronal populations, Npas4 affects synaptic connections in excitatory and inhibitory neurons, neural circuit plasticity, and memory formation. It may also be involved in circuit homeostasis through negative feedback and psychiatric disorders. We summarize these findings and discuss their implications. PMID:26987258

  8. Neuronal synaptobrevin promotes longevity in Drosophila photoreceptors

    PubMed Central

    Mejia, Jonathan; Haberman, Adam

    2012-01-01

    Neurons have unique challenges relative to other cell types. Unlike most other cells, neurons must remain healthy and functional throughout the lifespan of an animal. Premature neuronal loss underlies many age-related neurodegenerative diseases, including Alzheimer and Parkinson Diseases. Despite previous research aimed at understanding the mechanisms of age-related neurodegenerative diseases, little is known about the mechanisms that allow neurons to remain functional for the lifetime of a healthy animal. Understanding these cellular and biochemical processes is essential to promote healthful aging and reduce the severity of neurodegenerative disease. Here we discuss our recent identification of neuron-specific proteins that regulate endosome fusion events and the role of endosomes in maintaining healthy neurons. PMID:23740166

  9. Neuronal synaptobrevin promotes longevity in Drosophila photoreceptors.

    PubMed

    Mejia, Jonathan; Haberman, Adam

    2012-11-01

    Neurons have unique challenges relative to other cell types. Unlike most other cells, neurons must remain healthy and functional throughout the lifespan of an animal. Premature neuronal loss underlies many age-related neurodegenerative diseases, including Alzheimer and Parkinson Diseases. Despite previous research aimed at understanding the mechanisms of age-related neurodegenerative diseases, little is known about the mechanisms that allow neurons to remain functional for the lifetime of a healthy animal. Understanding these cellular and biochemical processes is essential to promote healthful aging and reduce the severity of neurodegenerative disease. Here we discuss our recent identification of neuron-specific proteins that regulate endosome fusion events and the role of endosomes in maintaining healthy neurons. PMID:23740166

  10. A new work mechanism on neuronal activity.

    PubMed

    Wang, Rubin; Tsuda, Ichiro; Zhang, Zhikang

    2015-05-01

    By re-examining the neuronal activity energy model, we show the inadequacies in the current understanding of the energy consumption associated with neuron activity. Specifically, we show computationally that a neuron first absorbs and then consumes energy during firing action potential, and this result cannot be produced from any current neuron models or biological neural networks. Based on this finding, we provide an explanation for the observation that when neurons are excited in the brain, blood flow increases significantly while the incremental oxygen consumption is very small. We can also explain why external stimulation and perception emergence are synchronized. We also show that negative energy presence in neurons at the sub-threshold state is an essential reason that leads to blood flow incremental response time in the brain rather than neural excitation to delay. PMID:25640576

  11. Porous substrates filled with nanomaterials

    DOEpatents

    Worsley, Marcus A.; Baumann, Theodore F.; Satcher, Jr., Joe H.; Stadermann, Michael

    2014-08-19

    A composition comprising: at least one porous carbon monolith, such as a carbon aerogel, comprising internal pores, and at least one nanomaterial, such as carbon nanotubes, disposed uniformly throughout the internal pores. The nanomaterial can be disposed in the middle of the monolith. In addition, a method for making a monolithic solid with both high surface area and good bulk electrical conductivity is provided. A porous substrate having a thickness of 100 microns or more and comprising macropores throughout its thickness is prepared. At least one catalyst is deposited inside the porous substrate. Subsequently, chemical vapor deposition is used to uniformly deposit a nanomaterial in the macropores throughout the thickness of the porous substrate. Applications include electrical energy storage, such as batteries and capacitors, and hydrogen storage.

  12. Coatings on reflective mask substrates

    DOEpatents

    Tong, William Man-Wai; Taylor, John S.; Hector, Scott D.; Mangat, Pawitter J. S.; Stivers, Alan R.; Kofron, Patrick G.; Thompson, Matthew A.

    2002-01-01

    A process for creating a mask substrate involving depositing: 1) a coating on one or both sides of a low thermal expansion material EUVL mask substrate to improve defect inspection, surface finishing, and defect levels; and 2) a high dielectric coating, on the backside to facilitate electrostatic chucking and to correct for any bowing caused by the stress imbalance imparted by either other deposited coatings or the multilayer coating of the mask substrate. An film, such as TaSi, may be deposited on the front side and/or back of the low thermal expansion material before the material coating to balance the stress. The low thermal expansion material with a silicon overlayer and a silicon and/or other conductive underlayer enables improved defect inspection and stress balancing.

  13. Nest of Origin Predicts Adult Neuron Addition Rates in the Vocal Control System of the Zebra Finch

    PubMed Central

    Hurley, Patrick; Pytte, Carolyn; Kirn, John R.

    2008-01-01

    Neurogenesis and neuronal replacement in adulthood represent dramatic forms of plasticity that might serve as a substrate for behavioral flexibility. In songbirds, neurons are continually replaced in HVC (used as a proper name), a pre-motor region necessary for the production of learned vocalizations. There are large individual differences in HVC neuron addition. Some of this variation is probably due to individual differences in adult experience; however, it is also possible that heritability or experience early in development constrains the levels of adult neuron addition. As a step toward addressing the latter two possibilities, we explored the extent to which nest of origin predicts rates of HVC neuron addition in adult male zebra finches. One month after injections of [3H]-thymidine to mark dividing cells, neuron addition in HVC was found to co-vary among birds that had been nest mates, even when they were housed in different cages as adults. We also tested whether nest mate co-variation might be due to shared adult auditory experience by measuring neuron addition in nest mate pairs after one member was deafened. There were significant differences in neuron addition between hearing and deaf birds but nest mate relationships persisted. These results suggest that variation in genotype and/or early pre- or postnatal experience can account for a large fraction of adult variation in rates of neuron addition. These results also suggest that a major constraint on neurogenesis and the capacity to adjust rates of neuron addition in response to adult auditory experience is established early in development. PMID:18431053

  14. Effects of attention and distractor contrast on the responses of middle temporal area neurons to transient motion direction changes.

    PubMed

    Khayat, Paul S; Martinez-Trujillo, Julio C

    2015-06-01

    The ability of primates to detect transient changes in a visual scene can be influenced by the allocation of attention, as well as by the presence of distractors. We investigated the neural substrates of these effects by recording the responses of neurons in the middle temporal area (MT) of two monkeys while they detected a transient motion direction change in a moving target. We found that positioning a distractor near the target impaired the change-detection performance of the animals. This impairment monotonically decreased as the distractor's contrast decreased. A neural correlate of this effect was a decrease in the ability of MT neurons to signal the direction change (detection sensitivity or DS) when a distractor was near the target, both located inside the neuron's receptive field. Moreover, decreasing distractor contrast increased neuronal DS. On the other hand, directing attention away from the target decreased neuronal DS. At the level of individual neurons, we found a negative correlation between the degree of response normalization and the DS. Finally, the intensity of a neuron's response to the change was predictive of the animal's reaction time, suggesting that the activity of our recorded neurons was linked to the animal's detection performance. Our results suggest that the ability of an MT neuron to signal a transient direction change is regulated by the degree of inhibitory drive into the cell. The presence of distractors, their contrast and the allocation of attention influence such inhibitory drive, therefore modulating the ability of the neurons to signal transient changes in stimulus features and consequently behavioral performance. PMID:25885809

  15. Flexible Metal Oxide/Graphene Oxide Hybrid Neuromorphic Transistors on Flexible Conducting Graphene Substrates.

    PubMed

    Wan, Chang Jin; Liu, Yang Hui; Feng, Ping; Wang, Wei; Zhu, Li Qiang; Liu, Zhao Ping; Shi, Yi; Wan, Qing

    2016-07-01

    Flexible metal oxide/graphene oxide hybrid multi-gate neuromorphic transistors are fabricated on flexible conducting graphene substrates. Dendritic integrations in both spatial and temporal modes are emulated, and spatiotemporal correlated logics are obtained. A proof-of-principle visual system model for emulating Lobula Giant Motion Detector neuron is also investigated. The results are of great significance for flexible sensors and neuromorphic cognitive systems. PMID:27159546

  16. Neuronal Networks on Nanocellulose Scaffolds.

    PubMed

    Jonsson, Malin; Brackmann, Christian; Puchades, Maja; Brattås, Karoline; Ewing, Andrew; Gatenholm, Paul; Enejder, Annika

    2015-11-01

    Proliferation, integration, and neurite extension of PC12 cells, a widely used culture model for cholinergic neurons, were studied in nanocellulose scaffolds biosynthesized by Gluconacetobacter xylinus to allow a three-dimensional (3D) extension of neurites better mimicking neuronal networks in tissue. The interaction with control scaffolds was compared with cationized nanocellulose (trimethyl ammonium betahydroxy propyl [TMAHP] cellulose) to investigate the impact of surface charges on the cell interaction mechanisms. Furthermore, coatings with extracellular matrix proteins (collagen, fibronectin, and laminin) were investigated to determine the importance of integrin-mediated cell attachment. Cell proliferation was evaluated by a cellular proliferation assay, while cell integration and neurite propagation were studied by simultaneous label-free Coherent anti-Stokes Raman Scattering and second harmonic generation microscopy, providing 3D images of PC12 cells and arrangement of nanocellulose fibrils, respectively. Cell attachment and proliferation were enhanced by TMAHP modification, but not by protein coating. Protein coating instead promoted active interaction between the cells and the scaffold, hence lateral cell migration and integration. Irrespective of surface modification, deepest cell integration measured was one to two cell layers, whereas neurites have a capacity to integrate deeper than the cell bodies in the scaffold due to their fine dimensions and amoeba-like migration pattern. Neurites with lengths of >50 μm were observed, successfully connecting individual cells and cell clusters. In conclusion, TMAHP-modified nanocellulose scaffolds promote initial cellular scaffold adhesion, which combined with additional cell-scaffold treatments enables further formation of 3D neuronal networks. PMID:26398224

  17. Fuel cells: A handbook

    NASA Astrophysics Data System (ADS)

    Kinoshita, K.; McLarnon, F. R.; Cairns, E. J.

    1988-05-01

    The purpose of this handbook is to present information describing fuel cells that is helpful to scientists, engineers, and technical managers who are not experienced in this technology, as well as to provide an update on the current technical status of the various types of fuel cells. Following the introduction, contents of this handbook are: fuel cell performance variables; phosphoric acid fuel cell; molten carbonate fuel cell; solid oxide fuel cell; alternative fuel cell technologies; fuel cell systems; and concluding remarks.

  18. Amyloid β-Protein as a Substrate Interacts with Extracellular Matrix to Promote Neurite Outgrowth

    NASA Astrophysics Data System (ADS)

    Koo, Edward H.; Park, Lisa; Selkoe, Dennis J.

    1993-05-01

    Progressive deposition of amyloid β-protein (Aβ) in brain parenchyma and blood vessels is a characteristic feature of Alzheimer disease. Recent evidence suggests that addition of solubilized synthetic Aβ to medium may produce toxic or trophic effects on cultured hippocampal neurons. Because soluble Aβ may not accumulate in significant quantities in brain, we asked whether immobilized Aβ peptide as a substrate alters neurite outgrowth from cultured rat peripheral sensory neurons. This paradigm may closely mimic the conditions in Alzheimer disease brain tissue, in which neurites contact insoluble, extracellular aggregates of β-amyloid. We detected no detrimental effects of Aβ substrate on neurite outgrowth. Rather, Aβ in combination with low doses of laminin or fibronectin enhanced neurite out-growth from these neuronal explants. Our results suggest that insoluble Aβ in the cerebral neuropil may serve as a neurite-promoting matrix, perhaps explaining the apparent regenerative response of neurites observed around amyloid plaques in Alzheimer disease. Moreover, in concert with the recent discovery of Aβ production by cultured neurons, our data suggest that Aβ plays a normal physiological role in brain by complexing with the extracellular matrix.

  19. Mechanotransduction of Neural Cells Through Cell-Substrate Interactions.

    PubMed

    Stukel, Jessica M; Willits, Rebecca Kuntz

    2016-06-01

    Neurons and neural stem cells are sensitive to their mechanical and topographical environment, and cell-substrate binding contributes to this sensitivity to activate signaling pathways for basic cell functions. Many transmembrane proteins transmit signals into and out of the cell, including integrins, growth factor receptors, G-protein-coupled receptors, cadherins, cell adhesion molecules, and ion channels. Specifically, integrins are one of the main transmembrane proteins that transmit force across the cell membrane between a cell and its extracellular matrix, making them critical in the study of cell-material interactions. This review focuses on mechanotransduction, defined as the conversion of force a cell generates through cell-substrate bonds to a chemical signal, of neural cells. The chemical signals relay information via pathways through the cellular cytoplasm to the nucleus, where signaling events can affect gene expression. Pathways and the cellular response initiated by substrate binding are explored to better understand their effect on neural cells mechanotransduction. As the results of mechanotransduction affect cell adhesion, cell shape, and differentiation, knowledge regarding neural mechanotransduction is critical for most regenerative strategies in tissue engineering, where novel environments are developed to improve conduit design for central and peripheral nervous system repair in vivo. PMID:26669274

  20. The genealogy of genealogy of neurons

    PubMed Central

    Moroz, Leonid L

    2014-01-01

    Two scenarios of neuronal evolution (monophyly and polyphyly) are discussed in the historical timeline starting from the 19th century. The recent genomic studies on Ctenophores re-initiated a broad interest in the hypotheses of independent origins of neurons. However, even earlier work on ctenophores suggested that their nervous systems are unique in many aspects of their organization and a possibility of the independent origin of neurons and synapses was introduced well before modern advances in genomic biology. PMID:26478767

  1. The genealogy of genealogy of neurons.

    PubMed

    Moroz, Leonid L

    2014-12-01

    Two scenarios of neuronal evolution (monophyly and polyphyly) are discussed in the historical timeline starting from the 19th century. The recent genomic studies on Ctenophores re-initiated a broad interest in the hypotheses of independent origins of neurons. However, even earlier work on ctenophores suggested that their nervous systems are unique in many aspects of their organization and a possibility of the independent origin of neurons and synapses was introduced well before modern advances in genomic biology. PMID:26478767

  2. High-Degree Neurons Feed Cortical Computations.

    PubMed

    Timme, Nicholas M; Ito, Shinya; Myroshnychenko, Maxym; Nigam, Sunny; Shimono, Masanori; Yeh, Fang-Chin; Hottowy, Pawel; Litke, Alan M; Beggs, John M

    2016-05-01

    Recent work has shown that functional connectivity among cortical neurons is highly varied, with a small percentage of neurons having many more connections than others. Also, recent theoretical developments now make it possible to quantify how neurons modify information from the connections they receive. Therefore, it is now possible to investigate how information modification, or computation, depends on the number of connections a neuron receives (in-degree) or sends out (out-degree). To do this, we recorded the simultaneous spiking activity of hundreds of neurons in cortico-hippocampal slice cultures using a high-density 512-electrode array. This preparation and recording method combination produced large numbers of neurons recorded at temporal and spatial resolutions that are not currently available in any in vivo recording system. We utilized transfer entropy (a well-established method for detecting linear and nonlinear interactions in time series) and the partial information decomposition (a powerful, recently developed tool for dissecting multivariate information processing into distinct parts) to quantify computation between neurons where information flows converged. We found that computations did not occur equally in all neurons throughout the networks. Surprisingly, neurons that computed large amounts of information tended to receive connections from high out-degree neurons. However, the in-degree of a neuron was not related to the amount of information it computed. To gain insight into these findings, we developed a simple feedforward network model. We found that a degree-modified Hebbian wiring rule best reproduced the pattern of computation and degree correlation results seen in the real data. Interestingly, this rule also maximized signal propagation in the presence of network-wide correlations, suggesting a mechanism by which cortex could deal with common random background input. These are the first results to show that the extent to which a neuron

  3. Neuron Model with Simplified Memristive Ionic Channels

    NASA Astrophysics Data System (ADS)

    Hegab, Almoatazbellah M.; Salem, Noha M.; Radwan, Ahmed G.; Chua, Leon

    2015-06-01

    A simplified neuron model is introduced to mimic the action potential generated by the famous Hodgkin-Huxley equations by using the genetic optimization algorithm. Comparison with different neuron models is investigated, and it is confirmed that the sodium and potassium channels in our simplified neuron model are made out of memristors. In addition, the channel equations in the simplified model may be adjusted to introduce a simplified memristor model that is in accordance with the theoretical conditions of the memristive systems.

  4. High-Degree Neurons Feed Cortical Computations

    PubMed Central

    Timme, Nicholas M.; Ito, Shinya; Shimono, Masanori; Yeh, Fang-Chin; Litke, Alan M.; Beggs, John M.

    2016-01-01

    Recent work has shown that functional connectivity among cortical neurons is highly varied, with a small percentage of neurons having many more connections than others. Also, recent theoretical developments now make it possible to quantify how neurons modify information from the connections they receive. Therefore, it is now possible to investigate how information modification, or computation, depends on the number of connections a neuron receives (in-degree) or sends out (out-degree). To do this, we recorded the simultaneous spiking activity of hundreds of neurons in cortico-hippocampal slice cultures using a high-density 512-electrode array. This preparation and recording method combination produced large numbers of neurons recorded at temporal and spatial resolutions that are not currently available in any in vivo recording system. We utilized transfer entropy (a well-established method for detecting linear and nonlinear interactions in time series) and the partial information decomposition (a powerful, recently developed tool for dissecting multivariate information processing into distinct parts) to quantify computation between neurons where information flows converged. We found that computations did not occur equally in all neurons throughout the networks. Surprisingly, neurons that computed large amounts of information tended to receive connections from high out-degree neurons. However, the in-degree of a neuron was not related to the amount of information it computed. To gain insight into these findings, we developed a simple feedforward network model. We found that a degree-modified Hebbian wiring rule best reproduced the pattern of computation and degree correlation results seen in the real data. Interestingly, this rule also maximized signal propagation in the presence of network-wide correlations, suggesting a mechanism by which cortex could deal with common random background input. These are the first results to show that the extent to which a neuron

  5. Performance limitations of relay neurons.

    PubMed

    Agarwal, Rahul; Sarma, Sridevi V

    2012-01-01

    Relay cells are prevalent throughout sensory systems and receive two types of inputs: driving and modulating. The driving input contains receptive field properties that must be transmitted while the modulating input alters the specifics of transmission. For example, the visual thalamus contains relay neurons that receive driving inputs from the retina that encode a visual image, and modulating inputs from reticular activating system and layer 6 of visual cortex that control what aspects of the image will be relayed back to visual cortex for perception. What gets relayed depends on several factors such as attentional demands and a subject's goals. In this paper, we analyze a biophysical based model of a relay cell and use systems theoretic tools to construct analytic bounds on how well the cell transmits a driving input as a function of the neuron's electrophysiological properties, the modulating input, and the driving signal parameters. We assume that the modulating input belongs to a class of sinusoidal signals and that the driving input is an irregular train of pulses with inter-pulse intervals obeying an exponential distribution. Our analysis applies to any [Formula: see text] order model as long as the neuron does not spike without a driving input pulse and exhibits a refractory period. Our bounds on relay reliability contain performance obtained through simulation of a second and third order model, and suggest, for instance, that if the frequency of the modulating input increases or the DC offset decreases, then relay increases. Our analysis also shows, for the first time, how the biophysical properties of the neuron (e.g. ion channel dynamics) define the oscillatory patterns needed in the modulating input for appropriately timed relay of sensory information. In our discussion, we describe how our bounds predict experimentally observed neural activity in the basal ganglia in (i) health, (ii) in Parkinson's disease (PD), and (iii) in PD during therapeutic deep

  6. Acute lower motor neuron tetraparesis.

    PubMed

    Añor, Sònia

    2014-11-01

    Flaccid nonambulatory tetraparesis or tetraplegia is an infrequent neurologic presentation; it is characteristic of neuromuscular disease (lower motor neuron [LMN] disease) rather than spinal cord disease. Paresis beginning in the pelvic limbs and progressing to the thoracic limbs resulting in flaccid tetraparesis or tetraplegia within 24 to 72 hours is a common presentation of peripheral nerve or neuromuscular junction disease. Complete body flaccidity develops with severe decrease or complete loss of spinal reflexes in pelvic and thoracic limbs. Animals with acute generalized LMN tetraparesis commonly show severe motor dysfunction in all limbs and severe generalized weakness in all muscles. PMID:25441630

  7. Nanostructured Substrates for Optical Sensing

    PubMed Central

    Kemling, Jonathan W.; Qavi, Abraham J.; Bailey, Ryan C.

    2011-01-01

    Sensors that change color have the advantages of versatility, ease of use, high sensitivity, and low cost. The recent development of optically based chemical sensing platforms has increasingly employed substrates manufactured with advanced processing or fabrication techniques to provide precise control over shape and morphology of the sensor micro- and nano-structure. New sensors have resulted with improved capabilities for a number of sensing applications, including the detection of biomolecules and environmental monitoring. This perspective focuses on recent optical sensor devices that utilize nanostructured substrates. PMID:22174955

  8. Silicon cladding for mirror substrates

    NASA Astrophysics Data System (ADS)

    Duston, Christopher J.; Gunda, Nilesh; Schwartz, Jay R.; Robichaud, Joseph L.

    2009-08-01

    To reduce the finishing costs of silicon carbide mirror substrates, silicon claddings are applied allowing the surfaces to be more easily diamond turned and polished than the bare chemical vapor deposited (CVD) silicon carbide or bimodal reaction bonded SiC (RB-SiC). The benefits of using silicon as the optical face will be reviewed as will the process for applying plasma enhanced chemical vapor (PE-CVD) deposited amorphous silicon cladding on substrates. Using one mirror as an example, the successful finishing results will be shared.

  9. Adsorption on a stepped substrate

    NASA Astrophysics Data System (ADS)

    Merikoski, J.; Timonen, J.; Kaski, K.

    1994-09-01

    The effect of substrate steps on the adsorption of particles is considered. The problem is formulated as a lattice-gas model with nearest neighbor interactions and it is studied by a numerical transfer-matrix method. In particular, the influence of the substrate-induced row potential on adsorbed monolayers is discussed. It is found that strong row-transition-like features appear in the presence of a row potential and it is suggested that these may be seen in adsorption on vicinal faces.

  10. Dopamine neurons control striatal cholinergic neurons via regionally heterogeneous dopamine and glutamate signaling

    PubMed Central

    Chuhma, Nao; Mingote, Susana; Moore, Holly; Rayport, Stephen

    2014-01-01

    Summary Midbrain dopamine neurons fire in bursts conveying salient information. Bursts are associated with pauses in tonic firing of striatal cholinergic interneurons. While the reciprocal balance of dopamine and acetylcholine in the striatum is well known, how dopamine neurons control cholinergic neurons has not been elucidated. Here we show that dopamine neurons make direct fast dopaminergic and glutamatergic connections with cholinergic interneurons, with regional heterogeneity. Dopamine neurons drive a burst-pause firing sequence in cholinergic interneurons in the medial shell of the nucleus accumbens, mixed actions in the accumbens core, and a pause in the dorsal striatum. This heterogeneity is due mainly to regional variation in dopamine-neuron glutamate cotransmission. A single dose of amphetamine attenuates dopamine neuron connections to cholinergic interneurons with dose-dependent regional specificity. Overall, the present data indicate that dopamine neurons control striatal circuit function via discrete, plastic connections with cholinergic interneurons. PMID:24559678

  11. Supplemental fuel vapor system

    SciTech Connect

    Foster, P.M.

    1991-01-08

    This patent describes a supplemental fuel system utilizing fuel vapor. It comprises: an internal combustion engine including a carburetor and an intake manifold; a fuel tank provided with air vents; a fuel conduit having a first end connected to the fuel tank and in communication with liquid fuel in the tank and a second end connected to the carburetor; the fuel conduit delivering the liquid fuel to the carburetor from the fuel tank; a fuel vapor conduit having a first end connected to the fuel tank at a location displaced from contact with the liquid fuel and a second end connected to a carbon canister; a PCV conduit having a first end connected to a pollution control valve and a second end connected to the intake manifold; and, an intermediate fuel vapor conduit having a first end connected to the fuel vapor conduit and a second end connected to the PCV conduit; wherein the air vents continuously provide air to the tank to mix with the liquid fuel and form fuel vapor. The fuel vapor drawn from the fuel tank by vacuum developed in the intake manifold and flows through the fuel vapor conduit. The intermediate fuel vapor conduit and the intake manifold to combustion chambers of the internal combustion engine so as to supplement fuel delivered to the engine by the fuel conduit. The liquid fuel and the fuel vapor constantly delivered to the engine during normal operation.

  12. A Postsynaptic AMPK→p21-Activated Kinase Pathway Drives Fasting-Induced Synaptic Plasticity in AgRP Neurons.

    PubMed

    Kong, Dong; Dagon, Yossi; Campbell, John N; Guo, Yikun; Yang, Zongfang; Yi, Xinchi; Aryal, Pratik; Wellenstein, Kerry; Kahn, Barbara B; Sabatini, Bernardo L; Lowell, Bradford B

    2016-07-01

    AMP-activated protein kinase (AMPK) plays an important role in regulating food intake. The downstream AMPK substrates and neurobiological mechanisms responsible for this, however, are ill defined. Agouti-related peptide (AgRP)-expressing neurons in the arcuate nucleus regulate hunger. Their firing increases with fasting, and once engaged they cause feeding. AgRP neuron activity is regulated by state-dependent synaptic plasticity: fasting increases dendritic spines and excitatory synaptic activity; feeding does the opposite. The signaling mechanisms underlying this, however, are also unknown. Using neuron-specific approaches to measure and manipulate kinase activity specifically within AgRP neurons, we establish that fasting increases AMPK activity in AgRP neurons, that increased AMPK activity in AgRP neurons is both necessary and sufficient for fasting-induced spinogenesis and excitatory synaptic activity, and that the AMPK phosphorylation target mediating this plasticity is p21-activated kinase. This provides a signaling and neurobiological basis for both AMPK regulation of energy balance and AgRP neuron state-dependent plasticity. PMID:27321921

  13. Targeting, Endocytosis, and Lysosomal Delivery of Active Enzymes to Model Human Neurons by ICAM-1-Targeted Nanocarriers

    PubMed Central

    Hsu, Janet; Hoenicka, Janet; Muro, Silvia

    2016-01-01

    Purpose Delivery of therapeutics to neurons is paramount to treat neurological conditions, including many lysosomal storage disorders. However, key aspects of drug-carrier behavior in neurons are relatively unknown: the occurrence of non-canonical endocytic pathways (present in other cells); whether carriers that traverse the blood-brain barrier are, contrarily, retained within neurons; if neuron-surface receptors are accessible to bulky carriers compared to small ligands; or if there are differences regarding neuronal compartments (neuron body vs. neurites) pertaining said parameters. We have explored these questions using model polymer nanocarriers targeting intercellular adhesion molecule-1 (ICAM-1). Methods Differentiated human neuroblastoma cells were incubated with anti-ICAM-coated polystyrene nanocarriers and analyzed by fluorescence microscopy. Results ICAM-1 expression and nanocarrier binding was enhanced in altered (TNFα) vs. control conditions. While small ICAM-1 ligands (anti-ICAM) preferentially accessed the cell body, anti-ICAM nanocarriers bound with faster kinetics to neurites, yet reached similar saturation over time. Anti-ICAM nanocarriers were also endocytosed with faster kinetics and lower saturation levels in neurites. Non-classical cell adhesion molecule (CAM) endocytosis ruled uptake, and neurite-to-cell body transport was inferred. Nanocarriers trafficked to lysosomes, delivering active enzymes (dextranase) with substrate reduction in a lysosomal-storage disease model. Conclusion ICAM-1-targeting holds potential for intracellular delivery of therapeutics to neurons. PMID:25319100

  14. Effective Stimuli for Constructing Reliable Neuron Models

    PubMed Central

    Druckmann, Shaul; Berger, Thomas K.; Schürmann, Felix; Hill, Sean; Markram, Henry; Segev, Idan

    2011-01-01

    The rich dynamical nature of neurons poses major conceptual and technical challenges for unraveling their nonlinear membrane properties. Traditionally, various current waveforms have been injected at the soma to probe neuron dynamics, but the rationale for selecting specific stimuli has never been rigorously justified. The present experimental and theoretical study proposes a novel framework, inspired by learning theory, for objectively selecting the stimuli that best unravel the neuron's dynamics. The efficacy of stimuli is assessed in terms of their ability to constrain the parameter space of biophysically detailed conductance-based models that faithfully replicate the neuron's dynamics as attested by their ability to generalize well to the neuron's response to novel experimental stimuli. We used this framework to evaluate a variety of stimuli in different types of cortical neurons, ages and animals. Despite their simplicity, a set of stimuli consisting of step and ramp current pulses outperforms synaptic-like noisy stimuli in revealing the dynamics of these neurons. The general framework that we propose paves a new way for defining, evaluating and standardizing effective electrical probing of neurons and will thus lay the foundation for a much deeper understanding of the electrical nature of these highly sophisticated and non-linear devices and of the neuronal networks that they compose. PMID:21876663

  15. Macroscopic Description for Networks of Spiking Neurons

    NASA Astrophysics Data System (ADS)

    Montbrió, Ernest; Pazó, Diego; Roxin, Alex

    2015-04-01

    A major goal of neuroscience, statistical physics, and nonlinear dynamics is to understand how brain function arises from the collective dynamics of networks of spiking neurons. This challenge has been chiefly addressed through large-scale numerical simulations. Alternatively, researchers have formulated mean-field theories to gain insight into macroscopic states of large neuronal networks in terms of the collective firing activity of the neurons, or the firing rate. However, these theories have not succeeded in establishing an exact correspondence between the firing rate of the network and the underlying microscopic state of the spiking neurons. This has largely constrained the range of applicability of such macroscopic descriptions, particularly when trying to describe neuronal synchronization. Here, we provide the derivation of a set of exact macroscopic equations for a network of spiking neurons. Our results reveal that the spike generation mechanism of individual neurons introduces an effective coupling between two biophysically relevant macroscopic quantities, the firing rate and the mean membrane potential, which together govern the evolution of the neuronal network. The resulting equations exactly describe all possible macroscopic dynamical states of the network, including states of synchronous spiking activity. Finally, we show that the firing-rate description is related, via a conformal map, to a low-dimensional description in terms of the Kuramoto order parameter, called Ott-Antonsen theory. We anticipate that our results will be an important tool in investigating how large networks of spiking neurons self-organize in time to process and encode information in the brain.

  16. Shaping Neuronal Network Activity by Presynaptic Mechanisms

    PubMed Central

    Ashery, Uri

    2015-01-01

    Neuronal microcircuits generate oscillatory activity, which has been linked to basic functions such as sleep, learning and sensorimotor gating. Although synaptic release processes are well known for their ability to shape the interaction between neurons in microcircuits, most computational models do not simulate the synaptic transmission process directly and hence cannot explain how changes in synaptic parameters alter neuronal network activity. In this paper, we present a novel neuronal network model that incorporates presynaptic release mechanisms, such as vesicle pool dynamics and calcium-dependent release probability, to model the spontaneous activity of neuronal networks. The model, which is based on modified leaky integrate-and-fire neurons, generates spontaneous network activity patterns, which are similar to experimental data and robust under changes in the model's primary gain parameters such as excitatory postsynaptic potential and connectivity ratio. Furthermore, it reliably recreates experimental findings and provides mechanistic explanations for data obtained from microelectrode array recordings, such as network burst termination and the effects of pharmacological and genetic manipulations. The model demonstrates how elevated asynchronous release, but not spontaneous release, synchronizes neuronal network activity and reveals that asynchronous release enhances utilization of the recycling vesicle pool to induce the network effect. The model further predicts a positive correlation between vesicle priming at the single-neuron level and burst frequency at the network level; this prediction is supported by experimental findings. Thus, the model is utilized to reveal how synaptic release processes at the neuronal level govern activity patterns and synchronization at the network level. PMID:26372048

  17. Glutamate Mediated Astrocytic Filtering of Neuronal Activity

    PubMed Central

    Herzog, Nitzan; De Pittà, Maurizio; Jacob, Eshel Ben; Berry, Hugues; Hanein, Yael

    2014-01-01

    Neuron-astrocyte communication is an important regulatory mechanism in various brain functions but its complexity and role are yet to be fully understood. In particular, the temporal pattern of astrocyte response to neuronal firing has not been fully characterized. Here, we used neuron-astrocyte cultures on multi-electrode arrays coupled to Ca2+ imaging and explored the range of neuronal stimulation frequencies while keeping constant the amount of stimulation. Our results reveal that astrocytes specifically respond to the frequency of neuronal stimulation by intracellular Ca2+ transients, with a clear onset of astrocytic activation at neuron firing rates around 3-5 Hz. The cell-to-cell heterogeneity of the astrocyte Ca2+ response was however large and increasing with stimulation frequency. Astrocytic activation by neurons was abolished with antagonists of type I metabotropic glutamate receptor, validating the glutamate-dependence of this neuron-to-astrocyte pathway. Using a realistic biophysical model of glutamate-based intracellular calcium signaling in astrocytes, we suggest that the stepwise response is due to the supralinear dynamics of intracellular IP3 and that the heterogeneity of the responses may be due to the heterogeneity of the astrocyte-to-astrocyte couplings via gap junction channels. Therefore our results present astrocyte intracellular Ca2+ activity as a nonlinear integrator of glutamate-dependent neuronal activity. PMID:25521344

  18. Novel Method for Neuronal Nanosurgical Connection

    PubMed Central

    Katchinskiy, Nir; Goez, Helly R.; Dutta, Indrani; Godbout, Roseline; Elezzabi, Abdulhakem Y.

    2016-01-01

    Neuronal injury may cause an irreversible damage to cellular, organ and organism function. While preventing neural injury is ideal, it is not always possible. There are multiple etiologies for neuronal injury including trauma, infection, inflammation, immune mediated disorders, toxins and hereditary conditions. We describe a novel laser application, utilizing femtosecond laser pulses, in order to connect neuronal axon to neuronal soma. We were able to maintain cellular viability, and demonstrate that this technique is universal as it is applicable to multiple cell types and media. PMID:26846892

  19. Neuronal polarity and the kinesin superfamily proteins.

    PubMed

    Nakata, Takao; Hirokawa, Nobutaka

    2007-02-01

    Neurons are highly polarized cells, typically with a long axon and relatively short dendrites. A wealth of recent data has identified a number of signaling molecules that are involved in neuronal polarization. Kinesin superfamily proteins (KIFs) contribute to the establishment and maintenance of neuronal polarity by selectively transporting various proteins and vesicles to either the axon or dendrites. Now evidence is emerging that KIFs also play an important role in axonal formation, the initial event of neuronal polarization. In particular, KIF13B transports phosphatidylinositol (3,4,5)-trisphosphate, which, based on current hypotheses, is one of the most upstream molecules in the intracellular signaling cascades involved in axonal formation. PMID:17284724

  20. Spiking Neurons for Analysis of Patterns

    NASA Technical Reports Server (NTRS)

    Huntsberger, Terrance

    2008-01-01

    Artificial neural networks comprising spiking neurons of a novel type have been conceived as improved pattern-analysis and pattern-recognition computational systems. These neurons are represented by a mathematical model denoted the state-variable model (SVM), which among other things, exploits a computational parallelism inherent in spiking-neuron geometry. Networks of SVM neurons offer advantages of speed and computational efficiency, relative to traditional artificial neural networks. The SVM also overcomes some of the limitations of prior spiking-neuron models. There are numerous potential pattern-recognition, tracking, and data-reduction (data preprocessing) applications for these SVM neural networks on Earth and in exploration of remote planets. Spiking neurons imitate biological neurons more closely than do the neurons of traditional artificial neural networks. A spiking neuron includes a central cell body (soma) surrounded by a tree-like interconnection network (dendrites). Spiking neurons are so named because they generate trains of output pulses (spikes) in response to inputs received from sensors or from other neurons. They gain their speed advantage over traditional neural networks by using the timing of individual spikes for computation, whereas traditional artificial neurons use averages of activity levels over time. Moreover, spiking neurons use the delays inherent in dendritic processing in order to efficiently encode the information content of incoming signals. Because traditional artificial neurons fail to capture this encoding, they have less processing capability, and so it is necessary to use more gates when implementing traditional artificial neurons in electronic circuitry. Such higher-order functions as dynamic tasking are effected by use of pools (collections) of spiking neurons interconnected by spike-transmitting fibers. The SVM includes adaptive thresholds and submodels of transport of ions (in imitation of such transport in biological

  1. Networks of neuroblastoma cells on porous silicon substrates reveal a small world topology.

    PubMed

    Marinaro, Giovanni; La Rocca, Rosanna; Toma, Andrea; Barberio, Marianna; Cancedda, Laura; Di Fabrizio, Enzo; Decuzzi, Paolo; Gentile, Francesco

    2015-02-01

    The human brain is a tightly interweaving network of neural cells where the complexity of the network is given by the large number of its constituents and its architecture. The topological structure of neurons in the brain translates into its increased computational capabilities, low energy consumption, and nondeterministic functions, which differentiate human behavior from artificial computational schemes. In this manuscript, we fabricated porous silicon chips with a small pore size ranging from 8 to 75 nm and large fractal dimensions up to Df ∼ 2.8. In culturing neuroblastoma N2A cells on the described substrates, we found that those cells adhere more firmly to and proliferate on the porous surfaces compared to the conventional nominally flat silicon substrates, which were used as controls. More importantly, we observed that N2A cells on the porous substrates create highly clustered, small world topology patterns. We conjecture that neurons with a similar architecture may elaborate information more efficiently than in random or regular grids. Moreover, we hypothesize that systems of neurons on nano-scale geometry evolve in time to form networks in which the propagation of information is maximized. PMID:25515929

  2. Electrogenic Steps Associated with Substrate Binding to the Neuronal Glutamate Transporter EAAC1.

    PubMed

    Tanui, Rose; Tao, Zhen; Silverstein, Nechama; Kanner, Baruch; Grewer, Christof

    2016-05-27

    Glutamate transporters actively take up glutamate into the cell, driven by the co-transport of sodium ions down their transmembrane concentration gradient. It was proposed that glutamate binds to its binding site and is subsequently transported across the membrane in the negatively charged form. With the glutamate binding site being located partially within the membrane domain, the possibility has to be considered that glutamate binding is dependent on the transmembrane potential and, thus, is electrogenic. Experiments presented in this report test this possibility. Rapid application of glutamate to the wild-type glutamate transporter subtype EAAC1 (excitatory amino acid carrier 1) through photo-release from caged glutamate generated a transient inward current, as expected for the electrogenic inward movement of co-transported Na(+) In contrast, glutamate application to a transporter with the mutation A334E induced transient outward current, consistent with movement of negatively charged glutamate into its binding site within the dielectric of the membrane. These results are in agreement with electrostatic calculations, predicting a valence for glutamate binding of -0.27. Control experiments further validate and rule out other possible explanations for the transient outward current. Electrogenic glutamate binding can be isolated in the mutant glutamate transporter because reactions, such as glutamate translocation and/or Na(+) binding to the glutamate-bound state, are inhibited by the A334E substitution. Electrogenic glutamate binding has to be considered together with other voltage-dependent partial reactions to cooperatively determine the voltage dependence of steady-state glutamate uptake and glutamate buffering at the synapse. PMID:27044739

  3. Neuronal Substrates of Relapse to Cocaine-Seeking Behavior: Role of Prefrontal Cortex

    ERIC Educational Resources Information Center

    Rebec, George V.; Sun, WenLin

    2005-01-01

    The return to drug seeking, even after prolonged periods of abstinence, is a defining feature of cocaine addiction. The neural circuitry underlying relapse has been identified in neuropharmacological studies of experimental animals, typically rats, and supported in brain imaging studies of human addicts. Although the nucleus accumbens (NAcc),…

  4. HDAC6 Regulates Mitochondrial Transport in Hippocampal Neurons

    PubMed Central

    Chen, Sigeng; Owens, Geoffrey C.; Makarenkova, Helen; Edelman, David B.

    2010-01-01

    Background Tubulin is a major substrate of the cytoplasmic class II histone deacetylase HDAC6. Inhibition of HDAC6 results in higher levels of acetylated tubulin and enhanced binding of the motor protein kinesin-1 to tubulin, which promotes transport of cargoes along microtubules. Microtubule-dependent intracellular trafficking may therefore be regulated by modulating the activity of HDAC6. We have shown previously that the neuromodulator serotonin increases mitochondrial movement in hippocampal neurons via the Akt-GSK3β signaling pathway. Here, we demonstrate a role for HDAC6 in this signaling pathway. Methodology/Principal Findings We found that the presence of tubacin, a specific HDAC6 inhibitor, dramatically enhanced mitochondrial movement in hippocampal neurons, whereas niltubacin, an inactive tubacin analog, had no effect. Compared to control cultures, higher levels of acetylated tubulin were found in neurons treated with tubacin, and more kinesin-1 was associated with mitochondria isolated from these neurons. Inhibition of GSK3β decreased cytoplasmic deacetylase activity and increased tubulin acetylation, whereas blockade of Akt, which phosphorylates and down-regulates GSK3β, increased cytoplasmic deacetylase activity and decreased tubulin acetylation. Concordantly, the administration of 5-HT, 8-OH-DPAT (a specific 5-HT1A receptor agonist), or fluoxetine (a 5-HT reuptake inhibitor) increased tubulin acetylation. GSK3β was found to co-localize with HDAC6 in hippocampal neurons, and inhibition of GSK3β resulted in decreased binding of antibody to phosphoserine-22, a potential GSK3β phosphorylation site in HDAC6. GSK3β may therefore regulate HDAC6 activity by phosphorylation. Conclusions/Significance This study demonstrates that HDAC6 plays an important role in the modulation of mitochondrial transport. The link between HDAC6 and GSK3β, established here, has important implications for our understanding of neurodegenerative disorders. In particular

  5. Substrate for thin silicon solar cells

    DOEpatents

    Ciszek, Theodore F.

    1998-01-01

    A substrate for a photovoltaic device wherein the substrate is the base upon which photosensitive material is to be grown and the substrate comprises an alloy having boron in a range from 0.1 atomic % of the alloy to 1.3 atomic % of the alloy and the substrate has a resistivity less than 3.times.10.sup.-3 ohm-cm.

  6. Semiconductor films on flexible iridium substrates

    DOEpatents

    Goyal, Amit

    2005-03-29

    A laminate semiconductor article includes a flexible substrate, an optional biaxially textured oxide buffer system on the flexible substrate, a biaxially textured Ir-based buffer layer on the substrate or the buffer system, and an epitaxial layer of a semiconductor. Ir can serve as a substrate with an epitaxial layer of a semiconductor thereon.

  7. Fuel composition

    SciTech Connect

    Johnson, T.H.

    1990-08-07

    This patent describes a concentrate suitable for use in liquid fuels in the gasoline boiling range. It comprises: from about 25 to about 500 ppm by weight of at least one poly(olefin)-N-substituted-carbamate; from about 0 to about 20 ppm by weight of a dehazer; and balance of diluent, boiling in the range from about 50{degrees}C. to about 232{degrees}C.

  8. Differential activation of serotonergic neurons during short- and long-term gregarization of desert locusts.

    PubMed

    Rogers, Stephen M; Ott, Swidbert R

    2015-02-01

    Serotonin is a neurochemical with evolutionarily conserved roles in orchestrating nervous system function and behavioural plasticity. A dramatic example is the rapid transformation of desert locusts from cryptic asocial animals into gregarious crop pests that occurs when drought forces them to accumulate on dwindling resources, triggering a profound alteration of behaviour within just a few hours. The onset of crowding induces a surge in serotonin within their thoracic ganglia that is sufficient and necessary to induce the switch from solitarious to gregarious behaviour. To identify the neurons responsible, we have analysed how acute exposure to three gregarizing stimuli--crowding, touching the hind legs or seeing and smelling other locusts--and prolonged group living affect the expression of serotonin in individual neurons in the thoracic ganglia. Quantitative analysis of cell body immunofluorescence revealed three classes of neurons with distinct expressional responses. All ganglia contained neurons that responded to multiple gregarizing stimuli with increased expression. A second class showed increased expression only in response to intense visual and olfactory stimuli from conspecifics. Prolonged group living affected a third and entirely different set of neurons, revealing a two-tiered role of the serotonergic system as both initiator and substrate of socially induced plasticity. This demonstrates the critical importance of ontogenetic time for understanding the function of serotonin in the reorganization of behaviour. PMID:25520357

  9. The synchronous activity of lateral habenular neurons is essential for regulating hippocampal theta oscillation.

    PubMed

    Aizawa, Hidenori; Yanagihara, Shin; Kobayashi, Megumi; Niisato, Kazue; Takekawa, Takashi; Harukuni, Rie; McHugh, Thomas J; Fukai, Tomoki; Isomura, Yoshikazu; Okamoto, Hitoshi

    2013-05-15

    Lateral habenula (LHb) has attracted growing interest as a regulator of serotonergic and dopaminergic neurons in the CNS. However, it remains unclear how the LHb modulates brain states in animals. To identify the neural substrates that are under the influence of LHb regulation, we examined the effects of rat LHb lesions on the hippocampal oscillatory activity associated with the transition of brain states. Our results showed that the LHb lesion shortened the theta activity duration both in anesthetized and sleeping rats. Furthermore, this inhibitory effect of LHb lesion on theta maintenance depended upon an intact serotonergic median raphe, suggesting that LHb activity plays an essential role in maintaining hippocampal theta oscillation via the serotonergic raphe. Multiunit recording of sleeping rats further revealed that firing of LHb neurons showed significant phase-locking activity at each theta oscillation cycle in the hippocampus. LHb neurons showing activity that was coordinated with that of the hippocampal theta were localized in the medial LHb division, which receives afferents from the diagonal band of Broca (DBB), a pacemaker region for the hippocampal theta oscillation. Thus, our findings indicate that the DBB may pace not only the hippocampus, but also the LHb, during rapid eye movement sleep. Since serotonin is known to negatively regulate theta oscillation in the hippocampus, phase-locking activity of the LHb neurons may act, under the influence of the DBB, to maintain the hippocampal theta oscillation by modulating the activity of serotonergic neurons. PMID:23678132

  10. DLK induces developmental neuronal degeneration via selective regulation of proapoptotic JNK activity.

    PubMed

    Ghosh, Arundhati Sengupta; Wang, Bei; Pozniak, Christine D; Chen, Mark; Watts, Ryan J; Lewcock, Joseph W

    2011-09-01

    The c-Jun N-terminal kinase (JNK) signaling pathway is essential for neuronal degeneration in multiple contexts but also regulates neuronal homeostasis. It remains unclear how neurons are able to dissociate proapoptotic JNK signaling from physiological JNK activity. In this paper, we show that the mixed lineage kinase dual leucine zipper kinase (DLK) selectively regulates the JNK-based stress response pathway to mediate axon degeneration and neuronal apoptosis without influencing other aspects of JNK signaling. This specificity is dependent on interaction of DLK with the scaffolding protein JIP3 to form a specialized JNK signaling complex. Local activation of DLK-based signaling in the axon results in phosphorylation of c-Jun and apoptosis after redistribution of JNK to the cell body. In contrast, regulation of axon degeneration by DLK is c-Jun independent and mediated by distinct JNK substrates. DLK-null mice displayed reduced apoptosis in multiple neuronal populations during development, demonstrating that prodegenerative DLK signaling is required in vivo. PMID:21893599

  11. Differential activation of serotonergic neurons during short- and long-term gregarization of desert locusts

    PubMed Central

    Rogers, Stephen M.; Ott, Swidbert R.

    2015-01-01

    Serotonin is a neurochemical with evolutionarily conserved roles in orchestrating nervous system function and behavioural plasticity. A dramatic example is the rapid transformation of desert locusts from cryptic asocial animals into gregarious crop pests that occurs when drought forces them to accumulate on dwindling resources, triggering a profound alteration of behaviour within just a few hours. The onset of crowding induces a surge in serotonin within their thoracic ganglia that is sufficient and necessary to induce the switch from solitarious to gregarious behaviour. To identify the neurons responsible, we have analysed how acute exposure to three gregarizing stimuli—crowding, touching the hind legs or seeing and smelling other locusts—and prolonged group living affect the expression of serotonin in individual neurons in the thoracic ganglia. Quantitative analysis of cell body immunofluorescence revealed three classes of neurons with distinct expressional responses. All ganglia contained neurons that responded to multiple gregarizing stimuli with increased expression. A second class showed increased expression only in response to intense visual and olfactory stimuli from conspecifics. Prolonged group living affected a third and entirely different set of neurons, revealing a two-tiered role of the serotonergic system as both initiator and substrate of socially induced plasticity. This demonstrates the critical importance of ontogenetic time for understanding the function of serotonin in the reorganization of behaviour. PMID:25520357

  12. AlGaN/GaN-based HEMTs for electrical stimulation of neuronal cell cultures

    NASA Astrophysics Data System (ADS)

    Witte, H.; Warnke, C.; Voigt, T.; de Lima, A.; Ivanov, I.; Vidakovic-Koch, T. R.; Sundmacher, K.; Krost, A.

    2011-09-01

    Unipolar source-drain voltage pulses of GaN/AlGaN-high electron mobility transistors (HEMTs) were used for stimulation of cultured neuronal networks obtained from embryonic rat cerebral cortex. The HEMT sensor was grown by metal organic vapour phase epitaxy on a 2 inch sapphire substrate consisting of 10 single HEMTs concentrically arranged around the wafer centre. Electrolytic reactions between the HEMT sensor surface and the culture medium were not detected using cyclic voltammetry. During voltage pulses and resulting neuronal excitation, capacitances were recharged giving indications of the contributions of the AlGaN and AlOx isolation layers between the two-dimensional electron gas channel and the neuron culture. The resulting threshold current for stimulation of neuron activity strongly depended on the culture and HEMT position on the sensor surface under consideration which was caused by different impedances of each neuron culture and position within the culture. The differences of culture impedances could be explained by variations of composition, thickness and conductivity of the culture areas.

  13. Functional metabolic interactions of human neuron-astrocyte 3D in vitro networks.

    PubMed

    Simão, Daniel; Terrasso, Ana P; Teixeira, Ana P; Brito, Catarina; Sonnewald, Ursula; Alves, Paula M

    2016-01-01

    The generation of human neural tissue-like 3D structures holds great promise for disease modeling, drug discovery and regenerative medicine strategies. Promoting the establishment of complex cell-cell interactions, 3D culture systems enable the development of human cell-based models with increased physiological relevance, over monolayer cultures. Here, we demonstrate the establishment of neuronal and astrocytic metabolic signatures and shuttles in a human 3D neural cell model, namely the glutamine-glutamate-GABA shuttle. This was indicated by labeling of neuronal GABA following incubation with the glia-specific substrate [2-(13)C]acetate, which decreased by methionine sulfoximine-induced inhibition of the glial enzyme glutamine synthetase. Cell metabolic specialization was further demonstrated by higher pyruvate carboxylase-derived labeling in glutamine than in glutamate, indicating its activity in astrocytes and not in neurons. Exposure to the neurotoxin acrylamide resulted in intracellular accumulation of glutamate and decreased GABA synthesis. These results suggest an acrylamide-induced impairment of neuronal synaptic vesicle trafficking and imbalanced glutamine-glutamate-GABA cycle, due to loss of cell-cell contacts at synaptic sites. This work demonstrates, for the first time to our knowledge, that neural differentiation of human cells in a 3D setting recapitulates neuronal-astrocytic metabolic interactions, highlighting the relevance of these models for toxicology and better understanding the crosstalk between human neural cells. PMID:27619889

  14. Assessment of GaN chips for culturing cerebellar granule neurons.

    PubMed

    Young, Tai-Horng; Chen, Chi-Ruei

    2006-06-01

    In this work, the behaviors of cerebellar granule neurons prepared from 7-day-old Wistar rats on gallium nitride (GaN) were investigated. We believe that this is the first time that the GaN has been used as a substrate for neuron cultures to examine its effect on cell response in vitro. The GaN surface structure and its relationship with cells were examined by atomic force microscopy (AFM), metallography microscopy, scanning electron microscopy (SEM), lactate dehydrogenase (LDH) release and Western blot analysis. GaN is a so-called III-V compound semiconductor material with a wide bandgap and a relatively high bandgap voltage. Compared with silicon used for most neural chips, neurons seeded on GaN were able to form an extensive neuritic network and expressed very high levels of GAP-43 coincident with the neurite outgrowth. Therefore, the GaN structure may spatially mediate cellular response that can promote neuronal cell attachment, differentiation and neuritic growth. The favorable biocompatibility characteristics of GaN can be used to measure electric signals from networks of neuronal cells in culture to make it a possible candidate for use in a microelectrode array. PMID:16516287

  15. Influence of GM1 gangliosides on the growth of cultured rat embryonic serotonergic neurons.

    PubMed

    Marlier, L; Poulat, P; König, N; Drian, M J; Privat, A

    1989-01-01

    GM1 gangliosides were added to the medium of cultured raphe neurons enriched in the serotonergic phenotype in order to study their influence on biochemical and morphological growth parameters of serotonergic neurons. After 2 days of culture in the presence of GM1, specific uptake of serotonin measured by scintillation counting exhibited a moderate but significant increase for a GM1 concentration of 5 X 10(-8) M. Morphological parameters of 5-HT neurons were measured after immunocytochemical staining with specific serotonin antiserum, and digitalization of immunoreactive cells. Eight parameters were studied; for concentrations of 5 X 10(-8) and 10(-7) M of GM1, the absolute neuritic field area and the total length of the segments were significantly increased, whereas the number of neuritic segments, and their mean length were not modified. We conclude that GM1 ganglioside has a significant influence on the growth of serotonergic neurons. Moreover, electron microscopy showed, on treated cultures, a dramatic increase of the number of spicules all along the neuron's process, suggesting that GM1 could act by modifying the attachment of cells to their substrate. The possible molecular mechanisms of the action of GM1 are discussed. PMID:2603760

  16. Nanotopography induced contact guidance of the F11 cell line during neuronal differentiation: a neuronal model cell line for tissue scaffold development

    NASA Astrophysics Data System (ADS)

    Wieringa, Paul; Tonazzini, Ilaria; Micera, Silvestro; Cecchini, Marco

    2012-07-01

    The F11 hybridoma, a dorsal root ganglion-derived cell line, was used to investigate the response of nociceptive sensory neurons to nanotopographical guidance cues. This established this cell line as a model of peripheral sensory neuron growth for tissue scaffold design. Cells were seeded on substrates of cyclic olefin copolymer (COC) films imprinted via nanoimprint lithography (NIL) with a grating pattern of nano-scale grooves and ridges. Different ridge widths were employed to alter the focal adhesion formation, thereby changing the cell/substrate interaction. Differentiation was stimulated with forskolin in culture medium consisting of either 1 or 10% fetal bovine serum (FBS). Per medium condition, similar neurite alignment was achieved over the four day period, with the 1% serum condition exhibiting longer, more aligned neurites. Immunostaining for focal adhesions found the 1% FBS condition to also have fewer, less developed focal adhesions. The robust response of the F11 to guidance cues further builds on the utility of this cell line as a sensory neuron model, representing a useful tool to explore the design of regenerative guidance tissue scaffolds.

  17. Dimethoxymethane and trimethoxymethane as alternative fuels for fuel cells

    NASA Astrophysics Data System (ADS)

    Chetty, Raghuram; Scott, Keith

    The electrooxidation of dimethoxymethane (DMM) and trimethoxymethane (TMM) was studied at different platinum-based electrocatalysts deposited onto a titanium mesh substrate by thermal decomposition of chloride precursors. Half-cell tests showed an increase in oxidation current for the methoxy fuels at the platinum electrode with the alloying of ruthenium and tin. Increase in reaction temperature and reactant concentration showed an increase in current density for the mesh-based anodes similar to carbon-supported catalysts. Single fuel cell tests, employing the titanium mesh anode with PtRu and PtSn catalysts showed maximum power densities up to 31 mW cm -2 and 48 mW cm -2 for 1.0 mol dm -3 aqueous solutions of DMM and TMM, respectively at 60 °C using oxygen.

  18. Neuronal Ceroid Lipofuscinosis (Batten's Disease)

    PubMed Central

    Gordon, N. S.; Marsden, H. B.; Noronha, M. J.

    1972-01-01

    Four patients are described, who on clinical, histological, and biochemical criteria are considered to be suffering from neuronal ceroid lipofuscinosis. It is suggested that this may be the commonest condition included under the term amaurotic family idiocy. A number of gangliosidoses can be classified on a biochemical basis and considerable advances have been made in identifying the enzyme deficiencies. The aetiology of neuronal ceroid lipofuscinosis is unknown, and it is possible that there is more than one cause. Visual symptoms and signs are not always present. Though generalized convulsions occur at the start of the illness, myoclonus tends increasingly to dominate the clinical picture. An abnormal sensitivity to photic stimulation at a very slow frequency is a suggestive finding. Evidence of cerebral atrophy on air-encephalography favours this diagnosis, as the brain tends to be enlarged in the gangliosidoses. A definite diagnosis can only be made in life by examination of a cortical biopsy. Biochemical analysis will show a normal ganglioside pattern, and histological examination by light and electron microscopy will reveal characteristic changes. An age dependent classification of amaurotic family idiocy is no longer justifiable, and if full investigations are carried out, an increasing number of these patients can be diagnosed as suffering from a specific type of disorder. ImagesFIG. 1FIG. 2 PMID:5023478

  19. Stages of neuronal network formation

    NASA Astrophysics Data System (ADS)

    Woiterski, Lydia; Claudepierre, Thomas; Luxenhofer, Robert; Jordan, Rainer; Käs, Josef A.

    2013-02-01

    Graph theoretical approaches have become a powerful tool for investigating the architecture and dynamics of complex networks. The topology of network graphs revealed small-world properties for very different real systems among these neuronal networks. In this study, we observed the early development of mouse retinal ganglion cell (RGC) networks in vitro using time-lapse video microscopy. By means of a time-resolved graph theoretical analysis of the connectivity, shortest path length and the edge length, we were able to discover the different stages during the network formation. Starting from single cells, at the first stage neurons connected to each other ending up in a network with maximum complexity. In the further course, we observed a simplification of the network which manifested in a change of relevant network parameters such as the minimization of the path length. Moreover, we found that RGC networks self-organized as small-world networks at both stages; however, the optimization occurred only in the second stage.

  20. Development of an advanced bond coat for solid oxide fuel cell interconnector applications

    NASA Astrophysics Data System (ADS)

    Yeh, An-Chou; Chen, Yu-Ming; Liu, Chien-Kuo; Shong, Wei-Ja

    2015-11-01

    An advanced bond coat has been developed for solid oxide fuel cell interconnector applications; a low thermal expansion superalloy has been selected as the substrate, and the newly developed bond coat is applied between the substrate and the LSM top coat. The bond coat composition is designed to be near thermodynamic equilibrium with the substrate to minimize interdiffusion with the substrate while providing oxidation protection for the substrate. The bond coat exhibits good oxidation resistance, a low area specific resistance, and a low thermal expansion coefficient at 800 °C; experimental results indicate that interdiffusion between the bond coat and the substrate can be hindered.

  1. Cerebellar Nuclear Neurons Use Time and Rate Coding to Transmit Purkinje Neuron Pauses.

    PubMed

    Sudhakar, Shyam Kumar; Torben-Nielsen, Benjamin; De Schutter, Erik

    2015-12-01

    Neurons of the cerebellar nuclei convey the final output of the cerebellum to their targets in various parts of the brain. Within the cerebellum their direct upstream connections originate from inhibitory Purkinje neurons. Purkinje neurons have a complex firing pattern of regular spikes interrupted by intermittent pauses of variable length. How can the cerebellar nucleus process this complex input pattern? In this modeling study, we investigate different forms of Purkinje neuron simple spike pause synchrony and its influence on candidate coding strategies in the cerebellar nuclei. That is, we investigate how different alignments of synchronous pauses in synthetic Purkinje neuron spike trains affect either time-locking or rate-changes in the downstream nuclei. We find that Purkinje neuron synchrony is mainly represented by changes in the firing rate of cerebellar nuclei neurons. Pause beginning synchronization produced a unique effect on nuclei neuron firing, while the effect of pause ending and pause overlapping synchronization could not be distinguished from each other. Pause beginning synchronization produced better time-locking of nuclear neurons for short length pauses. We also characterize the effect of pause length and spike jitter on the nuclear neuron firing. Additionally, we find that the rate of rebound responses in nuclear neurons after a synchronous pause is controlled by the firing rate of Purkinje neurons preceding it. PMID:26630202

  2. BigNeuron: Large-scale 3D Neuron Reconstruction from Optical Microscopy Images

    PubMed Central

    Peng, Hanchuan; Hawrylycz, Michael; Roskams, Jane; Hill, Sean; Spruston, Nelson; Meijering, Erik; Ascoli, Giorgio A.

    2016-01-01

    Understanding the structure of single neurons is critical for understanding how they function within neural circuits. BigNeuron is a new community effort that combines modern bioimaging informatics, recent leaps in labeling and microscopy, and the widely recognized need for openness and standardization to provide a community resource for automated reconstruction of dendritic and axonal morphology of single neurons. PMID:26182412

  3. Alcohol fuels

    SciTech Connect

    Not Available

    1990-07-01

    Ethanol is an alcohol made from grain that can be blended with gasoline to extend petroleum supplies and to increase gasoline octane levels. Congressional proposals to encourage greater use of alternative fuels could increase the demand for ethanol. This report evaluates the growth potential of the ethanol industry to meet future demand increases and the impacts increased production would have on American agriculture and the federal budget. It is found that ethanol production could double or triple in the next eight years, and that American farmers could provide the corn for this production increase. While corn growers would benefit, other agricultural segments would not; soybean producers, for example could suffer for increased corn oil production (an ethanol byproduct) and cattle ranchers would be faced with higher feed costs because of higher corn prices. Poultry farmers might benefit from lower priced feed. Overall, net farm cash income should increase, and consumers would see slightly higher food prices. Federal budget impacts would include a reduction in federal farm program outlays by an annual average of between $930 million (for double current production of ethanol) to $1.421 billion (for triple production) during the eight-year growth period. However, due to an partial tax exemption for ethanol blended fuels, federal fuel tax revenues could decrease by between $442 million and $813 million.

  4. Flexible substrate for printed wiring

    NASA Technical Reports Server (NTRS)

    Asakura, M.; Yabe, K.; Tanaka, H.; Soda, A.

    1982-01-01

    A very flexible substrate for printed wiring is disclosed which is composed of a blend of phenoxy resin-polyisocyanate-brominated epoxy resin in which the equivalent ration of the functional groups is hydroxyl grouped: isocyanate group: epoxy group = 1:0.2 to 2:0.5 to 3. The product has outstanding solder resistance and is applied to metal without using adhesives.

  5. Synthetic substrates for enzyme analysis

    DOEpatents

    Bissell, E.R.; Mitchell, A.R.; Pearson, K.W.; Smith, R.E.

    1983-06-14

    Synthetic substrates are provided which may be represented as A-D. The A moiety includes an amino acid, polypeptide, or derivative. The D moiety includes 7-amino coumarin derivatives having an electron withdrawing substituent group at the 3 position carbon or fused between the 3 and 4 position carbons. No Drawings

  6. Synthetic substrates for enzyme analysis

    DOEpatents

    Bissell, Eugene R.; Mitchell, Alexander R.; Pearson, Karen W.; Smith, Robert E.

    1983-01-01

    Synthetic substrates are provided which may be represented as A-D. The A moiety thereof includes an amino acid, polypeptide, or derivative thereof. The D moiety thereof includes 7-amino coumarin derivatives having an electron withdrawing substituent group at the 3 position carbon or fused between the 3 and 4 position carbons.

  7. Alternate Substrates for Bedding Plants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this work was to evaluate fresh Clean Chip Residual (CCR) as a substrate component for production of container-grown annuals. Loblolly pine trees (Pinus taeda) (12 year old planted pine plantation) were thinned and processed for clean chips using a total tree harvester. The residual...

  8. Cellulosic Substrates and Challenges Ahead

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The cost of production of butanol (acetone-butanol-ethanol; or ABE) is determined by feedstock prices, fermentation, recovery, by-product credits and the waste water treatment. Along these lines, we have an intensive research program on the use of various agricultural substrates, fermentation strate...

  9. Characterization of silicon carbide coatings on Zircaloy-4 substrates

    NASA Astrophysics Data System (ADS)

    Al-Olayyan, Yousif Abdullah

    The lifetime of light water reactor (LWR) fuels is limited by the corrosion and degradation of Zircaloy cladding in the high temperature and high pressure operating conditions. As the thickness of the oxide layer increases, stresses build up in the oxide layer due to density differences between the oxide and the zirconium metal which lead to degradation and spallation of the oxide layer. The main objective of this research is to form protective coatings on the Zircaloy clad to prevent or at least slow the oxidation which can allow higher burnup of the fuel resulting in major benefits in plant safety and economics. Silicon carbide was identified as a candidate protective coating to reduce the corrosion and degradation of Zircaloy cladding. Silicon carbide coatings were deposited on Zircaloy substrates using plasma-assisted chemical vapor deposition (PE-CVD) and were found to be amorphous as determined by X-ray analysis. Since the adhesion of the films to the substrate was the most important property of a coating, scratch tests were used to assess the adhesion. The effects of different parameters on the test results including residual stresses, plastic deformation and friction between the stylus and the surface are discussed. Critical loads, characterized by continuous delamination of the SiC coatings deposited on Zircaloy-4, occurred at 0.5--2.5 N. The experimental results indicated that all SiC coatings used in this project, without exception, showed an adhesive failure when tested by scratch and indentation tests. Plastic deformation of the substrate due to compressive stresses induced by the scratch stylus caused flaking of the films at the interface, which was attributed to the low interfacial toughness. The effects of film thickness and substrate surface treatment on the quality and adhesion of SiC coatings were studied in detail. Thick films (5mum) exhibited extensive cracking. The scratch tests indicated higher adhesion with intermediate substrate surface

  10. Inhibitory neurons modulate spontaneous signaling in cultured cortical neurons: density-dependent regulation of excitatory neuronal signaling

    NASA Astrophysics Data System (ADS)

    Serra, Michael; Guaraldi, Mary; Shea, Thomas B.

    2010-06-01

    Cortical neuronal activity depends on a balance between excitatory and inhibitory influences. Culturing of neurons on multi-electrode arrays (MEAs) has provided insight into the development and maintenance of neuronal networks. Herein, we seeded MEAs with murine embryonic cortical/hippocampal neurons at different densities (<150 or >1000 cells mm-2) and monitored resultant spontaneous signaling. Sparsely seeded cultures displayed a large number of bipolar, rapid, high-amplitude individual signals with no apparent temporal regularity. By contrast, densely seeded cultures instead displayed clusters of signals at regular intervals. These patterns were observed even within thinner and thicker areas of the same culture. GABAergic neurons (25% of total neurons in our cultures) mediated the differential signal patterns observed above, since addition of the inhibitory antagonist bicuculline to dense cultures and hippocampal slice cultures induced the signal pattern characteristic of sparse cultures. Sparsely seeded cultures likely lacked sufficient inhibitory neurons to modulate excitatory activity. Differential seeding of MEAs can provide a unique model for analyses of pertubation in the interaction between excitatory and inhibitory function during aging and neuropathological conditions where dysregulation of GABAergic neurons is a significant component.

  11. Mitochondrial Dysfunction during the Early Stages of Excitotoxic Spinal Motor Neuron Degeneration in Vivo.

    PubMed

    Santa-Cruz, Luz Diana; Guerrero-Castillo, Sergio; Uribe-Carvajal, Salvador; Tapia, Ricardo

    2016-07-20

    Glutamate excitotoxicity and mitochondrial dysfunction are involved in motor neuron degeneration process during amyotrophic lateral sclerosis (ALS). We have previously shown that microdialysis perfusion of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) in the lumbar region of the rat spinal cord produces permanent paralysis of the ipsilateral hindlimb and death of motor neurons by a Ca(2+)-dependent mechanism, in a process that starts 2-3 h after AMPA perfusion. Co-perfusion with different energy metabolic substrates, mainly pyruvate, prevented the paralysis and motor neuron degeneration induced by AMPA, suggesting that mitochondrial energetic deficiencies are involved in this excitotoxic motor neuron death. To test this, in the present work, we studied the functional and ultrastructural characteristics of mitochondria isolated from the ventral horns of lumbar spinal cords of rats, at the beginning of the AMPA-induced degeneration process, when motor neurons are still alive. Animals were divided in four groups: perfused with AMPA, AMPA + pyruvate, and pyruvate alone and Krebs-Ringer medium as controls. Mitochondria from the AMPA-treated group showed decreased oxygen consumption rates, respiratory controls, and transmembrane potentials. Additionally, activities of the respiratory chain complexes I and IV were significantly decreased. Electron microscopy showed that mitochondria from AMPA-treated rats presented swelling, disorganized cristae and disrupted membranes. Remarkably, in the animals co-perfused with AMPA and pyruvate all these abnormalities were prevented. We conclude that mitochondrial dysfunction plays a crucial role in spinal motor neuron degeneration induced by overactivation of AMPA receptors in vivo. These mechanisms could be involved in ALS motor neuron degeneration. PMID:27090876

  12. The neuronal basis of feeding in the snail, Helisoma, with comparisons to selected gastropods.

    PubMed

    Murphy, A D

    2001-03-01

    Research on identified neurons during the last quarter century was forecast at a conference in 1973 that discussed "neuronal mechanisms of coordination in simple systems." The focus of the conference was on the neuronal control of simple stereotyped behavioral acts. Participants discussing the future of such research called for a comparative approach; emphasis on structure-function interactions; attention to environmental and behavioral context; and the development of new techniques. Significantly, in some cases amazing progress has been made in these areas. Major conclusions of the last quarter century are that so-called simple behaviors and the neural circuitry underlying them tend to be less simple, more flexible, and more highly modulated than originally imagined. However, the comparative approach has, as yet, failed to reach its potential. Molluscan preparations, along with arthropods and annelids, have always been at the forefront of neuroethological studies. Circuitry underlying feeding has been studied in a handful of species of gastropod molluscs. These studies have contributed substantially to our understanding of sensorimotor organization, the hierarchical control of behavior and coordination of multiple behaviors, and the organization and modulation of central pattern generators. However, direct interspecific comparisons of feeding circuitry and potentially homologous neurons have been lacking. This is unfortunate because much of the vast radiation of the class Gastropoda is associated with variations in feeding behaviors and feeding apparatuses, providing ample substrates for comparative studies including the evolution of defined circuitry. Here, the neural organization of feeding in the snail, Helisoma, is examined critically. Possible direct interspecific comparisons of neural circuitry and potentially homologous neurons are made. A universal model for central pattern generators underlying rasping feeding is proposed. Future comparative studies can

  13. Augmentation of Normal and Glutamate-Impaired Neuronal Respiratory Capacity by Exogenous Alternative Biofuels

    PubMed Central

    Laird, Melissa D.; Clerc, Pascaline; Polster, Brian M.; Fiskum, Gary

    2013-01-01

    Mitochondrial respiratory capacity is critical for responding to changes in neuronal energy demand. One approach toward neuroprotection is administration of alternative energy substrates (“biofuels”) to overcome brain injury-induced inhibition of glucose-based aerobic energy metabolism. This study tested the hypothesis that exogenous pyruvate, lactate, β-hydroxybutyrate, and acetyl-L-carnitine each increase neuronal respiratory capacity in vitro either in the absence of, or following transient excitotoxic glutamate receptor stimulation. Compared to the presence of 5 mM glucose alone, the addition of pyruvate, lactate, or β-hydroxybutyrate (1.0 – 10.0 mM) to either day in vitro (DIV) 14 or 7 rat cortical neurons resulted in significant, dose-dependent stimulation of respiratory capacity, measured by cell respirometry as the maximal O2 consumption rate in the presence of the respiratory uncoupler FCCP. A thirty minute exposure to 100 μM glutamate impaired respiratory capacity for DIV 14 but not DIV 7 neurons. Glutamate reduced the respiratory capacity for DIV 14 neurons with glucose alone by 25% and also reduced respiratory capacity with glucose plus pyruvate, lactate or β-hydroxybutyrate. However, respiratory capacity in glutamate-exposed neurons following pyruvate or β-hydroxybutyrate addition was still at least as high as that obtained with glucose alone in the absence of glutamate exposure. These results support the interpretation that previously observed neuroprotection by exogenous pyruvate, lactate, or β-hydroxybutyrate is at least partially mediated by their preservation of neuronal respiratory capacity. PMID:24323418

  14. Functional and molecular defects of hiPSC-derived neurons from patients with ATM deficiency

    PubMed Central

    Carlessi, L; Poli, E Fusar; Bechi, G; Mantegazza, M; Pascucci, B; Narciso, L; Dogliotti, E; Sala, C; Verpelli, C; Lecis, D; Delia, D

    2014-01-01

    Loss of ataxia telangiectasia mutated (ATM) kinase, a key factor of the DNA damage response (DDR) pathway, causes the cancer predisposing and neurodegenerative syndrome ataxia-telangiectasia (A-T). To investigate the mechanisms of neurodegeneration, we have reprogrammed fibroblasts from ATM-null A-T patients and normal controls to pluripotency (human-induced pluripotent stem cells), and derived from these neural precursor cells able to terminally differentiate into post-mitotic neurons positive to >90% for β-tubulin III+/microtubule-associated protein 2+. We show that A-T neurons display similar voltage-gated potassium and sodium currents and discharges of action potentials as control neurons, but defective expression of the maturation and synaptic markers SCG10, SYP and PSD95 (postsynaptic density protein 95). A-T neurons exhibited defective repair of DNA double-strand breaks (DSBs) and repressed phosphorylation of ATM substrates (e.g., γH2AX, Smc1-S966, Kap1-S824, Chk2-T68, p53-S15), but normal repair of single-strand breaks, and normal short- and long-patch base excision repair activities. Moreover, A-T neurons were resistant to apoptosis induced by the genotoxic agents camptothecin and trabectedin, but as sensitive as controls to the oxidative agents. Most notably, A-T neurons exhibited abnormal accumulation of topoisomerase 1-DNA covalent complexes (Top1-ccs). These findings reveal that ATM deficiency impairs neuronal maturation, suppresses the response and repair of DNA DSBs, and enhances Top1-cc accumulation. Top1-cc could be a risk factor for neurodegeneration as they may interfere with transcription elongation and promote transcriptional decline. PMID:25032865

  15. Fuel densifier converts biomass into fuel cubes

    SciTech Connect

    Not Available

    1982-02-01

    A new cost-effective means to produce clean-burning and low cost commercial and industrial fuel is being introduced by Columbia Fuel Densification Corp., Phoenix. The Columbia Commercial Hydraulic Fuel Densifier converts raw biomass materials such as wood chips, paper, peat moss and rice hulls into densified fuel cubes. The densifier is mobile and its operation is briefly outlined.

  16. Motor neurons and the generation of spinal motor neuron diversity

    PubMed Central

    Stifani, Nicolas

    2014-01-01

    Motor neurons (MNs) are neuronal cells located in the central nervous system (CNS) controlling a variety of downstream targets. This function infers the existence of MN subtypes matching the identity of the targets they innervate. To illustrate the mechanism involved in the generation of cellular diversity and the acquisition of specific identity, this review will focus on spinal MNs (SpMNs) that have been the core of significant work and discoveries during the last decades. SpMNs are responsible for the contraction of effector muscles in the periphery. Humans possess more than 500 different skeletal muscles capable to work in a precise time and space coordination to generate complex movements such as walking or grasping. To ensure such refined coordination, SpMNs must retain the identity of the muscle they innervate. Within the last two decades, scientists around the world have produced considerable efforts to elucidate several critical steps of SpMNs differentiation. During development, SpMNs emerge from dividing progenitor cells located in the medial portion of the ventral neural tube. MN identities are established by patterning cues working in cooperation with intrinsic sets of transcription factors. As the embryo develop, MNs further differentiate in a stepwise manner to form compact anatomical groups termed pools connecting to a unique muscle target. MN pools are not homogeneous and comprise subtypes according to the muscle fibers they innervate. This article aims to provide a global view of MN classification as well as an up-to-date review of the molecular mechanisms involved in the generation of SpMN diversity. Remaining conundrums will be discussed since a complete understanding of those mechanisms constitutes the foundation required for the elaboration of prospective MN regeneration therapies. PMID:25346659

  17. Local and Commissural IC Neurons Make Axosomatic Inputs on Large GABAergic Tectothalamic Neurons

    PubMed Central

    Ito, Tetsufumi; Oliver, Douglas L.

    2014-01-01

    Large GABAergic (LG) neurons are a distinct type of neuron in the inferior colliculus (IC) identified by their dense VGLUT2-containing axosomatic synaptic terminals. Yet, the sources of these terminals are unknown. Since IC glutamatergic neurons express VGLUT2, and IC neurons are known to have local collaterals, we tested the hypothesis that these excitatory, glutamatergic axosomatic inputs on LG neurons come from local axonal collaterals and commissural IC neurons. We injected a recombinant viral tracer into the IC which enabled Golgi-like GFP labeling in both dendrites and axons. In all cases, we found terminals positive for both GFP and VGLUT2 (GFP+/VGLUT2+) that made axosomatic contacts on LG neurons. One to six axosomatic contacts were made on a single LG cell body by a single axonal branch. The GFP-labeled neurons giving rise to the VGLUT2+ terminals on LG neurons were close by. The density of GFP+/VGLUT2+ terminals on the LG neurons was related to the number of nearby GFP-labeled cells. On the contralateral side, a smaller number of LG neurons received axosomatic contacts from GFP+/VGLUT2+ terminals. In cases with a single GFP-labeled glutamatergic neuron, the labeled axonal plexus was flat, oriented in parallel to the fibrodendritic laminae, and contacted 9–30 LG cell bodies within the plexus. Our data demonstrated that within the IC microcircuitry, there is a convergence of inputs from local IC excitatory neurons on LG cell bodies. This suggests that LG neurons are heavily influenced by the activity of the nearby laminar glutamatergic neurons in the IC. PMID:24796971

  18. Influence of Substrate on PFSA Thin-Film Morphology

    NASA Astrophysics Data System (ADS)

    Dudenas, Peter; Kusoglu, Ahmet; Venkatakrishnan, Singanallur; Hexemer, Alexander; Weber, Adam

    Perfluorosulfonic-acid (PFSA) ionomers are the most commonly used electrolyte for polymer-electrolyte fuel cells (PEFCs) due to their high conductivity and good electrochemical and thermo-mechanical stability. A PFSA's chemical structure is comprised of a polytetrafluoroethylene (PTFE) backbone that provides mechanical and chemical stability, and randomly placed tethered perfluoroether side chains terminated with sulfonic-acid groups, which impart its remarkable proton-conduction capabilities. Controlled by substrate/film interactions, long-range structural order in PFSAs change when confined to thin films (<200 nm), as does its transport and mechanical properties. The nature of change is substrate dependent, where stronger interactions create a more dramatic change in properties. In this talk, grazing-incidence c-Ray scattering (GIXS) is used to demonstrate induced structural order on metallic substrates, which is not present on other substrates like silicon and carbon. The higher degree of ordering is correlated with measured changes in mechanical properties for the thin films. Scattering data is also modeled using the recently released program high-performance GISAXS (HipGISAXS), to estimate the size and distribution of the ordered domains. -/a

  19. Interface bonding between particle and substrate during HVOF spraying

    NASA Astrophysics Data System (ADS)

    Sun, Ce; Guo, Lei; Lu, Guanxiong; Lv, Yanbing; Ye, Fuxing

    2014-10-01

    The impact processes of Ni particles at initial temperature of 900 K on Al, Cu and Steel substrates were numerically analyzed by using ANSYS/LS-DYNA. Initial kinetic energy of the particle dissipated to particle and substrate simultaneously, the proportion of which was defined as energy distribution coefficient (K). The K values for Ni/Al, Ni/Cu and Ni/steel combinations were approximated to 4, 0.4 and 0.1, respectively. Individual Ni60 particles were deposited experimentally onto 6061-T6 aluminum alloy, copper and 304 stainless steel by High Velocity Oxy-fuel (HVOF) spraying. The contact between Ni particles and three substrates was not perfect. The bonding ratio, which is the effective contact area divided by total area, for Ni/Cu combination is 55.41%, larger than those for Ni/Al (40.78%) and Ni/steel (32.70%) combinations, indicating that moderate K value is beneficial for interface bonding between particle and substrate.

  20. PREFACE: Cell-substrate interactions Cell-substrate interactions

    NASA Astrophysics Data System (ADS)

    Gardel, Margaret; Schwarz, Ulrich

    2010-05-01

    One of the most striking achievements of evolution is the ability to build cellular systems that are both robust and dynamic. Taken by themselves, both properties are obvious requirements: robustness reflects the fact that cells are there to survive, and dynamics is required to adapt to changing environments. However, it is by no means trivial to understand how these two requirements can be implemented simultaneously in a physical system. The long and difficult quest to build adaptive materials is testimony to the inherent difficulty of this goal. Here materials science can learn a lot from nature, because cellular systems show that robustness and dynamics can be achieved in a synergetic fashion. For example, the capabilities of tissues to repair and regenerate are still unsurpassed in the world of synthetic materials. One of the most important aspects of the way biological cells adapt to their environment is their adhesive interaction with the substrate. Numerous aspects of the physiology of metazoan cells, including survival, proliferation, differentiation and migration, require the formation of adhesions to the cell substrate, typically an extracellular matrix protein. Adhesions guide these diverse processes both by mediating force transmission from the cell to the substrate and by controlling biochemical signaling pathways. While the study of cell-substrate adhesions is a mature field in cell biology, a quantitative biophysical understanding of how the interactions of the individual molecular components give rise to the rich dynamics and mechanical behaviors observed for cell-substrate adhesions has started to emerge only over the last decade or so. The recent growth of research activities on cell-substrate interactions was strongly driven by the introduction of new physical techniques for surface engineering into traditional cell biological work with cell culture. For example, microcontact printing of adhesive patterns was used to show that cell fate depends