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Sample records for ps-on sld neurons

  1. QCD at SLD

    Energy Technology Data Exchange (ETDEWEB)

    Plano, R. [Rutgers Univ., New Brunswick, NJ (United States)

    1997-01-01

    This talk reviews seven SLD papers, which provide useful, unique, and precise contributions to our understanding of hadron production in the decay of Z{sup 0} produced in e{sup +}e{sup -} collisions. The data were gathered by the SLAC Large Detector (SLD) at the SLAC Linear Collider (SLC). This accelerator/detector is able to systematic advantages including a tiny and stable interaction region combined with a precise high-resolution vertex detector, excellent particle identification, and a high-resolution vertex detector, excellent particle identification, and a highly polarized electron beam. The papers include studies of: (1) factorial and cumulant moments, (2) charged multiplicities produced by b, c, and uds quarks, (3) rapidity gaps, orientations and energy partitions of three-jet events, (4) jet handedness, (5) triple-product correlation in polarized Z{sup 0} decays to three jets, and {pi}{sup {+-}}, K{sup {+-}}, p, K{sup 0}, and {Lambda} production in Z{sup 0} decays. Comparisons are made to LEP results where appropriate.

  2. Dicty_cDB: SLD507 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available SL (Link to library) SLD507 (Link to dictyBase) - - - Contig-U13413-1 SLD507Z (Link... to Original site) - - SLD507Z 238 - - - - Show SLD507 Library SL (Link to library) Clone ID SLD507 (Link to...ycdb.biol.tsukuba.ac.jp/CSM/SL/SLD5-A/SLD507Q.Seq.d/ Representative seq. ID SLD50...7Z (Link to Original site) Representative DNA sequence >SLD507 (SLD507Q) /CSM/SL/SLD5-A/SLD507Q.Seq.d/ XXXXX...SLD566Q.Seq.d/ 319 1e-86 SLD507 (SLD507Q) /CSM/SL/SLD5-A/SLD507Q.Seq.d/ 319 1e-86 SLD326 (SLD326Q) /CSM/SL/S

  3. Dicty_cDB: SLD502 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available SL (Link to library) SLD502 (Link to dictyBase) - - - Contig-U16382-1 SLD502P (Link to Original site) SLD50...2F 297 SLD502Z 246 SLD502P 543 - - Show SLD502 Library SL (Link to library) Clone ID SLD50... URL http://dictycdb.biol.tsukuba.ac.jp/CSM/SL/SLD5-A/SLD502Q.Seq.d/ Representative seq. ID SLD50...2P (Link to Original site) Representative DNA sequence >SLD502 (SLD502Q) /CSM/SL/SLD5-A/SLD50...re E Sequences producing significant alignments: (bits) Value SLD502 (SLD502Q) /CSM/SL/SLD5-A/SLD502Q.Seq.d/

  4. Dicty_cDB: SLD508 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available SL (Link to library) SLD508 (Link to dictyBase) - - - Contig-U13482-1 SLD508P (Link to Original site) SLD50...8F 168 SLD508Z 205 SLD508P 373 - - Show SLD508 Library SL (Link to library) Clone ID SLD50... URL http://dictycdb.biol.tsukuba.ac.jp/CSM/SL/SLD5-A/SLD508Q.Seq.d/ Representative seq. ID SLD50...8P (Link to Original site) Representative DNA sequence >SLD508 (SLD508Q) /CSM/SL/SLD5-A/SLD50...significant alignments: (bits) Value SLD508 (SLD508Q) /CSM/SL/SLD5-A/SLD508Q.Seq.

  5. Dicty_cDB: SLD504 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available SL (Link to library) SLD504 (Link to dictyBase) - - - Contig-U16382-1 SLD504P (Link to Original site) SLD50...4F 322 SLD504Z 242 SLD504P 564 - - Show SLD504 Library SL (Link to library) Clone ID SLD50... URL http://dictycdb.biol.tsukuba.ac.jp/CSM/SL/SLD5-A/SLD504Q.Seq.d/ Representative seq. ID SLD50...4P (Link to Original site) Representative DNA sequence >SLD504 (SLD504Q) /CSM/SL/SLD5-A/SLD50....0 %: nuclear 24.0 %: cytoskeletal 4.0 %: mitochondrial >> prediction for SLD504 is cyt 5' end seq. ID SLD504F 5' end seq. >SLD50

  6. Latest Developments in SLD Scaling

    Science.gov (United States)

    Tsao, Jen-Ching; Anderson, David N.

    2006-01-01

    Scaling methods have been shown previously to work well for super cooled large droplet (SLD) main ice shapes. However, feather sizes for some conditions have not been well represented by scale tests. To determine if there are fundamental differences between the development of feathers for appendix C and SLD conditions, this study used time-sequenced photographs, viewing along the span of the model during icing sprays. An airspeed of 100 kt, cloud water drop MVDs of 30 and 140 microns, and stagnation freezing fractions of 0.30 and 0.50 were tested in the NASA Glenn Icing Research Tunnel using an unswept 91-cm-chord NACA0012 airfoil model mounted at 0deg AOA. The photos indicated that the feathers that developed in a distinct region downstream of the leading-edge ice determined the horn location and angle. The angle at which feathers grew from the surface were also measured; results are shown for an airspeed of 150 kt, an MVD of 30 microns, and stagnation freezing fractions of 0.30 to 0.60. Feather angles were found to depend strongly on the stagnation freezing fraction, and were independent of either chordwise position on the model or time into the spray. Feather angles also correlated well with horn angles. For these tests, there did not appear to be fundamental differences between the physics of SLD and appendix C icing; therefore, for these conditions similarity parameters used for appendix C scaling appear to be valid for SLD scaling as well. Further investigation into the cause for the large feather structures observed for some SLD conditions will continue.

  7. Localization of the brainstem GABAergic neurons controlling paradoxical (REM) sleep.

    Science.gov (United States)

    Sapin, Emilie; Lapray, Damien; Bérod, Anne; Goutagny, Romain; Léger, Lucienne; Ravassard, Pascal; Clément, Olivier; Hanriot, Lucie; Fort, Patrice; Luppi, Pierre-Hervé

    2009-01-01

    Paradoxical sleep (PS) is a state characterized by cortical activation, rapid eye movements and muscle atonia. Fifty years after its discovery, the neuronal network responsible for the genesis of PS has been only partially identified. We recently proposed that GABAergic neurons would have a pivotal role in that network. To localize these GABAergic neurons, we combined immunohistochemical detection of Fos with non-radioactive in situ hybridization of GAD67 mRNA (GABA synthesis enzyme) in control rats, rats deprived of PS for 72 h and rats allowed to recover after such deprivation. Here we show that GABAergic neurons gating PS (PS-off neurons) are principally located in the ventrolateral periaqueductal gray (vlPAG) and the dorsal part of the deep mesencephalic reticular nucleus immediately ventral to it (dDpMe). Furthermore, iontophoretic application of muscimol for 20 min in this area in head-restrained rats induced a strong and significant increase in PS quantities compared to saline. In addition, we found a large number of GABAergic PS-on neurons in the vlPAG/dDPMe region and the medullary reticular nuclei known to generate muscle atonia during PS. Finally, we showed that PS-on neurons triggering PS localized in the SLD are not GABAergic. Altogether, our results indicate that multiple populations of PS-on GABAergic neurons are distributed in the brainstem while only one population of PS-off GABAergic neurons localized in the vlPAG/dDpMe region exist. From these results, we propose a revised model for PS control in which GABAergic PS-on and PS-off neurons localized in the vlPAG/dDPMe region play leading roles.

  8. Localization of the brainstem GABAergic neurons controlling paradoxical (REM sleep.

    Directory of Open Access Journals (Sweden)

    Emilie Sapin

    Full Text Available Paradoxical sleep (PS is a state characterized by cortical activation, rapid eye movements and muscle atonia. Fifty years after its discovery, the neuronal network responsible for the genesis of PS has been only partially identified. We recently proposed that GABAergic neurons would have a pivotal role in that network. To localize these GABAergic neurons, we combined immunohistochemical detection of Fos with non-radioactive in situ hybridization of GAD67 mRNA (GABA synthesis enzyme in control rats, rats deprived of PS for 72 h and rats allowed to recover after such deprivation. Here we show that GABAergic neurons gating PS (PS-off neurons are principally located in the ventrolateral periaqueductal gray (vlPAG and the dorsal part of the deep mesencephalic reticular nucleus immediately ventral to it (dDpMe. Furthermore, iontophoretic application of muscimol for 20 min in this area in head-restrained rats induced a strong and significant increase in PS quantities compared to saline. In addition, we found a large number of GABAergic PS-on neurons in the vlPAG/dDPMe region and the medullary reticular nuclei known to generate muscle atonia during PS. Finally, we showed that PS-on neurons triggering PS localized in the SLD are not GABAergic. Altogether, our results indicate that multiple populations of PS-on GABAergic neurons are distributed in the brainstem while only one population of PS-off GABAergic neurons localized in the vlPAG/dDpMe region exist. From these results, we propose a revised model for PS control in which GABAergic PS-on and PS-off neurons localized in the vlPAG/dDPMe region play leading roles.

  9. Dicty_cDB: SLD501 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available SL (Link to library) SLD501 (Link to dictyBase) - - - Contig-U16513-1 SLD501P (Link to Original site) SLD50...1F 278 SLD501Z 263 SLD501P 541 - - Show SLD501 Library SL (Link to library) Clone ID SLD50... URL http://dictycdb.biol.tsukuba.ac.jp/CSM/SL/SLD5-A/SLD501Q.Seq.d/ Representative seq. ID SLD50...1P (Link to Original site) Representative DNA sequence >SLD501 (SLD501Q) /CSM/SL/SLD5-A/SLD50..... 551 e-153 1 ( AU061185 ) Dictyostelium discoideum slug cDNA, clone SLD501. 551

  10. The quaternary structure of the eukaryotic DNA replication proteins Sld7 and Sld3.

    Science.gov (United States)

    Itou, Hiroshi; Shirakihara, Yasuo; Araki, Hiroyuki

    2015-08-01

    The initiation of eukaryotic chromosomal DNA replication requires the formation of an active replicative helicase at the replication origins of chromosomes. Yeast Sld3 and its metazoan counterpart treslin are the hub proteins mediating protein associations critical for formation of the helicase. The Sld7 protein interacts with Sld3, and the complex formed is thought to regulate the function of Sld3. Although Sld7 is a non-essential DNA replication protein that is found in only a limited range of yeasts, its depletion slowed the growth of cells and caused a delay in the S phase. Recently, the Mdm2-binding protein was found to bind to treslin in humans, and its depletion causes defects in cells similar to the depletion of Sld7 in yeast, suggesting their functional relatedness and importance during the initiation step of DNA replication. Here, the crystal structure of Sld7 in complex with Sld3 is presented. Sld7 comprises two structural domains. The N-terminal domain of Sld7 binds to Sld3, and the C-terminal domains connect two Sld7 molecules in an antiparallel manner. The quaternary structure of the Sld3-Sld7 complex shown from the crystal structures appears to be suitable to activate two helicase molecules loaded onto replication origins in a head-to-head manner.

  11. Dicty_cDB: SLD503 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available SL (Link to library) SLD503 (Link to dictyBase) - G01943 DDB0203085 Contig-U12148-1 SLD50...3P (Link to Original site) SLD503F 298 SLD503Z 235 SLD503P 533 - - Show SLD503 Library SL (Link to library) Clone ID SLD50...ontig-U12148-1 Original site URL http://dictycdb.biol.tsukuba.ac.jp/CSM/SL/SLD5-A/SLD50...3Q.Seq.d/ Representative seq. ID SLD503P (Link to Original site) Representative DNA sequence >SLD503 (SLD50...3Q) /CSM/SL/SLD5-A/SLD503Q.Seq.d/ CTCATAAAAAAAAAAATTAATAATAATAATAATATTTTAAAAAATAATATCAAAAAAGTA AGAAAAAA

  12. Dicty_cDB: SLD509 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available SL (Link to library) SLD509 (Link to dictyBase) - - - Contig-U16328-1 SLD509Z (Link... to Original site) - - SLD509Z 216 - - - - Show SLD509 Library SL (Link to library) Clone ID SLD509 (Link to...ycdb.biol.tsukuba.ac.jp/CSM/SL/SLD5-A/SLD509Q.Seq.d/ Representative seq. ID SLD50...9Z (Link to Original site) Representative DNA sequence >SLD509 (SLD509Q) /CSM/SL/SLD5-A/SLD509Q.Seq.d/ XXXXX...cing significant alignments: (bits) Value SSF784 (SSF784Q) /CSM/SS/SSF7-D/SSF784Q.Seq.d/ 389 e-107 SLD509 (SLD50

  13. Sld7, an Sld3-associated protein required for efficient chromosomal DNA replication in budding yeast.

    Science.gov (United States)

    Tanaka, Tamon; Umemori, Toshiko; Endo, Shizuko; Muramatsu, Sachiko; Kanemaki, Masato; Kamimura, Yoichiro; Obuse, Chikashi; Araki, Hiroyuki

    2011-05-18

    Genetic screening of yeast for sld (synthetic lethality with dpb11) mutations has identified replication proteins, including Sld2, -3, and -5, and clarified the molecular mechanisms underlying eukaryotic chromosomal DNA replication. Here, we report a new replication protein, Sld7, identified by rescreening of sld mutations. Throughout the cell cycle, Sld7 forms a complex with Sld3, which associates with replication origins in a complex with Cdc45, binds to Dpb11 when phosphorylated by cyclin-dependent kinase, and dissociates from origins once DNA replication starts. However, Sld7 does not move with the replication fork. Sld7 binds to the nonessential N-terminal portion of Sld3 and reduces its affinity for Cdc45, a component of the replication fork. Although Sld7 is not essential for cell growth, its absence reduces the level of cellular Sld3, delays the dissociation from origins of GINS, a component of the replication fork, and slows S-phase progression. These results suggest that Sld7 is required for the proper function of Sld3 at the initiation of DNA replication.

  14. Dicty_cDB: SLD505 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available SL (Link to library) SLD505 (Link to dictyBase) - - - Contig-U14396-1 SLD505E (Link... to Original site) - - - - - - SLD505E 244 Show SLD505 Library SL (Link to library) Clone ID SLD505 (Link to...ycdb.biol.tsukuba.ac.jp/CSM/SL/SLD5-A/SLD505Q.Seq.d/ Representative seq. ID SLD50...5E (Link to Original site) Representative DNA sequence >SLD505 (SLD505Q) /CSM/SL/SLD5-A/SLD505Q.Seq.d/ CCCAG...telium discoideum slug cDNA, clone SLD505. 400 e-111 3 ( C93728 ) Dictyostelium discoideum slug cDNA, clone

  15. Heavy quark physics from SLD

    Energy Technology Data Exchange (ETDEWEB)

    Messner, R. [Stanford Univ., CA (United States)

    1997-01-01

    This report covers preliminary measurements from SLD on heavy quark production at the Z{sup 0}, using 150,000 hadronic Z{sup 0} decays accumulated during the 1993-1995 runs. A measurement of R{sub b} with a lifetime double tag is presented. The high electron beam polarization of the SLC is employed in the direct measurement of the parity-violating parameters A{sub b} and A{sub c} by use of the left-right forward-backward asymmetry. The lifetimes of B{sup +} and B{sup 0} mesons have been measured by two analyses. The first identifies semileptonic decays of B mesons with high (p,p{sub t}) leptons; the second analysis isolates a sample of B meson decays with a two-dimensional impact parameter tag and reconstructs the decay length and charge using a topological vertex reconstruction method.

  16. Electronic technology and the SLD detector

    Energy Technology Data Exchange (ETDEWEB)

    Fox, J.D.; Dean, T.; Fox, M.J.; Freytag, D.; Gioumousis, A.; Haller, G.; Hoeflich, J.; Horelick, D.; Kang, H; Mazaheri, G.; Nelson, D.J.; Olsen, J.J.; Oxoby, G.; Paffrath, L.; Stiles, P.; Yim, A. (Stanford Linear Accelerator Center, Menlo Park, CA (USA)); Bacchetta, N. (Istituto Nazionale di Fisica Nucleare, Padua (Italy)); Bilei, G.M. (Istituto Nazionale di Fisica Nucleare, Perugia (Italy)); Carpinelli, M.; Cast

    1990-06-01

    The SLD detector consists of five major subsystems, each with associated front-end electronics and an integrated FASTBUS control and data acquisition system. This paper highlights the choices among electronic technologies that have been developed for the SLD detector electronics. The common control, calibration, and data acquisition architectures are described. The functions of selected SLD integrated circuits, standard cells, gate arrays, and hybrids are summarized, and the integration of these functions into the common data acquisition path is described. Particular attention is directed to four areas of electronic technology developed for the SLD detector: the preamplifier hybrid designs are compared to their performance and implementation examined; the application of full custom CMOS digital circuits in SLD is compared to gate array and EPLD (electrically programmable logic device) implementations; the fiberoptic signal transmission techniques in SLD are examined and the data rates and link topology are presented; and finally, the packaging, power consumption, and cooling requirements for system functions resident inside the detector structure are explored. The rationale for the implementation choices in the SLD electronics is presented so that others might benefit from our experience.

  17. Dicty_cDB: SLD809 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available SL (Link to library) SLD809 (Link to dictyBase) - - - Contig-U16255-1 SLD809P (Link... to Original site) SLD809F 276 SLD809Z 277 SLD809P 553 - - Show SLD809 Library SL (Link to library) Clone ID SLD809 (Link to dict...yBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U16255-1 Original site URL http://dict...pdate 1999. 2.23 Translated Amino Acid sequence TSGGTPGSCDKVNCPNGYICTIVNQLAVCVSPSSSSSSSSSTTGSHTTTGGSTTGSHTTT...TTVMLMKKILMKISMVMMNLKLMLKVISKKMISKKNMHFIKLNFFS *knnnnnlitnhyhq**hynitlitilffniqrly Frame B: TSGGTPGSCDKVNCPNGYICT

  18. Dicty_cDB: SLD735 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available SL (Link to library) SLD735 (Link to dictyBase) - - - Contig-U16368-1 SLD735P (Link... to Original site) SLD735F 273 SLD735Z 143 SLD735P 416 - - Show SLD735 Library SL (Link to library) Clone ID SLD735 (Link to dict...yBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U16368-1 Original site URL http://dict...no Acid sequence ARPPHNLCRGFGCPEGSHXEVLEKHPVCVRNHVPPHPPPPPQICGSVNCGPGYICTIING HPTCIRGDGYLCNQTRCPHDYQCETISTNI...assaassessesssats*ikl*skkkkkkkkkvrtkx* Frame B: ARPPHNLCRGFGCPEGSHXEVLEKHPVCVRNHVPPHPPPPPQICGSVNCGPGYICT

  19. Dicty_cDB: SLD857 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 56 SLE791 (SLE791Q) /CSM/SL/SLE7-D/SLE791Q.Seq.d/ 218 4e-56 SLD503 (SLD503Q) /CSM/SL/SLD5-A/SLD503Q.Seq.d/ 2...( AU052545 ) Dictyostelium discoideum slug cDNA, clone SLD503. 218 9e-53 1 ( AU039585 ) Dictyostelium discoi

  20. Electroweak and heavy flavor physics at SLD

    Energy Technology Data Exchange (ETDEWEB)

    Willocq, S.; SLD Collaboration

    1997-12-01

    The authors review recent electroweak and B physics results obtained in polarized e{sup +}e{sup -} interactions at the SLC by the SLD experiment. Unique and precise measurements of the electroweak parameters A{sub e}, A{sub b}, A{sub c}, R{sub b} and R{sub c} provide powerful constraints on the Standard Model. The excellent 3-D vertexing capabilities of SLD are further exploited to extract precise B{sup +} and B{sub d}{sup 0} lifetimes, as well as measurements of the time evolution of B{sup 0}-{ovr B{sup 0}} mixing.

  1. Commissioning of SLAC SLD 45-Degree Chambers

    Energy Technology Data Exchange (ETDEWEB)

    Eschenburg, Vance O.

    2002-07-19

    The SLD experiment at the Stanford Linear Accelerator Center had a significant gap in its muon tracking coverage, provided by the Warm Iron Calorimeter. Supplemental planes of limited streamer tube chambers were added to improve the coverage in the vicinity of the gap at 0.65 < |cos{theta}| < 0.85. A software effort to upgrade the tracking software for this system is detailed. The commissioning of the forty-five degree chamber region of the SLAC SLD Warm Iron Calorimeter is presented. This task involved the completion of the forty-five degree chamber region geometry for the Warm Iron Calorimeter's fitter and swimmer and the changing of the way multiple scattering effects are treated in the fitter algorithm.

  2. Electroweak Measurements with Heavy Quarks at SLD

    Energy Technology Data Exchange (ETDEWEB)

    Bellodi, Giulia

    2000-10-03

    The SLD detector collected a sample of 550K hadronic events at the Z{sup 0} peak from e{sup +}e{sup -} collisions at the SLC during the 1993 to 1998 period. Polarized electron beams, a small and stable interaction point and the excellent performance of the 3-D CCD vertex detector provide a unique environment for precision electroweak tests of the Standard Model. Improved measurements of heavy quark electroweak parameters are presented here.

  3. Current Performance of the SLD VXD3

    Energy Technology Data Exchange (ETDEWEB)

    Abe, Toshinori

    1999-09-14

    During 1996, the SLD collaboration completed construction and began operation of a new charge-coupled device (CCD) vertex detector (VXD3). Since then, its performance has been studied in detail and a new topological vertexing technique has been developed. In this paper, we discuss the design of VXD3, procedures for aligning it, and the tracking and vertexing improvements that have led to its world-record performance.

  4. Early radiological diagnostics for scapholunate dissociation (SLD); Radiologische Fruehdiagnostik der skapholunaeren Dissoziation (SLD)

    Energy Technology Data Exchange (ETDEWEB)

    Schmitt, R.; Froehner, S.; Fodor, S.; Christopoulos, G. [Herz- und Gefaessklinik GmbH, Institut fuer Diagnostische und Interventionelle Radiologie, Bad Neustadt an der Saale (Germany); Kalb, K.H. [Herz- und Gefaessklinik GmbH, Bad Neustadt an der Saale (Germany). Klinik fuer Handchirurgie

    2006-08-15

    The partial tear of the scapholunate ligament (pre-dynamic stage of SLD) as well as the complete tear (dynamic stage) does not lead to carpal malalignment. However, if the completely ruptured ligament is accompanied by lesions of the extrinsic ligaments, both the scaphoid and the lunate are malaligned already at rest (static stage of SLD). Later, osteoarthritis will develop, beginning in the radioscaphoid compartment, progressing to the midcarpal joint, and ending in a carpal collapse (osteoarthrotic stage of SLD). Dynamic SLD is detectable only in stress views and in cinematography. The high utility of MRI for directly visualizing the injured ligament is emphasized: reparation tissue is focally enhanced at the rupture site by intravenously applied contrast agent; the individual segments of the scapholunate ligament can be visualized in direct MR arthrography, therefore allowing differentiation of partial and complete ligamentous tears. (orig.) [German] Die Teilruptur des Lig. scapholunatum (praedynamisches Stadium) und die isolierte Komplettruptur (dynamisches Stadium) fuehren zu keiner karpalen Gefuegestoerung in Ruhe. Erst wenn die Komplettruptur von Laesionen der extrinsischen Bandstabilisatoren begleitet wird, stehen das Skaphoid und Lunatum bereits in Ruhe in Fehlstellung (statisches Stadium). Spaeter kommt es zur Handgelenkarthrose, zuerst radioskaphoidal, dann mediokarpal mit Ausbildung eines karpalen Kollapses (arthrotisches Stadium). Die dynamische Instabilitaet ist nur mit Stressaufnahmen und kinematographisch nachweisbar. Die MRT vermag das rupturierte Lig. scapholunatum direkt darzustellen: Intravenoes verabreichtes Kontrastmittel reichert sich fokal am Reparationsgewebe der Rupturstelle an; mit der direkten MR-Arthrogaphie koennen die Bandsegmente besser abgegrenzt und Partial- von Komplettrupturen unterschieden werden. (orig.)

  5. Hadronic Charmless B Decays at the SLD

    Energy Technology Data Exchange (ETDEWEB)

    Reinertsen, Per L

    1999-09-02

    Rare decays of beauty particles were studied in several two-body exclusive hadronic charmless modes using the 19.4 pb-1 Z-pole data collected with the SLD detector at SLAC from 1993 to 1998. These decays are mediated by both tree level b {yields} u and one-loop penguin b {yields} s, d transitions. Upper limits for the branching ratios are set for the investigated modes Bs, B0 {yields} P+P-, B+ {yields} V P+ and Bs, B0 {yields} V V , where the pseudoscalar particle P+ is either {pi}+ or K+ and the vector particle V is either {rho}0, K* 0 or {phi}. Using an event selection algorithm consisting of a set of hard cuts combined with a set of discriminator functions, the efficiencies range between 24% and 37% with near zero background.

  6. QCD tests with SLD and polarized beams

    Energy Technology Data Exchange (ETDEWEB)

    Strauss, M.G. [Univ. of Massachusetts, Amherst, MA (United States)

    1994-12-01

    The author presents a measurement of the strong coupling {alpha}{sub s} derived from multijet rates using data collected by the SLD experiment at SLAC and find that {alpha}{sub s}(M{sub Z}{sup 2}) = 0.118 {+-} 0.002(stat.) {+-} 0.003(syst.) {+-} 0.010(theory). He presents tests of the flavor independence of strong interactions via preliminary measurements of the ratios {alpha}{sub s}(b)/{alpha}{sub s}(udsc) and {alpha}{sub s}(uds)/{alpha}{sub s}(bc). In addition, the group has measured the difference in charged particle multiplicity between Z{sup 0} {yields} b{bar b} and Z{sup 0} {yields} u{bar u}, d{bar d}, s{bar s} events, and find that it supports the prediction of perturbative QCD that the multiplicity difference be independent of center-of-mass energy. Finally, the group has made a preliminary study of jet polarization using the jet handedness technique.

  7. Managing the SLD Offline on a Shoestring via WWW

    CERN Document Server

    Dubois, R

    2003-01-01

    As a traditionally undermanned experiment, SLD has found it necessary to automate as much of its offline machinery and monitoring as possible. This includes all documentation, user education, group communication, monitoring of local and remote MC Farms, shift assignments, integrity of the code and monitoring of the analysis cluster. Additionally, monitoring of the data processing is performed on the web by remote users. They can access statistics, plots and event displays to ensure high data quality. The SLD web is designed to be an all-encompassing tool that allows maintenance of the offline system in good working order by a small group of people.

  8. An improved temperature compensation circuit for SLD light source of fiber-optic gyroscope

    Science.gov (United States)

    Chen, Xian; Yang, Jianhua; Zhou, Yilan; Shu, Xiaowu

    2017-10-01

    The super luminescent diode light source is commonly used in Fiber-optic gyroscope. The wavelength temperature stability is one of its key parameters. In this work, simulation model of temperature field of the SLD light source is established, and the temperature distribution of SLD internal structure is simulated and researched. A temperature compensation scheme is designed according to the simulation result and experiment is done to confirm the specific parameter of compensation circuit. Then the designed compensation scheme is used in temperature control circuit of SLD, and the performance of compensated SLD light source is tested. An improvement of 62% is demonstrated compared with uncompensated SLD.

  9. Further Assessment of MVD Effects in SLD Applications

    Science.gov (United States)

    Tsao, Jen-Ching; Anderson, David N.

    2006-01-01

    The study reported here is part of an effort to develop scaling methods for super cooled large droplet (SLD) conditions. Previously reported results showed that SLD main ice shapes can be simulated quite successfully by appendix C conditions using scaling methods developed for appendix C. However, when the velocity was higher than 100 kt, the feather size and density for SLD tests at MVDs well above 100 m was not well represented by the scaled appendix C conditions. This paper reports additional results of a study of the feather region with the objective of identifying differences between SLD and appendix C feathers. Both the feather appearance and the angle at which feathers grow from the airfoil surface were recorded over a range of MVD from 20 to 190 m for airspeeds of 100 and 200 kt and stagnation freezing fractions of 0.3 to 1.0. Tests were performed in the NASA Glenn Icing Research Tunnel (IRT) using a 91-cm-chord NACA0012 airfoil model mounted at 0 degrees AOA. Photographs are presented to illustrate details of feather appearance. Appearance was noticeably affected by the stagnation freezing fraction of the test, but not by velocity or MVD. The angle of feather growth relative to the chord line decreased with increasing stagnation freezing fraction. For a velocity of 100 kt, no significant effect of MVD on feather angle was apparent, but at 200 kt, feather angle tended to increase with MVD for glaze conditions, but not rime. This finding is based on limited data, and its significance with respect to icing physics has not been determined.

  10. Ice Roughness in Short Duration SLD Icing Events

    Science.gov (United States)

    McClain, Stephen T.; Reed, Dana; Vargas, Mario; Kreeger, Richard E.; Tsao, Jen-Ching

    2014-01-01

    Ice accretion codes depend on models of roughness parameters to account for the enhanced heat transfer during the ice accretion process. While mitigating supercooled large droplet (SLD or Appendix O) icing is a significant concern for manufacturers seeking future vehicle certification due to the pending regulation, historical ice roughness studies have been performed using Appendix C icing clouds which exhibit mean volumetric diameters (MVD) much smaller than SLD clouds. Further, the historical studies of roughness focused on extracting parametric representations of ice roughness using multiple images of roughness elements. In this study, the ice roughness developed on a 21-in. NACA 0012 at 0deg angle of attack exposed to short duration SLD icing events was measured in the Icing Research Tunnel at the NASA Glenn Research Center. The MVD's used in the study ranged from 100 micrometer to 200 micrometers, in a 67 m/s flow, with liquid water contents of either 0.6 gm/cubic meters or 0.75 gm/cubic meters. The ice surfaces were measured using a Romer Absolute Arm laser scanning system. The roughness associated with each surface point cloud was measured using the two-dimensional self-organizing map approach developed by McClain and Kreeger (2013) resulting in statistical descriptions of the ice roughness.

  11. Development and construction of the SLD Cerenkov Ring Imaging Detector

    Energy Technology Data Exchange (ETDEWEB)

    Aston, D.; Bean, A.; Bienz, T.; Bird, F.; Caldwell, D.; Cavalli-Sforza, M.; Coyle, P.; Coyne, D.; Dasu, S.; Dunwoodie, W.

    1989-06-01

    We report on the development and construction of the Cerenkov Ring Imaging Detector (CRID) for the SLD experiment at the SLAC linear collider. In particular, we outline recent progress in the construction, and results from testing the first components of the barrel CRID, including the drift boxes, liquid radiator trays and mirror system. We also review progress in the construction of the barrel CRID gas radiator vessel, the liquid radiator recirculator system, and the electronic readout system. The development of a comprehensive monitor and control system -- upon which the stable operation and physics efficacy of the CRID depend -- is also described. 19 refs., 9 figs.

  12. Regulation of DNA replication through Sld3-Dpb11 interaction is conserved from yeast to humans.

    Science.gov (United States)

    Boos, Dominik; Sanchez-Pulido, Luis; Rappas, Mathieu; Pearl, Laurence H; Oliver, Antony W; Ponting, Chris P; Diffley, John F X

    2011-07-12

    Cyclin-dependent kinases (CDKs) play crucial roles in promoting DNA replication and preventing rereplication in eukaryotic cells [1-4]. In budding yeast, CDKs promote DNA replication by phosphorylating two proteins, Sld2 and Sld3, which generates binding sites for pairs of BRCT repeats (breast cancer gene 1 [BRCA1] C terminal repeats) in the Dpb11 protein [5, 6]. The Sld3-Dpb11-Sld2 complex generated by CDK phosphorylation is required for the assembly and activation of the Cdc45-Mcm2-7-GINS (CMG) replicative helicase. In response to DNA replication stress, the interaction between Sld3 and Dpb11 is blocked by the checkpoint kinase Rad53 [7], which prevents late origin firing [7, 8]. Here we show that the two key CDK sites in Sld3 are conserved in the human Sld3-related protein Treslin/ticrr and are essential for DNA replication. Moreover, phosphorylation of these two sites mediates interaction with the orthologous pair of BRCT repeats in the human Dpb11 ortholog, TopBP1. Finally, we show that DNA replication stress prevents the interaction between Treslin/ticrr and TopBP1 via the Chk1 checkpoint kinase. Our results indicate that Treslin/ticrr is a genuine ortholog of Sld3 and that the Sld3-Dpb11 interaction has remained a critical nexus of S phase regulation through eukaryotic evolution. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Search for Bs Mixing with Inclusive Leptons at SLD

    CERN Document Server

    Baltay, C

    2003-01-01

    We have performed a sensitive search for B sub s sup 0 - (bar B) sub s sup 0 mixing using a sample of 400,000 hadronic Z sup 0 decays collected by the SLD experiment at the SLC between 1996 and 1998. B sub s sup 0 and (bar B) sub s sup 0 events were produced by Z sup 0 -> b(bar b) decays where each side hadronized independently to b hadrons. The analysis determines the b hadron flavor at production by exploiting the large polarized forward-backward asymmetry of the b quark as well as information from the hemisphere opposite that of the reconstructed B decay. The final state b quark flavor is determined by the charge of a high p sub T lepton. A novel, highly efficient vertexing technique has been developed to locate the B decay vertex by exploiting the high p sub T lepton and the semileptonic decay topology. No significant mixing signal was found and the following ranges of the oscillation frequency of B sub s sup 0 -(bar B) sub s sup 0 mixing are excluded at 95% CL from the analysis presented in this thesis: ...

  14. Preliminary results on heavy flavor physics at SLD

    Energy Technology Data Exchange (ETDEWEB)

    Usher, T. [Stanford Univ., CA (United States)

    1994-12-01

    The author reports on preliminary heavy flavor physics results from the SLD detector at the SLAC Linear Collider. Efficient tagging of b{bar b} events is achieved with an impact parameter technique that takes advantage of the small and stable interaction point of the SLC and all charged tracks in Z{sup 0} decays. This technique is applied to samples of Z{sup 0} events collected during the 1992 and 1993 physics runs. Preliminary measurements of the ratio R{sub b} = {Gamma}(Z{sup 0} {yields} b{bar b})/{Gamma}(Z{sup 0} {yields} hadrons) and the average B hadron lifetime <{tau}{sub B}> are reported. In a sample of 27K Z{sup 0} events, values of R{sub b} = 0.235 {+-} 0.006(stat.) {+-} 0.018(syst.) and <{tau}{sub B}> = 1.53 {+-} 0.006(stat.) {+-} 0.018(syst.) are obtained. In addition, the first measurement of the left-right asymmetry A{sub b} is reported. Using a sample of 38K Z{sup 0} events with a luminosity weighted electron polarization of 62%, the author obtains a preliminary value of A{sub b} = 0.94 {+-} 0.006(stat.) {+-} 0.018(syst.).

  15. A measurement of the tau Michel parameters at SLD

    Energy Technology Data Exchange (ETDEWEB)

    Quigley, James A. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

    1997-05-01

    This thesis presents a measurement of the tau Michel parameters. This measurement utilizes the highly polarized SLC electron beam to extract these quantities directly from the measured tau decay spectra using the 1993--95 SLD sample of 4,528 tau pair events. The results are ρe = 0.71 ± 0.14 ± 0.05, ζe = 1.16 ± 0.52 ± 0.06, and (ζδ)e = 0.85 ± 0.43 ± 0.08 for tau decays to electrons and ρμ = 0.54 ± 0.28 μ 0.14, ημ = -0.59 ± 0.82 ± 0.45, ζsup>μ = 0.75 ± 0.50 ± 0.14, and (ζδ)μ = 0.82 ± 0.32 ± 0.07 for tau decays to muons. Combining all leptonic tau decays gives ρ = 0.72 ± 0.09 ± 0.03, ζ = 1.05 ± 0.35 ± 0.04, and ζδ = 0.88 ± 0.27 ± 0.04. These results agree well with the current world average and the Standard Model.

  16. Crystal structure of the homology domain of the eukaryotic DNA replication proteins Sld3/Treslin.

    Science.gov (United States)

    Itou, Hiroshi; Muramatsu, Sachiko; Shirakihara, Yasuo; Araki, Hiroyuki

    2014-09-02

    The initiation of eukaryotic chromosomal DNA replication requires the formation of an active replicative helicase at the replication origins of chromosomal DNA. Yeast Sld3 and its metazoan counterpart Treslin are the hub proteins mediating protein associations critical for the helicase formation. Here, we show the crystal structure of the central domain of Sld3 that is conserved in Sld3/Treslin family of proteins. The domain consists of two segments with 12 helices and is sufficient to bind to Cdc45, the essential helicase component. The structure model of the Sld3-Cdc45 complex, which is crucial for the formation of the active helicase, is proposed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Search for Bs Mixing with Inclusive Leptons at SLD

    Energy Technology Data Exchange (ETDEWEB)

    Baltay, Charles

    2003-06-26

    We have performed a sensitive search for B{sub s}{sup 0} - {bar B}{sub s}{sup 0} mixing using a sample of 400,000 hadronic Z{sup 0} decays collected by the SLD experiment at the SLC between 1996 and 1998. B{sub s}{sup 0} and {bar B}{sub s}{sup 0} events were produced by Z{sup 0} {yields} b{bar b} decays where each side hadronized independently to b hadrons. The analysis determines the b hadron flavor at production by exploiting the large polarized forward-backward asymmetry of the b quark as well as information from the hemisphere opposite that of the reconstructed B decay. The final state b quark flavor is determined by the charge of a high p{sub T} lepton. A novel, highly efficient vertexing technique has been developed to locate the B decay vertex by exploiting the high p{sub T} lepton and the semileptonic decay topology. No significant mixing signal was found and the following ranges of the oscillation frequency of B{sub s}{sup 0}-{bar B}{sub s}{sup 0} mixing are excluded at 95% CL from the analysis presented in this thesis: {Delta}m{sub s} < 1.3 ps{sup -1}; 2.0 < {Delta}m{sub s} < 8.6 ps{sup -1}; and 9.8 < {Delta}m{sub s} < 12.2 ps{sup -1}. The gaps extending from 1.3 to 2.0 ps{sup -1} and 8.6 to 12.2 ps{sup -1} are excluded by other analyses. Combining results, {Delta}m{sub s} < 12.3 ps{sup -1} can be excluded at 95% CL. This limit puts significant constraints on the CKM unitarity triangle.

  18. High-speed 405-nm superluminescent diode (SLD) with 807-MHz modulation bandwidth

    KAUST Repository

    Shen, Chao

    2016-08-25

    III-nitride LEDs are fundamental components for visible-light communication (VLC). However, the modulation bandwidth is inherently limited by the relatively long carrier lifetime. In this letter, we present the 405 nm emitting superluminescent diode (SLD) with tilted facet design on semipolar GaN substrate, showing a broad emission of ∼9 nm at 20 mW optical power. Owing to the fast recombination (τ<0.35 ns) through the amplified spontaneous emission, the SLD exhibits a significantly large 3-dB bandwidth of 807 MHz. A data rate of 1.3 Gbps with a bit-error rate of 2.9 × 10 was obtained using on-off keying modulation scheme, suggesting the SLD being a high-speed transmitter for VLC applications.

  19. The impact of 4Ps on Purchase Decision: A case of Apple in Hanoi, Vietnam

    Directory of Open Access Journals (Sweden)

    Bui Trung Thieu

    2016-01-01

    Full Text Available By using quantitative research methods and deductive reasoning, this research paper aims to address the importance of four marketing mix components (4Ps on purchase decisions of customers of Apple Inc., by launching a survey in Hanoi, Vietnam, to generate primary data. The chosen sampling technique is quota sampling and several “quotas” were built. Descriptive analysis and hypothetical analysis (t-test, one-way ANOVA and Regression using SPSS 20.0 are applied. Other implications of the research and limitations were also discussed below.

  20. Stress Levels of Kuwaiti Mothers of Children with SLD: Does Work and Educational Status Matter?

    Science.gov (United States)

    Alazemi, Saad S.; Hadadian, Azar; Merbler, John B.; Wang, Cen

    2015-01-01

    Existing research literature indicates that parents of children with disabilities have higher stress. The purpose of this study was to examine differences in stress levels between mothers in relation to their children with specific learning disabilities (SLD). A sub sample of 91 mothers participated in the study. The outcome of the research…

  1. Analysis and simulation of the SLD WIC (Warm Iron Calorimeter) PADS hybrid preamplifier circuitry

    Energy Technology Data Exchange (ETDEWEB)

    Fox, J.D.; Horelick, D.

    1990-10-01

    The SLD PADS electronics consist of over 9000 channels of charge-sensitive preamplifiers followed by integrated sample/hold data storage, digitizing, and readout circuitry. This paper uses computer simulation techniques to analyze critical performance parameters of the preamplifier hybrid including its interactions with the detector system. Simulation results are presented and verified with measured performance. 6 refs., 9 figs.

  2. R{sub b},R{sub c} Measurements at SLD and LEP-I

    Energy Technology Data Exchange (ETDEWEB)

    Su, Dong

    2001-12-12

    This report summarizes the measurements of R{sub b}, R{sub c} at SLD and LEP-I. These measurements are sensitive probes of the Z{sup 0} couplings to heavy quarks, which provide precision tests of the Standard Model of electroweak interactions at {approx}0.3% and {approx}2% level respectively.

  3. When Theory Trumps Science: A Critique of the PSW Model for SLD Identification

    Science.gov (United States)

    McGill, Ryan J.; Busse, R. T.

    2017-01-01

    There has been vigorous debate within the state of California and elsewhere as to what constitutes appropriate procedures for determining whether an individual qualifies for special education and related services under the category of specific learning disability (SLD). Within the professional literature, there is growing support for educational…

  4. A Rejoinder on the PSW Model for SLD Identification: Still Concerned

    Science.gov (United States)

    McGill, Ryan J.; Busse, R. T.

    2017-01-01

    We address Christo, D'Incau, and Ponzuric's response to our original contribution to this journal "When theory trumps science: A critique of the PSW model for SLD identification." Christo and colleagues stated that there is an empirical support for pattern of strengths and weaknesses (PSW) procedures as a component in the identification…

  5. Measurement of the polarized forward-backward asymmetry of s-quarks at SLD

    Energy Technology Data Exchange (ETDEWEB)

    Narita, Shinya [Stanford Univ., CA (United States)

    1998-03-01

    This thesis presents a direct measurement of the parity-violating parameter As by analyzing the polarized forward-backward asymmetry of s quarks in e+e- →} Z0 → s$\\bar{s}$. The author has used the data taken at the Stanford Linear Accelerator Center (SLAC), from the SLAC Large Detector (SLD), which records the products of e+e- interactions at a center of mass energy √s = 91.2 GeV at the SLAC Linear Collider (SLC). The unique features of the SLC/SLD experimental apparatus provide interesting tests of the electroweak and the QCD physics. The small, stable SLC beam spot, and the precise tracking capability of the SLD allow the isolation of light flavor events. Charged hadrons are identified over wide momentum range with the Cherenkov Ring Imaging Detector (CRID). High momentum charged kaon, Λ0/$\\bar{Λ}$0, and K$0\\atop{s}$ are used to select Z0 → s$\\bar{s}$ events and to identify the s-quark direction. The averaged polarization was 63.0% in 1993 SLD run and 77.3% in 1994-95 run. The author obtained As = 0.86 ± 0.17(stat.) ± 0.10(syst.). This value is consistent with the prediction from the Standard Model and with the values of Ab measurements from SLD and LEP experiments.

  6. Parity Violation in Decays of Z Bosons into Heavy Quarks at SLD

    Energy Technology Data Exchange (ETDEWEB)

    Wright, Thomas R

    2002-09-16

    This work presents measurements of the parity-violation parameters A{sub c} and A{sub b} made at the Z pole. These measurements include the data taken with the SLD detector at the SLAC Linear Collider (SLC) during the period 1996-98. Heavy flavor events are selected with high efficiency and purity by searching for displaced vertices, identified with the SLD precision CCD vertex detector. Two methods are used for quark/antiquark discrimination: the net charge of the displaced vertex, and tracks in the displaced vertex identified as kaons by the SLD Cherenkov Ring Imaging Detector (CRID). The signal purities and analyzing powers are calibrated from the data to reduce the systematic errors and avoid experimental bias. The results are A{sub c} = 0.673 {+-} 0.029 {+-} 0.023 and A{sub b} = 0.919 {+-} 0.018 {+-} 0.017, where the first error is statistical and the second systematic. Fits to the electroweak data performed by the LEP Electroweak Working Group are used to study the consistency of the Standard Model, and to constrain the mass of the Standard Model Higgs boson.

  7. STS-55 Commander Nagel uses SAREX II inside the SL-D2 module aboard OV-102

    Science.gov (United States)

    1993-01-01

    STS-55 Commander Steven R. Nagel, wearing headset, holds the Shuttle Amateur Radio Experiment II (SAREX-II) transceiver during testing of the whip antenna protruding from the Spacelab Deutsche 2 (SL-D2) science module. Nagel is stationed in front of the SL-D2 aft end cone. The seven member crew participated in communications with students and licensed radio operators via SAREX. Attached to the aft end cone are a fire extinguisher and an STS-37 extravehicular activity (EVA) photo of Mission Specialist 1 (MS1) and Payload Commander (PLC) Jerry L. Ross (STS037-18-032).

  8. Measurement of the Z0 → $s\\bar{s}$ Coupling at the SLD

    Energy Technology Data Exchange (ETDEWEB)

    Staengle, Hermann

    1999-11-24

    This dissertation presents a direct measurement of the parity-violating coupling of the Z{sup 0} to strange quarks, A{sub s}, derived from e{sup +}e{sup -} collision data containing approximately 550,000 hadronic decays of polarized Z{sup 0} bosons. Data were recorded with the SLC Large Detector (SLD) at the SLAC Linear Collider (SLC) between 1993 and 1998 with an average electron beam polarization of 73% and 74% during the 1993-5 and 1996-8 run periods, respectively. Making use of several unique features of the SLC and SLD, this measurement relies on a new generation particle identification system, the Cherenkov Ring Imaging Detector, to test the Standard Model prediction of universality in the coupling of the Z{sup 0} to down-type quarks. Polarized Z{sup 0} --> s anti-s events are tagged by the presence in each event hemisphere of a high-momentum K {+-}, K{sub s}{sup 0} or Lambda{sup 0}/ anti-Lambda{sup 0} identified using particle identification and/or a mass tag. The background from heavy flavor events is suppressed with the CCD-based vertex detector. The event thrust axis is signed with the strangeness of the tagged particle to point in the direction of the initial s quark. The coupling A{sub s} is derived from a maximum likelihood fit to the polar angle distributions of the tagged s quark measured with left- and right-handed electron beams. To reduce the model dependence of the measurement, the background from u anti-u and d anti-d events as well as the analyzing power of the method for s anti-s events are constrained from the data. We obtain A{sub s} = 0.86 {+-} 0.08(stat.) {+-} 0.05(syst.). The result is consistent with both the Standard Model prediction and previous bottom quark coupling mA{sub b}, measurements performed by SLD and LEP, and therefore supports the predicted universality of the Z{sup 0} to down-type quark couplings.

  9. The left-right forward-backward asymmetry for B quarks at the SLD

    Energy Technology Data Exchange (ETDEWEB)

    Williams, David C. [Stanford Univ., CA (United States)

    1994-05-01

    The left-right asymmetry for b quarks, A{sub b}, is precisely predicted by the Weinberg-Salam-Glashow model of particle interactions, now the standard model for high-energy particle physics. As a test of this model, Ab is directly measured at the SLC Large Detector (SLD) by taking advantage of the unique polarized electron beam at the Stanford Linear Collider (SLC) and measuring the left-right forward-backward asymmetry of b quarks. To measure the asymmetry, b quarks are identified using muons of high total and transverse momenta. The result for the 1993 data sample of 37,843 hadronic Z`s is Ab = 0.91 ± 0.19 ± 0.06, where the first error is statistical and the second systematic. This result is in agreement with the standard model prediction of Ab = 0.935.

  10. Strangeonium spectroscopy at 11 GeV/c and Cherenkov Ring Imaging at the SLD

    Energy Technology Data Exchange (ETDEWEB)

    Bienz, T.L.

    1990-07-01

    This thesis is divided into two sections, which describe portions of the data acquisition system and online software for the Cherenkov Ring Imaging Detector (CRID) for the SLD, and analyses of several low cross section strangeonium channels in data from the LASS spectrometer. The CRID section includes a description of the data acquisition system, determination of the preamplifier gain, and development of an online pulse finding algorithm based on deconvolution. Deconvolution uses knowledge of the preamplifier impulse response to aid in pulse finding. The algorithm is fast and shows good single pulse resolution and excellent double pulse resolution in preliminary tests. The strangeonium analyses are based on data from a 4.1 event/nanobarn exposure of the LASS spectrometer in K{sup {minus}}p interactions at 11 GeV/c, and include studies of {Lambda}{eta}{pi}{sup {plus}}{pi}{sup {minus}}, {Lambda}{Kappa}*{Kappa}*, and {Lambda}{phi}{phi}.

  11. Archiving SLD Records in SRB: The Persistent Archives Test-Bed (PAT) Project at SLAC in 2004

    Energy Technology Data Exchange (ETDEWEB)

    Deken, J.

    2005-01-26

    Report on the first year of SLAC's participation in the collaboration to test the NARA prototype persistent archives' ability to perform the functions of accessioning, arrangement, description, preservation and access on the electronic records of the SLD (SLAC Large Detector) collaboration.

  12. Auditory perception of non-sense and familiar Bengali rhyming words in children with and without SLD.

    Science.gov (United States)

    Sinha, Anisha; Rout, Nachiketa

    2015-12-01

    Rhyming ability is among the earliest metaphonological skills to be acquired during the process of speech and language acquisition. Metalinguistic skills, particularly metaphonological skills, greatly influence language learning during early, school grades and reportedly children with learning disorders are poor at these skills. To develop and validate a Bengali rhyming checklist and study the auditory perception of non-sense and familiar Bengali rhyming words in children with and without specific learning disability (SLD). 60 children, age range 8-11years, participated in two groups; group-A included children with SLD and group-B, typically developing children (TDC). All participants were native Bengali speakers, attending regular school, with hearing sensitivity less than 25dBHL, no history of ear discharge and middle socioeconomic background. A rhyming checklist was developed in Bengali, consisting of familiar (section-A) and non-sense (section-B) words. Test-retest reliability and validity measures were obtained. The items on the checklist were audio recorded and presented to the participants in a rhyming judgment task in one to one set up. Scores were obtained and statistically analyzed using SPSS software (version-11.0). Children with SLD scored significantly low on the rhyming judgment task as against TDC (p.05). Semantic content influences rhyming perception in children with SLD but has no significant effect on TDC. The developed rhyming checklist may be used as a screening tool for children at risk of SLD at primary school grades. Rhyming activities may be utilized by teachers and parents, to promote language learning in young learners. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. A Measurement of the Parity Violating Parameter Ab with a Muon Tag at the SLD

    Energy Technology Data Exchange (ETDEWEB)

    Bellodi, Giulia

    2001-02-12

    We present a direct measurement of the parity violation parameter A{sub b}, derived from the left-right forward-backward asymmetry of b quarks tagged via muons from semileptonic decays. The value of A{sub b} is extracted using a maximum likelihood fit to the differential cross section for fermion production. The novelty of this measurement consists in the use of topological vertexing information alongside the more traditional decay kinematics to discriminate among the different sources of tagged leptons. The small and stable SLC beam spot and the CCD based vertex detector are used to reconstruct secondary decay vertices and to provide precise kinematic information and a highly efficient and pure B mass tag. A multivariate approach has been used, with a total of 4 tagging variables, whose correlation with each other has been taken into account. The final result has been cross-checked both with a classical cut-and-count method and combining all the information into a neural net. Based on the full SLD dataset of 550K Z{sup 0} events with highly polarized electron beams, this measurement represents an improvement of a factor of 2 with respect to the previously published result (1993-1995 only and with no vertexing information). The statistical sensitivity achieved is around 4% for A{sub b}, making this a world-class single measurement. An estimate of A{sub c} has been simultaneously derived from a common fit, with a precision of about 10%.

  14. Search for B0(S) Anti-B0(S) Oscillations at SLD

    CERN Document Server

    Moore, T

    2003-01-01

    We present preliminary results on the time dependence of B sub s sup 0 - (bar B) sub s sup 0 and B sub d sup 0 - (bar B) sub d sup 0 mixing using a sample of 400,000 hadronic Z sup 0 decays collected by the SLD experiment at the SLC. The analyses take advantage of the excellent decay length resolution of the CCD vertex detector. The B or (bar B) production flavor is determined by exploiting the large forward-backward asymmetry of polarized Z sup 0 -> b(bar b) decays. This flavor tag is enhanced by incorporating additional information from the hemisphere opposite that of the reconstructed B decay. The B sub d sup 0 - (bar B) sub d sup 0 mixing analysis uses the charge of high momentum kaons to identify the B or (bar B) decay flavor. The result is DELTA m sub d = 0.503 +- 0.028(stat) +- 0.020(syst) ps sup - sup 1. The results of three separate B sub s sup 0 - (bar B) sub s sup 0 mixing analyses are presented. These analyses determine the B decay flavor using the lepton charge in B semileptonic decays, the charg...

  15. GA-DoSLD: Genetic Algorithm Based Denial-of-Sleep Attack Detection in WSN

    Directory of Open Access Journals (Sweden)

    Mahalakshmi Gunasekaran

    2017-01-01

    Full Text Available Denial-of-sleep (DoSL attack is a special category of denial-of-service attack that prevents the battery powered sensor nodes from going into the sleep mode, thus affecting the network performance. The existing schemes used for the DoSL attack detection do not provide an optimal energy conservation and key pairing operation. Hence, in this paper, an efficient Genetic Algorithm (GA based denial-of-sleep attack detection (GA-DoSLD algorithm is suggested for analyzing the misbehaviors of the nodes. The suggested algorithm implements a Modified-RSA (MRSA algorithm in the base station (BS for generating and distributing the key pair among the sensor nodes. Before sending/receiving the packets, the sensor nodes determine the optimal route using Ad Hoc On-Demand Distance Vector Routing (AODV protocol and then ensure the trustworthiness of the relay node using the fitness calculation. The crossover and mutation operations detect and analyze the methods that the attackers use for implementing the attack. On determining an attacker node, the BS broadcasts the blocked information to all the other sensor nodes in the network. Simulation results prove that the suggested algorithm is optimal compared to the existing algorithms such as X-MAC, ZKP, and TE2P schemes.

  16. DNA damage enhanced by the attenuation of SLD5 delays cell cycle restoration in normal cells but not in cancer cells.

    Directory of Open Access Journals (Sweden)

    Zhi-Yuan Gong

    Full Text Available SLD5 is a member of the GINS complex composed of PSF1, PSF2, PSF3 and SLD5, playing a critical role in the formation of the DNA replication fork with CDC45 in yeast. Previously, we had isolated a PSF1 orthologue from a murine hematopoietic stem cell DNA library and were then able to identify orthologues of all the other GINS members by the yeast two hybrid approach using PSF1 as the bait. These GINS orthologues may also function in DNA replication in mammalian cells because they form tetrameric complexes as observed in yeast, and gene deletion mutants of both PSF1 and SLD5 result in a lack of epiblast proliferation and early embryonic lethality. However, we found that PSF1 is also involved in chromosomal segregation in M phase, consistent with recent suggestions that homologues of genes associated with DNA replication in lower organisms also regulate cellular events other than DNA replication in mammalian cells. Here we analyzed the function of SLD5 other than DNA replication and found that it is active in DNA damage and repair. Attenuation of SLD5 expression results in marked DNA damage in both normal cells and cancer cells, suggesting that it protects against DNA damage. Attenuation of SLD5 delays the DNA repair response and cell cycle restoration in normal cells but not in cancer cells. These findings suggest that SLD5 might represent a therapeutic target molecule acting at the level of tumor stromal cells rather than the cancerous cells themselves, because development of the tumor microenvironment could be delayed or disrupted by the suppression of its expression in the normal cell types within the tumor.

  17. Measurement of the polarized forward-backward asymmetry of B quarks using momentum-weighted track charge at SLD

    Energy Technology Data Exchange (ETDEWEB)

    Junk, Thomas Robert [Stanford Univ., CA (United States)

    1995-11-01

    This thesis presents a direct measurement of the parity-violating parameter Ab by analyzing the polarized forward-backward asymmetry of b quarks in e+e- → Z0 → b$\\bar{b}$. Data were taken at the Stanford Linear Accelerator Center (SLAC), with the Stanford Large Detector (SLD), which records the products of e+e- interactions at a center of mass energy √s = 91.2 GeV/c2 at the SLAC Linear Collider (SLC). The SLC/SLD experimental apparatus provides a unique and ideal environment for measuring electroweak asymmetries. Heavy flavor decays of the Z0 were identified inclusively by taking advantage of the long lifetime of B hadrons, the small, stable SLC beam spot, and SLD`s precise tracking detectors. Two analysis techniques for measuring Ab are presented: a binned fit to the left-right forward-backwards asymmetry of tagged events signed with momentum-weighted track charge, and a self-calibrating maximum-likelihood technique using momentum-weighted charge from the two hemispheres in each tagged event. From our 1994-1995 sample of 3.6 pb-1, having a luminosity-weighted average e- polarization of 77.3%, and our 1993 sample of 1.8 pb-1, having a luminosity-weighted polarization of 63.1%, we obtain Ab = 0.848 ± 0.046(stat.) ± 0.050(syst.).

  18. A measurement of the parity-violating parameter A(B) with electrons at the SLD using a neural network

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, J.

    2004-01-05

    The parity violating parameter A{sub b} of the Z{sup 0} {yields} b{bar b} coupling has been measured directly using the angular dependence of the Z{sup 0}-pole polarized cross section. Bottom hadrons are tagged via semileptonic decays. The semileptonic channel used in this analysis is the electron channel. The analysis takes advantage of a new Neural network algorithm to classify electrons according to the sources: b {yields} e, b {yields} c {yields} e, c {yields} e and background events. Based on the 1996-1998 SLD sample of 350,000 Z{sup 0} decays produced with highly polarized electron beams, this technique yields: A{sub b} = 0.877 {+-} 0.030(stat) {+-} 0.028(syst).

  19. Noisy Neurons

    Indian Academy of Sciences (India)

    IAS Admin

    Nerves are fibres that conduct electrical signals and hence pass on information from and to the brain. Nerves are made of nerve cells called neurons (Figure 1). Instructions in our body are sent via electrical signals that present themselves as variations in the potential across neuronal membranes. These potential differences ...

  20. Motor Neurons

    DEFF Research Database (Denmark)

    Hounsgaard, Jorn

    2017-01-01

    Motor neurons translate synaptic input from widely distributed premotor networks into patterns of action potentials that orchestrate motor unit force and motor behavior. Intercalated between the CNS and muscles, motor neurons add to and adjust the final motor command. The identity and functional...

  1. Strange meson spectroscopy in K[omega] and K[phi] at 11 GeV/c and Cherenkov ring imaging at SLD

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Youngjoon.

    1993-01-01

    This thesis consists of two independent parts; development of Cherenkov Ring Imaging Detector (CRID) system and analysis of high-statistics data of strange meson reactions from the LASS spectrometer. Part 1: The CRID system is devoted to charged particle identification in the SLAC Large Detector (SLD) to study e[sup +]e[sup [minus

  2. A measurement of the parity violating parameter A sub b with a muon tag at the SLD

    CERN Document Server

    Bellodi, G

    2000-01-01

    We present a direct measurement of the parity violation parameter A sub b , derived from the left-right forward-backward asymmetry of b quarks tagged via unions from semileptonic decays. The value of A sub b is extracted using a maximum likelihood fit to the differential cross section for fermion production. The novelty of this measurement consists in the use of topological vertexing information alongside the more traditional decay kinematics to discriminate among the different sources of tagged leptons. The small and stable SLC beam spot and the CCD based vertex detector are used to reconstruct secondary decay vertices and to provide precise kinematic information and a highly efficient and pure B mass tag. A multivariate approach has been used, with a total of 4 tagging variables, whose correlation with each other has been taken into account. The final result has been cross-checked both with a classical cut-and-count method and combining all the information into a neural net. Based on the full SLD dataset of...

  3. QCD Test in Three-Jet Z0 Decays at SLD and Detector Development for H0 --> Gamma Gamma Searches in High-Energy Hadron Colliders

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, H

    2004-01-06

    Polarized Z{sup 0} decays into three jets have been detected and measured in the SLD (SLAC Large Detector) experiment at the Stanford Linear Accelerator Center (SLAC). The hadrons from the jets were detected in the SLD liquid argon calorimeter, providing a sensitivity over 98% of the solid angle. The spin of the gluon was tested by studying the scaled jet energies (x{sub 1}, x{sub 2}, x{sub 3}) the Ellis-Karliner angle (cos{theta}{sub EK}) and the parameters of event plane orientation ({alpha}, {alpha}{sub N} {chi}). These measured variables are compared with quantum chromodynamics (QCD) and a scalar gluon model. Good agreement is found between data and the vector QCD model for the distributions of x{sub 1}, x{sub 2}, x{sub 3} and cos{theta}{sub EK}.

  4. A measurement of the electroweak asymmetry parameter for the tau lepton using the 1993 and 1994--95 SLD data sample

    Energy Technology Data Exchange (ETDEWEB)

    Bolen, B.D.

    1996-07-01

    A measurement of the electroweak asymmetry parameter A{sub t} is presented using e{sup +}E{sub LR}{sup -} {yields} {tau}{sup +}{tau}{sup -} events from the 1993, 1994--95 data runs at the SLD experiment at SLAC. The analysis takes advantage of the polarized electron beam in the SLAC Linear Collider (SLC) to improve the precision of the analysis over the standard forward-backward asymmetry techniques.

  5. Noisy Neurons

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 20; Issue 1. Noisy Neurons: Hodgkin-Huxley Model and Stochastic Variants. Shurti Paranjape. General Article Volume 20 Issue 1 January 2015 pp 34-43. Fulltext. Click here to view fulltext PDF. Permanent link:

  6. SLD Design Report

    Energy Technology Data Exchange (ETDEWEB)

    1984-05-01

    This Design Report describes the plans for the construction of the second detector for the SLAC Linear Collider to study e/sup +/e/sup -/ collisions at energies of up to 100 GeV in the center-of-mass. Particle tracking and momentum measurement are provided by a vertex detector, a high-precision central drift chamber, and pairs of endcap drift chambers, all in a 1 Tesla magnetic field produced by a superconducting solenoid. Particle identification is provided by CRIDs (Cerenkov Ring Imaging Detectors). Calorimetry is done in two parts; a liquid argon calorimeter (LAC) with uranium and iron radiators is located inside the coil, and the laminated iron of the flux return is instrumented with limited-streamer-mode tubes to complete the hadron calorimetry. The streamer tubes of this warm-iron calorimeter, called the WIC, are instrumented with strip readout to provide muon tracking in addition to calorimetry. The same technology is used on the end structures of the detector and the central region, thus providing uniform response in both regions.

  7. Strange meson spectroscopy in Kω and KΦ at 11 GeV/c and Cherenkov ring imaging at SLD

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Youngjoon [Stanford Univ., CA (United States)

    1993-01-01

    This thesis consists of two independent parts; development of Cherenkov Ring Imaging Detector (CRID) system and analysis of high-statistics data of strange meson reactions from the LASS spectrometer. Part 1: The CRID system is devoted to charged particle identification in the SLAC Large Detector (SLD) to study e+e- collisions at √s = mZ0. By measuring the angles of emission of the Cherenkov photons inside liquid and gaseous radiators, {pi}/K/p separation will be achieved up to ~30 GeV/c. The signals from CRID are read in three coordinates, one of which is measured by charge-division technique. To obtain a ~1% spatial resolution in the charge-division, low-noise CRID preamplifier prototypes were developed and tested resulting in <1000 electrons noise for an average photoelectron signal with 2 x 105 gain. To help ensure the long-term stability of CRID operation at high efficiency, a comprehensive monitoring and control system was developed. Part 2: Results from the partial wave analysis of strange meson final states in the reactions K-p → K-ωp and K-p → $\\bar{K}$0Φn are presented. The analyses are based on data from a 4.1 event/nb exposure of the LASS spectrometer in K-p interactions at 11 GeV/c. The data sample of K-ωp final state contains {approximately}105 events. From the partial wave analysis, resonance structures of JP= 2-, 3- and 2+ amplitudes are observed in the Kω system. The analysis of 2- amplitudes provides an evidence for two strange meson states in the mass region around 1.75 GeV/c2. The appropriate branching fractions are calculated and compared with the SU(3) predictions. The partial wave analysis of $\\bar{K}$0Φ system favors JP = 1- and 2+ states in the 1.9--2.0 GeV/c2 region.

  8. A measurement of R{sub b} = {Gamma}(Z{sup 0} {yields} b{bar b})/{Gamma}(Z{sup 0} {yields} hadrons) at SLD

    Energy Technology Data Exchange (ETDEWEB)

    SLD Collaboration

    1993-09-01

    A measurement of the ratio R{sub b} = {Gamma}(Z{sup 0} {yields} b{bar b})/{Gamma}(Z{sup 0} {yields} hadrons) is reported. This measurement is made using the CCD-based vertex detector of the SLD detector at the SLAC Linear Collider. Efficient tagging of b{bar b} events is performed with an impact parameter technique that takes advantage of the small and stable interaction point of the SLC and all charged tracks in Z{sup 0} decays. In a sample of 27K Z{sup 0} events, a value R{sub b}=0.235{plus_minus}0.006{plus_minus}0.018 is obtained.

  9. Juvenil neuronal ceroid lipofuscinosis

    DEFF Research Database (Denmark)

    Ostergaard, J R; Hertz, Jens Michael

    1998-01-01

    Neuronal ceroid-lipofuscinosis is a group of neurodegenerative diseases which are characterized by an abnormal accumulation of lipopigment in neuronal and extraneuronal cells. The diseases can be differentiated into several subgroups according to age of onset, the clinical picture...

  10. The effect of emotion regulation training in decreasing emotion failures and self-injurious behaviors among students suffering from specific learning disorder (SLD).

    Science.gov (United States)

    Habibzadeh, Abbas; Pourabdol, Saeed; Saravani, Shahzad

    2015-01-01

    A great deal of attention has been given to the study of learning disorders. Hence, the aim of this research was to study the effect of emotion regulation training in decreasing emotion failures and self-injurious behaviors among students suffering from specific learning disorder. This was an experimental study with the pre-test, post-test and a control group. Research population included all 5th grade male students suffering from specific learning disorder (case study: 5th grade students in Ardabil in 2015). Research sample included 40 male students suffering from specific learning disorder (SLD) who were selected through multi-step cluster sampling and classified into two groups: Experimental group (n= 20) and control group (n= 20). The following tools were used for data collection: Kay Math mathematic Test, Raven Intelligence Test, Reading Test of Shafiei et al, Falahchay Writing Expression, Emotion Failures Scale, Self-Injurious Behavior Questionnaire and Diagnostic Interview based on DSM-5. Data were analyzed by multivariate of variance analysis (MANOVA) model in the SPSS software version 22. The results of MANOVA revealed that emotion regulation training was effective in decreasing emotion failures in all parameters (difficulty in describing feelings, difficulty in identifying feelings, and externally oriented thinking style) and self-injurious behaviors in students suffering from specific learning disorder (peffect on reducing negative emotions and increasing the positive ones; this treatment can play an eminent role in decreasing emotion failures and self-injurious behaviors in such students.

  11. NEURON and Python.

    Science.gov (United States)

    Hines, Michael L; Davison, Andrew P; Muller, Eilif

    2009-01-01

    The NEURON simulation program now allows Python to be used, alone or in combination with NEURON's traditional Hoc interpreter. Adding Python to NEURON has the immediate benefit of making available a very extensive suite of analysis tools written for engineering and science. It also catalyzes NEURON software development by offering users a modern programming tool that is recognized for its flexibility and power to create and maintain complex programs. At the same time, nothing is lost because all existing models written in Hoc, including graphical user interface tools, continue to work without change and are also available within the Python context. An example of the benefits of Python availability is the use of the xml module in implementing NEURON's Import3D and CellBuild tools to read MorphML and NeuroML model specifications.

  12. PSF1 (Partner of SLD Five 1) is a Prognostic Biomarker in Patients with Non-small Cell Lung Cancer Treated with Surgery Following Preoperative Chemotherapy or Chemoradiotherapy.

    Science.gov (United States)

    Kanzaki, Ryu; Naito, Hisamichi; Kise, Kazuyoshi; Takara, Kazuhiro; Eino, Daisuke; Minami, Masato; Shintani, Yasushi; Funaki, Soichiro; Kawamura, Tomohiro; Kimura, Toru; Okumura, Meinoshin; Takakura, Nobuyuki

    2016-11-01

    PSF1 (Partner of SLD Five 1) is an evolutionarily conserved DNA replication factor that is part of the GINS (Go, Ichi, Nii, and San) complex . The objective of this study was to evaluate the relationship between PSF1 expression and prognosis in patients with non-small cell lung cancer (NSCLC) treated with surgery following preoperative chemotherapy or chemoradiotherapy. Sixty-nine patients with NSCLC treated with surgery following preoperative chemotherapy or chemoradiotherapy who did not achieve pathologic complete response were enrolled. The status of PSF1 expression was evaluated by immunohistochemistry, and the relationship between expression of PSF1 and Ki-67 was determined, as well as correlations between PSF1 expression and prognosis. We found that 27 of 69 patients' tumors (39 %) were positive for PSF1 expression. The Ki-67 index was significantly higher in the PSF1-positive versus the PSF1-negative group (p = 0.0026). Five-year, disease-free survival of the PSF1-positive group was significantly worse (17.7 vs. 44.3 %, p = 0.0088), and the 5-year overall survival also was worse (16.6 vs. 47.2 %, p = 0.0059). Moreover, PSF1 expression was found to be a significant independent prognostic factor for shorter survival by Cox multivariate analysis (hazard ratio 2.43, 95 % confidence interval 1.27-4.60, p = 0.0076). PSF1 is a useful prognostic biomarker to stratify NSCLC patients treated with surgery following preoperative chemotherapy or chemoradiotherapy.

  13. Measurements of {Gamma}(Z{sup O} {yields} b{bar b})/{Gamma}(Z{sup O} {yields} hadrons) using the SLD

    Energy Technology Data Exchange (ETDEWEB)

    Neal, H.A. Jr. II

    1995-07-01

    The quantity R{sub b} = {Gamma}(Z{sup o} {yields}b{bar b})/{Gamma}(Z{sup o} {yields} hadrons) is a sensitive measure of corrections to the Zbb vertex. The precision necessary to observe the top quark mass dependent corrections is close to being achieved. LEP is already observing a 1.8{sigma} deviation from the Standard Model prediction. Knowledge of the top quark mass combined with the observation of deviations from the Standard Model prediction would indicate new physics. Models which include charged Higgs or light SUSY particles yield predictions for R{sub b} appreciably different from the Standard Model. In this thesis two independent methods are used to measure R{sub b}. One uses a general event tag which determines R{sub b} from the rate at which events are tagged as Z{sup o} {yields} b{bar b} in data and the estimated rates at which various flavors of events are tagged from the Monte Carlo. The second method reduces the reliance on the Monte Carlo by separately tagging each hemisphere as containing a b-decay. The rates of single hemisphere tagged events and both hemisphere tagged events are used to determine the tagging efficiency for b-quarks directly from the data thus eliminating the main sources of systematic error present in the event tag. Both measurements take advantage of the unique environment provided by the SLAC Linear Collider (SLC) and the SLAC Large Detector (SLD). From the event tag a result of R{sub b} = 0.230{plus_minus}0.004{sub statistical}{plus_minus}0.013{sub systematic} is obtained. The higher precision hemisphere tag result obtained is R{sub b} = 0.218{plus_minus}0.004{sub statistical}{plus_minus}0.004{sub systematic}{plus_minus}0.003{sub Rc}.

  14. Single neuron computation

    CERN Document Server

    McKenna, Thomas M; Zornetzer, Steven F

    1992-01-01

    This book contains twenty-two original contributions that provide a comprehensive overview of computational approaches to understanding a single neuron structure. The focus on cellular-level processes is twofold. From a computational neuroscience perspective, a thorough understanding of the information processing performed by single neurons leads to an understanding of circuit- and systems-level activity. From the standpoint of artificial neural networks (ANNs), a single real neuron is as complex an operational unit as an entire ANN, and formalizing the complex computations performed by real n

  15. Neuromorphic Silicon Neuron Circuits

    Science.gov (United States)

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

    2011-01-01

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

  16. Neuromorphic Silicon Neuron Circuits

    National Research Council Canada - National Science Library

    Indiveri, Giacomo; Linares-Barranco, Bernabé; Hamilton, Tara Julia; Schaik, André van; 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...

  17. Neuromorphic silicon neuron circuits

    Directory of Open Access Journals (Sweden)

    Giacomo eIndiveri

    2011-05-01

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

  18. Lumping Izhikevich neurons

    OpenAIRE

    Visser Sid; van Gils Stephan A

    2014-01-01

    We present the construction of a planar vector field that yields the firing rate of a bursting Izhikevich neuron can be read out, while leaving the sub-threshold behaviour intact. This planar vector field is used to derive lumped formulations of two complex heterogeneous networks of bursting Izhikevich neurons. In both cases, the lumped model is compared with the spiking network. There is excellent agreement in terms of duration and number of action potentials within the bursts, but there is ...

  19. NeuronBank: A Tool for Cataloging Neuronal Circuitry

    Science.gov (United States)

    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

  20. Neuronal avalanches and learning

    Energy Technology Data Exchange (ETDEWEB)

    Arcangelis, Lucilla de, E-mail: dearcangelis@na.infn.it [Department of Information Engineering and CNISM, Second University of Naples, 81031 Aversa (Italy)

    2011-05-01

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

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

    Science.gov (United States)

    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.

  2. Lumping Izhikevich neurons

    Directory of Open Access Journals (Sweden)

    Visser Sid

    2014-12-01

    Full Text Available We present the construction of a planar vector field that yields the firing rate of a bursting Izhikevich neuron can be read out, while leaving the sub-threshold behavior intact. This planar vector field is used to derive lumped formulations of two complex heterogeneous networks of bursting Izhikevich neurons. In both cases, the lumped model is compared with the spiking network. There is excellent agreement in terms of duration and number of action potentials within the bursts, but there is a slight mismatch of the burst frequency. The lumped model accurately accounts for both intrinsic bursting and post inhibitory rebound potentials in the neuron model, features which are absent in prevalent neural mass models.

  3. Stochastic neuron models

    CERN Document Server

    Greenwood, Priscilla E

    2016-01-01

    This book describes a large number of open problems in the theory of stochastic neural systems, with the aim of enticing probabilists to work on them. This includes problems arising from stochastic models of individual neurons as well as those arising from stochastic models of the activities of small and large networks of interconnected neurons. The necessary neuroscience background to these problems is outlined within the text, so readers can grasp the context in which they arise. This book will be useful for graduate students and instructors providing material and references for applying probability to stochastic neuron modeling. Methods and results are presented, but the emphasis is on questions where additional stochastic analysis may contribute neuroscience insight. An extensive bibliography is included. Dr. Priscilla E. Greenwood is a Professor Emerita in the Department of Mathematics at the University of British Columbia. Dr. Lawrence M. Ward is a Professor in the Department of Psychology and the Brain...

  4. Imaging voltage in neurons

    Science.gov (United States)

    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. Glutamate gated spiking Neuron Model.

    Science.gov (United States)

    Deka, Krisha M; Roy, Soumik

    2014-01-01

    Biological neuron models mainly analyze the behavior of neural networks. Neurons are described in terms of firing rates viz an analog signal. The Izhikevich neuron model is an efficient, powerful model of spiking neuron. This model is a reduction of Hodgkin-Huxley model to a two variable system and is capable of producing rich firing patterns for many biological neurons. In this paper, the Regular Spiking (RS) neuron firing pattern is used to simulate the spiking of Glutamate gated postsynaptic membrane. Simulation is done in MATLAB environment for excitatory action of synapses. Analogous simulation of spiking of excitatory postsynaptic membrane potential is obtained.

  6. Photosensitive neurons in mollusks

    Directory of Open Access Journals (Sweden)

    Kartelija Gordana

    2005-01-01

    Full Text Available In addition to regular photoreceptors, some invertebrates possess simple extra ocular photoreceptors. For ex­ample, the central ganglia of mollusks contain photosensitive neurons. These neurons are located on the dorsal surface of the ganglia and based on their electrophysiological properties it has been postulated that they are internal photoreceptors. Besides the eye, transduction of light also occurs in these extra-ocular photoreceptors. In the present work, we analyze the reactivity of these nerve cells to light and describe the underlying mechanism mediating the light-induced response.

  7. From Neurons to Newtons

    DEFF Research Database (Denmark)

    Nielsen, Bjørn Gilbert

    2001-01-01

    proteins generate forces, to the macroscopic levels where overt arm movements are vol- untarily controlled within an unpredictable environment by legions of neurons¯ring in orderly fashion. An extensive computer simulation system has been developed for this thesis, which at present contains a neural...... network scripting language for specifying arbitrary neural architectures, de¯nition ¯les for detailed spinal networks, various biologically realistic models of neurons, and dynamic synapses. Also included are structurally accurate models of intrafusal and extra-fusal muscle ¯bers and a general body...

  8. Neuronal survival in the brain: neuron type-specific mechanisms

    DEFF Research Database (Denmark)

    Pfisterer, Ulrich Gottfried; Khodosevich, Konstantin

    2017-01-01

    numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether......Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial...... a particular neuron will die. To accommodate this signaling, immature neurons in the brain express a number of transmembrane factors as well as intracellular signaling molecules that will regulate the cell survival/death decision, and many of these factors cease being expressed upon neuronal maturation...

  9. Neuronal survival in the brain: neuron type-specific mechanisms

    DEFF Research Database (Denmark)

    Pfisterer, Ulrich Gottfried; Khodosevich, Konstantin

    2017-01-01

    Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial...... numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether...... a particular neuron will die. To accommodate this signaling, immature neurons in the brain express a number of transmembrane factors as well as intracellular signaling molecules that will regulate the cell survival/death decision, and many of these factors cease being expressed upon neuronal maturation...

  10. Lumping Izhikevich neurons

    NARCIS (Netherlands)

    Visser, S.; van Gils, Stephanus A.

    2014-01-01

    We present the construction of a planar vector field that yields the firing rate of a bursting Izhikevich neuron can be read out, while leaving the sub-threshold behaviour intact. This planar vector field is used to derive lumped formulations of two complex heterogeneous networks of bursting

  11. Spiking neuron network Helmholtz machine

    National Research Council Canada - National Science Library

    Sountsov, Pavel; Miller, Paul

    2015-01-01

    .... This paper aims to unify the two fields of probabilistic inference and synaptic plasticity by using a neuronal network of realistic model spiking neurons to implement a well-studied computational...

  12. Identifying neuronal oscillations using rhythmicity

    NARCIS (Netherlands)

    Fransen, A.M.M.; Ede, F.L. van; Maris, E.G.G.

    2015-01-01

    Neuronal oscillations are a characteristic feature of neuronal activity and are typically investigated through measures of power and coherence. However, neither of these measures directly reflects the distinctive feature of oscillations: their rhythmicity. Rhythmicity is the extent to which future

  13. Effect of phosphatidylserine on the basal and GABA-activated Cl- permeation across single nerve membranes from rabbit Deiters' neurons

    Energy Technology Data Exchange (ETDEWEB)

    Rapallino, M.V.; Cupello, A.; Mainardi, P.; Besio, G.; Loeb, C.W. (Centro di Studio per la Neurofisiologia Cerebrale, C.N.R., Genova (Italy))

    1990-06-01

    The permeation of labeled Cl- ions across single plasma membranes from Deiters' neurons has been studied in the presence of various concentrations of phosphatidylserine (PS) on their extracellular side. PS reduces significantly basal Cl- permeation only at 10(-5) M on the membrane exterior. No effect was found at other concentrations. GABA activable 36Cl- permeation is heavily reduced and almost abolished at 10(-11) - 10(-5) M phosphatidylserine. This exogenous phosphatidylserine effect is difficult to interpret in relation to the function of the endogenous phospholipid. However, it may be involved in the epileptogenic effect in vivo of exogenous phosphatidylserine administration to rats.

  14. Motor neuron disease in blacks

    African Journals Online (AJOL)

    1989-08-19

    Aug 19, 1989 ... We reported earlier that motor neuron disease occurs more commonly among blacks than Parkinson's disease, which is relatively rare in this race group.! The hypothesis that these conditions, and other neuronal abiotrophies, are the result of previous subclinical neuronal insult and subsequent age-related.

  15. Simple model of spiking neurons.

    Science.gov (United States)

    Izhikevich, E M

    2003-01-01

    A model is presented that reproduces spiking and bursting behavior of known types of cortical neurons. The model combines the biologically plausibility of Hodgkin-Huxley-type dynamics and the computational efficiency of integrate-and-fire neurons. Using this model, one can simulate tens of thousands of spiking cortical neurons in real time (1 ms resolution) using a desktop PC.

  16. Moving Neurons back into place

    OpenAIRE

    Kerjan, Geraldine; Gleeson, Joseph G.

    2009-01-01

    Subcortical band heterotopia (SBH) is a neuron migration disorder characterized by an aberrant ‘band-like’ accumulation of neurons within the neocortical white matter, frequently leading to mental retardation and epilepsy. SBH can now be regressed by reactivating neuronal migration.

  17. Neuronal substrate of eating disorders

    OpenAIRE

    Timofeeva, Elena; Calvez, Juliane

    2014-01-01

    Eating disorders are devastating and life-threatening psychiatric diseases. Although clinical and experimental investigations have significantly progressed in discovering the neuronal causes of eating disorders, the exact neuronal and molecular mechanisms of the development and maintenance of these pathologies are not fully understood. The complexity of the neuronal substrate of eating disorders hampers progress in revealing the precise mechanisms. The present re...

  18. Understanding Neuronal Mechanisms of Epilepsy ...

    Indian Academy of Sciences (India)

    Admin

    Control il ti. Human brain. Control epileptic. Mutani et al., 1994 ... of Calcium Transients Evoked in. Response to Spontaneous Epileptic ... Proof : Feed forward inhibition in subiculum. CA1. Subiculum. Stimulation artifact. -60 mV. Excitatory neuron. Inhibitory neuron. Excitatory neuron. Excitatory. Synapse. Inhibitory. Synapse.

  19. Vasculo-Neuronal Coupling: Retrograde Vascular Communication to Brain Neurons.

    Science.gov (United States)

    Kim, Ki Jung; Ramiro Diaz, Juan; Iddings, Jennifer A; Filosa, Jessica A

    2016-12-14

    Continuous cerebral blood flow is essential for neuronal survival, but whether vascular tone influences resting neuronal function is not known. Using a multidisciplinary approach in both rat and mice brain slices, we determined whether flow/pressure-evoked increases or decreases in parenchymal arteriole vascular tone, which result in arteriole constriction and dilation, respectively, altered resting cortical pyramidal neuron activity. We present evidence for intercellular communication in the brain involving a flow of information from vessel to astrocyte to neuron, a direction opposite to that of classic neurovascular coupling and referred to here as vasculo-neuronal coupling (VNC). Flow/pressure increases within parenchymal arterioles increased vascular tone and simultaneously decreased resting pyramidal neuron firing activity. On the other hand, flow/pressure decreases evoke parenchymal arteriole dilation and increased resting pyramidal neuron firing activity. In GLAST-CreERT2; R26-lsl-GCaMP3 mice, we demonstrate that increased parenchymal arteriole tone significantly increased intracellular calcium in perivascular astrocyte processes, the onset of astrocyte calcium changes preceded the inhibition of cortical pyramidal neuronal firing activity. During increases in parenchymal arteriole tone, the pyramidal neuron response was unaffected by blockers of nitric oxide, GABAA, glutamate, or ecto-ATPase. However, VNC was abrogated by TRPV4 channel, GABAB, as well as an adenosine A1 receptor blocker. Differently to pyramidal neuron responses, increases in flow/pressure within parenchymal arterioles increased the firing activity of a subtype of interneuron. Together, these data suggest that VNC is a complex constitutive active process that enables neurons to efficiently adjust their resting activity according to brain perfusion levels, thus safeguarding cellular homeostasis by preventing mismatches between energy supply and demand. We present evidence for vessel-to-neuron

  20. A mechanism for cognitive dynamics: neuronal communication through neuronal coherence.

    Science.gov (United States)

    Fries, Pascal

    2005-10-01

    At any one moment, many neuronal groups in our brain are active. Microelectrode recordings have characterized the activation of single neurons and fMRI has unveiled brain-wide activation patterns. Now it is time to understand how the many active neuronal groups interact with each other and how their communication is flexibly modulated to bring about our cognitive dynamics. I hypothesize that neuronal communication is mechanistically subserved by neuronal coherence. Activated neuronal groups oscillate and thereby undergo rhythmic excitability fluctuations that produce temporal windows for communication. Only coherently oscillating neuronal groups can interact effectively, because their communication windows for input and for output are open at the same times. Thus, a flexible pattern of coherence defines a flexible communication structure, which subserves our cognitive flexibility.

  1. Phosphoinositide signaling in somatosensory neurons

    Science.gov (United States)

    Rohacs, Tibor

    2015-01-01

    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 these neurons, with special focus on effects on sensory and other ion channels. PMID:26724974

  2. Neuron-specific splicing.

    Science.gov (United States)

    Hakim, Nor Hakimah Ab; Majlis, Burhanuddin Yeop; Suzuki, Hitoshi; Tsukahara, Toshifumi

    2017-03-22

    During pre-mRNA splicing events, introns are removed from the pre-mRNA, and the remaining exons are connected together to form a single continuous molecule. Alternative splicing is a common mechanism for the regulation of gene expression in eukaryotes. More than 90% of human genes are known to undergo alternative splicing. The most common type of alternative splicing is exon skipping, which is also known as cassette exon. Other known alternative splicing events include alternative 5' splice sites, alternative 3' splice sites, intron retention, and mutually exclusive exons. Alternative splicing events are controlled by regulatory proteins responsible for both positive and negative regulation. In this review, we focus on neuronal splicing regulators and discuss several notable regulators in depth. In addition, we have also included an example of splicing regulation mediated by the RBFox protein family. Lastly, as previous studies have shown that a number of splicing factors are associated with neuronal diseases such as Alzheime's disease (AD) and Autism spectrum disorder (ASD), here we consider their importance in neuronal diseases wherein the underlying mechanisms have yet to be elucidated.

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

    Science.gov (United States)

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

    2015-01-01

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

  4. Astroglial networks promote neuronal coordination.

    Science.gov (United States)

    Chever, Oana; Dossi, Elena; Pannasch, Ulrike; Derangeon, Mickael; Rouach, Nathalie

    2016-01-12

    Astrocytes interact with neurons to regulate network activity. Although the gap junction subunits connexin 30 and connexin 43 mediate the formation of extensive astroglial networks that cover large functional neuronal territories, their role in neuronal synchronization remains unknown. Using connexin 30- and connexin 43-deficient mice, we showed that astroglial networks promoted sustained population bursts in hippocampal slices by setting the basal active state of neurons. Astroglial networks limited excessive neuronal depolarization induced by spontaneous synaptic activity, increased neuronal release probability, and favored the recruitment of neurons during bursting, thus promoting the coordinated activation of neuronal networks. In vivo, this sustained neuronal coordination translated into increased severity of acutely evoked epileptiform events and convulsive behavior. These results revealed that connexin-mediated astroglial networks synchronize bursting of neuronal assemblies, which can exacerbate pathological network activity and associated behavior. Our data thus provide molecular and biophysical evidence predicting selective astroglial gap junction inhibitors as anticonvulsive drugs. Copyright © 2016, American Association for the Advancement of Science.

  5. Motor neurons and the generation of spinal motor neurons diversity

    OpenAIRE

    Nicolas eStifani

    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 motor neurons (SpMNs) that have been the core of significant work and discoveries during the last decades. SpMNs a...

  6. Nasal neuron PET imaging quantifies neuron generation and degeneration

    National Research Council Canada - National Science Library

    Van de Bittner, Genevieve C; Riley, Misha M; Cao, Luxiang; Ehses, Janina; Herrick, Scott P; Ricq, Emily L; Wey, Hsiao-Ying; O'Neill, Michael J; Ahmed, Zeshan; Murray, Tracey K; Smith, Jaclyn E; Wang, Changning; Schroeder, Frederick A; Albers, Mark W; Hooker, Jacob M

    2017-01-01

    .... Quantification of the olfactory sensory neurons (OSNs), which detect odors within the nasal cavity, would provide insight into the etiology of olfactory dysfunction associated with disease and mortality...

  7. Resonate-and-fire neurons.

    Science.gov (United States)

    Izhikevich, E M

    2001-01-01

    We suggest a simple spiking model-resonate-and-fire neuron, which is similar to the integrate-and-fire neuron except that the state variable is complex. The model provides geometric illustrations to many interesting phenomena occurring in biological neurons having subthreshold damped oscillations of membrane potential. For example, such neurons prefer a certain resonant frequency of the input that is nearly equal to their eigenfrequency, they can be excited or inhibited by a doublet (two pulses) depending on its interspike interval, and they can fire in response to an inhibitory input. All these properties could be observed in Hodgkin-Huxley-type models. We use the resonate-and-fire model to illustrate possible sensitivity of biological neurons to the fine temporal structure of the input spike train. Being an analogue of the integrate-and-fire model, the resonate-and-fire model is computationally efficient and suitable for simulations of large networks of spiking neurons.

  8. STDP in recurrent neuronal networks

    Directory of Open Access Journals (Sweden)

    Matthieu Gilson

    2010-09-01

    Full Text Available Recent results about spike-timing-dependent plasticity (STDP in recurrently connected neurons are reviewed, with a focus on the relationship between the weight dynamics and the emergence of network structure. In particular, the evolution of synaptic weights in the two cases of incoming connections for a single neuron and recurrent connections are compared and contrasted. A theoretical framework is used that is based upon Poisson neurons with a temporally inhomogeneous firing rate and the asymptotic distribution of weights generated by the learning dynamics. Different network configurations examined in recent studies are discussed and an overview of the current understanding of STDP in recurrently connected neuronal networks is presented.

  9. The biophysics of neuronal growth

    Energy Technology Data Exchange (ETDEWEB)

    Franze, Kristian; Guck, Jochen [Cavendish Laboratory, Department of Physics, University of Cambridge, JJ Thomson Avenue, Cambridge, CB3 0HE (United Kingdom)

    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.

  10. Neuronal avalanches and coherence potentials

    Science.gov (United States)

    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.

  11. [Neurons and values].

    Science.gov (United States)

    Camps, Victoria

    2013-09-01

    This article examines the advances made by neuroscience in the attempt to find an answer to the question regarding the origin and foundation of moral judgements and of human behaviour in compliance with them. The conception of the brain as something dynamic and capable of adapting to the social and cultural surroundings is seen to be an important point for philosophy. At the same time, the complexity of ethical issues that cannot be reduced to observations based strictly on neurons alone also becomes quite apparent. Nevertheless, scientists and philosophers should get together and communicate with one another so as to be able to pose their questions with greater rigour and take advantage of each other's respective knowledge.

  12. Multiplying with Neurons

    Science.gov (United States)

    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.

  13. Postmitotic specification of Drosophila insulinergic neurons from pioneer neurons.

    Directory of Open Access Journals (Sweden)

    Irene Miguel-Aliaga

    2008-03-01

    Full Text Available Insulin and related peptides play important and conserved functions in growth and metabolism. Although Drosophila has proved useful for the genetic analysis of insulin functions, little is known about the transcription factors and cell lineages involved in insulin production. Within the embryonic central nervous system, the MP2 neuroblast divides once to generate a dMP2 neuron that initially functions as a pioneer, guiding the axons of other later-born embryonic neurons. Later during development, dMP2 neurons in anterior segments undergo apoptosis but their posterior counterparts persist. We show here that surviving posterior dMP2 neurons no longer function in axonal scaffolding but differentiate into neuroendocrine cells that express insulin-like peptide 7 (Ilp7 and innervate the hindgut. We find that the postmitotic transition from pioneer to insulin-producing neuron is a multistep process requiring retrograde bone morphogenetic protein (BMP signalling and four transcription factors: Abdominal-B, Hb9, Fork Head, and Dimmed. These five inputs contribute in a partially overlapping manner to combinatorial codes for dMP2 apoptosis, survival, and insulinergic differentiation. Ectopic reconstitution of this code is sufficient to activate Ilp7 expression in other postmitotic neurons. These studies reveal striking similarities between the transcription factors regulating insulin expression in insect neurons and mammalian pancreatic beta-cells.

  14. A Neuron Model for FPGA Spiking Neuronal Network Implementation

    Directory of Open Access Journals (Sweden)

    BONTEANU, G.

    2011-11-01

    Full Text Available We propose a neuron model, able to reproduce the basic elements of the neuronal dynamics, optimized for digital implementation of Spiking Neural Networks. Its architecture is structured in two major blocks, a datapath and a control unit. The datapath consists of a membrane potential circuit, which emulates the neuronal dynamics at the soma level, and a synaptic circuit used to update the synaptic weight according to the spike timing dependent plasticity (STDP mechanism. The proposed model is implemented into a Cyclone II-Altera FPGA device. Our results indicate the neuron model can be used to build up 1K Spiking Neural Networks on reconfigurable logic suport, to explore various network topologies.

  15. Neuronal responses to physiological stress

    DEFF Research Database (Denmark)

    Kagias, Konstantinos; Nehammer, Camilla; Pocock, Roger David John

    2012-01-01

    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....

  16. Evidence of involvement of neurone-glia/neurone-neurone communications via gap junctions in synchronised activity of KNDy neurones.

    Science.gov (United States)

    Ikegami, K; Minabe, S; Ieda, N; Goto, T; Sugimoto, A; Nakamura, S; Inoue, N; Oishi, S; Maturana, A D; Sanbo, M; Hirabayashi, M; Maeda, K-I; Tsukamura, H; Uenoyama, Y

    2017-06-01

    Pulsatile secretion of gonadotrophin-releasing hormone (GnRH)/luteinising hormone is indispensable for the onset of puberty and reproductive activities at adulthood in mammalian species. A cohort of neurones expressing three neuropeptides, namely kisspeptin, encoded by the Kiss1 gene, neurokinin B (NKB) and dynorphin A, localised in the hypothalamic arcuate nucleus (ARC), so-called KNDy neurones, comprises a putative intrinsic source of the GnRH pulse generator. Synchronous activity among KNDy neurones is considered to be required for pulsatile GnRH secretion. It has been reported that gap junctions play a key role in synchronising electrical activity in the central nervous system. Thus, we hypothesised that gap junctions are involved in the synchronised activities of KNDy neurones, which is induced by NKB-NK3R signalling. We determined the role of NKB-NK3R signalling in Ca 2+ oscillation (an indicator of neuronal activities) of KNDy neurones and its synchronisation mechanism among KNDy neurones. Senktide, a selective agonist for NK3R, increased the frequency of Ca 2+ oscillations in cultured Kiss1-GFP cells collected from the mediobasal hypothalamus of the foetal Kiss1-green fluorescent protein (GFP) mice. The senktide-induced Ca 2+ oscillations were synchronised in the Kiss1-GFP and neighbouring glial cells. Confocal microscopy analysis of these cells, which have shown synchronised Ca 2+ oscillations, revealed close contacts between Kiss1-GFP cells, as well as between Kiss1-GFP cells and glial cells. Dye coupling experiments suggest cell-to-cell communication through gap junctions between Kiss1-GFP cells and neighbouring glial cells. Connexin-26 and -37 mRNA were found in isolated ARC Kiss1 cells taken from adult female Kiss1-GFP transgenic mice. Furthermore, 18β-glycyrrhetinic acids and mefloquine, which are gap junction inhibitors, attenuated senktide-induced Ca 2+ oscillations in Kiss1-GFP cells. Taken together, these results suggest that NKB-NK3R signalling

  17. Nonsulfated cholecystokinins in cerebral neurons

    DEFF Research Database (Denmark)

    Agersnap, Mikkel; Zhang, Ming-Dong; Harkany, Tibor

    2016-01-01

    Cholecystokinin (CCK) is a widely expressed neuropeptide system originally discovered in the gut. Both cerebral and peripheral neurons as well as endocrine I-cells in the small intestine process proCCK to tyrosyl-O-sulfated and α-carboxyamidated peptides. Recently, we reported that gut endocrine I...... for nonsulfated CCK-8 with an antibody recognizing both sulfated and nonsulfated CCK. However, nonsulfated CCK immunoreactivity was stronger than that of sulfated CCK in cell bodies and weaker in nerve terminals. We conclude that only a small fraction of neuronal CCK is nonsulfated. The intracellular distribution...... of nonsulfated CCK in neurons suggests that they contribute only modestly to the CCK transmitter activity....

  18. Neurones and neuropeptides in coelenterates

    DEFF Research Database (Denmark)

    Grimmelikhuijzen, C J; Ebbesen, Ditte Graff; McFarlane, I D

    1989-01-01

    The first nervous system probably evolved in coelenterates. Many neurons in coelenterates have morphological characteristics of both sensory and motor neurones, and appear to be multifunctional. Using immunocytochemistry with antisera to the sequence Arg-Phe-NH2 (RFamide), RFamide-like peptides......) was isolated, which also belongs to the less than Glu...Arg-X-NH2 family. Using specific antisera it was shown that all four peptides were located in neurones. Application of low doses of Antho-RFamide, or Antho-RWamide I or II induced contractions of endodermal muscles of sea anemones. This indicates...

  19. Statistical inference on spontaneous neuronal discharge patterns. I. Single neuron.

    Science.gov (United States)

    Lánský, P; Radil, T

    1987-01-01

    A statistical analysis was performed on extracellularly recorded spike trains of spontaneously active mesencephalic reticular neurons of rats. Only stationary records were used for detailed examination. The moments of interspike intervals were computed, hypothesis of renewal process and its specific forms was tested. Implications for statistical methodology are considered on the basis of the results. The main emphasis is laid on the connection between experimental results and stochastic neuronal models.

  20. A Search for Time Dependent B{sub S}{sup 0}-{bar B}{sub S}{sup 0} Oscillations Using Exclusively Reconstructed D{sub S}{sup +} AT SLD

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Cheng-Ju S

    2002-01-10

    The authors set a preliminary 95% C.L. exclusion on the oscillation frequency of B{sub s}{sup 0} - {bar B}{sub s}{sup 0} mixing using a sample of 400,000 hadronic Z{sup 0} decays collected by the SLD experiment at the SLC during the 1996-98 run. In this analysis, B{sub s}{sup 0} mesons are partially reconstructed by combining a fully reconstructed D{sub s} with other B{sub s}{sup 0} decay products. The D{sub s} decays are reconstructed via the {phi}{pi} and K*K channels. The b-hadron flavor at production is determined by exploiting the large forward-backward asymmetry of polarized Z{sup 0} {yields} b{bar b} decays as well as information from the hemisphere opposite to the reconstructed B decay. The flavor of the B{sub s}{sup 0} at the decay vertex is determined by the charge of the D{sub s}. A total of 361 candidates passed the final event selection cuts. This analysis excludes the following values of the B{sub s}{sup 0}-{bar B}{sub s}{sup 0} mixing oscillation frequency: {Delta}m{sub s} < 1.4 psec{sup -1} and 2.5 < {Delta}m{sub s} < 5.3 psec{sup -1} at the 95% confidence level.

  1. Neuronal boost to evolutionary dynamics.

    Science.gov (United States)

    de Vladar, Harold P; Szathmáry, Eörs

    2015-12-06

    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.

  2. Information processing by neuronal populations

    National Research Council Canada - National Science Library

    Hölscher, Christian; Munk, Matthias

    2009-01-01

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

  3. Hydrodynamic Limit for Interacting Neurons

    Science.gov (United States)

    De Masi, A.; Galves, A.; Löcherbach, E.; Presutti, E.

    2015-02-01

    This paper studies the hydrodynamic limit of a stochastic process describing the time evolution of a system with N neurons with mean-field interactions produced both by chemical and by electrical synapses. This system can be informally described as follows. Each neuron spikes randomly following a point process with rate depending on its membrane potential. At its spiking time, the membrane potential of the spiking neuron is reset to the value 0 and, simultaneously, the membrane potentials of the other neurons are increased by an amount of potential . This mimics the effect of chemical synapses. Additionally, the effect of electrical synapses is represented by a deterministic drift of all the membrane potentials towards the average value of the system. We show that, as the system size N diverges, the distribution of membrane potentials becomes deterministic and is described by a limit density which obeys a non linear PDE which is a conservation law of hyperbolic type.

  4. Neuronal control of energy homeostasis

    OpenAIRE

    Gao, Qian; Horvath, Tamas L.

    2007-01-01

    Neuronal control of body energy homeostasis is the key mechanism by which animals and humans regulate their long-term energy balance. Various hypothalamic neuronal circuits (which include the hypothalamic melanocortin, midbrain dopamine reward and caudal brainstem autonomic feeding systems) control energy intake and expenditure to maintain body weight within a narrow range for long periods of a life span. Numerous peripheral metabolic hormones and nutrients target these structures providing f...

  5. Novel model of neuronal bioenergetics

    DEFF Research Database (Denmark)

    Bak, Lasse Kristoffer; Obel, Linea Lykke Frimodt; Walls, Anne B

    2012-01-01

    We have previously investigated the relative roles of extracellular glucose and lactate as fuels for glutamatergic neurons during synaptic activity. The conclusion from these studies was that cultured glutamatergic neurons utilize glucose rather than lactate during NMDA (N-methyl-d-aspartate)-ind......We have previously investigated the relative roles of extracellular glucose and lactate as fuels for glutamatergic neurons during synaptic activity. The conclusion from these studies was that cultured glutamatergic neurons utilize glucose rather than lactate during NMDA (N...... of an ionomycin-induced increase in intracellular Ca2+ (i.e. independent of synaptic activity) on neuronal energy metabolism employing 13C-labelled glucose and lactate and subsequent mass spectrometric analysis of labelling in glutamate, alanine and lactate. The results demonstrate that glucose utilization...... is positively correlated with intracellular Ca2+ whereas lactate utilization is not. This result lends further support for a significant role of glucose in neuronal bioenergetics and that Ca2+ signalling may control the switch between glucose and lactate utilization during synaptic activity. Based...

  6. Communication among neurons.

    Science.gov (United States)

    Marner, Lisbeth

    2012-04-01

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

  7. Culture of Mouse Olfactory Sensory Neurons

    OpenAIRE

    Gong, Qizhi

    2012-01-01

    Olfactory sensory neurons, located in the nasal epithelium, detect and transmit odorant information to the central nervous system. This requires that these neurons form specific neuronal connections within the olfactory bulb and express receptors and signaling molecules specific for these functions. This protocol describes a primary olfactory sensory neuron culture technique that allows in vitro investigation of olfactory sensory neuron differentiation, axon outgrowth, odorant receptor expres...

  8. Ephaptic coupling in cortical neurons

    Directory of Open Access Journals (Sweden)

    Costas Anastassiou

    2014-03-01

    Full Text Available The electrochemical processes that underlie neural function manifest themselves in ceaseless spatial and temporal fluctuations in the extracellular electric field. The local field potential (LFP, used to study neural interactions during various brain states, is regarded as an epiphenomenon of coordinated neural activity. Yet the extracellular field activity feeds back onto the electrical potential across the neuronal membrane via ephaptic coupling (Jefferys et al, Physiol Rev, 1995. The extent to which such ephaptic coupling alters the functioning of individual neurons and neural assemblies under physiological conditions has remained largely speculative despite recent advances (Ozen et al, JNeurosci, 2010; Fröhlich & McCormick, Neuron, 2010, Anastassiou et al, JNeurosci, 2010. To address this question we use a 12-pipette setup that allows independent positioning of each pipette under visual control with μm accuracy, with the flexibility of using an arbitrary number of these as patching, extracellularly stimulating or extracellular recording pipettes only a few μm away from the cell body of patched neurons (Anastassiou et al, Nat Neurosci, 2011. We stimulated in rat somatosensory cortical slices a variety of layer 5 neural types and recorded inside and outside their cell bodies while pharmacologically silencing synaptic transmission. Pyramidal cells couple to the extracellular field distinctly different from interneurons. Ephaptic coupling strength depends both on the field strength (as measured at the neuron soma as well as the spike-history of neurons. In particular, we find that ephaptic coupling strength depends both on the field strength (as measured at the cell body as well as the spike-history of neurons. How do such effects manifest themselves in vivo? We address this question through detailed large-scale simulations from thousands of biophysically realistic and interconnected neurons (Reimann, Anastassiou et al, Neuron, 2013 emulating

  9. Neuronal factors determining high intelligence.

    Science.gov (United States)

    Dicke, Ursula; Roth, Gerhard

    2016-01-05

    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. © 2015 The Author(s).

  10. Brain Neurons as Quantum Computers:

    Science.gov (United States)

    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.

  11. Neuronal vulnerability in Parkinson's disease.

    Science.gov (United States)

    Double, Kay L

    2012-01-01

    The classic motor symptoms of Parkinson's disease result from the progressive death of dopaminergic neurons within the substantia nigra. To date the relatively selective vulnerability of this brain region is not understood. The unique feature of dopaminergic neurons of the human substantia nigra pars compacta is the presence of the polymer pigment neuromelanin which gives this region its characteristic dark colour. In the healthy brain, neuromelanin appears to play a functional role to protect neurons from oxidative load but we have shown that in the Parkinson's disease brain the pigment undergoes structural changes and is associated with aggregation of α-synuclein protein, even early in the disease process. Further, the role of the pigment as a metal binder has also been suggested to underlie the relative vulnerability of these neurons, as changes in metal levels are suggested to be associated with neurodegenerative cascades in Parkinson's disease. While most research to date has focused on the role of iron in these pathways we have recently shown that changes in copper may contribute to neuronal vulnerability in this disorder. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Prospective Coding by Spiking Neurons.

    Directory of Open Access Journals (Sweden)

    Johanni Brea

    2016-06-01

    Full Text Available 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.

  13. Copying and evolution of neuronal topology.

    Directory of Open Access Journals (Sweden)

    Chrisantha Fernando

    Full Text Available 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.

  14. Neuronal involvement in cisplatin neuropathy

    DEFF Research Database (Denmark)

    Krarup-Hansen, A; Helweg-Larsen, Susanne Elisabeth; Schmalbruch, H

    2007-01-01

    Although it is well known that cisplatin causes a sensory neuropathy, the primary site of involvement is not established. The clinical symptoms localized in a stocking-glove distribution may be explained by a length dependent neuronopathy or by a distal axonopathy. To study whether the whole neuron...... of large dorsal root ganglion cells. Motor conduction studies, autonomic function and warm and cold temperature sensation remained unchanged at all doses of cisplatin treatment. The results of these studies are consistent with degeneration of large sensory neurons whereas there was no evidence of distal...

  15. Neuronal coherence and its functional role in communication between neurons

    NARCIS (Netherlands)

    Zeitler-Geurds, M.

    2010-01-01

    Neuronal oscillations are observed in many brain areas in various frequency bands. Each of the frequency bands is associated with a particular functional role. Gamma oscillations (30-80 Hz) are thought to be related to cognitive tasks like memory and attention and possibly also involved in the

  16. Characterization of cutaneous and articular sensory neurons.

    Science.gov (United States)

    da Silva Serra, Ines; Husson, Zoé; Bartlett, Jonathan D; Smith, Ewan St John

    2016-01-01

    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. 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. 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, possibly reflecting different

  17. What do mirror neurons mirror?

    NARCIS (Netherlands)

    Uithol, S.; Rooij, I.J.E.I. van; Bekkering, H.; Haselager, W.F.G.

    2011-01-01

    Single cell recordings in monkeys provide strong evidence for an important role of the motor system in action understanding. This evidence is backed up by data from studies of the (human) mirror neuron system using neuroimaging or TMS techniques, and behavioral experiments. Although the data

  18. The Neuronal Infrastructure of Speaking

    Science.gov (United States)

    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…

  19. ULTRASTRUCTURAL CHANGES OF THE NEURONAL ...

    African Journals Online (AJOL)

    Objectives To study ultrastructural changes in the neuronal component of the detrusor muscle during the spinal shock phase and following early electric neurostimulation in an animal model. Material and Methods 12 dogs were decentralized at the levels from S1 to S3, while three animals were provided as normal controls.

  20. Bursting deep dorsal horn neurons

    DEFF Research Database (Denmark)

    Carlsen, Eva Meier; Rasmussen, Rune

    2017-01-01

    In a recent publication, Thaweerattanasinp et al. (J Neurophysiol 116: 1644–1653, 2016) investigated spinal cord injury and firing properties of deep dorsal horn neurons during NMDA or zolmitriptan application by employing electrophysiology in an in vitro spinal cord preparation. Deep dorsal horn...

  1. Computing with Spiking Neuron Networks

    NARCIS (Netherlands)

    H. Paugam-Moisy; S.M. Bohte (Sander); G. Rozenberg; T.H.W. Baeck (Thomas); J.N. Kok (Joost)

    2012-01-01

    htmlabstractAbstract Spiking Neuron Networks (SNNs) are often referred to as the 3rd gener- ation of neural networks. Highly inspired from natural computing in the brain and recent advances in neurosciences, they derive their strength and interest from an ac- curate modeling of synaptic interactions

  2. Uncertainty propagation in neuronal dynamical systems

    NARCIS (Netherlands)

    A. Torres Valderrama (Aldemar); J.G. Blom (Joke)

    2013-01-01

    htmlabstractOne of the most notorious characteristics of neuronal electrical activity is its variability, whose origin is not just instrumentation noise, but mainly the intrinsically stochastic nature of neural computations. Neuronal models based on deterministic differential equations cannot

  3. Shape, connectedness and dynamics in neuronal networks.

    Science.gov (United States)

    Comin, Cesar Henrique; da Fontoura Costa, Luciano

    2013-11-15

    The morphology of neurons is directly related to several aspects of the nervous system, including its connectedness, health, development, evolution, dynamics and, ultimately, behavior. Such interplays of the neuronal morphology can be understood within the more general shape-function paradigm. The current article reviews, in an introductory way, some key issues regarding the role of neuronal morphology in the nervous system, with emphasis on works developed in the authors' group. The following topics are addressed: (a) characterization of neuronal shape; (b) stochastic synthesis of neurons and neuronal systems; (c) characterization of the connectivity of neuronal networks by using complex networks concepts; and (d) investigations of influences of neuronal shape on network dynamics. The presented concepts and methods are useful also for several other multiple object systems, such as protein-protein interaction, tissues, aggregates and polymers. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Spiking Neuron Network Helmholtz Machine

    Directory of Open Access Journals (Sweden)

    Pavel eSountsov

    2015-04-01

    Full Text Available An increasing amount of behavioral and neurophysiological data suggests that the brain performs optimal (or near-optimal probabilistic inference and learning during perception and other tasks. Although many machine learning algorithms exist that perform inference and learning in an optimal way, the complete description of how one of those algorithms (or a novel algorithm can be implemented in the brain is currently incomplete. There have been many proposed solutions that address how neurons can perform optimal inference but the question of how synaptic plasticity can implement optimal learning is rarely addressed. This paper aims to unify the two fields of probabilistic inference and synaptic plasticity by using a neuronal network of realistic model spiking neurons to implement a well studied computational model called the Helmholtz Machine. The Helmholtz Machine is amenable to neural implementation as the algorithm it uses to learn its parameters, called the wake-sleep algorithm, uses a local delta learning rule. Our spiking-neuron network implements both the delta rule and a small example of a Helmholtz machine. This neuronal network can learn an internal model of continuous-valued training data sets without supervision. The network can also perform inference on the learned internal models. We show how various biophysical features of the neural implementation constrain the parameters of the wake-sleep algorithm, such as the duration of the wake and sleep phases of learning and the minimal sample duration. We examine the deviations from optimal performance and tie them to the properties of the synaptic plasticity rule.

  5. Numerical Simulation of SLD Ice Accretions

    NARCIS (Netherlands)

    Hospers, Jacco; Hoeijmakers, Hendrik Willem Marie

    2011-01-01

    In this study, computational methods are presented that compute ice accretion on multiple-element airfoils in specified icing conditions. The ¿Droplerian¿ numerical simulation method used is based on an Eulerian method for predicting droplet trajectories and the resulting droplet catching efficiency

  6. Ecological constraints on the origin of neurones.

    Science.gov (United States)

    Monk, Travis; Paulin, Michael G; Green, Peter

    2015-12-01

    The basic functional characteristics of spiking neurones are remarkably similar throughout the animal kingdom. Their core design and function features were presumably established very early in their evolutionary history. Identifying the selection pressures that drove animals to evolve spiking neurones could help us interpret their design and function today. This paper provides a quantitative argument, based on ecology, that animals evolved neurones after they started eating each other, about 550 million years ago. We consider neurones as devices that aid an animal's foraging performance, but incur an energetic cost. We introduce an idealised stochastic model ecosystem of animals and their food, and obtain an analytic expression for the probability that an animal with a neurone will fix in a neurone-less population. Analysis of the fixation probability reveals two key results. First, a neurone will never fix if an animal forages low-value food at high density, even if that neurone incurs no cost. Second, a neurone will fix with high probability if an animal is foraging high-value food at low density, even if that neurone is expensive. These observations indicate that the transition from neurone-less to neurone-armed animals can be facilitated by a transition from filter-feeding or substrate grazing to episodic feeding strategies such as animal-on-animal predation (macrophagy).

  7. Oscillating from Neurosecretion to Multitasking Dopamine Neurons

    Directory of Open Access Journals (Sweden)

    David R. Grattan

    2016-04-01

    Full Text Available 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.

  8. Effect of Methamidophos on cerebellar neuronal cells

    African Journals Online (AJOL)

    olayemitoyin

    Taken together, our study shows that low dose methamidophos may negatively impact. TH-mediated cerebellar neuronal cell development and function, and consequently could interfere with TH-regulated neuronal events. Keywords: Methamidophos, Thyroid hormone, Purkinje cells, Granule cell, Neuronal development.

  9. Neuronal Network Mechanisms of Gamma Oscillations

    NARCIS (Netherlands)

    Viriyopase, A.

    2017-01-01

    Neuronal oscillations at various frequency bands play an important role in neuronal information processing. In this thesis, we mathematically and computationally investigated the properties of the gamma band (30-80 Hz) with different networks: a simplified network with two neurons, a large network

  10. Oscillatory integration windows in neurons

    Science.gov (United States)

    Gupta, Nitin; Singh, Swikriti Saran; Stopfer, Mark

    2016-01-01

    Oscillatory synchrony among neurons occurs in many species and brain areas, and has been proposed to help neural circuits process information. One hypothesis states that oscillatory input creates cyclic integration windows: specific times in each oscillatory cycle when postsynaptic neurons become especially responsive to inputs. With paired local field potential (LFP) and intracellular recordings and controlled stimulus manipulations we directly test this idea in the locust olfactory system. We find that inputs arriving in Kenyon cells (KCs) sum most effectively in a preferred window of the oscillation cycle. With a computational model, we show that the non-uniform structure of noise in the membrane potential helps mediate this process. Further experiments performed in vivo demonstrate that integration windows can form in the absence of inhibition and at a broad range of oscillation frequencies. Our results reveal how a fundamental coincidence-detection mechanism in a neural circuit functions to decode temporally organized spiking. PMID:27976720

  11. Selective serotonergic excitation of callosal projection neurons

    Directory of Open Access Journals (Sweden)

    Daniel eAvesar

    2012-03-01

    Full Text Available Serotonin (5-HT acting as a neurotransmitter in the cerebral cortex is critical for cognitive function, yet how 5-HT regulates information processing in cortical circuits is not well understood. We tested the serotonergic responsiveness of layer 5 pyramidal neurons (L5PNs of the mouse medial prefrontal cortex (mPFC, and found 3 distinct response types: long-lasting 5-HT1A (1A receptor-dependent inhibitory responses (84% of L5PNs, 5-HT2A (2A receptor-dependent excitatory responses (9%, and biphasic responses in which 2A-dependent excitation followed brief inhibition (5%. Relative to 5-HT-inhibited neurons, those excited by 5-HT had physiological properties characteristic of callosal/commissural (COM neurons that project to the contralateral cortex. We tested whether serotonergic responses in cortical pyramidal neurons are correlated with their axonal projection pattern using retrograde fluorescent labeling of COM and corticopontine-projecting (CPn neurons. 5-HT generated excitatory or biphasic responses in all 5-HT-responsive layer 5 COM neurons. Conversely, CPn neurons were universally inhibited by 5-HT. Serotonergic excitation of COM neurons was blocked by the 2A antagonist MDL 11939, while serotonergic inhibition of CPn neurons was blocked by the 1A antagonist WAY 100635, confirming a role for these two receptor subtypes in regulating pyramidal neuron activity. Selective serotonergic excitation of COM neurons was not layer-specific, as COM neurons in layer 2/3 were also selectively excited by 5-HT relative to their non-labeled pyramidal neuron neighbors. Because neocortical 2A receptors are implicated in the etiology and pathophysiology of schizophrenia, we propose that COM neurons may represent a novel cellular target for intervention in psychiatric disease.

  12. Results on a Binding Neuron Model and Their Implications for Modified Hourglass Model for Neuronal Network

    Directory of Open Access Journals (Sweden)

    Viswanathan Arunachalam

    2013-01-01

    Full Text Available The classical models of single neuron like Hodgkin-Huxley point neuron or leaky integrate and fire neuron assume the influence of postsynaptic potentials to last till the neuron fires. Vidybida (2008 in a refreshing departure has proposed models for binding neurons in which the trace of an input is remembered only for a finite fixed period of time after which it is forgotten. The binding neurons conform to the behaviour of real neurons and are applicable in constructing fast recurrent networks for computer modeling. This paper develops explicitly several useful results for a binding neuron like the firing time distribution and other statistical characteristics. We also discuss the applicability of the developed results in constructing a modified hourglass network model in which there are interconnected neurons with excitatory as well as inhibitory inputs. Limited simulation results of the hourglass network are presented.

  13. Single-cell axotomy of cultured hippocampal neurons integrated in neuronal circuits.

    Science.gov (United States)

    Gomis-Rüth, Susana; Stiess, Michael; Wierenga, Corette J; Meyn, Liane; Bradke, Frank

    2014-05-01

    An understanding of the molecular mechanisms of axon regeneration after injury is key for the development of potential therapies. Single-cell axotomy of dissociated neurons enables the study of the intrinsic regenerative capacities of injured axons. This protocol describes how to perform single-cell axotomy on dissociated hippocampal neurons containing synapses. Furthermore, to axotomize hippocampal neurons integrated in neuronal circuits, we describe how to set up coculture with a few fluorescently labeled neurons. This approach allows axotomy of single cells in a complex neuronal network and the observation of morphological and molecular changes during axon regeneration. Thus, single-cell axotomy of mature neurons is a valuable tool for gaining insights into cell intrinsic axon regeneration and the plasticity of neuronal polarity of mature neurons. Dissociation of the hippocampus and plating of hippocampal neurons takes ∼2 h. Neurons are then left to grow for 2 weeks, during which time they integrate into neuronal circuits. Subsequent axotomy takes 10 min per neuron and further imaging takes 10 min per neuron.

  14. Motor neurons and the generation of spinal motor neurons diversity

    Directory of Open Access Journals (Sweden)

    Nicolas eStifani

    2014-10-01

    Full Text Available 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 motor neurons (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.

  15. Somal size of prefrontal cortical pyramidal neurons in schizophrenia: differential effects across neuronal subpopulations.

    Science.gov (United States)

    Pierri, Joseph N; Volk, Christine L E; Auh, Sungyoung; Sampson, Allan; Lewis, David A

    2003-07-15

    Cognitive dysfunction in schizophrenia may be related to morphologic abnormalities of pyramidal neurons in the dorsal prefrontal cortex (dPFC) and the largest pyramidal neurons in deep layer 3 may be most affected. Immunoreactivity (IR) for the nonphosphorylated epitopes of neurofilament protein (NNFP) identifies a subset of large dPFC deep layer 3 pyramidal neurons. We tested the hypotheses that the average size of NNFP-IR neurons is smaller in schizophrenia and that the decrease in size of these neurons is greater than that observed in the general population of deep layer 3 pyramidal neurons. We estimated the mean somal volume of NNFP-IR neurons in deep layer 3 of 9 in 13 matched pairs of control and schizophrenia subjects and compared the differences in somal size of NNFP-IR neurons to the differences in size of all deep layer 3 pyramidal neurons identified in Nissl-stained material. In subjects with schizophrenia, the somal volume of NNFP-IR neurons was nonsignificantly decreased by 6.6%, whereas that of the Nissl-stained pyramidal neurons was significantly decreased by 14.2%. These results suggest that the NNFP-IR subpopulation of dPFC pyramidal neurons are not preferentially affected in schizophrenia. Thus, a subpopulation of dPFC deep layer 3 pyramidal neurons, other than those identified by NNFP-IR, may be selectively vulnerable in schizophrenia.

  16. Glutamatergic Nonpyramidal Neurons From Neocortical Layer VI and Their Comparison With Pyramidal and Spiny Stellate Neurons

    Science.gov (United States)

    Andjelic, Sofija; Gallopin, Thierry; Cauli, Bruno; Hill, Elisa L.; Roux, Lisa; Badr, Sammy; Hu, Emilie; Tamás, Gábor; Lambolez, Bertrand

    2009-01-01

    The deeper part of neocortical layer VI is dominated by nonpyramidal neurons, which lack a prominent vertically ascending dendrite and predominantly establish corticocortical connections. These neurons were studied in rat neocortical slices using patch-clamp, single-cell reverse transcription–polymerase chain reaction, and biocytin labeling. The majority of these neurons expressed the vesicular glutamate transporter but not glutamic acid decarboxylase, suggesting that a high proportion of layer VI nonpyramidal neurons are glutamatergic. Indeed, they exhibited numerous dendritic spines and established asymmetrical synapses. Our sample of glutamatergic nonpyramidal neurons displayed a wide variety of somatodendritic morphologies and a subset of these cells expressed the Nurr1 mRNA, a marker for ipsilateral, but not commissural corticocortical projection neurons in layer VI. Comparison with spiny stellate and pyramidal neurons from other layers showed that glutamatergic neurons consistently exhibited a low occurrence of GABAergic interneuron markers and regular spiking firing patterns. Analysis of electrophysiological diversity using unsupervised clustering disclosed three groups of cells. Layer V pyramidal neurons were segregated into a first group, whereas a second group consisted of a subpopulation of layer VI neurons exhibiting tonic firing. A third heterogeneous cluster comprised spiny stellate, layer II/III pyramidal, and layer VI neurons exhibiting adaptive firing. The segregation of layer VI neurons in two different clusters did not correlate either with their somatodendritic morphologies or with Nurr1 expression. Our results suggest that electrophysiological similarities between neocortical glutamatergic neurons extend beyond layer positioning, somatodendritic morphology, and projection specificity. PMID:19052106

  17. A chimeric path to neuronal synchronization

    Energy Technology Data Exchange (ETDEWEB)

    Essaki Arumugam, Easwara Moorthy; Spano, Mark L. [School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona 85287-9709 (United States)

    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)

  18. L-system modeling of neurons

    Science.gov (United States)

    McCormick, Bruce H.; Mulchandani, K.

    1994-09-01

    A formal representation of neuron morphology, adequate for the geometric modeling of manually-traced neurons, is presented. The concept of a stochastic L-system is then introduced and the critical distribution functions governing the stochastic generation of dendritic and axonal trees are defined. Experiments with various stochastic L-system models for pyramidal, motoneuron, and Purkinje cells are reported which generate synthetic neurons with promising proximity to neurons in the neurobiology literature. Work is in progress to improve this degree of proximity, but more importantly to validate the derived stochastic models against available databases of manually-traced neurons. To this end a neuron morphology modeler is described which provides a methodology for iterative refinement of the stochastic L-system model.

  19. Performance limitations of relay neurons.

    Directory of Open Access Journals (Sweden)

    Rahul Agarwal

    Full Text Available 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

  20. Neuronal communication: firing spikes with spikes.

    Science.gov (United States)

    Brecht, Michael

    2012-08-21

    Spikes of single cortical neurons can exert powerful effects even though most cortical synapses are too weak to fire postsynaptic neurons. A recent study combining single-cell stimulation with population imaging has visualized in vivo postsynaptic firing in genetically identified target cells. The results confirm predictions from in vitro work and might help to understand how the brain reads single-neuron activity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. High-Degree Neurons Feed Cortical Computations.

    Directory of Open Access Journals (Sweden)

    Nicholas M Timme

    2016-05-01

    Full Text Available 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

  2. Sensory Neurons in the Human Geniculate Ganglion.

    Science.gov (United States)

    Sato, Tadasu; Yamaguma, Yu; Sasaki, Yu; Kanda, Noriyuki; Sasahara, Nobuyuki; Kokubun, Souichi; Yajima, Takehiro; Ichikawa, Hiroyuki

    2017-01-01

    The geniculate ganglion (GG) contains visceral and somatic sensory neurons of the facial nerve. In this study, the number and cell size of sensory neurons in the human GG were investigated. The estimated number of GG neurons ranged from 1,580 to 2,561 (mean ± SD = 1,960 ± 364.6). The cell size of GG neurons ranged from 393.0 to 2,485.4 μm2 (mean ± SD = 1,067.4 ± 99.5 μm2). Sensory neurons in the GG were significantly smaller in size than those in the dorsal root (range = 326.6-5343.4 μm2, mean ± SD = 1,683.2 ± 203.8 μm2) or trigeminal ganglia (range = 349.6-4,889.28 μm2, mean ± SD = 1,529.0 ± 198.48 μm2). Sensory neurons had similar cell body sizes in the GG and nodose ganglion (range = 357.2-3,488.33 μm2, mean ± SD = 1,160.4 ± 156.61 μm2). These findings suggest that viscerosensory neurons have smaller cell bodies than somatosensory neurons. In addition, immunohistochemistry for several neurochemical substances was performed on the human GG. In the ganglion, sensory neurons were mostly immunoreactive for secreted protein, acidic and rich in cysteine-like 1 (94.3%). One third of GG neurons showed vesicular glutamate transporter 2 immunoreactivity (31.3%). Only 7.3% of GG neurons were immunoreactive for transient receptor potential cation channel subfamily V member 1. Sensory neurons in the human GG may respond to gustatory, nociceptive, and/or mechanoreceptive stimuli from tongues, soft palates, and external auditory canals. © 2017 S. Karger AG, Basel.

  3. Functions of class V myosins in neurons.

    Science.gov (United States)

    Hammer, John A; Wagner, Wolfgang

    2013-10-04

    This minireview focuses on recent studies implicating class V myosins in organelle and macromolecule transport within neurons. These studies reveal that class V myosins play important roles in a wide range of fundamental processes occurring within neurons, including the transport into dendritic spines of organelles that support synaptic plasticity, the establishment of neuronal shape, the specification of polarized cargo transport, and the subcellular localization of mRNA.

  4. Glutamate Mediated Astrocytic Filtering of Neuronal Activity

    Science.gov (United States)

    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

  5. Role of DAPK in neuronal cell death.

    Science.gov (United States)

    Fujita, Yuki; Yamashita, Toshihide

    2014-02-01

    Neuronal cell death happens as a result of the normal physiological process that occurs during development, or as part of the pathological process that occurs during disease. Death-associated protein kinase (DAPK) is an intracellular protein that mediates cell death by its serine/threonine kinase activity, and transmits apoptotic cell death signals in various cells, including neurons. DAPK is elevated in injured neurons in acute models of injury such as ischemia and seizure. The absence of DAPK has been shown to protect neurons from a wide variety of acute toxic insults. Moreover, DAPK also regulates neuronal cell death during central nervous system development. Neurons are initially overproduced in the developing nervous system, following which approximately one-half of the original cell population dies. This "naturally-occurring" or "programmed" cell death is essential for the construction of the developing nervous system. In this review, we focus on the role of DAPK in neuronal cell death after neuronal injury. The participation of DAPK in developmental neuronal death is also explained.

  6. Tuning curves, neuronal variability, and sensory coding.

    Directory of Open Access Journals (Sweden)

    Daniel A Butts

    2006-04-01

    Full Text Available Tuning curves are widely used to characterize the responses of sensory neurons to external stimuli, but there is an ongoing debate as to their role in sensory processing. Commonly, it is assumed that a neuron's role is to encode the stimulus at the tuning curve peak, because high firing rates are the neuron's most distinct responses. In contrast, many theoretical and empirical studies have noted that nearby stimuli are most easily discriminated in high-slope regions of the tuning curve. Here, we demonstrate that both intuitions are correct, but that their relative importance depends on the experimental context and the level of variability in the neuronal response. Using three different information-based measures of encoding applied to experimentally measured sensory neurons, we show how the best-encoded stimulus can transition from high-slope to high-firing-rate regions of the tuning curve with increasing noise level. We further show that our results are consistent with recent experimental findings that correlate neuronal sensitivities with perception and behavior. This study illustrates the importance of the noise level in determining the encoding properties of sensory neurons and provides a unified framework for interpreting how the tuning curve and neuronal variability relate to the overall role of the neuron in sensory encoding.

  7. Cognition and behaviour in motor neurone disease.

    Science.gov (United States)

    Lillo, Patricia; Hodges, John R

    2010-12-01

    Motor neurone disease has traditionally been considered a pure motor syndrome which spares aspects of cognition and behaviour, although in recent years it has been suggested that up to 50% of patients with motor neurone disease may develop frontal dysfunction which, in some cases, is severe enough to reach criteria for frontotemporal dementia. We review the cognitive and behavioural changes in motor neurone disease emphasizing the recent advances. A major advance in pathology has been the recent discovery of TDP-43 and FUS inclusions as the key components in cases of motor neurone disease, frontotemporal dementia-motor neurone disease and some cases with pure frontotemporal dementia. In addition, mutations in TARDBP and FUS genes have been reported in recent years. Longitudinal studies showed that progression of cognitive impairment over the course of motor neurone disease appears to be mild and occurs only in a proportion of motor neurone disease patients. The presence of cognitive impairment seems to be related to a faster disease and a shorter survival. Motor neurone disease is a multi-system disorder which overlaps with frontotemporal dementia. Behavioural and cognitive changes appear to occur in a subset of patients with motor neurone disease, but the cause of this variability remains unclear.

  8. Functional connectivity in in vitro neuronal assemblies

    Science.gov (United States)

    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

  9. Shaping Neuronal Network Activity by Presynaptic Mechanisms.

    Directory of Open Access Journals (Sweden)

    Ayal Lavi

    2015-09-01

    Full Text Available 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.

  10. Shaping Neuronal Network Activity by Presynaptic Mechanisms

    Science.gov (United States)

    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

  11. Macroscopic Description for Networks of Spiking Neurons

    Science.gov (United States)

    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.

  12. Effective stimuli for constructing reliable neuron models.

    Directory of Open Access Journals (Sweden)

    Shaul Druckmann

    2011-08-01

    Full Text Available 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.

  13. Odor processing by adult-born neurons.

    Science.gov (United States)

    Livneh, Yoav; Adam, Yoav; Mizrahi, Adi

    2014-03-05

    The adult mammalian brain is continuously supplied with adult-born neurons in the olfactory bulb (OB) and hippocampus, where they are thought to be important for circuit coding and plasticity. However, direct evidence for the actual involvement of these neurons in neural processing is still lacking. We recorded the spiking activity of adult-born periglomerular neurons in the mouse OB in vivo using two-photon-targeted patch recordings. We show that odor responsiveness reaches a peak during neuronal development and then recedes at maturity. Sensory enrichment during development enhances the selectivity of adult-born neurons after maturation, without affecting neighboring resident neurons. Thus, in the OB circuit, adult-born neurons functionally integrate into the circuit, where they acquire distinct response profiles in an experience-dependent manner. The constant flow of these sensitive neurons into the circuit provides it with a mechanism of long-term plasticity, wherein new neurons mature to process odor information based on past demands. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. NETMORPH: a framework for the stochastic generation of large scale neuronal networks with realistic neuron morphologies

    NARCIS (Netherlands)

    Koene, R.A.; Tijms, B.; van Hees, P.; Postma, F.; de Ridder, A.; Ramakers, G.J.A.; van Pelt, J.; van Ooyen, A.

    2009-01-01

    We present a simulation framework, called NETMORPH, for the developmental generation of 3D large-scale neuronal networks with realistic neuron morphologies. In NETMORPH, neuronal morphogenesis is simulated from the perspective of the individual growth cone. For each growth cone in a growing axonal

  15. Glucose-sensing neurons of the hypothalamus.

    Science.gov (United States)

    Burdakov, Denis; Luckman, Simon M; Verkhratsky, Alexei

    2005-12-29

    Specialized subgroups of hypothalamic neurons exhibit specific excitatory or inhibitory electrical responses to changes in extracellular levels of glucose. Glucose-excited neurons were traditionally assumed to employ a 'beta-cell' glucose-sensing strategy, where glucose elevates cytosolic ATP, which closes KATP channels containing Kir6.2 subunits, causing depolarization and increased excitability. Recent findings indicate that although elements of this canonical model are functional in some hypothalamic cells, this pathway is not universally essential for excitation of glucose-sensing neurons by glucose. Thus glucose-induced excitation of arcuate nucleus neurons was recently reported in mice lacking Kir6.2, and no significant increases in cytosolic ATP levels could be detected in hypothalamic neurons after changes in extracellular glucose. Possible alternative glucose-sensing strategies include electrogenic glucose entry, glucose-induced release of glial lactate, and extracellular glucose receptors. Glucose-induced electrical inhibition is much less understood than excitation, and has been proposed to involve reduction in the depolarizing activity of the Na+/K+ pump, or activation of a hyperpolarizing Cl- current. Investigations of neurotransmitter identities of glucose-sensing neurons are beginning to provide detailed information about their physiological roles. In the mouse lateral hypothalamus, orexin/hypocretin neurons (which promote wakefulness, locomotor activity and foraging) are glucose-inhibited, whereas melanin-concentrating hormone neurons (which promote sleep and energy conservation) are glucose-excited. In the hypothalamic arcuate nucleus, excitatory actions of glucose on anorexigenic POMC neurons in mice have been reported, while the appetite-promoting NPY neurons may be directly inhibited by glucose. These results stress the fundamental importance of hypothalamic glucose-sensing neurons in orchestrating sleep-wake cycles, energy expenditure and

  16. Heavy metals in locus ceruleus and motor neurons in motor neuron disease

    Science.gov (United States)

    2013-01-01

    Background The causes of sporadic amyotrophic lateral sclerosis (SALS) and other types of motor neuron disease (MND) remain largely unknown. Heavy metals have long been implicated in MND, and it has recently been shown that inorganic mercury selectively enters human locus ceruleus (LC) and motor neurons. We therefore used silver nitrate autometallography (AMG) to look for AMG-stainable heavy metals (inorganic mercury and bismuth) in LC and motor neurons of 24 patients with MND (18 with SALS and 6 with familial MND) and in the LC of 24 controls. Results Heavy metals in neurons were found in significantly more MND patients than in controls when comparing: (1) the presence of any versus no heavy metal-containing LC neurons (MND 88%, controls 42%), (2) the median percentage of heavy metal-containing LC neurons (MND 9.5%, control 0.0%), and (3) numbers of individuals with heavy metal-containing LC neurons in the upper half of the percentage range (MND 75%, controls 25%). In MND patients, 67% of remaining spinal motor neurons contained heavy metals; smaller percentages were found in hypoglossal, nucleus ambiguus and oculomotor neurons, but none in cortical motor neurons. The majority of MND patients had heavy metals in both LC and spinal motor neurons. No glia or other neurons, including neuromelanin-containing neurons of the substantia nigra, contained stainable heavy metals. Conclusions Uptake of heavy metals by LC and lower motor neurons appears to be fairly common in humans, though heavy metal staining in the LC, most likely due to inorganic mercury, was seen significantly more often in MND patients than in controls. The LC innervates many cell types that are affected in MND, and it is possible that MND is triggered by toxicant-induced interactions between LC and motor neurons. PMID:24330485

  17. Neuronal dynamics on FPGA: Izhikevich's model

    Science.gov (United States)

    La Rosa, M.; Caruso, E.; Fortuna, L.; Frasca, M.; Occhipinti, L.; Rivoli, F.

    2005-06-01

    The study of spatio-temporal patterns generation and processing in systems with high parallelism like biological neuronal networks gives birth to a new technology able to realize architectures with robust performance even in noisy environments. The behavioural properties of neural assemblies warrant an effective exchange and use of information in presence of high-level neuronal noise. Neuron population processing and self-organization have been reproduced by connecting several neuron through synaptic connections, which can be either electrical or chemical, in artificial information processing architectures based on Field Programmable Gate Arrays (FPGA). The adopted neuron model is based on Izhikevich"s description of cortical neuron dynamics [1]. The development of biological neuronal network models has been focused on architecture features like changes over time of topologies, uniformity of the connections, node diversity, etc. The hardware reproduction of neuron dynamical behaviour, by giving high computation performance, allows the development of innovative computational methods and models based on self-organizing nonlinear architectures.

  18. Bursting and synaptic plasticity in neuronal networks

    NARCIS (Netherlands)

    Stegenga, J.

    2010-01-01

    Networks of neonatal cortical neurons, cultured on multi electrode arrays (MEAs) exhibit spontaneous action potential firings. The electrodes embedded in the glass surface of a MEA can be used to record and stimulate activity at 60 sites in a network of ~50.000 neurons. Such in-vitro networks enable

  19. Sorting out polarized transport mechanisms in neurons

    NARCIS (Netherlands)

    Lipka, J.

    2015-01-01

    Neurons are highly polarized cells with two distinct processes called axons and dendrites. To establish and maintain their specialized morphology and function, neurons use molecular motors: kinesins, myosins and dynein to steer cargo transport along the cytoskeleton into axons and dendrites.

  20. Polarity and intracellular compartmentalization of Drosophila neurons

    Directory of Open Access Journals (Sweden)

    Henner Astra L

    2007-04-01

    Full Text Available Abstract Background Proper neuronal function depends on forming three primary subcellular compartments: axons, dendrites, and soma. Each compartment has a specialized function (the axon to send information, dendrites to receive information, and the soma is where most cellular components are produced. In mammalian neurons, each primary compartment has distinctive molecular and morphological features, as well as smaller domains, such as the axon initial segment, that have more specialized functions. How neuronal subcellular compartments are established and maintained is not well understood. Genetic studies in Drosophila have provided insight into other areas of neurobiology, but it is not known whether flies are a good system in which to study neuronal polarity as a comprehensive analysis of Drosophila neuronal subcellular organization has not been performed. Results Here we use new and previously characterized markers to examine Drosophila neuronal compartments. We find that: axons and dendrites can accumulate different microtubule-binding proteins; protein synthesis machinery is concentrated in the cell body; pre- and post-synaptic sites localize to distinct regions of the neuron; and specializations similar to the initial segment are present. In addition, we track EB1-GFP dynamics and determine microtubules in axons and dendrites have opposite polarity. Conclusion We conclude that Drosophila will be a powerful system to study the establishment and maintenance of neuronal compartments.

  1. Adaptive Neurons For Artificial Neural Networks

    Science.gov (United States)

    Tawel, Raoul

    1990-01-01

    Training time decreases dramatically. In improved mathematical model of neural-network processor, temperature of neurons (in addition to connection strengths, also called weights, of synapses) varied during supervised-learning phase of operation according to mathematical formalism and not heuristic rule. Evidence that biological neural networks also process information at neuronal level.

  2. Power laws from linear neuronal cable theory

    DEFF Research Database (Denmark)

    Pettersen, Klas H; Lindén, Henrik Anders; Tetzlaff, Tom

    2014-01-01

    suggested to be at the root of this phenomenon, we here demonstrate a possible origin of such power laws in the biophysical properties of single neurons described by the standard cable equation. Taking advantage of the analytical tractability of the so called ball and stick neuron model, we derive general...

  3. Locally active Hindmarsh-Rose neurons

    Energy Technology Data Exchange (ETDEWEB)

    Arena, Paolo [Dipartimento di Ingegneria Elettrica, Elettronica e dei Sistemi, Universita degli Studi di Catania, viale A. Doria 6, 95100 Catania (Italy); Fortuna, Luigi [Dipartimento di Ingegneria Elettrica, Elettronica e dei Sistemi, Universita degli Studi di Catania, viale A. Doria 6, 95100 Catania (Italy)] e-mail: lfortuna@diees.unict.it; Frasca, Mattia [Dipartimento di Ingegneria Elettrica, Elettronica e dei Sistemi, Universita degli Studi di Catania, viale A. Doria 6, 95100 Catania (Italy)] e-mail: mfrasca@diees.unict.it; Rosa, Manuela La [SST Group, Corporate R and D, STMicroelectronics, Stradale Primosole 50, 95121 Catania (Italy)] e-mail: manuela.la-rosa@st.com

    2006-01-01

    In this paper the locally active and the edge of chaos regions of the Hindmarsh-Rose (HR) model for neuron dynamics are studied. From these regions parameters are chosen to set emergent phenomena both in 2D and 3D grids of HR neurons.

  4. Neuronal involvement in cisplatin neuropathy

    DEFF Research Database (Denmark)

    Krarup-Hansen, A; Helweg-Larsen, Susanne Elisabeth; Schmalbruch, H

    2007-01-01

    Although it is well known that cisplatin causes a sensory neuropathy, the primary site of involvement is not established. The clinical symptoms localized in a stocking-glove distribution may be explained by a length dependent neuronopathy or by a distal axonopathy. To study whether the whole neuron...... higher than 300 mg/m2 the patients lost distal tendon and H-reflexes and displayed reduced vibration sense in the feet and the fingers. The amplitudes of sensory nerve action potentials (SNAP) from the fingers innervated by the median nerve and the dorsolateral side of the foot innervated by the sural...... of the foot evoked by a tactile probe showed similar changes to those observed in SNAPs evoked by electrical stimulation. At these doses, somatosensory evoked potentials (SEPs) from the tibial nerve had increased latencies of peripheral, spinal and central responses suggesting loss of central processes...

  5. Optogenetic stimulation of MCH neurons increases sleep.

    Science.gov (United States)

    Konadhode, Roda Rani; Pelluru, Dheeraj; Blanco-Centurion, Carlos; Zayachkivsky, Andrew; Liu, Meng; Uhde, Thomas; Glen, W Bailey; van den Pol, Anthony N; Mulholland, Patrick J; Shiromani, Priyattam J

    2013-06-19

    Melanin concentrating hormone (MCH) is a cyclic neuropeptide present in the hypothalamus of all vertebrates. MCH is implicated in a number of behaviors but direct evidence is lacking. To selectively stimulate the MCH neurons the gene for the light-sensitive cation channel, channelrhodopsin-2, was inserted into the MCH neurons of wild-type mice. Three weeks later MCH neurons were stimulated for 1 min every 5 min for 24 h. A 10 Hz stimulation at the start of the night hastened sleep onset, reduced length of wake bouts by 50%, increased total time in non-REM and REM sleep at night, and increased sleep intensity during the day cycle. Sleep induction at a circadian time when all of the arousal neurons are active indicates that MCH stimulation can powerfully counteract the combined wake-promoting signal of the arousal neurons. This could be potentially useful in treatment of insomnia.

  6. Neuronal Migration and AUTS2 Syndrome.

    Science.gov (United States)

    Hori, Kei; Hoshino, Mikio

    2017-05-14

    Neuronal migration is one of the pivotal steps to form a functional brain, and disorganization of this process is believed to underlie the pathology of psychiatric disorders including schizophrenia, autism spectrum disorders (ASD) and epilepsy. However, it is not clear how abnormal neuronal migration causes mental dysfunction. Recently, a key gene for various psychiatric diseases, the Autism susceptibility candidate 2 (AUTS2), has been shown to regulate neuronal migration, which gives new insight into understanding this question. Interestingly, the AUTS2 protein has dual functions: Cytoplasmic AUTS2 regulates actin cytoskeleton to control neuronal migration and neurite extension, while nuclear AUTS2 controls transcription of various genes as a component of the polycomb complex 1 (PRC1). In this review, we discuss AUTS2 from the viewpoint of human genetics, molecular function, brain development, and behavior in animal models, focusing on its role in neuronal migration.

  7. Neuronal hyperplasia in the anal canal

    DEFF Research Database (Denmark)

    Fenger, C; Schrøder, H D

    1990-01-01

    In a consecutive series of minor surgical specimens from the anal canal, neuronal hyperplasia was found in nine of 56 haemorrhoidectomy specimens and in four of 23 fibrous polyps. In an additional series of 14 resections of the anal canal, neuronal hyperplasia was present in six cases, of which...... five showed haemorrhoids. In all cases, neuronal hyperplasia was located in the submucosa beneath squamous epithelium and extended over an area from 5 to 12 mm. Immunohistochemically, the foci of hyperplasia were found to consist of both neuronal and Schwann cell components. Staining for vasoactive...... intestinal peptide, neuropeptide Y and calcitonin gene related peptide, did not demonstrate any increased terminal density. It is suggested that anal neuronal hyperplasia in these cases represents an acquired lesion due to local mechanical influence....

  8. Attractor dynamics in local neuronal networks

    Directory of Open Access Journals (Sweden)

    Jean-Philippe eThivierge

    2014-03-01

    Full Text Available Patterns of synaptic connectivity in various regions of the brain are characterized by the presence of synaptic motifs, defined as unidirectional and bidirectional synaptic contacts that follow a particular configuration and link together small groups of neurons. Recent computational work proposes that a relay network (two populations communicating via a third, relay population of neurons can generate precise patterns of neural synchronization. Here, we employ two distinct models of neuronal dynamics and show that simulated neural circuits designed in this way are caught in a global attractor of activity that prevents neurons from modulating their response on the basis of incoming stimuli. To circumvent the emergence of a fixed global attractor, we propose a mechanism of selective gain inhibition that promotes flexible responses to external stimuli. We suggest that local neuronal circuits may employ this mechanism to generate precise patterns of neural synchronization whose transient nature delimits the occurrence of a brief stimulus.

  9. Multidisciplinary Interventions in Motor Neuron Disease

    Directory of Open Access Journals (Sweden)

    U. E. Williams

    2014-01-01

    Full Text Available Motor neuron disease is a neurodegenerative disease characterized by loss of upper motor neuron in the motor cortex and lower motor neurons in the brain stem and spinal cord. Death occurs 2–4 years after the onset of the disease. A complex interplay of cellular processes such as mitochondrial dysfunction, oxidative stress, excitotoxicity, and impaired axonal transport are proposed pathogenetic processes underlying neuronal cell loss. Currently evidence exists for the use of riluzole as a disease modifying drug; multidisciplinary team care approach to patient management; noninvasive ventilation for respiratory management; botulinum toxin B for sialorrhoea treatment; palliative care throughout the course of the disease; and Modafinil use for fatigue treatment. Further research is needed in management of dysphagia, bronchial secretion, pseudobulbar affect, spasticity, cramps, insomnia, cognitive impairment, and communication in motor neuron disease.

  10. Neuron-derived IgG Protects Neurons from Complement-dependent Cytotoxicity

    Science.gov (United States)

    Zhang, Jie; Li, Bingjie; McNutt, Michael A.

    2013-01-01

    Passive immunity of the nervous system has traditionally been thought to be predominantly due to the blood-brain barrier. This concept must now be revisited based on the existence of neuron-derived IgG. The conventional concept is that IgG is produced solely by mature B lymphocytes, but it has now been found to be synthesized by murine and human neurons. However, the function of this endogenous IgG is poorly understood. In this study, we confirm IgG production by rat cortical neurons at the protein and mRNA levels, with 69.0 ± 5.8% of cortical neurons IgG-positive. Injury to primary-culture neurons was induced by complement leading to increases in IgG production. Blockage of neuron-derived IgG resulted in more neuronal death and early apoptosis in the presence of complement. In addition, FcγRI was found in microglia and astrocytes. Expression of FcγR I in microglia was increased by exposure to neuron-derived IgG. Release of NO from microglia triggered by complement was attenuated by neuron-derived IgG, and this attenuation could be reversed by IgG neutralization. These data demonstrate that neuron-derived IgG is protective of neurons against injury induced by complement and microglial activation. IgG appears to play an important role in maintaining the stability of the nervous system. PMID:23979841

  11. Coupled activation of primary sensory neurons contributes to chronic pain

    Science.gov (United States)

    Kim, Yu Shin; Anderson, Michael; Park, Kyoungsook; Zheng, Qin; Agarwal, Amit; Gong, Catherine; Saijilafu; Young, LeAnne; He, Shaoqiu; LaVinka, Pamela Colleen; Zhou, Fengquan; Bergles, Dwight; Hanani, Menachem; Guan, Yun; Spray, David C.; Dong, Xinzhong

    2016-01-01

    SUMMARY Primary sensory neurons in the DRG play an essential role in initiating pain by detecting painful stimuli in the periphery. Tissue injury can sensitize DRG neurons, causing heightened pain sensitivity, often leading to chronic pain. Despite the functional importance, how DRG neurons function at a population level is unclear due to the lack of suitable tools. Here we developed an imaging technique that allowed us to simultaneously monitor the activities of >1,600 neurons/DRG in live mice and discovered a striking neuronal coupling phenomenon that adjacent neurons tend to activate together following tissue injury. This coupled activation occurs among various neurons and is mediated by an injury-induced upregulation of gap junctions in glial cells surrounding DRG neurons. Blocking gap junctions attenuated neuronal coupling and mechanical hyperalgesia. Therefore, neuronal coupling represents a new form of neuronal plasticity in the DRG and contributes to pain hypersensitivity by “hijacking” neighboring neurons through gap junctions. PMID:27568517

  12. Distinct Corticostriatal GABAergic Neurons Modulate Striatal Output Neurons and Motor Activity

    Directory of Open Access Journals (Sweden)

    Sarah Melzer

    2017-05-01

    Full Text Available The motor cortico-basal ganglion loop is critical for motor planning, execution, and learning. Balanced excitation and inhibition in this loop is crucial for proper motor output. Excitatory neurons have been thought to be the only source of motor cortical input to the striatum. Here, we identify long-range projecting GABAergic neurons in the primary (M1 and secondary (M2 motor cortex that target the dorsal striatum. This population of projecting GABAergic neurons comprises both somatostatin-positive (SOM+ and parvalbumin-positive (PV+ neurons that target direct and indirect pathway striatal output neurons as well as cholinergic interneurons differentially. Notably, optogenetic stimulation of M1 PV+ and M2 SOM+ projecting neurons reduced locomotion, whereas stimulation of M1 SOM+ projecting neurons enhanced locomotion. Thus, corticostriatal GABAergic projections modulate striatal output and motor activity.

  13. Physiological functions of glucose-inhibited neurones.

    Science.gov (United States)

    Burdakov, D; González, J A

    2009-01-01

    Glucose-inhibited neurones are an integral part of neurocircuits regulating cognitive arousal, body weight and vital adaptive behaviours. Their firing is directly suppressed by extracellular glucose through poorly understood signalling cascades culminating in opening of post-synaptic K(+) or possibly Cl(-) channels. In mammalian brains, two groups of glucose-inhibited neurones are best understood at present: neurones of the hypothalamic arcuate nucleus (ARC) that express peptide transmitters NPY and agouti-related peptide (AgRP) and neurones of the lateral hypothalamus (LH) that express peptide transmitters orexins/hypocretins. The activity of ARC NPY/AgRP neurones promotes food intake and suppresses energy expenditure, and their destruction causes a severe reduction in food intake and body weight. The physiological actions of ARC NPY/AgRP cells are mediated by projections to numerous hypothalamic areas, as well as extrahypothalamic sites such as the thalamus and ventral tegmental area. Orexin/hypocretin neurones of the LH are critical for normal wakefulness, energy expenditure and reward-seeking, and their destruction causes narcolepsy. Orexin actions are mediated by highly widespread central projections to virtually all brain areas except the cerebellum, including monosynaptic innervation of the cerebral cortex and autonomic pre-ganglionic neurones. There, orexins act on two specific G-protein-coupled receptors generally linked to neuronal excitation. In addition to sensing physiological changes in sugar levels, the firing of both NPY/AgRP and orexin neurones is inhibited by the 'satiety' hormone leptin and stimulated by the 'hunger' hormone ghrelin. Glucose-inhibited neurones are thus well placed to coordinate diverse brain states and behaviours based on energy levels.

  14. Death of Neurons following Injury Requires Conductive Neuronal Gap Junction Channels but Not a Specific Connexin.

    Science.gov (United States)

    Fontes, Joseph D; Ramsey, Jon; Polk, Jeremy M; Koop, Andre; Denisova, Janna V; Belousov, Andrei B

    2015-01-01

    Pharmacological blockade or genetic knockout of neuronal connexin 36 (Cx36)-containing gap junctions reduces neuronal death caused by ischemia, traumatic brain injury and NMDA receptor (NMDAR)-mediated excitotoxicity. However, whether Cx36 gap junctions contribute to neuronal death via channel-dependent or channel-independent mechanism remains an open question. To address this, we manipulated connexin protein expression via lentiviral transduction of mouse neuronal cortical cultures and analyzed neuronal death twenty-four hours following administration of NMDA (a model of NMDAR excitotoxicity) or oxygen-glucose deprivation (a model of ischemic injury). In cultures prepared from wild-type mice, over-expression and knockdown of Cx36-containing gap junctions augmented and prevented, respectively, neuronal death from NMDAR-mediated excitotoxicity and ischemia. In cultures obtained form from Cx36 knockout mice, re-expression of functional gap junction channels, containing either neuronal Cx36 or non-neuronal Cx43 or Cx31, resulted in increased neuronal death following insult. In contrast, the expression of communication-deficient gap junctions (containing mutated connexins) did not have this effect. Finally, the absence of ethidium bromide uptake in non-transduced wild-type neurons two hours following NMDAR excitotoxicity or ischemia suggested the absence of active endogenous hemichannels in those neurons. Taken together, these results suggest a role for neuronal gap junctions in cell death via a connexin type-independent mechanism that likely relies on channel activities of gap junctional complexes among neurons. A possible contribution of gap junction channel-permeable death signals in neuronal death is discussed.

  15. Contribution of synchronized GABAergic neurons to dopaminergic neuron firing and bursting

    Science.gov (United States)

    Myroshnychenko, Maxym; Zakharov, Denis; di Volo, Matteo; Gutkin, Boris; Lapish, Christopher C.; Kuznetsov, Alexey

    2016-01-01

    In the ventral tegmental area (VTA), interactions between dopamine (DA) and γ-aminobutyric acid (GABA) neurons are critical for regulating DA neuron activity and thus DA efflux. To provide a mechanistic explanation of how GABA neurons influence DA neuron firing, we developed a circuit model of the VTA. The model is based on feed-forward inhibition and recreates canonical features of the VTA neurons. Simulations revealed that γ-aminobutyric acid (GABA) receptor (GABAR) stimulation can differentially influence the firing pattern of the DA neuron, depending on the level of synchronization among GABA neurons. Asynchronous activity of GABA neurons provides a constant level of inhibition to the DA neuron and, when removed, produces a classical disinhibition burst. In contrast, when GABA neurons are synchronized by common synaptic input, their influence evokes additional spikes in the DA neuron, resulting in increased measures of firing and bursting. Distinct from previous mechanisms, the increases were not based on lowered firing rate of the GABA neurons or weaker hyperpolarization by the GABAR synaptic current. This phenomenon was induced by GABA-mediated hyperpolarization of the DA neuron that leads to decreases in intracellular calcium (Ca2+) concentration, thus reducing the Ca2+-dependent potassium (K+) current. In this way, the GABA-mediated hyperpolarization replaces Ca2+-dependent K+ current; however, this inhibition is pulsatile, which allows the DA neuron to fire during the rhythmic pauses in inhibition. Our results emphasize the importance of inhibition in the VTA, which has been discussed in many studies, and suggest a novel mechanism whereby computations can occur locally. PMID:27440240

  16. Generation of sensory neurons is stimulated by leukemia inhibitory factor.

    OpenAIRE

    Murphy, M; Reid, K; Hilton, D J; Bartlett, P F

    1991-01-01

    The processes that regulate the development of peripheral neurons from their precursors in the embryonic neural crest are essentially unknown. In this report, we show that leukemia inhibitory factor stimulates the generation of neurons in cultures of mouse neural crest. These neurons have the morphology of sensory neurons and contain neuropeptides found in mammalian sensory neurons. Consistent with these neurons being of the sensory lineage is the finding that they arise from nondividing prec...

  17. Forced neuronal interactions cause poor communication.

    Science.gov (United States)

    Krzisch, Marine; Toni, Nicolas

    2017-01-01

    Post-natal hippocampal neurogenesis plays a role in hippocampal function, and neurons born post-natally participate to spatial memory and mood control. However, a great proportion of granule neurons generated in the post-natal hippocampus are eliminated during the first 3 weeks of their maturation, a mechanism that depends on their synaptic integration. In a recent study, we examined the possibility of enhancing the synaptic integration of neurons born post-natally, by specifically overexpressing synaptic cell adhesion molecules in these cells. Synaptic cell adhesion molecules are transmembrane proteins mediating the physical connection between pre- and post-synaptic neurons at the synapse, and their overexpression enhances synapse formation. Accordingly, we found that overexpressing synaptic adhesion molecules increased the synaptic integration and survival of newborn neurons. Surprisingly, the synaptic adhesion molecule with the strongest effect on new neurons' survival, Neuroligin-2A, decreased memory performances in a water maze task. We present here hypotheses explaining these surprising results, in the light of the current knowledge of the mechanisms of synaptic integration of new neurons in the post-natal hippocampus.

  18. Staufen2 Regulates Neuronal Target RNAs

    Directory of Open Access Journals (Sweden)

    Jacki E. Heraud-Farlow

    2013-12-01

    Full Text Available RNA-binding proteins play crucial roles in directing RNA translation to neuronal synapses. Staufen2 (Stau2 has been implicated in both dendritic RNA localization and synaptic plasticity in mammalian neurons. Here, we report the identification of functionally relevant Stau2 target mRNAs in neurons. The majority of Stau2-copurifying mRNAs expressed in the hippocampus are present in neuronal processes, further implicating Stau2 in dendritic mRNA regulation. Stau2 targets are enriched for secondary structures similar to those identified in the 3′ UTRs of Drosophila Staufen targets. Next, we show that Stau2 regulates steady-state levels of many neuronal RNAs and that its targets are predominantly downregulated in Stau2-deficient neurons. Detailed analysis confirms that Stau2 stabilizes the expression of one synaptic signaling component, the regulator of G protein signaling 4 (Rgs4 mRNA, via its 3′ UTR. This study defines the global impact of Stau2 on mRNAs in neurons, revealing a role in stabilization of the levels of synaptic targets.

  19. Responses of MST neurons to plaid stimuli.

    Science.gov (United States)

    Khawaja, Farhan A; Liu, Liu D; Pack, Christopher C

    2013-07-01

    The estimation of motion information from retinal input is a fundamental function of the primate dorsal visual pathway. Previous work has shown that this function involves multiple cortical areas, with each area integrating information from its predecessors. Compared with neurons in the primary visual cortex (V1), neurons in the middle temporal (MT) area more faithfully represent the velocity of plaid stimuli, and the observation of this pattern selectivity has led to two-stage models in which MT neurons integrate the outputs of component-selective V1 neurons. Motion integration in these models is generally complemented by motion opponency, which refines velocity selectivity. Area MT projects to a third stage of motion processing, the medial superior temporal (MST) area, but surprisingly little is known about MST responses to plaid stimuli. Here we show that increased pattern selectivity in MST is associated with greater prevalence of the mechanisms implemented by two-stage MT models: Compared with MT neurons, MST neurons integrate motion components to a greater degree and exhibit evidence of stronger motion opponency. Moreover, when tested with more challenging unikinetic plaid stimuli, an appreciable percentage of MST neurons are pattern selective, while such selectivity is rare in MT. Surprisingly, increased motion integration is found in MST even for transparent plaid stimuli, which are not typically integrated perceptually. Thus the relationship between MST and MT is qualitatively similar to that between MT and V1, as repeated application of basic motion mechanisms leads to novel selectivities at each stage along the pathway.

  20. AgRP Neurons Regulate Bone Mass

    Directory of Open Access Journals (Sweden)

    Jae Geun Kim

    2015-10-01

    Full Text Available The hypothalamus has been implicated in skeletal metabolism. Whether hunger-promoting neurons of the arcuate nucleus impact the bone is not known. We generated multiple lines of mice to affect AgRP neuronal circuit integrity. We found that mice with Ucp2 gene deletion, in which AgRP neuronal function was impaired, were osteopenic. This phenotype was rescued by cell-selective reactivation of Ucp2 in AgRP neurons. When the AgRP circuitry was impaired by early postnatal deletion of AgRP neurons or by cell autonomous deletion of Sirt1 (AgRP-Sirt1−/−, mice also developed reduced bone mass. No impact of leptin receptor deletion in AgRP neurons was found on bone homeostasis. Suppression of sympathetic tone in AgRP-Sirt1−/− mice reversed osteopenia in transgenic animals. Taken together, these observations establish a significant regulatory role for AgRP neurons in skeletal bone metabolism independent of leptin action.

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

    Science.gov (United States)

    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.

    2015-01-01

    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

  2. Human embryonic stem cell-derived neuronal cells form spontaneously active neuronal networks in vitro.

    Science.gov (United States)

    Heikkilä, Teemu J; Ylä-Outinen, Laura; Tanskanen, Jarno M A; Lappalainen, Riikka S; Skottman, Heli; Suuronen, Riitta; Mikkonen, Jarno E; Hyttinen, Jari A K; Narkilahti, Susanna

    2009-07-01

    The production of functional human embryonic stem cell (hESC)-derived neuronal cells is critical for the application of hESCs in treating neurodegenerative disorders. To study the potential functionality of hESC-derived neurons, we cultured and monitored the development of hESC-derived neuronal networks on microelectrode arrays. Immunocytochemical studies revealed that these networks were positive for the neuronal marker proteins beta-tubulin(III) and microtubule-associated protein 2 (MAP-2). The hESC-derived neuronal networks were spontaneously active and exhibited a multitude of electrical impulse firing patterns. Synchronous bursts of electrical activity similar to those reported for hippocampal neurons and rodent embryonic stem cell-derived neuronal networks were recorded from the differentiated cultures until up to 4 months. The dependence of the observed neuronal network activity on sodium ion channels was examined using tetrodotoxin (TTX). Antagonists for the glutamate receptors NMDA [D(-)-2-amino-5-phosphonopentanoic acid] and AMPA/kainate [6-cyano-7-nitroquinoxaline-2,3-dione], and for GABAA receptors [(-)-bicuculline methiodide] modulated the spontaneous electrical activity, indicating that pharmacologically susceptible neuronal networks with functional synapses had been generated. The findings indicate that hESC-derived neuronal cells can generate spontaneously active networks with synchronous communication in vitro, and are therefore suitable for use in developmental and drug screening studies, as well as for regenerative medicine.

  3. Context-aware modeling of neuronal morphologies

    Science.gov (United States)

    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

  4. Context-aware modeling of neuronal morphologies

    Directory of Open Access Journals (Sweden)

    Benjamin eTorben-Nielsen

    2014-09-01

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

  5. Reaction-Diffusion in the NEURON Simulator

    Directory of Open Access Journals (Sweden)

    Robert A. McDougal

    2013-11-01

    Full Text Available In order to support research on the role of cell biological principles (genomics, proteomics, signaling cascades and reaction dynamics on the dynamics of neuronal response in health and disease, NEURON has developed a Reaction-Diffusion (rxd module in Python which provides specification and simulation for these dynamics, coupled with the electrophysiological dynamics of the cell membrane. Arithmetic operations on species and parameters are overloaded, allowing arbitrary reaction formulas to be specified using Python syntax. These expressions are then transparently compiled into bytecode that uses NumPy for fast vectorized calculations. At each time step, rxd combines NEURON's integrators with SciPy’s sparse linear algebra library.

  6. Managing Brain Extracellular K(+) during Neuronal Activity

    DEFF Research Database (Denmark)

    Larsen, Brian Roland; Stoica, Anca; MacAulay, Nanna

    2016-01-01

    isoform compositions of the Na(+)/K(+)-ATPase remain unresolved. The various cell types in the brain serve a certain temporal contribution in the face of network activity; astrocytes respond directly to the immediate release of K(+) from neurons, whereas the neurons themselves become the primary K...... characteristics required to fulfill their distinct physiological roles in clearance of K(+) from the extracellular space in the face of neuronal activity. Understanding the nature, impact and effects of the various Na(+)/K(+)-ATPase isoform combinations in K(+) management in the central nervous system might...

  7. Evoking prescribed spike times in stochastic neurons

    Science.gov (United States)

    Doose, Jens; Lindner, Benjamin

    2017-09-01

    Single cell stimulation in vivo is a powerful tool to investigate the properties of single neurons and their functionality in neural networks. We present a method to determine a cell-specific stimulus that reliably evokes a prescribed spike train with high temporal precision of action potentials. We test the performance of this stimulus in simulations for two different stochastic neuron models. For a broad range of parameters and a neuron firing with intermediate firing rates (20-40 Hz) the reliability in evoking the prescribed spike train is close to its theoretical maximum that is mainly determined by the level of intrinsic noise.

  8. Tracing lineages to uncover neuronal identity

    Directory of Open Access Journals (Sweden)

    Perlmann Thomas

    2011-07-01

    Full Text Available Abstract Many previous studies have focused on understanding how midbrain dopamine neurons, which are implicated in many neurological conditions, are generated during embryogenesis. One of the remaining questions concerns how different dopamine neuron subtypes are specified. A recent paper in Neural Development has revealed features of a spatial and temporal lineage map that, together with other studies, begins to elucidate the developmental origin of distinct neuronal subtypes within the developing midbrain. See research article http://www.neuraldevelopment.com/content/6/1/29

  9. Statistical Mechanics Characterization of Neuronal Mosaics

    CERN Document Server

    Costa, Luciano da Fontoura; de Lima, Silene Maria Araujo

    2005-01-01

    The spatial distribution of neuronal cells is an important requirement for achieving proper neuronal function in several parts of the nervous system of most animals. For instance, specific distribution of photoreceptors and related neuronal cells, particularly the ganglion cells, in mammal's retina is required in order to properly sample the projected scene. This work presents how two concepts from the areas of statistical mechanics and complex systems, namely the \\emph{lacunarity} and the \\emph{multiscale entropy} (i.e. the entropy calculated over progressively diffused representations of the cell mosaic), have allowed effective characterization of the spatial distribution of retinal cells.

  10. Neuron-glia interactions in glutamatergic neurotransmission

    DEFF Research Database (Denmark)

    Schousboe, A; Sickmann, H M; Bak, Lasse Kristoffer

    2011-01-01

    theses processes also has not been fully elucidated. Cultured astrocytes and neurons were utilized to monitor these processes related to glutamatergic neurotransmission. Inhibitors of glycolysis and TCA cycle in combination with pathway-selective substrates were used to study glutamate uptake and release...... in providing energy for glutamate uptake both in astrocytes and in neurons. The neuronal vesicular glutamate release was less dependent on glycolytic ATP. Dependence of glutamate uptake on glycolytic ATP may be at least partially explained by a close association in the membrane of GAPDH and PGK...

  11. Neuronal damage by secretory phospholipase A2

    DEFF Research Database (Denmark)

    Kolko, Miriam; Rodriguez de Turco, Elena B; Diemer, Nils H

    2003-01-01

    signal transduction has previously been suggested (J Biol Chem 271:32722; 1996). Here we show, using neuronal cell cultures, an up-regulation of cPLA(2) expression and an inhibition by the selective cPLA(2) inhibitor AACOCF3 after exposure to neurotoxic concentrations of sPLA(2)-OS2. Pretreatment...... of neuronal cultures with recombinant PAF acetylhydrolase (rPAF-AH) or the presynaptic PAF receptor antagonist, BN52021, partially blocked neuronal cell death induced by sPLA(2)-OS2. Furthermore, selective COX-2 inhibitors ameliorated sPLA(2)-OS2-induced neurotoxicity. We conclude that sPLA(2)-OS2 activates...

  12. A novel enteric neuron-glia coculture system reveals the role of glia in neuronal development.

    Science.gov (United States)

    Le Berre-Scoul, Catherine; Chevalier, Julien; Oleynikova, Elena; Cossais, François; Talon, Sophie; Neunlist, Michel; Boudin, Hélène

    2017-01-15

    Unlike astrocytes in the brain, the potential role of enteric glial cells (EGCs) in the formation of the enteric neuronal circuit is currently unknown. To examine the role of EGCs in the formation of the neuronal network, we developed a novel neuron-enriched culture model from embryonic rat intestine grown in indirect coculture with EGCs. We found that EGCs shape axonal complexity and synapse density in enteric neurons, through purinergic- and glial cell line-derived neurotrophic factor-dependent pathways. Using a novel and valuable culture model to study enteric neuron-glia interactions, our study identified EGCs as a key cellular actor regulating neuronal network maturation. In the nervous system, the formation of neuronal circuitry results from a complex and coordinated action of intrinsic and extrinsic factors. In the CNS, extrinsic mediators derived from astrocytes have been shown to play a key role in neuronal maturation, including dendritic shaping, axon guidance and synaptogenesis. In the enteric nervous system (ENS), the potential role of enteric glial cells (EGCs) in the maturation of developing enteric neuronal circuit is currently unknown. A major obstacle in addressing this question is the difficulty in obtaining a valuable experimental model in which enteric neurons could be isolated and maintained without EGCs. We adapted a cell culture method previously developed for CNS neurons to establish a neuron-enriched primary culture from embryonic rat intestine which was cultured in indirect coculture with EGCs. We demonstrated that enteric neurons grown in such conditions showed several structural, phenotypic and functional hallmarks of proper development and maturation. However, when neurons were grown without EGCs, the complexity of the axonal arbour and the density of synapses were markedly reduced, suggesting that glial-derived factors contribute strongly to the formation of the neuronal circuitry. We found that these effects played by EGCs were

  13. Cellular and molecular neuronal plasticity.

    Science.gov (United States)

    Griesbach, Grace S; Hovda, David A

    2015-01-01

    The brain has the capability to adapt to function when tissue is compromised. This capability of adaptation paves the road to recovery and allows for rehabilitation after a traumatic brain injury (TBI). This chapter addresses neuroplasticity within the context of TBI. Here neuroplasticity is defined as changes in neuronal structure and function, including synaptic changes as well as modifications in neural pathways. First, the influence of TBI pathology on neuroplasticity is addressed. Here, proteins that are important in neuroplasticity are introduced and a description given of how these are affected in a temporal and severity-dependent manner. Secondly, given that we are becoming increasingly aware that the brain's response to injury is highly influenced by the environmental milieu, the manner in which behavioral manipulations have an effect on TBI-associated neuroplasticity is addressed. A description is given of how specific environmental qualities may facilitate or hinder neuroplasticity. Finally, the long-term effects of neuroplasticity and the relevance it has to rehabilitation are described. © 2015 Elsevier B.V. All rights reserved.

  14. Sensory neuron-derived eph regulates glomerular arbors and modulatory function of a central serotonergic neuron.

    Directory of Open Access Journals (Sweden)

    Ajeet Pratap Singh

    2013-04-01

    Full Text Available Olfactory sensory neurons connect to the antennal lobe of the fly to create the primary units for processing odor cues, the glomeruli. Unique amongst antennal-lobe neurons is an identified wide-field serotonergic neuron, the contralaterally-projecting, serotonin-immunoreactive deutocerebral neuron (CSDn. The CSDn spreads its termini all over the contralateral antennal lobe, suggesting a diffuse neuromodulatory role. A closer examination, however, reveals a restricted pattern of the CSDn arborization in some glomeruli. We show that sensory neuron-derived Eph interacts with Ephrin in the CSDn, to regulate these arborizations. Behavioural analysis of animals with altered Eph-ephrin signaling and with consequent arborization defects suggests that neuromodulation requires local glomerular-specific patterning of the CSDn termini. Our results show the importance of developmental regulation of terminal arborization of even the diffuse modulatory neurons to allow them to route sensory-inputs according to the behavioural contexts.

  15. Anatomical characterization of PDF-Tri neurons and peptidergic neurons associated with eclosion behavior in Drosophila.

    Science.gov (United States)

    Selcho, Mareike; Mühlbauer, Barbara; Hensgen, Ronja; Shiga, Sakiko; Wegener, Christian; Yasuyama, Kouji

    2018-02-10

    The peptidergic PDF-Tri neurons are a group of non-clock neurons that appear transiently around the time of adult ecdysis (=eclosion) in the fruit fly Drosophila melanogaster. This specific developmental pattern points to a function of these neurons in eclosion or other processes that are active around pupal-adult transition. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  16. Frizzled-5 receptor is involved in neuronal polarity and morphogenesis of hippocampal neurons.

    Directory of Open Access Journals (Sweden)

    Paula G Slater

    Full Text Available The Wnt signaling pathway plays important roles during different stages of neuronal development, including neuronal polarization and dendritic and axonal outgrowth. However, little is known about the identity of the Frizzled receptors mediating these processes. In the present study, we investigated the role of Frizzled-5 (Fzd5 on neuronal development in cultured Sprague-Dawley rat hippocampal neurons. We found that Fzd5 is expressed early in cultured neurons on actin-rich structures localized at minor neurites and axonal growth cones. At 4 DIV, Fzd5 polarizes towards the axon, where its expression is detected mainly at the peripheral zone of axonal growth cones, with no obvious staining at dendrites; suggesting a role of Fzd5 in neuronal polarization. Overexpression of Fzd5 during the acquisition of neuronal polarity induces mislocalization of the receptor and a loss of polarized axonal markers. Fzd5 knock-down leads to loss of axonal proteins, suggesting an impaired neuronal polarity. In contrast, overexpression of Fzd5 in neurons that are already polarized did not alter polarity, but decreased the total length of axons and increased total dendrite length and arborization. Fzd5 activated JNK in HEK293 cells and the effects triggered by Fzd5 overexpression in neurons were partially prevented by inhibition of JNK, suggesting that a non-canonical Wnt signaling mechanism might be involved. Our results suggest that, Fzd5 has a role in the establishment of neuronal polarity, and in the morphogenesis of neuronal processes, in part through the activation of the non-canonical Wnt mechanism involving JNK.

  17. Transient Synchronization in Complex Neuronal Networks

    CERN Document Server

    Costa, Luciano da Fontoura

    2008-01-01

    Transient synchronization in complex neuronal networks as a consequence of activation-conserved dynamics induced by having sources placed at specific neurons is investigated. The basic integrate-and-fire neuron is adopted, and the dynamics is estimated computationally so as to obtain the activation at each node along each instant of time. The dynamics is implemented so as to conserve the total activation entering the system, which is a distinctive feature of the current work. The synchronization of the activation of the network is then quantified along time in terms of its normalized instantaneous entropy. The potential of such concepts and measurements is explored with respect to 6 theoretical models, as well as for the neuronal network of \\emph{C. elegans}. A series of interesting results are obtained and discussed, including the fact that all models led to a transient period of synchronization, whose specific features depend heavily on the topological features of the networks.

  18. Growth control mechanisms in neuronal regeneration

    National Research Council Canada - National Science Library

    Doron-Mandel, Ella; Fainzilber, Mike; Terenzio, Marco

    2015-01-01

    Neurons grow during development and extend long axons to make contact with their targets with the help of an intrinsic program of axonal growth as well as a range of extrinsic cues and a permissive milieu...

  19. The Age of Human Cerebral Cortex Neurons

    Energy Technology Data Exchange (ETDEWEB)

    Bhardwaj, R D; Curtis, M A; Spalding, K L; Buchholz, B A; Fink, D; Bjork-Eriksson, T; Nordborg, C; Gage, F H; Druid, H; Eriksson, P S; Frisen, J

    2006-04-06

    The traditional static view of the adult mammalian brain has been challenged by the realization of continuous generation of neurons from stem cells. Based mainly on studies in experimental animals, adult neurogenesis may contribute to recovery after brain insults and decreased neurogenesis has been implicated in the pathogenesis of neurological and psychiatric diseases in man. The extent of neurogenesis in the adult human brain has, however, been difficult to establish. We have taken advantage of the integration of {sup 14}C, generated by nuclear bomb tests during the Cold War, in DNA to establish the age of neurons in the major areas of the human cerebral cortex. Together with the analysis of the cortex from patients who received BrdU, which integrates in the DNA of dividing cells, our results demonstrate that whereas non-neuronal cells turn over, neurons in the human cerebral cortex are not generated postnatally at detectable levels, but are as old as the individual.

  20. Review Paper: Polyphenolic Antioxidants and Neuronal Regeneration

    Directory of Open Access Journals (Sweden)

    Amin Ataie

    2016-05-01

    Full Text Available 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.

  1. The Neuronal Network Orchestration behind Motor Behaviors

    DEFF Research Database (Denmark)

    Petersen, Peter Christian

    In biological networks, millions of neurons organize themselves from microscopic noisy individuals to robust macroscopic entities. These entities are capable of producing higher functions like sensory processing, decision-making, and elaborate behavioral responses. Every aspect of these behaviors...... is the outcome of an advanced orchestration of the activity of populations of neurons. Through spiking activity, neurons are able to interact; yet we know little about how this interaction occurs in spinal networks. How is the activity distributed across the population? What is the composition of synaptic input...... that is received by the individual neurons and how is the synaptic input processed? This thesis focuses on aspects of these questions for spinal networks involved in the generation of stereotypical motor behaviors. The thesis consists of two studies. In the first study, I investigated the synaptic input...

  2. Sigma-1 Receptor and Neuronal Excitability.

    Science.gov (United States)

    Kourrich, Saïd

    2017-01-01

    The sigma-1 receptor (Sig-1R), via interaction with various proteins, including voltage-gated and ligand-gated ion channels (VGICs and LGICs), is involved in a plethora of neuronal functions. This capability to regulate a variety of ion channel targets endows the Sig-1R with a powerful capability to fine tune neuronal excitability, and thereby the transmission of information within brain circuits. This versatility may also explain why the Sig-1R is associated to numerous diseases at both peripheral and central levels. To date, how the Sig-1R chooses its targets and how the combinations of target modulations alter overall neuronal excitability is one of the challenges in the field of Sig-1R-dependent regulation of neuronal activity. Here, we will describe and discuss the latest findings on Sig-1R-dependent modulation of VGICs and LGICs, and provide hypotheses that may explain the diverse excitability outcomes that have been reported so far.

  3. Transition to Chaos in Random Neuronal Networks

    National Research Council Canada - National Science Library

    Jonathan Kadmon; Haim Sompolinsky

    2015-01-01

    .... Indeed, simplified rate-based neuronal networks with synaptic connections drawn from Gaussian distribution and sigmoidal nonlinearity are known to exhibit chaotic dynamics when the synaptic gain (i.e...

  4. How Might New Neurons Buffer Against Stress?

    Science.gov (United States)

    ... other possible mechanisms involving stress-related thinking and emotion circuitry. VIDEO Maturation and function of new neurons ... A college student’s stint in a Porter neuroscience lab Heather Frank, then a senior majoring in neuroscience ...

  5. Integrated microfluidic platforms for investigating neuronal networks

    Science.gov (United States)

    Kim, Hyung Joon

    This dissertation describes the development and application of integrated microfluidics-based assay platforms to study neuronal activities in the nervous system in-vitro. The assay platforms were fabricated using soft lithography and micro/nano fabrication including microfluidics, surface patterning, and nanomaterial synthesis. The use of integrated microfluidics-based assay platform allows culturing and manipulating many types of neuronal tissues in precisely controlled microenvironment. Furthermore, they provide organized multi-cellular in-vitro model, long-term monitoring with live cell imaging, and compatibility with molecular biology techniques and electrophysiology experiment. In this dissertation, the integrated microfluidics-based assay platforms are developed for investigation of neuronal activities such as local protein synthesis, impairment of axonal transport by chemical/physical variants, growth cone path finding under chemical/physical cues, and synaptic transmission in neuronal circuit. Chapter 1 describes the motivation, objectives, and scope for developing in-vitro platform to study various neuronal activities. Chapter 2 introduces microfluidic culture platform for biochemical assay with large-scale neuronal tissues that are utilized as model system in neuroscience research. Chapter 3 focuses on the investigation of impaired axonal transport by beta-Amyloid and oxidative stress. The platform allows to control neuronal processes and to quantify mitochondrial movement in various regions of axons away from applied drugs. Chapter 4 demonstrates the development of microfluidics-based growth cone turning assay to elucidate the mechanism underlying axon guidance under soluble factors and shear flow. Using this platform, the behaviors of growth cone of mammalian neurons are verified under the gradient of inhibitory molecules and also shear flow in well-controlled manner. In Chapter 5, I combine in-vitro multicellular model with microfabricated MEA

  6. Neuronal organization of olfactory bulb circuits

    Science.gov (United States)

    Nagayama, Shin; Homma, Ryota; Imamura, Fumiaki

    2014-01-01

    Olfactory sensory neurons extend their axons solely to the olfactory bulb, which is dedicated to odor information processing. The olfactory bulb is divided into multiple layers, with different types of neurons found in each of the layers. Therefore, neurons in the olfactory bulb have conventionally been categorized based on the layers in which their cell bodies are found; namely, juxtaglomerular cells in the glomerular layer, tufted cells in the external plexiform layer, mitral cells in the mitral cell layer, and granule cells in the granule cell layer. More recently, numerous studies have revealed the heterogeneous nature of each of these cell types, allowing them to be further divided into subclasses based on differences in morphological, molecular, and electrophysiological properties. In addition, technical developments and advances have resulted in an increasing number of studies regarding cell types other than the conventionally categorized ones described above, including short-axon cells and adult-generated interneurons. Thus, the expanding diversity of cells in the olfactory bulb is now being acknowledged. However, our current understanding of olfactory bulb neuronal circuits is mostly based on the conventional and simplest classification of cell types. Few studies have taken neuronal diversity into account for understanding the function of the neuronal circuits in this region of the brain. This oversight may contribute to the roadblocks in developing more precise and accurate models of olfactory neuronal networks. The purpose of this review is therefore to discuss the expanse of existing work on neuronal diversity in the olfactory bulb up to this point, so as to provide an overall picture of the olfactory bulb circuit. PMID:25232305

  7. Progranulin regulates neuronal outgrowth independent of Sortilin

    Directory of Open Access Journals (Sweden)

    Gass Jennifer

    2012-07-01

    Full Text Available Abstract Background Progranulin (PGRN, a widely secreted growth factor, is involved in multiple biological functions, and mutations located within the PGRN gene (GRN are a major cause of frontotemporal lobar degeneration with TDP-43-positive inclusions (FLTD-TDP. In light of recent reports suggesting PGRN functions as a protective neurotrophic factor and that sortilin (SORT1 is a neuronal receptor for PGRN, we used a Sort1-deficient (Sort1−/− murine primary hippocampal neuron model to investigate whether PGRN’s neurotrophic effects are dependent on SORT1. We sought to elucidate this relationship to determine what role SORT1, as a regulator of PGRN levels, plays in modulating PGRN’s neurotrophic effects. Results As the first group to evaluate the effect of PGRN loss in Grn knockout primary neuronal cultures, we show neurite outgrowth and branching are significantly decreased in Grn−/− neurons compared to wild-type (WT neurons. More importantly, we also demonstrate that PGRN overexpression can rescue this phenotype. However, the recovery in outgrowth is not observed following treatment with recombinant PGRN harboring missense mutations p.C139R, p.P248L or p.R432C, indicating that these mutations adversely affect the neurotrophic properties of PGRN. In addition, we also present evidence that cleavage of full-length PGRN into granulin peptides is required for increased neuronal outgrowth, suggesting that the neurotrophic functions of PGRN are contained within certain granulins. To further characterize the mechanism by which PGRN impacts neuronal morphology, we assessed the involvement of SORT1. We demonstrate that PGRN induced-outgrowth occurs in the absence of SORT1 in Sort1−/− cultures. Conclusion We demonstrate that loss of PGRN impairs proper neurite outgrowth and branching, and that exogenous PGRN alleviates this impairment. Furthermore, we determined that exogenous PGRN induces outgrowth independent of SORT1, suggesting another

  8. Efavirenz Induces Neuronal Autophagy and Mitochondrial Alterations

    OpenAIRE

    Purnell, Phillip R; Fox, Howard S.

    2014-01-01

    Efavirenz (EFV) is a non-nucleoside reverse-transcriptase inhibitor in wide use for the treatment of human immunodeficiency virus infection. Although EFV is generally well tolerated, neuropsychiatric toxicity has been well documented. The toxic effects of EFV in hepatocytes and keratinocytes have been linked to mitochondrial perturbations and changes in autophagy. Here, we studied the effect of EFV on mitochondria and autophagy in neuronal cell lines and primary neurons. In SH-SY5Y cells, EFV...

  9. On the dynamics of random neuronal networks

    OpenAIRE

    Robert, Philippe; Touboul, Jonathan D.

    2014-01-01

    We study the mean-field limit and stationary distributions of a pulse-coupled network modeling the dynamics of a large neuronal assemblies. Our model takes into account explicitly the intrinsic randomness of firing times, contrasting with the classical integrate-and-fire model. The ergodicity properties of the Markov process associated to finite networks are investigated. We derive the limit in distribution of the sample path of the state of a neuron of the network when its size gets large. T...

  10. Spatio-Temporal Modeling of Neuron Fields

    DEFF Research Database (Denmark)

    Lund, Adam

    The starting point and focal point for this thesis was stochastic dynamical modelling of neuronal imaging data with the declared objective of drawing inference, within this model framework, in a large-scale (high-dimensional) data setting. Implicitly this objective entails carrying out three......-temporal array data. This framework was developed with neuron field models in mind but may in turn be applied to other settings conforming to the spatio-temporal array data setup....

  11. Inducible gene manipulations in serotonergic neurons

    Directory of Open Access Journals (Sweden)

    Tillmann Weber

    2009-11-01

    Full Text Available An impairment of the serotonergic (5-HT system has been implicated in the etiology of many neuropsychiatric disorders. Despite the considerable genetic evidence, the exact molecular and pathophysiological mechanisms underlying this dysfunction remain largely unknown. To address the lack of instruments for the molecular dissection of gene function in serotonergic neurons we have developed a new mouse transgenic tool that allows inducible Cre-mediated recombination of genes selectively in 5-HT neurons of all raphe nuclei. In this transgenic mouse line, the tamoxifen-inducible CreERT2 recombinase is expressed under the regulatory control of the mouse tryptophan hydroxylase 2 (Tph2 gene locus (177kb. Tamoxifen treatment efficiently induced recombination selectively in serotonergic neurons with minimal background activity in vehicle-treated mice. These genetic manipulations can be initiated at any desired time during embryonic development, neonatal stage or adulthood. To illustrate the versatility of this new tool, we show that Brainbow-1.0LTPH2-CreERT2 mice display highly efficient recombination in serotonergic neurons with individual 5-HT neurons labelling with multiple distinct fluorescent colors. This labelling is well suited for visualization and tracing of serotonergic neurons and their network architecture. Finally, the applicability of TPH2-CreERT2 for loxP-flanked candidate gene manipulation is evidenced by our successful knockout induction of the ubiquitously expressed glucocorticoid-receptor (GR exclusively in 5-HT neurons of adult mice. The TPH2-CreERT2 line will allow detailed analysis of gene function in both developing and adult serotonergic neurons

  12. Action observation: Inferring intentions without mirror neurons

    DEFF Research Database (Denmark)

    Frith, Christopher; Kilner, James M

    2008-01-01

    A recent study has shown, using fMRI, that the mirror neuron system does not mediate action understanding when the observed action is novel or when it is hard to understand.......A recent study has shown, using fMRI, that the mirror neuron system does not mediate action understanding when the observed action is novel or when it is hard to understand....

  13. Neuronal organization of olfactory bulb circuits

    Directory of Open Access Journals (Sweden)

    Shin eNagayama

    2014-09-01

    Full Text Available Olfactory sensory neurons extend their axons solely to the olfactory bulb, which is dedicated to odor information processing. The olfactory bulb is divided into multiple layers, with different types of neurons found in each of the layers. Therefore, neurons in the olfactory bulb have conventionally been categorized based on the layers in which their cell bodies are found; namely, juxtaglomerular cells in the glomerular layer, tufted cells in the external plexiform layer, mitral cells in the mitral cell layer, and granule cells in the granule cell layer. More recently, numerous studies have revealed the heterogeneous nature of each of these cell types, allowing them to be further divided into subclasses based on differences in morphological, molecular, and electrophysiological properties. In addition, technical developments and advances have resulted in an increasing number of studies regarding cell types other than the conventionally categorized ones described above, including short-axon cells and adult-generated interneurons. Thus, the expanding diversity of cells in the olfactory bulb is now being acknowledged. However, our current understanding of olfactory bulb neuronal circuits is mostly based on the conventional and simplest classification of cell types. Few studies have taken neuronal diversity into account for understanding the function of the neuronal circuits in this region of the brain. This oversight may contribute to the roadblocks in developing more precise and accurate models of olfactory neuronal networks. The purpose of this review is therefore to discuss the expanse of existing work on neuronal diversity in the olfactory bulb up to this point, so as to provide an overall picture of the olfactory bulb circuit.

  14. Inducible Gene Manipulations in Serotonergic Neurons

    Science.gov (United States)

    Weber, Tillmann; Böhm, Gerald; Hermann, Elke; Schütz, Günther; Schönig, Kai; Bartsch, Dusan

    2009-01-01

    An impairment of the serotonergic (5-HT) system has been implicated in the etiology of many neuropsychiatric disorders. Despite the considerable genetic evidence, the exact molecular and pathophysiological mechanisms underlying this dysfunction remain largely unknown. To address the lack of instruments for the molecular dissection of gene function in serotonergic neurons we have developed a new mouse transgenic tool that allows inducible Cre-mediated recombination of genes selectively in 5-HT neurons of all raphe nuclei. In this transgenic mouse line, the tamoxifen-inducible CreERT2 recombinase is expressed under the regulatory control of the mouse tryptophan hydroxylase 2 (Tph2) gene locus (177 kb). Tamoxifen treatment efficiently induced recombination selectively in serotonergic neurons with minimal background activity in vehicle-treated mice. These genetic manipulations can be initiated at any desired time during embryonic development, neonatal stage or adulthood. To illustrate the versatility of this new tool, we show that Brainbow-1.0LTPH2-CreERT2 mice display highly efficient recombination in serotonergic neurons with individual 5-HT neurons labeling with multiple distinct fluorescent colors. This labeling is well suited for visualization and tracing of serotonergic neurons and their network architecture. Finally, the applicability of TPH2-CreERT2 for loxP-flanked candidate gene manipulation is evidenced by our successful knockout induction of the ubiquitously expressed glucocorticoid-receptor exclusively in 5-HT neurons of adult mice. The TPH2-CreERT2 line will allow detailed analysis of gene function in both developing and adult serotonergic neurons. PMID:19936315

  15. Unidirectional synchronization of Hodgkin-Huxley neurons

    Energy Technology Data Exchange (ETDEWEB)

    Cornejo-Perez, Octavio [Division de Matematicas Aplicadas y Sistemas, Computacionales, IPICYT, Apdo. Postal 3-74 Tangamanga, 78231 San Luis Potosi (Mexico)]. E-mail: octavio@ipicyt.edu.mx; Femat, Ricardo [Division de Matematicas Aplicadas y Sistemas, Computacionales, IPICYT, Apdo. Postal 3-74 Tangamanga, 78231 San Luis Potosi (Mexico)]. E-mail: rfemat@ipicyt.edu.mx

    2005-07-01

    Synchronization dynamics of two noiseless Hodgkin-Huxley (HH) neurons under the action of feedback control is studied. The spiking patterns of the action potentials evoked by periodic external modulations attain synchronization states under the feedback action. Numerical simulations for the synchronization dynamics of regular-irregular desynchronized spiking sequences are displayed. The results are discussed in context of generalized synchronization. It is also shown that the HH neurons can be synchronized in face of unmeasured states.

  16. Analysis of Neuronal Sequences Using Pairwise Biases

    Science.gov (United States)

    2015-08-27

    Traversal of a series of place fields results in the generation of a neuronal sequence called a place-field sequence , such as pictured in Figure 1.1. It...16. SECURITY CLASSIFICATION OF: Sequences of neuronal activation have long been implicated in a variety of brain func- tions. In particular, these... sequences have been tied to memory formation and spatial navigation in the hippocampus, a region of mammalian brains. Traditionally, neu- ronal

  17. Non-linear dendrites can tune neurons

    Directory of Open Access Journals (Sweden)

    Romain Daniel Cazé

    2014-03-01

    Full Text Available A signature of visual, auditory, and motor cortices is the presence of neurons tuned to distinct features of the environment. While neuronal tuning can be observed in most brain areas, its origin remains enigmatic, and new calcium imaging data complicate this problem. Dendritic calcium signals, in a L2/3 neuron from the mouse visual cortex, display a wide range of tunings that could be different from the neuronal tuning (Jia et al 2010. To elucidate this observation we use multi-compartmental models of increasing complexity, from a binary to a realistic biophysical model of L2/3 neuron. These models possess non-linear dendritic subunits inside which the result of multiple excitatory inputs is smaller than their arithmetic sum. While dendritic non-linear subunits are ad-hoc in the binary model, non-linearities in the realistic model come from the passive saturation of synaptic currents. Because of these non-linearities our neuron models are scatter sensitive: the somatic membrane voltage is higher when presynaptic inputs target different dendrites than when they target a single dendrite. This spatial bias in synaptic integration is, in our models, the origin of neuronal tuning. Indeed, assemblies of presynaptic inputs encode the stimulus property through an increase in correlation or activity, and only the assembly that encodes the preferred stimulus targets different dendrites. Assemblies coding for the non-preferred stimuli target single dendrites, explaining the wide range of observed tunings and the possible difference between dendritic and somatic tuning. We thus propose, in accordance with the latest experimental observations, that non-linear integration in dendrites can generate neuronal tuning independently of the coding regime.

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

    Science.gov (United States)

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

    2014-03-11

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

  19. Neuronal somatic ATP release triggers neuron-satellite glial cell communication in dorsal root ganglia.

    Science.gov (United States)

    Zhang, X; Chen, Y; Wang, C; Huang, L-Y M

    2007-06-05

    It has been generally assumed that the cell body (soma) of a neuron, which contains the nucleus, is mainly responsible for synthesis of macromolecules and has a limited role in cell-to-cell communication. Using sniffer patch recordings, we show here that electrical stimulation of dorsal root ganglion (DRG) neurons elicits robust vesicular ATP release from their somata. The rate of release events increases with the frequency of nerve stimulation; external Ca(2+) entry is required for the release. FM1-43 photoconversion analysis further reveals that small clear vesicles participate in exocytosis. In addition, the released ATP activates P2X7 receptors in satellite cells that enwrap each DRG neuron and triggers the communication between neuronal somata and glial cells. Blocking L-type Ca(2+) channels completely eliminates the neuron-glia communication. We further show that activation of P2X7 receptors can lead to the release of tumor necrosis factor-alpha (TNFalpha) from satellite cells. TNFalpha in turn potentiates the P2X3 receptor-mediated responses and increases the excitability of DRG neurons. This study provides strong evidence that somata of DRG neurons actively release transmitters and play a crucial role in bidirectional communication between neurons and surrounding satellite glial cells. These results also suggest that, contrary to the conventional view, neuronal somata have a significant role in cell-cell signaling.

  20. A neuron-astrocyte transistor-like model for neuromorphic dressed neurons.

    Science.gov (United States)

    Valenza, G; Pioggia, G; Armato, A; Ferro, M; Scilingo, E P; De Rossi, D

    2011-09-01

    Experimental evidences on the role of the synaptic glia as an active partner together with the bold synapse in neuronal signaling and dynamics of neural tissue strongly suggest to investigate on a more realistic neuron-glia model for better understanding human brain processing. Among the glial cells, the astrocytes play a crucial role in the tripartite synapsis, i.e. the dressed neuron. A well-known two-way astrocyte-neuron interaction can be found in the literature, completely revising the purely supportive role for the glia. The aim of this study is to provide a computationally efficient model for neuron-glia interaction. The neuron-glia interactions were simulated by implementing the Li-Rinzel model for an astrocyte and the Izhikevich model for a neuron. Assuming the dressed neuron dynamics similar to the nonlinear input-output characteristics of a bipolar junction transistor, we derived our computationally efficient model. This model may represent the fundamental computational unit for the development of real-time artificial neuron-glia networks opening new perspectives in pattern recognition systems and in brain neurophysiology. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Computational Modeling of Neuronal Current MRI Signals with Rat Somatosensory Cortical Neurons.

    Science.gov (United States)

    BagheriMofidi, Seyed Mehdi; Pouladian, Majid; Jameie, Seyed Behnammodin; Abbaspour Tehrani-Fard, Ali

    2016-09-01

    Magnetic field generated by active neurons has recently been considered to determine location of neuronal activity directly with magnetic resonance imaging (MRI), but controversial results have been reported about detection of such small magnetic fields. In this study, multiple neuronal morphologies of rat tissue were modeled to investigate better estimation of MRI signal change produced by neuronal magnetic field (NMF). Ten pyramidal neurons from layer II to VI of rat somatosensory area with realistic morphology, biophysics, and neuronal density were modeled to simulate NMF of neuronal tissue, from which effects of NMF on MRI signals were obtained. Neuronal current MRI signals, which consist of relative magnitude signal change (RMSC) and phase signal change (PSC), were at least three and one orders of magnitude less than a tissue with single neuron type, respectively. Also, a reduction in voxel size could increase signal alterations. Furthermore, with selection of zenith angle of external main magnetic field related to tissue surface near to 90°, RMSC could be maximized. This value for PSC would be 90° for small voxel size and zero degree for large ones.

  2. Statistics of Visual Responses to Image Object Stimuli from Primate AIT Neurons to DNN Neurons.

    Science.gov (United States)

    Dong, Qiulei; Wang, Hong; Hu, Zhanyi

    2018-02-01

    Under the goal-driven paradigm, Yamins et al. ( 2014 ; Yamins & DiCarlo, 2016 ) have shown that by optimizing only the final eight-way categorization performance of a four-layer hierarchical network, not only can its top output layer quantitatively predict IT neuron responses but its penultimate layer can also automatically predict V4 neuron responses. Currently, deep neural networks (DNNs) in the field of computer vision have reached image object categorization performance comparable to that of human beings on ImageNet, a data set that contains 1.3 million training images of 1000 categories. We explore whether the DNN neurons (units in DNNs) possess image object representational statistics similar to monkey IT neurons, particularly when the network becomes deeper and the number of image categories becomes larger, using VGG19, a typical and widely used deep network of 19 layers in the computer vision field. Following Lehky, Kiani, Esteky, and Tanaka ( 2011 , 2014 ), where the response statistics of 674 IT neurons to 806 image stimuli are analyzed using three measures (kurtosis, Pareto tail index, and intrinsic dimensionality), we investigate the three issues in this letter using the same three measures: (1) the similarities and differences of the neural response statistics between VGG19 and primate IT cortex, (2) the variation trends of the response statistics of VGG19 neurons at different layers from low to high, and (3) the variation trends of the response statistics of VGG19 neurons when the numbers of stimuli and neurons increase. We find that the response statistics on both single-neuron selectivity and population sparseness of VGG19 neurons are fundamentally different from those of IT neurons in most cases; by increasing the number of neurons in different layers and the number of stimuli, the response statistics of neurons at different layers from low to high do not substantially change; and the estimated intrinsic dimensionality values at the low

  3. Effect of the heterogeneous neuron and information transmission delay on stochastic resonance of neuronal networks.

    Science.gov (United States)

    Wang, Qingyun; Zhang, Honghui; Chen, Guanrong

    2012-12-01

    We study the effect of heterogeneous neuron and information transmission delay on stochastic resonance of scale-free neuronal networks. For this purpose, we introduce the heterogeneity to the specified neuron with the highest degree. It is shown that in the absence of delay, an intermediate noise level can optimally assist spike firings of collective neurons so as to achieve stochastic resonance on scale-free neuronal networks for small and intermediate α(h), which plays a heterogeneous role. Maxima of stochastic resonance measure are enhanced as α(h) increases, which implies that the heterogeneity can improve stochastic resonance. However, as α(h) is beyond a certain large value, no obvious stochastic resonance can be observed. If the information transmission delay is introduced to neuronal networks, stochastic resonance is dramatically affected. In particular, the tuned information transmission delay can induce multiple stochastic resonance, which can be manifested as well-expressed maximum in the measure for stochastic resonance, appearing every multiple of one half of the subthreshold stimulus period. Furthermore, we can observe that stochastic resonance at odd multiple of one half of the subthreshold stimulus period is subharmonic, as opposed to the case of even multiple of one half of the subthreshold stimulus period. More interestingly, multiple stochastic resonance can also be improved by the suitable heterogeneous neuron. Presented results can provide good insights into the understanding of the heterogeneous neuron and information transmission delay on realistic neuronal networks.

  4. Intrinsically Active and Pacemaker Neurons in Pluripotent Stem Cell-Derived Neuronal Populations

    Science.gov (United States)

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

    2014-01-01

    Summary Neurons generated from pluripotent stem cells (PSCs) self-organize into functional neuronal assemblies in vitro, generating synchronous network activities. Intriguingly, PSC-derived neuronal assemblies develop spontaneous activities that are independent of external stimulation, suggesting the presence of thus far undetected intrinsically active neurons (IANs). Here, by using mouse embryonic stem cells, we provide evidence for the existence of IANs in PSC-neuronal networks based on extracellular multielectrode array and intracellular patch-clamp recordings. IANs remain active after pharmacological inhibition of fast synaptic communication and possess intrinsic mechanisms required for autonomous neuronal activity. PSC-derived IANs are functionally integrated in PSC-neuronal populations, contribute to synchronous network bursting, and exhibit pacemaker properties. The intrinsic activity and pacemaker properties of the neuronal subpopulation identified herein may be particularly relevant for interventions involving transplantation of neural tissues. IANs may be a key element in the regulation of the functional activity of grafted as well as preexisting host neuronal networks. PMID:24672755

  5. Arsenic Trioxide Modulates the Central Snail Neuron Action Potential

    Directory of Open Access Journals (Sweden)

    Guan-Ling Lu

    2009-09-01

    Conclusion: As2O3 at 10 mM elicits BoPs in central snail neurons and this effect may relate to the PLC activity of the neuron, rather than protein kinase A activity, or calcium influxes of the neuron. As2O3 at higher concentration irreversibly abolishes the spontaneous action potentials of the neuron.

  6. Functional maps within a single neuron

    Science.gov (United States)

    Johnston, Daniel

    2012-01-01

    The presence and plasticity of dendritic ion channels are well established. However, the literature is divided on what specific roles these dendritic ion channels play in neuronal information processing, and there is no consensus on why neuronal dendrites should express diverse ion channels with different expression profiles. In this review, we present a case for viewing dendritic information processing through the lens of the sensory map literature, where functional gradients within neurons are considered as maps on the neuronal topograph. Under such a framework, drawing analogies from the sensory map literature, we postulate that the formation of intraneuronal functional maps is driven by the twin objectives of efficiently encoding inputs that impinge along different dendritic locations and of retaining homeostasis in the face of changes that are required in the coding process. In arriving at this postulate, we relate intraneuronal map physiology to the vast literature on sensory maps and argue that such a metaphorical association provides a fresh conceptual framework for analyzing and understanding single-neuron information encoding. We also describe instances where the metaphor presents specific directions for research on intraneuronal maps, derived from analogous pursuits in the sensory map literature. We suggest that this perspective offers a thesis for why neurons should express and alter ion channels in their dendrites and provides a framework under which active dendrites could be related to neural coding, learning theory, and homeostasis. PMID:22933729

  7. Spike-timing dynamics of neuronal groups.

    Science.gov (United States)

    Izhikevich, Eugene M; Gally, Joseph A; Edelman, Gerald M

    2004-08-01

    A neuronal network inspired by the anatomy of the cerebral cortex was simulated to study the self-organization of spiking neurons into neuronal groups. The network consisted of 100 000 reentrantly interconnected neurons exhibiting known types of cortical firing patterns, receptor kinetics, short-term plasticity and long-term spike-timing-dependent plasticity (STDP), as well as a distribution of axonal conduction delays. The dynamics of the network allowed us to study the fine temporal structure of emerging firing patterns with millisecond resolution. We found that the interplay between STDP and conduction delays gave rise to the spontaneous formation of neuronal groups--sets of strongly connected neurons capable of firing time-locked, although not necessarily synchronous, spikes. Despite the noise present in the model, such groups repeatedly generated patterns of activity with millisecond spike-timing precision. Exploration of the model allowed us to characterize various group properties, including spatial distribution, size, growth, rate of birth, lifespan, and persistence in the presence of synaptic turnover. Localized coherent input resulted in shifts of receptive and projective fields in the model similar to those observed in vivo.

  8. Rewiring of neuronal networks during synaptic silencing.

    Science.gov (United States)

    Wrosch, Jana Katharina; Einem, Vicky von; Breininger, Katharina; Dahlmanns, Marc; Maier, Andreas; Kornhuber, Johannes; Groemer, Teja Wolfgang

    2017-09-15

    Analyzing the connectivity of neuronal networks, based on functional brain imaging data, has yielded new insight into brain circuitry, bringing functional and effective networks into the focus of interest for understanding complex neurological and psychiatric disorders. However, the analysis of network changes, based on the activity of individual neurons, is hindered by the lack of suitable meaningful and reproducible methodologies. Here, we used calcium imaging, statistical spike time analysis and a powerful classification model to reconstruct effective networks of primary rat hippocampal neurons in vitro. This method enables the calculation of network parameters, such as propagation probability, path length, and clustering behavior through the measurement of synaptic activity at the single-cell level, thus providing a fuller understanding of how changes at single synapses translate to an entire population of neurons. We demonstrate that our methodology can detect the known effects of drug-induced neuronal inactivity and can be used to investigate the extensive rewiring processes affecting population-wide connectivity patterns after periods of induced neuronal inactivity.

  9. Simulation of developing human neuronal cell networks.

    Science.gov (United States)

    Lenk, Kerstin; Priwitzer, Barbara; Ylä-Outinen, Laura; Tietz, Lukas H B; Narkilahti, Susanna; Hyttinen, Jari A K

    2016-08-30

    Microelectrode array (MEA) is a widely used technique to study for example the functional properties of neuronal networks derived from human embryonic stem cells (hESC-NN). With hESC-NN, we can investigate the earliest developmental stages of neuronal network formation in the human brain. In this paper, we propose an in silico model of maturating hESC-NNs based on a phenomenological model called INEX. We focus on simulations of the development of bursts in hESC-NNs, which are the main feature of neuronal activation patterns. The model was developed with data from developing hESC-NN recordings on MEAs which showed increase in the neuronal activity during the investigated six measurement time points in the experimental and simulated data. Our simulations suggest that the maturation process of hESC-NN, resulting in the formation of bursts, can be explained by the development of synapses. Moreover, spike and burst rate both decreased at the last measurement time point suggesting a pruning of synapses as the weak ones are removed. To conclude, our model reflects the assumption that the interaction between excitatory and inhibitory neurons during the maturation of a neuronal network and the spontaneous emergence of bursts are due to increased connectivity caused by the forming of new synapses.

  10. The neuronal insulin receptor in its environment.

    Science.gov (United States)

    Gralle, Matthias

    2017-02-01

    Insulin is known mainly for its effects in peripheral tissues, such as the liver, skeletal muscles and adipose tissue, where the activation of the insulin receptor (IR) has both short-term and long-term effects. Insulin and the IR are also present in the brain, and since there is evidence that neuronal insulin signaling regulates synaptic plasticity and that it is impaired in disease, this pathway might be the key to protection or reversal of symptoms, especially in Alzheimer's disease. However, there are controversies about the importance of the neuronal IR, partly because biophysical data on its activation and signaling are much less complete than for the peripheral IR. This review briefly summarizes the neuronal IR signaling in health and disease, and then focuses on known differences between the neuronal and peripheral IR with regard to alternative splicing and glycosylation, and lack of data with respect to phosphorylation and membrane subdomain localization. Particularities in the neuronal IR itself and its environment may have consequences for downstream signaling and impact synaptic plasticity. Furthermore, establishing the relative importance of insulin signaling through IR or through hybrids with its homolog, the insulin-like growth factor 1 receptor, is crucial for evaluating the consequences of brain IR activation. An improved biophysical understanding of the neuronal IR may help predict the consequences of insulin-targeted interventions. © 2016 International Society for Neurochemistry.

  11. Optimal stimulus shapes for neuronal excitation.

    Directory of Open Access Journals (Sweden)

    Daniel B Forger

    2011-07-01

    Full Text Available An important problem in neuronal computation is to discern how features of stimuli control the timing of action potentials. One aspect of this problem is to determine how an action potential, or spike, can be elicited with the least energy cost, e.g., a minimal amount of applied current. Here we show in the Hodgkin & Huxley model of the action potential and in experiments on squid giant axons that: 1 spike generation in a neuron can be highly discriminatory for stimulus shape and 2 the optimal stimulus shape is dependent upon inputs to the neuron. We show how polarity and time course of post-synaptic currents determine which of these optimal stimulus shapes best excites the neuron. These results are obtained mathematically using the calculus of variations and experimentally using a stochastic search methodology. Our findings reveal a surprising complexity of computation at the single cell level that may be relevant for understanding optimization of signaling in neurons and neuronal networks.

  12. Purification of dopamine neurons by flow cytometry.

    Science.gov (United States)

    Kerr, C W; Lee, L J; Romero, A A; Stull, N D; Iacovitti, L

    1994-12-05

    The heterogeneity and preponderence of other cell types present in cultures has greatly impeded our ability to study dopamine neurons. In this report, we describe methods for isolating nearly pure dopamine neurons for study in culture. To do so, the lipid-soluble dye, 1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate (diI) was injected into the embryonic rat striata where it was taken up by nerve terminals and transported overnight back to the innervating perikarya in the ventral midbrain. Midbrain cells were then dissected, dissociated and separated on the basis of their (rhodamine) fluorescence by flow cytometry. Nearly all cells recovered as fluorescent positive (> 98%) were also immunoreactive for the dopamine specific enzyme tyrosine hydroxylase (80%-96%). Little contamination by other cells types was observed after labeling for specific neuronal and glial markers. Purified dopamine neurons continued to thrive and elaborate neuronal processes for at least 3 days in culture. Using this new model, it may now be possible to directly study the cellular and molecular processes regulating the survival and functioning of developing, injured and transplanted dopamine neurons.

  13. NeuronMetrics: software for semi-automated processing of cultured neuron images.

    Science.gov (United States)

    Narro, Martha L; Yang, Fan; Kraft, Robert; Wenk, Carola; Efrat, Alon; Restifo, Linda L

    2007-03-23

    Using primary cell culture to screen for changes in neuronal morphology requires specialized analysis software. We developed NeuronMetrics for semi-automated, quantitative analysis of two-dimensional (2D) images of fluorescently labeled cultured neurons. It skeletonizes the neuron image using two complementary image-processing techniques, capturing fine terminal neurites with high fidelity. An algorithm was devised to span wide gaps in the skeleton. NeuronMetrics uses a novel strategy based on geometric features called faces to extract a branch number estimate from complex arbors with numerous neurite-to-neurite contacts, without creating a precise, contact-free representation of the neurite arbor. It estimates total neurite length, branch number, primary neurite number, territory (the area of the convex polygon bounding the skeleton and cell body), and Polarity Index (a measure of neuronal polarity). These parameters provide fundamental information about the size and shape of neurite arbors, which are critical factors for neuronal function. NeuronMetrics streamlines optional manual tasks such as removing noise, isolating the largest primary neurite, and correcting length for self-fasciculating neurites. Numeric data are output in a single text file, readily imported into other applications for further analysis. Written as modules for ImageJ, NeuronMetrics provides practical analysis tools that are easy to use and support batch processing. Depending on the need for manual intervention, processing time for a batch of approximately 60 2D images is 1.0-2.5 h, from a folder of images to a table of numeric data. NeuronMetrics' output accelerates the quantitative detection of mutations and chemical compounds that alter neurite morphology in vitro, and will contribute to the use of cultured neurons for drug discovery.

  14. Neuronal and glial purinergic receptors functions in neuron development and brain disease.

    Science.gov (United States)

    Del Puerto, Ana; Wandosell, Francisco; Garrido, Juan José

    2013-10-28

    Brain development requires the interaction of complex signaling pathways, involving different cell types and molecules. For a long time, most attention has focused on neurons in a neuronocentric conceptualization of central nervous system development, these cells fulfilling an intrinsic program that establishes the brain's morphology and function. By contrast, glia have mainly been studied as support cells, offering guidance or as the cells that react to brain injury. However, new evidence is appearing that demonstrates a more fundamental role of glial cells in the control of different aspects of neuronal development and function, events in which the influence of neurons is at best weak. Moreover, it is becoming clear that the function and organization of the nervous system depends heavily on reciprocal neuron-glia interactions. During development, neurons are often generated far from their final destination and while intrinsic mechanisms are responsible for neuronal migration and growth, they need support and regulatory influences from glial cells in order to migrate correctly. Similarly, the axons emitted by neurons often have to reach faraway targets and in this sense, glia help define the way that axons grow. Moreover, oligodendrocytes and Schwann cells ultimately envelop axons, contributing to the generation of nodes of Ranvier. Finally, recent publications show that astrocytes contribute to the modulation of synaptic transmission. In this sense, purinergic receptors are expressed widely by glial cells and neurons, and recent evidence points to multiple roles of purines and purinergic receptors in neuronal development and function, from neurogenesis to axon growth and functional axonal maturation, as well as in pathological conditions in the brain. This review will focus on the role of glial and neuronal secreted purines, and on the purinergic receptors, fundamentally in the control of neuronal development and function, as well as in diseases of the nervous

  15. Small molecules enable highly efficient neuronal conversion of human fibroblasts.

    Science.gov (United States)

    Ladewig, Julia; Mertens, Jerome; Kesavan, Jaideep; Doerr, Jonas; Poppe, Daniel; Glaue, Finnja; Herms, Stefan; Wernet, Peter; Kögler, Gesine; Müller, Franz-Josef; Koch, Philipp; Brüstle, Oliver

    2012-06-01

    Forced expression of proneural transcription factors has been shown to direct neuronal conversion of fibroblasts. Because neurons are postmitotic, conversion efficiencies are an important parameter for this process. We present a minimalist approach combining two-factor neuronal programming with small molecule-based inhibition of glycogen synthase kinase-3β and SMAD signaling, which converts postnatal human fibroblasts into functional neuron-like cells with yields up to >200% and neuronal purities up to >80%.

  16. Channel properties of Nax expressed in neurons.

    Directory of Open Access Journals (Sweden)

    Masahito Matsumoto

    Full Text Available Nax is a sodium-concentration ([Na+]-sensitive Na channel with a gating threshold of ~150 mM for extracellular [Na+] ([Na+]o in vitro. We previously reported that Nax was preferentially expressed in the glial cells of sensory circumventricular organs including the subfornical organ, and was involved in [Na+] sensing for the control of salt-intake behavior. Although Nax was also suggested to be expressed in the neurons of some brain regions including the amygdala and cerebral cortex, the channel properties of Nax have not yet been adequately characterized in neurons. We herein verified that Nax was expressed in neurons in the lateral amygdala of mice using an antibody that was newly generated against mouse Nax. To investigate the channel properties of Nax expressed in neurons, we established an inducible cell line of Nax using the mouse neuroblastoma cell line, Neuro-2a, which is endogenously devoid of the expression of Nax. Functional analyses of this cell line revealed that the [Na+]-sensitivity of Nax in neuronal cells was similar to that expressed in glial cells. The cation selectivity sequence of the Nax channel in cations was revealed to be Na+ ≈ Li+ > Rb+ > Cs+ for the first time. Furthermore, we demonstrated that Nax bound to postsynaptic density protein 95 (PSD95 through its PSD95/Disc-large/ZO-1 (PDZ-binding motif at the C-terminus in neurons. The interaction between Nax and PSD95 may be involved in promoting the surface expression of Nax channels because the depletion of endogenous PSD95 resulted in a decrease in Nax at the plasma membrane. These results indicated, for the first time, that Nax functions as a [Na+]-sensitive Na channel in neurons as well as in glial cells.

  17. Ancient origin of somatic and visceral neurons

    Science.gov (United States)

    2013-01-01

    Background A key to understanding the evolution of the nervous system on a large phylogenetic scale is the identification of homologous neuronal types. Here, we focus this search on the sensory and motor neurons of bilaterians, exploiting their well-defined molecular signatures in vertebrates. Sensorimotor circuits in vertebrates are of two types: somatic (that sense the environment and respond by shaping bodily motions) and visceral (that sense the interior milieu and respond by regulating vital functions). These circuits differ by a small set of largely dedicated transcriptional determinants: Brn3 is expressed in many somatic sensory neurons, first and second order (among which mechanoreceptors are uniquely marked by the Brn3+/Islet1+/Drgx+ signature), somatic motoneurons uniquely co-express Lhx3/4 and Mnx1, while the vast majority of neurons, sensory and motor, involved in respiration, blood circulation or digestion are molecularly defined by their expression and dependence on the pan-visceral determinant Phox2b. Results We explore the status of the sensorimotor transcriptional code of vertebrates in mollusks, a lophotrochozoa clade that provides a rich repertoire of physiologically identified neurons. In the gastropods Lymnaea stagnalis and Aplysia californica, we show that homologues of Brn3, Drgx, Islet1, Mnx1, Lhx3/4 and Phox2b differentially mark neurons with mechanoreceptive, locomotory and cardiorespiratory functions. Moreover, in the cephalopod Sepia officinalis, we show that Phox2 marks the stellate ganglion (in line with the respiratory — that is, visceral— ancestral role of the mantle, its target organ), while the anterior pedal ganglion, which controls the prehensile and locomotory arms, expresses Mnx. Conclusions Despite considerable divergence in overall neural architecture, a molecular underpinning for the functional allocation of neurons to interactions with the environment or to homeostasis was inherited from the urbilaterian ancestor by

  18. Functional Comparison of Neuronal Cells Differentiated from Human Induced Pluripotent Stem Cell-Derived Neural Stem Cells under Different Oxygen and Medium Conditions.

    Science.gov (United States)

    Yamazaki, Kazuto; Fukushima, Kazuyuki; Sugawara, Michiko; Tabata, Yoshikuni; Imaizumi, Yoichi; Ishihara, Yasuharu; Ito, Masashi; Tsukahara, Kappei; Kohyama, Jun; Okano, Hideyuki

    2016-12-01

    Because neurons are difficult to obtain from humans, generating functional neurons from human induced pluripotent stem cells (hiPSCs) is important for establishing physiological or disease-relevant screening systems for drug discovery. To examine the culture conditions leading to efficient differentiation of functional neural cells, we investigated the effects of oxygen stress (2% or 20% O2) and differentiation medium (DMEM/F12:Neurobasal-based [DN] or commercial [PhoenixSongs Biologicals; PS]) on the expression of genes related to neural differentiation, glutamate receptor function, and the formation of networks of neurons differentiated from hiPSCs (201B7) via long-term self-renewing neuroepithelial-like stem (lt-NES) cells. Expression of genes related to neural differentiation occurred more quickly in PS and/or 2% O2 than in DN and/or 20% O2, resulting in high responsiveness of neural cells to glutamate, N-methyl-d-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), and ( S)-3,5-dihydroxyphenylglycine (an agonist for mGluR1/5), as revealed by calcium imaging assays. NMDA receptors, AMPA receptors, mGluR1, and mGluR5 were functionally validated by using the specific antagonists MK-801, NBQX, JNJ16259685, and 2-methyl-6-(phenylethynyl)-pyridine, respectively. Multielectrode array analysis showed that spontaneous firing occurred earlier in cells cultured in 2% O2 than in 20% O2. Optimization of O2 tension and culture medium for neural differentiation of hiPSCs can efficiently generate physiologically relevant cells for screening systems.

  19. Neuronal Survival, Morphology and Outgrowth of Spiral Ganglion Neurons Using a Defined Growth Factor Combination.

    Directory of Open Access Journals (Sweden)

    Jana Schwieger

    Full Text Available The functionality of cochlear implants (CI depends, among others, on the number and excitability of surviving spiral ganglion neurons (SGN. The spatial separation between the SGN, located in the bony axis of the inner ear, and the CI, which is inserted in the scala tympani, results in suboptimal performance of CI patients and may be decreased by attracting the SGN neurites towards the electrode contacts. Neurotrophic factors (NTFs can support neuronal survival and neurite outgrowth.Since brain-derived neurotrophic factor (BDNF is well known for its neuroprotective effect and ciliary neurotrophic factor (CNTF increases neurite outgrowth, we evaluated if the combination of BDNF and CNTF leads to an enhanced neuronal survival with extended neurite outgrowth. Both NTFs were added in effective high concentrations (BDNF 50 ng/ml, CNTF 100 ng/ml, alone and in combination, to cultured dissociated SGN of neonatal rats for 48 hours.The neuronal survival and neurite outgrowth were significantly higher in SGN treated with the combination of the two NTFs compared to treatment with each factor alone. Additionally, with respect to the morphology, the combination of BDNF and CNTF leads to a significantly higher number of bipolar neurons and a decreased number of neurons without neurites in culture.The combination of BDNF and CNTF shows a great potential to increase the neuronal survival and the number of bipolar neurons in vitro and to regenerate retracted nerve fibers.

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

    NARCIS (Netherlands)

    Bardy, C.; Hurk, M. van den; Eames, T.; Marchand, C.; Hernandez, R.V.; Kellogg, M.; Gorris, M.A.J.; Galet, B.; Palomares, V.; Brown, J.; Bang, A.G.; Mertens, J.; Bohnke, L.; Boyer, L.; Simon, S.; Gage, F.H.

    2015-01-01

    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

  1. Closing the Phenotypic Gap between Transformed Neuronal Cell Lines in Culture and Untransformed Neurons

    Science.gov (United States)

    Myers, Tereance A.; Nickerson, Cheryl A.; Kaushal, Deepak; Ott, C. Mark; HonerzuBentrup, Kerstin; Ramamurthy, Rajee; Nelman-Gonzales, Mayra; Pierson, Duane L.; Philipp, Mario T.

    2008-01-01

    Studies of neuronal dysfunction in the central nervous system (CNS) are frequently limited by the failure of primary neurons to propagate in vitro. Neuronal cell lines can be substituted for primary cells but they often misrepresent normal conditions. We hypothesized that a dimensional (3-D) cell culture system would drive the phenotype of transformed neurons closer to that of untransformed cells. In our studies comparing 3-D versus 2-dimensional (2-D) culture, neuronal SH-SY5Y (SY) cells underwent distinct morphological changes combined with a significant drop in their rate of cell division. Expression of the proto-oncogene N-myc and the RNA binding protein HuD was decreased in 3-D culture as compared to standard 2-D conditions. We observed a decline in the anti-apoptotic protein Bcl-2 in 3-D culture, coupled with increased expression of the pro-apoptotic proteins Bax and Bak. Moreover, thapsigargin (TG)-induced apoptosis was enhanced in the 3-D cells. Microarray analysis demonstrated significantly differing mRNA levels for over 700 genes in the cells of each culture type. These results indicate that a 3-D culture approach narrows the phenotypic gap between neuronal cell lines and primary neurons. The resulting cells may readily be used for in vitro research of neuronal pathogenesis.

  2. Neuronal migration illuminated: a look under the hood of the living neuron.

    Science.gov (United States)

    Trivedi, Niraj; Solecki, David J

    2011-01-01

    During vertebrate brain development, migration of neurons from the germinal zones to their final laminar positions is essential to establish functional neural circuits. Whereas key insights into neuronal migration initially came from landmark studies identifying the genes mutated in human cortical malformations, cell biology has recently greatly advanced our understanding of how cytoskeletal proteins and molecular motors drive the morphogenic cell movements that build the developing brain. This Commentary & View reviews recent studies examining the role of the molecular motors during neuronal migration and critically examines current models of acto-myosin function in the two-step neuronal migration cycle. Given the apparent emerging diversity of neuronal sub-type cytoskeletal organizations, we propose that two approaches must be taken to resolve differences between the current migration models: the mechanisms of radial and tangential migration must be compared and the loci of tension generation, migration substrates, and sites of adhesion dynamics must be precisely examined in an integrated manner.

  3. Reliable neuronal systems: the importance of heterogeneity.

    Science.gov (United States)

    Lengler, Johannes; Jug, Florian; Steger, Angelika

    2013-01-01

    For every engineer it goes without saying: in order to build a reliable system we need components that consistently behave precisely as they should. It is also well known that neurons, the building blocks of brains, do not satisfy this constraint. Even neurons of the same type come with huge variances in their properties and these properties also vary over time. Synapses, the connections between neurons, are highly unreliable in forwarding signals. In this paper we argue that both these fact add variance to neuronal processes, and that this variance is not a handicap of neural systems, but that instead predictable and reliable functional behavior of neural systems depends crucially on this variability. In particular, we show that higher variance allows a recurrently connected neural population to react more sensitively to incoming signals, and processes them faster and more energy efficient. This, for example, challenges the general assumption that the intrinsic variability of neurons in the brain is a defect that has to be overcome by synaptic plasticity in the process of learning.

  4. Reliable neuronal systems: the importance of heterogeneity.

    Directory of Open Access Journals (Sweden)

    Johannes Lengler

    Full Text Available For every engineer it goes without saying: in order to build a reliable system we need components that consistently behave precisely as they should. It is also well known that neurons, the building blocks of brains, do not satisfy this constraint. Even neurons of the same type come with huge variances in their properties and these properties also vary over time. Synapses, the connections between neurons, are highly unreliable in forwarding signals. In this paper we argue that both these fact add variance to neuronal processes, and that this variance is not a handicap of neural systems, but that instead predictable and reliable functional behavior of neural systems depends crucially on this variability. In particular, we show that higher variance allows a recurrently connected neural population to react more sensitively to incoming signals, and processes them faster and more energy efficient. This, for example, challenges the general assumption that the intrinsic variability of neurons in the brain is a defect that has to be overcome by synaptic plasticity in the process of learning.

  5. Spin orbit torque based electronic neuron

    Energy Technology Data Exchange (ETDEWEB)

    Sengupta, Abhronil, E-mail: asengup@purdue.edu; Choday, Sri Harsha; Kim, Yusung; Roy, Kaushik [School of Electrical and Computer Engineering, Purdue University, West Lafayette, Indiana 47907 (United States)

    2015-04-06

    A device based on current-induced spin-orbit torque (SOT) that functions as an electronic neuron is proposed in this work. The SOT device implements an artificial neuron's thresholding (transfer) function. In the first step of a two-step switching scheme, a charge current places the magnetization of a nano-magnet along the hard-axis, i.e., an unstable point for the magnet. In the second step, the SOT device (neuron) receives a current (from the synapses) which moves the magnetization from the unstable point to one of the two stable states. The polarity of the synaptic current encodes the excitatory and inhibitory nature of the neuron input and determines the final orientation of the magnetization. A resistive crossbar array, functioning as synapses, generates a bipolar current that is a weighted sum of the inputs. The simulation of a two layer feed-forward artificial neural network based on the SOT electronic neuron shows that it consumes ∼3× lower power than a 45 nm digital CMOS implementation, while reaching ∼80% accuracy in the classification of 100 images of handwritten digits from the MNIST dataset.

  6. Doubly stochastic coherence in complex neuronal networks

    Science.gov (United States)

    Gao, Yang; Wang, Jianjun

    2012-11-01

    A system composed of coupled FitzHugh-Nagumo neurons with various topological structures is investigated under the co-presence of two independently additive and multiplicative Gaussian white noises, in which particular attention is paid to the neuronal networks spiking regularity. As the additive noise intensity and the multiplicative noise intensity are simultaneously adjusted to optimal values, the temporal periodicity of the output of the system reaches the maximum, indicating the occurrence of doubly stochastic coherence. The network topology randomness exerts different influences on the temporal coherence of the spiking oscillation for dissimilar coupling strength regimes. At a small coupling strength, the spiking regularity shows nearly no difference in the regular, small-world, and completely random networks. At an intermediate coupling strength, the temporal periodicity in a small-world neuronal network can be improved slightly by adding a small fraction of long-range connections. At a large coupling strength, the dynamical behavior of the neurons completely loses the resonance property with regard to the additive noise intensity or the multiplicative noise intensity, and the spiking regularity decreases considerably with the increase of the network topology randomness. The network topology randomness plays more of a depressed role than a favorable role in improving the temporal coherence of the spiking oscillation in the neuronal network research study.

  7. Memristors Empower Spiking Neurons With Stochasticity

    KAUST Repository

    Al-Shedivat, Maruan

    2015-06-01

    Recent theoretical studies have shown that probabilistic spiking can be interpreted as learning and inference in cortical microcircuits. This interpretation creates new opportunities for building neuromorphic systems driven by probabilistic learning algorithms. However, such systems must have two crucial features: 1) the neurons should follow a specific behavioral model, and 2) stochastic spiking should be implemented efficiently for it to be scalable. This paper proposes a memristor-based stochastically spiking neuron that fulfills these requirements. First, the analytical model of the memristor is enhanced so it can capture the behavioral stochasticity consistent with experimentally observed phenomena. The switching behavior of the memristor model is demonstrated to be akin to the firing of the stochastic spike response neuron model, the primary building block for probabilistic algorithms in spiking neural networks. Furthermore, the paper proposes a neural soma circuit that utilizes the intrinsic nondeterminism of memristive switching for efficient spike generation. The simulations and analysis of the behavior of a single stochastic neuron and a winner-take-all network built of such neurons and trained on handwritten digits confirm that the circuit can be used for building probabilistic sampling and pattern adaptation machinery in spiking networks. The findings constitute an important step towards scalable and efficient probabilistic neuromorphic platforms. © 2011 IEEE.

  8. Development of dendrite polarity in Drosophila neurons

    Directory of Open Access Journals (Sweden)

    Hill Sarah E

    2012-10-01

    Full Text Available Abstract Background Drosophila neurons have dendrites that contain minus-end-out microtubules. This microtubule arrangement is different from that of cultured mammalian neurons, which have mixed polarity microtubules in dendrites. Results To determine whether Drosophila and mammalian dendrites have a common microtubule organization during development, we analyzed microtubule polarity in Drosophila dendritic arborization neuron dendrites at different stages of outgrowth from the cell body in vivo. As dendrites initially extended, they contained mixed polarity microtubules, like mammalian neurons developing in culture. Over a period of several days this mixed microtubule array gradually matured to a minus-end-out array. To determine whether features characteristic of dendrites were localized before uniform polarity was attained, we analyzed dendritic markers as dendrites developed. In all cases the markers took on their characteristic distribution while dendrites had mixed polarity. An axonal marker was also quite well excluded from dendrites throughout development, although this was perhaps more efficient in mature neurons. To confirm that dendrite character could be acquired in Drosophila while microtubules were mixed, we genetically disrupted uniform dendritic microtubule organization. Dendritic markers also localized correctly in this case. Conclusions We conclude that developing Drosophila dendrites initially have mixed microtubule polarity. Over time they mature to uniform microtubule polarity. Dendrite identity is established before the mature microtubule arrangement is attained, during the period of mixed microtubule polarity.

  9. Magnetic skyrmion-based artificial neuron device

    Science.gov (United States)

    Li, Sai; Kang, Wang; Huang, Yangqi; Zhang, Xichao; Zhou, Yan; Zhao, Weisheng

    2017-08-01

    Neuromorphic computing, inspired by the biological nervous system, has attracted considerable attention. Intensive research has been conducted in this field for developing artificial synapses and neurons, attempting to mimic the behaviors of biological synapses and neurons, which are two basic elements of a human brain. Recently, magnetic skyrmions have been investigated as promising candidates in neuromorphic computing design owing to their topologically protected particle-like behaviors, nanoscale size and low driving current density. In one of our previous studies, a skyrmion-based artificial synapse was proposed, with which both short-term plasticity and long-term potentiation functions have been demonstrated. In this work, we further report on a skyrmion-based artificial neuron by exploiting the tunable current-driven skyrmion motion dynamics, mimicking the leaky-integrate-fire function of a biological neuron. With a simple single-device implementation, this proposed artificial neuron may enable us to build a dense and energy-efficient spiking neuromorphic computing system.

  10. Motor neuron disease after electric injury

    Science.gov (United States)

    Jafari, H; Couratier, P; Camu, W

    2001-01-01

    The occurrence of motor neuron disease after electrical injury in six patients is reported and compared with patients from the literature. The patients were five men with spinal onset and one woman with bulbar motor neuron disease after electric shock. Two patients were struck by lightning and four by industrial electric shock. For all six of them, the disease started at the site of the electrical trauma. The mean delay for onset of motor neuron disease was 44 months. In four of the spinal patients the disease progressed slowly with mild handicap after several years. For the fifth patient, improvement was noted progressively. The patient with bulbar disease died 26 months after onset. A link between electric shock and motor neuron disease is likely, given the homogenous profile of the patients both in the five spinal cases presented here and in the literature. Bulbar onset has not been reported to date. However, in this patient the long delay between the electrical injury and motor neuron disease, together with the rapid evolution may suggest a chance association.

 PMID:11459909

  11. Persistent Histamine Excitation of Glutamatergic Preoptic Neurons

    Science.gov (United States)

    Tabarean, Iustin V.

    2012-01-01

    Thermoregulatory neurons of the median preoptic nucleus (MnPO) represent a target at which histamine modulates body temperature. The mechanism by which histamine excites a population of MnPO neurons is not known. In this study it was found that histamine activated a cationic inward current and increased the intracellular Ca2+ concentration, actions that had a transient component as well as a sustained one that lasted for tens of minutes after removal of the agonist. The sustained component was blocked by TRPC channel blockers. Single-cell reverse transcription-PCR analysis revealed expression of TRPC1, TRPC5 and TRPC7 subunits in neurons excited by histamine. These studies also established the presence of transcripts for the glutamatergic marker Vglut2 and for the H1 histamine receptor in neurons excited by histamine. Intracellular application of antibodies directed against cytoplasmic sites of the TRPC1 or TRPC5 channel subunits decreased the histamine-induced inward current. The persistent inward current and elevation in intracellular Ca2+ concentration could be reversed by activating the PKA pathway. This data reveal a novel mechanism by which histamine induces persistent excitation and sustained intracellular Ca2+ elevation in glutamatergic MnPO neurons. PMID:23082195

  12. Magnetic skyrmion-based artificial neuron device.

    Science.gov (United States)

    Li, Sai; Kang, Wang; Huang, Yangqi; Zhang, Xichao; Zhou, Yan; Zhao, Weisheng

    2017-08-04

    Neuromorphic computing, inspired by the biological nervous system, has attracted considerable attention. Intensive research has been conducted in this field for developing artificial synapses and neurons, attempting to mimic the behaviors of biological synapses and neurons, which are two basic elements of a human brain. Recently, magnetic skyrmions have been investigated as promising candidates in neuromorphic computing design owing to their topologically protected particle-like behaviors, nanoscale size and low driving current density. In one of our previous studies, a skyrmion-based artificial synapse was proposed, with which both short-term plasticity and long-term potentiation functions have been demonstrated. In this work, we further report on a skyrmion-based artificial neuron by exploiting the tunable current-driven skyrmion motion dynamics, mimicking the leaky-integrate-fire function of a biological neuron. With a simple single-device implementation, this proposed artificial neuron may enable us to build a dense and energy-efficient spiking neuromorphic computing system.

  13. WNT signaling in neuronal maturation and synaptogenesis

    Science.gov (United States)

    Rosso, Silvana B.; Inestrosa, Nibaldo C.

    2013-01-01

    The Wnt signaling pathway plays a role in the development of the central nervous system and growing evidence indicates that Wnts also regulates the structure and function of the adult nervous system. Wnt components are key regulators of a variety of developmental processes, including embryonic patterning, cell specification, and cell polarity. In the nervous system, Wnt signaling also regulates the formation and function of neuronal circuits by controlling neuronal differentiation, axon outgrowth and guidance, dendrite development, synaptic function, and neuronal plasticity. Wnt factors can signal through three very well characterized cascades: canonical or β-catenin pathway, planar cell polarity pathway and calcium pathway that control different processes. However, divergent downstream cascades have been identified to control neuronal morphogenesis. In the nervous system, the expression of Wnt proteins is a highly controlled process. In addition, deregulation of Wnt signaling has been associated with neurodegenerative diseases. Here, we will review different aspects of neuronal and dendrite maturation, including spinogenesis and synaptogenesis. Finally, the role of Wnt pathway components on Alzheimer’s disease will be revised. PMID:23847469

  14. Binding by asynchrony: the neuronal phase code

    Directory of Open Access Journals (Sweden)

    Zoltan Nadasdy

    2010-09-01

    Full Text Available Neurons display continuous subthreshold oscillations and discrete action potentials. When action potentials are phase-locked to the subthreshold oscillation, we hypothesize they represent two types of information: the presence/absence of a sensory feature and the phase of subthreshold oscillation. If subthreshold oscillation phases are neuron-specific, then the sources of action potentials can be recovered based on the action potential times. If the spatial information about the stimulus is converted to action potential phases, then action potentials from multiple neurons can be combined into a single axon and the spatial configuration reconstructed elsewhere. For the reconstruction to be successful, we introduce two assumptions: that a subthreshold oscillation field has a constant phase gradient and that coincidences between action potentials and intracellular subthreshold oscillations are neuron-specific as defined by the "interference principle." Under these assumptions, a phase coding model enables information transfer between structures and reproduces experimental phenomenons such as phase precession, grid cell architecture, and phase modulation of cortical spikes. This article reviews a recently proposed neuronal algorithm for information encoding and decoding from the phase of action potentials (Nadasdy 2009. The focus is given to the principles common across different systems instead of emphasizing system specific differences.

  15. Exploring neuronal bistability at the depolarization block.

    Directory of Open Access Journals (Sweden)

    Andrey Dovzhenok

    Full Text Available Many neurons display bistability--coexistence of two firing modes such as bursting and tonic spiking or tonic spiking and silence. Bistability has been proposed to endow neurons with richer forms of information processing in general and to be involved in short-term memory in particular by allowing a brief signal to elicit long-lasting changes in firing. In this paper, we focus on bistability that allows for a choice between tonic spiking and depolarization block in a wide range of the depolarization levels. We consider the spike-producing currents in two neurons, models of which differ by the parameter values. Our dopaminergic neuron model displays bistability in a wide range of applied currents at the depolarization block. The Hodgkin-Huxley model of the squid giant axon shows no bistability. We varied parameter values for the model to analyze transitions between the two parameter sets. We show that bistability primarily characterizes the inactivation of the Na(+ current. Our study suggests a connection between the amount of the Na(+ window current and the length of the bistability range. For the dopaminergic neuron we hypothesize that bistability can be linked to a prolonged action of antipsychotic drugs.

  16. WNT signalling in neuronal maturation and synaptogenesis

    Directory of Open Access Journals (Sweden)

    Silvana Beatriz Rosso

    2013-07-01

    Full Text Available The Wnt signaling pathway plays a role in the development of the central nervous system (CNS and growing evidence indicates that Wnts also regulates the structure and function of the adult nervous system. Wnt components are key regulators of a variety of developmental processes, including embryonic patterning, cell specification, and cell polarity. In the nervous system, Wnt signaling also regulates the formation and function of neuronal circuits by controlling neuronal differentiation, axon outgrowth and guidance, dendrite development, synaptic function and neuronal plasticity. Wnt factors can signal through three very well characterized cascades: canonical or β-catenin pathway, planar cell polarity pathway and calcium pathway that control different processes. However, divergent downstream cascades have been identified to control neuronal morphogenesis. In the nervous system, the expression of Wnt proteins is a highly controlled process. In addition, deregulation of Wnt signaling has been associated with neurodegenerative diseases. Here, we will review different aspects of neuronal and dendrite maturation, including spinogenesis and synaptogenesis. Finally, the role of Wnt pathway components on Alzheimer’s disease will be revised.

  17. Energy-efficient neural information processing in individual neurons and neuronal networks.

    Science.gov (United States)

    Yu, Lianchun; Yu, Yuguo

    2017-11-01

    Brains are composed of networks of an enormous number of neurons interconnected with synapses. Neural information is carried by the electrical signals within neurons and the chemical signals among neurons. Generating these electrical and chemical signals is metabolically expensive. The fundamental issue raised here is whether brains have evolved efficient ways of developing an energy-efficient neural code from the molecular level to the circuit level. Here, we summarize the factors and biophysical mechanisms that could contribute to the energy-efficient neural code for processing input signals. The factors range from ion channel kinetics, body temperature, axonal propagation of action potentials, low-probability release of synaptic neurotransmitters, optimal input and noise, the size of neurons and neuronal clusters, excitation/inhibition balance, coding strategy, cortical wiring, and the organization of functional connectivity. Both experimental and computational evidence suggests that neural systems may use these factors to maximize the efficiency of energy consumption in processing neural signals. Studies indicate that efficient energy utilization may be universal in neuronal systems as an evolutionary consequence of the pressure of limited energy. As a result, neuronal connections may be wired in a highly economical manner to lower energy costs and space. Individual neurons within a network may encode independent stimulus components to allow a minimal number of neurons to represent whole stimulus characteristics efficiently. This basic principle may fundamentally change our view of how billions of neurons organize themselves into complex circuits to operate and generate the most powerful intelligent cognition in nature. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. Optogenetic identification of hypothalamic orexin neuron projections to paraventricular spinally projecting neurons.

    Science.gov (United States)

    Dergacheva, Olga; Yamanaka, Akihiro; Schwartz, Alan R; Polotsky, Vsevolod Y; Mendelowitz, David

    2017-04-01

    Orexin neurons, and activation of orexin receptors, are generally thought to be sympathoexcitatory; however, the functional connectivity between orexin neurons and a likely sympathetic target, the hypothalamic spinally projecting neurons (SPNs) in the paraventricular nucleus of the hypothalamus (PVN) has not been established. To test the hypothesis that orexin neurons project directly to SPNs in the PVN, channelrhodopsin-2 (ChR2) was selectively expressed in orexin neurons to enable photoactivation of ChR2-expressing fibers while examining evoked postsynaptic currents in SPNs in rat hypothalamic slices. Selective photoactivation of orexin fibers elicited short-latency postsynaptic currents in all SPNs tested (n = 34). These light-triggered responses were heterogeneous, with a majority being excitatory glutamatergic responses (59%) and a minority of inhibitory GABAergic (35%) and mixed glutamatergic and GABAergic currents (6%). Both glutamatergic and GABAergic responses were present in the presence of tetrodotoxin and 4-aminopyridine, suggesting a monosynaptic connection between orexin neurons and SPNs. In addition to generating postsynaptic responses, photostimulation facilitated action potential firing in SPNs (current clamp configuration). Glutamatergic, but not GABAergic, postsynaptic currents were diminished by application of the orexin receptor antagonist almorexant, indicating orexin release facilitates glutamatergic neurotransmission in this pathway. This work identifies a neuronal circuit by which orexin neurons likely exert sympathoexcitatory control of cardiovascular function.NEW & NOTEWORTHY This is the first study to establish, using innovative optogenetic approaches in a transgenic rat model, that there are robust heterogeneous projections from orexin neurons to paraventricular spinally projecting neurons, including excitatory glutamatergic and inhibitory GABAergic neurotransmission. Endogenous orexin release modulates glutamatergic, but not GABAergic

  19. Crosstalks between kisspeptin neurons and somatostatin neurons are not photoperiod dependent in the ewe hypothalamus.

    Science.gov (United States)

    Dufourny, Laurence; Lomet, Didier

    2017-12-01

    Seasonal reproduction is under the control of gonadal steroid feedback, itself synchronized by day-length or photoperiod. As steroid action on GnRH neurons is mostly indirect and therefore exerted through interneurons, we looked for neuroanatomical interactions between kisspeptin (KP) neurons and somatostatin (SOM) neurons, two populations targeted by sex steroids, in three diencephalic areas involved in the central control of ovulation and/or sexual behavior: the arcuate nucleus (ARC), the preoptic area (POA) and the ventrolateral part of the ventromedial hypothalamus (VMHvl). KP is the most potent secretagogue of GnRH secretion while SOM has been shown to centrally inhibit LH pulsatile release. Notably, hypothalamic contents of these two neuropeptides vary with photoperiod in specific seasonal species. Our hypothesis is that SOM inhibits KP neuron activity and therefore indirectly modulate GnRH release and that this effect may be seasonally regulated. We used sections from ovariectomized estradiol-replaced ewes killed after photoperiodic treatment mimicking breeding or anestrus season. We performed triple immunofluorescent labeling to simultaneously detect KP, SOM and synapsin, a marker for synaptic vesicles. Sections from the POA and from the mediobasal hypothalamus were examined using a confocal microscope. Randomly selected KP or SOM neurons were observed in the POA and ARC. SOM neurons were also observed in the VMHvl. In both the ARC and POA, nearly all KP neurons presented numerous SOM contacts. SOM neurons presented KP terminals more frequently in the ARC than in the POA and VMHvl. Quantitative analysis failed to demonstrate major seasonal variations of KP and SOM interactions. Our data suggest a possible inhibitory action of SOM on all KP neurons in both photoperiodic statuses. On the other hand, the physiological significance of KP modulation of SOM neuron activity and vice versa remain to be determined. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Neuronal replacement therapy: previous achievements and challenges ahead

    Science.gov (United States)

    Grade, Sofia; Götz, Magdalena

    2017-10-01

    Lifelong neurogenesis and incorporation of newborn neurons into mature neuronal circuits operates in specialized niches of the mammalian brain and serves as role model for neuronal replacement strategies. However, to which extent can the remaining brain parenchyma, which never incorporates new neurons during the adulthood, be as plastic and readily accommodate neurons in networks that suffered neuronal loss due to injury or neurological disease? Which microenvironment is permissive for neuronal replacement and synaptic integration and which cells perform best? Can lost function be restored and how adequate is the participation in the pre-existing circuitry? Could aberrant connections cause malfunction especially in networks dominated by excitatory neurons, such as the cerebral cortex? These questions show how important connectivity and circuitry aspects are for regenerative medicine, which is the focus of this review. We will discuss the impressive advances in neuronal replacement strategies and success from exogenous as well as endogenous cell sources. Both have seen key novel technologies, like the groundbreaking discovery of induced pluripotent stem cells and direct neuronal reprogramming, offering alternatives to the transplantation of fetal neurons, and both herald great expectations. For these to become reality, neuronal circuitry analysis is key now. As our understanding of neuronal circuits increases, neuronal replacement therapy should fulfill those prerequisites in network structure and function, in brain-wide input and output. Now is the time to incorporate neural circuitry research into regenerative medicine if we ever want to truly repair brain injury.

  1. Merkel cells and neurons keep in touch

    Science.gov (United States)

    Woo, Seung-Hyun; Lumpkin, Ellen A.; Patapoutian, Ardem

    2014-01-01

    The Merkel cell-neurite complex is a unique vertebrate touch receptor comprising two distinct cell types in the skin. Its presence in touch-sensitive skin areas was recognized more than a century ago, but the functions of each cell type in sensory transduction have been unclear. Three recent studies demonstrate that Merkel cells are mechanosensitive cells that function in touch transduction via Piezo2. One study concludes that Merkel cells rather than sensory neurons are principal sites of mechanotransduction, whereas the other two studies report that both Merkel cells and neurons encode mechanical inputs. Together, these studies settle a longstanding debate on whether Merkel cells are mechanosensory cells, and enable future investigations of how these skin cells communicate with neurons. PMID:25480024

  2. Microglia in neuronal plasticity: Influence of stress.

    Science.gov (United States)

    Delpech, Jean-Christophe; Madore, Charlotte; Nadjar, Agnes; Joffre, Corinne; Wohleb, Eric S; Layé, Sophie

    2015-09-01

    The central nervous system (CNS) has previously been regarded as an immune-privileged site with the absence of immune cell responses but this dogma was not entirely true. Microglia are the brain innate immune cells and recent findings indicate that they participate both in CNS disease and infection as well as facilitate normal CNS function. Microglia are highly plastic and play integral roles in sculpting the structure of the CNS, refining neuronal circuitry and connectivity, and contribute actively to neuronal plasticity in the healthy brain. Interestingly, psychological stress can perturb the function of microglia in association with an impaired neuronal plasticity and the development of emotional behavior alterations. As a result it seemed important to describe in this review some findings indicating that the stress-induced microglia dysfunction may underlie neuroplasticity deficits associated to many mood disorders. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Stochastic resonance in noisy threshold neurons.

    Science.gov (United States)

    Kosko, Bart; Mitaim, Sanya

    2003-01-01

    Stochastic resonance occurs when noise improves how a nonlinear system performs. This paper presents two general stochastic-resonance theorems for threshold neurons that process noisy Bernoulli input sequences. The performance measure is Shannon mutual information. The theorems show that small amounts of independent additive noise can increase the mutual information of threshold neurons if the neurons detect subthreshold signals. The first theorem shows that this stochastic-resonance effect holds for all finite-variance noise probability density functions that obey a simple mean constraint that the user can control. A corollary shows that this stochastic-resonance effect occurs for the important family of (right-sided) gamma noise. The second theorem shows that this effect holds for all infinite-variance noise types in the broad family of stable distributions. Stable bell curves can model extremely impulsive noise environments. So the second theorem shows that this stochastic-resonance effect is robust against violent fluctuations in the additive noise process.

  4. Mirror Neurons and Mirror-Touch Synesthesia.

    Science.gov (United States)

    Linkovski, Omer; Katzin, Naama; Salti, Moti

    2016-05-30

    Since mirror neurons were introduced to the neuroscientific community more than 20 years ago, they have become an elegant and intuitive account for different cognitive mechanisms (e.g., empathy, goal understanding) and conditions (e.g., autism spectrum disorders). Recently, mirror neurons were suggested to be the mechanism underlying a specific type of synesthesia. Mirror-touch synesthesia is a phenomenon in which individuals experience somatosensory sensations when seeing someone else being touched. Appealing as it is, careful delineation is required when applying this mechanism. Using the mirror-touch synesthesia case, we put forward theoretical and methodological issues that should be addressed before relying on the mirror-neurons account. © The Author(s) 2016.

  5. Nicotinic activation of laterodorsal tegmental neurons

    DEFF Research Database (Denmark)

    Ishibashi, Masaru; Leonard, Christopher S; Kohlmeier, Kristi A

    2009-01-01

    ). However, recent data suggest that neurons of the laterodorsal tegmental (LDT) nucleus, which sends cholinergic, GABAergic, and glutamatergic-containing projections to DA-containing neurons of the VTA, are critical to gating normal functioning of this nucleus. The actions of nicotine on LDT neurons...... depolarization that often induced firing and TTX-resistant inward currents. Nicotine also enhanced sensitivity to injected current; and, baseline changes in intracellular calcium were elicited in the dendrites of some cholinergic LDT cells. In addition, activity-dependent calcium transients were increased......, suggesting that nicotine exposure sufficient to induce firing may lead to enhancement of levels of intracellular calcium. Nicotine also had strong actions on glutamate and GABA-releasing presynaptic terminals, as it greatly increased the frequency of miniature EPSCs and IPSCs to both cholinergic and non...

  6. Mechanosensor Channels in Mammalian Somatosensory Neurons

    Directory of Open Access Journals (Sweden)

    Patrick Delmas

    2007-09-01

    Full Text Available Mechanoreceptive sensory neurons innervating the skin, skeletal muscles andviscera signal both innocuous and noxious information necessary for proprioception, touchand pain. These neurons are responsible for the transduction of mechanical stimuli intoaction potentials that propagate to the central nervous system. The ability of these cells todetect mechanical stimuli impinging on them relies on the presence of mechanosensitivechannels that transduce the external mechanical forces into electrical and chemical signals.Although a great deal of information regarding the molecular and biophysical properties ofmechanosensitive channels in prokaryotes has been accumulated over the past two decades,less is known about the mechanosensitive channels necessary for proprioception and thesenses of touch and pain. This review summarizes the most pertinent data onmechanosensitive channels of mammalian somatosensory neurons, focusing on theirproperties, pharmacology and putative identity.

  7. Runx transcription factors in neuronal development

    Directory of Open Access Journals (Sweden)

    Shiga Takashi

    2008-08-01

    Full Text Available Abstract Runt-related (Runx transcription factors control diverse aspects of embryonic development and are responsible for the pathogenesis of many human diseases. In recent years, the functions of this transcription factor family in the nervous system have just begun to be understood. In dorsal root ganglion neurons, Runx1 and Runx3 play pivotal roles in the development of nociceptive and proprioceptive sensory neurons, respectively. Runx appears to control the transcriptional regulation of neurotrophin receptors, numerous ion channels and neuropeptides. As a consequence, Runx contributes to diverse aspects of the sensory system in higher vertebrates. In this review, we summarize recent progress in determining the role of Runx in neuronal development.

  8. Coping with Variability in Small Neuronal Networks

    Science.gov (United States)

    Calabrese, Ronald L.; Norris, Brian J.; Wenning, Angela; Wright, Terrence M.

    2011-01-01

    Experimental and corresponding modeling studies indicate that there is a 2- to 5-fold variation of intrinsic and synaptic parameters across animals while functional output is maintained. Here, we review experiments, using the heartbeat central pattern generator (CPG) in medicinal leeches, which explore the consequences of animal-to-animal variation in synaptic strength for coordinated motor output. We focus on a set of segmental heart motor neurons that all receive inhibitory synaptic input from the same four premotor interneurons. These four premotor inputs fire in a phase progression and the motor neurons also fire in a phase progression because of differences in synaptic strength profiles of the four inputs among segments. Our work tested the hypothesis that functional output is maintained in the face of animal-to-animal variation in the absolute strength of connections because relative strengths of the four inputs onto particular motor neurons is maintained across animals. Our experiments showed that relative strength is not strictly maintained across animals even as functional output is maintained, and animal-to-animal variations in strength of particular inputs do not correlate strongly with output phase. Further experiments measured the precise temporal pattern of the premotor inputs, the segmental synaptic strength profiles of their connections onto motor neurons, and the temporal pattern (phase progression) of those motor neurons all in the same animal for a series of 12 animals. The analysis of input and output in this sample of 12 individuals suggests that the number (four) of inputs to each motor neuron and the variability of the temporal pattern of input from the CPG across individuals weaken the influence of the strength of individual inputs. Moreover, the temporal pattern of the output varies as much across individuals as that of the input. Essentially, each animal arrives at a unique solution for how the network produces functional output. PMID

  9. Dopamine inhibits mitochondrial motility in hippocampal neurons.

    Directory of Open Access Journals (Sweden)

    Sigeng Chen

    2008-07-01

    Full Text Available The trafficking of mitochondria within neurons is a highly regulated process. In an earlier study, we found that serotonin (5-HT, acting through the 5-HT1A receptor subtype, promotes axonal transport of mitochondria in cultured hippocampal neurons by increasing Akt activity, and consequently decreasing glycogen synthase kinase (GSK3beta activity. This finding suggests a critical role for neuromodulators in the regulation of mitochondrial trafficking in neurons. In the present study, we investigate the effects of a second important neuromodulator, dopamine, on mitochondrial transport in hippocampal neurons.Here, we show that dopamine, like 5-HT, regulates mitochondrial motility in cultured hippocampal neurons through the Akt-GSK3beta signaling cascade. But, in contrast to the stimulatory effect of 5-HT, administration of exogenous dopamine or bromocriptine, a dopamine 2 receptor (D2R agonist, caused an inhibition of mitochondrial movement. Moreover, pretreatment with bromocriptine blocked the stimulatory effect of 5-HT on mitochondrial movement. Conversely, in cells pretreated with 5-HT, no further increases in movement were observed after administration of haloperidol, a D2R antagonist. In contrast to the effect of the D2R agonist, addition of SKF38393, a dopamine 1 receptor (D1R agonist, promoted mitochondrial transport, indicating that the inhibitory effect of dopamine was actually the net summation of opposing influences of the two receptor subtypes. The most pronounced effect of dopamine signals was on mitochondria that were already moving directionally. Western blot analysis revealed that treatment with either a D2R agonist or a D1R antagonist decreased Akt activity, and conversely, treatment with either a D2R antagonist or a D1R agonist increased Akt activity.Our observations strongly suggest a role for both dopamine and 5-HT in regulating mitochondrial movement, and indicate that the integrated effects of these two neuromodulators may be

  10. Nuclear Calcium Buffering Capacity Shapes Neuronal Architecture*

    Science.gov (United States)

    Mauceri, Daniela; Hagenston, Anna M.; Schramm, Kathrin; Weiss, Ursula; Bading, Hilmar

    2015-01-01

    Calcium-binding proteins (CaBPs) such as parvalbumin are part of the cellular calcium buffering system that determines intracellular calcium diffusion and influences the spatiotemporal dynamics of calcium signals. In neurons, CaBPs are primarily localized to the cytosol and function, for example, in nerve terminals in short-term synaptic plasticity. However, CaBPs are also expressed in the cell nucleus, suggesting that they modulate nuclear calcium signals, which are key regulators of neuronal gene expression. Here we show that the calcium buffering capacity of the cell nucleus in mouse hippocampal neurons regulates neuronal architecture by modulating the expression levels of VEGFD and the complement factor C1q-c, two nuclear calcium-regulated genes that control dendrite geometry and spine density, respectively. Increasing the levels of nuclear calcium buffers by means of expression of a nuclearly targeted form of parvalbumin fused to mCherry (PV.NLS-mC) led to a reduction in VEGFD expression and, as a result, to a decrease in total dendritic length and complexity. In contrast, mRNA levels of the synapse pruning factor C1q-c were increased in neurons expressing PV.NLS-mC, causing a reduction in the density and size of dendritic spines. Our results establish a close link between nuclear calcium buffering capacity and the transcription of genes that determine neuronal structure. They suggest that the development of cognitive deficits observed in neurological conditions associated with CaBP deregulation may reflect the loss of necessary structural features of dendrites and spines. PMID:26231212

  11. Leader neurons in leaky integrate and fire neural network simulations.

    Science.gov (United States)

    Zbinden, Cyrille

    2011-10-01

    In this paper, we highlight the topological properties of leader neurons whose existence is an experimental fact. Several experimental studies show the existence of leader neurons in population bursts of activity in 2D living neural networks (Eytan and Marom, J Neurosci 26(33):8465-8476, 2006; Eckmann et al., New J Phys 10(015011), 2008). A leader neuron is defined as a neuron which fires at the beginning of a burst (respectively network spike) more often than we expect by chance considering its mean firing rate. This means that leader neurons have some burst triggering power beyond a chance-level statistical effect. In this study, we characterize these leader neuron properties. This naturally leads us to simulate neural 2D networks. To build our simulations, we choose the leaky integrate and fire (lIF) neuron model (Gerstner and Kistler 2002; Cessac, J Math Biol 56(3):311-345, 2008), which allows fast simulations (Izhikevich, IEEE Trans Neural Netw 15(5):1063-1070, 2004; Gerstner and Naud, Science 326:379-380, 2009). The dynamics of our lIF model has got stable leader neurons in the burst population that we simulate. These leader neurons are excitatory neurons and have a low membrane potential firing threshold. Except for these two first properties, the conditions required for a neuron to be a leader neuron are difficult to identify and seem to depend on several parameters involved in the simulations themselves. However, a detailed linear analysis shows a trend of the properties required for a neuron to be a leader neuron. Our main finding is: A leader neuron sends signals to many excitatory neurons as well as to few inhibitory neurons and a leader neuron receives only signals from few other excitatory neurons. Our linear analysis exhibits five essential properties of leader neurons each with different relative importance. This means that considering a given neural network with a fixed mean number of connections per neuron, our analysis gives us a way of

  12. An introduction to modeling neuronal dynamics

    CERN Document Server

    Börgers, Christoph

    2017-01-01

    This book is intended as a text for a one-semester course on Mathematical and Computational Neuroscience for upper-level undergraduate and beginning graduate students of mathematics, the natural sciences, engineering, or computer science. An undergraduate introduction to differential equations is more than enough mathematical background. Only a slim, high school-level background in physics is assumed, and none in biology. Topics include models of individual nerve cells and their dynamics, models of networks of neurons coupled by synapses and gap junctions, origins and functions of population rhythms in neuronal networks, and models of synaptic plasticity. An extensive online collection of Matlab programs generating the figures accompanies the book. .

  13. Neuronal release of proBDNF

    OpenAIRE

    Yang, Jianmin; Siao, Chia-Jen; Nagappan, Guhan; Marinic, Tina; Jing, Deqiang; McGrath, Kelly; Chen, Zhe-Yu; Mark, Willie; Tessarollo, Lino; Lee, Francis S; Lu, Bai; Hempstead, Barbara L

    2009-01-01

    Pro–brain-derived neurotrophic factor (proBDNF) and mature BDNF utilize distinct receptors to mediate divergent neuronal actions. Using new tools to quantitate endogenous BDNF isoforms, we found that mouse neurons secrete both proBDNF and mature BDNF. The highest levels of proBDNF and p75 were observed perinatally and declined, but were still detectable, in adulthood. Thus, BDNF actions are developmentally regulated by secretion of proBDNF or mature BDNF and by local expression of p75 and Trk...

  14. Imaging neuronal pathways with 52Mn PET

    DEFF Research Database (Denmark)

    Napieczynska, Hanna; Severin, Gregory; Fonslet, Jesper

    2017-01-01

    tomography (PET) neuronal tract tracer. We used 52Mn for imaging dopaminergic pathways after a unilateral injection into the ventral tegmental area (VTA), as well as the striatonigral pathway after an injection into the dorsal striatum (STR) in rats. Furthermore, we tested potentially noxious effects...... of the radioactivity dose with a behavioral test and histological staining. 24 h after 52Mn administration, the neuronal tracts were clearly visible in PET images and statistical analysis confirmed the observed distribution of the tracer. We noticed a behavioral impairment in some animals treated with 170 kBq of 52Mn...... for PET imaging....

  15. Chemosensory organs as models of neuronal synapses.

    Science.gov (United States)

    Shaham, Shai

    2010-03-01

    Neuronal synapses are important microstructures that underlie complex cognitive capacities. Recent studies, primarily in Caenorhabditis elegans and Drosophila melanogaster, have revealed surprising parallels between these synapses and the 'chemosensory synapses' that reside at the tips of chemosensory cells that respond to environmental stimuli. Similarities in the structures, mechanisms of action and specific molecules found at these sites extend to the presynaptic, postsynaptic and glial entities composing both synapse types. In this article I propose that chemosensory synapses may serve as useful models of neuronal synapses, and consider the possibility that the two synapse types derive from a common ancestral structure.

  16. Optophysiological approach to resolve neuronal action potentials with high spatial and temporal resolution in cultured neurons

    Directory of Open Access Journals (Sweden)

    Stephane ePages

    2011-10-01

    Full Text Available Cell to cell communication in the central nervous system is encoded into transient and local membrane potential changes (ΔVm. Deciphering the rules that govern synaptic transmission and plasticity entails to be able to perform Vm recordings throughout the entire neuronal arborization. Classical electrophysiology is, in most cases, not able to do so within small and fragile neuronal subcompartments. Thus, optical techniques based on the use of fluorescent voltage-sensitive dyes (VSDs have been developed. However, reporting spontaneous or small ΔVm from neuronal ramifications has been challenging, in part due to the limited sensitivity and phototoxicity of VSD-based optical measurements. Here we demonstrate the use of water soluble VSD, ANNINE-6plus, with laser scanning microscopy to optically record ΔVm in cultured neurons. We show that the sensitivity (> 10 % of fluorescence change for 100 mV depolarization and time response (submillisecond of the dye allows the robust detection of action potentials (APs even without averaging, allowing the measurement of spontaneous neuronal firing patterns. In addition, we show that back-propagating APs can be recorded, along distinct dendritic sites and within dendritic spines. Importantly, our approach does not induce any detectable phototoxic effect on cultured neurons. This optophysiological approach provides a simple, minimally invasive and versatile optical method to measure electrical activity in cultured neurons with high temporal (ms resolution and high spatial (µm resolution.

  17. Direct Neuronal Reprogramming for Disease Modeling Studies Using Patient-Derived Neurons: What Have We Learned?

    Directory of Open Access Journals (Sweden)

    Janelle Drouin-Ouellet

    2017-09-01

    Full Text Available Direct neuronal reprogramming, by which a neuron is formed via direct conversion from a somatic cell without going through a pluripotent intermediate stage, allows for the possibility of generating patient-derived neurons. A unique feature of these so-called induced neurons (iNs is the potential to maintain aging and epigenetic signatures of the donor, which is critical given that many diseases of the CNS are age related. Here, we review the published literature on the work that has been undertaken using iNs to model human brain disorders. Furthermore, as disease-modeling studies using this direct neuronal reprogramming approach are becoming more widely adopted, it is important to assess the criteria that are used to characterize the iNs, especially in relation to the extent to which they are mature adult neurons. In particular: i what constitutes an iN cell, ii which stages of conversion offer the earliest/optimal time to assess features that are specific to neurons and/or a disorder and iii whether generating subtype-specific iNs is critical to the disease-related features that iNs express. Finally, we discuss the range of potential biomedical applications that can be explored using patient-specific models of neurological disorders with iNs, and the challenges that will need to be overcome in order to realize these applications.

  18. Rewiring Neuronal Circuits: A New Method for Fast Neurite Extension and Functional Neuronal Connection.

    Science.gov (United States)

    Magdesian, Margaret H; Anthonisen, Madeleine; Lopez-Ayon, G Monserratt; Chua, Xue Ying; Rigby, Matthew; Grütter, Peter

    2017-06-13

    Brain and spinal cord injury may lead to permanent disability and death because it is still not possible to regenerate neurons over long distances and accurately reconnect them with an appropriate target. Here a procedure is described to rapidly initiate, elongate, and precisely connect new functional neuronal circuits over long distances. The extension rates achieved reach over 1.2 mm/h, 30-60 times faster than the in vivo rates of the fastest growing axons from the peripheral nervous system (0.02 to 0.04 mm/h)(28) and 10 times faster than previously reported for the same neuronal type at an earlier stage of development(4). First, isolated populations of rat hippocampal neurons are grown for 2-3 weeks in microfluidic devices to precisely position the cells, enabling easy micromanipulation and experimental reproducibility. Next, beads coated with poly-D-lysine (PDL) are placed on neurites to form adhesive contacts and pipette micromanipulation is used to move the resulting bead-neurite complex. As the bead is moved, it pulls out a new neurite that can be extended over hundreds of micrometers and functionally connected to a target cell in less than 1 h. This process enables experimental reproducibility and ease of manipulation while bypassing slower chemical strategies to induce neurite growth. Preliminary measurements presented here demonstrate a neuronal growth rate far exceeding physiological ones. Combining these innovations allows for the precise establishment of neuronal networks in culture with an unprecedented degree of control. It is a novel method that opens the door to a plethora of information and insights into signal transmission and communication within the neuronal network as well as being a playground in which to explore the limits of neuronal growth. The potential applications and experiments are widespread with direct implications for therapies that aim to reconnect neuronal circuits after trauma or in neurodegenerative diseases.

  19. Recurrently connected and localized neuronal communities initiate coordinated spontaneous activity in neuronal networks.

    Science.gov (United States)

    Lonardoni, Davide; Amin, Hayder; Di Marco, Stefano; Maccione, Alessandro; Berdondini, Luca; Nieus, Thierry

    2017-07-01

    Developing neuronal systems intrinsically generate coordinated spontaneous activity that propagates by involving a large number of synchronously firing neurons. In vivo, waves of spikes transiently characterize the activity of developing brain circuits and are fundamental for activity-dependent circuit formation. In vitro, coordinated spontaneous spiking activity, or network bursts (NBs), interleaved within periods of asynchronous spikes emerge during the development of 2D and 3D neuronal cultures. Several studies have investigated this type of activity and its dynamics, but how a neuronal system generates these coordinated events remains unclear. Here, we investigate at a cellular level the generation of network bursts in spontaneously active neuronal cultures by exploiting high-resolution multielectrode array recordings and computational network modelling. Our analysis reveals that NBs are generated in specialized regions of the network (functional neuronal communities) that feature neuronal links with high cross-correlation peak values, sub-millisecond lags and that share very similar structural connectivity motifs providing recurrent interactions. We show that the particular properties of these local structures enable locally amplifying spontaneous asynchronous spikes and that this mechanism can lead to the initiation of NBs. Through the analysis of simulated and experimental data, we also show that AMPA currents drive the coordinated activity, while NMDA and GABA currents are only involved in shaping the dynamics of NBs. Overall, our results suggest that the presence of functional neuronal communities with recurrent local connections allows a neuronal system to generate spontaneous coordinated spiking activity events. As suggested by the rules used for implementing our computational model, such functional communities might naturally emerge during network development by following simple constraints on distance-based connectivity.

  20. Recurrently connected and localized neuronal communities initiate coordinated spontaneous activity in neuronal networks.

    Directory of Open Access Journals (Sweden)

    Davide Lonardoni

    2017-07-01

    Full Text Available Developing neuronal systems intrinsically generate coordinated spontaneous activity that propagates by involving a large number of synchronously firing neurons. In vivo, waves of spikes transiently characterize the activity of developing brain circuits and are fundamental for activity-dependent circuit formation. In vitro, coordinated spontaneous spiking activity, or network bursts (NBs, interleaved within periods of asynchronous spikes emerge during the development of 2D and 3D neuronal cultures. Several studies have investigated this type of activity and its dynamics, but how a neuronal system generates these coordinated events remains unclear. Here, we investigate at a cellular level the generation of network bursts in spontaneously active neuronal cultures by exploiting high-resolution multielectrode array recordings and computational network modelling. Our analysis reveals that NBs are generated in specialized regions of the network (functional neuronal communities that feature neuronal links with high cross-correlation peak values, sub-millisecond lags and that share very similar structural connectivity motifs providing recurrent interactions. We show that the particular properties of these local structures enable locally amplifying spontaneous asynchronous spikes and that this mechanism can lead to the initiation of NBs. Through the analysis of simulated and experimental data, we also show that AMPA currents drive the coordinated activity, while NMDA and GABA currents are only involved in shaping the dynamics of NBs. Overall, our results suggest that the presence of functional neuronal communities with recurrent local connections allows a neuronal system to generate spontaneous coordinated spiking activity events. As suggested by the rules used for implementing our computational model, such functional communities might naturally emerge during network development by following simple constraints on distance-based connectivity.

  1. Efficient Reprogramming of Mouse Fibroblasts to Neuronal Cells including Dopaminergic Neurons

    OpenAIRE

    Seung-ick Oh; Hang-soo Park; Insik Hwang; Han-kyul Park; Kyung-Ah Choi; Hyesun Jeong; Suhng Wook Kim; Sunghoi Hong

    2014-01-01

    Somatic cells were directly converted to functional neurons through the use of a combination of transcription factors, including Ascl1, Brn2, and Myt1l. However, a major limitation is the lack of a reliable source of cell-replacement therapy for neurological diseases. Here, we show that a combination of the transcription factors Ascl1 and Nurr1 (AN) and neurotrophic factors including SHH and FGF8b directly reprogrammed embryonic mouse fibroblasts to induced neuronal (iN) cells: pan-neuronal ...

  2. Single-neuron RNA-Seq: technical feasibility and reproducibility

    Directory of Open Access Journals (Sweden)

    Shenfeng eQiu

    2012-07-01

    Full Text Available Understanding brain function involves improved knowledge about how the genome specifies such a large diversity of neuronal types. Transcriptome analysis of single neurons has been previously described using gene expression microarrays. Using high-throughput transcriptome sequencing (RNA-Seq, we have developed a method to perform single-neuron RNA-Seq. Following electrophysiology recording from an individual neuron, total RNA was extracted by aspirating the cellular contents into a fine glass electrode tip. The mRNAs were reverse transcribed and amplified to construct a single neuron cDNA library, and subsequently subjected to high-throughput sequencing. This approach was applicable to both individual neurons cultured from embryonic mouse hippocampus, as well as neocortical neurons from live brain slices. We found that the average pairwise Spearman’s rank correlation coefficient of gene expression level expressed as RPKM (reads per kilobase of transcript per million mapped reads was 0.51 between five cultured neuronal cells, whereas the same measure between three cortical layer V neurons in situ was 0.25. The data suggest that there may be greater heterogeneity of the cortical neurons, as compared to neurons in vitro. The results demonstrate the technical feasibility and reproducibility of RNA-Seq in capturing a part of the transcriptome landscape of single neurons, and confirmed that morphologically identical neurons, even from the same region, have distinct gene expression patterns.

  3. Multiparametric characterization of neuronal subpopulations in the ventrolateral preoptic nucleus.

    Science.gov (United States)

    Dubourget, Romain; Sangare, Aude; Geoffroy, Hélène; Gallopin, Thierry; Rancillac, Armelle

    2017-04-01

    The characterization of neuronal properties is a necessary first step toward understanding how the ventrolateral preoptic nucleus (VLPO) neuronal network regulates slow-wave sleep (SWS). Indeed, the electrophysiological heterogeneity of VLPO neurons suggests the existence of subtypes that could differently contribute in SWS induction and maintenance. The aim of the present study was to define cell classes in the VLPO using an unsupervised clustering classification method. Electrophysiological features extracted from 289 neurons recorded in whole-cell patch-clamp allowed the identification of three main classes of VLPO neurons subdivided into five distinct subpopulations (cluster 1, 2a, 2b, 3a and 3b). The high occurrence of a low-threshold calcium spike (LTS) was one of the most distinctive features of cluster 1 and 3. Since sleep-promoting neurons are generally identified by their ability to generate an LTS and by their inhibitory response to noradrenaline (NA), 189 neurons from our dataset were also tested for this neurotransmitter. Neurons from cluster 3 were the most frequently inhibited by NA. Biocytin labeling and Neurolucida reconstructions of 112 neurons furthermore revealed a small dendritic arbor of cluster 3b neurons compared, in particular, to cluster 2b neurons. Altogether, we performed an exhaustive characterization of VLPO neuronal subtypes that is a crucial step toward a better understanding of the neuronal network within the VLPO and thereby sleep physiology.

  4. [Death of neurons and glial cells, induced by a photodynamic injury: signaling processes and neurone-glial interactions].

    Science.gov (United States)

    Uzdenskiĭ, A B; Kolosov, M S; Lobanov, A V

    2007-01-01

    The mechanisms of photodynamic (PD) injury of neurons and glial cells are reviewed. Neuron responses: firing stimulation at high photosensitizer concentrations and inhibition at low concentrations (neuron enhanced PD-induced apoptosis of glial cells, thus indicating that neuron maintained the survival of glia. Inter- and intracellular signaling mediated photodamage of these cells. Using inhibitors or activators of signaling proteins, the involvement of Ca(2+)-, adenylate cyclase- and tyrosine kinase-mediated signaling pathways in responses of neurons and glial cells to photosensitization was shown. Their pharmacological modulation can change selectivity of PD injury of neuronal and glial cells and efficiency of PD therapy.

  5. Spinal Cord Neuronal Pathology in Multiple Sclerosis

    NARCIS (Netherlands)

    Gilmore, C.P.; DeLuca, G.C.; Bo, L.; Owens, T; Lowe, J.; Esiri, M.M.; Evangelou, N.

    2009-01-01

    The objective of this study was to assess neuronal pathology in the spinal cord in multiple sclerosis (MS), both within myelinated and demyelinated tissue. Autopsy material was obtained from 38 MS cases and 21 controls. Transverse sections were taken from three spinal cord levels and stained using

  6. Efavirenz induces neuronal autophagy and mitochondrial alterations.

    Science.gov (United States)

    Purnell, Phillip R; Fox, Howard S

    2014-11-01

    Efavirenz (EFV) is a non-nucleoside reverse-transcriptase inhibitor in wide use for the treatment of human immunodeficiency virus infection. Although EFV is generally well tolerated, neuropsychiatric toxicity has been well documented. The toxic effects of EFV in hepatocytes and keratinocytes have been linked to mitochondrial perturbations and changes in autophagy. Here, we studied the effect of EFV on mitochondria and autophagy in neuronal cell lines and primary neurons. In SH-SY5Y cells, EFV induced a drop in ATP production, which coincided with increased autophagy, mitochondrial fragmentation, and mitochondrial depolarization. EFV-induced mitophagy was also detected by colocalization of mitochondria and autophagosomes and use of an outer mitochondrial membrane tandem fluorescent vector. Pharmacologic inhibition of autophagy with 3-methyladenine increased the cytotoxic effect of EFV, suggesting that autophagy promotes cell survival. EFV also reduces ATP production in primary neurons, induces autophagy, and changes mitochondrial morphology. Overall, EFV is able to acutely induce autophagy and mitochondrial changes in neurons. These changes may be involved in the mechanism leading to central nervous system toxicity observed in clinical EFV use. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  7. The mirror neuron system : New frontiers

    NARCIS (Netherlands)

    Keysers, Christian; Fadiga, Luciano

    2008-01-01

    Since the discovery of mirror neurons, much effort has been invested into Studying their location and properties in the human brain. Here we review these original findings and introduce the Main topics of this special issue of Social Neuroscience. What does the mirror system code? How is the mirror

  8. Suicide in patients with motor neuron disease

    DEFF Research Database (Denmark)

    Bak, Søren; Stenager, E N; Stenager, Egon

    1994-01-01

    The aim of the present study was to assess, through an epidemiological study, whether suicide risk is increased in patients with motor neuron disease (MND). The study involved 116 patients with MND. In the study period 92 patients died, 47 males and 45 females. No patients committed suicide...

  9. CASE STUDY – HIV AND THE NEURONS

    African Journals Online (AJOL)

    2011-04-02

    Apr 2, 2011 ... There was complete bilateral lower motor neuron 7th cranial nerve palsy in keeping with bilateral Bell's palsy. She was unable to close her eyes or mouth on request and could not speak without the support of her hand. No other focal neurology was present. There was a small aphthous ulcer on her upper ...

  10. Computer Simulation of the Neuronal Action Potential.

    Science.gov (United States)

    Solomon, Paul R.; And Others

    1988-01-01

    A series of computer simulations of the neuronal resting and action potentials are described. Discusses the use of simulations to overcome the difficulties of traditional instruction, such as blackboard illustration, which can only illustrate these events at one point in time. Describes systems requirements necessary to run the simulations.…

  11. Daidzein induces neuritogenesis in DRG neuronal cultures

    Directory of Open Access Journals (Sweden)

    Yang Shih-Hung

    2012-08-01

    Full Text Available Absract Background Daidzein, a phytoestrogen found in isoflavone, is known to exert neurotrophic and neuroprotective effects on the nervous system. Using primary rat dorsal root ganglion (DRG neuronal cultures, we have examined the potential neurite outgrowth effect of daidzein. Methods Dissociated dorsal root ganglia (DRG cultures were used to study the signaling mechanism of daidzein-induced neuritogenesis by immunocytochemistry and Western blotting. Results In response to daidzein treatment, DRG neurons showed a significant increase in total neurite length and in tip number per neuron. The neuritogenic effect of daidzein was significantly hampered by specific blockers for Src, protein kinase C delta (PKCδ and mitogen-activated protein kinase/extracellular signal-regulated kinase kinases (MEK/ERK, but not by those for estrogen receptor (ER. Moreover, daidzein induced phosphorylation of Src, PKCδ and ERK. The activation of PKCδ by daidzein was attenuated in the presence of a Src kinase inhibitor, and that of ERK by daidzein was diminished in the presence of either a Src or PKCδ inhibitor. Conclusion Daidzein may stimulate neurite outgrowth of DRG neurons depending on Src kinase, PKCδ and ERK signaling pathway.

  12. Daidzein induces neuritogenesis in DRG neuronal cultures

    Science.gov (United States)

    2012-01-01

    Absract Background Daidzein, a phytoestrogen found in isoflavone, is known to exert neurotrophic and neuroprotective effects on the nervous system. Using primary rat dorsal root ganglion (DRG) neuronal cultures, we have examined the potential neurite outgrowth effect of daidzein. Methods Dissociated dorsal root ganglia (DRG) cultures were used to study the signaling mechanism of daidzein-induced neuritogenesis by immunocytochemistry and Western blotting. Results In response to daidzein treatment, DRG neurons showed a significant increase in total neurite length and in tip number per neuron. The neuritogenic effect of daidzein was significantly hampered by specific blockers for Src, protein kinase C delta (PKCδ) and mitogen-activated protein kinase/extracellular signal-regulated kinase kinases (MEK/ERK), but not by those for estrogen receptor (ER). Moreover, daidzein induced phosphorylation of Src, PKCδ and ERK. The activation of PKCδ by daidzein was attenuated in the presence of a Src kinase inhibitor, and that of ERK by daidzein was diminished in the presence of either a Src or PKCδ inhibitor. Conclusion Daidzein may stimulate neurite outgrowth of DRG neurons depending on Src kinase, PKCδ and ERK signaling pathway. PMID:22931352

  13. Astrocytic actions on extrasynaptic neuronal currents

    Directory of Open Access Journals (Sweden)

    Balazs ePal

    2015-12-01

    Full Text Available In the last few decades, knowledge about astrocytic functions has significantly increased. It was demonstrated that astrocytes are not passive elements of the central nervous system, but active partners of neurons. There is a growing body of knowledge about the calcium excitability of astrocytes, the actions of different gliotransmitters and their release mechanisms, as well as the participation of astrocytes in the regulation of synaptic functions and their contribution to synaptic plasticity. However, astrocytic functions are even more complex than being a partner of the 'tripartite synapse', as they can influence extrasynaptic neuronal currents either by releasing substances or regulating ambient neurotransmitter levels. Several types of currents or changes of membrane potential with different kinetics and via different mechanisms can be elicited by astrocytic activity. Astrocyte-dependent phasic or tonic, inward or outward currents were described in several brain areas. Such currents, together with the synaptic actions of astrocytes, can contribute to neuromodulatory mechanisms, neurosensory and –secretory processes, cortical oscillatory activity, memory and learning or overall neuronal excitability. This mini-review is an attempt to give a brief summary of astrocyte-dependent extrasynaptic neuronal currents and their possible functional significance.

  14. Beyond the frontiers of neuronal types

    Science.gov (United States)

    Battaglia, Demian; Karagiannis, Anastassios; Gallopin, Thierry; Gutch, Harold W.; Cauli, Bruno

    2012-01-01

    Cortical neurons and, particularly, inhibitory interneurons display a large diversity of morphological, synaptic, electrophysiological, and molecular properties, as well as diverse embryonic origins. Various authors have proposed alternative classification schemes that rely on the concomitant observation of several multimodal features. However, a broad variability is generally observed even among cells that are grouped into a same class. Furthermore, the attribution of specific neurons to a single defined class is often difficult, because individual properties vary in a highly graded fashion, suggestive of continua of features between types. Going beyond the description of representative traits of distinct classes, we focus here on the analysis of atypical cells. We introduce a novel paradigm for neuronal type classification, assuming explicitly the existence of a structured continuum of diversity. Our approach, grounded on the theory of fuzzy sets, identifies a small optimal number of model archetypes. At the same time, it quantifies the degree of similarity between these archetypes and each considered neuron. This allows highlighting archetypal cells, which bear a clear similarity to a single model archetype, and edge cells, which manifest a convergence of traits from multiple archetypes. PMID:23403725

  15. Specific vulnerability of substantia nigra compacta neurons

    NARCIS (Netherlands)

    Smidt, M.P.; Giovanni, G.; Di Matteo, V.; Esposito, E.

    2009-01-01

    The specific loss of substantia nigra compacta (SNc) neurons in Parkinson's disease (PD) has been the main driving force in initiating research efforts to unravel the apparent SNc-specific vulnerability. Initially, metabolic constraints due to high dopamine turnover have been the main focus in the

  16. Beyond the frontiers of neuronal types

    Directory of Open Access Journals (Sweden)

    Demian eBattaglia

    2013-02-01

    Full Text Available Cortical neurons and, particularly, inhibitory interneurons display a large diversity of morphological, synaptic, electrophysiological and molecular properties, as well as diverse embryonic origins. Various authors have proposed alternative classification schemes that rely on the concomitant observation of several multimodal features. However, a broad variability is generally observed even among cells that are grouped into a same class. Furthermore, the attribution of specific neurons to a single defined class is often difficult, because individual properties vary in a highly graded fashion, suggestive of continua of features between types. Going beyond the description of representative traits of distinct classes, we focus here on the analysis of atypical cells. We introduce a novel paradigm for neuronal type classification, assuming explicitly the existence of a structured continuum of diversity. Our approach, grounded on the theory of fuzzy sets, identifies a small optimal number of model archetypes. At the same time, it quantifies the degree of similarity between these archetypes and each considered neuron. This allows highlighting archetypal cells, which bear a clear similarity to a single model archetype, and edge cells, which manifest a convergence of traits from multiple archetypes.

  17. Modulation of neuronal network activity with ghrelin

    NARCIS (Netherlands)

    Stoyanova, Irina; Rutten, Wim; le Feber, Jakob

    2012-01-01

    Ghrelin is a neuropeptide regulating multiple physiological processes, including high brain functions such as learning and memory formation. However, the effect of ghrelin on network activity patterns and developments has not been studied yet. Therefore, we used dissociated cortical neurons plated

  18. Visualizing the spinal neuronal dynamics of locomotion

    Science.gov (United States)

    Subramanian, Kalpathi R.; Bashor, D. P.; Miller, M. T.; Foster, J. A.

    2004-06-01

    Modern imaging and simulation techniques have enhanced system-level understanding of neural function. In this article, we present an application of interactive visualization to understanding neuronal dynamics causing locomotion of a single hip joint, based on pattern generator output of the spinal cord. Our earlier work visualized cell-level responses of multiple neuronal populations. However, the spatial relationships were abstract, making communication with colleagues difficult. We propose two approaches to overcome this: (1) building a 3D anatomical model of the spinal cord with neurons distributed inside, animated by the simulation and (2) adding limb movements predicted by neuronal activity. The new system was tested using a cat walking central pattern generator driving a pair of opposed spinal motoneuron pools. Output of opposing motoneuron pools was combined into a single metric, called "Net Neural Drive", which generated angular limb movement in proportion to its magnitude. Net neural drive constitutes a new description of limb movement control. The combination of spatial and temporal information in the visualizations elegantly conveys the neural activity of the output elements (motoneurons), as well as the resulting movement. The new system encompasses five biological levels of organization from ion channels to observed behavior. The system is easily scalable, and provides an efficient interactive platform for rapid hypothesis testing.

  19. Characterization of astrocytic and neuronal benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Bender, A.S.

    1988-01-01

    Primary cultures of astrocytes and neurons express benzodiazepine receptors. Neuronal benzodiazepine receptors were of high-affinity, K{sub D} values were 7.5-43 nM and the densities of receptors (B{sub max}) were 924-4131 fmol/mg protein. Astrocytes posses a high-affinity benzodiazepine receptor, K{sub D} values were 6.6-13 nM. The B{sub max} values were 6,033-12,000 fmol/mg protein. The pharmacological profile of the neuronal benzodiazepine receptor was that of the central-type benzodiazepine receptor, where clonazepam has a high-affinity and Ro 5-4864 (4{prime}-chlorodiazepam) has a low-affinity. Whereas astrocytic benzoidazepine receptor was characteristic of the so called peripheral-type benzodiazepine receptors, which shows a high-affinity towards Ro 5-4863, and a low-affinity towards clonazepam. The astrocytic benzodiazepine receptors was functionally correlated with voltage dependent calcium channels, since dihydropyridines and benzodiazepines interacted with ({sup 3}H) diazepam and ({sup 3}H) nitrendipine receptors with the same rank order of potency, showing a statistically significant correlation. No such correlation was observed in neurons.

  20. Protective effect of parvalbumin on excitotoxic motor neuron death

    DEFF Research Database (Denmark)

    Van den Bosch, L.; Schwaller, B.; Vleminckx, V.

    2002-01-01

    Amyotrophic lateral sclerosis, ALS, AMPA receptor, calcium-binding proteins, calcium buffering, excitotoxity, kainic acid, motor neuron, parvalbumin......Amyotrophic lateral sclerosis, ALS, AMPA receptor, calcium-binding proteins, calcium buffering, excitotoxity, kainic acid, motor neuron, parvalbumin...

  1. Chaotic States Induced By Resetting Process In Izhikevich Neuron Model

    National Research Council Canada - National Science Library

    Sou Nobukawa; Haruhiko Nishimura; Teruya Yamanishi; Jian-Qin Liu

    2015-01-01

    ... potential between spike and hyperpolarization. As one of the hybrid spiking neuron models, Izhikevich neuron model can reproduce major spike patterns observed in the cerebral cortex only by tuning a few parameters and also exhibit chaotic states...

  2. GABAA receptor-expressing neurons promote consumption in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Samantha K Cheung

    Full Text Available Feeding decisions are highly plastic and bidirectionally regulated by neurons that either promote or inhibit feeding. In Drosophila melanogaster, recent studies have identified four GABAergic interneurons that act as critical brakes to prevent incessant feeding. These GABAergic neurons may inhibit target neurons that drive consumption. Here, we tested this hypothesis by examining GABA receptors and neurons that promote consumption. We find that Resistance to dieldrin (RDL, a GABAA type receptor, is required for proper control of ingestion. Knockdown of Rdl in a subset of neurons causes overconsumption of tastants. Acute activation of these neurons is sufficient to drive consumption of appetitive substances and non-appetitive substances and acute silencing of these neurons decreases consumption. Taken together, these studies identify GABAA receptor-expressing neurons that promote Drosophila ingestive behavior and provide insight into feeding regulation.

  3. GABAA receptor-expressing neurons promote consumption in Drosophila melanogaster.

    Science.gov (United States)

    Cheung, Samantha K; Scott, Kristin

    2017-01-01

    Feeding decisions are highly plastic and bidirectionally regulated by neurons that either promote or inhibit feeding. In Drosophila melanogaster, recent studies have identified four GABAergic interneurons that act as critical brakes to prevent incessant feeding. These GABAergic neurons may inhibit target neurons that drive consumption. Here, we tested this hypothesis by examining GABA receptors and neurons that promote consumption. We find that Resistance to dieldrin (RDL), a GABAA type receptor, is required for proper control of ingestion. Knockdown of Rdl in a subset of neurons causes overconsumption of tastants. Acute activation of these neurons is sufficient to drive consumption of appetitive substances and non-appetitive substances and acute silencing of these neurons decreases consumption. Taken together, these studies identify GABAA receptor-expressing neurons that promote Drosophila ingestive behavior and provide insight into feeding regulation.

  4. Astrocyte calcium signalling orchestrates neuronal synchronization in organotypic hippocampal slices

    Science.gov (United States)

    Sasaki, Takuya; Ishikawa, Tomoe; Abe, Reimi; Nakayama, Ryota; Asada, Akiko; Matsuki, Norio; Ikegaya, Yuji

    2014-01-01

    Astrocytes are thought to detect neuronal activity in the form of intracellular calcium elevations; thereby, astrocytes can regulate neuronal excitability and synaptic transmission. Little is known, however, about how the astrocyte calcium signal regulates the activity of neuronal populations. In this study, we addressed this issue using functional multineuron calcium imaging in hippocampal slice cultures. Under normal conditions, CA3 neuronal networks exhibited temporally correlated activity patterns, occasionally generating large synchronization among a subset of cells. The synchronized neuronal activity was correlated with astrocyte calcium events. Calcium buffering by an intracellular injection of a calcium chelator into multiple astrocytes reduced the synaptic strength of unitary transmission between pairs of surrounding pyramidal cells and caused desynchronization of the neuronal networks. Uncaging the calcium in the astrocytes increased the frequency of neuronal synchronization. These data suggest an essential role of the astrocyte calcium signal in the maintenance of basal neuronal function at the circuit level. PMID:24710057

  5. Water diffusion in brain cortex closely tracks underlying neuronal activity

    National Research Council Canada - National Science Library

    Tomokazu Tsurugizawa; Luisa Ciobanu; Denis Le Bihan

    2013-01-01

    ...). Here we establish that water molecular diffusion is directly modulated by underlying neuronal activity using a rat forepaw stimulation model under different conditions of neuronal stimulation and neurovascular coupling...

  6. Control of neuronal excitability by NMDA‐type glutamate receptors in early developing binaural auditory neurons

    National Research Council Canada - National Science Library

    Sanchez, Jason Tait; Seidl, Armin H; Rubel, Edwin W; Barria, Andres

    2012-01-01

    •  Mature nucleus laminaris (NL) neurons in the avian auditory brainstem respond with one or two action potentials to repetitive synaptic stimulation due to strong expression of low‐voltage‐activated K + channels (K LVA...

  7. Design-based estimation of neuronal number and individual neuronal volume in the rat hippocampus

    DEFF Research Database (Denmark)

    Hosseini-Sharifabad, Mohammad; Nyengaard, Jens Randel

    2007-01-01

    Tools recently developed in stereology were employed for unbiased estimation of the neuronal number and volume in three major subdivisions of rat hippocampus (dentate granular, CA1 and CA3 pyramidal layers). The optical fractionator is used extensively in quantitative studies of the hippocampus......; however, the classical optical fractionator design may be affected by tissue deformation in the z-axis of the section. In this study, we applied an improved optical fractionator design to estimate total number of neurons on 100 microm thick vibratome sections that had been deformed, in the z...... vertical sections from the hippocampus. The volume of hippocampal neurons was estimated using the rotator principle on 40 microm thick plastic vertical uniform random sections and corrected for tissue shrinkage. Application of the proposed new design should result in more accurate estimates of neuron...

  8. Neurons versus Networks: The Interplay between Individual Neurons and Neural Networks in Cognitive Functions.

    Science.gov (United States)

    Arshavsky, Yuri I

    2016-09-22

    The main paradigm of cognitive neuroscience is the connectionist concept postulating that the higher nervous activity is performed through interactions of neurons forming complex networks, whereas the function of individual neurons is restricted to generating electrical potentials and transmitting signals to other cells. In this article, I describe the observations from three fields-neurolinguistics, physiology of memory, and sensory perception-that can hardly be explained within the constraints of a purely connectionist concept. Rather, these examples suggest that cognitive functions are determined by specific properties of individual neurons and, therefore, are likely to be accomplished primarily at the intracellular level. This view is supported by the recent discovery that the brain's ability to create abstract concepts of particular individuals, animals, or places is performed by neurons ("concept cells") sparsely distributed in the medial temporal lobe. © The Author(s) 2016.

  9. Global dynamics of a stochastic neuronal oscillator

    Science.gov (United States)

    Yamanobe, Takanobu

    2013-11-01

    Nonlinear oscillators have been used to model neurons that fire periodically in the absence of input. These oscillators, which are called neuronal oscillators, share some common response structures with other biological oscillations such as cardiac cells. In this study, we analyze the dependence of the global dynamics of an impulse-driven stochastic neuronal oscillator on the relaxation rate to the limit cycle, the strength of the intrinsic noise, and the impulsive input parameters. To do this, we use a Markov operator that both reflects the density evolution of the oscillator and is an extension of the phase transition curve, which describes the phase shift due to a single isolated impulse. Previously, we derived the Markov operator for the finite relaxation rate that describes the dynamics of the entire phase plane. Here, we construct a Markov operator for the infinite relaxation rate that describes the stochastic dynamics restricted to the limit cycle. In both cases, the response of the stochastic neuronal oscillator to time-varying impulses is described by a product of Markov operators. Furthermore, we calculate the number of spikes between two consecutive impulses to relate the dynamics of the oscillator to the number of spikes per unit time and the interspike interval density. Specifically, we analyze the dynamics of the number of spikes per unit time based on the properties of the Markov operators. Each Markov operator can be decomposed into stationary and transient components based on the properties of the eigenvalues and eigenfunctions. This allows us to evaluate the difference in the number of spikes per unit time between the stationary and transient responses of the oscillator, which we show to be based on the dependence of the oscillator on past activity. Our analysis shows how the duration of the past neuronal activity depends on the relaxation rate, the noise strength, and the impulsive input parameters.

  10. Neuronal networks and energy bursts in epilepsy.

    Science.gov (United States)

    Wu, Y; Liu, D; Song, Z

    2015-02-26

    Epilepsy can be defined as the abnormal activities of neurons. The occurrence, propagation and termination of epileptic seizures rely on the networks of neuronal cells that are connected through both synaptic- and non-synaptic interactions. These complicated interactions contain the modified functions of normal neurons and glias as well as the mediation of excitatory and inhibitory mechanisms with feedback homeostasis. Numerous spread patterns are detected in disparate networks of ictal activities. The cortical-thalamic-cortical loop is present during a general spike wave seizure. The thalamic reticular nucleus (nRT) is the major inhibitory input traversing the region, and the dentate gyrus (DG) controls CA3 excitability. The imbalance between γ-aminobutyric acid (GABA)-ergic inhibition and glutamatergic excitation is the main disorder in epilepsy. Adjustable negative feedback that mediates both inhibitory and excitatory components affects neuronal networks through neurotransmission fluctuation, receptor and transmitter signaling, and through concomitant influences on ion concentrations and field effects. Within a limited dynamic range, neurons slowly adapt to input levels and have a high sensitivity to synaptic changes. The stability of the adapting network depends on the ratio of the adaptation rates of both the excitatory and inhibitory populations. Thus, therapeutic strategies with multiple effects on seizures are required for the treatment of epilepsy, and the therapeutic functions on networks are reviewed here. Based on the high-energy burst theory of epileptic activity, we propose a potential antiepileptic therapeutic strategy to transfer the high energy and extra electricity out of the foci. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Replaceable neurons and neurodegenerative disease share depressed UCHL1 levels

    OpenAIRE

    Lombardino, Anthony J.; Li, Xiao-Ching; Hertel, Moritz; Nottebohm, Fernando

    2005-01-01

    Might there be systematic differences in gene expression between neurons that undergo spontaneous replacement in the adult brain and those that do not? We first explored this possibility in the high vocal center (HVC) of male zebra finches by using a combination of neuronal tracers, laser capture microdissection, and RNA profiling. HVC has two kinds of projection neurons, one of which continues to be produced and replaced in adulthood. HVC neurons of the replaceable kind showed a consistent a...

  12. Single-neuron NMDA receptor phenotype influences neuronal rewiring and reintegration following traumatic injury.

    Science.gov (United States)

    Patel, Tapan P; Ventre, Scott C; Geddes-Klein, Donna; Singh, Pallab K; Meaney, David F

    2014-03-19

    Alterations in the activity of neural circuits are a common consequence of traumatic brain injury (TBI), but the relationship between single-neuron properties and the aggregate network behavior is not well understood. We recently reported that the GluN2B-containing NMDA receptors (NMDARs) are key in mediating mechanical forces during TBI, and that TBI produces a complex change in the functional connectivity of neuronal networks. Here, we evaluated whether cell-to-cell heterogeneity in the connectivity and aggregate contribution of GluN2B receptors to [Ca(2+)]i before injury influenced the functional rewiring, spontaneous activity, and network plasticity following injury using primary rat cortical dissociated neurons. We found that the functional connectivity of a neuron to its neighbors, combined with the relative influx of calcium through distinct NMDAR subtypes, together contributed to the individual neuronal response to trauma. Specifically, individual neurons whose [Ca(2+)]i oscillations were largely due to GluN2B NMDAR activation lost many of their functional targets 1 h following injury. In comparison, neurons with large GluN2A contribution or neurons with high functional connectivity both independently protected against injury-induced loss in connectivity. Mechanistically, we found that traumatic injury resulted in increased uncorrelated network activity, an effect linked to reduction of the voltage-sensitive Mg(2+) block of GluN2B-containing NMDARs. This uncorrelated activation of GluN2B subtypes after injury significantly limited the potential for network remodeling in response to a plasticity stimulus. Together, our data suggest that two single-cell characteristics, the aggregate contribution of NMDAR subtypes and the number of functional connections, influence network structure following traumatic injury.

  13. Modeling of inter-neuronal coupling medium and its impact on neuronal synchronization.

    Science.gov (United States)

    Iqbal, Muhammad; Rehan, Muhammad; Hong, Keum-Shik

    2017-01-01

    In this paper, modeling of the coupling medium between two neurons, the effects of the model parameters on the synchronization of those neurons, and compensation of coupling strength deficiency in synchronization are studied. Our study exploits the inter-neuronal coupling medium and investigates its intrinsic properties in order to get insight into neuronal-information transmittance and, there from, brain-information processing. A novel electrical model of the coupling medium that represents a well-known RLC circuit attributable to the coupling medium's intrinsic resistive, inductive, and capacitive properties is derived. Surprisingly, the integration of such properties reveals the existence of a natural three-term control strategy, referred to in the literature as the proportional integral derivative (PID) controller, which can be responsible for synchronization between two neurons. Consequently, brain-information processing can rely on a large number of PID controllers based on the coupling medium properties responsible for the coherent behavior of neurons in a neural network. Herein, the effects of the coupling model (or natural PID controller) parameters are studied and, further, a supervisory mechanism is proposed that follows a learning and adaptation policy based on the particle swarm optimization algorithm for compensation of the coupling strength deficiency.

  14. Modeling of inter-neuronal coupling medium and its impact on neuronal synchronization

    Science.gov (United States)

    Iqbal, Muhammad; Hong, Keum-Shik

    2017-01-01

    In this paper, modeling of the coupling medium between two neurons, the effects of the model parameters on the synchronization of those neurons, and compensation of coupling strength deficiency in synchronization are studied. Our study exploits the inter-neuronal coupling medium and investigates its intrinsic properties in order to get insight into neuronal-information transmittance and, there from, brain-information processing. A novel electrical model of the coupling medium that represents a well-known RLC circuit attributable to the coupling medium’s intrinsic resistive, inductive, and capacitive properties is derived. Surprisingly, the integration of such properties reveals the existence of a natural three-term control strategy, referred to in the literature as the proportional integral derivative (PID) controller, which can be responsible for synchronization between two neurons. Consequently, brain-information processing can rely on a large number of PID controllers based on the coupling medium properties responsible for the coherent behavior of neurons in a neural network. Herein, the effects of the coupling model (or natural PID controller) parameters are studied and, further, a supervisory mechanism is proposed that follows a learning and adaptation policy based on the particle swarm optimization algorithm for compensation of the coupling strength deficiency. PMID:28486505

  15. An FPGA-Based Silicon Neuronal Network with Selectable Excitability Silicon Neurons.

    Science.gov (United States)

    Li, Jing; Katori, Yuichi; Kohno, Takashi

    2012-01-01

    This paper presents a digital silicon neuronal network which simulates the nerve system in creatures and has the ability to execute intelligent tasks, such as associative memory. Two essential elements, the mathematical-structure-based digital spiking silicon neuron (DSSN) and the transmitter release based silicon synapse, allow us to tune the excitability of silicon neurons and are computationally efficient for hardware implementation. We adopt mixed pipeline and parallel structure and shift operations to design a sufficient large and complex network without excessive hardware resource cost. The network with 256 full-connected neurons is built on a Digilent Atlys board equipped with a Xilinx Spartan-6 LX45 FPGA. Besides, a memory control block and USB control block are designed to accomplish the task of data communication between the network and the host PC. This paper also describes the mechanism of associative memory performed in the silicon neuronal network. The network is capable of retrieving stored patterns if the inputs contain enough information of them. The retrieving probability increases with the similarity between the input and the stored pattern increasing. Synchronization of neurons is observed when the successful stored pattern retrieval occurs.

  16. Synaptic plasticity and neuronal refractory time cause scaling behaviour of neuronal avalanches

    Science.gov (United States)

    Michiels van Kessenich, L.; de Arcangelis, L.; Herrmann, H. J.

    2016-08-01

    Neuronal avalanches measured in vitro and in vivo in different cortical networks consistently exhibit power law behaviour for the size and duration distributions with exponents typical for a mean field self-organized branching process. These exponents are also recovered in neuronal network simulations implementing various neuronal dynamics on different network topologies. They can therefore be considered a very robust feature of spontaneous neuronal activity. Interestingly, this scaling behaviour is also observed on regular lattices in finite dimensions, which raises the question about the origin of the mean field behavior observed experimentally. In this study we provide an answer to this open question by investigating the effect of activity dependent plasticity in combination with the neuronal refractory time in a neuronal network. Results show that the refractory time hinders backward avalanches forcing a directed propagation. Hebbian plastic adaptation plays the role of sculpting these directed avalanche patterns into the topology of the network slowly changing it into a branched structure where loops are marginal.

  17. Dcc regulates asymmetric outgrowth of forebrain neurons in zebrafish.

    Directory of Open Access Journals (Sweden)

    Jingxia Gao

    Full Text Available The guidance receptor DCC (deleted in colorectal cancer ortholog UNC-40 regulates neuronal asymmetry development in Caenorhabditis elegans, but it is not known whether DCC plays a role in the specification of neuronal polarity in vertebrates. To examine the roles of DCC in neuronal asymmetry regulation in vertebrates, we studied zebrafish anterior dorsal telencephalon (ADt neuronal axons. We generated transgenic zebrafish animals expressing the photo-convertible fluorescent protein Kaede in ADt neurons and then photo-converted Kaede to label specifically the ADt neuron axons. We found that ADt axons normally project ventrally. Knock down of Dcc function by injecting antisense morpholino oligonucleotides caused the ADt neurons to project axons dorsally. To examine the axon projection pattern of individual ADt neurons, we labeled single ADt neurons using a forebrain-specific promoter to drive fluorescent protein expression. We found that individual ADt neurons projected axons dorsally or formed multiple processes after morpholino knock down of Dcc function. We further found that knock down of the Dcc ligand, Netrin1, also caused ADt neurons to project axons dorsally. Knockdown of Neogenin1, a guidance receptor closely related to Dcc, enhanced the formation of aberrant dorsal axons in embryos injected with Dcc morpholino. These experiments provide the first evidence that Dcc regulates polarized axon initiation and asymmetric outgrowth of forebrain neurons in vertebrates.

  18. Asynchronous updating of threshold-coupled chaotic neurons

    Indian Academy of Sciences (India)

    Abstract. We study a network of chaotic model neurons incorporating threshold- activated coupling. We obtain a wide range of spatiotemporal patterns under varying degrees of asynchronicity in the evolution of the neuronal components. For instance, we find that sequential updating of threshold-coupled chaotic neurons ...

  19. Von Economo neurons: A review of the anatomy and functions ...

    African Journals Online (AJOL)

    Von Economo neurons (VENs) are large bipolar neurons found in the anterior cingulate, fronto‑insular, and dorsolateral prefrontal cortices of great apes and the humans. VENs are defined by their thin, elongated cell body, and long dendrites projecting from the apical and basal ends. These neurons are mostly present in ...

  20. Asynchronous updating of threshold-coupled chaotic neurons

    Indian Academy of Sciences (India)

    We study a network of chaotic model neurons incorporating threshold activated coupling. We obtain a wide range of spatiotemporal patterns under varying degrees of asynchronicity in the evolution of the neuronal components. For instance, we find that sequential updating of threshold-coupled chaotic neurons can yield ...

  1. Developmental time windows for axon growth influence neuronal network topology.

    Science.gov (United States)

    Lim, Sol; Kaiser, Marcus

    2015-04-01

    Early brain connectivity development consists of multiple stages: birth of neurons, their migration and the subsequent growth of axons and dendrites. Each stage occurs within a certain period of time depending on types of neurons and cortical layers. Forming synapses between neurons either by growing axons starting at similar times for all neurons (much-overlapped time windows) or at different time points (less-overlapped) may affect the topological and spatial properties of neuronal networks. Here, we explore the extreme cases of axon formation during early development, either starting at the same time for all neurons (parallel, i.e., maximally overlapped time windows) or occurring for each neuron separately one neuron after another (serial, i.e., no overlaps in time windows). For both cases, the number of potential and established synapses remained comparable. Topological and spatial properties, however, differed: Neurons that started axon growth early on in serial growth achieved higher out-degrees, higher local efficiency and longer axon lengths while neurons demonstrated more homogeneous connectivity patterns for parallel growth. Second, connection probability decreased more rapidly with distance between neurons for parallel growth than for serial growth. Third, bidirectional connections were more numerous for parallel growth. Finally, we tested our predictions with C. elegans data. Together, this indicates that time windows for axon growth influence the topological and spatial properties of neuronal networks opening up the possibility to a posteriori estimate developmental mechanisms based on network properties of a developed network.

  2. Neuronal trafficking of voltage-gated potassium channels

    DEFF Research Database (Denmark)

    Jensen, Camilla S; Rasmussen, Hanne Borger; Misonou, Hiroaki

    2011-01-01

    The computational ability of CNS neurons depends critically on the specific localization of ion channels in the somatodendritic and axonal membranes. Neuronal dendrites receive synaptic inputs at numerous spines and integrate them in time and space. The integration of synaptic potentials...... and discuss how they contribute to the establishment and maintenance of the specific localization of Kv channels in neurons....

  3. Synchronization properties of heterogeneous neuronal networks with mixed excitability type.

    Science.gov (United States)

    Leone, Michael J; Schurter, Brandon N; Letson, Benjamin; Booth, Victoria; Zochowski, Michal; Fink, Christian G

    2015-03-01

    We study the synchronization of neuronal networks with dynamical heterogeneity, showing that network structures with the same propensity for synchronization (as quantified by master stability function analysis) may develop dramatically different synchronization properties when heterogeneity is introduced with respect to neuronal excitability type. Specifically, we investigate networks composed of neurons with different types of phase response curves (PRCs), which characterize how oscillating neurons respond to excitatory perturbations. Neurons exhibiting type 1 PRC respond exclusively with phase advances, while neurons exhibiting type 2 PRC respond with either phase delays or phase advances, depending on when the perturbation occurs. We find that Watts-Strogatz small world networks transition to synchronization gradually as the proportion of type 2 neurons increases, whereas scale-free networks may transition gradually or rapidly, depending upon local correlations between node degree and excitability type. Random placement of type 2 neurons results in gradual transition to synchronization, whereas placement of type 2 neurons as hubs leads to a much more rapid transition, showing that type 2 hub cells easily "hijack" neuronal networks to synchronization. These results underscore the fact that the degree of synchronization observed in neuronal networks is determined by a complex interplay between network structure and the dynamical properties of individual neurons, indicating that efforts to recover structural connectivity from dynamical correlations must in general take both factors into account.

  4. Reliable activation of immature neurons in the adult hippocampus.

    Directory of Open Access Journals (Sweden)

    Lucas A Mongiat

    Full Text Available Neurons born in the adult dentate gyrus develop, mature, and connect over a long interval that can last from six to eight weeks. It has been proposed that, during this period, developing neurons play a relevant role in hippocampal signal processing owing to their distinctive electrical properties. However, it has remained unknown whether immature neurons can be recruited into a network before synaptic and functional maturity have been achieved. To address this question, we used retroviral expression of green fluorescent protein to identify developing granule cells of the adult mouse hippocampus and investigate the balance of afferent excitation, intrinsic excitability, and firing behavior by patch clamp recordings in acute slices. We found that glutamatergic inputs onto young neurons are significantly weaker than those of mature cells, yet stimulation of cortical excitatory axons elicits a similar spiking probability in neurons at either developmental stage. Young neurons are highly efficient in transducing ionic currents into membrane depolarization due to their high input resistance, which decreases substantially in mature neurons as the inward rectifier potassium (Kir conductance increases. Pharmacological blockade of Kir channels in mature neurons mimics the high excitability characteristic of young neurons. Conversely, Kir overexpression induces mature-like firing properties in young neurons. Therefore, the differences in excitatory drive of young and mature neurons are compensated by changes in membrane excitability that render an equalized firing activity. These observations demonstrate that the adult hippocampus continuously generates a population of highly excitable young neurons capable of information processing.

  5. Parameter estimation in neuronal stochastic differential equation models from intracellular recordings of membrane potentials in single neurons

    DEFF Research Database (Denmark)

    Ditlevsen, Susanne; Samson, Adeline

    2016-01-01

    Dynamics of the membrane potential in a single neuron can be studied by estimating biophysical parameters from intracellular recordings. Diffusion processes, given as continuous solutions to stochastic differential equations, are widely applied as models for the neuronal membrane potential evolut...

  6. Leptin Acts via Lateral Hypothalamic Area Neurotensin Neurons to Inhibit Orexin Neurons by Multiple GABA-Independent Mechanisms

    Science.gov (United States)

    Goforth, Paulette B.; Leinninger, Gina M.; Patterson, Christa M.

    2014-01-01

    The adipocyte-derived hormone leptin modulates neural systems appropriately for the status of body energy stores. Leptin inhibits lateral hypothalamic area (LHA) orexin (OX; also known as hypocretin)-producing neurons, which control feeding, activity, and energy expenditure, among other parameters. Our previous results suggest that GABAergic LHA leptin receptor (LepRb)-containing and neurotensin (Nts)-containing (LepRbNts) neurons lie in close apposition with OX neurons and control Ox mRNA expression. Here, we show that, similar to leptin, activation of LHA Nts neurons by the excitatory hM3Dq DREADD (designer receptor exclusively activated by designer drugs) hyperpolarizes membrane potential and suppresses action potential firing in OX neurons in mouse hypothalamic slices. Furthermore, ablation of LepRb from Nts neurons abrogated the leptin-mediated inhibition, demonstrating that LepRbNts neurons mediate the inhibition of OX neurons by leptin. Leptin did not significantly enhance GABAA-mediated inhibitory synaptic transmission, and GABA receptor antagonists did not block leptin-mediated inhibition of OX neuron activity. Rather, leptin diminished the frequency of spontaneous EPSCs onto OX neurons. Furthermore, leptin indirectly activated an ATP-sensitive potassium (KATP) channel in OX neurons, which was required for the hyperpolarization of OX neurons by leptin. Although Nts did not alter OX activity, galanin, which is coexpressed in LepRbNts neurons, inhibited OX neurons, whereas the galanin receptor antagonist M40 (galanin-(1–12)-Pro3-(Ala-Leu)2-Ala amide) prevented the leptin-induced hyperpolarization of OX cells. These findings demonstrate that leptin indirectly inhibits OX neurons by acting on LHA LepRbNts neurons to mediate two distinct GABA-independent mechanisms of inhibition: the presynaptic inhibition of excitatory neurotransmission and the opening of KATP channels. PMID:25143620

  7. Trans-neuronal transduction of spinal neurons following cortical injection and anterograde axonal transport of a bicistronic AAV1 vector

    OpenAIRE

    Hutson, Thomas Haynes; Kathe, Claudia; Moon, Lawrence David Falcon

    2015-01-01

    Adeno-associated viral (AAV) vectors are one of the most promising gene delivery systems to the central nervous system. We now report, that AAV1 can be used to express transgenes trans-neuronally in neurons distant from the injection site. Specifically, intracortical injection of a bicistronic AAV1 vector trans-neuronally transduced spinal neurons as shown by fluorescence microscopy, the presence of AAV genome and AAV transcript in the contralateral spinal cord. Prior pyramidotomy abolished s...

  8. Progranulin is expressed within motor neurons and promotes neuronal cell survival

    Directory of Open Access Journals (Sweden)

    Kay Denis G

    2009-10-01

    Full Text Available Abstract Background Progranulin is a secreted high molecular weight growth factor bearing seven and one half copies of the cysteine-rich granulin-epithelin motif. While inappropriate over-expression of the progranulin gene has been associated with many cancers, haploinsufficiency leads to atrophy of the frontotemporal lobes and development of a form of dementia (frontotemporal lobar degeneration with ubiquitin positive inclusions, FTLD-U associated with the formation of ubiquitinated inclusions. Recent reports indicate that progranulin has neurotrophic effects, which, if confirmed would make progranulin the only neuroprotective growth factor that has been associated genetically with a neurological disease in humans. Preliminary studies indicated high progranulin gene expression in spinal cord motor neurons. However, it is uncertain what the role of Progranulin is in normal or diseased motor neuron function. We have investigated progranulin gene expression and subcellular localization in cultured mouse embryonic motor neurons and examined the effect of progranulin over-expression and knockdown in the NSC-34 immortalized motor neuron cell line upon proliferation and survival. Results In situ hybridisation and immunohistochemical techniques revealed that the progranulin gene is highly expressed by motor neurons within the mouse spinal cord and in primary cultures of dissociated mouse embryonic spinal cord-dorsal root ganglia. Confocal microscopy coupled to immunocytochemistry together with the use of a progranulin-green fluorescent protein fusion construct revealed progranulin to be located within compartments of the secretory pathway including the Golgi apparatus. Stable transfection of the human progranulin gene into the NSC-34 motor neuron cell line stimulates the appearance of dendritic structures and provides sufficient trophic stimulus to survive serum deprivation for long periods (up to two months. This is mediated at least in part through

  9. Sensory Neurons Do Not Induce Motor Neuron Loss in a Human Stem Cell Model of Spinal Muscular Atrophy

    Science.gov (United States)

    Schwab, Andrew J.; Ebert, Allison D.

    2014-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive disorder leading to paralysis and early death due to reduced SMN protein. It is unclear why there is such a profound motor neuron loss, but recent evidence from fly and mouse studies indicate that cells comprising the whole sensory-motor circuit may contribute to motor neuron dysfunction and loss. Here, we used induced pluripotent stem cells derived from SMA patients to test whether sensory neurons directly contribute to motor neuron loss. We generated sensory neurons from SMA induced pluripotent stem cells and found no difference in neuron generation or survival, although there was a reduced calcium response to depolarizing stimuli. Using co-culture of SMA induced pluripotent stem cell derived sensory neurons with control induced pluripotent stem cell derived motor neurons, we found no significant reduction in motor neuron number or glutamate transporter boutons on motor neuron cell bodies or neurites. We conclude that SMA sensory neurons do not overtly contribute to motor neuron loss in this human stem cell system. PMID:25054590

  10. Micropatterning Facilitates the Long-Term Growth and Analysis of iPSC-Derived Individual Human Neurons and Neuronal Networks.

    Science.gov (United States)

    Burbulla, Lena F; Beaumont, Kristin G; Mrksich, Milan; Krainc, Dimitri

    2016-08-01

    The discovery of induced pluripotent stem cells (iPSCs) and their application to patient-specific disease models offers new opportunities for studying the pathophysiology of neurological disorders. However, current methods for culturing iPSC-derived neuronal cells result in clustering of neurons, which precludes the analysis of individual neurons and defined neuronal networks. To address this challenge, cultures of human neurons on micropatterned surfaces are developed that promote neuronal survival over extended periods of time. This approach facilitates studies of neuronal development, cellular trafficking, and related mechanisms that require assessment of individual neurons and specific network connections. Importantly, micropatterns support the long-term stability of cultured neurons, which enables time-dependent analysis of cellular processes in living neurons. The approach described in this paper allows mechanistic studies of human neurons, both in terms of normal neuronal development and function, as well as time-dependent pathological processes, and provides a platform for testing of new therapeutics in neuropsychiatric disorders. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Neurogenic differentiation of dental pulp stem cells to neuron-like cells in dopaminergic and motor neuronal inductive media

    Directory of Open Access Journals (Sweden)

    Chia-Chieh Chang

    2014-12-01

    Conclusion: These findings suggest that in response to the neuronal inductive stimuli, a greater proportion of DPSCs stop proliferation and acquire a phenotype resembling mature neurons. Such neural crest-derived adult DPSCs may provide an alternative stem cell source for therapy-based treatments of neuronal disorders and injury.

  12. Nonsmooth dynamics in spiking neuron models

    Science.gov (United States)

    Coombes, S.; Thul, R.; Wedgwood, K. C. A.

    2012-11-01

    Large scale studies of spiking neural networks are a key part of modern approaches to understanding the dynamics of biological neural tissue. One approach in computational neuroscience has been to consider the detailed electrophysiological properties of neurons and build vast computational compartmental models. An alternative has been to develop minimal models of spiking neurons with a reduction in the dimensionality of both parameter and variable space that facilitates more effective simulation studies. In this latter case the single neuron model of choice is often a variant of the classic integrate-and-fire model, which is described by a nonsmooth dynamical system. In this paper we review some of the more popular spiking models of this class and describe the types of spiking pattern that they can generate (ranging from tonic to burst firing). We show that a number of techniques originally developed for the study of impact oscillators are directly relevant to their analysis, particularly those for treating grazing bifurcations. Importantly we highlight one particular single neuron model, capable of generating realistic spike trains, that is both computationally cheap and analytically tractable. This is a planar nonlinear integrate-and-fire model with a piecewise linear vector field and a state dependent reset upon spiking. We call this the PWL-IF model and analyse it at both the single neuron and network level. The techniques and terminology of nonsmooth dynamical systems are used to flesh out the bifurcation structure of the single neuron model, as well as to develop the notion of Lyapunov exponents. We also show how to construct the phase response curve for this system, emphasising that techniques in mathematical neuroscience may also translate back to the field of nonsmooth dynamical systems. The stability of periodic spiking orbits is assessed using a linear stability analysis of spiking times. At the network level we consider linear coupling between voltage

  13. Bifurcation transitions in gap-junction-coupled neurons

    Science.gov (United States)

    Shaffer, Annabelle; Harris, Allison L.; Follmann, Rosangela; Rosa, Epaminondas

    2016-10-01

    Here we investigate transitions occurring in the dynamical states of pairs of distinct neurons electrically coupled, with one neuron tonic and the other bursting. Depending on the dynamics of the individual neurons, and for strong enough coupling, they synchronize either in a tonic or a bursting regime, or initially tonic transitioning to bursting via a period doubling cascade. Certain intrinsic properties of the individual neurons such as minimum firing rates are carried over into the dynamics of the coupled neurons affecting their ultimate synchronous state.

  14. A Simple Picaxe Microcontroller Pulse Source for Juxtacellular Neuronal Labelling.

    Science.gov (United States)

    Verberne, Anthony J M

    2016-10-19

    Juxtacellular neuronal labelling is a method which allows neurophysiologists to fill physiologically-identified neurons with small positively-charged marker molecules. Labelled neurons are identified by histochemical processing of brain sections along with immunohistochemical identification of neuropeptides, neurotransmitters, neurotransmitter transporters or biosynthetic enzymes. A microcontroller-based pulser circuit and associated BASIC software script is described for incorporation into the design of a commercially-available intracellular electrometer for use in juxtacellular neuronal labelling. Printed circuit board construction has been used for reliability and reproducibility. The current design obviates the need for a separate digital pulse source and simplifies the juxtacellular neuronal labelling procedure.

  15. Neuronal nitric oxide synthase immunopositive neurons in cat vestibular complex: a light and electron microscopic study.

    Science.gov (United States)

    Papantchev, V; Paloff, A; Hinova-Palova, D; Hristov, S; Todorova, D; Ovtscharoff, W

    2006-11-01

    Nitric oxide is a unique neurotransmitter, which participates in many physiological and pathological processes in the organism. Nevertheless, there are little data about the neuronal nitric oxide synthase immunoreactivity (nNOS-ir) in the vestibular complex of a cat. In this respect, the aims of this study were to: (1) demonstrate nNOS-ir in the neurons and fibers, from all major and accessory vestibular nuclei; (2) describe their light microscopic morphology and distribution; (3) investigate and analyze the ultrastructure of the NOS I-immunopositive neurons, fibers, and synaptic boutons. For demonstration of the nNOS-ir, the peroxidase-antiperoxidase-diaminobenzidin method was applied. Immunopositive for nNOS neurons and fibers were present in all major and accessory vestibular nuclei. On the light microscope level, the immunopositive neurons were different in shape and size. According to the latter, they were divided into four groups--small (with diameter less than 15 microm), medium-sized (with diameter from 15 to 30 microm), large type I (with diameter from 30 to 40 microm), and large type II (with diameter greater than 40 microm). On the electron microscope level, the immunoproduct was observed in neurons, dendrites, and terminal boutons. According to the ultrastructural features, the neurons were divided into three groups--small (with diameter less than 15 microm), medium-sized (with diameter from 15 to 30 microm), and large (with diameter greater than 30 microm). At least two types of nNOS-ir synaptic boutons were easily distinguished. As a conclusion, we hope that this study will contribute to a better understanding of the functioning of the vestibular complex in cat and that some of the data presented could be extrapolated to other mammals, including human.

  16. Integrative Mechanisms of Oriented Neuronal Migration in the Developing Brain

    Science.gov (United States)

    Evsyukova, Irina; Plestant, Charlotte; Anton, E.S.

    2014-01-01

    The emergence of functional neuronal connectivity in the developing cerebral cortex depends on neuronal migration. This process enables appropriate positioning of neurons and the emergence of neuronal identity so that the correct patterns of functional synaptic connectivity between the right types and numbers of neurons can emerge. Delineating the complexities of neuronal migration is critical to our understanding of normal cerebral cortical formation and neurodevelopmental disorders resulting from neuronal migration defects. For the most part, the integrated cell biological basis of the complex behavior of oriented neuronal migration within the developing mammalian cerebral cortex remains an enigma. This review aims to analyze the integrative mechanisms that enable neurons to sense environmental guidance cues and translate them into oriented patterns of migration toward defined areas of the cerebral cortex. We discuss how signals emanating from different domains of neurons get integrated to control distinct aspects of migratory behavior and how different types of cortical neurons coordinate their migratory activities within the developing cerebral cortex to produce functionally critical laminar organization. PMID:23937349

  17. Developmental regulation of a local positive autocontrol of supraoptic neurons.

    Science.gov (United States)

    Chevaleyre, V; Dayanithi, G; Moos, F C; Desarmenien, M G

    2000-08-01

    Mature oxytocin (OT) and vasopressin (AVP) magnocellular neurons of the hypothalamic supraoptic nuclei (SON) autocontrol their electrical activity via somatodendritic release of their respective peptides. Because OT and AVP are synthesized early in development and could play an important role in the maturation of these neurons, we checked whether the peptides are released within the SON and act on their secreting neurons during 3 weeks of postnatal development. We used patch-clamp recordings from SON neurons in rat hypothalamic horizontal slices to show that the spontaneous electrical activity of immature SON neurons is blocked by OT or AVP receptor antagonists, demonstrating a basal somatodendritic release of the peptides. Application of OT or AVP depolarizes SON neurons and stimulates activity typical of the corresponding mature neurons. This effect is directly on SON neurons because it is recorded in dissociated neurons. Radioimmunoassays from isolated SON were used to show that each peptide facilitates its own release at a somatodendritic level, exhibiting a self-sustaining positive feedback loop. This autocontrol is not uniform during development because the proportion of neurons depolarized by the peptides, the amplitude of the depolarization, and the propensity of the peptides to facilitate their own release are maximal during the second postnatal week and decrease thereafter. These data are consistent with a role of autocontrol in the maturation of SON neurons because it is maximal during the delimited period of postnatal development that corresponds to the period of major synapse formation.

  18. Gold Nanoparticles for Modulating Neuronal Behavior

    Directory of Open Access Journals (Sweden)

    Chiara Paviolo

    2017-04-01

    Full Text Available Understanding the detailed functioning and pathophysiology of the brain and the nervous system continues to challenge the scientific community, particularly in terms of scaling up techniques for monitoring and interfacing with complex 3D networks. Nanotechnology has the potential to support this scaling up, where the eventual goal would be to address individual nerve cells within functional units of both the central and peripheral nervous system. Gold nanoparticles provide a variety of physical and chemical properties that have attracted attention as a light-activated nanoscale neuronal interface. This review provides a critical overview of the photothermal and photomechanical properties of chemically functionalized gold nanoparticles that have been exploited to trigger a range of biological responses in neuronal tissues, including modulation of electrical activity and nerve regeneration. The prospects and challenges for further development are also discussed.

  19. Axon-soma communication in neuronal injury.

    Science.gov (United States)

    Rishal, Ida; Fainzilber, Mike

    2014-01-01

    The extensive lengths of neuronal processes necessitate efficient mechanisms for communication with the cell body. Neuronal regeneration after nerve injury requires new transcription; thus, long-distance retrograde signalling from axonal lesion sites to the soma and nucleus is required. In recent years, considerable progress has been made in elucidating the mechanistic basis of this system. This has included the discovery of a priming role for early calcium waves; confirmation of central roles for mitogen-activated protein kinase signalling effectors, the importin family of nucleocytoplasmic transport factors and molecular motors such as dynein; and demonstration of the importance of local translation as a key regulatory mechanism. These recent findings provide a coherent mechanistic framework for axon-soma communication in the injured nerve and shed light on the integration of cytoplasmic and nuclear transport in all eukaryotic cells.

  20. Model Reduction of Strong-Weak Neurons

    Directory of Open Access Journals (Sweden)

    Steven James Cox

    2014-12-01

    Full Text Available We consider neurons with large dendritic trees that are weakly excitable in the sense that back propagating action potentials are severly attenuated as they travelfrom the small, strongly excitable, spike initiation zone. In previous workwe have shown that the computational size of weakly excitable cell modelsmay be reduced by two or more orders of magnitude, and that the size of stronglyexcitable models may be reduced by at least one order of magnitude,without sacrificing thespatio-temporal nature of its inputs (in the sense we reproduce the cell's precise mapping of inputs to outputs. We combine the best of these twostrategies via a predictor--corrector decomposition scheme andachieve a drastically reduced highly accurate model of a caricature of the neuron responsible for collision detection in the locust.

  1. Model reduction of strong-weak neurons.

    Science.gov (United States)

    Du, Bosen; Sorensen, Danny; Cox, Steven J

    2014-01-01

    We consider neurons with large dendritic trees that are weakly excitable in the sense that back propagating action potentials are severly attenuated as they travel from the small, strongly excitable, spike initiation zone. In previous work we have shown that the computational size of weakly excitable cell models may be reduced by two or more orders of magnitude, and that the size of strongly excitable models may be reduced by at least one order of magnitude, without sacrificing the spatio-temporal nature of its inputs (in the sense we reproduce the cell's precise mapping of inputs to outputs). We combine the best of these two strategies via a predictor-corrector decomposition scheme and achieve a drastically reduced highly accurate model of a caricature of the neuron responsible for collision detection in the locust.

  2. The buzz on fly neuronal remodeling.

    Science.gov (United States)

    Hewes, Randall S

    2008-11-01

    Hormone-dependent rewiring of axons and dendrites is a conserved feature of nervous system development and plasticity. During metamorphosis in insects, steroid hormones (the ecdysteroids) and terpenoid hormones (the juvenile hormones) regulate extensive remodeling of the nervous system. These changes retool the nervous system for new behavioral and physiological functions that are required for the adult stage of the life cycle. In honey bees and other highly social insects, hormones also regulate behavioral changes and neuronal plasticity associated with transitions between social caste roles. This review focuses on recent work in fruit flies and honey bees that reveals hormonal and molecular mechanisms underlying metamorphic and caste-dependent neuronal remodeling, with specific emphasis on the role of Krüppel homolog 1.

  3. Choline acetyltransferase-containing neurons in the human parietal neocortex

    Directory of Open Access Journals (Sweden)

    V Benagiano

    2009-06-01

    Full Text Available A number of immunocytochemical studies have indicated the presence of cholinergic neurons in the cerebral cortex of various species of mammals. Whether such cholinergic neurons in the human cerebral cortex are exclusively of subcortical origin is still debated. In this immunocytochemical study, the existence of cortical cholinergic neurons was investigated on surgical samples of human parietal association neocortex using a highly specific monoclonal antibody against choline acetyltransferase (ChAT, the acetylcholine biosynthesising enzyme. ChAT immunoreactivity was detected in a subpopulation of neurons located in layers II and III. These were small or medium-sized pyramidal neurons which showed cytoplasmic immunoreactivity in the perikarya and processes, often in close association to blood microvessels. This study, providing demonstration of ChAT neurons in the human parietal neocortex, strongly supports the existence of intrinsic cholinergic innervation of the human neocortex. It is likely that these neurons contribute to the cholinergic innervation of the intracortical microvessels.

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

    Science.gov (United States)

    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

  5. Regulation of Irregular Neuronal Firing by Autaptic Transmission

    Science.gov (United States)

    Guo, Daqing; Wu, Shengdun; Chen, Mingming; Perc, Matjaž; Zhang, Yangsong; Ma, Jingling; Cui, Yan; Xu, Peng; Xia, Yang; Yao, Dezhong

    2016-05-01

    The importance of self-feedback autaptic transmission in modulating spike-time irregularity is still poorly understood. By using a biophysical model that incorporates autaptic coupling, we here show that self-innervation of neurons participates in the modulation of irregular neuronal firing, primarily by regulating the occurrence frequency of burst firing. In particular, we find that both excitatory and electrical autapses increase the occurrence of burst firing, thus reducing neuronal firing regularity. In contrast, inhibitory autapses suppress burst firing and therefore tend to improve the regularity of neuronal firing. Importantly, we show that these findings are independent of the firing properties of individual neurons, and as such can be observed for neurons operating in different modes. Our results provide an insightful mechanistic understanding of how different types of autapses shape irregular firing at the single-neuron level, and they highlight the functional importance of autaptic self-innervation in taming and modulating neurodynamics.

  6. Edge-orientation processing in first-order tactile neurons.

    Science.gov (United States)

    Pruszynski, J Andrew; Johansson, Roland S

    2014-10-01

    A fundamental feature of first-order neurons in the tactile system is that their distal axon branches in the skin and forms many transduction sites, yielding complex receptive fields with many highly sensitive zones. We found that this arrangement constitutes a peripheral neural mechanism that allows individual neurons to signal geometric features of touched objects. Specifically, we observed that two types of first-order tactile neurons that densely innervate the glabrous skin of the human fingertips signaled edge orientation via both the intensity and the temporal structure of their responses. Moreover, we found that the spatial layout of a neuron's highly sensitive zones predicted its sensitivity to particular edge orientations. We submit that peripheral neurons in the touch-processing pathway, as with peripheral neurons in the visual-processing pathway, perform feature extraction computations that are typically attributed to neurons in the cerebral cortex.

  7. Bidirectional Anticipation of Future Osmotic Challenges by Vasopressin Neurons.

    Science.gov (United States)

    Mandelblat-Cerf, Yael; Kim, Angela; Burgess, Christian R; Subramanian, Siva; Tannous, Bakhos A; Lowell, Bradford B; Andermann, Mark L

    2017-01-04

    Ingestion of water and food are major hypo- and hyperosmotic challenges. To protect the body from osmotic stress, posterior pituitary-projecting, vasopressin-secreting neurons (VPpp neurons) counter osmotic perturbations by altering their release of vasopressin, which controls renal water excretion. Vasopressin levels begin to fall within minutes of water consumption, even prior to changes in blood osmolality. To ascertain the precise temporal dynamics by which water or food ingestion affect VPpp neuron activity, we directly recorded the spiking and calcium activity of genetically defined VPpp neurons. In states of elevated osmolality, water availability rapidly decreased VPpp neuron activity within seconds, beginning prior to water ingestion, upon presentation of water-predicting cues. In contrast, food availability following food restriction rapidly increased VPpp neuron activity within seconds, but only following feeding onset. These rapid and distinct changes in activity during drinking and feeding suggest diverse neural mechanisms underlying anticipatory regulation of VPpp neurons. Published by Elsevier Inc.

  8. Mapping extracellular excitability in an insect mechanoreceptor neuron.

    Science.gov (United States)

    Torkkeli, P H; French, A S

    1993-12-31

    The cockroach tactile spine contains a single bipolar mechanosensory neuron. Extracellular stimulation of the neuron is possible by cutting the spine and lowering a microelectrode into the lumen, where the neuron is located, but neither the microelectrode nor the neuron can be visualized during stimulation. The threshold for electrical stimulation of the neuron was measured as a function of spatial position in the lumen. The spine was then fixed and serially sectioned for computer-aided reconstruction. Alignment of threshold measurements with reconstructions produced maps of excitability around the neuron. The lowest threshold was always close to the sensory dendrite or the adjacent soma. These results are discussed in terms of models of action potential initiation in this class of sensory neurons.

  9. Neuronal encoding of the switch from specific to generalized fear.

    Science.gov (United States)

    Ghosh, Supriya; Chattarji, Sumantra

    2015-01-01

    Fear memories are crucial for survival. However, excessive generalization of such memories, characterized by a failure to discriminate dangerous from safe stimuli, is common in anxiety disorders. Neuronal encoding of the transition from cue-specific to generalized fear is poorly understood. We identified distinct neuronal populations in the lateral amygdala (LA) of rats that signaled generalized versus cue-specific associations and determined how their distributions switched during fear generalization. Notably, the same LA neurons that were cue specific before the behavioral shift to generalized fear lost their specificity afterwards, thereby tilting the balance of activity toward a greater proportion of generalizing neurons. Neuronal activity in the LA, but not the auditory cortex, was necessary for fear generalization. Furthermore, targeted activation of cAMP-PKA signaling in the LA increased neuronal excitability of LA neurons and led to generalized fear. These results provide a cellular basis in the amygdala for the alteration of emotional states from normal to pathological fear.

  10. Serotonergic neurons signal reward and punishment on multiple timescales.

    Science.gov (United States)

    Cohen, Jeremiah Y; Amoroso, Mackenzie W; Uchida, Naoshige

    2015-02-25

    Serotonin's function in the brain is unclear. One challenge in testing the numerous hypotheses about serotonin's function has been observing the activity of identified serotonergic neurons in animals engaged in behavioral tasks. We recorded the activity of dorsal raphe neurons while mice experienced a task in which rewards and punishments varied across blocks of trials. We 'tagged' serotonergic neurons with the light-sensitive protein channelrhodopsin-2 and identified them based on their responses to light. We found three main features of serotonergic neuron activity: (1) a large fraction of serotonergic neurons modulated their tonic firing rates over the course of minutes during reward vs punishment blocks; (2) most were phasically excited by punishments; and (3) a subset was phasically excited by reward-predicting cues. By contrast, dopaminergic neurons did not show firing rate changes across blocks of trials. These results suggest that serotonergic neurons signal information about reward and punishment on multiple timescales.

  11. Exocytosis in non-neuronal cells.

    Science.gov (United States)

    Thorn, Peter; Zorec, Robert; Rettig, Jens; Keating, Damien J

    2016-06-01

    Exocytosis is the process by which stored neurotransmitters and hormones are released via the fusion of secretory vesicles with the plasma membrane. It is a dynamic, rapid and spatially restricted process involving multiple steps including vesicle trafficking, tethering, docking, priming and fusion. For many years great steps have been undertaken in our understanding of how exocytosis occurs in different cell types, with significant focus being placed on synaptic release and neurotransmission. However, this process of exocytosis is an essential component of cell signalling throughout the body and underpins a diverse array of essential physiological pathways. Many similarities exist between different cell types with regard to key aspects of the exocytosis pathway, such as the need for Ca(2+) to trigger it or the involvement of members of the N-ethyl maleimide-sensitive fusion protein attachment protein receptor protein families. However, it is also equally clear that non-neuronal cells have acquired highly specialized mechanisms to control the release of their own unique chemical messengers. This review will focus on several important non-neuronal cell types and discuss what we know about the mechanisms they use to control exocytosis and how their specialized output is relevant to the physiological role of each individual cell type. These include enteroendocrine cells, pancreatic β cells, astrocytes, lactotrophs and cytotoxic T lymphocytes. Non-neuronal cells have acquired highly specialized mechanisms to control the release of unique chemical messengers, such as polarised fusion of insulin granules in pancreatic β cells targeted towards the vasculature (top). This review discusses mechanisms used in several important non-neuronal cell types to control exocytosis, and the relevance of intermediate vesicle fusion pore states (bottom) and their specialized output to the physiological role of each cell type. These include enteroendocrine cells, pancreatic β cells

  12. Associative memory in phasing neuron networks

    Energy Technology Data Exchange (ETDEWEB)

    Nair, Niketh S [ORNL; Bochove, Erik J. [United States Air Force Research Laboratory, Kirtland Air Force Base; Braiman, Yehuda [ORNL

    2014-01-01

    We studied pattern formation in a network of coupled Hindmarsh-Rose model neurons and introduced a new model for associative memory retrieval using networks of Kuramoto oscillators. Hindmarsh-Rose Neural Networks can exhibit a rich set of collective dynamics that can be controlled by their connectivity. Specifically, we showed an instance of Hebb's rule where spiking was correlated with network topology. Based on this, we presented a simple model of associative memory in coupled phase oscillators.

  13. Coping with Variability in Small Neuronal Networks

    OpenAIRE

    Calabrese, Ronald L.; Norris, Brian J.; Wenning, Angela; Wright, Terrence M.

    2011-01-01

    Experimental and corresponding modeling studies indicate that there is a 2- to 5-fold variation of intrinsic and synaptic parameters across animals while functional output is maintained. Here, we review experiments, using the heartbeat central pattern generator (CPG) in medicinal leeches, which explore the consequences of animal-to-animal variation in synaptic strength for coordinated motor output. We focus on a set of segmental heart motor neurons that all receive inhibitory synaptic input f...

  14. Daidzein induces neuritogenesis in DRG neuronal cultures

    OpenAIRE

    Yang Shih-Hung; Liao Chih-Chen; Chen Ying; Syu Jhih-Pu; Jeng Chung-Jiuan; Wang Seu-Mei

    2012-01-01

    Absract Background Daidzein, a phytoestrogen found in isoflavone, is known to exert neurotrophic and neuroprotective effects on the nervous system. Using primary rat dorsal root ganglion (DRG) neuronal cultures, we have examined the potential neurite outgrowth effect of daidzein. Methods Dissociated dorsal root ganglia (DRG) cultures were used to study the signaling mechanism of daidzein-induced neuritogenesis by immunocytochemistry and Western blotting. Results In response to daidzein treatm...

  15. Towards Reproducible Descriptions of Neuronal Network Models

    Science.gov (United States)

    Nordlie, Eilen; Gewaltig, Marc-Oliver; Plesser, Hans Ekkehard

    2009-01-01

    Progress in science depends on the effective exchange of ideas among scientists. New ideas can be assessed and criticized in a meaningful manner only if they are formulated precisely. This applies to simulation studies as well as to experiments and theories. But after more than 50 years of neuronal network simulations, we still lack a clear and common understanding of the role of computational models in neuroscience as well as established practices for describing network models in publications. This hinders the critical evaluation of network models as well as their re-use. We analyze here 14 research papers proposing neuronal network models of different complexity and find widely varying approaches to model descriptions, with regard to both the means of description and the ordering and placement of material. We further observe great variation in the graphical representation of networks and the notation used in equations. Based on our observations, we propose a good model description practice, composed of guidelines for the organization of publications, a checklist for model descriptions, templates for tables presenting model structure, and guidelines for diagrams of networks. The main purpose of this good practice is to trigger a debate about the communication of neuronal network models in a manner comprehensible to humans, as opposed to machine-readable model description languages. We believe that the good model description practice proposed here, together with a number of other recent initiatives on data-, model-, and software-sharing, may lead to a deeper and more fruitful exchange of ideas among computational neuroscientists in years to come. We further hope that work on standardized ways of describing—and thinking about—complex neuronal networks will lead the scientific community to a clearer understanding of high-level concepts in network dynamics, and will thus lead to deeper insights into the function of the brain. PMID:19662159

  16. Neurons as an Information-theoretic Engine

    OpenAIRE

    Shimazaki, Hideaki

    2015-01-01

    We show that dynamical gain modulation of neurons' stimulus response is described as an information-theoretic cycle that generates entropy associated with the stimulus-related activity from entropy produced by the modulation. To articulate this theory, we describe stimulus-evoked activity of a neural population based on the maximum entropy principle with constraints on two types of overlapping activities, one that is controlled by stimulus conditions and the other, termed internal activity, t...

  17. System identification of Drosophila olfactory sensory neurons

    OpenAIRE

    Kim, Anmo J.; Lazar, Aurel A.; Slutskiy, Yevgeniy B.

    2010-01-01

    The lack of a deeper understanding of how olfactory sensory neurons (OSNs) encode odors has hindered the progress in understanding the olfactory signal processing in higher brain centers. Here we employ methods of system identification to investigate the encoding of time-varying odor stimuli and their representation for further processing in the spike domain by Drosophila OSNs. In order to apply system identification techniques, we built a novel low-turbulence odor delivery system that allowe...

  18. Effects of Hallucinogens on Neuronal Activity.

    Science.gov (United States)

    Lladó-Pelfort, L; Celada, P; Riga, M S; Troyano-Rodríguez, E; Santana, N; Artigas, F

    2017-02-26

    Hallucinogens evoke sensory, perceptual, affective, and cognitive effects that may be useful to understand the neurobiological basis of mood and psychotic disorders. The present chapter reviews preclinical research carried out in recent years in order to better understand the action of psychotomimetic agents such as the noncompetitive NMDA receptor (NMDA-R) antagonists and serotonergic hallucinogens. Our studies have focused on the mechanisms through which these agents alter cortical activity. Noncompetitive NMDA-R antagonists, such as phencyclidine (PCP) and MK-801 (dizocilpine), as well as the serotonergic hallucinogens DOI and 5-MeO-DMT, produce similar effects on cellular and population activity in prefrontal cortex (PFC); these effects include alterations of pyramidal neuron discharge (with an overall increase in firing), as well as a marked attenuation of the low frequency oscillations (0.2-4 Hz) to which neuronal discharge is coupled in anesthetized rodents. PCP increases c-fos expression in excitatory neurons from various cortical and subcortical areas, particularly the thalamus. This effect of PCP involves the preferential blockade of NMDA-R on GABAergic neurons of the reticular nucleus of the thalamus, which provides feedforward inhibition to the rest of thalamic nuclei. It is still unknown whether serotonergic hallucinogens also affect thalamocortical networks. However, when examined, similar alterations in other cortical areas, such as the primary visual cortex (V1), have been observed, suggesting that these agents affect cortical activity in sensory and associative areas. Interestingly, the disruption of PFC activity induced by PCP, DOI and 5-MeO-DMT is reversed by classical and atypical antipsychotic drugs. This effect suggests a possible link between the mechanisms underlying the disruption of perception by multiple classes of hallucinogenic agents and the therapeutic efficacy of antipsychotic agents.

  19. Towards reproducible descriptions of neuronal network models.

    Directory of Open Access Journals (Sweden)

    Eilen Nordlie

    2009-08-01

    Full Text Available Progress in science depends on the effective exchange of ideas among scientists. New ideas can be assessed and criticized in a meaningful manner only if they are formulated precisely. This applies to simulation studies as well as to experiments and theories. But after more than 50 years of neuronal network simulations, we still lack a clear and common understanding of the role of computational models in neuroscience as well as established practices for describing network models in publications. This hinders the critical evaluation of network models as well as their re-use. We analyze here 14 research papers proposing neuronal network models of different complexity and find widely varying approaches to model descriptions, with regard to both the means of description and the ordering and placement of material. We further observe great variation in the graphical representation of networks and the notation used in equations. Based on our observations, we propose a good model description practice, composed of guidelines for the organization of publications, a checklist for model descriptions, templates for tables presenting model structure, and guidelines for diagrams of networks. The main purpose of this good practice is to trigger a debate about the communication of neuronal network models in a manner comprehensible to humans, as opposed to machine-readable model description languages. We believe that the good model description practice proposed here, together with a number of other recent initiatives on data-, model-, and software-sharing, may lead to a deeper and more fruitful exchange of ideas among computational neuroscientists in years to come. We further hope that work on standardized ways of describing--and thinking about--complex neuronal networks will lead the scientific community to a clearer understanding of high-level concepts in network dynamics, and will thus lead to deeper insights into the function of the brain.

  20. Presynaptic calcium dynamics of learning neurons

    OpenAIRE

    Meyer-Hermann, Michael; Erler, Frido; Soff, Gerhard

    2002-01-01

    We present a new model for the dynamics of the presynaptic intracellular calcium concentration in neurons evoked by various stimulation protocols. The aim of the model is twofold: We want to discuss the calcium transients during and after specific stimulation protocols as they are used to induce long-term-depression and long-term-potentiation. In addition we would like to provide a general tool which allows the comparison of different calcium experiments. This may help to draw conclusions on ...

  1. Sensory neurons : Stem cells and development

    OpenAIRE

    Hjerling-Leffler, Jens

    2006-01-01

    The sensory nervous system is the only means we have of communicating with the surrounding world. The neurons responsible for the sensation of pain, touch, the ability to know the position of our limbs and part of maintenance of body posture are located in the dorsal root ganglia (DRG). Stem cell biology has, during the recent years greatly enhanced our understanding of developmental processes. The aim of this thesis was to isolate and characterize stem cells from the sensor...

  2. Turning neurons into a nervous system.

    Science.gov (United States)

    Grove, Elizabeth A

    2008-07-01

    The RIKEN Center for Developmental Biology recently held its 2008 Symposium ;Turning Neurons into a Nervous System' in Kobe, Japan. The program, organized by Masatoshi Takeichi, Joshua Sanes, Hideki Enomoto and Raj Ladher, provided a rich sampling from current work in developmental neurobiology. Researchers from Japan, Europe and the USA gathered at this meeting to share insights into neural development and to admire the opening of the cherry blossom season.

  3. Early steps toward understanding neuronal communication.

    Science.gov (United States)

    Snyder, Adam C; Smith, Matthew A

    2017-10-25

    The computational power of the brain arises from the complex interactions between neurons. One straightforward method to quantify the strength of neuronal interactions is by measuring correlation and coherence. Efforts to measure correlation have been advancing rapidly of late, spurred by the development of advanced recording technologies enabling recording from many neurons and brain areas simultaneously. This review highlights recent results that provide clues into the principles of neural coordination, connections to cognitive and neurological phenomena, and key directions for future research. The correlation structure of neural activity in the brain has important consequences for the encoding properties of neural populations. Recent studies have shown that this correlation structure is not fixed, but adapts in a variety of contexts in ways that appear beneficial to task performance. By studying these changes in biological neural networks and computational models, researchers have improved our understanding of the principles guiding neural communication. Correlation and coherence are highly informative metrics for studying coding and communication in the brain. Recent findings have emphasized how the brain modifies correlation structure dynamically in order to improve information-processing in a goal-directed fashion. One key direction for future research concerns how to leverage these dynamic changes for therapeutic purposes.

  4. Necrostatin-1 protection of dopaminergic neurons

    Directory of Open Access Journals (Sweden)

    Jing-ru Wu

    2015-01-01

    Full Text Available Necroptosis is characterized by programmed necrotic cell death and autophagic activation and might be involved in the death process of dopaminergic neurons in Parkinson′s disease. We hypothesized that necrostatin-1 could block necroptosis and give protection to dopaminergic neurons. There is likely to be crosstalk between necroptosis and other cell death pathways, such as apoptosis and autophagy. PC12 cells were pretreated with necroststin-1 1 hour before exposure to 6-hydroxydopamine. We examined cell viability, mitochondrial membrane potential and expression patterns of apoptotic and necroptotic death signaling proteins. The results showed that the autophagy/lysosomal pathway is involved in the 6-hydroxydopamine-induced death process of PC12 cells. Mitochondrial disability induced overactive autophagy, increased cathepsin B expression, and diminished Bcl-2 expression. Necrostatin-1 within a certain concentration range (5-30 μM elevated the viability of PC12 cells, stabilized mitochondrial membrane potential, inhibited excessive autophagy, reduced the expression of LC3-II and cathepsin B, and increased Bcl-2 expression. These findings suggest that necrostatin-1 exerted a protective effect against injury on dopaminergic neurons. Necrostatin-1 interacts with the apoptosis signaling pathway during this process. This pathway could be a new neuroprotective and therapeutic target in Parkinson′s disease.

  5. Neuronal sensitivity to tetanus toxin requires gangliosides.

    Science.gov (United States)

    Williamson, L C; Bateman, K E; Clifford, J C; Neale, E A

    1999-08-27

    Tetanus toxin produces spastic paralysis in situ by blocking inhibitory neurotransmitter release in the spinal cord. Although di- and trisialogangliosides bind tetanus toxin, their role as productive toxin receptors remains unclear. We examined toxin binding and action in spinal cord cell cultures grown in the presence of fumonisin B(1), an inhibitor of ganglioside synthesis. Mouse spinal cord neurons grown for 3 weeks in culture in 20 microM fumonisin B(1) develop dendrites, axons, and synaptic terminals similar to untreated neurons, even though thin layer chromatography shows a greater than 90% inhibition of ganglioside synthesis. Absence of tetanus and cholera toxin binding by toxin-horseradish peroxidase conjugates or immunofluorescence further indicates loss of mono- and polysialogangliosides. In contrast to control cultures, tetanus toxin added to fumonisin B(1)-treated cultures does not block potassium-stimulated glycine release, inhibit activity-dependent uptake of FM1-43, or abolish immunoreactivity for vesicle-associated membrane protein, the toxin substrate. Supplementing fumonisin B(1)-treated cultures with mixed brain gangliosides completely restores the ability of tetanus toxin to bind to the neuronal surface and to block neurotransmitter release. These data demonstrate that fumonisin B(1) protects against toxin-induced synaptic blockade and that gangliosides are a necessary component of the receptor mechanism for tetanus toxin.

  6. [Brain and memory: new neurons to remember].

    Science.gov (United States)

    Gros, Alexandra; Veyrac, Alexandra; Laroche, Serge

    2015-01-01

    A defining characteristic of the brain is its remarkable capacity to undergo activity-dependent functional and structural remodelling via mechanisms of plasticity that form the basis of our capacity to encode and retain memories. The prevailing model of how our brain stores new information about relationships between events or new abstract constructs suggests it resides in activity-driven modifications of synaptic strength and remodelling of neural networks brought about by cellular and molecular changes within the neurons activated during learning. To date, the idea that a form of activity-dependent synaptic plasticity known as long-term potentiation, or LTP, and the associated synaptic growth play a central role in the laying down of memories has received considerable support. Beyond this mechanism of plasticity at the synapse, adult neurogenesis, i.e. the birth and growth of new neurons, is another form of neural plasticity that occurs continuously in defined brain regions such as the dentate gyrus of the hippocampus. Here, based on work in the hippocampus, we review the processes and mechanisms of the generation and selection of new neurons in the adult brain and the accumulating evidence that supports the idea that this form of neural plasticity is essential to store and lead to retrievable hippocampal-dependent memories. © Société de Biologie, 2016.

  7. Transcriptional profiling of fetal hypothalamic TRH neurons.

    Science.gov (United States)

    Guerra-Crespo, Magdalena; Pérez-Monter, Carlos; Janga, Sarath Chandra; Castillo-Ramírez, Santiago; Gutiérrez-Rios, Rosa María; Joseph-Bravo, Patricia; Pérez-Martínez, Leonor; Charli, Jean-Louis

    2011-05-10

    During murine hypothalamic development, different neuroendocrine cell phenotypes are generated in overlapping periods; this suggests that cell-type specific developmental programs operate to achieve complete maturation. A balance between programs that include cell proliferation, cell cycle withdrawal as well as epigenetic regulation of gene expression characterizes neurogenesis. Thyrotropin releasing hormone (TRH) is a peptide that regulates energy homeostasis and autonomic responses. To better understand the molecular mechanisms underlying TRH neuron development, we performed a genome wide study of its transcriptome during fetal hypothalamic development. In primary cultures, TRH cells constitute 2% of the total fetal hypothalamic cell population. To purify these cells, we took advantage of the fact that the segment spanning -774 to +84 bp of the Trh gene regulatory region confers specific expression of the green fluorescent protein (GFP) in the TRH cells. Transfected TRH cells were purified by fluorescence activated cell sorting, various cell preparations pooled, and their transcriptome compared to that of GFP- hypothalamic cells. TRH cells undergoing the terminal phase of differentiation, expressed genes implicated in protein biosynthesis, intracellular signaling and transcriptional control. Among the transcription-associated transcripts, we identified the transcription factors Klf4, Klf10 and Atf3, which were previously uncharacterized within the hypothalamus. To our knowledge, this is one of the first reports identifying transcripts with a potentially important role during the development of a specific hypothalamic neuronal phenotype. This genome-scale study forms a rational foundation for identifying genes that might participate in the development and function of hypothalamic TRH neurons.

  8. Visualization of cyclic nucleotide dynamics in neurons

    Directory of Open Access Journals (Sweden)

    Kirill eGorshkov

    2014-12-01

    Full Text Available The second messengers cAMP and cGMP transduce many neuromodulatory signals from hormones and neurotransmitters into specific functional outputs. Their production, degradation and signaling are spatiotemporally regulated to achieve high specificity in signal transduction. The development of genetically encodable fluorescent biosensors has provided researchers with useful tools to study these versatile second messengers and their downstream effectors with unparalleled spatial and temporal resolution in cultured cells and living animals. In this review, we introduce the general design of these fluorescent biosensors and describe several of them in more detail. Then we discuss a few examples of using cyclic nucleotide fluorescent biosensors to study regulation of neuronal function and finish with a discussion of advances in the field. Although there has been significant progress made in understanding how the specific signaling of cyclic nucleotide second messengers is achieved, the mechanistic details in complex cell types like neurons are only just beginning to surface. Current and future fluorescent protein reporters will be essential to elucidate the role of cyclic nucleotide signaling dynamics in the functions of individual neurons and their networks.

  9. Identification of Rat Ventral Tegmental Area GABAergic Neurons

    Science.gov (United States)

    Margolis, Elyssa B.; Toy, Brian; Himmels, Patricia; Morales, Marisela; Fields, Howard L.

    2012-01-01

    The canonical two neuron model of opioid reward posits that mu opioid receptor (MOR) activation produces reward by disinhibiting midbrain ventral tegmental area (VTA) dopamine neurons through inhibition of local GABAergic interneurons. Although indirect evidence supports the neural circuit postulated by this model, its validity has been called into question by growing evidence for VTA neuronal heterogeneity and the recent demonstration that MOR agonists inhibit GABAergic terminals in the VTA arising from extrinsic neurons. In addition, VTA MOR reward can be dopamine-independent. To directly test the assumption that MOR activation directly inhibits local GABAergic neurons, we investigated the properties of rat VTA GABA neurons directly identified with either immunocytochemistry for GABA or GAD65/67, or in situ hybridization for GAD65/67 mRNA. Utilizing co-labeling with an antibody for the neural marker NeuN and in situ hybridization against GAD65/67, we found that 23±3% of VTA neurons are GAD65/67(+). In contrast to the assumptions of the two neuron model, VTA GABAergic neurons are heterogeneous, both physiologically and pharmacologically. Importantly, only 7/13 confirmed VTA GABA neurons were inhibited by the MOR selective agonist DAMGO. Interestingly, all confirmed VTA GABA neurons were insensitive to the GABAB receptor agonist baclofen (0/6 inhibited), while all confirmed dopamine neurons were inhibited (19/19). The heterogeneity of opioid responses we found in VTA GABAergic neurons, and the fact that GABA terminals arising from neurons outside the VTA are inhibited by MOR agonists, make further studies essential to determine the local circuit mechanisms underlying VTA MOR reward. PMID:22860119

  10. Dynamics of Phosphoinositide-Dependent Signaling in Sympathetic Neurons

    Science.gov (United States)

    Kruse, Martin; Vivas, Oscar; Traynor-Kaplan, Alexis

    2016-01-01

    In neurons, loss of plasma membrane phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] leads to a decrease in exocytosis and changes in electrical excitability. Restoration of PI(4,5)P2 levels after phospholipase C activation is therefore essential for a return to basal neuronal activity. However, the dynamics of phosphoinositide metabolism have not been analyzed in neurons. We measured dynamic changes of PI(4,5)P2, phosphatidylinositol 4-phosphate, diacylglycerol, inositol 1,4,5-trisphosphate, and Ca2+ upon muscarinic stimulation in sympathetic neurons from adult male Sprague-Dawley rats with electrophysiological and optical approaches. We used this kinetic information to develop a quantitative description of neuronal phosphoinositide metabolism. The measurements and analysis show and explain faster synthesis of PI(4,5)P2 in sympathetic neurons than in electrically nonexcitable tsA201 cells. They can be used to understand dynamic effects of receptor-mediated phospholipase C activation on excitability and other PI(4,5)P2-dependent processes in neurons. SIGNIFICANCE STATEMENT Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is a minor phospholipid in the cytoplasmic leaflet of the plasma membrane. Depletion of PI(4,5)P2 via phospholipase C-mediated hydrolysis leads to a decrease in exocytosis and alters electrical excitability in neurons. Restoration of PI(4,5)P2 is essential for a return to basal neuronal activity. However, the dynamics of phosphoinositide metabolism have not been analyzed in neurons. We studied the dynamics of phosphoinositide metabolism in sympathetic neurons upon muscarinic stimulation and used the kinetic information to develop a quantitative description of neuronal phosphoinositide metabolism. The measurements and analysis show a several-fold faster synthesis of PI(4,5)P2 in sympathetic neurons than in an electrically nonexcitable cell line, and provide a framework for future studies of PI(4,5)P2-dependent processes in neurons. PMID:26818524

  11. Automatically tracking neurons in a moving and deforming brain.

    Directory of Open Access Journals (Sweden)

    Jeffrey P Nguyen

    2017-05-01

    Full Text Available Advances in optical neuroimaging techniques now allow neural activity to be recorded with cellular resolution in awake and behaving animals. Brain motion in these recordings pose a unique challenge. The location of individual neurons must be tracked in 3D over time to accurately extract single neuron activity traces. Recordings from small invertebrates like C. elegans are especially challenging because they undergo very large brain motion and deformation during animal movement. Here we present an automated computer vision pipeline to reliably track populations of neurons with single neuron resolution in the brain of a freely moving C. elegans undergoing large motion and deformation. 3D volumetric fluorescent images of the animal's brain are straightened, aligned and registered, and the locations of neurons in the images are found via segmentation. Each neuron is then assigned an identity using a new time-independent machine-learning approach we call Neuron Registration Vector Encoding. In this approach, non-rigid point-set registration is used to match each segmented neuron in each volume with a set of reference volumes taken from throughout the recording. The way each neuron matches with the references defines a feature vector which is clustered to assign an identity to each neuron in each volume. Finally, thin-plate spline interpolation is used to correct errors in segmentation and check consistency of assigned identities. The Neuron Registration Vector Encoding approach proposed here is uniquely well suited for tracking neurons in brains undergoing large deformations. When applied to whole-brain calcium imaging recordings in freely moving C. elegans, this analysis pipeline located 156 neurons for the duration of an 8 minute recording and consistently found more neurons more quickly than manual or semi-automated approaches.

  12. How neurons migrate: a dynamic in-silico model of neuronal migration in the developing cortex

    LENUS (Irish Health Repository)

    Setty, Yaki

    2011-09-30

    Abstract Background Neuronal migration, the process by which neurons migrate from their place of origin to their final position in the brain, is a central process for normal brain development and function. Advances in experimental techniques have revealed much about many of the molecular components involved in this process. Notwithstanding these advances, how the molecular machinery works together to govern the migration process has yet to be fully understood. Here we present a computational model of neuronal migration, in which four key molecular entities, Lis1, DCX, Reelin and GABA, form a molecular program that mediates the migration process. Results The model simulated the dynamic migration process, consistent with in-vivo observations of morphological, cellular and population-level phenomena. Specifically, the model reproduced migration phases, cellular dynamics and population distributions that concur with experimental observations in normal neuronal development. We tested the model under reduced activity of Lis1 and DCX and found an aberrant development similar to observations in Lis1 and DCX silencing expression experiments. Analysis of the model gave rise to unforeseen insights that could guide future experimental study. Specifically: (1) the model revealed the possibility that under conditions of Lis1 reduced expression, neurons experience an oscillatory neuron-glial association prior to the multipolar stage; and (2) we hypothesized that observed morphology variations in rats and mice may be explained by a single difference in the way that Lis1 and DCX stimulate bipolar motility. From this we make the following predictions: (1) under reduced Lis1 and enhanced DCX expression, we predict a reduced bipolar migration in rats, and (2) under enhanced DCX expression in mice we predict a normal or a higher bipolar migration. Conclusions We present here a system-wide computational model of neuronal migration that integrates theory and data within a precise

  13. PDF neuron firing phase-shifts key circadian activity neurons in Drosophila.

    Science.gov (United States)

    Guo, Fang; Cerullo, Isadora; Chen, Xiao; Rosbash, Michael

    2014-06-17

    Our experiments address two long-standing models for the function of the Drosophila brain circadian network: a dual oscillator model, which emphasizes the primacy of PDF-containing neurons, and a cell-autonomous model for circadian phase adjustment. We identify five different circadian (E) neurons that are a major source of rhythmicity and locomotor activity. Brief firing of PDF cells at different times of day generates a phase response curve (PRC), which mimics a light-mediated PRC and requires PDF receptor expression in the five E neurons. Firing also resembles light by causing TIM degradation in downstream neurons. Unlike light however, firing-mediated phase-shifting is CRY-independent and exploits the E3 ligase component CUL-3 in the early night to degrade TIM. Our results suggest that PDF neurons integrate light information and then modulate the phase of E cell oscillations and behavioral rhythms. The results also explain how fly brain rhythms persist in constant darkness and without CRY.

  14. An FPGA-based silicon neuronal network with selectable excitability silicon neurons

    Directory of Open Access Journals (Sweden)

    Jing eLi

    2012-12-01

    Full Text Available This paper presents a digital silicon neuronal network which simulates the nerve system in creatures and has the ability to execute intelligent tasks, such as associative memory. Two essential elements, the mathematical-structure-based digital spiking silicon neuron (DSSN and the transmitter release based silicon synapse, allow the network to show rich dynamic behaviors and are computationally efficient for hardware implementation. We adopt mixed pipeline and parallel structure and shift operations to design a sufficient large and complex network without excessive hardware resource cost. The network with $256$ full-connected neurons is built on a Digilent Atlys board equipped with a Xilinx Spartan-6 LX45 FPGA. Besides, a memory control block and USB control block are designed to accomplish the task of data communication between the network and the host PC. This paper also describes the mechanism of associative memory performed in the silicon neuronal network. The network is capable of retrieving stored patterns if the inputs contain enough information of them. The retrieving probability increases with the similarity between the input and the stored pattern increasing. Synchronization of neurons is observed when the successful stored pattern retrieval occurs.

  15. Human von Economo neurons express transcription factors associated with Layer V subcerebral projection neurons.

    Science.gov (United States)

    Cobos, Inma; Seeley, William W

    2015-01-01

    The von Economo neurons (VENs) are large bipolar Layer V projection neurons found chiefly in the anterior cingulate and frontoinsular cortices. Although VENs have been linked to prevalent illnesses such as frontotemporal dementia, autism, and schizophrenia, little is known about VEN identity, including their major projection targets. Here, we undertook a developmental transcription factor expression study, focusing on markers associated with specific classes of Layer V projection neurons. Using mRNA in situ hybridization, we found that VENs prominently express FEZF2 and CTIP2, transcription factors that regulate the fate and differentiation of subcerebral projection neurons, in humans aged 3 months to 65 years. In contrast, few VENs expressed markers associated with callosal or corticothalamic projections. These findings suggest that VENs may represent a specialized Layer V projection neuron for linking cortical autonomic control sites to brainstem or spinal cord regions. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Connectivity and dynamics of neuronal networks as defined by the shape of individual neurons

    Science.gov (United States)

    Ahnert, Sebastian E.; Travençolo, Bruno A. N.; da Fontoura Costa, Luciano

    2009-10-01

    Biological neuronal networks constitute a special class of dynamical systems, as they are formed by individual geometrical components, namely the neurons. In the existing literature, relatively little attention has been given to the influence of neuron shape on the overall connectivity and dynamics of the emerging networks. The current work addresses this issue by considering simplified neuronal shapes consisting of circular regions (soma/axons) with spokes (dendrites). Networks are grown by placing these patterns randomly in the two-dimensional (2D) plane and establishing connections whenever a piece of dendrite falls inside an axon. Several topological and dynamical properties of the resulting graph are measured, including the degree distribution, clustering coefficients, symmetry of connections, size of the largest connected component, as well as three hierarchical measurements of the local topology. By varying the number of processes of the individual basic patterns, we can quantify relationships between the individual neuronal shape and the topological and dynamical features of the networks. Integrate-and-fire dynamics on these networks is also investigated with respect to transient activation from a source node, indicating that long-range connections play an important role in the propagation of avalanches.

  17. Connectivity and dynamics of neuronal networks as defined by the shape of individual neurons

    Energy Technology Data Exchange (ETDEWEB)

    Ahnert, Sebastian E [Theory of Condensed Matter, Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE (United Kingdom); A N Travencolo, Bruno; Costa, Luciano da Fontoura [Instituto de FIsica de Sao Carlos, Universidade de Sao Paulo, Av. Trabalhador Sao Carlense 400, Caixa Postal 369, CEP 13560-970, Sao Carlos, Sao Paulo (Brazil)], E-mail: luciano@if.sc.usp.br

    2009-10-15

    Biological neuronal networks constitute a special class of dynamical systems, as they are formed by individual geometrical components, namely the neurons. In the existing literature, relatively little attention has been given to the influence of neuron shape on the overall connectivity and dynamics of the emerging networks. The current work addresses this issue by considering simplified neuronal shapes consisting of circular regions (soma/axons) with spokes (dendrites). Networks are grown by placing these patterns randomly in the two-dimensional (2D) plane and establishing connections whenever a piece of dendrite falls inside an axon. Several topological and dynamical properties of the resulting graph are measured, including the degree distribution, clustering coefficients, symmetry of connections, size of the largest connected component, as well as three hierarchical measurements of the local topology. By varying the number of processes of the individual basic patterns, we can quantify relationships between the individual neuronal shape and the topological and dynamical features of the networks. Integrate-and-fire dynamics on these networks is also investigated with respect to transient activation from a source node, indicating that long-range connections play an important role in the propagation of avalanches.

  18. Scaling of brain metabolism with a fixed energy budget per neuron: implications for neuronal activity, plasticity and evolution.

    Directory of Open Access Journals (Sweden)

    Suzana Herculano-Houzel

    Full Text Available It is usually considered that larger brains have larger neurons, which consume more energy individually, and are therefore accompanied by a larger number of glial cells per neuron. These notions, however, have never been tested. Based on glucose and oxygen metabolic rates in awake animals and their recently determined numbers of neurons, here I show that, contrary to the expected, the estimated glucose use per neuron is remarkably constant, varying only by 40% across the six species of rodents and primates (including humans. The estimated average glucose use per neuron does not correlate with neuronal density in any structure. This suggests that the energy budget of the whole brain per neuron is fixed across species and brain sizes, such that total glucose use by the brain as a whole, by the cerebral cortex and also by the cerebellum alone are linear functions of the number of neurons in the structures across the species (although the average glucose consumption per neuron is at least 10× higher in the cerebral cortex than in the cerebellum. These results indicate that the apparently remarkable use in humans of 20% of the whole body energy budget by a brain that represents only 2% of body mass is explained simply by its large number of neurons. Because synaptic activity is considered the major determinant of metabolic cost, a conserved energy budget per neuron has several profound implications for synaptic homeostasis and the regulation of firing rates, synaptic plasticity, brain imaging, pathologies, and for brain scaling in evolution.

  19. Nitric Oxide in Astrocyte-Neuron Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Li, Nianzhen [Iowa State Univ., Ames, IA (United States)

    2002-01-01

    Astrocytes, a subtype of glial cell, have recently been shown to exhibit Ca2+ elevations in response to neurotransmitters. A Ca2+ elevation can propagate to adjacent astrocytes as a Ca2+ wave, which allows an astrocyte to communicate with its neighbors. Additionally, glutamate can be released from astrocytes via a Ca2+-dependent mechanism, thus modulating neuronal activity and synaptic transmission. In this dissertation, the author investigated the roles of another endogenous signal, nitric oxide (NO), in astrocyte-neuron signaling. First the author tested if NO is generated during astrocytic Ca2+ signaling by imaging NO in purified murine cortical astrocyte cultures. Physiological concentrations of a natural messenger, ATP, caused a Ca2+-dependent NO production. To test the roles of NO in astrocytic Ca2+ signaling, the author applied NO to astrocyte cultures via addition of a NO donor, S-nitrosol-N-acetylpenicillamine (SNAP). NO induced an influx of external Ca2+, possibly through store-operated Ca2+ channels. The NO-induced Ca2+ signaling is cGMP-independent since 8-Br-cGMP, an agonistic analog of cGMP, did not induce a detectable Ca2+ change. The consequence of this NO-induced Ca2+ influx was assessed by simultaneously monitoring of cytosolic and internal store Ca2+ using fluorescent Ca2+ indicators x-rhod-1 and mag-fluo-4. Blockage of NO signaling with the NO scavenger PTIO significantly reduced the refilling percentage of internal stores following ATP-induced Ca2+ release, suggesting that NO modulates internal store refilling. Furthermore, locally photo-release of NO to a single astrocyte led to a Ca2+ elevation in the stimulated astrocyte and a subsequent Ca2+ wave to neighbors. Finally, the author tested the role of NO inglutamate-mediated astrocyte-neuron signaling by

  20. Tetracycline inducible gene manipulation in serotonergic neurons.

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    Tillmann Weber

    Full Text Available The serotonergic (5-HT neuronal system has important and diverse physiological functions throughout development and adulthood. Its dysregulation during development or later in adulthood has been implicated in many neuropsychiatric disorders. Transgenic animal models designed to study the contribution of serotonergic susceptibility genes to a pathological phenotype should ideally allow to study candidate gene overexpression or gene knockout selectively in serotonergic neurons at any desired time during life. For this purpose, conditional expression systems such as the tet-system are preferable. Here, we generated a transactivator (tTA mouse line (TPH2-tTA that allows temporal and spatial control of tetracycline (Ptet controlled transgene expression as well as gene deletion in 5-HT neurons. The tTA cDNA was inserted into a 196 kb PAC containing a genomic mouse Tph2 fragment (177 kb by homologous recombination in E. coli. For functional analysis of Ptet-controlled transgene expression, TPH2-tTA mice were crossed to a Ptet-regulated lacZ reporter line (Ptet-nLacZ. In adult double-transgenic TPH2-tTA/Ptet-nLacZ mice, TPH2-tTA founder line L62-20 showed strong serotonergic β-galactosidase expression which could be completely suppressed with doxycycline (Dox. Furthermore, Ptet-regulated gene expression could be reversibly activated or inactivated when Dox was either withdrawn or added to the system. For functional analysis of Ptet-controlled, Cre-mediated gene deletion, TPH2-tTA mice (L62-20 were crossed to double transgenic Ptet-Cre/R26R reporter mice to generate TPH2-tTA/Ptet-Cre/R26R mice. Without Dox, 5-HT specific recombination started at E12.5. With permanent Dox administration, Ptet-controlled Cre-mediated recombination was absent. Dox withdrawal either postnatally or during adulthood induced efficient recombination in serotonergic neurons of all raphe nuclei, respectively. In the enteric nervous system, recombination could not be detected. We

  1. Exploring how extracellular electric field modulates neuron activity through dynamical analysis of a two-compartment neuron model.

    Science.gov (United States)

    Yi, Guo-Sheng; Wang, Jiang; Wei, Xi-Le; Tsang, Kai-Ming; Chan, Wai-Lok; Deng, Bin; Han, Chun-Xiao

    2014-06-01

    To investigate how extracellular electric field modulates neuron activity, a reduced two-compartment neuron model in the presence of electric field is introduced in this study. Depending on neuronal geometric and internal coupling parameters, the behaviors of the model have been studied extensively. The neuron model can exist in quiescent state or repetitive spiking state in response to electric field stimulus. Negative electric field mainly acts as inhibitory stimulus to the neuron, positive weak electric field could modulate spiking frequency and spike timing when the neuron is already active, and positive electric fields with sufficient intensity could directly trigger neuronal spiking in the absence of other stimulations. By bifurcation analysis, it is observed that there is saddle-node on invariant circle bifurcation, supercritical Hopf bifurcation and subcritical Hopf bifurcation appearing in the obtained two parameter bifurcation diagrams. The bifurcation structures and electric field thresholds for triggering neuron firing are determined by neuronal geometric and coupling parameters. The model predicts that the neurons with a nonsymmetric morphology between soma and dendrite, are more sensitive to electric field stimulus than those with the spherical structure. These findings suggest that neuronal geometric features play a crucial role in electric field effects on the polarization of neuronal compartments. Moreover, by determining the electric field threshold of our biophysical model, we could accurately distinguish between suprathreshold and subthreshold electric fields. Our study highlights the effects of extracellular electric field on neuronal activity from the biophysical modeling point of view. These insights into the dynamical mechanism of electric field may contribute to the investigation and development of electromagnetic therapies, and the model in our study could be further extended to a neuronal network in which the effects of electric fields on

  2. Bistability induces episodic spike communication by inhibitory neurons in neuronal networks

    Science.gov (United States)

    Kazantsev, V. B.; Asatryan, S. Yu.

    2011-09-01

    Bistability is one of the important features of nonlinear dynamical systems. In neurodynamics, bistability has been found in basic Hodgkin-Huxley equations describing the cell membrane dynamics. When the neuron is clamped near its threshold, the stable rest potential may coexist with the stable limit cycle describing periodic spiking. However, this effect is often neglected in network computations where the neurons are typically reduced to threshold firing units (e.g., integrate-and-fire models). We found that the bistability may induce spike communication by inhibitory coupled neurons in the spiking network. The communication is realized in the form of episodic discharges with synchronous (correlated) spikes during the episodes. A spiking phase map is constructed to describe the synchronization and to estimate basic spike phase locking modes.

  3. Bistability induces episodic spike communication by inhibitory neurons in neuronal networks.

    Science.gov (United States)

    Kazantsev, V B; Asatryan, S Yu

    2011-09-01

    Bistability is one of the important features of nonlinear dynamical systems. In neurodynamics, bistability has been found in basic Hodgkin-Huxley equations describing the cell membrane dynamics. When the neuron is clamped near its threshold, the stable rest potential may coexist with the stable limit cycle describing periodic spiking. However, this effect is often neglected in network computations where the neurons are typically reduced to threshold firing units (e.g., integrate-and-fire models). We found that the bistability may induce spike communication by inhibitory coupled neurons in the spiking network. The communication is realized in the form of episodic discharges with synchronous (correlated) spikes during the episodes. A spiking phase map is constructed to describe the synchronization and to estimate basic spike phase locking modes.

  4. Regulation of the Hypothalamic Thyrotropin Releasing Hormone (TRH) Neuron by Neuronal and Peripheral Inputs

    Science.gov (United States)

    Nillni, Eduardo A.

    2010-01-01

    The hypothalamic pituitary thyroid (HPT) axis plays a critical role in mediating changes in metabolism and thermogenesis. Thus, the central regulation of the thyroid axis by Thyrotropin Releasing Hormone (TRH) neurons in the paraventricular nucleus of the hypothalamus (PVN) is of key importance for the normal function of the axis under different physiological conditions including cold stress and changes in nutritional status. Before the TRH peptide becomes biologically active, a series of tightly regulated processes occur including the proper folding of the prohormone for targeting to the secretory pathway, its post-translational processing, and targeting of the processed peptides to the secretory granules near the plasma membrane of the cell ready for secretion. Multiple inputs coming from the periphery or from neurons present in different areas of the brain including the hypothalamus are responsible for the activation or inhibition of the TRH neuron and in turn affect the output of TRH and the set point of the axis. PMID:20074584

  5. Neuronal and non-neuronal Trk neurotrophin receptor-like proteins in Eisenia foetida (Annelida Oligochaeta).

    Science.gov (United States)

    Lucini, C; Castaldo, L; Lamanna, C; Maruccio, L; Vega, J A; Gargiulo, G

    1999-02-19

    The occurrence and distribution of Trk proteins, which are the high-affinity signal-transducing receptors for neurotrophins, have been investigated in earthworms (Eisenia foetida) using polyclonal antibodies which map within their catalytic domain. Western-blot analysis identified major protein bands whose estimated molecular masses were consistent with those of the full-length Trk proteins in vertebrates. Specific immunoreactivity for TrkA-, TrkB-, and TrkC-like was observed in neuronal populations of the dorsal cerebral, subpharyngeal and ventral cord ganglia. Furthermore, TrkA-like immunoreactivity was observed in subcutaneous neurons and nerve fibers between muscle layers in the peripheral nervous system. TrkB- and TrkC-like immunoreactivity was observed in the gut innervation. Non-neuronal expression of TrkB and TrkC proteins was found in epidermal cells, and TrkC-like immunoreactivity was detected in the gut epithelium.

  6. Bidirectional microglia-neuron communication in the healthy brain.

    Science.gov (United States)

    Eyo, Ukpong B; Wu, Long-Jun

    2013-01-01

    Unlike other resident neural cells that are of neuroectodermal origin, microglia are resident neural cells of mesodermal origin. Traditionally recognized for their immune functions during disease, new roles are being attributed to these cells in the development and maintenance of the central nervous system (CNS) including specific communication with neurons. In this review, we highlight some of the recent findings on the bidirectional interaction between neurons and microglia. We discuss these interactions along two lines. First, we review data that suggest that microglial activity is modulated by neuronal signals, focusing on evidence that (i) neurons are capable of regulating microglial activation state and influence basal microglial activities; (ii) classic neurotransmitters affect microglial behavior; (iii) chemotactic signals attract microglia during acute neuronal injury. Next, we discuss some of the recent data on how microglia signal to neurons. Signaling mechanisms include (i) direct physical contact of microglial processes with neuronal elements; (ii) microglial regulation of neuronal synapse and circuit by fractalkine, complement, and DAP12 signaling. In addition, we discuss the use of microglial depletion strategies in studying the role of microglia in neuronal development and synaptic physiology. Deciphering the mechanisms of bidirectional microglial-neuronal communication provides novel insights in understanding microglial function in both the healthy and diseased brain.

  7. Intraganglionic interactions between satellite cells and adult sensory neurons.

    Science.gov (United States)

    Christie, Kimberly; Koshy, Dilip; Cheng, Chu; Guo, GuiFang; Martinez, Jose A; Duraikannu, Arul; Zochodne, Douglas W

    2015-07-01

    Perineuronal satellite cells have an intimate anatomical relationship with sensory neurons that suggests close functional collaboration and mutual support. We examined several facets of this relationship in adult sensory dorsal root ganglia (DRG). Collaboration included the support of process outgrowth by clustering of satellite cells, induction of distal branching behavior by soma signaling, the capacity of satellite cells to respond to distal axon injury of its neighboring neurons, and evidence of direct neuron-satellite cell exchange. In vitro, closely adherent coharvested satellite cells routinely clustered around new outgrowing processes and groups of satellite cells attracted neurite processes. Similar clustering was encountered in the pseudounipolar processes of intact sensory neurons within intact DRG in vivo. While short term exposure of distal growth cones of unselected adult sensory neurons to transient gradients of a PTEN inhibitor had negligible impacts on their behavior, exposure of the soma induced early and substantial growth of their distant neurites and branches, an example of local soma signaling. In turn, satellite cells sensed when distal neuronal axons were injured by enlarging and proliferating. We also observed that satellite cells were capable of internalizing and expressing a neuron fluorochrome label, diamidino yellow, applied remotely to distal injured axons of the neuron and retrogradely transported to dorsal root ganglia sensory neurons. The findings illustrate a robust interaction between intranganglionic neurons and glial cells that involve two way signals, features that may be critical for both regenerative responses and ongoing maintenance. Copyright © 2015. Published by Elsevier Inc.

  8. Norepinephrine metabolism in neuronal cultures is increased by angiotensin II

    Energy Technology Data Exchange (ETDEWEB)

    Sumners, C.; Shalit, S.L.; Kalberg, C.J.; Raizada, M.K.

    1987-06-01

    In this study the authors have examined the actions of angiotensin II (ANG II) on catecholamine metabolism in neuronal brain cell cultures prepared from the hypothalamus and brain stem. Neuronal cultures prepared from the brains of 1-day-old Sprague-Dawley rats exhibit specific neuronal uptake mechanisms for both norepinephrine (NE) and dopamine (DA), and also monoamine oxidase (MAO) and catechol O-methyltransferase (COMT) activity. Separate neuronal uptake sites for NE and DA were identified by using specific neuronal uptake inhibitors for each amine. In previous studies, they determined that ANG II (10 nM-1 ..mu..M) stimulates increased neuronal (/sup 3/H)NE uptake by acting as specific receptors. They have confirmed these results here and in addition have shown that ANG II has not significant effects on neuronal (/sup 3/H)DA uptake. These results suggest that the actions of ANG II are restricted to the NE transporter in neuronal cultures. It is possible that ANG II stimulates the intraneuronal metabolism of at least part of the NE that is taken up, because the peptide stimulates MAO activity, an effect mediated by specific ANG II receptors. ANG II had no effect on COMT activity in neuronal cultures. Therefore, the use of neuronal cultures of hypothalamus and brain stem they have determined that ANG II can specifically alter NE metabolism in these areas, while apparently not altering DA metabolism.

  9. Bidirectional Microglia-Neuron Communication in the Healthy Brain

    Directory of Open Access Journals (Sweden)

    Ukpong B. Eyo

    2013-01-01

    Full Text Available Unlike other resident neural cells that are of neuroectodermal origin, microglia are resident neural cells of mesodermal origin. Traditionally recognized for their immune functions during disease, new roles are being attributed to these cells in the development and maintenance of the central nervous system (CNS including specific communication with neurons. In this review, we highlight some of the recent findings on the bidirectional interaction between neurons and microglia. We discuss these interactions along two lines. First, we review data that suggest that microglial activity is modulated by neuronal signals, focusing on evidence that (i neurons are capable of regulating microglial activation state and influence basal microglial activities; (ii classic neurotransmitters affect microglial behavior; (iii chemotactic signals attract microglia during acute neuronal injury. Next, we discuss some of the recent data on how microglia signal to neurons. Signaling mechanisms include (i direct physical contact of microglial processes with neuronal elements; (ii microglial regulation of neuronal synapse and circuit by fractalkine, complement, and DAP12 signaling. In addition, we discuss the use of microglial depletion strategies in studying the role of microglia in neuronal development and synaptic physiology. Deciphering the mechanisms of bidirectional microglial-neuronal communication provides novel insights in understanding microglial function in both the healthy and diseased brain.

  10. Control of neuronal excitability by NMDA-type glutamate receptors in early developing binaural auditory neurons.

    Science.gov (United States)

    Sanchez, Jason Tait; Seidl, Armin H; Rubel, Edwin W; Barria, Andres

    2012-10-01

    Precise control of neuronal excitability in the auditory brainstem is fundamental for processing timing cues used for sound localization and signal discrimination in complex acoustic environments. In mature nucleus laminaris (NL), the first nucleus responsible for binaural processing in chickens, neuronal excitability is governed primarily by voltage-activated potassium conductances (K(VA)). High levels of K(VA) expression in NL neurons result in one or two initial action potentials (APs) in response to high-frequency synaptic activity or sustained depolarization. Here we show that during a period of synaptogenesis and circuit refinement, before hearing onset, K(VA) conductances are relatively small, in particular low-voltage-activated K(+) conductances (K(LVA)). In spite of this, neuronal output is filtered and repetitive synaptic activity generates only one or two initial APs during a train of stimuli. During this early developmental time period, synaptic NMDA-type glutamate receptors (NMDA-Rs) contain primarily the GluN2B subunit. We show that the slow decay kinetics of GluN2B-containing NMDA-Rs allows synaptic responses to summate, filtering the output of NL neurons before intrinsic properties are fully developed. Weaker Mg(2+) blockade of NMDA-Rs and ambient glutamate early in development generate a tonic NMDA-R-mediated current that sets the membrane potential at more depolarized values. Small KLVA conductances, localized in dendrites, prevent excessive depolarization caused by tonic activation of NMDA-Rs. Thus, before intrinsic properties are fully developed, NMDA-Rs control the output of NL neurons during evoked synaptic transmission.

  11. Dicer maintains the identity and function of proprioceptive sensory neurons.

    Science.gov (United States)

    O'Toole, Sean M; Ferrer, Monica M; Mekonnen, Jennifer; Zhang, Haihan; Shima, Yasuyuki; Ladle, David R; Nelson, Sacha B

    2017-03-01

    Neuronal cell identity is established during development and must be maintained throughout an animal's life (Fishell G, Heintz N. Neuron 80: 602-612, 2013). Transcription factors critical for establishing neuronal identity can be required for maintaining it (Deneris ES, Hobert O. Nat Neurosci 17: 899-907, 2014). Posttranscriptional regulation also plays an important role in neuronal differentiation (Bian S, Sun T. Mol Neurobiol 44: 359-373, 2011), but its role in maintaining cell identity is less established. To better understand how posttranscriptional regulation might contribute to cell identity, we examined the proprioceptive neurons in the dorsal root ganglion (DRG), a highly specialized sensory neuron class, with well-established properties that distinguish them from other neurons in the ganglion. By conditionally ablating Dicer in mice, using parvalbumin (Pvalb)-driven Cre recombinase, we impaired posttranscriptional regulation in the proprioceptive sensory neuron population. Knockout (KO) animals display a progressive form of ataxia at the beginning of the fourth postnatal week that is accompanied by a cell death within the DRG. Before cell loss, expression profiling shows a reduction of proprioceptor specific genes and an increased expression of nonproprioceptive genes normally enriched in other ganglion neurons. Furthermore, although central connections of these neurons are intact, the peripheral connections to the muscle are functionally impaired. Posttranscriptional regulation is therefore necessary to retain the transcriptional identity and support functional specialization of the proprioceptive sensory neurons. NEW & NOTEWORTHY We have demonstrated that selectively impairing Dicer in parvalbumin-positive neurons, which include the proprioceptors, triggers behavioral changes, a lack of muscle connectivity, and a loss of transcriptional identity as observed through RNA sequencing. These results suggest that Dicer and, most likely by extension, micro

  12. Neurons controlling Aplysia feeding inhibit themselves by continuous NO production.

    Directory of Open Access Journals (Sweden)

    Nimrod Miller

    Full Text Available BACKGROUND: Neural activity can be affected by nitric oxide (NO produced by spiking neurons. Can neural activity also be affected by NO produced in neurons in the absence of spiking? METHODOLOGY/PRINCIPAL FINDINGS: Applying an NO scavenger to quiescent Aplysia buccal ganglia initiated fictive feeding, indicating that NO production at rest inhibits feeding. The inhibition is in part via effects on neurons B31/B32, neurons initiating food consumption. Applying NO scavengers or nitric oxide synthase (NOS blockers to B31/B32 neurons cultured in isolation caused inactive neurons to depolarize and fire, indicating that B31/B32 produce NO tonically without action potentials, and tonic NO production contributes to the B31/B32 resting potentials. Guanylyl cyclase blockers also caused depolarization and firing, indicating that the cGMP second messenger cascade, presumably activated by the tonic presence of NO, contributes to the B31/B32 resting potential. Blocking NO while voltage-clamping revealed an inward leak current, indicating that NO prevents this current from depolarizing the neuron. Blocking nitrergic transmission had no effect on a number of other cultured, isolated neurons. However, treatment with NO blockers did excite cerebral ganglion neuron C-PR, a command-like neuron initiating food-finding behavior, both in situ, and when the neuron was cultured in isolation, indicating that this neuron also inhibits itself by producing NO at rest. CONCLUSION/SIGNIFICANCE: Self-inhibitory, tonic NO production is a novel mechanism for the modulation of neural activity. Localization of this mechanism to critical neurons in different ganglia controlling different aspects of a behavior provides a mechanism by which a humeral signal affecting background NO production, such as the NO precursor L-arginine, could control multiple aspects of the behavior.

  13. AgRP Neurons Can Increase Food Intake during Conditions of Appetite Suppression and Inhibit Anorexigenic Parabrachial Neurons.

    Science.gov (United States)

    Essner, Rachel A; Smith, Alison G; Jamnik, Adam A; Ryba, Anna R; Trutner, Zoe D; Carter, Matthew E

    2017-09-06

    To maintain energy homeostasis, orexigenic (appetite-inducing) and anorexigenic (appetite suppressing) brain systems functionally interact to regulate food intake. Within the hypothalamus, neurons that express agouti-related protein (AgRP) sense orexigenic factors and orchestrate an increase in food-seeking behavior. In contrast, calcitonin gene-related peptide (CGRP)-expressing neurons in the parabrachial nucleus (PBN) suppress feeding. PBN CGRP neurons become active in response to anorexigenic hormones released following a meal, including amylin, secreted by the pancreas, and cholecystokinin (CCK), secreted by the small intestine. Additionally, exogenous compounds, such as lithium chloride (LiCl), a salt that creates gastric discomfort, and lipopolysaccharide (LPS), a bacterial cell wall component that induces inflammation, exert appetite-suppressing effects and activate PBN CGRP neurons. The effects of increasing the homeostatic drive to eat on feeding behavior during appetite suppressing conditions are unknown. Here, we show in mice that food deprivation or optogenetic activation of AgRP neurons induces feeding to overcome the appetite suppressing effects of amylin, CCK, and LiCl, but not LPS. AgRP neuron photostimulation can also increase feeding during chemogenetic-mediated stimulation of PBN CGRP neurons. AgRP neuron stimulation reduces Fos expression in PBN CGRP neurons across all conditions. Finally, stimulation of projections from AgRP neurons to the PBN increases feeding following administration of amylin, CCK, and LiCl, but not LPS. These results demonstrate that AgRP neurons are sufficient to increase feeding during noninflammatory-based appetite suppression and to decrease activity in anorexigenic PBN CGRP neurons, thereby increasing food intake during homeostatic need.SIGNIFICANCE STATEMENT The motivation to eat depends on the relative balance of activity in distinct brain regions that induce or suppress appetite. An abnormal amount of activity in

  14. Muscle and motor neuron ciliary neurotrophic factor receptor α together maintain adult motor neuron axons in vivo.

    Science.gov (United States)

    Lee, Nancy; Serbinski, Carolyn R; Braunlin, Makayla R; Rasch, Matthew S; Rydyznski, Carolyn E; MacLennan, A John

    2016-12-01

    The molecular mechanisms maintaining adult motor innervation are comparatively unexplored relative to those involved during development. In addition to the fundamental neuroscience question, this area has important clinical ramifications given that loss of neuromuscular contact is thought to underlie several adult onset human neuromuscular diseases including amyotrophic lateral sclerosis. Indirect evidence suggests that ciliary neurotrophic factor (CNTF) receptors may contribute to adult motor neuron axon maintenance. To directly address this in vivo, we used adult onset mouse genetic disruption techniques to deplete motor neuron and muscle CNTF receptor α (CNTFRα), the essential ligand binding subunit of the receptor, and incorporated reporters labelling affected motor neuron axons and terminals. The combined depletion of motor neuron and muscle CNTFRα produced a large loss of motor neuron terminals and retrograde labelling of motor neurons with FluoroGold indicated axon die-back well beyond muscle, together revealing an essential role for CNTFRα in adult motor axon maintenance. In contrast, selective depletion of motor neuron CNTFRα did not affect motor innervation. These data, along with our previous work indicating no effect of muscle specific CNTFRα depletion on motor innervation, suggest that motor neuron and muscle CNTFRα function in concert to maintain motor neuron axons. The data also raise the possibility of motor neuron and/or muscle CNTFRα as therapeutic targets for adult neuromuscular denervating diseases. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  15. MicroRNAs in neuronal communication.

    Science.gov (United States)

    Higa, Guilherme Shigueto Vilar; de Sousa, Erica; Walter, Lais Takata; Kinjo, Erika Reime; Resende, Rodrigo Ribeiro; Kihara, Alexandre Hiroaki

    2014-06-01

    MicroRNAs (miRNAs) are short nucleotides sequences that regulate the expression of genes in different eukaryotic cell types. A tremendous amount of knowledge on miRNAs has rapidly accumulated over the last few years, revealing the growing interest in this field of research. On the other hand, clarifying the physiological regulation of gene expression in the central nervous system is important for establishing a reference for comparison to the diseased state. It is well known that the fine tuning of neuronal networks relies on intricate molecular mechanisms, such as the adjustment of the synaptic transmission. As determined by recent studies, regulation of neuronal interactions by miRNAs has critical consequences in the development, adaptation to ambient demands, and degeneration of the nervous system. In contrast, activation of synaptic receptors triggers downstream signaling cascades that generate a vast array of effects, which includes the regulation of novel genes involved in the control of the miRNA life cycle. In this review, we have examined the hot topics on miRNA gene-regulatory activities in the broad field of neuronal communication-related processes. Furthermore, in addition to indicating the newly described effect of miRNAs on the regulation of specific neurotransmitter systems, we have pointed out how these systems affect the expression, transport, and stability of miRNAs. Moreover, we discuss newly described and under-investigation mechanisms involving the intercellular transfer of miRNAs, aided by exosomes and gap junctions. Thus, in the current review, we were able to highlight recent findings related to miRNAs that indisputably contributed towards the understanding of the nervous system in health and disease.

  16. Differential production of superoxide by neuronal mitochondria

    Directory of Open Access Journals (Sweden)

    Levin Leonard A

    2008-01-01

    Full Text Available Abstract Background Mitochondrial DNA (mtDNA mutations, which are present in all mitochondria-containing cells, paradoxically cause tissue-specific disease. For example, Leber's hereditary optic neuropathy (LHON results from one of three point mutations mtDNA coding for complex I components, but is only manifested in retinal ganglion cells (RGCs, a central neuron contained within the retina. Given that RGCs use superoxide for intracellular signaling after axotomy, and that LHON mutations increase superoxide levels in non-RGC transmitochondrial cybrids, we hypothesized that RGCs regulate superoxide levels differently than other neuronal cells. To study this, we compared superoxide production and mitochondrial electron transport chain (METC components in isolated RGC mitochondria to mitochondria isolated from cerebral cortex and neuroblastoma SK-N-AS cells. Results In the presence of the complex I substrate glutamate/malate or the complex II substrate succinate, the rate of superoxide production in RGC-5 cells was significantly lower than cerebral or neuroblastoma cells. Cerebral but not RGC-5 or neuroblastoma cells increased superoxide production in response to the complex I inhibitor rotenone, while neuroblastoma but not cerebral or RGC-5 cells dramatically decreased superoxide production in response to the complex III inhibitor antimycin A. Immunoblotting and real-time quantitative PCR of METC components demonstrated different patterns of expression among the three different sources of neuronal mitochondria. Conclusion RGC-5 mitochondria produce superoxide at significantly lower rates than cerebral and neuroblastoma mitochondria, most likely as a result of differential expression of complex I components. Diversity in METC component expression and function could explain tissue specificity in diseases associated with inherited mtDNA abnormalities.

  17. Synchronization transition in gap-junction-coupled leech neurons

    Science.gov (United States)

    Wang, Qingyun; Duan, Zhisheng; Feng, Zhaosheng; Chen, Guanrong; Lu, Qishao

    2008-07-01

    Real neurons can exhibit various types of firings including tonic spiking, bursting as well as silent state, which are frequently observed in neuronal electrophysiological experiments. More interestingly, it is found that neurons can demonstrate the co-existing mode of stable tonic spiking and bursting, which depends on initial conditions. In this paper, synchronization in gap-junction-coupled neurons with co-existing attractors of spiking and bursting firings is investigated as the coupling strength gets increased. Synchronization transitions can be identified by means of the bifurcation diagram and the correlation coefficient. It is illustrated that the coupled neurons can exhibit different types of synchronization transitions between spiking and bursting when the coupling strength increases. In the course of synchronization transitions, an intermittent synchronization can be observed. These results may be instructive to understand synchronization transitions in neuronal systems.

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

    Energy Technology Data Exchange (ETDEWEB)

    Li Xiaoli [Institute of Electrical Engineering, Yanshan University, Qinhuangdao 066004 (China)]. E-mail: xiaoli.avh@gmail.com

    2006-08-07

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

  19. Robust Master-Slave Synchronization of Neuronal Systems

    Directory of Open Access Journals (Sweden)

    Hector Puebla

    2017-01-01

    Full Text Available The desire to understand physiological mechanisms of neuronal systems has led to the introduction of engineering concepts to explain how the brain works. The synchronization of neurons is a central topic in understanding the behavior of living organisms in neurosciences and has been addressed using concepts from control engineering. We introduce a simple and reliable robust synchronization approach for neuronal systems. The proposed synchronization method is based on a master-slave configuration in conjunction with a coupling input enhanced with compensation of model uncertainties. Our approach has two nice features for the synchronization of neuronal systems: (i a simple structure that uses the minimum information and (ii good robustness properties against model uncertainties and noise. Two benchmark neuronal systems, Hodgkin-Huxley and Hindmarsh-Rose neurons, are used to illustrate our findings. The proposed synchronization approach is aimed at gaining insight into the effect of external electrical stimulation of nerve cells.

  20. Hunger neurons drive feeding through a sustained, positive reinforcement signal.

    Science.gov (United States)

    Chen, Yiming; Lin, Yen-Chu; Zimmerman, Christopher A; Essner, Rachel A; Knight, Zachary A

    2016-08-24

    The neural mechanisms underlying hunger are poorly understood. AgRP neurons are activated by energy deficit and promote voracious food consumption, suggesting these cells may supply the fundamental hunger drive that motivates feeding. However recent in vivo recording experiments revealed that AgRP neurons are inhibited within seconds by the sensory detection of food, raising the question of how these cells can promote feeding at all. Here we resolve this paradox by showing that brief optogenetic stimulation of AgRP neurons before food availability promotes intense appetitive and consummatory behaviors that persist for tens of minutes in the absence of continued AgRP neuron activation. We show that these sustained behavioral responses are mediated by a long-lasting potentiation of the rewarding properties of food and that AgRP neuron activity is positively reinforcing. These findings reveal that hunger neurons drive feeding by transmitting a positive valence signal that triggers a stable transition between behavioral states.

  1. Sialin expression in the CNS implicates extralysosomal function in neurons.

    Science.gov (United States)

    Aula, Nina; Kopra, Outi; Jalanko, Anu; Peltonen, Leena

    2004-03-01

    SLC17A5 encodes a lysosomal membrane protein, sialin, which transports sialic acid from lysosomes. Mutations in sialin result in neurodegenerative sialic acid storage disorders, Salla disease (SD) and infantile sialic acid storage disease (ISSD). Here we analyzed sialin in mouse central nervous system (CNS) and primary cortical and hippocampal neurons and glia. In the CNS, sialin was predominantly expressed in neurons, especially in the proliferative zone of the prospective neocortex and the hippocampus in developing brain. In nonneuronal cells and primary glial cell cultures, mouse sialin was localized into lysosomes but interestingly, in primary neuronal cultures sialin was not targeted into lysosomes but rather revealed a punctate staining along the neuronal processes and was also seen in the plasma membrane. These data demonstrate a nonlysosomal localization of sialin in neurons and would imply a role for sialin in the secretory processes of neuronal cells.

  2. [Two-nuclear neurons: sincitial fusion or amitotic division].

    Science.gov (United States)

    Sotnikov, O S; Frumkina, L E; Lactionova, A A; Paramonova, N M; Novakovskaia, S A

    2011-01-01

    In the review the history of research two-nuclear neurons is stated and two hypotheses about mechanisms of their formation are analysed: by sincitial fusion or amytotic divisions. The facts of discrepancy of the former orthodox cellular theory categorically denying possibility sincitial of communications in nervous system and of sincitial fusion neurons are mentioned. As an example results of ultrastructural researches of occurrence sincitium in a cortex of the big brain of rats, in autonomic ganglions, in hypocampus and a cerebellum of adult animals are presented. The video data of the sincitial fusion of live neurons and the mechanism of formation multinuclear neurons in tissue culture are analyzed. Existing data about amytotic a way of formation two-nuclear neurons are critically considered. The conclusion becomes, that the mechanism of formation two-nuclear neurons is cellular fusion. Simultaneously the review confirms our representations about existence in nervous system sincitial interneural communications.

  3. Expression of dystrophin in the mouse myenteric neurones.

    Science.gov (United States)

    Vannucchi, M G; Corsani, L; Giovannini, M G; Faussone-Pellegrini, M S

    2001-03-09

    Dystrophin, a membrane-associated protein, plays relevant roles in cell functions. Its lack or trunkated expression results in Duchenne muscular dystrophy (DMD), a pathology associated with alterations in gastrointestinal motility considered to be neural in origin. No data are available on the presence of dystrophin in myenteric neurones. We labelled mouse myenteric neurones with DYS1-, DYS2-, DYS3-antibodies; staining was located on the perikarya and processes, with no differences in distribution or intensity among the antibodies; the western immunoblot analysis indicated that myenteric neurones express several dystrophin isoforms; anti-dystrophins/anti-neuronal specific enolase double-labeling confirmed that all neurones express dystrophin. Dystrophin in myenteric neurones might play a role in cytoskeletal organization, axonal transport and signal pathways; its lack might cause the intestinal motor abnormalities reported in DMD patients.

  4. The emergence of spontaneous activity in neuronal cultures

    Science.gov (United States)

    Orlandi, J. G.; Alvarez-Lacalle, E.; Teller, S.; Soriano, J.; Casademunt, J.

    2013-01-01

    In vitro neuronal networks of dissociated hippocampal or cortical tissues are one of the most attractive model systems for the physics and neuroscience communities. Cultured neurons grow and mature, develop axons and dendrites, and quickly connect to their neighbors to establish a spontaneously active network within a week. The resulting neuronal network is characterized by a combination of excitatory and inhibitory neurons coupled through synaptic connections that interact in a highly nonlinear manner. The nonlinear behavior emerges from the dynamics of both the neurons' spiking activity and synaptic transmission, together with biological noise. These ingredients give rise to a rich repertoire of phenomena that are still poorly understood, including the emergence and maintenance of periodic spontaneous activity, avalanches, propagation of fronts and synchronization. In this work we present an overview on the rich activity of cultured neuronal networks, and detail the minimal theoretical considerations needed to describe experimental observations.

  5. Revisiting the role of neurons in neurovascular coupling

    Directory of Open Access Journals (Sweden)

    Bruno Cauli

    2010-06-01

    Full Text Available In this article, we will review molecular, anatomical, physiological and pharmacological data in an attempt to better understand how excitatory and inhibitory neurons recruited by distinct afferent inputs to the cerebral cortex contribute to the coupled hemodynamic response, and how astrocytes can act as intermediaries to these neuronal populations. We aim at providing the pros and cons to the following statements that, depending on the nature of the afferent input to the neocortex, (i different neuronal or astroglial messengers, likely acting in sequence, mediate the hemodynamic changes, (ii some recruited neurons release messengers that directly alter blood vessel tone, (iii others act by modulating neuronal and astroglial activity, and (iv astrocytes act as intermediaries for both excitatory and inhibitory neurotransmitters. We will stress that a given afferent signal activates a precise neuronal circuitry that determines the mediators of the hemodynamic response as well as the level of interaction with surrounding astrocytes.

  6. Role of GSK3 signaling in neuronal morphogenesis

    Directory of Open Access Journals (Sweden)

    Yun Tai eKim

    2011-11-01

    Full Text Available Glycogen synthase kinase 3 (GSK3 is emerging as a key regulator of several aspects of neuronal morphogenesis including neuronal polarization, axon growth and axon branching. Multiple signaling pathways have been identified that control neuronal polarization, including PI3K, Rho-GTPases, Par3/6, TSC-mTOR, and PKA-LKB1. However, how these pathways are coordinated is not clear. As GSK3 signaling exhibits crosstalk with each of these pathways it has the potential to integrate these polarity signals in the control neuronal polarization. After neurons establish polarity, GSK3 acts as an important signaling mediator in the regulation of axon extension and axon branching by transducing upstream signaling to reorganizion of the axonal cytoskeleton, especially microtubules. Here we review the roles of GSK3 signaling in neuronal morphogenesis and discuss the underlying molecular mechanisms.

  7. Dopamine neurons learn relative chosen value from probabilistic rewards.

    Science.gov (United States)

    Lak, Armin; Stauffer, William R; Schultz, Wolfram

    2016-10-27

    Economic theories posit reward probability as one of the factors defining reward value. Individuals learn the value of cues that predict probabilistic rewards from experienced reward frequencies. Building on the notion that responses of dopamine neurons increase with reward probability and expected value, we asked how dopamine neurons in monkeys acquire this value signal that may represent an economic decision variable. We found in a Pavlovian learning task that reward probability-dependent value signals arose from experienced reward frequencies. We then assessed neuronal response acquisition during choices among probabilistic rewards. Here, dopamine responses became sensitive to the value of both chosen and unchosen options. Both experiments showed also the novelty responses of dopamine neurones that decreased as learning advanced. These results show that dopamine neurons acquire predictive value signals from the frequency of experienced rewards. This flexible and fast signal reflects a specific decision variable and could update neuronal decision mechanisms.

  8. Soft chitosan microbeads scaffold for 3D functional neuronal networks.

    Science.gov (United States)

    Tedesco, Maria Teresa; Di Lisa, Donatella; Massobrio, Paolo; Colistra, Nicolò; Pesce, Mattia; Catelani, Tiziano; Dellacasa, Elena; Raiteri, Roberto; Martinoia, Sergio; Pastorino, Laura

    2018-02-01

    The availability of 3D biomimetic in vitro neuronal networks of mammalian neurons represents a pivotal step for the development of brain-on-a-chip experimental models to study neuronal (dys)functions and particularly neuronal connectivity. The use of hydrogel-based scaffolds for 3D cell cultures has been extensively studied in the last years. However, limited work on biomimetic 3D neuronal cultures has been carried out to date. In this respect, here we investigated the use of a widely popular polysaccharide, chitosan (CHI), for the fabrication of a microbead based 3D scaffold to be coupled to primary neuronal cells. CHI microbeads were characterized by optical and atomic force microscopies. The cell/scaffold interaction was deeply characterized by transmission electron microscopy and by immunocytochemistry using confocal microscopy. Finally, a preliminary electrophysiological characterization by micro-electrode arrays was carried out. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Memory recall and modifications by activating neurons with elevated CREB.

    Science.gov (United States)

    Kim, Jieun; Kwon, Jeong-Tae; Kim, Hyung-Su; Josselyn, Sheena A; Han, Jin-Hee

    2014-01-01

    Memory is supported by a specific ensemble of neurons distributed in the brain that form a unique memory trace. We previously showed that neurons in the lateral amygdala expressing elevated levels of cAMP response-element binding protein are preferentially recruited into fear memory traces and are necessary for the expression of those memories. However, it is unknown whether artificially activating just these selected neurons in the absence of behavioral cues is sufficient to recall that fear memory. Using an ectopic rat vanilloid receptor TRPV1 and capsaicin system, we found that activating this specific ensemble of neurons was sufficient to recall established fear memory. Furthermore, this neuronal activation induced a reconsolidation-like reorganization process, or strengthening of the fear memory. Thus, our findings establish a direct link between the activation of specific ensemble of neurons in the lateral amygdala and the recall of fear memory and its subsequent modifications.

  10. Synaptic Plasticity onto Dopamine Neurons Shapes Fear Learning.

    Science.gov (United States)

    Pignatelli, Marco; Umanah, George Kwabena Essien; Ribeiro, Sissi Palma; Chen, Rong; Karuppagounder, Senthilkumar Senthil; Yau, Hau-Jie; Eacker, Stephen; Dawson, Valina Lynn; Dawson, Ted Murray; Bonci, Antonello

    2017-01-18

    Fear learning is a fundamental behavioral process that requires dopamine (DA) release. Experience-dependent synaptic plasticity occurs on DA neurons while an organism is engaged in aversive experiences. However, whether synaptic plasticity onto DA neurons is causally involved in aversion learning is unknown. Here, we show that a stress priming procedure enhances fear learning by engaging VTA synaptic plasticity. Moreover, we took advantage of the ability of the ATPase Thorase to regulate the internalization of AMPA receptors (AMPARs) in order to selectively manipulate glutamatergic synaptic plasticity on DA neurons. Genetic ablation of Thorase in DAT + neurons produced increased AMPAR surface expression and function that lead to impaired induction of both long-term depression (LTD) and long-term potentiation (LTP). Strikingly, animals lacking Thorase in DAT + neurons expressed greater associative learning in a fear conditioning paradigm. In conclusion, our data provide a novel, causal link between synaptic plasticity onto DA neurons and fear learning. Published by Elsevier Inc.

  11. Mirror neurons, language, and embodied cognition.

    Science.gov (United States)

    Perlovsky, Leonid I; Ilin, Roman

    2013-05-01

    Basic mechanisms of the mind, cognition, language, its semantic and emotional mechanisms are modeled using dynamic logic (DL). This cognitively and mathematically motivated model leads to a dual-model hypothesis of language and cognition. The paper emphasizes that abstract cognition cannot evolve without language. The developed model is consistent with a joint emergence of language and cognition from a mirror neuron system. The dual language-cognition model leads to the dual mental hierarchy. The nature of cognition embodiment in the hierarchy is analyzed. Future theoretical and experimental research is discussed. Published by Elsevier Ltd.

  12. Random Bin for Analyzing Neuron Spike Trains

    Directory of Open Access Journals (Sweden)

    Shinichi Tamura

    2012-01-01

    Full Text Available When analyzing neuron spike trains, it is always the problem of how to set the time bin. Bin width affects much to analyzed results of such as periodicity of the spike trains. Many approaches have been proposed to determine the bin setting. However, these bins are fixed through the analysis. In this paper, we propose a randomizing method of bin width and location instead of conventional fixed bin setting. This technique is applied to analyzing periodicity of interspike interval train. Also the sensitivity of the method is presented.

  13. Artificial Neuron Modelling Based on Wave Shape

    Directory of Open Access Journals (Sweden)

    Kieran Greer

    2013-10-01

    Full Text Available This paper describes a new model for an artificial neural network processing unit or neuron. It is slightly different to a traditional feedforward network by the fact that it favours a mechanism of trying to match the wave-like ‘shape’ of the input with the shape of the output against specific value error corrections. The expectation is then that a best fit shape can be transposed into the desired output values more easily. This allows for notions of reinforcement through resonance and also the construction of synapses.

  14. Differential sensitivity to nicotine among hypothalamic magnocellular neurons

    DEFF Research Database (Denmark)

    Mikkelsen, J D; Jacobsen, Julie; Kiss, Adrian Emil

    2012-01-01

    The magnocellular neurons in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) either contain vasopressin or oxytocin. Even though both hormones are released after systemic administration of nicotine, the mechanism through which the two populations of neurons are activated...... is not known. This study was carried out in the rat to investigate the effect of increasing doses of nicotine on subsets of magnocellular neurons containing either oxytocin or vasopressin....

  15. A systematic approach to selecting task relevant neurons.

    Science.gov (United States)

    Kahn, Kevin; Saxena, Shreya; Eskandar, Emad; Thakor, Nitish; Schieber, Marc; Gale, John T; Averbeck, Bruno; Eden, Uri; Sarma, Sridevi V

    2015-04-30

    Since task related neurons cannot be specifically targeted during surgery, a critical decision to make is to select which neurons are task-related when performing data analysis. Including neurons unrelated to the task degrade decoding accuracy and confound neurophysiological results. Traditionally, task-related neurons are selected as those with significant changes in firing rate when a stimulus is applied. However, this assumes that neurons' encoding of stimuli are dominated by their firing rate with little regard to temporal dynamics. This paper proposes a systematic approach for neuron selection, which uses a likelihood ratio test to capture the contribution of stimulus to spiking activity while taking into account task-irrelevant intrinsic dynamics that affect firing rates. This approach is denoted as the model deterioration excluding stimulus (MDES) test. MDES is compared to firing rate selection in four case studies: a simulation, a decoding example, and two neurophysiology examples. The MDES rankings in the simulation match closely with ideal rankings, while firing rate rankings are skewed by task-irrelevant parameters. For decoding, 95% accuracy is achieved using the top 8 MDES-ranked neurons, while the top 12 firing-rate ranked neurons are needed. In the neurophysiological examples, MDES matches published results when firing rates do encode salient stimulus information, and uncovers oscillatory modulations in task-related neurons that are not captured when neurons are selected using firing rates. These case studies illustrate the importance of accounting for intrinsic dynamics when selecting task-related neurons and following the MDES approach accomplishes that. MDES selects neurons that encode task-related information irrespective of these intrinsic dynamics which can bias firing rate based selection. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Axotomy depletes intracellular calcium stores in primary sensory neurons.

    Science.gov (United States)

    Rigaud, Marcel; Gemes, Geza; Weyker, Paul D; Cruikshank, James M; Kawano, Takashi; Wu, Hsiang-En; Hogan, Quinn H

    2009-08-01

    The cellular mechanisms of neuropathic pain are inadequately understood. Previous investigations have revealed disrupted Ca signaling in primary sensory neurons after injury. The authors examined the effect of injury on intracellular Ca stores of the endoplasmic reticulum, which critically regulate the Ca signal and neuronal function. Intracellular Ca levels were measured with Fura-2 or mag-Fura-2 microfluorometry in axotomized fifth lumbar (L5) dorsal root ganglion neurons and adjacent L4 neurons isolated from hyperalgesic rats after L5 spinal nerve ligation, compared to neurons from control animals. Endoplasmic reticulum Ca stores released by the ryanodine-receptor agonist caffeine decreased by 46% in axotomized small neurons. This effect persisted in Ca-free bath solution, which removes the contribution of store-operated membrane Ca channels, and after blockade of the mitochondrial, sarco-endoplasmic Ca-ATPase and the plasma membrane Ca ATPase pathways. Ca released by the sarco-endoplasmic Ca-ATPase blocker thapsigargin and by the Ca-ionophore ionomycin was also diminished by 25% and 41%, respectively. In contrast to control neurons, Ca stores in axotomized neurons were not expanded by neuronal activation by K depolarization, and the proportionate rate of refilling by sarco-endoplasmic Ca-ATPase was normal. Luminal Ca concentration was also reduced by 38% in axotomized neurons in permeabilized neurons. The adjacent neurons of the L4 dorsal root ganglia showed modest and inconsistent changes after L5 spinal nerve ligation. Painful nerve injury leads to diminished releasable endoplasmic reticulum Ca stores and a reduced luminal Ca concentration. Depletion of Ca stores may contribute to the pathogenesis of neuropathic pain.

  17. Distribution, structure and projections of the frog intracardiac neurons.

    Science.gov (United States)

    Batulevicius, Darius; Skripkiene, Gertruda; Batuleviciene, Vaida; Skripka, Valdas; Dabuzinskiene, Anita; Pauza, Dainius H

    2012-05-21

    Histochemistry for acetylcholinesterase was used to determine the distribution of intracardiac neurons in the frog Rana temporaria. Seventy-nine intracardiac neurons from 13 frogs were labelled iontophoretically by the intracellular markers Alexa Fluor 568 and Lucifer Yellow CH to determine their structure and projections. Total neuronal number per frog heart was (Mean ± SE) 1374 ± 56. Largest collections of neurons were found in the interatrial septum (46%), atrioventricular junction (25%) and venal sinus (12%). Among the intracellularly labelled neurons, we found the cells of unipolar (71%), multipolar (20%) and bipolar (9%) types. Multiple processes originated from the neuron soma, hillock and proximal axon. These processes projected onto adjacent neuron somata and cardiac muscle fibers within the interatrial septum. Average total length of the processes from proximal axon was 348 ± 50 μm. Average total length of processes from soma and hillock was less, 118 ± 27 μm and 109 ± 24 μm, respectively. The somata of 59% of neurons had bubble- or flake-shaped extensions. Most neurons from the major nerves in the interatrial septum sent their axons towards the ventricle. In contrast, most neurons from the ventral part of the interatrial septum sent their axons towards the atria. Our findings contradict to a view that the frog intracardiac ganglia contain only non-dendritic neurons of the unipolar type. We conclude that the frog intracardiac neurons are structurally complex and diverse. This diversity may account for the complicated integrative functions of the frog intrinsic cardiac ganglia. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Vagal Sensory Neuron Subtypes that Differentially Control Breathing

    OpenAIRE

    Chang, Rui B.; Strochlic, David E.; Williams, Erika K.; Umans, Benjamin D.; Liberles, Stephen D.

    2015-01-01

    Breathing is essential for survival and under precise neural control. The vagus nerve is a major conduit between lung and brain required for normal respiration. Here, we identify two populations of mouse vagus nerve afferents (P2ry1, Npy2r), each a few hundred neurons, that exert powerful and opposing effects on breathing. Genetically guided anatomical mapping revealed that these neurons densely innervate the lung and send long-range projections to different brainstem targets. Npy2r neurons a...

  19. Neurite outgrowth in human iPSC-derived neurons

    Science.gov (United States)

    Data on morphology of rat and human neurons in cell cultureThis dataset is associated with the following publication:Druwe, I., T. Freudenrich , K. Wallace , T. Shafer , and W. Mundy. Comparison of Human Induced PluripotentStem Cell-Derived Neurons and Rat Primary CorticalNeurons as In Vitro Models of Neurite Outgrowth. Applied In vitro Toxicology. Mary Ann Liebert, Inc., Larchmont, NY, USA, 2(1): 26-36, (2016).

  20. Extracellular clusterin promotes neuronal network complexity in vitro

    DEFF Research Database (Denmark)

    Wicher, Grzegorz; Velsecchi, Isabel; Charnay, Yves

    2008-01-01

    of cellular debris. Intracellularly, clusterin may regulate signal transduction and is upregulated after cell stress. After neural injury, clusterin may be involved in nerve cell survival and postinjury neuroplasticity. In this study, we investigated the role of extracellular clusterin on neuronal network...... complexity in vitro. Quantitative analysis of clustrin-treated neuronal cultures showed significantly higher network complexity. These findings suggest that in addition to previously demonstrated neuroprotective roles, clusterin may also be involved in neuronal process formation, elongation, and plasticity....

  1. Dissecting Neuronal Participation to Focal Epileptic Events in Vivo

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-15-1-0631 TITLE: Dissecting Neuronal Participation to Focal Epileptic Events in Vivo PRINCIPAL INVESTIGATOR: Stelios M...SUBTITLE 5a. CONTRACT NUMBER Dissecting Neuronal Participation to Focal Epileptic Events in Vivo 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...rational approaches to therapy we need to understand the role that individual neurons of different types play in epileptic events. The two-photon

  2. Light-neuron interactions: key to understanding the brain

    Science.gov (United States)

    Go, Mary Ann; Daria, Vincent R.

    2017-02-01

    In recent years, advances in light-based technology have driven an ongoing optical revolution in neuroscience. Synergistic technologies in laser microscopy, molecular biology, organic and synthetic chemistry, genetic engineering and materials science have allowed light to overcome the limitations of and to replace many conventional tools used by physiologists to record from and to manipulate single cells or whole cellular networks. Here we review the different optical techniques for stimulating neurons, influencing neuronal growth, manipulating neuronal structures and neurosurgery.

  3. Phagocytosis executes delayed neuronal death after focal brain ischemia

    OpenAIRE

    Neher, Jonas J.; Emmrich, Julius V.; Fricker, Michael; Mander, Palwinder K.; Théry, Clotilde; Brown, Guy C.

    2013-01-01

    Brain ischemia is a major cause of death and disability worldwide, but the cellular mechanisms of delayed neuronal loss and brain atrophy after cerebral ischemia are poorly understood and thus currently untreatable. Surprisingly, we find that after cerebral ischemia, brain macrophages phagocytose viable and functional neurons, causing brain atrophy and motor dysfunction. Our data show that delayed neuronal death and functional impairment after cerebral ischemia can be prevented by blocking sp...

  4. Somatodendritic and excitatory postsynaptic distribution of neuron-type dystrophin isoform, Dp40, in hippocampal neurons.

    Science.gov (United States)

    Fujimoto, Takahiro; Itoh, Kyoko; Yaoi, Takeshi; Fushiki, Shinji

    2014-09-12

    The Duchenne muscular dystrophy (DMD) gene produces multiple dystrophin (Dp) products due to the presence of several promoters. We previously reported the existence of a novel short isoform of Dp, Dp40, in adult mouse brain. However, the exact biochemical expression profile and cytological distribution of the Dp40 protein remain unknown. In this study, we generated a polyclonal antibody against the NH2-terminal region of the Dp40 and identified the expression profile of Dp40 in the mouse brain. Through an analysis using embryonic and postnatal mouse cerebrums, we found that Dp40 emerged from the early neonatal stages until adulthood, whereas Dp71, an another Dp short isoform, was highly detected in both prenatal and postnatal cerebrums. Intriguingly, relative expressions of Dp40 and Dp71 were prominent in cultured dissociated neurons and non-neuronal cells derived from mouse hippocampus, respectively. Furthermore, the immunocytological distribution of Dp40 was analyzed in dissociated cultured neurons, revealing that Dp40 is detected in the soma and its dendrites, but not in the axon. It is worthy to note that Dp40 is localized along the subplasmalemmal region of the dendritic shafts, as well as at excitatory postsynaptic sites. Thus, Dp40 was identified as a neuron-type Dp possibly involving dendritic and synaptic functions. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Nucleoli numbers and neuronal growth in supraoptic nucleus neurons during postnatal development in the rat.

    Science.gov (United States)

    Crespo, D; Viadero, C F; Villegas, J; Lafarga, M

    1988-11-01

    We present a quantitative study of the variations in the number of nucleoli in supraoptic nucleus neurons during the postnatal period, as well as a morphometric and stereological analysis of the nuclear and cytoplasmic volume changes of these maturing neurons. The mean number of nucleoli per cell was 1.59 +/- 0.28 (mean +/- S.D.) at P1; it then began to decrease until P14 (1.32 +/- 0.67) at which age the adult pattern in the number of nucleoli was attained. The mean nuclear volume increased steadily from 214.56 +/- 6.48 microns 3 (mean +/- S.E.) at P1 to 326.1 +/- 10.93 microns 3 at P14 where it remained constant. The average cytoplasmic volume underwent a remarkable increase during postnatal period from 256.38 +/- 12.66 microns 3 at P1 to 3791.18 +/- 204.88 microns 3 at P90. It is noteworthy that the stabilization of the number of nucleoli coincides with the termination of the nuclear growth phase of supraoptic neurons. We suggest that these nuclear and nucleolar changes reflect the attainment of the fully-differentiated state of the protein synthesis machinery in these neurosecretory neurons.

  6. A high-throughput model for investigating neuronal function and synaptic transmission in cultured neuronal networks.

    Science.gov (United States)

    Virdee, Jasmeet K; Saro, Gabriella; Fouillet, Antoine; Findlay, Jeremy; Ferreira, Filipa; Eversden, Sarah; O'Neill, Michael J; Wolak, Joanna; Ursu, Daniel

    2017-11-03

    Loss of synapses or alteration of synaptic activity is associated with cognitive impairment observed in a number of psychiatric and neurological disorders, such as schizophrenia and Alzheimer's disease. Therefore successful development of in vitro methods that can investigate synaptic function in a high-throughput format could be highly impactful for neuroscience drug discovery. We present here the development, characterisation and validation of a novel high-throughput in vitro model for assessing neuronal function and synaptic transmission in primary rodent neurons. The novelty of our approach resides in the combination of the electrical field stimulation (EFS) with data acquisition in spatially separated areas of an interconnected neuronal network. We integrated our methodology with state of the art drug discovery instrumentation (FLIPR Tetra) and used selective tool compounds to perform a systematic pharmacological validation of the model. We investigated pharmacological modulators targeting pre- and post-synaptic receptors (AMPA, NMDA, GABA-A, mGluR2/3 receptors and Nav, Cav voltage-gated ion channels) and demonstrated the ability of our model to discriminate and measure synaptic transmission in cultured neuronal networks. Application of the model described here as an unbiased phenotypic screening approach will help with our long term goals of discovering novel therapeutic strategies for treating neurological disorders.

  7. Electrical silencing of PDF neurons advances the phase of non-PDF clock neurons in Drosophila.

    Science.gov (United States)

    Wu, Ying; Cao, Guan; Nitabach, Michael N

    2008-04-01

    Drosophila clock neurons exhibit self-sustaining cellular oscillations that rely in part on rhythmic transcriptional feedback loops. We have previously determined that electrical silencing of the pigment dispersing factor (PDF)-expressing lateral-ventral (LN(V)) pacemaker subset of fly clock neurons via expression of an inward-rectifier K(+) channel (Kir2.1) severely disrupts free-running rhythms of locomotor activity-most flies are arrhythmic and those that are not exhibit weak short-period rhythms-and abolishes LN(V) molecular oscillation in constant darkness. PDF is known to be an important LN(V) output signal. Here we examine the effects of electrical silencing of the LN(V) pacemakers on molecular rhythms in other, nonsilenced, subsets of clock neurons. In contrast to previously described cell-autonomous abolition of free-running molecular rhythms, we find that electrical silencing of the LN(V) pacemakers via Kir2.1 expression does not impair molecular rhythms in LN(D), DN1, and DN2 subsets of clock neurons. However, free-running molecular rhythms in these non-LN(V) clock neurons occur with advanced phase. Electrical silencing of LN(V)s phenocopies PDF null mutation (pdf (01) ) at both behavioral and molecular levels except for the complete abolition of free-running cellular oscillation in the LN(V)s themselves. LN(V) electrically silenced or pdf 01 flies exhibit weak free-running behavioral rhythms with short period, and the molecular oscillation in non-LN(V) neurons phase advances in constant darkness. That LN( V) electrical silencing leads to the same behavioral and non-LN( V) molecular phenotypes as pdf 01 suggests that persistence of LN(V) molecular oscillation in pdf 01 flies has no functional effect, either on behavioral rhythms or on non-LN(V) molecular rhythms. We thus conclude that functionally relevant signals from LN(V)s to non-LN(V) clock neurons and other downstream targets rely both on PDF signaling and LN(V) electrical activity, and that LN( V

  8. Visualization of Sensory Neurons and Their Projections in an Upper Motor Neuron Reporter Line.

    Science.gov (United States)

    Genç, Barış; Lagrimas, Amiko Krisa Bunag; Kuru, Pınar; Hess, Robert; Tu, Michael William; Menichella, Daniela Maria; Miller, Richard J; Paller, Amy S; Özdinler, P Hande

    2015-01-01

    Visualization of peripheral nervous system axons and cell bodies is important to understand their development, target recognition, and integration into complex circuitries. Numerous studies have used protein gene product (PGP) 9.5 [a.k.a. ubiquitin carboxy-terminal hydrolase L1 (UCHL1)] expression as a marker to label sensory neurons and their axons. Enhanced green fluorescent protein (eGFP) expression, under the control of UCHL1 promoter, is stable and long lasting in the UCHL1-eGFP reporter line. In addition to the genetic labeling of corticospinal motor neurons in the motor cortex and degeneration-resistant spinal motor neurons in the spinal cord, here we report that neurons of the peripheral nervous system are also fluorescently labeled in the UCHL1-eGFP reporter line. eGFP expression is turned on at embryonic ages and lasts through adulthood, allowing detailed studies of cell bodies, axons and target innervation patterns of all sensory neurons in vivo. In addition, visualization of both the sensory and the motor neurons in the same animal offers many advantages. In this report, we used UCHL1-eGFP reporter line in two different disease paradigms: diabetes and motor neuron disease. eGFP expression in sensory axons helped determine changes in epidermal nerve fiber density in a high-fat diet induced diabetes model. Our findings corroborate previous studies, and suggest that more than five months is required for significant skin denervation. Crossing UCHL1-eGFP with hSOD1G93A mice generated hSOD1G93A-UeGFP reporter line of amyotrophic lateral sclerosis, and revealed sensory nervous system defects, especially towards disease end-stage. Our studies not only emphasize the complexity of the disease in ALS, but also reveal that UCHL1-eGFP reporter line would be a valuable tool to visualize and study various aspects of sensory nervous system development and degeneration in the context of numerous diseases.

  9. Spiking Activity of a LIF Neuron in Distributed Delay Framework

    Directory of Open Access Journals (Sweden)

    Saket Kumar Choudhary

    2016-06-01

    Full Text Available Evolution of membrane potential and spiking activity for a single leaky integrate-and-fire (LIF neuron in distributed delay framework (DDF is investigated. DDF provides a mechanism to incorporate memory element in terms of delay (kernel function into a single neuron models. This investigation includes LIF neuron model with two different kinds of delay kernel functions, namely, gamma distributed delay kernel function and hypo-exponential distributed delay kernel function. Evolution of membrane potential for considered models is studied in terms of stationary state probability distribution (SPD. Stationary state probability distribution of membrane potential (SPDV for considered neuron models are found asymptotically similar which is Gaussian distributed. In order to investigate the effect of membrane potential delay, rate code scheme for neuronal information processing is applied. Firing rate and Fano-factor for considered neuron models are calculated and standard LIF model is used for comparative study. It is noticed that distributed delay increases the spiking activity of a neuron. Increase in spiking activity of neuron in DDF is larger for hypo-exponential distributed delay function than gamma distributed delay function. Moreover, in case of hypo-exponential delay function, a LIF neuron generates spikes with Fano-factor less than 1.

  10. Coexistence of tonic firing and bursting in cortical neurons

    Science.gov (United States)

    Fröhlich, Flavio; Bazhenov, Maxim

    2006-09-01

    Sustained neuronal activity can be broadly classified as either tonic firing or bursting. These two major patterns of neuronal oscillations are state dependent and may coexist. The dynamics and intracellular mechanisms of transitions between tonic firing and bursting in cortical networks remain poorly understood. Here we describe a detailed two-compartment conductance-based cortical neuron model which exhibits bistability with hysteresis between tonic firing and bursting for elevated extracellular potassium concentration. The study explains the ionic and dynamical mechanisms of burst generation and reveals the conditions underlying coexistence of two different oscillatory modes as a function of neuronal excitability.

  11. Disruption of Axonal Transport in Motor Neuron Diseases

    Directory of Open Access Journals (Sweden)

    Gen Sobue

    2012-01-01

    Full Text Available Motor neurons typically have very long axons, and fine-tuning axonal transport is crucial for their survival. The obstruction of axonal transport is gaining attention as a cause of neuronal dysfunction in a variety of neurodegenerative motor neuron diseases. Depletions in dynein and dynactin-1, motor molecules regulating axonal trafficking, disrupt axonal transport in flies, and mutations in their genes cause motor neuron degeneration in humans and rodents. Axonal transport defects are among the early molecular events leading to neurodegeneration in mouse models of amyotrophic lateral sclerosis (ALS. Gene expression profiles indicate that dynactin-1 mRNA is downregulated in degenerating spinal motor neurons of autopsied patients with sporadic ALS. Dynactin-1 mRNA is also reduced in the affected neurons of a mouse model of spinal and bulbar muscular atrophy, a motor neuron disease caused by triplet CAG repeat expansion in the gene encoding the androgen receptor. Pathogenic androgen receptor proteins also inhibit kinesin-1 microtubule-binding activity and disrupt anterograde axonal transport by activating c-Jun N-terminal kinase. Disruption of axonal transport also underlies the pathogenesis of spinal muscular atrophy and hereditary spastic paraplegias. These observations suggest that the impairment of axonal transport is a key event in the pathological processes of motor neuron degeneration and an important target of therapy development for motor neuron diseases.

  12. Modulation of neuronal dynamic range using two different adaptation mechanisms

    Science.gov (United States)

    Wang, Lei; Wang, Ye; Fu, Wen-long; Cao, Li-hong

    2017-01-01

    The capability of neurons to discriminate between intensity of external stimulus is measured by its dynamic range. A larger dynamic range indicates a greater probability of neuronal survival. In this study, the potential roles of adaptation mechanisms (ion currents) in modulating neuronal dynamic range were numerically investigated. Based on the adaptive exponential integrate-and-fire model, which includes two different adaptation mechanisms, i.e. subthreshold and suprathreshold (spike-triggered) adaptation, our results reveal that the two adaptation mechanisms exhibit rather different roles in regulating neuronal dynamic range. Specifically, subthreshold adaptation acts as a negative factor that observably decreases the neuronal dynamic range, while suprathreshold adaptation has little influence on the neuronal dynamic range. Moreover, when stochastic noise was introduced into the adaptation mechanisms, the dynamic range was apparently enhanced, regardless of what state the neuron was in, e.g. adaptive or non-adaptive. Our model results suggested that the neuronal dynamic range can be differentially modulated by different adaptation mechanisms. Additionally, noise was a non-ignorable factor, which could effectively modulate the neuronal dynamic range. PMID:28469660

  13. Commissural neurons in the rat ventral cochlear nucleus.

    Science.gov (United States)

    Doucet, John R; Lenihan, Nicole M; May, Bradford J

    2009-06-01

    Commissural neurons connect the cochlear nucleus complexes of both ears. Previous studies have suggested that the neurons may be separated into two anatomical subtypes on the basis of percent apposition (PA); that is, the percentage of the soma apposed by synaptic terminals. The present study combined tract tracing with synaptic immunolabeling to compare the soma area, relative number, and location of Type I (low PA) and Type II (high PA) commissural neurons in the ventral cochlear nucleus (VCN) of rats. Confocal microscopic analysis revealed that 261 of 377 (69%) commissural neurons have medium-sized somata with Type I axosomatic innervation. The commissural neurons also showed distinct topographical distributions. The majority of Type I neurons were located in the small cell cap of the VCN, which serves as a nexus for regulatory pathways within the auditory brainstem. Most Type II neurons were found in the magnocellular core. This anatomical dichotomy should broaden current views on the function of the commissural pathway that stress the fast inhibitory interactions generated by Type II neurons. The more prevalent Type I neurons may underlie slow regulatory influences that enhance binaural processing or the recovery of function after injury.

  14. Subtypes of GABAergic neurons project axons in the neocortex

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    Shigeyoshi Higo

    2009-11-01

    Full Text Available γ-aminobutyric acid (GABAergic neurons in the neocortex have been regarded as interneurons and speculated to modulate the activity of neurons locally. Recently, however, several experiments revealed that neuronal nitric oxide synthase (nNOS-positive GABAergic neurons project cortico-cortically with long axons. In this study, we illustrate Golgi-like images of the nNOS-positive GABAergic neurons using a nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d reaction and follow the emanating axon branches in cat brain sections. These axon branches projected cortico-cortically with other non-labeled arcuate fibers, contra-laterally via the corpus callosum and anterior commissure. The labeled fibers were not limited to the neocortex but found also in the fimbria of the hippocampus. In order to have additional information on these GABAergic neuron projections, we investigated green fluorescent protein (GFP-labeled GABAergic neurons in GAD67-Cre knock-in / GFP Cre-reporter mice. GFP-labeled axons emanate densely, especially in the fimbria, a small number in the anterior commissure, and very sparsely in the corpus callosum. These two different approaches confirm that not only nNOS-positive GABAergic neurons but also other subtypes of GABAergic neurons project long axons in the cerebral cortex and are in a position to be involved in information processing.

  15. Modulatory Mechanism of Nociceptive Neuronal Activity by Dietary Constituent Resveratrol

    National Research Council Canada - National Science Library

    Takeda, Mamoru; Takehana, Shiori; Sekiguchi, Kenta; Kubota, Yoshiko; Shimazu, Yoshihito

    2016-01-01

    ...) candidate, specifically a therapeutic agent. The focus of this review is on the mechanisms underlying the modulatory effects of resveratrol on nociceptive neuronal activity associated with pain relief...

  16. The Application of Big-Neuron Theory in Expert Systems

    Institute of Scientific and Technical Information of China (English)

    李涛

    2001-01-01

    With a new way of knowledge representation and acquirement, inference, and building an expert system based on big-neurons composed of different field expert knowledge presented, the fundamental theory and architecture of expert system based upon big-neuron theory has thus been built. It is unnecessary to organize a large number of production rules when using big-neurons to build an expert system. The facts and rules of an expert system have already been hidden in big-neurons. And also, it is unnecessary to do a great quantity of tree searching when using this method to do logic reasoning. Machine can do self-organizing and self-learning.

  17. Redefining the gonadotrophin-releasing hormone neurone dendrite.

    Science.gov (United States)

    Campbell, R E; Suter, K J

    2010-07-01

    Gonadotrophin-releasing hormone (GnRH) neurones are the final output neurones of the complex synaptic network responsible for the central control of fertility. This scattered population of neurones has been shown to have remarkably long dendritic processes by cell-filling of GnRH neurones in situ with low-molecular weight dyes. This review focuses on how the functional significance of these long dendritic extensions is being explored through dual somatic-dendritic electrophysiological recordings, computational modelling, immunolabelling for specific channels and multiple modes of microscopy and imaging. Remarkably, recent work has discovered that GnRH neurone dendrites not only actively propagate action potentials, but also comprise the primary site of action potential initiation. These findings, along with the discovery of regionalized expression of active conductances, highlight dendrites of single GnRH neurones as being central sites of signal integration. Moreover, imaging studies have shown that the long dendrites of GnRH neurones intertwine and bundle with one another. The presence of shared synaptic input to bundling dendrites, coupled with their active properties and the increased potency of distally placed synaptic inputs, is suggestive of a novel mechanism of GnRH neurone synchronisation, a feature critical for mammalian reproduction. Together, these discoveries of the GnRH neurone dendrite structure and function are changing the way that we view the central regulation of fertility.

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

    Science.gov (United States)

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

    2015-05-28

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

  19. Identifying local and descending inputs for primary sensory neurons.

    Science.gov (United States)

    Zhang, Yi; Zhao, Shengli; Rodriguez, Erica; Takatoh, Jun; Han, Bao-Xia; Zhou, Xiang; Wang, Fan

    2015-10-01

    Primary pain and touch sensory neurons not only detect internal and external sensory stimuli, but also receive inputs from other neurons. However, the neuronal derived inputs for primary neurons have not been systematically identified. Using a monosynaptic rabies viruses-based transneuronal tracing method combined with sensory-specific Cre-drivers, we found that sensory neurons receive intraganglion, intraspinal, and supraspinal inputs, the latter of which are mainly derived from the rostroventral medulla (RVM). The viral-traced central neurons were largely inhibitory but also consisted of some glutamatergic neurons in the spinal cord and serotonergic neurons in the RVM. The majority of RVM-derived descending inputs were dual GABAergic and enkephalinergic (opioidergic). These inputs projected through the dorsolateral funiculus and primarily innervated layers I, II, and V of the dorsal horn, where pain-sensory afferents terminate. Silencing or activation of the dual GABA/enkephalinergic RVM neurons in adult animals substantially increased or decreased behavioral sensitivity, respectively, to heat and mechanical stimuli. These results are consistent with the fact that both GABA and enkephalin can exert presynaptic inhibition of the sensory afferents. Taken together, this work provides a systematic view of and a set of tools for examining peri- and extrasynaptic regulations of pain-afferent transmission.

  20. Structural properties of the Caenorhabditis elegans neuronal network

    National Research Council Canada - National Science Library

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

    2011-01-01

    .... 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...

  1. Structural properties of the Caenorhabditis elegans neuronal network

    National Research Council Canada - National Science Library

    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...

  2. Behavioral plasticity through the modulation of switch neurons.

    Science.gov (United States)

    Vassiliades, Vassilis; Christodoulou, Chris

    2016-02-01

    A central question in artificial intelligence is how to design agents capable of switching between different behaviors in response to environmental changes. Taking inspiration from neuroscience, we address this problem by utilizing artificial neural networks (NNs) as agent controllers, and mechanisms such as neuromodulation and synaptic gating. The novel aspect of this work is the introduction of a type of artificial neuron we call "switch neuron". A switch neuron regulates the flow of information in NNs by selectively gating all but one of its incoming synaptic connections, effectively allowing only one signal to propagate forward. The allowed connection is determined by the switch neuron's level of modulatory activation which is affected by modulatory signals, such as signals that encode some information about the reward received by the agent. An important aspect of the switch neuron is that it can be used in appropriate "switch modules" in order to modulate other switch neurons. As we show, the introduction of the switch modules enables the creation of sequences of gating events. This is achieved through the design of a modulatory pathway capable of exploring in a principled manner all permutations of the connections arriving on the switch neurons. We test the model by presenting appropriate architectures in nonstationary binary association problems and T-maze tasks. The results show that for all tasks, the switch neuron architectures generate optimal adaptive behaviors, providing evidence that the switch neuron model could be a valuable tool in simulations where behavioral plasticity is required. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Distinctive glial and neuronal interfacing on nanocrystalline diamond.

    Directory of Open Access Journals (Sweden)

    Amel Bendali

    Full Text Available Direct electrode/neuron interfacing is a key challenge to achieve high resolution of neuronal stimulation required for visual prostheses. Neuronal interfacing on biomaterials commonly requires the presence of glial cells and/or protein coating. Nanocrystalline diamond is a highly mechanically stable biomaterial with a remarkably large potential window for the electrical stimulation of tissues. Using adult retinal cell cultures from rats, we found that glial cells and retinal neurons grew equally well on glass and nanocrystalline diamond. The use of a protein coating increased cell survival, particularly for glial cells. However, bipolar neurons appeared to grow even in direct contact with bare diamond. We investigated whether the presence of glial cells contributed to this direct neuron/diamond interface, by using purified adult retinal ganglion cells to seed diamond and glass surfaces with and without protein coatings. Surprisingly, these fully differentiated spiking neurons survived better on nanocrystalline diamond without any protein coating. This greater survival was indicated by larger cell numbers and the presence of longer neurites. When a protein pattern was drawn on diamond, neurons did not grow preferentially on the coated area, by contrast to their behavior on a patterned glass. This study highlights the interesting biocompatibility properties of nanocrystalline diamond, allowing direct neuronal interfacing, whereas a protein coating was required for glial cell growth.

  4. Electrophysiological properties of embryonic stem cell-derived neurons.

    Directory of Open Access Journals (Sweden)

    Jessica R Risner-Janiczek

    Full Text Available In vitro generation of functional neurons from embryonic stem (ES cells and induced pluripotent stem cells offers exciting opportunities for dissecting gene function, disease modelling, and therapeutic drug screening. To realize the potential of stem cells in these biomedical applications, a complete understanding of the cell models of interest is required. While rapid advances have been made in developing the technologies for directed induction of defined neuronal subtypes, most published works focus on the molecular characterization of the derived neural cultures. To characterize the functional properties of these neural cultures, we utilized an ES cell model that gave rise to neurons expressing the green fluorescent protein (GFP and conducted targeted whole-cell electrophysiological recordings from ES cell-derived neurons. Current-clamp recordings revealed that most neurons could fire single overshooting action potentials; in some cases multiple action potentials could be evoked by depolarization, or occurred spontaneously. Voltage-clamp recordings revealed that neurons exhibited neuronal-like currents, including an outward current typical of a delayed rectifier potassium conductance and a fast-activating, fast-inactivating inward current, typical of a sodium conductance. Taken together, these results indicate that ES cell-derived GFP(+ neurons in culture display functional neuronal properties even at early stages of differentiation.

  5. Glutamate and GABA as rapid effectors of hypothalamic peptidergic neurons

    Directory of Open Access Journals (Sweden)

    Cornelia eSchöne

    2012-11-01

    Full Text Available Vital hypothalamic neurons regulating hunger, wakefulness, reward-seeking, and body weight are often defined by unique expression of hypothalamus-specific neuropeptides. Gene-ablation studies show that some of these peptides, notably orexin/hypocretin (hcrt/orx, are themselves critical for stable states of consciousness and metabolic health. However, neuron-ablation studies often reveal more severe phenotypes, suggesting key roles for co-expressed transmitters. Indeed, most hypothalamic neurons, including hcrt/orx cells, contain fast transmitters glutamate and GABA, as well as several neuropeptides. What are the roles and relations between different transmitters expressed by the same neuron? Here, we consider signaling codes for releasing different transmitters in relation to transmitter and receptor diversity in behaviorally-defined, widely-projecting peptidergic neurons, such as hcrt/orx cells. We then discuss latest optogenetic studies of endogenous transmitter release from defined sets of axons in situ, which suggest that recently-characterized vital peptidergic neurons (e.g. hcrt/orx, proopiomelanocortin , and agouti-related peptide cells, as well as classical modulatory neurons (e.g. dopamine and acetylcholine cells, all use fast transmitters to control their postsynaptic targets. These optogenetic insights are complemented by recent observations of behavioral deficiencies caused by genetic ablation of fast transmission from specific neuropeptidergic and aminergic neurons. Powerful and fast (millisecond-scale GABAergic and glutamatergic signaling from neurons previously considered to be primarily modulatory raises new questions about the roles of slower co-transmitters they co-express.

  6. Neuronal Rac1 is required for learning-evoked neurogenesis

    DEFF Research Database (Denmark)

    Haditsch, Ursula; Anderson, Matthew P; Freewoman, Julia

    2013-01-01

    Hippocampus-dependent learning and memory relies on synaptic plasticity as well as network adaptations provided by the addition of adult-born neurons. We have previously shown that activity-induced intracellular signaling through the Rho family small GTPase Rac1 is necessary in forebrain projection...... neurons for normal synaptic plasticity in vivo, and here we show that selective loss of neuronal Rac1 also impairs the learning-evoked increase in neurogenesis in the adult mouse hippocampus. Earlier work has indicated that experience elevates the abundance of adult-born neurons in the hippocampus...

  7. Innervation by a GABAergic neuron depresses spontaneous release in glutamatergic neurons and unveils the clamping phenotype of synaptotagmin-1

    DEFF Research Database (Denmark)

    Wierda, Keimpe D B; Sørensen, Jakob Balslev

    2014-01-01

    The role of spontaneously occurring release events in glutamatergic and GABAergic neurons and their regulation is intensely debated. To study the interdependence of glutamatergic and GABAergic spontaneous release, we compared reciprocally connected "mixed" glutamatergic/GABAergic neuronal pairs...... from mice cultured on astrocyte islands with "homotypic" glutamatergic or GABAergic pairs and autaptic neurons. We measured mEPSC and mIPSC frequencies simultaneously from both neurons. Neuronal pairs formed both interneuronal synaptic and autaptic connections indiscriminately. We find that whereas m......EPSC and mIPSC frequencies did not deviate between autaptic and synaptic connections, the frequency of mEPSCs in mixed pairs was strongly depressed compared with either autaptic neurons or glutamatergic pairs. Simultaneous imaging of synapses, or comparison to evoked release amplitudes, showed...

  8. Somatodendritic and excitatory postsynaptic distribution of neuron-type dystrophin isoform, Dp40, in hippocampal neurons

    Energy Technology Data Exchange (ETDEWEB)

    Fujimoto, Takahiro; Itoh, Kyoko, E-mail: kxi14@koto.kpu-m.ac.jp; Yaoi, Takeshi; Fushiki, Shinji

    2014-09-12

    Highlights: • Identification of dystrophin (Dp) shortest isoform, Dp40, is a neuron-type Dp. • Dp40 expression is temporally and differentially regulated in comparison to Dp71. • Somatodendritic and nuclear localization of Dp40. • Dp40 is localized to excitatory postsynapses. • Dp40 might play roles in dendritic and synaptic functions. - Abstract: The Duchenne muscular dystrophy (DMD) gene produces multiple dystrophin (Dp) products due to the presence of several promoters. We previously reported the existence of a novel short isoform of Dp, Dp40, in adult mouse brain. However, the exact biochemical expression profile and cytological distribution of the Dp40 protein remain unknown. In this study, we generated a polyclonal antibody against the NH{sub 2}-terminal region of the Dp40 and identified the expression profile of Dp40 in the mouse brain. Through an analysis using embryonic and postnatal mouse cerebrums, we found that Dp40 emerged from the early neonatal stages until adulthood, whereas Dp71, an another Dp short isoform, was highly detected in both prenatal and postnatal cerebrums. Intriguingly, relative expressions of Dp40 and Dp71 were prominent in cultured dissociated neurons and non-neuronal cells derived from mouse hippocampus, respectively. Furthermore, the immunocytological distribution of Dp40 was analyzed in dissociated cultured neurons, revealing that Dp40 is detected in the soma and its dendrites, but not in the axon. It is worthy to note that Dp40 is localized along the subplasmalemmal region of the dendritic shafts, as well as at excitatory postsynaptic sites. Thus, Dp40 was identified as a neuron-type Dp possibly involving dendritic and synaptic functions.

  9. Subset specification of central serotonergic neurons

    Directory of Open Access Journals (Sweden)

    Marten P Smidt

    2013-10-01

    Full Text Available The last decade the serotonin (5-hydroxytryptamine; 5-HT system has received enormous attention due to its role in regulation of behavior, exemplified by the discovery that increased 5-HT tone in the central nervous system is able to alleviate affective disorders. Here, we review the developmental processes, with a special emphasis on subset specification, leading to the formation of the 5-HT system in the brain. Molecular classification of 5-HT neuronal groups leads to the definition of two independent rostral groups positioned in rhombomere 1 and 2/3 and a caudal group in rhombomere 5-8. In addition, more disperse refinement of these subsets is present as shown by the selective expression of the 5-HT1A autoreceptor, indicating functional diversity between 5-HT subsets. The functional significance of the molecular coding differences is not well known and the molecular basis of described specific connectivity patterns remain to be elucidated. Recent developments in genetic lineage tracing models will provide these data and form a major step-up towards the full understanding of the importance of developmental programming and function of 5-HT neuronal subsets.

  10. Antioxidant gene therapy against neuronal cell death

    Science.gov (United States)

    Navarro-Yepes, Juliana; Zavala-Flores, Laura; Annadurai, Anandhan; Wang, Fang; Skotak, Maciej; Chandra, Namas; Li, Ming; Pappa, Aglaia; Martinez-Fong, Daniel; Razo, Luz Maria Del; Quintanilla-Vega, Betzabet; Franco, Rodrigo

    2014-01-01

    Oxidative stress is a common hallmark of neuronal cell death associated with neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, as well as brain stroke/ischemia and traumatic brain injury. Increased accumulation of reactive species of both oxygen (ROS) and nitrogen (RNS) has been implicated in mitochondrial dysfunction, energy impairment, alterations in metal homeostasis and accumulation of aggregated proteins observed in neurodegenerative disorders, which lead to the activation/modulation of cell death mechanisms that include apoptotic, necrotic and autophagic pathways. Thus, the design of novel antioxidant strategies to selectively target oxidative stress and redox imbalance might represent important therapeutic approaches against neurological disorders. This work reviews the evidence demonstrating the ability of genetically encoded antioxidant systems to selectively counteract neuronal cell loss in neurodegenerative diseases and ischemic brain damage. Because gene therapy approaches to treat inherited and acquired disorders offer many unique advantages over conventional therapeutic approaches, we discussed basic research/clinical evidence and the potential of virus-mediated gene delivery techniques for antioxidant gene therapy. PMID:24333264

  11. Models of the stochastic activity of neurones

    CERN Document Server

    Holden, Arun Vivian

    1976-01-01

    These notes have grown from a series of seminars given at Leeds between 1972 and 1975. They represent an attempt to gather together the different kinds of model which have been proposed to account for the stochastic activity of neurones, and to provide an introduction to this area of mathematical biology. A striking feature of the electrical activity of the nervous system is that it appears stochastic: this is apparent at all levels of recording, ranging from intracellular recordings to the electroencephalogram. The chapters start with fluctuations in membrane potential, proceed through single unit and synaptic activity and end with the behaviour of large aggregates of neurones: L have chgaen this seque~~e\\/~~';uggest that the interesting behaviourr~f :the nervous system - its individuality, variability and dynamic forms - may in part result from the stochastic behaviour of its components. I would like to thank Dr. Julio Rubio for reading and commenting on the drafts, Mrs. Doris Beighton for producing the fin...

  12. Investigating neuronal function with optically controllable proteins

    Directory of Open Access Journals (Sweden)

    Xin X Zhou

    2015-07-01

    Full Text Available In the nervous system, protein activities are highly regulated in space and time. This regulation allows for fine modulation of neuronal structure and function during development and adaptive responses. For example, neurite extension and synaptogenesis both involve localized and transient activation of cytoskeletal and signaling proteins, allowing changes in microarchitecture to occur rapidly and in a localized manner. To investigate the role of specific protein regulation events in these processes, scientists have been developing tools for optical control of the activity of specific proteins. In this review, we focus on how some recently developed optical control modules have been used in neuroscience applications. These tools have demonstrated impressive versatility in controlling various protein families and thereby cellular functions, and possess enormous potential for future applications in nervous systems. Just as optogenetic control of neuronal firings using rhodopsins has changed how we investigate circuitry function in vivo, optical control may yet yield another revolution in how we study intracellular signaling activities in the brain.

  13. Slow waves in mutually inhibitory neuronal networks

    Science.gov (United States)

    Jalics, Jozsi

    2004-05-01

    A variety of experimental and modeling studies have been performed to investigate wave propagation in networks of thalamic neurons and their relationship to spindle sleep rhythms. It is believed that spindle oscillations result from the reciprocal interaction between thalamocortical (TC) and thalamic reticular (RE) neurons. We consider a network of TC and RE cells reduced to a one-layer network model and represented by a system of singularly perturbed integral-differential equations. Geometric singular perturbation methods are used to prove the existence of a locally unique slow wave pulse that propagates along the network. By seeking a slow pulse solution, we reformulate the problem to finding a heteroclinic orbit in a 3D system of ODEs with two additional constraints on the location of the orbit at two distinct points in time. In proving the persistence of the singular heteroclinic orbit, difficulties arising from the solution passing near points where normal hyperbolicity is lost on a 2D critical manifold are overcome by employing results by Wechselberger [Singularly perturbed folds and canards in R3, Thesis, TU-Wien, 1998].

  14. Neuropeptide Y stimulates autophagy in hypothalamic neurons.

    Science.gov (United States)

    Aveleira, Célia A; Botelho, Mariana; Carmo-Silva, Sara; Pascoal, Jorge F; Ferreira-Marques, Marisa; Nóbrega, Clévio; Cortes, Luísa; Valero, Jorge; Sousa-Ferreira, Lígia; Álvaro, Ana R; Santana, Magda; Kügler, Sebastian; Pereira de Almeida, Luís; Cavadas, Cláudia

    2015-03-31

    Aging is characterized by autophagy impairment that contributes to age-related disease aggravation. Moreover, it was described that the hypothalamus is a critical brain area for whole-body aging development and has impact on lifespan. Neuropeptide Y (NPY) is one of the major neuropeptides present in the hypothalamus, and it has been shown that, in aged animals, the hypothalamic NPY levels decrease. Because caloric restriction (CR) delays aging, at least in part, by stimulating autophagy, and also increases hypothalamic NPY levels, we hypothesized that NPY could have a relevant role on autophagy modulation in the hypothalamus. Therefore, the aim of this study was to investigate the role of NPY on autophagy in the hypothalamus. Using both hypothalamic neuronal in vitro models and mice overexpressing NPY in the hypothalamus, we observed that NPY stimulates autophagy in the hypothalamus. Mechanistically, in rodent hypothalamic neurons, NPY increases autophagy through the activation of NPY Y1 and Y5 receptors, and this effect is tightly associated with the concerted activation of PI3K, MEK/ERK, and PKA signaling pathways. Modulation of hypothalamic NPY levels may be considered a potential strategy to produce protective effects against hypothalamic impairments associated with age and to delay aging.

  15. Sleep disordered breathing in motor neurone disease.

    Science.gov (United States)

    D'Cruz, Rebecca F; Murphy, Patrick B; Kaltsakas, Georgios

    2018-01-01

    Motor neurone disease (MND) is a neurodegenerative disease defined by axonal loss and gliosis of upper and lower motor neurones in the motor cortex, lower brainstem nuclei and ventral horn of the spinal cord. MND is currently incurable and has a poor prognosis, with death typically occurring 3 to 5 years after disease onset. The disease is characterised by rapidly progressive weakness leading to paralysis, fasciculations, bulbar symptoms (including dysarthria and dysphagia) and respiratory compromise. Respiratory complications arise as a result of weakness of upper airway (pharyngeal and laryngeal) muscles and respiratory muscles (diaphragm, intercostal and accessory muscles) leading to respiratory failure. Due to early involvement of respiratory muscles in MND, sleep disordered breathing (SDB) occurs at a higher frequency than compared to the general population. SDB usually precedes daytime respiratory symptoms and chronic respiratory failure. It significantly impacts upon patients' quality of life and survival and its presence may predict prognosis. Managing SDB in MND with non-invasive ventilation (NIV) improves quality of life and survival. Early identification and management of SDB in MND patients is therefore crucial. This update will review assessments of respiratory muscle function, types of SDB and the effects of NIV in patients with MND.

  16. Stochastic resonance in hippocampal CA1 neurons

    Science.gov (United States)

    Stacey, William Charles

    Stochastic Resonance (SR) is a phenomenon observed in nonlinear systems whereby the introduction of noise enhances the detection of a subthreshold signal for a certain range of noise intensity. Many central neurons, such as hippocampal CAI cells, are good candidates for SR due to their function of signal detection in a noisy environment, but the role of SR in the CNS is unclear. Physiological levels of noise are able to improve signal detection through SR, as found in simulated CAI neurons and in vitro rat hippocampal slices. Further investigation, utilizing a novel method of in vitro noise modulation, shows that endogenous noise sources can generate SR activity. These results suggest SR may provide a means for the hippocampus to modulate detection of specific inputs through endogenous noise sources. The role of noise in signal detection for a network of CAI cells is tested with a network simulation. The network shows improved detection as the number of cells and coupling increase for noise with low variance. One cell receiving the signal cannot recruit the remaining cells unless the network is very active and tuned by the coupling and noise. Periodic oscillations at high noise amplitudes corrupt all outputs. These oscillations develop into synchronized, periodic bursts as a function of both noise and coupling. These findings are relevant for the analysis of the role of physiological noise in signal processing in the brain and in the synchronization of neural activity as in epilepsy.

  17. Robust Multiobjective Controllability of Complex Neuronal Networks.

    Science.gov (United States)

    Tang, Yang; Gao, Huijun; Du, Wei; Lu, Jianquan; Vasilakos, Athanasios V; Kurths, Jurgen

    2016-01-01

    This paper addresses robust multiobjective identification of driver nodes in the neuronal network of a cat's brain, in which uncertainties in determination of driver nodes and control gains are considered. A framework for robust multiobjective controllability is proposed by introducing interval uncertainties and optimization algorithms. By appropriate definitions of robust multiobjective controllability, a robust nondominated sorting adaptive differential evolution (NSJaDE) is presented by means of the nondominated sorting mechanism and the adaptive differential evolution (JaDE). The simulation experimental results illustrate the satisfactory performance of NSJaDE for robust multiobjective controllability, in comparison with six statistical methods and two multiobjective evolutionary algorithms (MOEAs): nondominated sorting genetic algorithms II (NSGA-II) and nondominated sorting composite differential evolution. It is revealed that the existence of uncertainties in choosing driver nodes and designing control gains heavily affects the controllability of neuronal networks. We also unveil that driver nodes play a more drastic role than control gains in robust controllability. The developed NSJaDE and obtained results will shed light on the understanding of robustness in controlling realistic complex networks such as transportation networks, power grid networks, biological networks, etc.

  18. A novel phase portrait for neuronal excitability.

    Directory of Open Access Journals (Sweden)

    Guillaume Drion

    Full Text Available Fifty years ago, FitzHugh introduced a phase portrait that became famous for a twofold reason: it captured in a physiological way the qualitative behavior of Hodgkin-Huxley model and it revealed the power of simple dynamical models to unfold complex firing patterns. To date, in spite of the enormous progresses in qualitative and quantitative neural modeling, this phase portrait has remained a core picture of neuronal excitability. Yet, a major difference between the neurophysiology of 1961 and of 2011 is the recognition of the prominent role of calcium channels in firing mechanisms. We show that including this extra current in Hodgkin-Huxley dynamics leads to a revision of FitzHugh-Nagumo phase portrait that affects in a fundamental way the reduced modeling of neural excitability. The revisited model considerably enlarges the modeling power of the original one. In particular, it captures essential electrophysiological signatures that otherwise require non-physiological alteration or considerable complexification of the classical model. As a basic illustration, the new model is shown to highlight a core dynamical mechanism by which calcium channels control the two distinct firing modes of thalamocortical neurons.

  19. A developmental approach to predicting neuronal connectivity from small biological datasets: a gradient-based neuron growth model.

    Science.gov (United States)

    Borisyuk, Roman; Al Azad, Abul Kalam; Conte, Deborah; Roberts, Alan; Soffe, Stephen R

    2014-01-01

    Relating structure and function of neuronal circuits is a challenging problem. It requires demonstrating how dynamical patterns of spiking activity lead to functions like cognitive behaviour and identifying the neurons and connections that lead to appropriate activity of a circuit. We apply a "developmental approach" to define the connectome of a simple nervous system, where connections between neurons are not prescribed but appear as a result of neuron growth. A gradient based mathematical model of two-dimensional axon growth from rows of undifferentiated neurons is derived for the different types of neurons in the brainstem and spinal cord of young tadpoles of the frog Xenopus. Model parameters define a two-dimensional CNS growth environment with three gradient cues and the specific responsiveness of the axons of each neuron type to these cues. The model is described by a nonlinear system of three difference equations; it includes a random variable, and takes specific neuron characteristics into account. Anatomical measurements are first used to position cell bodies in rows and define axon origins. Then a generalization procedure allows information on the axons of individual neurons from small anatomical datasets to be used to generate larger artificial datasets. To specify parameters in the axon growth model we use a stochastic optimization procedure, derive a cost function and find the optimal parameters for each type of neuron. Our biologically realistic model of axon growth starts from axon outgrowth from the cell body and generates multiple axons for each different neuron type with statistical properties matching those of real axons. We illustrate how the axon growth model works for neurons with axons which grow to the same and the opposite side of the CNS. We then show how, by adding a simple specification for dendrite morphology, our model "developmental approach" allows us to generate biologically-realistic connectomes.

  20. A developmental approach to predicting neuronal connectivity from small biological datasets: a gradient-based neuron growth model.

    Directory of Open Access Journals (Sweden)

    Roman Borisyuk

    Full Text Available Relating structure and function of neuronal circuits is a challenging problem. It requires demonstrating how dynamical patterns of spiking activity lead to functions like cognitive behaviour and identifying the neurons and connections that lead to appropriate activity of a circuit. We apply a "developmental approach" to define the connectome of a simple nervous system, where connections between neurons are not prescribed but appear as a result of neuron growth. A gradient based mathematical model of two-dimensional axon growth from rows of undifferentiated neurons is derived for the different types of neurons in the brainstem and spinal cord of young tadpoles of the frog Xenopus. Model parameters define a two-dimensional CNS growth environment with three gradient cues and the specific responsiveness of the axons of each neuron type to these cues. The model is described by a nonlinear system of three difference equations; it includes a random variable, and takes specific neuron characteristics into account. Anatomical measurements are first used to position cell bodies in rows and define axon origins. Then a generalization procedure allows information on the axons of individual neurons from small anatomical datasets to be used to generate larger artificial datasets. To specify parameters in the axon growth model we use a stochastic optimization procedure, derive a cost function and find the optimal parameters for each type of neuron. Our biologically realistic model of axon growth starts from axon outgrowth from the cell body and generates multiple axons for each different neuron type with statistical properties matching those of real axons. We illustrate how the axon growth model works for neurons with axons which grow to the same and the opposite side of the CNS. We then show how, by adding a simple specification for dendrite morphology, our model "developmental approach" allows us to generate biologically-realistic connectomes.

  1. Sodium entry during action potentials of mammalian central neurons: incomplete inactivation and reduced metabolic efficiency in fast-spiking neurons

    OpenAIRE

    Carter, Brett C.; Bean, Bruce P.

    2009-01-01

    We measured the time course of sodium entry during action potentials of mouse central neurons at 37 °C to examine how efficiently sodium entry is coupled to depolarization. In cortical pyramidal neurons, sodium entry was nearly completely confined to the rising phase of the spike: only ~25% more sodium enters than the theoretical minimum necessary for spike depolarization. However, in fast-spiking GABAergic neurons (cerebellar Purkinje cells and cortical interneurons), twice as much sodium en...

  2. Expression, transport, and axonal sorting of neuronal CCL21 in large dense-core vesicles.

    NARCIS (Netherlands)

    Jong, E.K. de; Vinet, J.; Stanulovic, V.S.; Meijer, Michel; Wesseling, E.; Sjollema, K.; Boddeke, H.W.; Biber, K.

    2008-01-01

    Neurons are highly polarized cells, and neuron-neuron communication is based on directed transport and release of neurotransmitters, neuropeptides, and neurotrophins. Directed communication may also be attributed to neuron-microglia signaling, since neuronal damage can induce a microglia reaction at

  3. Expression, transport, and axonal sorting of neuronal CCL21 in large dense-core vesicles

    NARCIS (Netherlands)

    de Jong, Eiko K.; Vinet, Jonathan; Stanulovic, Vesna S.; Meijer, Michel; Wesseling, Evelyn; Sjollema, Klaas; Boddeke, Hendrikus W. G. M.; Biber, Knut

    2008-01-01

    Neurons are highly polarized cells, and neuron-neuron communication is based on directed transport and release of neurotransmitters, neuropeptides, and neurotrophins. Directed communication may also be attributed to neuron-microglia signaling, since neuronal damage can induce a microglia reaction at

  4. Neuronal cell fate decisions:  O2 and CO2 sensing neurons require egl-13/Sox5

    DEFF Research Database (Denmark)

    Gramstrup Petersen, Jakob; Pocock, Roger David John

    2013-01-01

    to drive O2 and CO2 sensing neuron fate and is therefore essential for O2 and CO2 sensing-induced behaviors. Through systematic dissection of the egl-13 promoter we identified upstream regulators of egl-13 and proposed a model of how differentiation of O2 and CO2 sensing neurons is regulated......We recently conducted a study that aimed to describe the differentiation mechanisms used to generate O2 and CO2 sensing neurons in C. elegans. We identified egl-13/Sox5 to be required for the differentiation of both O2 and CO2 sensing neurons. We found that egl-13 functions cell autonomously...

  5. Homogeneous generation of iDA neurons with high similarity to bona fide DA neurons using a drug inducible system.

    Science.gov (United States)

    Park, Hanseul; Kim, Hongwon; Yoo, Junsang; Lee, Jaekwang; Choi, Hwan; Baek, Soonbong; Lee, C Justin; Kim, Janghwan; Lengner, Christopher J; Sung, Jung-Suk; Kim, Jongpil

    2015-12-01

    Recent work generating induced dopaminergic (iDA) neurons using direct lineage reprogramming potentially provides a novel platform for the study and treatment Parkinson's disease (PD). However, one of the most important issues for iDA-based applications is the degree to which iDA neurons resemble the molecular and functional properties of their endogenous DA neuron counterparts. Here we report that the homogeneity of the reprogramming gene expression system is critical for the generation of iDA neuron cultures that are highly similar to endogenous DA neurons. We employed an inducible system that carries iDA-inducing factors as defined transgenes for direct lineage reprogramming to iDA neurons. This system circumvents the need for viral transduction, enabling a more efficient and reproducible reprogramming process for the generation of genetically homogenous iDA neurons. We showed that this inducible system generates iDA neurons with high similarity to their bona fide in vivo counterparts in comparison to direct infection methods. Thus, our results suggest that homogenous expression of exogenous genes in direct lineage reprogramming is critical for the generation of high quality iDA neuron cultures, making such culture systems a valuable resource for iDA-based drug screening and, ultimately, potential therapeutic intervention in PD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Expression of tyrosine hydroxylase in neurons of cultured cerebral cortex: evidence for phenotypic plasticity in neurons of the CNS.

    Science.gov (United States)

    Iacovitti, L; Lee, J; Joh, T H; Reis, D J

    1987-04-01

    In vivo, neurons of the cerebral cortex of rat embryos did not stain with antibodies to the catecholamine (CA) biosynthetic enzyme tyrosine hydroxylase (TH) even when examined using a highly sensitive technique for radioimmunocytochemistry. However, when embryonic day (E) 13 cortex was grown 1 d in culture, several thousand cells expressed immunoreactive and catalytically active TH. All TH cells simultaneously labeled with the neuronal enzyme, neuronal specific enolase, indicating that the TH was exclusively localized in neurons. Moreover, all TH neurons were postmitotic since they did not incorporate 3H-thymidine. With time in culture, the number of TH cells selectively declined from nearly 3000 cells at 2 d to several cells at 14 d. Similarly, the number of neurons competent to express TH in culture declined with advancing age of the donor embryo. Thus, by E18, very few cortical neurons had the capacity to express TH. We conclude that during a critical period of development, postmitotic cerebral cortical neurons can express catecholamine traits in vitro but not in vivo. Thus, the neurotransmitter phenotype of certain classes of central neurons is not fixed but can be influenced by epigenetic factors found in their environment, thereby providing evidence of phenotypic plasticity in the central nervous system (CNS).

  7. Visualization of neurotransmitter uptake and release in serotonergic neurons.

    Science.gov (United States)

    Lau, Thorsten; Proissl, Verena; Ziegler, Janina; Schloss, Patrick

    2015-02-15

    To study serotonergic volume neurotransmission at cellular level it needs to investigate neurotransmitter release and re-uptake sites in serotonergic neurons. However, due to the low number of cell bodies in the raphe nuclei and their widely branching neurites, serotonergic neuronal cultures are not accessible ex vivo. We have combined differentiation protocols for the generation of stem cell-derived serotonergic neurons together with confocal microscopy to study the uptake and release of fluorescent substrates known to be selectively taken up by monoaminergic neurons. These substances include: (i) 4-(4-(dimethylamino)styryl)-N-methylpyridiunium (ASP+), an analog of the neurotoxin MPP+; (ii) the fluorescent false neurotransmitter (FFN511); and (iii) serotonin (5-hydroxytryptamine; 5-HT) itself, which is known to emit fluorescence upon excitation at 320-460nm. ASP+ is taken up into living serotonergic neurons through the serotonin transporter, but not accumulated into synaptic vesicles; FFN511 diffuses in a SERT-independent way into serotonergic neurons and accumulated into synaptic vesicles. KCl-induced release of FFN511 and 5-HT can be visualized and quantified in living serotonergic neurons. Application of ASP+ so far has been used to investigate substrate/transporter interactions; studies on FFN511 uptake and release have only been performed in dopaminergic neurons; quantitative studies on uptake and release of 5-HT in living serotonergic neurons have not been reported yet. The differentiation protocols for the generation of stem cell-derived serotonergic neurons combined with the application of different fluorescent dyes allow to quantify neurotransmitter uptake and release in living serotonergic neurons in vitro. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. YAP regulates neuronal differentiation through Sonic hedgehog signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Yi-Ting; Ding, Jing-Ya [Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan (China); Li, Ming-Yang [Department of Life Science, National Taiwan Normal University, Taipei 116, Taiwan (China); Yeh, Tien-Shun [Department of Anatomy and Cell Biology, National Yang-Ming University, Taipei 112, Taiwan (China); Wang, Tsu-Wei, E-mail: twwang@ntnu.edu.tw [Department of Life Science, National Taiwan Normal University, Taipei 116, Taiwan (China); Yu, Jenn-Yah, E-mail: jyyu@ym.edu.tw [Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan (China); Brain Research Center, National Yang-Ming University, Taipei 112, Taiwan (China)

    2012-09-10

    Tight regulation of cell numbers by controlling cell proliferation and apoptosis is important during development. Recently, the Hippo pathway has been shown to regulate tissue growth and organ size in Drosophila. In mammalian cells, it also affects cell proliferation and differentiation in various tissues, including the nervous system. Interplay of several signaling cascades, such as Notch, Wnt, and Sonic Hedgehog (Shh) pathways, control cell proliferation during neuronal differentiation. However, it remains unclear whether the Hippo pathway coordinates with other signaling cascades in regulating neuronal differentiation. Here, we used P19 cells, a mouse embryonic carcinoma cell line, as a model to study roles of YAP, a core component of the Hippo pathway, in neuronal differentiation. P19 cells can be induced to differentiate into neurons by expressing a neural bHLH transcription factor gene Ascl1. Our results showed that YAP promoted cell proliferation and inhibited neuronal differentiation. Expression of Yap activated Shh but not Wnt or Notch signaling activity during neuronal differentiation. Furthermore, expression of Yap increased the expression of Patched homolog 1 (Ptch1), a downstream target of the Shh signaling. Knockdown of Gli2, a transcription factor of the Shh pathway, promoted neuronal differentiation even when Yap was over-expressed. We further demonstrated that over-expression of Yap inhibited neuronal differentiation in primary mouse cortical progenitors and Gli2 knockdown rescued the differentiation defect in Yap over-expressing cells. In conclusion, our study reveals that Shh signaling acts downstream of YAP in regulating neuronal differentiation. -- Highlights: Black-Right-Pointing-Pointer YAP promotes cell proliferation and inhibits neuronal differentiation in P19 cells. Black-Right-Pointing-Pointer YAP promotes Sonic hedgehog signaling activity during neuronal differentiation. Black-Right-Pointing-Pointer Knockdown of Gli2 rescues the Yap

  9. Microtubules are organized independently of the centrosome in Drosophila neurons

    Directory of Open Access Journals (Sweden)

    Nguyen Michelle M

    2011-12-01

    Full Text Available Abstract Background The best-studied arrangement of microtubules is that organized by the centrosome, a cloud of microtubule nucleating and anchoring proteins is clustered around centrioles. However, noncentrosomal microtubule arrays are common in many differentiated cells, including neurons. Although microtubules are not anchored at neuronal centrosomes, it remains unclear whether the centrosome plays a role in organizing neuronal microtubules. We use Drosophila as a model system to determine whether centrosomal microtubule nucleation is important in mature neurons. Results In developing and mature neurons, centrioles were not surrounded by the core nucleation protein γ-tubulin. This suggests that the centrioles do not organize functional centrosomes in Drosophila neurons in vivo. Consistent with this idea, centriole position was not correlated with a specific region of the cell body in neurons, and growing microtubules did not cluster around the centriole, even after axon severing when the number of growing plus ends is dramatically increased. To determine whether the centrosome was required for microtubule organization in mature neurons, we used two approaches. First, we used DSas-4 centriole duplication mutants. In these mutants, centrioles were present in many larval sensory neurons, but they were not fully functional. Despite reduced centriole function, microtubule orientation was normal in axons and dendrites. Second, we used laser ablation to eliminate the centriole, and again found that microtubule polarity in axons and dendrites was normal, even 3 days after treatment. Conclusion We conclude that the centrosome is not a major site of microtubule nucleation in Drosophila neurons, and is not required for maintenance of neuronal microtubule organization in these cells.

  10. Rhythmic activities of hypothalamic magnocellular neurons: autocontrol mechanisms.

    Science.gov (United States)

    Richard, P; Moos, F; Dayanithi, G; Gouzènes, L; Sabatier, N

    1997-12-01

    Electrophysiological recordings in lactating rats show that oxytocin (OT) and vasopressin (AVP) neurons exhibit specific patterns of activities in relation to peripheral stimuli: periodic bursting firing for OT neurons during suckling, phasic firing for AVP neurons during hyperosmolarity (systemic injection of hypertonic saline). These activities are autocontrolled by OT and AVP released somato-dentritically within the hypothalamic magnocellular nuclei. In vivo, OT enhances the amplitude and frequency of bursts, an effect accompanied with an increase in basal firing rate. However, the characteristics of firing change as facilitation proceeds: the spike patterns become very irregular with clusters of spikes spaced by long silences; the firing rate is highly variable and clearly oscillates before facilitated bursts. This unstable behaviour dramatically decreases during intense tonic activation which temporarily interrupts bursting, and could therefore be a prerequisite for bursting. In vivo, the effects of AVP depend on the initial firing pattern of AVP neurons: AVP excites weakly active neurons (increasing duration of active periods and decreasing silences), inhibits highly active neurons, and does not affect neurons with intermediate phasic activity. AVP brings the entire population of AVP neurons to discharge with a medium phasic activity characterised by periods of firing and silence lasting 20-40 s, a pattern shown to optimise the release of AVP from the neurohypophysis. Each of the peptides (OT or AVP) induces an increase in intracellular Ca2+ concentration, specifically in the neurons containing either OT or AVP respectively. OT evokes the release of Ca2+ from IP3-sensitive intracellular stores. AVP induces an influx of Ca2+ through voltage-dependent Ca2+ channels of T-, L- and N-types. We postulate that the facilitatory autocontrol of OT and AVP neurons could be mediated by Ca2+ known to play a key role in the control of the patterns of phasic neurons.

  11. Glutamate and GABA in vestibulo-sympathetic pathway neurons

    Directory of Open Access Journals (Sweden)

    Gay R Holstein

    2016-02-01

    Full Text Available The vestibulo-sympathetic reflex actively modulates blood pressure during changes in posture. This reflex allows humans to stand up and quadrupeds to rear or climb without a precipitous decline in cerebral perfusion. The vestibulo-sympathetic reflex pathway conveys signals from the vestibular end organs to the caudal vestibular nuclei. These cells, in turn, project to pre-sympathetic neurons in the rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively. The present study assessed glutamate- and GABA-related immunofluorescence associated with central vestibular neurons of the vestibulo-sympathetic reflex pathway in rats. Retrograde FluoroGold tract tracing was used to label vestibular neurons with projections to RVLM or CVLM, and sinusoidal galvanic vestibular stimulation was employed to activate these pathways. Central vestibular neurons of the vestibulo-sympathetic reflex were identified by co-localization of FluoroGold and cFos protein, which accumulates in some vestibular neurons following galvanic stimulation. Triple-label immunofluorescence was used to co-localize glutamate- or GABA- labeling in the identified vestibulo-sympathetic reflex pathway neurons. Most activated projection neurons displayed intense glutamate immunofluorescence, suggestive of glutamatergic neurotransmission. To support this, anterograde tracer was injected into the caudal vestibular nuclei. Vestibular axons and terminals in RVLM and CVLM co-localized the anterograde tracer and vesicular glutamate transporter-2 signals. Other retrogradely-labeled cFos-positive neurons displayed intense GABA immunofluorescence. Vestibulo-sympathetic reflex pathway neurons of both phenotypes were present in the caudal medial and spinal vestibular nuclei, and projected to both RVLM and CVLM. As a group, however, triple-labeled vestibular cells with intense glutamate immunofluorescence were located more rostrally in the vestibular nuclei than the GABAergic neurons. Only the

  12. Dicty_cDB: SLD494 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 1999. 2.23 Translated Amino Acid sequence QYGAEGLKFFENGAFGEDAAYIAKLMGSLKLIACTGFLILLIAILFPIFIVVKTKGAVDW ...Amino Acid sequence (All Frames) Frame A: QYGAEGLKFFENGAFGEDAAYIAKLMGSLKLIACTGFLILLIAILFPIFIVVKTKGAVDW

  13. Dicty_cDB: SLD704 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 1( DQ167408 |pid:none) Volvariella volvacea S-adenosyl-L-... 87 2e-16 CP000820_11...3.3.1.1) - slim... 111 7e-24 ( O13639 ) RecName: Full=Adenosylhomocysteinase; Short=Ad... 90 3e-17 DQ167408_

  14. Dicty_cDB: SLD676 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available Full=ADAM 22; AltName: Full=A disintegrin and ... 33 3.0 S00670( S00670 ;A26637) neurogenic repetitive locus... delta protein ... 33 3.0 A31246( A31246 )neurogenic protein Delta precursor - fr

  15. Dicty_cDB: SLD147 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 2.23 Translated Amino Acid sequence NSLYSSSAPTNSGMANYKPISPNSSIISPSKPEPLVLPSSISTTTTPTNST--- ---IISPSKP...Acid sequence (All Frames) Frame A: NSLYSSSAPTNSGMANYKPISPNSSIISPSKPEPLVLPSSISTTTTPTNST--- ---v*shqvn

  16. Dicty_cDB: SLD447 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available Acid sequence YHFIQGYTAKVAGTEVGVTEPTATFSSCYGEPFIVWHPTKYAEMLASQLHKHSARAWLIN TGWTGGSHGVGSRIKLAYTRAIIDAIHSGELEKIPTTKM---...-- Frame B: YHFIQGYTAKVAGTEVGVTEPTATFSSCYGEPFIVWHPTKYAEMLASQLHKHSARAWLIN TGWTGGSHGVGSRIKLAYTRAIIDAIHSGELEKIPTTKM---

  17. Dicty_cDB: SLD725 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available ptrpnsstilfvhnhttssllk**yl**fytshtyyniniy*nhflck**SHPTILRRTI VIFVILKNNKKKK--- ---NFFNEFFNFLKRKN**yy****...ptrpnsstilfvhnhttssllk**yl**fytshtyyniniy*nhflck**SHPTILRRTI VIFVILKNNKKKK--- ---NFFNEFFNFLKRKN**yy****

  18. Dicty_cDB: SLD872 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available AK146453 |pid:none) Mus musculus 16 days embryo heart ... 75 9e-13 AK146055_1( AK146055 |pid:none) Mus...AK146583 |pid:none) Mus musculus 17 days embryo heart ... 75 9e-13 protein update 2009. 6. 2 PSORT psg:

  19. Bimodal SLD Ice Accretion on a NACA 0012 Airfoil Model

    Science.gov (United States)

    Potapczuk, Mark; Tsao, Jen-Ching; King-Steen, Laura

    2016-01-01

    This presentation describes the results of ice accretion measurements on a NACA 0012 airfoil model, from the NASA Icing Research Tunnel, using an icing cloud composed of a bimodal distribution of Supercooled Large Droplets. The data consists of photographs, laser scans of the ice surface, and measurements of the mass of ice for each icing condition. The results of ice shapes accumulated as a result of exposure to an icing cloud with a bimodal droplet distribution were compared to the ice shapes resulting from an equivalent cloud composed of a droplet distribution with a standard bell curve shape.

  20. Dicty_cDB: SLD739 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available . 50 0.027 1 ( AM979751 ) Sparus aurata EST, clone cDN14P0005A06, 5'-end se... 42 6.5 1 ( FE224212 ) O053E12 Antarctic... fish Dissostichus mawsoni adult... 42 6.5 1 ( FE221128 ) O019B05 Antarctic fish Dissostichus maws...oni adult... 42 6.5 1 ( FE203112 ) B385G09 Antarctic fish Dissostichus mawsoni ad...ult... 42 6.5 1 ( FE196180 ) B197B12 Antarctic fish Dissostichus mawsoni adult... 42 6.5 1 ( FE195928 ) B193H07 Antarctic