TY - JOUR AB - Bayesian inference is becoming a common statistical approach to phylogenetic estimation because, among other reasons, it allows for rapid analysis of large data sets with complex evolutionary models. Conveniently, Bayesian phylogenetic methods use currently available stochastic models of sequence evolution. However, as with other model-based approaches, the results of Bayesian inference are conditional on the assumed model of evolution: inadequate models (models that poorly fit the data) may result in erroneous inferences. In this article, I present a Bayesian phylogenetic method that evaluates the adequacy of evolutionary models using posterior predictive distributions. By evaluating a model's posterior predictive performance, an adequate model can be selected for a Bayesian phylogenetic study. Although I present a single test statistic that assesses the overall (global) performance of a phylogenetic model, a variety of test statistics can be tailored to evaluate specific features (local performance) of evolutionary models to identify sources failure. The method presented here, unlike the likelihood-ratio test and parametric bootstrap, accounts for uncertainty in the phylogeny and model parameters. AU - Bollback, Jonathan P ID - 4349 IS - 7 JF - Molecular Biology and Evolution SN - 0737-4038 TI - Bayesian model adequacy and choice in phylogenetics VL - 19 ER - TY - JOUR AB - We introduce a general recursion for the probability of identity in state of two individuals sampled from a population subject to mutation, migration, and random drift in a two-dimensional continuum. The recursion allows for the interactions induced by density-dependent regulation of the population, which are inevitable in a continuous population. We give explicit series expansions for large neighbourhood size and for low mutation rates respectively and investigate the accuracy of the classical Malécot formula for these general models. When neighbourhood size is small, this formula does not give the identity even over large scales. However, for large neighbourhood size, it is an accurate approximation which summarises the local population structure in terms of three quantities: the effective dispersal rate, σe; the effective population density, ρe; and a local scale, κ, at which local interactions become significant. The results are illustrated by simulations. AU - Barton, Nicholas H AU - Depaulis, Frantz AU - Etheridge, Alison ID - 4263 IS - 1 JF - Theoretical Population Biology SN - 0040-5809 TI - Neutral evolution in spatially continuous populations VL - 61 ER - TY - JOUR AB - Until recently, it was impracticable to identify the genes that are responsible for variation in continuous traits, or to directly observe the effects of their different alleles. Now, the abundance of genetic markers has made it possible to identify quantitative trait loci (QTL) — the regions of a chromosome or, ideally, individual sequence variants that are responsible for trait variation. What kind of QTL do we expect to find and what can our observations of QTL tell us about how organisms evolve? The key to understanding the evolutionary significance of QTL is to understand the nature of inherited variation, not in the immediate mechanistic sense of how genes influence phenotype, but, rather, to know what evolutionary forces maintain genetic variability. AU - Barton, Nicholas H AU - Keightley, Peter ID - 4261 JF - Nature Reviews Genetics SN - 1471-0056 TI - Understanding quantitative genetic variation VL - 3 ER - TY - JOUR AB - Phylogenetic trees can be rooted by a number of criteria. Here, we introduce a Bayesian method for inferring the root of a phylogenetic tree by using one of several criteria: the outgroup, molecular clock, and nonreversible model of DNA substitution. We perform simulation analyses to examine the relative ability of these three criteria to correctly identify the root of the tree. The outgroup and molecular clock criteria were best able to identify the root of the tree, whereas the nonreversible model was able to identify the root only when the substitution process was highly nonreversible. We also examined the performance of the criteria for a tree of four species for which the topology and root position are well supported. Results of the analyses of these data are consistent with the simulation results. AU - Huelsenbeck, John AU - Bollback, Jonathan P AU - Levine, Amy ID - 4347 IS - 1 JF - Systematic Biology SN - 0039-7989 TI - Inferring the root of a phylogenetic tree VL - 51 ER - TY - JOUR AB - This paper presents a complete axiomatization of two decidable propositional real-time linear temporal logics: Event Clock Logic (EventClockTL) and Metric Interval Temporal Logic with past (MetricIntervalTL). The completeness proof consists of an effective proof building procedure for EventClockTL. From this result we obtain a complete axiomatization of MetricIntervalTL by providing axioms translating MetricIntervalTL formulae into EventClockTL formulae, the two logics being equally expressive. Our proof is structured to yield axiomatizations also for interesting fragments of these logics, such as the linear temporal logic of the real numbers (TLR). AU - Raskin, Jean AU - Schobbens, Pierre AU - Henzinger, Thomas A ID - 4407 IS - 1-2 JF - Theoretical Computer Science SN - 0304-3975 TI - Axioms for real-time logics VL - 274 ER - TY - JOUR AB - We studied the effect of multilocus balancing selection on neutral nucleotide variability at linked sites by simulating a model where diallelic polymorphisms are maintained at an arbitrary number of selected loci by means of symmetric overdominance. Different combinations of alleles define different genetic backgrounds that subdivide the population and strongly affect variability. Several multilocus fitness regimes with different degrees of epistasis and gametic disequilibrium are allowed. Analytical results based on a multilocus extension of the structured coalescent predict that the expected linked neutral diversity increases exponentially with the number of selected loci and can become extremely large. Our simulation results show that although variability increases with the number of genetic backgrounds that are maintained in the population, it is reduced by random fluctuations in the frequencies of those backgrounds and does not reach high levels even in very large populations. We also show that previous results on balancing selection in single-locus systems do not extend to the multilocus scenario in a straightforward way. Different patterns of linkage disequilibrium and of the frequency spectrum of neutral mutations are expected under different degrees of epistasis. Interestingly, the power to detect balancing selection using deviations from a neutral distribution of allele frequencies seems to be diminished under the fitness regime that leads to the largest increase of variability over the neutral case. This and other results are discussed in the light of data from the Mhc. AU - Navarro, Arcadio AU - Barton, Nicholas H ID - 4258 IS - 2 JF - Genetics SN - 0016-6731 TI - The effects of multilocus balancing selection on neutral variability VL - 161 ER - TY - JOUR AB - We extend current multilocus models to describe the effects of migration, recombination, selection, and nonrandom mating on sets of genes in diploids with varied modes of inheritance, allowing us to consider the patterns of nuclear and cytonuclear associations (disequilibria) under various models of migration. We show the relationship between the multilocus notation recently presented by Kirkpatrick, Johnson, and Barton (developed from previous work by Barton and Turelli) and the cytonuclear parameterization of Asmussen, Arnold, and Avise and extend this notation to describe associations between cytoplasmic elements and multiple nuclear genes. Under models with sexual symmetry, both nuclear-nuclear and cytonuclear disequilibria are equivalent. They differ, however, in cases involving some type of sexual asymmetry, which is then reflected in the asymmetric inheritance of cytoplasmic markers. An example given is the case of different migration rates in males and females; simulations using 2, 3, 4, or 5 unlinked autosomal markers with a maternally inherited cytoplasmic marker illustrate how nuclear-nuclear and cytonuclear associations can be used to separately estimate female and male migration rates. The general framework developed here allows us to investigate conditions where associations between loci with different modes of inheritance are not equivalent and to use this nonequivalence to test for deviations from simple models of admixture. AU - Orive, Maria AU - Barton, Nicholas H ID - 4259 IS - 3 JF - Genetics SN - 0016-6731 TI - Associations between cytoplasmic and nuclear loci in hybridizing populations VL - 162 ER - TY - JOUR AB - We have identified widerborst (wdb), a B' regulatory subunit of PP2A, as a conserved component of planar cell polarization mechanisms in both Drosophila and in zebrafish. In Drosophila, wdb acts at two steps during planar polarization of wing epithelial cells. It is required to organize tissue polarity proteins into proximal and distal cortical domains, thus determining wing hair orientation. It is also needed to generate the polarized membrane outgrowth that becomes the wing hair. Widerborst activates the catalytic subunit of PP2A and localizes to the distal side of a planar microtubule web that lies at the level of apical cell junctions. This suggests that polarized PP2A activation along the planar microtubule web is important for planar polarization. In zebrafish, two wdb homologs are required for convergent extension during gastrulation, supporting the conjecture that Drosophila planar cell polarization and vertebrate gastrulation movements are regulated by similar mechanisms. AU - Hannus, Michael AU - Feiguin, Fabian AU - Heisenberg, Carl-Philipp J AU - Eaton, Suzanne ID - 4209 IS - 14 JF - Development SN - 0950-1991 TI - Planar cell polarization requires Widerborst, a B′ regulatory subunit of protein phosphatase 2A VL - 129 ER - TY - JOUR AB - Vertebrate homologues of the Strabismus/van Gogh (stbm/vang) gene have been implicated in patterning and morphogenesis during gastrulation. Recent work shows that stbm/vang is mutated in zebrafish trilobite mutants and that stbm/vang is required for morphogenesis but not patterning during zebrafish gastrulation. AU - Heisenberg, Carl-Philipp J ID - 4207 IS - 19 JF - Current Biology SN - 0960-9822 TI - Wnt signalling: Refocusing on Strabismus VL - 12 ER - TY - JOUR AB - Cells at the anterior boundary of the neural plate (ANB) can induce telencephalic gene expression when transplanted to more posterior regions. Here, we identify a secreted Frizzled-related Wnt antagonist, Tic, that is expressed in ANB cells and can cell nonautonomously promote telencephalic gene expression in a concentration-dependent manner. Moreover, abrogation of Tlc function compromises telencephalic development. We also identify Wnt8b as a locally acting modulator of regional fate in the anterior neural plate and a likely target for antagonism by Tic. Finally, we show that tlc expression is regulated by signals that establish early antero-posterior and dorso-ventral ectodermal pattern. From these studies, we propose that local antagonism of Wnt activity within the anterior ectoderm is required to establish the telencephalon. AU - Houart, Corinne AU - Caneparo, Luca AU - Heisenberg, Carl-Philipp J AU - Barth, K Anukampa AU - Take Uchi, Masaya AU - Wilson, Stephen ID - 4194 IS - 2 JF - Neuron SN - 0896-6273 TI - Establishment of the telencephalon during gastrulation by local antagonism of Wnt signaling VL - 35 ER - TY - JOUR AB - Members of the Wnt family have been implicated in a variety of developmental processes including axis formation, Patterning of the central nervous system and tissue morphogenesis. Recent studies have shown that a Wnt signalling pathway similar to that involved in the establishment of planar cell polarity in Drosophila regulates convergent extension movements during zebrafish and Xenopus gastrulation. This finding provides a good starting point to dissect the complex cell biology and genetic regulation of vertebrate gastrulation movements. AU - Tada, Masazumi AU - Concha, Miguel AU - Heisenberg, Carl-Philipp J ID - 4148 IS - 3 JF - Seminars in Cell & Developmental Biology SN - 1084-9521 TI - Non-canonical Wnt signalling and regulation of gastrulation movements VL - 13 ER - TY - JOUR AB - During vertebrate gastrulation, large cellular rearrangements lead to the formation of the three germ layers, ectoderm, mesoderm and endoderm. Zebrafish offer many genetic and experimental advantages for studying vertebrate gastrulation movements. For instance, several mutants, including silberblick, knypek and trilobite, exhibit defects in morphogenesis during gastrulation. The identification of the genes mutated in these lines together with the analysis of the mutant phenotypes has provided new insights into the molecular and cellular mechanisms that underlie vertebrate gastrulation movements. AU - Heisenberg, Carl-Philipp J AU - Tada, Masazumi ID - 4196 IS - 6 JF - Seminars in Cell & Developmental Biology SN - 1084-9521 TI - Zebrafish gastrulation movements: bridging cell and developmental biology VL - 13 ER - TY - JOUR AB - Recent studies on vertebrate homologues of the van gogh/strabismus (vang/stbm) gene, a key player in planar cell polarity signalling in Drosophila, show that vang/stbm is involved in patterning and morphogenesis during vertebrate gastrulation where it modulates two distinct Wnt signals. AU - Heisenberg, Carl-Philipp J AU - Tada, Masazumi ID - 4199 IS - 4 JF - Current Biology SN - 0960-9822 TI - Wnt signalling: A moving picture emerges from van gogh VL - 12 ER - TY - JOUR AB - Pilot studies in England by Stopka and Macdonald revealed that allogrooming in the Old World wood mouse, Apodemus sylvaticus, is a commodity that males can trade for reproductive benefits with females. This study, which used a combination of field study and observations in experimental enclosures, revealed that specific experimental conditions such as group-size and sex-ratio manipulations have a significant effect on the pattern of allogrooming exchanged between individuals. Furthermore, females from the Czech population were more likely to associate with each other as revealed by the clustering of activity centers of females (i.e., as opposed to almost exclusive ranges in English populations), and also by the higher intensity of allogrooming exchanged between females (i.e., virtually lacking in the previous experiment with English mice). Therefore, geographic variation and specific social conditions seem to be important driving factors for allogrooming behavior. Together with changes in overall grooming patterns, allogrooming between males and females remained invariably asymmetrical over all four experimental groups (i.e., two conditions for each sex) in that males provided more allogrooming to females than they received from them. AU - Polechova, Jitka AU - Stopka, P. ID - 4139 IS - 8 JF - Canadian Journal of Zoology SN - 0008-4301 TI - Geometry of social relationships in the Old World wood mouse, Apodemus sylvaticus VL - 80 ER - TY - CONF AB - The writhing number measures the global geometry of a closed space curve or knot. We show that this measure is related to the average winding number of its Gauss map. Using this relationship, we give an algorithm for computing the writhing number for a polygonal knot with n edges in time roughly proportional to n(1.6). We also implement a different, simple algorithm and provide experimental evidence for its practical efficiency. AU - Agarwal, Pankaj AU - Edelsbrunner, Herbert AU - Wang, Yusu ID - 4003 SN - 9780898715132 T2 - Proceedings of the 13th annual ACM-SIAM symposium on Discrete algorithms TI - Computing the writhing number of a polygonal knot ER - TY - JOUR AB - This article is a survey of research areas in which motion plays a pivotal role. The aim of the article is to review current approaches to modeling motion together with related data structures and algorithms, and to summarize the challenges that lie ahead in producing a more unified theory of motion representation that would be useful across several disciplines. AU - Agarwal, Pankaj AU - Guibas, Leonidas AU - Edelsbrunner, Herbert AU - Erickson, Jeff AU - Isard, Michael AU - Har Peled, Sariel AU - Hershberger, John AU - Jensen, Christian AU - Kavraki, Lydia AU - Koehl, Patrice AU - Lin, Ming AU - Manocha, Dinesh AU - Metaxas, Dimitris AU - Mirtich, Brian AU - Mount, David AU - Muthukrishnan, Sankara AU - Pai, Dinesh AU - Sacks, Elisha AU - Snoeyink, Jack AU - Suri, Subhash AU - Wolefson, Ouri ID - 3995 IS - 4 JF - ACM Computing Surveys SN - 0360-0300 TI - Algorithmic issues in modeling motion VL - 34 ER - TY - JOUR AB - We present fast implementations of a hybrid algorithm for reporting box and cube intersections. Our algorithm initially takes a divide-and-conquer approach and switches to simpler algorithms for low numbers of boxes. We use our implementations as engines to solve problems about geometric primitives. We look at two such problems in the category of quality analysis of surface triangulations. AU - Zomorodian, Afra AU - Edelsbrunner, Herbert ID - 4000 IS - 1-2 JF - International Journal of Computational Geometry and Applications SN - 0218-1959 TI - Fast software for box intersections VL - 12 ER - TY - JOUR AB - We present results on a two-step improvement of mesh quality in three-dimensional Delaunay triangulations. The first step refines the triangulation by inserting sinks and eliminates tetrahedra with large circumradius over shortest edge length ratio. The second step assigns weights to the vertices to eliminate slivers. Our experimental findings provide evidence for the practical effectiveness of sliver exudation. AU - Edelsbrunner, Herbert AU - Guoy, Damrong ID - 3998 IS - 3 JF - Engineering with Computers SN - 0177-0667 TI - An experimental study of sliver exudation VL - 18 ER - TY - JOUR AB - The presynaptic Ca2+ signal is a key determinant of transmitter release at chemical synapses. In cortical synaptic terminals, however, little is known about the kinetic properties of the presynaptic Ca2+ channels. To investigate the timing and magnitude of the presynaptic Ca2+ inflow, we performed whole-cell patch-clamp recordings from mossy fiber boutons (MFBs) in rat hippocampus. MFBs showed large high-voltage-activated Ca(2+) currents, with a maximal amplitude of approximately 100 pA at a membrane potential of 0 mV. Both activation and deactivation were fast, with time constants in the submillisecond range at a temperature of approximately 23 degrees C. An MFB action potential (AP) applied as a voltage-clamp command evoked a transient Ca2+ current with an average amplitude of approximately 170 pA and a half-duration of 580 microsec. A prepulse to +40 mV had only minimal effects on the AP-evoked Ca2+ current, indicating that presynaptic APs open the voltage-gated Ca2+ channels very effectively. On the basis of the experimental data, we developed a kinetic model with four closed states and one open state, linked by voltage-dependent rate constants. Simulations of the Ca2+ current could reproduce the experimental data, including the large amplitude and rapid time course of the current evoked by MFB APs. Furthermore, the simulations indicate that the shape of the presynaptic AP and the gating kinetics of the Ca2+ channels are tuned to produce a maximal Ca2+ influx during a minimal period of time. The precise timing and high efficacy of Ca2+ channel activation at this cortical glutamatergic synapse may be important for synchronous transmitter release and temporal information processing. AU - Bischofberger, Josef AU - Geiger, Jörg AU - Jonas, Peter M ID - 3802 IS - 24 JF - Journal of Neuroscience SN - 0270-6474 TI - Timing and efficacy of Ca(2+) channel activation in hippocampal mossy fiber boutons VL - 22 ER - TY - JOUR AB - Hamilton's concept of local mate competition (LMC) is the standard model to explain female-biased sex ratios in solitary Hymenoptera. In social Hymenoptera, however, LMC has remained controversial, mainly because manipulation of sex allocation by workers in response to relatedness asymmetries is an additional powerful mechanism of female bias. Furthermore, the predominant mating systems in the social insects are thought to make LMC unlikely. Nevertheless, several species exist in which dispersal of males is limited and mating occurs in the nest. Some of these species, such as the ant Cardiocondyla obscurior, have evolved dimorphic males, with one morph being specialized for dispersal and the other for fighting with nest-mate males over access to females. Such life history, combining sociality and alternative reproductive tactics in males, provides a unique opportunity to test the power of LMC as a selective force leading to female-biased sex ratios in social Hymenoptera. We show that, in concordance with LMC predictions, an experimental increase in queen number leads to a shift in sex allocation in favour of non-dispersing males, but does not influence the proportion of disperser males. Furthermore, we can assign this change in sex allocation at the colony level to the queens and rule out worker manipulation. AU - Cremer, Sylvia AU - Heinze, Jürgen ID - 3919 IS - 1489 JF - Proceedings of the Royal Society of London Series B Biological Sciences SN - 0962-8452 TI - Adaptive production of fighter males: queens of the ant Cardiocondyla adjust the sex ratio under local mate competition VL - 269 ER - TY - JOUR AB - Males of the ant Cardiocondyla show a dispersal dimorphism of a winged and wingless morph. The loss of flight has lead to morphological reductions in the wingless (ergatoid) males and also affected body size, eye size and pigmentation. As ergatoid males mate exclusively inside the maternal nest, they underlie increased male-male competition and therefore have also evolved additional changes in behaviour and physiology: in contrast to winged males, ergatoid males are highly aggressive towards each other and their spermatogenesis is prolonged compared to all other hymenopteran males. In addition to these two male morphs, we found males with an intermediate appearance. These "intermorphic" males provide a transitional stage between normal males in most investigated morphological and physiological parameters. As they are produced extremely rarely and only in colonies that switch between pure ergatoid to mixed male production, we argue that they likely represent a developmental mistake. Parallels between the determination of male morphs and female castes (queen-worker dimorphism and worker polymorphism) might help to understand how the large potential of phenotypic plasticity in both sexes of social insects is realised during development. AU - Cremer, Sylvia AU - Lautenschläger, Birgit AU - Heinze, Jürgen ID - 3924 IS - 3 JF - Insectes Sociaux SN - 0020-1812 TI - A transitional stage between the ergatoid and winged male morph in the ant Cardiocondyla obscurior VL - 49 ER - TY - JOUR AB - Males of the tropical ant Cardiocondyla obscurior are either wingless and aggressive or winged and docile, and both compete for access to virgin queens in the nest1, 2. Although the fighter males (ergatoids) attack and kill other ergatoids, they tolerate and even attempt to mate with their winged rivals. Here we show that the winged males avoid the aggression of wingless males by mimicking the chemical bouquet of virgin queens, but that their mating success is not reduced as a result. This example of female mimicry by vigorous males is surprising, as in other species it is typically used as a protective strategy by weaker males, and may explain the coexistence and equal mating success of two male morphs. AU - Cremer, Sylvia AU - Sledge, Matthew AU - Heinze, Jürgen ID - 3925 JF - Nature SN - 0028-0836 TI - Chemical mimicry: Male ants disguised by the queen's bouquet VL - 419 ER - TY - JOUR AB - We formalize a notion of topological simplification within the framework of a filtration, which is the history of a growing complex. We classify a topological change that happens during growth as either a feature or noise depending on its lifetime or persistence within the filtration. We give fast algorithms for computing persistence and experimental evidence for their speed and utility. AU - Edelsbrunner, Herbert AU - Letscher, David AU - Zomorodian, Afra ID - 3996 IS - 4 JF - Discrete & Computational Geometry SN - 0179-5376 TI - Topological persistence and simplification VL - 28 ER - TY - JOUR AB - A particular Solid Injector needle, suitable for GC-MS analyses of small specimens, is described together with its application in a study on ants. AU - Turillazzi, Stefano AU - Sledge, Matthew AU - Cremer, Sylvia AU - Heinze, Jürgen ID - 3920 JF - Insect Social Life TI - A method for analysing small-size specimens in GC-MS VL - 4 ER - TY - JOUR AB - Networks of GABAergic interneurons are of critical importance for the generation of gamma frequency oscillations in the brain. To examine the underlying synaptic mechanisms, we made paired recordings from "basket cells" (BCs) in different subfields of hippocampal slices, using transgenic mice that express enhanced green fluorescent protein (EGFP) under the control of the parvalbumin promoter. Unitary inhibitory postsynaptic currents (IPSCs) showed large amplitude and fast time course with mean amplitude-weighted decay time constants of 2.5, 1.2, and 1.8 ms in the dentate gyrus, and the cornu ammonis area 3 (CA3) and 1 (CA1), respectively (33-34 degrees C). The decay of unitary IPSCs at BC-BC synapses was significantly faster than that at BC-principal cell synapses, indicating target cell-specific differences in IPSC kinetics. In addition, electrical coupling was found in a subset of BC-BC pairs. To examine whether an interneuron network with fast inhibitory synapses can act as a gamma frequency oscillator, we developed an interneuron network model based on experimentally determined properties. In comparison to previous interneuron network models, our model was able to generate oscillatory activity with higher coherence over a broad range of frequencies (20-110 Hz). In this model, high coherence and flexibility in frequency control emerge from the combination of synaptic properties, network structure, and electrical coupling. AU - Bartos, Marlene AU - Vida, Imre AU - Frotscher, Michael AU - Meyer, Axel AU - Monyer, Hannah AU - Geiger, Jörg AU - Jonas, Peter M ID - 3800 IS - 20 JF - PNAS SN - 0027-8424 TI - Fast synaptic inhibition promotes synchronized gamma oscillations in hippocampal interneuron networks VL - 99 ER - TY - JOUR AB - Mossy fiber (MF) synapses are key stations for flow of information through the hippocampal formation. A major component of the output of the MF system is directed towards inhibitory interneurons. Recent studies have revealed that the functional properties of MF-interneuron synapses differ substantially from those of MF-CA3 pyramidal neuron synapses. Mossy-fiber-interneuron synapses in the stratum lucidum represent a continuum of functional subtypes, in which the subunit composition of postsynaptic AMPA receptors and NMDA receptors appears to be regulated in a coordinated manner. AU - Bischofberger, Josef AU - Jonas, Peter M ID - 3803 IS - 12 JF - Trends in Neurosciences SN - 0166-2236 TI - TwoB or not twoB: differential transmission at glutamatergic mossy fiber-interneuron synapses in the hippocampus VL - 25 ER - TY - JOUR AB - To examine possible interactions between fast depression and modulation of inhibitory synaptic transmission in the hippocampus, we recorded from pairs of synaptically connected basket cells (BCs) and granule cells (GCs) in the dentate gyrus of rat brain slices at 34 degrees C. Multiple-pulse depression (MPD) was examined in trains of 5 or 10 inhibitory postsynaptic currents (IPSCs) evoked at frequencies of 10-100 Hz under several conditions that inhibit transmitter release: block of voltage-dependent Ca2+ channels by Cd2+ (10 microM), activation of gamma-amino-butyric acid type B receptors (GABA(B)Rs) by baclofen (10 microM) and activation of muscarinic acetylcholine receptors (mAchRs) by carbachol (2 microM). All manipulations led to a substantial inhibition of synaptic transmission, reducing the amplitude of the first IPSC in the train (IPSC1) by 72%, 61% and 29%, respectively. However, MPD was largely preserved under these conditions (0.34 in control versus 0.31, 0.50 and 0.47 in the respective conditions at 50 Hz). Similarly, a theta burst stimulation (TBS) protocol reduced IPSC1 by 54%, but left MPD unchanged (0.40 in control and 0.39 during TBS). Analysis of both fractions of transmission failures and coefficients of variation (CV) of IPSC peak amplitudes suggested that MPD had a presynaptic expression site, independent of release probability. In conclusion, different types of presynaptic modulation of inhibitory synaptic transmission converge on a reduction of synaptic strength, while short-term dynamics are largely unchanged. AU - Hefft, Stefan AU - Kraushaar, Udo AU - Geiger, Jörg AU - Jonas, Peter M ID - 3801 IS - Pt 1 JF - Journal of Physiology SN - 0022-3751 TI - Presynaptic short-term depression is maintained during regulation of transmitter release at a GABAergic synapse in rat hippocampus VL - 539 ER - TY - JOUR AB - GABAergic interneurones are diverse in their morphological and functional properties. Perisomatic inhibitory cells show fast spiking during sustained current injection, whereas dendritic inhibitory cells fire action potentials with lower frequency. We examined functional and molecular properties of K(+) channels in interneurones with horizontal dendrites in stratum oriens-alveus (OA) of the hippocampal CA1 region, which mainly comprise somatostatin-positive dendritic inhibitory cells. Voltage-gated K(+) currents in nucleated patches isolated from OA interneurones consisted of three major components: a fast delayed rectifier K(+) current component that was highly sensitive to external 4-aminopyridine (4-AP) and tetraethylammonium (TEA) (half-maximal inhibitory concentrations < 0.1 mM for both blockers), a slow delayed rectifier K(+) current component that was sensitive to high concentrations of TEA, but insensitive to 4-AP, and a rapidly inactivating A-type K(+) current component that was blocked by high concentrations of 4-AP, but resistant to TEA. The relative contributions of these components to the macroscopic K(+) current were estimated as 57 +/- 5, 25 +/- 6, and 19 +/- 2 %, respectively. Dendrotoxin, a selective blocker of Kv1 channels had only minimal effects on K(+) currents in nucleated patches. Coapplication of the membrane-permeant cAMP analogue 8-(4-chlorophenylthio)-adenosine 3':5'-cyclic monophosphate (cpt-cAMP) and the phosphodiesterase blocker isobutyl-methylxanthine (IBMX) resulted in a selective inhibition of the fast delayed rectifier K(+) current component. This inhibition was absent in the presence of the protein kinase A (PKA) inhibitor H-89, implying the involvement of PKA-mediated phosphorylation. Single-cell reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed a high abundance of Kv3.2 mRNA in OA interneurones, whereas the expression level of Kv3.1 mRNA was markedly lower. Similarly, RT-PCR analysis showed a high abundance of Kv4.3 mRNA, whereas Kv4.2 mRNA was undetectable. This suggests that the fast delayed rectifier K(+) current and the A-type K(+) current component are mediated predominantly by homomeric Kv3.2 and Kv4.3 channels. Selective modulation of Kv3.2 channels in OA interneurones by cAMP is likely to be an important factor regulating the activity of dendritic inhibitory cells in principal neurone-interneurone microcircuits. AU - Lien, Cheng AU - Martina, Marco AU - Schultz, Jobst AU - Ehmke, Heimo AU - Jonas, Peter M ID - 3799 IS - Pt 2 JF - Journal of Physiology SN - 0022-3751 TI - Gating, modulation and subunit composition of voltage-gated K(+) channels in dendritic inhibitory interneurones of rat hippocampus VL - 538 ER - TY - JOUR AB - In 1991, Barton and Turelli developed recursions to describe the evolution of multilocus systems under arbitrary forms of selection. This article generalizes their approach to allow for arbitrary modes of inheritance, including diploidy, polyploidy, sex linkage, cytoplasmic inheritance, and genomic imprinting. The framework is also extended to allow for other deterministic evolutionary forces, including migration and mutation. Exact recursions that fully describe the state of the population are presented; these are implemented in a computer algebra package (available on the Web at http://helios.bto.ed.ac.uk/evolgen). Despite the generality of our framework, it can describe evolutionary dynamics exactly by just two equations. These recursions can be further simplified using a "quasi-linkage equilibrium" (QLE) approximation. We illustrate the methods by finding the effect of natural selection, sexual selection, mutation, and migration on the genetic composition of a population. AU - Kirkpatrick, Mark AU - Johnson, Toby AU - Barton, Nicholas H ID - 3621 IS - 4 JF - Genetics SN - 0016-6731 TI - General models of multilocus evolution VL - 161 ER - TY - JOUR AB - A central problem in biology is determining how genes interact as parts of functional networks. Creation and analysis of synthetic networks, composed of well-characterized genetic elements, provide a framework for theoretical modeling. Here, with the use of a combinatorial method, a library of networks with varying connectivity was generated in Escherichia coli. These networks were composed of genes encoding the transcriptional regulators Lacl, TetR, and lambda Cl, as well as the corresponding promoters. They displayed phenotypic behaviors resembling binary logical circuits, with two chemical “inputs” and a fluorescent protein “output.” Within this simple system, diverse computational functions arose through changes in network connectivity. Combinatorial synthesis provides an alternative approach for studying biological networks, as well as an efficient method for producing diverse phenotypes in vivo. AU - Guet, Calin C AU - Elowitz, Michael AU - Hsing, Weihong AU - Leibler, Stanislas ID - 3757 IS - 5572 JF - Science SN - 0036-8075 TI - Combinatorial synthesis of genetic networks VL - 296 ER - TY - JOUR AB - The use of advanced patch-clamp recording techniques in brain slices, such as simultaneous recording from multiple neurons and recording from dendrites or presynaptic terminals, demands slices of the highest quality. In this context the mechanics of the tissue slicer are an important factor. Ideally, a tissue slicer should generate large-amplitude and high-frequency movements of the cutting blade in a horizontal axis, with minimal vibrations in the vertical axis. We developed a vibroslicer that fulfils these in part conflicting requirements. The oscillator is a permanent-magnet-coil-leaf-spring system. Using an auto-resonant mechano-electrical feedback circuit, large horizontal oscillations (up to 3 mm peak-to-peak) with high frequency (,90 Hz) are generated. To minimize vertical vibrations, an adjustment mechanism was employed that allowed alignment of the cutting edge of the blade with the major axis of the oscillation. A vibroprobe device was used to monitor vertical vibrations during adjustment. The system is based on the shading of the light path between a light-emitting diode (LED) and a photodiode. Vibroprobe monitoring revealed that the vibroslicer, after appropriate adjustment, generated vertical vibrations of <1 µm, significantly less than many commercial tissue slicers. Light- and electron-microscopic analysis of surface layers of slices cut with the vibroslicer showed that cellular elements, dendritic processes and presynaptic terminals are well preserved under these conditions, as required for patch-clamp recording from these structures. AU - Geiger, Jörg AU - Bischofberger, Joseph AU - Vida, Imre AU - Fröbe, Ulrich AU - Pfitzinger, S AU - Weber, H. AU - Haverkampf, Klaus AU - Jonas, Peter M ID - 3497 IS - 3 JF - Pflugers Archiv : European Journal of Physiology SN - 0031-6768 TI - Patch-clamp recording in brain slices with improved slicer technology VL - 443 ER - TY - JOUR AB - Information in neuronal networks is thought to be represented by the rate of discharge and the temporal relationship between the discharging neurons. The discharge frequency of neurons is affected by their afferents and intrinsic properties, and shows great individual variability. The temporal coordination of neurons is greatly facilitated by network oscillations. In the hippocampus, population synchrony fluctuates during theta and gamma oscillations (10-100 ms scale) and can increase almost 10-fold during sharp wave bursts. Despite these large changes in excitability in the sub-second scale, longer-term (minute-scale) firing rates of individual neurons are relatively constant in an unchanging environment. As a result, mean hippocampal output remains stable over time. To understand the mechanisms responsible for this homeostasis, we address the following issues: (i) Can firing rates of single cells be modified? (ii) Once modified, what mechanism(s) can maintain the changes? We show that firing rates of hippocampal pyramidal cells can be altered in a novel environment and by Hebbian pairing of physiological input patterns with postsynaptic burst discharge. We also illustrate a competition between single spikes and the occurrence of spike bursts. Since spike-inducing (suprathreshold) inputs decrease the ability of strong ('teaching') inputs to induce a burst discharge, we propose that the single spike versus burst competition presents a homeostatic regulatory mechanism to maintain synaptic strength and, consequently, firing rate in pyramidal cells. AU - Buzsáki, György AU - Csicsvari, Jozsef L AU - Dragoi, George AU - Harris, Kenneth AU - Henze, D. AU - Hirase, Hajima ID - 3533 IS - 9 JF - Cerebral Cortex SN - 1047-3211 TI - Homeostatic maintenance of neuronal excitability by burst discharges in vivo VL - 12 ER - TY - CONF AB - We give a brief overview of the current understanding of the explosion mechanism of core collapse supernovae. Our main focus is the impact of rotation on the explosion. Recent observations of the polarization of the light emitted by supernova explosions indicate that there are large deviations from spherical symmetry in the very heart of the explosion the origin of which is unknown. We use the new approach of a three dimensional test particle based simulation to simulate the infall phase of a supernova event. The underlying microphysics is simplified to make this computationally possible. A systematic study of the influence of rotation mainly during the infall phase of the collapse of a typical iron core is performed. Indications for significant deviations from spherical symmetry are found in our very rapidly rotating models. © 2002 American Institute of Physics AU - Bollenbach, Mark Tobias AU - Bauer, Wolfgang ID - 3424 SN - 9781510832008 TI - 3d supernovae collapse calculations VL - 644 ER - TY - JOUR AB - Coordination of cell and tissue polarity commonly involves directional signaling [1]. In the Arabidopsis root epidermis, cell polarity is revealed by basal, root tip-oriented, hair outgrowth from hair-forming cells (trichoblasts) [2]. The plant hormone auxin displays polar movements [1, 3] and accumulates at maximum concentration in the root tip [4, 5]. The application of polar auxin transport inhibitors [3] evokes changes in trichoblast polarity only at high concentrations and after long-term application [2, 4]. Thus, it remains open whether components of the auxin transport machinery mediate establishment of trichoblast polarity. Here we report that the presumptive auxin influx carrier AUX1 [6, 7] contributes to apical-basal hair cell polarity. AUX1 function is required for polarity changes induced by exogenous application of the auxin 2,4-D, a preferential influx carrier substrate. Similar to aux1 mutants, the vesicle trafficking inhibitor brefeldin A (BFA) interferes with polar hair initiation, and AUX1 function is required for BFA-mediated polarity changes. Consistently, BFA inhibits membrane trafficking of AUX1, trichoblast hyperpolarization induced by 2,4-D, and alters the distal auxin maximum. Our results identify AUX1 as one component of a novel BFA-sensitive auxin transport pathway polarizing cells toward a hormone maximum. AU - Grebe, Markus AU - Friml, Jirí AU - Swarup, Ranjan AU - Ljung, Karin AU - Sandberg, Göran AU - Terlou, Maarten AU - Palme, Klaus AU - Bennett, Malcolm AU - Scheres, Ben ID - 2988 IS - 4 JF - Current Biology SN - 0960-9822 TI - Cell polarity signaling in Arabidopsis involves a BFA sensitive auxin influx pathway VL - 12 ER - TY - JOUR AB - Single molecule experiments provide insight into the individuality of biological macromolecules, their unique function, reaction pathways, trajectories and molecular interactions. The exceptional signal-to-noise ratio of the atomic force microscope allows individual proteins to be imaged under physiologically relevant conditions at a lateral resolution of 0.5–1 nm and a vertical resolution of 0.1–0.2 nm. Recently, it has become possible to observe single molecule events using this technique. This capability is reviewed on various water-soluble and membrane proteins. Examples of the observation of function, variability, and assembly of single proteins are discussed. Statistical analysis is important to extend conclusions derived from single molecule experiments to protein species. Such approaches allow the classification of protein conformations and movements. Recent developments of probe microscopy techniques allow simultaneous measurement of multiple signals on individual macromolecules, and greatly extend the range of experiments possible for probing biological systems at the molecular level. Biologists exploring molecular mechanisms will benefit from a burgeoning of scanning probe microscopes and of their future combination with molecular biological experiments. AU - Mueller, Daniel AU - Janovjak, Harald L AU - Lehto, Tiina AU - Kuerschner, Lars AU - Anderson, Kurt ID - 3421 IS - 1-3 JF - Progress in Biophysics and Molecular Biology SN - 0079-6107 TI - Observing structure, function and assembly of single proteins by AFM VL - 79 ER - TY - JOUR AB - In contrast to animals, little is known about pattern formation in plants. Physiological and genetic data suggest the involvement of the phytohormone auxin in this process. Here, we characterize a novel member of the PIN family of putative auxin efflux carriers, Arabidopsis PIN4, that is localized in developing and mature root meristems. Atpin4 mutants are defective in establishment and maintenance of endogenous auxin gradients, fail to canalize externally applied auxin, and display various patterning defects in both embryonic and seedling roots. We propose a role for AtPIN4 in generating a sink for auxin below the quiescent center of the root meristem that is essential for auxin distribution and patterning. AU - Friml, Jirí AU - Benková, Eva AU - Blilou, Ikram AU - Wiśniewska, Justyna AU - Hamann, Thorsten AU - Ljung, Karin AU - Woody, Scott AU - Sandberg, Göran AU - Scheres, Ben AU - Jürgens, Gerd AU - Palme, Klaus ID - 2989 IS - 5 JF - Cell SN - 0092-8674 TI - AtPIN4 mediates sink-driven auxin gradients and root patterning in Arabidopsis VL - 108 ER - TY - JOUR AB - Quantitative real-time PCR represents a highly sensitive and powerful technique for the quantitation of nucleic acids. It has a tremendous potential for the high-throughput analysis of gene expression in research and routine diagnostics. However, the major hurdle is not the practical performance of the experiments themselves but rather the efficient evaluation and the mathematical and statistical analysis of the enormous amount of data gained by this technology, as these functions are not included in the software provided by the manufacturers of the detection systems. In this work, we focus on the mathematical evaluation and analysis of the data generated by quantitative real-time PCR, the calculation of the final results, the propagation of experimental variation of the measured values to the final results, and the statistical analysis. We developed a Microsoft Excel-based software application coded in Visual Basic for Applications, called Q-Gene, which addresses these points. Q-Gene manages and expedites the planning, performance, and evaluation of quantitative real-time PCR experiments, as well as the mathematical and statistical analysis, storage, and graphical presentation of the data. The Q-Gene software application is a tool to cope with complex quantitative real-time PCR experiments at a high-throughput scale and considerably expedites and rationalizes the experimental setup, data analysis, and data management while ensuring highest reproducibility. AU - Müller, Patrick AU - Janovjak, Harald L AU - Miserez, Andre AU - Dobbie, Zuzana ID - 3422 IS - 6 JF - Biotechniques SN - 0736-6205 TI - Processing of gene expression data generated by quantitative real-time RT-PCR VL - 32 ER - TY - JOUR AB - The maturation of synaptic structures depends on inductive interactions between axons and their prospective targets. One example of such an interaction is the influence of proprioceptive sensory axons on the differentiation of muscle spindles. We have monitored the expression of three transcription factors, Egr3, Pea3, and Erm, that delineate early muscle spindle development in an assay of muscle spindle-inducing signals. We provide genetic evidence that Neuregulin1 (Nrg1) is required for proprioceptive afferent-evoked induction of muscle spindle differentiation in the mouse. Ig-Nrg1 isoforms are preferentially expressed by proprioceptive sensory neurons and are sufficient to induce muscle spindle differentiation in vivo, whereas CRD-Nrg1 isoforms are broadly expressed in sensory and motor neurons but are not required for muscle spindle induction. AU - Hippenmeyer, Simon AU - Shneider, Neil AU - Birchmeier, Carmen AU - Burden, Steven AU - Jessell, Thomas AU - Arber, Silvia ID - 3140 IS - 6 JF - Neuron SN - 0896-6273 TI - A role for Neuregulin1 signaling in muscle spindle differentiation VL - 36 ER - TY - CONF AU - Bauer, Wolfgang AU - Bollenbach, Mark Tobias AU - Kleine Berkenbusch, Marko AU - Harreis, Holger ID - 3423 T2 - Proceedings of the 18th Winter Workshop on Nuclear Dynamics TI - The percolation interpretation of the nuclear fragmentation phase transition ER - TY - JOUR AB - Long-standing models propose that plant growth responses to light or gravity are mediated by asymmetric distribution of the phytohormone auxin. Physiological studies implicated a specific transport system that relocates auxin laterally, thereby effecting differential growth; however, neither the molecular components of this system nor the cellular mechanism of auxin redistribution on light or gravity perception have been identified. Here, we show that auxin accumulates asymmetrically during differential growth in an efflux-dependent manner. Mutations in the Arabidopsis gene PIN3, a regulator of auxin efflux, alter differential growth. PIN3 is expressed in gravity-sensing tissues, with PIN3 protein accumulating predominantly at the lateral cell surface. PIN3 localizes to the plasma membrane and to vesicles that cycle in an actin-dependent manner. In the root columella, PIN3 is positioned symmetrically at the plasma membrane but rapidly relocalizes laterally on gravity stimulation. Our data indicate that PIN3 is a component of the lateral auxin transport system regulating tropic growth. In addition, actin-dependent relocalization of PIN3 in response to gravity provides a mechanism for redirecting auxin flux to trigger asymmetric growth. AU - Friml, Jirí AU - Wiśniewska, Justyna AU - Benková, Eva AU - Mendgen, Kurt AU - Palme, Klaus ID - 2986 IS - 6873 JF - Nature SN - 0028-0836 TI - Lateral relocation of auxin efflux regulator PIN3 mediates tropism in Arabidopsis VL - 415 ER - TY - JOUR AB - The hydra mutants of Arabidopsis are characterized by a pleiotropic phenotype that shows defective embryonic and seedling cell patterning, morphogenesis, and root growth. We demonstrate that the HYDRA1 gene encodes a Δ8-Δ7 sterol isomerase, whereas HYDRA2 encodes a sterol C14 reductase, previously identified as the FACKEL gene product. Seedlings mutant for each gene are similarly defective in the concentrations of the three major Arabidopsis sterols. Promoter::reporter gene analysis showed misexpression of the auxin-regulated DR5 and ACS1 promoters and of the epidermal cell file-specific GL2 promoter in the mutants. The mutants exhibit enhanced responses to auxin. The phenotypes can be rescued partially by inhibition of auxin and ethylene signaling but not by exogenous sterols or brassinosteroids. We propose a model in which correct sterol profiles are required for regulated auxin and ethylene signaling through effects on membrane function. AU - Souter, Martin AU - Topping, Jennifer AU - Pullen, Margaret AU - Friml, Jirí AU - Palme, Klaus AU - Hackett, Rachel AU - Grierson, Don AU - Lindsey, Keith ID - 2987 IS - 5 JF - Plant Cell SN - 1040-4651 TI - Hydra mutants of Arabidopsis are defective in sterol profiles and auxin and ethylene signaling VL - 14 ER - TY - JOUR AB - Developmental responses to the plant hormone auxin are thought to be mediated by interacting pairs from two protein families: short-lived inhibitory IAA proteins and ARF transcription factors binding to auxin-response elements. Monopteros mutants lacking activating ARF5 and the auxin-insensitive mutant bodenlos fail to initiate the root meristem during early embryogenesis. Here we show that the bodenlos phenotype results from an amino-acid exchange in the conserved degradation domain of IAA12. BODENLOS and MONOPTEROS interact in the yeast two-hybrid assay and the two genes are coexpressed in early embryogenesis, suggesting that BODENLOS inhibits MONOPTEROS action in root meristem initiation. AU - Hamann, Thorsten AU - Benková, Eva AU - Bäurle, Isabel AU - Kientz, Marika AU - Jürgens, Gerd ID - 2866 IS - 13 JF - Genes and Development SN - 0890-9369 TI - The Arabidopsis BODENLOS gene encodes an auxin response protein inhibiting MONOPTEROS-mediated embryo patterning VL - 16 ER - TY - CONF AB - In the last few years, several new algorithms based on graph cuts have been developed to solve energy minimization problems in computer vision. Each of these techniques constructs a graph such that the minimum cut on the graph also minimizes the energy. Yet because these graph constructions are complex and highly specific to a particular energy function, graph cuts have seen limited application to date. In this paper we characterize the energy functions that can be minimized by graph cuts. Our results are restricted to energy functions with binary variables. However, our work generalizes many previous constructions, and is easily applicable to vision problems that involve large numbers of labels, such as stereo, motion, image restoration and scene reconstruction. We present three main results: a necessary condition for any energy function that can be minimized by graph cuts; a sufficient condition for energy functions that can be written as a sum of functions of up to three variables at a time; and a general-purpose construction to minimize such an energy function. Researchers who are considering the use of graph cuts to optimize a particular energy function can use our results to determine if this is possible, and then follow our construction to create the appropriate graph. AU - Kolmogorov, Vladimir AU - Zabih, Ramin ID - 2927 SN - 9783540437468 T2 - Proceedings of the 7th European Conference on Computer Vision TI - Multi-camera scene reconstruction via graph cuts ER - TY - JOUR AB - We define the two dimensional Pauli operator and identify its core for magnetic fields that are regular Borel measures. The magnetic field is generated by a scalar potential hence we bypass the usual A L 2loc condition on the vector potential, which does not allow to consider such singular fields. We extend the Aharonov-Casher theorem for magnetic fields that are measures with finite total variation and we present a counterexample in case of infinite total variation. One of the key technical tools is a weighted L 2 estimate on a singular integral operator. AU - Erdös, László AU - Vougalter, Vitali ID - 2739 IS - 2 JF - Communications in Mathematical Physics SN - 0010-3616 TI - Pauli operator and Aharonov–Casher theorem¶ for measure valued magnetic fields VL - 225 ER - TY - JOUR AB - We consider the long time evolution of a quantum particle weakly interacting with a phonon field. We show that in the weak coupling limit the Wigner distribution of the electron density matrix converges to the solution of the linear Boltzmann equation globally in time. The collision kernel is identified as the sum of an emission and an absorption term that depend on the equilibrium distribution of the free phonon modes. AU - Erdös, László ID - 2738 IS - 5-6 JF - Journal of Statistical Physics SN - 0022-4715 TI - Linear Boltzmann equation as the long time dynamics of an electron weakly coupled to a phonon field VL - 107 ER - TY - JOUR AB - We show that the lowest eigenvalue of the magnetic Schrödinger operator on a line bundle over a compact Riemann surface M is bounded by the L1-norm of the magnetic field B. This implies a similar bound on the multiplicity of the ground state. An example shows that this degeneracy can indeed be comparable with ∫M |B| even in case of the trivial bundle. AU - Erdös, László ID - 2740 IS - 6 JF - Annales de l'Institut Fourier SN - 0373-0956 TI - Spectral shift and multiplicity of the first eigenvalue of the magnetic Schrödinger operator in two dimensions VL - 52 ER - TY - JOUR AB - We derive the time-dependent Schrödinger–Poisson equation as the weak coupling limit of the N-body linear Schrödinger equation with Coulomb potential. AU - Bardos, Claude AU - Erdös, László AU - Golse, François AU - Mauser, Norbert AU - Yau, Horng ID - 2737 IS - 6 JF - Comptes Rendus Mathematique SN - 1631-073X TI - Derivation of the Schrödinger-Poisson equation from the quantum N-body problem VL - 334 ER - TY - JOUR AB - Metabotropic γ-aminobutyric acid receptors (GABABRs) are involved in modulation of synaptic transmission and activity of cerebellar and thalamic neurons. We used subtype-specific antibodies in pre- and postembedding immunohistochemistry combined with three-dimensional reconstruction of labelled profiles and quantification of immunoparticles to reveal the subcellular distribution of pre- and postsynaptic GABABR1a/b and GABABR2 in the rat cerebellum and ventrobasal thalamus. GABABR1a/b and R2 were extensively colocalized in most brain regions including the cerebellum and thalamus. In the cerebellum, immunoreactivity for both subtypes was prevalent in the molecular layer. The most intense immunoreactivity was found in Purkinje cell spines with a high density of immunoparticles at extrasynaptic sites peaking at around 240 nm from glutamatergic synapses between spines and parallel fibre varicosities. This is in contrast to dendrites at sites around GABAergic synapses where sparse and random distribution was found for both subtypes. In addition, more than one-tenth of the synaptic membrane specialization of spine-parallel fibre synapses were labelled at pre- or postsynaptic sites. Weak immunolabelling for both subtypes was also seen in parallel fibres but only rarely in GABAergic axons. In the ventrobasal thalamus, immunolabelling for both receptor subtypes was intense over the dendritic field of thalamocortical cells. Electron microscopy demonstrated an extrasynaptic localization of GABABR1a/b and R2 exclusively in postsynaptic elements. Quantitative analysis further revealed the density of GABABR1a/b around GABAergic synapses was higher than glutamatergic synapses on thalamocortical cell dendrites. The distinct localization of GABABRs relative to synaptic sites in the cerebellum and ventrobasal thalamus suggests that GABABRs differentially regulate activity of different neuronal populations. AU - Kulik, Ákos AU - Nakadate, Kazuhiko AU - Nyíri, Gábor AU - Notomi, Takuya AU - Malitschek, Barbara AU - Bettler, Bernhard AU - Shigemoto, Ryuichi ID - 2624 IS - 2 JF - European Journal of Neuroscience SN - 0953-816X TI - Distinct localization of GABAB receptors relative to synaptic sites in the rat cerebellum and ventrobasal thalamus VL - 15 ER - TY - CHAP AB - We outline the status of rigorous derivations of certain classical evolution equations as limits of Schrödinger dynamics. We explain two recent results jointly with H.T. Yau in more details. The first one is the derivation of the linear Boltzmann equation as the long time limit of the one-body Schrödinger equation with a random potential. The second one is the mean field limit of high density bosons with Coulomb interaction that leads to the nonlinear Hartree equation. AU - Erdös, László ID - 2694 SN - 9783540441113 T2 - Dynamics of Dissipation TI - Scaling limits of Schrödinger quantum mechanics ER - TY - JOUR AB - To understand the possible contribution of metabotropic γ-aminobutyric acid receptors (GABABR) in cortical development, we investigated the expression pattern and the cellular and subcellular localization of the GABABR1 and GABABR2 subtypes in the rat neocortex from embryonic day 14 (E14) to adulthood. At the light microscopic level, both GABABR1 and GABABR2 were detected as early as E14. During prenatal development, both subtypes were expressed highly in the cortical plate. Using double immunofluorescence, GABABR1 colocalized with GABABR2 in neurons of the marginal zone and subplate, indicating that these proteins are coexpressed and could be forming functional GABABRs during prenatal development in vivo. In contrast, only GABABR1 but not GABABR2 was detected in the tangentially migratory cells in the lower intermediate zone. During postnatal development, immunoreactivity for GABABR1 and GABABR2 was distributed mainly in pyramidal cells. Discrete GABABR1-immunopositive cell bodies of interneurons were present throughout the neocortex. In addition, GABABR1 but not GABABR2 was found in identified Cajal-Retzius cells in layer I. At the electron microscopic level, immunoreactivity for GABABR1 and GABABR2 was found in dendritic spines and dendritic shafts at extrasynaptic and perisynaptic sites throughout postnatal development. We further demonstrated the presynaptic localization of GABABR1 and GABABR2, as well as the association of the receptors with asymmetrical synaptic junctions. These results indicate potentially important roles for the GABABRs in the regulation of migratory processes during corticogenesis and in the modulation of synaptic transmission during early development of cortical circuitry. AU - López Bendito, Guillermina AU - Shigemoto, Ryuichi AU - Kulik, Ákos AU - Paulsen, Ole AU - Fairén, Alfonso AU - Luján, Rafael ID - 2622 IS - 11 JF - European Journal of Neuroscience SN - 0953-816X TI - Expression and distribution of metabotropic GABA receptor subtypes GABABR1 and GABABR2 during rat neocortical development VL - 15 ER -