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    Integration of grid maps in merged environments

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    Natural environments are represented by local maps of grid cells and place cells that are stitched together. The manner by which transitions between map fragments are generated is unknown. We recorded grid cells while rats were trained in two rectangular compartments, A and B (each 1 m Ã\u97 2 m), separated by a wall. Once distinct grid maps were established in each environment, we removed the partition and allowed the rat to explore the merged environment (2 m Ã\u97 2 m). The grid patterns were largely retained along the distal walls of the box. Nearer the former partition line, individual grid fields changed location, resulting almost immediately in local spatial periodicity and continuity between the two original maps. Grid cells belonging to the same grid module retained phase relationships during the transformation. Thus, when environments are merged, grid fields reorganize rapidly to establish spatial periodicity in the area where the environments meet

    Development of behavioral learning paradigms in mice using auditory cues for positive and negative reinforcement

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    Unsere Hirnstrukturen sind aeusserst dynamisch und weisen ein hohes Mass an Plastizitaet auf, um Lernen und die Anpassung unseres Verhaltens an eine sich staendig veraendernde Umwelt zu ermoeglichen. In den letzten Jahren wurden vor allem im Bereich der Neurowissenschaften essentielle Beweise dafuer erbracht, dass das Grundprinzip jeglicher Erinnerung ‚synaptische Plastizitaet‘ ist, welches Aktivitaets bedingte Veraenderungen in der Staerke von neuronalen Verbindungen darstellt. Bislang ist jedoch nicht bekannt auf welche Weise diese neuronalen Veraenderungen auf Netzwerkebene organisiert werden. Es ist daher nowtwendig, um Lernprozesse und die Herausbildung von Gedaechtnisinhalten moeglichst genau untersuchen zu koennen, eine angemessene Anzahl an genau definierten Verhaltensexperimenten zu entwickeln,. Zusaetzlich sollte es moeglich sein neuronale Veraenderung auf Lernprozesse an sich oder auf nicht-assoziative Vorgaenge zurueckfuehren zu koennen. Der erste Teil dieser Diplomarbeit beschreibt die Entwicklung von drei verschiedenenen Verhaltensexperimenten in welchen Maeuse spezifisch zu positiver bzw. negativer auditorischer Reizverstaerkung konditioniert wurden. (1) Die Spezifitaet und Variabilitaet erlernter Reizantworten und damit verbundener Gedaechtnisinhalte ist entscheidend von der Art und Weise des zur Untersuchung verwendeten Verhaltens abhaengig. Aus diesem Grund fuehrte ich eine klassische auditorische Angstkonditionierung in Maeusen durch und untersuchte anschliessend zwei unterschiedliche Arten von Angstverahlten, Erstarren (‚freezing‘) und die Unterdrueckung fortwaehrenden Verhaltens, im speziellen des Trinkverhaltens (‚lick suppression‘). Allgemein ist in Verhaltensexperimenten zu bereucksichtigen, dass Reizantworten sowohl durch den spezifisch konditionierten Reiz als auch durch nicht assoziative Aspekte der Konditionierung hervorgerufen werden koennen. Deshalb ist es notwendig die Spezifitaet jeglichen erlernten Verhaltens zu bestimmen. Zu diesem Zweck werden konditionierte Reizantworten mit Verhalten verglichen, das durch nicht konditionierte Reize ausgeloest wird. In meinen Experimenten konnte ich nach der Konditionionierung in allen Maeusen deutliches Angstverhalten feststellen. Allerdings war die Spezifitaet der Reizantworten entscheidend von dem zur Untersuchung herangezogenen Verhalten abhaengig. (2) Neuronale Plastizitaet wird entweder durch bestimmte Eigenschaften eines konditionierten Reizes oder durch die Art der verwendeten Reizverstaerkung hervorgerufen. Eine Moeglichkeit diese beiden Aspekte bestmoeglich unterscheiden zu koennen, ist die Konditionierung eines neutralen Reizes mit sowohl positiver als auch mit negativer Reizverstaerkung. Die Methode der operanten Konditionierung basiert ueblicherweise auf positiver Reizverstaerkung, und nimmt relativ viel Zeit in Anspruch, da neben einer einfachen Reiz-Belohnungs-Assoziation auch verschiedene Verhaltensregeln erlernt werden muessen. Im Gegensatz dazu ist die klassische Angstkonditionierung von vergleichsweise kurzer Dauer und eine robuste Reiz-Antwort kann bereits innerhalb weniger Minuten festgestellt werden. Dieser zeitliche Unterschied erschwert natuerlich den Vergleich von operanter und klassischer Konditionierung. Daher entwickelte ich, um die Dauer der operanten Konditionierung zu verkuerzen, ein Verhaltensexperiment, welches auf einer klassischen Mehrfach-Konditionierung zu einem ersten visuellen und einem zweiten auditorischen Reiz (‚second order conditioning‘) basierte. Die Trennung von prozeduralen und assoziativen Aspekten des Lernprozesses sollte eine beschleunigte Konditionierung zum zweiten auditorischen Reiz ermoeglichen. Ich konnte zeigen, dass alle untersuchten Mauese erfolgreich zu beiden Reizen konditioniert werden konnten. Allerdings, war nach einer einzigen Konditionierung zum auditorischen Reiz der Lernprozess noch nicht vollstaendig abgeschlossen. (3) Verhaltensexperimente sollten einerseits robust und rasch durchfuehrbar sein, andererseits jedoch auch das Erlernen spezifischer Gedaechtnisinhalte ermoeglichen. Daher entwickelte ich ein disckriminatives operantes Verhaltensexperiment (‚go/no go task‘), in welchem Maeuse spezifisch zu zwei komplexen Toenen konditioniert wurden, wobei jeweils nur ein Ton positiv verstaerkt wurde. Es konnten alle Mauese erfolgreich zu komplexen auditorischen Reizen konditioniert werden, jedoch war die Genauigkeit der Unterscheidung schwaecher als in aehnlichen, auf olfaktorischen Reizen basierenden Experimenten. Es ist daher anzunehmen, dass die Faehigkeit von Mauesen spezifische Reize zu unterscheiden betraechtlich von der jeweiligen sensorischen Modalitaet abhaengt. Milliarden von vernetzten Neuronen, welche den unterschiedlichsten Zellarten angehoeren, bewerkstelligen im Gehirn eines jeden Saeugetieres Lernen und Gedaechtnis und erfuellen somit die verschiedensten Funktionen. Um einen besseren Einblick in besagte Komplexitaet zu gewinnen und die zugrunde liegenden neuronalen Netzwerkmechanismen besser zu verstehen, waere es von Vorteil ein einziges Neuron mitsamt seiner praesynatpischen Verbindungen untersuchen zu koennen. Bislang ist es jedoch, neben den unterschiedlichsten Methoden zur Visualisierung von neuronalen Verbindungen, noch nicht moeglich selektiv ein einziges Neuron und spezifisch dessen praesynatpische Verbindungen zu untersuchen. Der zweite Teil dieser Diplomarbeit beschreibt die Entwicklung von Expressions Vektoren, welche die Expression zahlreicher Varianten eines Fusionsproteins zwischen Cre-Recombinase und des schweren Strangs des Tetanus Toxins ermoeglichen. Der zugrunde liegende Gedanke ist, die Vielseitigkeit und Flexibilitaet der Cre-Rekombinase mit den spezifischen retrograden Transporteigenschaften des Tetanus Toxins zu verbinden und somit spezifisch alle praesynaptischen Verbindungen eines einzigen Neurons bestimmen zu koennen. In naher Zukunft sollte die Anwendung eines solchen Fusionproteins in Verbindung mit Elektroporation eines einzelnen Neurons es ermoeglichen neuronale Netzwerkverbindungen in transgenen Maeusen zu untersuchen, welche eine Cre-Rekombinase bedingte Expression eines Reportergens aufweisen.Our brains are highly dynamic and plastic in structure in order to allow learning and adaption of behavior to a constantly changing environment. Recent years of research found substantial evidence that the substrate of memory is ‘synaptic plasticity’ which represents activity dependent changes in strength of neuronal network connections However, little is known about the organization of such neural changes on circuit and network level. Therefore, it is essential to establish a specific set of well defined behavioral learning paradigms that allow the sensitive measurement of memory and its specificity. Furthermore, it is important to be able to dissociate between learning-related neuronal plasticity and simply non-associative processes. The first part of this thesis describes the establishment of three behavioral learning paradigms in mice including positive and negative reinforcement of complex auditory stimuli. (1) The specificity and variability of the memory assessment depends crucially on particular properties of the behavior used as read out. Therefore, I tested auditory fear conditioning to complex sounds in mice using freezing and lick suppression as two alternative behavioral memory read outs. I find that after conditioning mice show robust fear responses for both behaviors. However, the specificity of the memory, as measured by the induction of fear behavior by stimuli that were not used for conditioned, is dependent on the behavioral assay. (2) A strategy to dissociate neuronal plasticity induced by the way a particular stimulus was reinforced from neuronal plasticity that is induced by particular conditioned stimuli itself is to compare learning paradigms involving either positive or negative reinforcement for the same stimulus. Typically, operant conditioning paradigms involving positive reinforcement are time consuming since they include learning of several procedural aspects of the task beyond the simple stimulus→reward association. This makes the comparison between operant and classical fear conditioning, which usually occurs within the order of minutes, difficult. Here, I established a learning paradigm based on classical second-order conditioning using visual and auditory stimuli as salient cues for reward. This allowed the temporal separation of procedural and associative aspects of learning thus accelerating operant conditioning. I find that in this learning paradigm mice reliably form the association of sound to reward and that initial, but not complete, learning occurs within the first conditioning session. (3) Beside the implementation of fast learning paradigms that allow sensitive measurement of memory it is also important to assess the specificity of the memory formation. I tested behavioral responses of mice specific to properties of conditioned sound stimuli through the establishment of an auditory operant go/no-go discrimination task in which one of two complex sounds was positively reinforced. I find that mice can be trained to discriminate between two complex sounds, however, the fraction of mice achieving high performance levels is low compared to similar olfactory learning paradigms. Therefore, it seems that discrimination of stimuli of different modalities might pose different challenging tasks for mice. In general, learning and memory is mediated in the mammalian brain through billions of neurons which are highly variable in cell type and function and interconnected in complex networks. A major step towards a better understanding of neuronal circuit computations would be the ability to map out all the input neurons to a given postsynaptic neuron. Despite considerable progress in labeling interconnected neurons, a system sensitive enough to selectively label input neurons of a single target neuron is still lacking. The second part of this thesis describes the design and construction of expression vectors that allow the expression of variants of a fusion protein of the tetanus toxin heavy chain and Cre-recombinase. The idea is to take advantage of the sensitivity and versatility of Cre-recombinase and the selective transsynaptic transport of tetanus toxin for specific identification of input neurons. In the future, these constructs will hopefully allow identification of synaptically coupled neurons after electroporation of single neurons in a transgenic mouse allowing conditional expression of a fluorescent protein depending on Cre mediated recombination

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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